MYCOVIRO

MYCOLOGY&VIROLOGY
MLS028-MYCO-VIRO
COMPREHENSIVE EXAMINATION
MYCOLOGY
38 of 40 points
The branching filaments of molds and mushrooms *
2/2
Hyaline
Hyphae
Mycelia
Thallus
Mass of hyphae constructing the thallus *
2/2
Hyaline
Hyphae
Mycelia
Thallus
Dematiaceous hyphae is also known as the dark colored hyphae, on the other hand , clear hyphae is known as? *
2/2
Clear Dematiaceous hyphae
Hyaline hyphae
Bleached hyphae
None of the choices
Which of the following statement below is NOT true regarding , Sabouraud dextrose agar (SDA). *
2/2
Inhibits the growth of many bacteria.
Allows fungal contaminants and pathogenic fungi to grow
Alkaline in pH
Acidic in pH
It is used to demonstrate germ tube production by the yeast Candida albicans *
2/2
Mycosel agar
Germ tube media
SDA
Birdseen agar
It is used for growth of Cryptococcus neoformans *
2/2
Mycosel agar
Germ tube media
SDA
Birdseed agar
It is used to recover dermatophytes. *
2/2
Mycosel agar
Germ tube media
SDA
Birdseed agar
Option 1
Direct exam method used to dissolve nonfungal materials in skin, hair, and nail samples *
2/2
Calcium hydroxide 10%
Potassium oxide 10%
KOH 30%
None of the choices.
Infection of the scalp Caused by Microsporum and Trichophyton *
2/2
Tinea capitis
Tinea barbae
Tinea corporis
Tinea cruris
Tinea is a mycotic organism? *
2/2
TRUE
FALSE
Tinea is the medical term for the infection/s caused by dermatophytic mycotic organism? *
2/2
TRUE
FALSE
Histoplasma capsulatum does not have any capsule. *
2/2
true
false
Histoplasma capsulatum and Sporothrix schenckii are both dimorphic. *
2/2
true
falsle
Which of the following organism below is considered to be achlorophyllous. *
1/1
Candida albicans
Aspergillus fumigatus
Histoplasma capsulatum
All of the options.
Which pair below is correctly matched: *
1/1
FUNGI : APPROX 7um in dm.
FUNGI: EUKARYOTIC
BACTERIA : 4um in dm.

BACTERIA: EUKARYOTIC.
Examine the cell wall below: Given the key elements in this cell wall, this belongs to a: *
2/2
FUNGI
BACTERIA
VIRUS
PLANT
Displayed below are spores of the bacteria Clostridium tetani (blue background), and of a fungus (black background).
Which statements below is false regarding spores. *
2/2
Spore in fungi is primarily used for reproduction.
Spore in bacteria is mainly dormant.
Spore in bacteria is for heat resistance.
All are TRUE.
Perfect fungus characteristic refers to the ability of the organism to reproduce both via sexual and asexual method.
2/2
True
False
Both H. capsulatum and C. neoformans can be acquired via bird droppings. *
2/2
true
false
Most systemic mycoses affects primarily the lungs. *
2/2
true
false
Opportunistic fungi usually have hyaline hyphae. *
2/2
TRUE
FALSE
VIROLOGY
30 of 30 points
This is the temperature of the refrigerator at which all specimens submitted for viral recovery regardless of source should
be transported. *
2/2
-5 to -15 C
70 C
-70 C
0-4 C
If Inoculation of the specimen into tissue culture media will exceed 5 days this is the temperature the spcimen should be
at: *
2/2
-5 to -15 C
70 C
-70 C
0-4 C
It is a technique that employs single-stranded , complementary nucleic acid probes for detection of human
immunodeficiency virus (HIV) in the blood of seronegative individuals *
2/2
Eastern-Blot technique
Western- Blot technique
Southern-Blot technique
Classify : Picronavirus *
2/2
Non-enveloped
Enveloped
Classify : Coronovirus *
2/2
Non-enveloped
Enveloped
Classify : Paramyxovirus *
2/2
Non-enveloped
Enveloped
Classify : Orthomyxovirus *
2/2
Non-enveloped
Enveloped
Causative agent of AIDS:
2/2
Lentevirus
Orthomyxovirus
Adenovirus
Retrovirus
Causative agent of HEPATITIS B: *
2/2
Hepadnavirus
Orthomyxovirus
Adenovirus
Picornavirus
Causative agent of HEPATITIS A: *
2/2
Hepadnavirus
Orthomyxovirus
Adenovirus
Picornavirus
Causative agent of DENGUE: *
2/2
Flavivirus
Parvovirus
Adenovirus
Picornavirus
Causative agent of MUMPS: *
2/2
Flavivirus
Orthomyxovirus
Adenovirus
Paramyxovirus
Causative agent of Influenza type A: *
2/2
Flavivirus
Orthomyxovirus
Adenovirus
Paramyxovirus
Causative agent of Influenza type B: *
2/2
Flavivirus
Orthomyxovirus
Adenovirus
Paramyxovirus
It causes a primary disease (chicken pox) and a recurrent disease (shingles) *
2/2
Papillomavirus
Rotavirus
Varicella zoster virus
Paramyxovirus
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Forms
QUIZ 1
The preferred pH range for bacterial growth *
ACIDIC
Alkaline
NEUTRAL
The preferred pH range for Mycotic/fungal growth *
ACIDIC
ALKALINE
NEUTRAL
The pH range/value which is considered to be Neutral is *
pH 8
pH 13
pH 7
pH care
The pH range/value which is considered to be Acidic. *
pH 8
pH 13
pH 7
pH 2
The pH range/value which is considered to be Alkaline. *
pH 1
pH 13
pH 7
pH 2
Do some fungi produce substances that may kill bacteria? *
Yes
No
Maybe
QUIZ 2
1. Which of the following organism below is considered to be achlorophyllous. *
Candida albicans
All of the options.
2. Which statement below is not true regarding fungi. *
They exist in nature as saprophytic.

They are resistant to high temperatures.
They grow in large amounts of Sugar.
All are false.
3. Fungi are said to have no true cell wall but has true roots. *
True
False
4. Fungi are much closely associated to _______ in terms of structure. *
Plants
Bacteria
Viruses
5. Which pair below is correctly matched: *
FUNGI : APPROX 7um in dm.

FUNGI: EUKARYOTIC
BACTERIA : 4um in dm.
BACTERIA: EUKARYOTIC.
6. Examine the cell wall below: Given the key elements in this cell wall, this belongs to a: *
FUNGI
BACTERIA
VIRUS
PLANT
7. The cell wall content of a bacteria is mostly composed of: *
Chitin
Ergosterol
Peptidogylcan
8. Displayed below are spores of the bacteria Clostridium tetani (blue background), and of a fungus (black background). Which
statements below is false regarding spores. *
Spore in fungi is primarily used for reproduction.

Spore in bacteria is mainly dormant.
Spore in bacteria is for heat resistance.
All are TRUE.
9. What type of hyphae is responsible for nutrient absorption and stability. *

Aerial hyphae
Sexual hyphae
Vegetative hyphae
10. The ability of an organism to grow in more than one form under different environmental conditions. *
Monomorphic
Anamorphic
Dimorphism
11. In Lactophenol cotton blue staining, what part of the mixture acts as the mounting agent. *
Lactophenol
Cotton blue
Methyl blue
12. Classify the following condition/disease as to the choices given: Tinea nigra *
SUPERFICIAL MYCOSES
CUTANEOUS MYCOSES
SUBCUTANEOUS MYCOSES
13. Classify the following condition/disease as to the choices given: Mycotic Otitis Externa *
SUPERFICIAL MYCOSES
CUTANEOUS MYCOSES
14. Classify the following condition/disease as to the choices given: Biegel's disease *
SUPERFICIAL MYCOSES
CUTANEOUS MYCOSES
15. Classify the following condition/disease as to the choices given: Presents with patchy "blotchy" desquamating rash. *
SUPERFICIAL MYCOSES
CUTANEOUS MYCOSES
16. 1porothrix schenkii is a dimorphic fungus, same as Candida albicans. *
True
False
17. Madura's foot is a condition caused by a fungal specie only. *
True
False
18. JOCK ITCH IS otherwise known : *
Tinea pedis
Tinea cruris
Tinea capitis
19. Trichophyton that has a distinct colony color of Port wine to deep violet. *
Trichophyton tonsurans
Trichophyton violaceum
Trichophyton rubrum
QUIZ 3
1. HALLMARK: MACROCONIDIA WITH TUBERCULATE-FINGER LIKE PROJECTIONS.
* C.immitis
B. dermatitidis
P. brasiliensis
H. capsulatum
2. HALLMARK: INTRACELLULAR YEAST CELLS, MOSTLY RESISTANT TO PHAGOCYTIC ACTION OF MACROPHAGES. *
C.immitis
B. dermatitidis
P. brasiliensis
H. capsulatum
3. HALLMARK: COB-WEB LIKE GROWTH OF MYCELIUM.
* C.immitis
B. dermatitidis
P. brasiliensis
H. capsulatum
4. HALLMARK: INTRACELLULAR YEAST CELLS, MOSTLY RESISTANT TO PHAGOCYTIC ACTION OF MACROPHAGES.
* C.immitis
B. dermatitidis
P. brasiliensis
H. capsulatum
5. HALLMARK: MULTINUCLEATED YEAST CELLS WITH MLTIPLE BUDDING.
* C.immitis
B. dermatitidis
P. brasiliensis
H. capsulatum
6. HALLMARK: BROAD BASED BUDDING YEAST CELL, LOLLIPOP APPEARANCE OF CONIDIA. * C.immitis B. dermatitidis
P. brasiliensis
H. capsulatum
7. What type of WBC is mostly responsible for the defense against opportunistic fungi (dissimenated form).
* T-CELL
B-CELL
PLASMA CELL
BASOPHILS
8. Spelunker's disease is otherwise known as histoplasmosis. What is Spelunking?

* Exploring underwater caves.
Study of exotic bird species.
Exploring caves.
Study of caves and underground structures.
9. Spherules and Endospores are often seen in the mycotic elements of this fungi.
* C. immitis
B. dematitidis
H. capsulatum
10. Which of the ff. Opportunistic fungi is strictly exogenous in nature:

* C. immitis
H. capsulatum
C. albicans
C. neoformans
11. Microscopic appearance of this fungi is often confused with the amastigote form of L. donovani.
* H. nana
H. capsulatum
H. diminuta
C. immitis
12. Darling's disease is otherwise known as Histoplasmosis. Who is Darling?

* I don't know and I don't care.
The name of the patient who first have the infection.
The name of the pathologist who first described the infection.
Darling is not a person, rather a place where it is first discovered.
13. Histoplasma capsulatum and Sporothrix schenckii are both dimorphic.
* true falsle
14. Perfect fungus characteristic refers to the ability of the organism to reproduce both via sexual and asexual method.
True False
15. Histoplasma capsulatum does not have any capsule.
* true false
16. 1Both H. capsulatum and C. neoformans can be acquired via bird droppings.
* true false
17. Most systemic mycoses affects primarily the lungs.
* true false
MYCOLOGY&VIROLOGY ONLINE QUIZLETS

Molds Multicellular fungi
Yeasts Unicellular fungi
MycosisFungal infection
Systemic mycosisMultiorgan infection caused by fungi
Opportunistic mycosisFungal disease that occur primarily in immunocompromised

patients
Dimorphic fungiFungi that show both a yeast and mold phase
SaprophyteOrganism capable of living on decaying organic material
HyphaeBasic structural unit of molds
MyceliumHyphae come together to form:
Septate hyphaeHyphae that have cellular separations or cross-walls
Sparsely septate hyphae (formerly aseptate)Hyphae that contain few if any cellular
separations
CoenocyticLacking cross-walls
PseudohyphaeChain of cells formed by budding that resemble true hyphae
Vegetative hyphaeHyphae that function in food absorption

Extend below the agar surface or nutrient substrate
Aerial hyphaeHyphae that support reproductive structures called conidia
Extend above the agar surface
ConidiaSpore-like asexual reproductive structures Only formed by imperfect fungi
MicroconidiaUnicellular, small conidia
MacroconidiaMulticellular, large conidia
ArthroconidiaConidia resulting from fragmentation of hyphae into individual cells
BlastoconidiaConidia that form as a result of budding
ChlamydoconidiaConidia that result from terminal cells in the hyphae that enlarge and
have thick walls
PoroconidiaConidia formed by being pushed through a small pore in the parent cell
PhialoconidiaTube-shaped conidia that can be branched
AnnelloconidiaVase-shaped conidia; the remaining parent outer cell wall takes on

a saw-toothed appearance as the conidia are released
SporesSpecialized sexual reproductive structures
AscosporesSpores contained in a sac-like structure
BasidiosporesSpores contained in a club-shaped structure
OosporesSpores resulting from the fusion of cells from two different hyphae
ZygosporesSpores resulting from the fusion of two identical hyphae
Sabouraud dextrose agar (SDA)General-purpose fungal media; nutritionally poor

medium mildly selective for fungi; acidic pH (5.6) inhibits most bacteria
Modified SDA (Emmons)Fungal media with neutral pH which better supports fungal
growth but less inhibitory for bacteria
Sabouraud-brain heart infusion agar (SABHI)Nonselective medium for isolation of all

fungi Contains dextrose, peptone, & brain heart infusion
Cyclohexamide
Chloramphenicol
Gentamicin
 These drugs can be added to make SABHI selective for dimorphic fungi
Brain heart infusion agar with blood (BHIB)Used to grow most fungi, especially those
from sterile body sites; contains brain heart infusion and sheep blood
CyclohexamideInhibits the saprophytic fungi
ChloramphenicolInhibits many gram-postive and gram-negative bacteria
GentamicinInhibits primarily gram-negative bacteria
Inhibitory mold agar (IMA)Medium used to grow most fungal pathogens; especially
formulated to recover cyclohexamide-sensitive Cryptococcus; contains gentamicin &
chloramphenicol
Dermatophyte test medium (DTM)Medium used to isolate dermatophytes; contains

cyclohexamide & gentamicin; phenol red as a pH indicator
Selective agarsAgars containing various antimicrobial agents that will enhance growth of
specific fungal pathogens
Differential agarsAgars used to enhance pigment development, conidia production &

mold-yeast phase transition
Potato dextrose agar (PDA)Medium used to enhance conidia development

Enhances pigment development of Trichophyton rubrum
Birdseed (niger seed) and caffeic acid agarsSelective and differential media used to
grow C. neoformans
Phenol oxidaseC. neoformans forms black to brown colonies on birdseed agar due to the
activity of this enzyme
Cornmeal agar with Tween 80Medium used to differentiate Candida spp.
Agars containing rice, casein, and other nutrientsMedia used to differentiate

Trichophyton spp.
30 C Fungal cultures are incubated at this temp
Tease mount methodDissecting needle is used to pull apart a fungal colony and then
placed on a slide; may damage fungal structure, especially conidia
Cellophane tape methodTape is used to transfer aerial hyphae from the colony to a slide
for examination
Slide culture methodUses a block of agar overlaid with a coverslip; fungal colonies are
grown on the side of the agar block; coverslip is removed then examined
Saline wet mountDirect examination method used to view fungal elements such as
hyphae, conidia, and budding yeasts; most commonly applicable for vaginal secretions to
diagnose vaginitis
Lactophenol cotton blue wet mountDirect exam method used to stain and preserve
fungal elements in culture isolates
Potassium hydroxide (10%)Direct exam method used to dissolve nonfungal materials in

skin, hair, and nail samples
Gram stainStain that can be used to view yeasts
India inkStain that can be used to reveal capsules surrounding C. neoformans found in
CSF
Calcofluor white stainFlurochrome that stains chitin found in fungal cell walls; fungi will
appear white to blue to green depending on wavelength of light
Candida spp.
Blastomyces dermatitidis
Cryptococcus neoformans
 Possible fungal pathogens in blood
Candida spp.
Coccidioides immitis
 Possible fungal pathogens in CSF
Microsporum
Trichophyton
 Possible fungal pathogens in hair
Aspergillus
Epidermophyton
Trichophyton
 Possible fungal pathogens in nails
Candida
Microsporum
Trichophyton
Epidermophyton
 Possible fungal pathogens in skin
Candida albicans
Aspergillus
Rhizopus
Penicillium
 Possible fungal pathogens in the lungs
Candida albicans
Geotrichum candidum
 Possible fungal pathogens in the throat
Candida albicans
Candida glabrata
 Possible fungal pathogens in urine
Candida albicansPossible fungal pathogens in the genital tract
Candida albicansMost common cause of yeast infections
22-30 C Yeasts are grown on SABHI at this temp range
Germ tubesHyphae-like extensions of young yeast cells showing parallel sides, are
aseptate, and no constriction at the point of origin
Thrush (oral cavity)

Vulvovaginitis (vagina)
Onychomycosis (nail)
Paronychomycosis (cuticle)
 Types of candidiasis
Cryptococcus neoformansOnly forms blastoconidia Positive for urease and phenol

oxidase Negative for nitrate reduction
Trichosporon beigeliiCausative agent of white piedra Produces blastoconidia

arthroconidia Urease positive
Geotrichum candidumForms true hyphae with rectangular arthroconidia
T/F::Opportunistic fungi usually have hyaline hyphae T
Aspergillus fumigatusMost common cause of aspergillosis
Aspergillus nigerImportant cause of otomycosis
A. niger Colonies are yellow to black with yellow reverse
A. flavusColonies are green to brown with red-brown reverse
A. terreusColonies are green to yellow with yellow reverse
A. clavatusColonies are blue to green with white reverse

A. fumigatusColonies are green to gray with tan reverse
Absidia
Mucor
Rhizomucor
Rhizopus
Syncephalastrum
 Members of the class Zygomycetes
Absidia spp.Zygomycetes exhibiting branching sporangiophores between the rhizoids;

slight swelling below columella
Mucor spp.Zygomycetes with single or branching sporangiophores; no rhizoids; no

swelling below columella
Rhizopus spp.Zygomycetes with unbranched sporangiophores that

arise opposite rhizoids; no swelling below columella
TineaDermatophyte skin infection
Tinea pedis (athlete's foot)Infection between the toes

Caused by Trichophyton and Epidermophyton
Tinea corporis (ringworm)Infection of smooth skin

Caused by Microsporum and Trichophyton
Tinea unguium (onychomycosis)Infection of the nails

Caused by Epidermophyton and Trichophyton
Tinea capitisInfection of the scalp

Tinea barbae (barber's itch)Infection of beard hair

Tinea cruris (jock itch)Infection of the groin

Caused by Trichophyton and Epidermophyton
1. A bulldozer operator became ill while working on a new highway in the San Joaquin
Valley. He developed chest pain, anorexia, headache and general malaise, and myalgia
with fever. Chest X-ray showed pneumonic infiltrate and a single, well-defined nodule in
the left lower lobe. His leukocyte count and sedimentation rate were slightly elevated.
Although no fungus was seen in direct examination of a sputum specimen, processing
included a culture on Sabouraud dextrose agar with chloramphenicol and cycloheximide.
Within 3 days at30°C,this culture produced moist, grayish growth, and white aerial mycelia
began to develop (see Color Plate 30B). A lactophenol cotton blue wet mount of this
organismisseeninColorPlate31•. Whatis the most likely identification of this fungus?
A. Asperigillus fumigatus
B. Blastomyces dermatitidis
C. Coccidioides immitis
D. Histoplasma capsulatum
2. A 38-year-old male from Ohio presented to his physician with a mild influenzalike illness
that included headache and malaise. His chest X-ray showed no infiltrates. His past medical
history was unremarkable. He had no history of travel but reported recently cleaning the
bell tower at his church, which was littered with bird excrement. The most likely agent
causing his disease is
A. Aspergillus fumigatus
B. Coccidioides immitis
C. Candida albicans
D. Histoplasma capsulatum
3. . A 44-year-old gardener pricked herself with a rose thorn. A subcutaneous fungal

infection characterized by the development of necrotic ulcers followed this direct
inoculation of fungal spores into the skin. The causative fungus was cultured as a small
yeast form at 35°C (see Color Plate 32 •) and as a mould at room temperature with
delicate hyphae and conidia. This disease is
A. Blastomycosis
B. Chromomycosis
C. Mycetoma
D. Sporotrichosis
4. A yeastlike fungus was isolated from

a sputum sample. No hyphae were produced on cornmeal agar with Tween 80. The isolate
was negative for nitrate assimilation and positive for inositol assimilation and produced
urease at 37°C. These findings are typical of
A. Candida krusei
B. Cryptococcus terreus
C. Cryptococcus neoformans
D. Trichospown beigelii
5. A 24-year-old Vietnamese refugee was seen at a clinic in Houston. His chief complaints
were weight loss and fever.
A complete blood count confirmed he was suffering from anemia as well. Multiple skin
lesions were present on his arms, some of them draining pus. Gram stain
of the pus revealed what appeared to be yeastlike cells. A culture of the pus grew a green
mould at 22°C, which produced a red soluble pigment (see Color Plate 33«). A lactophenol
cotton blue wet mount of this organism is seen in Color Plate 34«. The causative agent in
this case is
A. Aspergillus fumigatus
B. Fusariumsp.
C. Trichoderma sp.
D. Penicillium marneffei
6. A section of a lymph node stained with the Gomori silver and hematoxylin and eosin
stains is shown in Color Plate 35 •. A lactophenol cotton blue wet mount of
a mould that grew from this specimen
is shown in Color Plate 36 •. Large, one- celled, smooth to tuberculate macroconidia and
smooth or echinulate microconidia are typical of mycelial phase growth of
A. Blastomyces dermatitidis
C. Histoplasma capsulatum
D. Paracoccidioides brasiliensis
7. Which of the following types of Candida albicans infection is commonly acquired from an
exogenous source?
A. Diaper rash
B. Neonatal thrush
C. Perianal infection
D. Urinary tract infection
8. In a direct examination of a KOH wet

mountofanailspecimen, Epidermophyton floccosum could be detected
as
A. Arthroconidia
B. Blastoconidia
C. Macroconidia
D. Microconidia
9. The mould phase of the systemic fungus Blastomyces dermatitidis can be confused with
A. Scedosporium apiospermum
B. Sporothrix schenckii
C. Aspergillus sp.
D. Penicillium notatum
10. It is usually difficult or impossible to identify a fungal culture before it is mature.

However, hyaline, septate hyphae, and a young conidiophore with a foot cell (see Color
Plate 37B) and a swollen vesicle are excellent clues to the identification of
A. Acremonium
B. Aspergillus
C. Paecilomyces
D. Penicillium
11. Zygomycetes are rapidly growing, airborne saprobes. In clinical specimens they
A. Are common as normal, human

microflora
B. Are found only as contaminants
C. May be seen in a dimorphic tissue
phase
D. May be found as a cause of rapidly
fatal infection
12. Trichophyton rubrum and T. mentagrophytes may be differentiated by the
A. Consistently different appearance of their colonies

B. Endothrix hair infection produced by T. rubrum
C. Fluorescence of hairs infected with T. rubrum
D. In vitro hair penetration by T. mentagrophytes
13. Broad, coenocytic hyphae found in tissue would be most typical of infection with
A. Aspergillus
B. Blastomyces
C. Microsporum
D. Rhizopus
14. A fungus infecting only skin and nails typically produces in culture
A. Spindle-shaped, hyaline, echinulate macroconidia and microconidia

B. Cylindrical or club-shaped, smooth,
thin-walled macroconidia and microconidia
C. Many microconidia in clusters or along the hyphae
D. Large, thin-walled, club-shaped macroconidia without microconidia
15. The most useful finding for prompt, presumptive identification of C. albicans is its
A. Failure to assimilate sucrose

B. "Feathering" on EMB
C. Production of chlamydospores
D. Production of germ tubes
16. Identify the dimorphic fungus that typically has a tissue phase in which the large
mother cells have one to a dozen narrow-necked buds and a slowly growing mycelial form
with intercalary chlamydoconidia and coiled hyphae.
A. Blastomyces dermatitidis
C. Histoplasma capsulatum
D. Paracoccidioides brasiliensis
17. Which of the following stains greatly enhances the visibility of fungi by binding to the
cell walls, causing the fungi to fluoresce blue-white or apple green?
A. Rhodamine-auramine
B. Warthin-Starry
C. Calcofluor white
D. Periodic acid-Schiff
18. The formation of arthroconidia is not an important characteristic in the identification of
A. Coccidioides
B. Geotrichum
C. Trichosporon
D. Sporothrix
19. A black pigment produced by colonies growing on bird seed agar is due to
A. Urease
B. Phenol oxidase
C. Sucrose assimilation
D. Arthroconidia production
20. Which of the following fungi is not considered an opportunistic pathogen?
A. Absidia
B. Aspergillus
C. Coccidioides
D. Fusarium
21. Observation of hyaline or dematiaceous hyphae is an early clue in the identification of
common, airborne fungi. Which of the following genera contains species found as
dematiaceous contaminants?
A. Alternaria
B. Aspergillus
C. Fusarium
D. Penicillium
22. Which of the following fungi is most likely to be found as a common saprobe and as an
agent of keratitis?
A. Exophiala
B. Phialophora
C. Fusarium
D. Wamgiella
23. The microscopic identification of Pneumocystis jirovecii is based on the detection of

A. Arthroconidia in subcutaneous tissue
biopsies
B. Cysts and trophozoites in respiratory
specimens
C. Yeasts in respiratory specimens
D. Tuberculate macroconidia in lung
biopsies
24. Fungi that undergo asexual reproduction are termed
A. Imperfect
B. Perfect
C. Aseptate
D. Septate
25. Hyaline septate hyphae, branched

or unbranched conidiophores, and multicelled banana-shaped conidia are characteristic of
which of the following
A. Fusarium
B. Curvularia
C. Acremonium
D. Trichophyton
26. Which of the following does not correctly describe the yeast Rhodotorula rubra?
A. It has been isolated from dairy

products, soil, and water.
B. It is the most common fungal cause
of diaper rash.
C. It has been identified as a nosocomial
pathogen.
D. It has been found as a contaminant or
commensal in specimens of urine, sputum, and feces.
27. A 21-year-old male member of a university track team presents to student health
services with a light brown circular lesion on his upper back. The agent most likely
responsible for this condition is
A. Candida albicans
B. Fusarium spp.
C. Geotrichum candidum
D. Malassezia furfur
28. Which of the following is likely to be found in clinical specimens as normal microflora
and as clinically significant isolates?
A. Aspergillus niger
B. Paracoccidioides brasiliensis
C. Penicillium marneffei
D. Candida albicans
29. A 4-year-old child's hair is falling out in patches. The hair fluoresces when subjected to
the UV light from a Wood's lamp. When the hair is cultured, a white cottony mould grows
at 25°C on potato dextrose agar. Microscopically, rare microconidia, septate hyphae, and
terminal chlamydospores are seen. Macroconidia are absent. The mould fails to grow on
polished rice grains. The causative agent is
A. Microsporum audouinii
B. Microsporum gypseum
C. Trichophyton mentagrophytes
D. Trichophyton rubrum
30. In tissues infected with Histoplasma capsulatum
A. The hyphae usually invade blood vessels

B. Encapsulated yeast cells are typical
C. Tuberculate macroconidia are typical
D. The fungus is usually intracellular
31. Blastomycosis
A. Lower Sonoran Life Zone

B. Mississippi and Ohio River basins
C. Pigeon roosts
D. Bat roosts
32. Coccidiodomycosis

C. Pigeon roosts
D. Bat roosts
33. Cryptococcosis

C. Pigeon roosts
D. Bat roosts
34. Histoplasmosis
A. Sphagnum moss
B. Starling roosts
C. Stagnant fresh water
D. Colorado RiverValley
35. Sporotrichosis
A. Sphagnum moss
B. Starling roosts
C. Stagnant fresh water
D. Colorado RiverValley
36. The cause of white piedra
A. Hortaea werneckii
B. Trichosporon sp.
C. Piedraia hortae
D. Fonsecaea compacta
37. The cause of black piedra
B. Trichosporon sp.
C. Piedraia hortae
38. The cause of tinea nigra
B. Trichosporon sp.
C. Piedraia hortae
39. The cause of tinea versicolor
B. Malassesia furfur
C. Microsporum gypseum
D. Geotrichum Candida
40. A keratinophilic saprophyte
B. Malassesiafurfur
41 A cause of otomycosis
B. Malassesia furfur
42. True hyphae and arthroconidia only
A. Candida albicans
B. Geotrichum
C. Trichosporon
D. Aspergillus fumigatus
43. True hyphae, arthroconidia, and blastoconidia
A. Candida albicans
B. Geotrichum
C. Trichosporon
D. Aspergillusfumigatus
44. Pseudohyphae, blastoconidia, and chlamydospores
A. Candida albicans
B. Geotrichum
C. Trichosporon
D. Aspergillusfumigatus
45. Pseudohyphae and blastospores only
A. Mucor sp.
B. Candida tropicalis
D. Candida albicans
46. Blastospores only, without hyphae or pseudohyphae
A. Mucor sp.
B. Candida tropicalis
D. Candida albicans
47. Cryptococcus neoformans
A. Bone marrow
B. Cerebrospinal fluid
C. Chronic draining sinus tract of foot
D. Chronic interdigital lesion of foot
48. Histoplasma capsulatum

mentagrophytes
A. Bone marrow
49. Pseudallescheria boydii
A. Bone marrow
50. Trichophyton mentagrophytes
A. Bone marrow
Viruses/virions
 Are the smallest known form of infectious disease causing agents
Nucleocapsid
 The nucleic acid is surrounded by this protein matrix
Viral replication
 Can occur only in living cells and involves many host-cell enzymes and functions
Attachment
Penetration
Uncoating
Synthesis of early proteins
Synthesis of late proteins
Assembly
Release
 (7) Steps in Replication
Attachment / adsorption
 Occurs when the virion comes in contact with the host cell
Penetration
 Occurs when the virus passes thrugh the plasma membrane
Fusion
 This is how enveloped viruses penetrate
Transversely
 This is how naked viruses penetrate
Pinocytosis
 It is the process of pinching through the plasma membrane, which results in viruses
entering within cytoplasmic vacuoles
Uncoating
 It is typically mediated by cellular proteases and results in the separation of the
capsid from the viral genome
Synthesis of early proteins

 These proteins are involved in genome replication
Synthesis of late proteins

 These proteins are used in the development of structural components of virion
Assembly
 It is the packaging of the new copies of the genome nucleic acid into the capsid
proteins
Release / egress
 The lipid envelope is acquired along with the glycoproteins as the progeny viral
nucleocapsid buds through the membrane
First presentation of symptoms

 Specimens for viral identification are best collected during this time
Virus titer
 Concentration of virus
 These are usually the highest in the early part of illness
Fourfold rise
 This rise in the antibody titer between acute and convalescent sera has been used to
identify a particular infectious agent as the cause at a recent disease.
Hank's balanced salt solution

0.2 M sucrose-phosphate
2% fetal calf serum
 (3) Viral transport media
Gelatin media
 Stabilizes protein
Urine for viral culture

 Should not be collected into containers with preservatives
Blood for viral culture

 Should be collected into heparin/EDTA tubes
0-4 deg celcius

• This is the temperature of the refrigerator at which all specimens submitted for viral
recovery regardless of source should be transported.
-70 deg celcius
• If Inoculation of the specimen into tissue culture media will exceed 5 days this is the
temperature the spcimen should be at
Tissue culture
 It is the inoculation of patient specimens into cells to determine the growth of a viral
agent
Primary culture
 These are cells derived directly from the donor (animal/human sources)
Primary rabbit kidney

 It is the first choice for herpes simplex virus types 1 and 2
Influenza A and B
Parainfluenza viruses types 1,2, and 3
Mumps
Measles
Rubella
Enteroviruses
 (6) Viruses that the first choice for culture is Primary monkey kidney
Parainfuenza virus
Measles
Rubella
Adenoviruses
Rhinoviruses
Herpes simplex virus type 1 and 2
Varicella zoster
 (7) Viruses that the first choice for culture is Primary human embryonic kidney
Cell lines
 Primary cultures that have been subcultured
Diploid cell line

 Cell lines that have at least 75% of the cells with a normal chromosome complement
 Usually die after 30-50 passages
WI-38
MRC-5
IMR-90
 (3) Diploid cell lines that are choices for culturing CMV
Heteroploid cell line

 Cell lines that have a predominance of cells containing an abnormal number of
chromosomes
 Continuous and have an indefinite number of passages
A549 cells
 These cells are derived from a human lung carcinoma
 Used to culture adenoviruses and varicella zoster
HEp-2 cells
 These cells are derived from a human laryngeal carcinoma
 These are used to culture respiratory syncytial virus (RSV) and adenoviruses
HeLa cells
 These cells are derived from a human laryngeal carcinoma
 These are used to culture RSV, rhinoviruses, and adenoviruses
Diploid cell > Continuous cell > primary cell

 Order of inoculation
Viral adsorption
 It refers to the time point when the virus comes in contact with the tissue culture
cells
Stationary adsorption
 It is the procedure of simply incubating the cell and virus for 30-60 minutes at 35
deg celcius
Roller drum method

 It refers to the gentle rotation of the culture tubes to enhance adsorption
Low-speed centrifugation method

 This requires that shell vials be centrifuged at 750-1000 x g for 30-40 minutes at 25
deg celcius
Immunohistochemical staining
 It uses fixed or fresh specimens incubated with chemically labeled (fluorescein) or
enzymatically labeled (peroxidase) antibodies to detect viral antigens
Nucleic acid hybridization

 It involves the detection of viral DNA or RNA sequences in nucleic acid extracted from
specimens
Polymerase chain reaction

 It is a technique that allows the viral genes to be amplified to enhance detection
The Western blot (dot blot)

 It is a technique that employs single-stranded , complementary nucleic acid probes
for detection of human immunodeficiency virus (HIV) in the blood of seronegative
individuals
Solid-phase immunoassays
 It uses antibodies and radioimmunoassay or enzyme-link immunosorbent assay
(ELISA) to detect viral antigens
Parvoviridae
Papillomaviridae
Polyomaviridae
Adenoviridae
Hepadnaviridae
 (5) naked DNA viruses with an icosahedral symmetry
Parvovirus B19
 It is spread by close physical contact
 It causes erythema infectiosum, or fifth disease
Papillomavirus
Papovavirus
 (2) significant genera of papillomaviridae
Human papillomavirus
 It causes warts in humans and is associated with some genital cancers
Polyomaviridae
 It produces histologically diverse tumors in various parts of the body (JCV and BKV)
Adenoviridae
 They have more than 47 serotypes of adenovirus
 This virus causes infection of the respiratory tract (nasopharyngitis); the eye
(keratoconunctivitis); and the intestines (e.g., diarrhea, vomiting)
Hepadnaviridae
 They have a tropism for infection of the liver
Hepatitis B virus
 It is also known as serum hepatitis and chronic hepatitis
Herpesviridae
 The enveloped DNA virus with icosahedral symmetry
HSV-1
HSV-2
 (3) viruses within the group Alphaherpesvirinae
HSV-1
 It is usually seen on the lips or skin or as an eye lesion
 It may be diagnosed by the Tzanck cell test
HSV-2
 It affects the genital or lips area and is frequently transmitted sexually

 It causes a primary disease (chicken pox) and a recurrent disease (shingles)
Chickenpox
 It is a mild, self-limiting, highly infectious disease that occurs mainly in children
Shingles / zosteer
 It is caused by the reactivation of varicella zoster virus that has been latent in the
neurons
 Severely painful vesicles form on the trunk area
CMV
 The significant viral pathogen
CMV
 It is typically an inapparent disease of childhood
 The infection occurs in the uterus or soon after birth, it may cause fetal or infant
death
Epstein-barr virus
 Viral pathogen in the gammaherpesvirinae
 Causes infectious mononucleosis
 Associated with Burkitt's lymphoma
Infectious mononucleosis
 Aka kissing disease
Kissing disease
 It produces atypical lymphocytes and immunoglobulin (IgM) heterophile antibodies
that are detected by the monospot test
Burkitt's lymphoma
 they have elevated titers of EBV antibodies
Human herpes virus type 6

 It causes a common exanthem disease (roseola infantum), or sixth disease
Poxviridae
 They are naked DNA viruses with a complex symmetry
Vaccinia
Variola
Molluscum contagiosum
 (3) human viruses that are part of the POxviridae family
Vaccinia
 It is the variant of the variola virus and produces a mild disease
 It is used as the immunogen in the smallpox vaccination
Variola virus
 It is the causative agent of smallpox, a disease that the world health organization
presumes to be eradicated
Molluscum contangiosum
 It causes small wart-like lesions on the face, arms, buttocks, and genitals
 It mimics genital herpes
 It forms eosinophilic inclusion bodies in infected cells
Orthomyxoviridae
Paramyxoviridae
Arenaviridae
Rhabdoviridae
Coronaviridae
Bunyaviridae
 (7) The envelopes RNA viruses with helical symmetry
Orthomyxoviruses
 They have a hemagglutinin, a neuraminidase, and a matrix protein associated with
the envelope
Influenza A and B
 Responsible for the epidemics of respiratory tract infection
Influenza B
 Influenza that is associated with Reye's syndrome
Antigenic drift
 It is caused by a minor mutation i the hemagglutinin glycoprotein that leads to yearly
epidemics
Antigenic shift
 It is caused by a majorr shift in the hemagglutinin glycoprotein that leads too
intermittent pandemics
Paramyxoviruses
Morbiliviruses
Pneumoviruses
 (3) Genera of Paramyxoviridae
Paramyxoviruses
 Are associated with parainfluenza and mumps viruses
Parainfluenza virus
 Causes croup in infants
Mumps virus
 They results in a generalised disease associated with enlargement of parotid glands
Morbilivirus
 It associated with the measles virus and causes a maculopapular rash, fever, and
Koplik's spots on the buccal mucosa
RSV
 It is the pneumovirus responsible for brochiolitis and pneumoni in infants
Arenaviridae
 The family that causes hemorrhagic fevers and the flu-like illness caused by the
lymphocytic choriomeningitis virus
Rhabdoviruses
 They are bullet-shaped viruses associated with the human pathogenic rabies virus
and bovine vesicular stomatitis virus
Negri bodies
 Cytoplasmic inclusion bodies
Coronaviruses
 2nd most frequent cause of the common cold and have been implicated in infant
gastroenteritis
Hanta virus
 Has been associated with severe life-threatening respiratory tract infections in the
southwestern United States.
Hanta virus
 Transmission has been through exposure to infected deer mice droppings
California and LaCrosse viruses

 Produce encephalitis, mainly in the Mississippi and Ohio River Valleys
 Transmission is via an infected mosquito bite
Togaviridae
Flaviviridae
Retroviridae
 (3) enveloped RNA viruses with icosahedral symmetry
Alphaviruses
 They are arboviruses with mosquito vectors and animal reservoirs
Rubella virus
 Causes german measles
German measles
 A systemic infection characterized by lymphadenopathy and a morbilliform rash
Dengue virus
Hepatitis V
St. Louis encephalitis virus
Yellow fever virus
Wes Nile virus
 (5) viruses that is Flaviviridae
Hepatitis C
 Causes 90% of the hepatitis cases associated with blood transfusion or infected blood
products
Retroviridae
 It contains a reverse transcriptase enzyme- RNA-dependent DNA polymerase
Lentivirus
Spumaviruses
Oncoviruses
 (3) genera of Retroviridae
Lentivirus
 Coontains HIV-1 and HIV-2
Kaposi's sarcoma
Pneumocystis carinii pneumonia
CMV
AIDS-related dementia
 (4) Characteristics of Full-blown AIDS
Gp41
P24
Gp120
Gp160
 (4) bands that will appear in western blot of HIV +
Viral Load
 It is a more sensitive test that detects low quantities of HIV-1 RNA
CD4 Lymphocyte count

 Marker of disease progression of HIV
Human T-cell leukemia virus I

 It is classified within the type C oncoviruses
Picornaviridae
Reoviridae
 (2) naked RNA viruses with icosahedral symmetry
Enterovirus
Rhinovirus
 (2) Picornaviruses
Poliviruses
Coxsackievirus A and B
Echovirus
Enterovirus
Hepatities A
 (5) Enteroviruses
Polioviruses
 An enterovirus that cause mild illness, aseptic meningitis, or poliomyelitis
 Flaccid paralysis`
Coxsackievirus type A
 Associated with the following:
- hand-foot-and-mouth disease
- hemorrhagic conjunctivitis
- aseptic meningitis
- colds
Coxsackievirus type B
 Associated with the following diseases: herpangina, viral heart disease, and Bornholm
disease (pleurodynia)
Echovirus
 Primarily infects the enteric tract but can cause a range of diseases from the common
cold to meningitis and hemorrhagic conjunctivitis
Enterovirus
 Associated with respiratory tract infections, central nervous system disease, and
hemorrhagic conjunctivitis
Hepatitis A
 Referred to as infectious hepatitis
 Can cause epidemics
Rhinoviruses
 The most frequent cause of the common cold
Rotavirus
 The primary cause of acuute infantile diarrhea
Hyphae
 Branching filaments of molds and mushrooms
Mycelium
 Mass of hyphae constructing the thallus
Thallus
 The vegetative body of a fungus
Dematiaceous hyphae
 Dark hyphae
Hyaline hyphae
 Light hyphae
Coenocytic
 Aseptate fungi
Pseudohyphae
 A series if elongated blastoconidia made by some yeast
 Characteristic of Candida albicans
Dupont isolater tubes

 Use of this for transport and processing enhances fungal recovery from blood and
bone marrow specimens
Sabouraud dextrose agar (SDA)

 Inhibits the growth of many bacteria because its pH is 5.6
 Allows fungal contaminants and pathogenic fuungi to grow
Nocardia asteroids
 (2) fungi that fails to grow on SDA medium
SDA with cycloheximide and chloramphenicol

 Reserved for skin , hair, and nail specimens
Brain-Heart infusion agar (BHI)

 A very nutritious agar that supports the growth of bacteria and fungi, including
Histoplasma and Nocardia
BHI with blood

 Agar recommended for converting dimorphic fungi from the mold to the tissue
(yeast) phase
BHI with blood, cycloheximide, and chloramphenicol

 A very nutritious agar that inhibits the growth of Nocardia
It supports the growth of dermatophytes, isolated from skin, hair and nail specimens,
Chloramphenicol
 Inhibits the yeast phase of dimorphic fungi
Corn meal Tween 80 agar (CMT 80)
 It is used for the demonstration of blastoconidia, pseudohyphae, arthoconidia, and
chlamydospores in the identification of Candida species and other yeasts
Potato dextrose agar (PDA)

 It is a medium used to enhance sporulation and pigmentation.
 It is used as a subculture medium rather than a primary plating medium
Inhibitory mold agar

 It is used primarily to recover pathogenic fungi exclusive of dermatophytes
Mycosel agar
 It is used to recover dermatophytes
Dermatophyte test medium (DTM)

 It is a screening medium used for the isolation of dermatophytes
Birdseed agar (Caffeic Acid Agar)

 It is used for growth of Cryptococcus neoformans
Trichophyton Test Agars

 Are used for speciation of the Trichophyton species
Germ tube media

 Composed of rabbit/fetal calf/human serum
 It is used to demonstrate germ tube production by the yeast Candida albicans
Urea agar slant

 It used to demonstrate urease production
 A positive test is development of a pinkish purple with in 48 hours after inoculation
Trichosporon
Rhodotorula
Cryptococcus
 (3) Urease-positive
Geotrichium
Saccharomyces
Candida
 (3) Urease-negative
Saline wet mounts

 Allow the observation of budding yeast, hyphae, condida, and hyphal filaments,
 These mounts are primarily used for the observation of vaginal specimens
Lactophenol cotton blue stain (LPCB)

 It can be used for direct smears or stains of fungal isolates
 Tease mounts for permanent smears and scotch tape preps can be made using this
stain
Phenol
 Kills organisms
Lactic acid
 Preserves the fungal structures
Cotton blue
 Stains the chitin in the fungal cell walls
Potassium hydroxide (KOH)

 It is ideal for observing skin, hair, or nails
 10% of this dissolves the keratin and enhances visibility of the fungi
Gram's stain
 The fungi appear gram-positive or blue
 This stain is used primarily to observe yeast and pseudohyphae present in clinical
specimens
Kinyoun Acid-fast stain

 Recommended for staining the partially acid-fast Nocardia
India ink
 This background stain is recommended for observing encapsulate yeast, especially
Periodic acid-Schiff (PAS)

 Stains fungi (except Actinomycetes) magenta against a light pink or green
background
Calcofluor white stain

 It is observed using fluorescence microscope.
 With this sensitive stain, fungal elements fluoresce against a dark background
Opportunistic fungi
 Exogenous saprophytes capable of causing infections in immunocompromised
individuals
 These fungi are routinely encountered in routine fungal cultures must be
differentiated from pathogenic fungi
Zygomycetes
Deuteromycetes
Ascomycetes
 (3) opportunistic fungi
Acremonium
Aspergillus
Fusarium
Gliocladium
Paecilomyces
Penicillium
Scopulariopsis
Sepedonium
 (8) Hyaline opportinists-septate fungi
Acremonium spp
 Microscopically demonstrate tapering conidiophores that support closely packed balls
of sickle- or elliptical-shaped conidia
Aspergillus spp
 Have a rough or smooth ubranched conidiophores with a foot cell at the base and a
vesicle (head) at the tip
 Rows of flask-shaped phialides in single or double rows support chains of rough or
smooth phialoconidia
 The most common opportunistic pathogen in the genus
 It grows at 45 deg celcius, and the phialides cover the upper two thirds of the vesicle
 Colonies are dark greenish to gray
Aspergillus niger
 Has black radiate head with phialides and chains of phialoconidia covering the entire
vesicle
 Colonies are dark black
Aspergillus flavus
 Has a spiny/rough conidiophores and phialides and chains of phialides cover the
entire vesicle
 Colonies are usually yellow-green color
Aspergillus terreus
 Produces cinnamon-brown colonies
Aspergillus clavatus
 Has huge, elongated vesicles with short phialides

Fusarium spp
 have single or branching conidiophores that terminate in tapered phialides.
 Macrophialoconidia are banana or cylindrical-shaped with two to five cells.
Gliocladium spp
 produce terminal masses of phialoconidia supported by flask-shaped phialides.
 Terminal masses of phialoconidia are held together in a large ball by a gelatinous
matrix.
 Mature colonies are a characteristic "green lawn" of growth.
Paecilomyces spp
 have single, short, or penicillus-type phialides with very delicate chains of smooth or
rough, oval conidia.
 This fungus resembles Penicillium.
Penicillium spp.
 have single, short, or penicillus-type phialides with very delicate chains of smooth or
rough, oval conidia.
 This fungus resembles Penicillium.
Penicillium marneffei
 is a dimorphic fungus that produces yeast-like colonies at 37◦C.
 In the mycelial form (25-30◦C), chains of lemon-shaped phialoconidia are supported
by wide phialides on broad metulae (conidiophores).
Scopulariopsis spp
 have echinulate (spiny) lemon-shaped annelloconidia in chains, supported on flask-
shaped annellides.
 Unbranched annellophores support the annellides.
Sepedonium spp
 have simple or branched conidiophores supporting single or clustered thick-walled,
smooth or rough macroconidia.
 This hyaline fungus resembles the yeast phase of the dimorphic pathogen
Histoplasma capsulatum.
Alternaria
Bipolaris
Cladosporium
Curvularia
Exserohilum
Epicoccum
Nigrospora
 (7) dematiaceous (dark) opportunists-septate fungi
Alternaria spp
 colonies are dark brown to black, and the hyphae and conidia are dematiaceous.
 Chained poroconidia with horizontal and vertical septa have club-shaped bases with
tapered apices.
Bipolaris spp
 have dark, septate hyphae with cylindrical, four-to five-celled poroconidia.
 "Bent-knee" shaped conidiophores support the poroconidia, with truncate hila at the
points of attachment.
 Bipolar germ tube formation is produced by these fungi.
Cladosporium spp
 produce short chains of blastoconidia from repeatedly forking shield cells.
 There is a scar at the point of attachment to the shield cells.
Curvularia spp
 have large four-to five-celled poroconidia with an overenlarged central cell and bent-
knee conidiophores.
Exserohilum spp
 have "bent-knee" conidiophores and protruding truncate hila at the ends of dark
cylindrical poroconidia with 6 to 14 cells.
Epicoccum spp
 have thick clusters of sporodchia (short conidiophores) that support terminal dark,
round conidia with horizontal and vertical septa.
Nigrospora spp
 Have dark hyphae and short fat conidiophores supporting supporting single, oval,
smooth-walled, black conidio
Absidia
Mucor
Rhizopus
Saksenaea
Cunninghamella
Syncephalastrum
 (6) Zygomycetes-aseptate opportunists with large, ribbon-like hyphae
Absidia spp
 Have stalk-like, branching sporangiospores with a columellae (base) supporting pear-
shaped sporangio (a sac)
 Asexual sporangiospores are produced within the sporangia by free-cell formation
 These aseptate Zygomycetes have rhizoids, or root-like structures, between the
interconnecting runners (stolons) connecting the sporangiosphores
Mucor spp
 Have a single or branching sporangiophores supporting round, spore-filled sporangio
 There are no rhizoids or stolons`
Rhizopus spp
 Produce black sporangia on unbranched sporangiophores opposite rhizoids
 Stolons connect the groups of rhizoids
Saksenaea spp
 Have large, flask-shaped sporangia filled with elongated sporangiospores
 Rhizoids are opposite the sporangiophores
Cunninghamella spp
 Have branched sporangiophores supporting terminal, round vesicles.
 Denticles protrude from the vesicles and support one-celled round sporangiola
Syncephalastrum spp
 Produce terminal, round vesicles
 Rows of round sporangiospores are in cylindrical merosporangia that radiate the
surface of the vesicle.
Candida albicans
 Part of the normal flora of the skin, mucous membranes, and gastrointestinal tract
 Predominantly the causative agent of these opportunistic infections
 Form chlamydospores, blastoconidia, and pseudohyphae on CMT 80 agar.
 Germ tubes are formed following incubation in germ tube media
 Assimilated the carbohydrate sucrose
Torulopsis glabrata
 Normal vaginal flora and may be associated with vaginal and urinary tract infections
Candida tropicalis
Candida parapsilosis
Candida krusei
 (3) emerging opportunistic pathogens
Candidiasis
 An acute-to-chronic fungal infection that can involve the mouth, vagina, skin, nails,
bronchi, lungs, alimentary tract, bloodstream, or urinary tract
Oral thrush
 A yeast infection that forms while curd-like patches on the oral muco-cutaneous
membranes
Vulvovaginitis / Vaginal thrush

 Manifests as a thick yellow-white discharge
 Diabetes, antibiotic therapy, oral contraceptives, and pregnancy predispose the
patient to this condition
Candida parapsilosis
 Primarily caused by candidemias
Candidemias
 Occurs in patients who have indwelling catheters
Malassezia furfur
 Can be an opportunist, causing septicemia in patients who receive intravenous lipid
infusions
 The fungus grows well in sebaceous glands
Malassezia furfur
 Also the causative agent of the superficial mycoses, pityriasis versicolor
Malassezia furfur
 Requires a medium overlayed with a lipid, such as olive oil
 Microscopically, this septate fungus appears as thick, round oval cells in clusters with
hyphae (spaghetti and meatballs)
Cryptococcosis
 Infections primarily involve the lungs and meninges and often occurs in AIDS patients
 The causative agent of cutaneous and disseminated disease
 Inhalation of fungal spored is usually the means of transmission
 Has a capsule that is demonstrated with the India ink preparation
 It is urease positive
 It is associated with pigeon and bird feces.
 It may also be associated with fruits, milk, or plants
Aspergilloses
 Are a variety of infections and allergic diseases primarily caused by Aspergillus
fumigatus
Allergic aspergillosis
 Involves inhalation of the conidia, colonization of the mucous plugs in the lung, and
subsequent asthma attacks
 A high titer of IgE antibody to Aspergillus is present
Fungus ball
 A localized abscess that forms in the lung, is another form of aspergillosis
 No tissue invasion
Invasive aspergillosis
 Occurs in neutroenic patients
 Initially, the patient has sinusitis, followed by dissemination throughout the body
(e.g., brain, bones) occurs.
Pencilliosis
 Is caused by the penicillus-producing fungi, Penicillium, Scopulariopsis, and
Paecilomyces.
Penicillium marneffei
 Causes a disseminated form of penicilliosis with flu-like symptoms, followed by
enlarged lymph node, spleen, and liver.
 Transmission may be via inhalation or ingestion of the fungal spores
Zygomycoses
 Also known as phycomycoses of mucormycoses, are acute infections caused by the
aseptate fungi in the phylum Zygomycota
Rhizopus
Absidia
Mucor
 (3) phylum Zygomycota
Systemic mycoses
 Affect internal organs and disseminate to multiple organs in the body
 Causative agents are typically the slow-growing, dimorphic fungal pathogens
 These fungi grow a molds at 25 deg Celcius and as yeast t 35 deg celcius
Histoplasmosis
 Aka Darling's disease
Darling's disease
 It is a granulomatous fungal infection caused by Histoplasma capsulatum
 Causative agent of Darling's disease
Darling's disease
 The progressive disease is transmitted via inhalation or direct inoculation into the
skin, and is not contagious or transmissible via person-to-person
Yeast of H. capsulatum
 Also tissue phase at 37 deg celcius
 It is small, single-budding yeast cells
Mold of H. capsulatum
 It demonstrates a large tuberculate macroconidia and small rough or smooth
microconidia along the sides of the hyphae
 This is the diagnostic stage
 The fungus resides in soil enriched with bat or bird guano (inhalation transmission)
North american blastomycosis

 Aka Gilchrist's disease
Gilchrist's disease
 Causative agent of Blastomyces dermatitidis
Yeast of Blastomyces dermatitidis

 Demonstrates large yeast with a double refractile wall and a broad-based bud
Mold phase of Blastomyces dermatitidis
 It is a single oval conidia at the ends of short conidiophores or directly on the hyphae
Coccidioidomycosis
 Aka San Joaquin valley fever
 Causative agent of San Joaquin valley fever
San Joaquin valley fever

 Transmission is via inhalation of the arthroconidia from sand and dirt
 The primary respiratory infection rapidly disseminated in immunocompromised
patients
Mold phase of Coccidioides immitis

 Alternating barrel-shaped arthroconidia between disjunctor cells
Yeast phase of Coccidioides immitis

 Large, thick-walled spherules filled with endospores
Paracoccidioidomycosis
 Aka South American Blastomycosis
Paracoccidioides brasiliensis
 Causative agent of South American Blastomycosis
South American Blastomycosis

 Transmission is via inhalation and primary infections are pulmonary or
mucocutaneous
 The prognosis is death within 2-3 years of dissemination of the disease
Yeast phase of Paracoccidioides brasiliensis

 Large, thick-walled yeast with multiple buds, resembling a "ship's wheel"
Mold phase of Paracoccidioides brasiliensis

 Intercalary and terminal chlamydocondidia are observed
Superficial mycoses
 Noninvasive infections that affect the outermost layer of skin and hair
Pityriasis versicolor
 Infects the stratum corneum epidermidis and causes hypopigmentation or
hyperpigmentation on the trunk of the body
Malassezia furfur
 Causative agent of Pityriasis versicolor
Pityriasis versicolor
 Scaly patches of skin fluoresce with a Wood's lamp
Malassezia furfur
 Characteristic "spaghetti and meatballs" morphology is observed microscopically and
a lipid oil overlay is required for culture
Tinea nigra
 Superficial infection of the stratum corneum epidermidis caused by the dematiaceous
fungus
 The infection is characterized by brown to black, nonscaly patches on the palms of
the hands
Exophiala werneckii
 Causative agent of Tinea nigra
Piedra
 It is an infection of the hair shaft that produces hair breakage
 Treatment is cutting or shaving infected hairs and use of topical antifungals
Trichosporon beigelli
 Causative agent of white piedra
White Piedra
 Forms soft , light brown nodules around the beard and mustache hairs
White Piedra
 Microscopically, the fungus demonstrated hyaline hyphae with blastoconidia and
arthrocondia on CMT 80 agar
Piedraia hortai
 Causative agent of Black piedra
Black Piedra
 Forms firmly attached hard, black nodules around the outside of scalp hairs
 Microscopically, it produces dark thick-walled hyphae with swellings
Cutaneous mycoses
 Typically caused by dermatophytic fungi
Tinea capitis
 It is dermatophytic infection of the scalp
Microsporom audouinii
 Causative agent of epidemic tinea capitis
 Fluoresces under a Wood's lamp
Microsporum canis
 Commonly causes zoophilic tinea capitis
 It has a few microconidia and numerous rough thick-walled, spindle-shaped
macroconidia with 6-15 cells
Microsporum canis
Trichophyton mentagrophytes
 Causative agents of zoophilic tinea capitis
 Also a causative agent of zoophilic tinea capitis
 It demonstrates grape-like clusters of microconidia and numerous pencil-shaped
macroconidia with 5-8 cells
Trichophyton tonsurans
 Causative agent of black-dot tinea capitis (chronic infection in adults)
Trichophyton schoenleinii
 Causative agent of Favus/tinea favosa (severe tinea capitis)
 Macroconidia are only observed if the fungus is grown on sterile rice grains
Microsporum gypseum
 Transmitted via contact w/ contaminated soil
 Numerous rough, thin-walled, elliptical macroconidia with 4-6 cells are produced by
the fungus
Tinea barbae
 It is an infection of the beard, neck, or fae
Trichophyton verrucosum
Trichophyton rubrub
 (3) Causative agent of tinea barbae
Trichophyton verrucosum
 Requires thiamine for growth and microscopically produces rare 3-5 celled
macroconidia with a rat-tail end
Trichophyton rubrum
 It produces numberous club-shaped microconidia, which occur singly alog the hyphae
 Rare to numerous smooth-walled, pencil-shaped macroconidia with 3-8 cells are also
produced
Trichophyton rubrum
 This dermatophyte is characterized by a deep red reverse
Tinea corporis
 It is a dermatophytosis of the body which usually affects the inside skin folds
Trichophyton rubrum
Trichophton violaceum
 (3) causative agent of tinea corporis
Trichophyton violaceum
 It has a characteristic violet colonies with a lavendar in 2-3 weeks.
Tinea cruris
 It is a dermatophytosis of the groin caused by the following dungi
Epidermophyton floccosum
Trichophyton rubrum
Candida spp
 (4) Causative agents of tinea cruris
Subcutaneous mycoses
 It is typically result from traumaticc implantation of a fungus into the cutaneous and
subcutaneos tossue
 Invades tissue, lymph nodes, and causes hard, lumpy, crusted ulcerations on
extremities.
Rose Gardener's disease

 Aka sporotrichosis
Sporothrix schenckii
 Causative agent of Rose Gardener's disease
 Found on plant material, such as rose thorn, sphagnum mss, and timbers
Yeast of Sporothrix schenckii

 Cigar-shaped budding yeast
 Referred to as cigar bodies
Mold of Sporothrix schenckii

 Mycelial form of the fungus is a daisy head or floweret of microconidia, which is
produced a the end of unbranched conidiophores on delicate hyphae
MYCOLOGY&VIROLOGY SIDE NOTES
Fungal Structure: Hyphae (aerial/vegetative) and Spore (reproductive)
Sexual spores: Ascospores, Basidiospores, and Oospores
Asexual spores:
 Chlamydospores (rounding terminal hyphae)
 Blastospores (budding off)
 Conidia (dematophytes)
 Arthrospores (produced from fragmentation of mycelium)
Mycosel: medium for dermatophytes (Cyclohexemide: inhibits fungal contaminants)
Saboraud’s Dextrose Agar: General Culture Media
Brain Heart Infusion Agar: Dimorphic Fungi
Coenocytic/Aseptate: phycomycetes/zygomycetes
LPCB: Stain
 Lactic Acid: preservative
 Phenol: killing agent
 Cotton blue: stains the cell wall (chitin)
SUPERFICIAL MYCOSES
- Affects hair, skin epidermis, sometimes the corneal surface (outermost layer only)
- Does not illicit immune response
DISEASE CLINICAL PICTURE ETIOLOGIC AGENT NOTES

Keratomycosis Blindness, corneal plaques 1. Candida spp. (yeast)
2. Fusarium (mold)
3. Aspergillus (mold)
4. Mucor (mold)
Otitis externa Outer Ear Canal Infection 1. Candida albicans
2. Candida tropicalis
3. Aspergillus fumigatus
4. Aspergillus niger
Piedras (Beigel’s a. Black Piedra (Scalp) a. Piedraia hortae a. Septate, dematiaceous,
Disease) b. White Piedra (Facial b. Trichosporon beigelii Ascopores (Sexual)
and Genital Hair) b. Septate, not dematiaceous,
Arthrospores (Asexual)
Tinea nigra Soles of foot and palm 1. Cladosporium werneckii
2. Hortae werneckii
3. Exophiala werneckii
4. Phaeoanellomyces werneckii 4.Phaeoanellomyces (Exophiala)
Dematiaceous: moist, shiny-black
and yeast-like colonies
Pityriasis Patchy “blotchy” 1. Malassezia furfur Lipophilic yeast: SDA + Olive oil
versicolor desquamating rash KOH: Spaghetti and meatball
(ap-ap) appearance
Diagnosis: coppery-orange
fluorescence under wood lamp
(UV)
CUTANEOUS MYCOSES
- Affects skin and nail, caused by dermatophytes

- Skin layer affected: dermis
- Dermatophytes: Keratinophilic
Endothrix: T. tonsurans, T. violaceum
Ectothrix: M. gypseum, M. canis, T. verrucosum
- Treatment: Miconazole, Tolnaltate, Griseofulvin, Ketoconazole
A. Ringworm: common fungal skin infection otherwise known as Tinea

B. Athlete’s Foot: fungal infection that usually begins between toes
C. Onchomycosis: nail fungal infection
MICROSPORUM TRICHOPHYTON EPIDERMOPHYTON

Infects hair and skin Infects skin, hair and nails Infects nail and skin
Diagnosis: bright yellow-green (Wood
lamp)
1. M. audonii – 1. T. mentagrophytes – 1. E. flocossum –
 white-pinkish, granular Macroconidia: cigar-shaped Macroconidia: club-shaped
and fluffy colonies Microconidia: grape-like cluster in pairs
 rice medium negative  Hair baiting test: v-shaped Microconidia: absent
2. M. canis –  Urease positive Dutch pants fuseaux
Macroconidia: spindle-shaped 2. T. rubrum –
 common cause of Macroconidia: pencil-shaped
ringworms in dogs and Microconidia: tear-drop
cats  Fluffy white colony with red
 canary yellow pigment color reverse (Red pigment)
 boat-shaped 3. T. concentricum –
 agent of dandruff Chlamydoconidia: balloon-shaped
 wood’s lamp: positive 4. T. tonsurans –
 rice medium positive Macroconidia: balloon-shaped
3. M. gypseum – Microconidia: club-shaped, tear-
Macoconidia: ellipsoidal with drop
blunt/rounded ends  Black dot tinea capitis
 Cinnamon powdery  Requires thiamine
colored colony  Creamy white colony with
 Wood’s lamp: negative crater-like depression
4. M. ferrugineum – 5. T. verrucosum –
 Bamboo hyphae Macroconidia: Rat-tail
Microconidia: large tear-drop,
pyriform
6. T. violaceum –
Colony: deep violet color
7. T. schoenleinii –
Hyphae: favic chandelier (antler)
 Causes Favus: Chronic Hair
Infection
 Requires thiamine and
inositol
INFECTION LOCATION CAUSATIVE AGENT

Tinea capitis Head or Scalp 1. Microsporum canis
2. Trichophyton tonsurans
Tinea barbae (barber’s itch) Beard 1. Trichophyton rubrum
Tinea ungium Nail 1. Trichophyton rubrum
3. Epidermophyton floccosum
Tinea corporis Body/non-hairy skin 1. Microsporum canis
Tinea pedis (Athlete’s foot) Foot (Interdigital spaces) 1. Trichophyton rubrum
Tinea cruris (Jock itch) Groin/Inguinal area 1. Trichophyton rubrum
- Infection that involves the skin and subcutaneous tissue

- Habitat: soil
CAUSATIVE AGENT DISEASE

Sporothrix schenkii Rose Gardener’s Disease - Sporotrichosis; causes
redness, swelling & open ulcers at puncture sites,
cigar-shaped yeasts in pus
a. Cladosporium type: Cladosporium carrionii Chromoblastomycosis - verrucous dermatitidis;
b. Philaophora: Phialophora verrucosa formation of cauliflower-like warts
c. Acrotheca: Fonsecaea pedrosoi & Fonsecaea Infected tissue: brown medlar bodies
compactum Colonies: dark with jet black reverse
a. Bacteria: Actinomyces israelii Maduramycosis – Madura foot; formation of
b. Fungi: Pseudoallescheria boydii granulomatous sinus lesion of the foot
Loboa loboi Lobomycosis – small and hard nodules appearing on

the extremities
Rhinosporidium seeberi Rhinosporidiosis – formation of tumor-like polyp on

the nose
1. Sporothrix schenkii – dimorphic fungus, mold form (25-30’C), yeast form (35-37’C)
Yeast: Asteroidal body formation = Methenamine Silver Stain
Mold: Flowerette/Bouquet-like conidia
Subcutaneous or lymphocutaneous lesions (Cord-like multiple subcutaneous nodules
2. Actinomyces israelii – bacterial cause of madura’s foot, “Molar tooth-like colonies”
3. Pseudoallescheria boydii – large, coarse septate hyphae; most common cause of eumycotic mycetoma
4. Phialophora verrucosa - vase-like
5. Fonsecaea pedrosoi - short chain
6. Cladosporium carrionii - long chain (branching)
7. Rhinosporidium seeberi - polypoid masses in nose and pharynx, tissue form: sporangium, MOT: swimming
8. Loboa loboi - keloid-like subcutaneous nodule involving extremities, tissue form: multiple budding cells
SYSTEMIC MYCOSES
- Dimorphic
- MOT: inhalation of spores (mold)
- BSC II – BSL III
- Specimen: sputum
Blastomyces dermatitidis North American Blastomycosis

Chicago Disease, Gilchrist’s Disease
Pneumonia and skin infections
Mold: lollipop
Yeast: single-budding with broad based (Mickey mouse_
Culture medium with cyclohexemide
Cottonseed Agar
Paracoccidioides brasiliensis South American Blastomycosis
Lutz-Splendore Almeida Disease
Pneumonia and skin infections, involves spleen liver,
lymph node
Mold: lollipop
Yeast: Multiple budding yeast (Mariner’s Wheel)
Histoplasma capsulatum Reticuloendothelial system
Darling’s Disease
MOT: inhalation of spores from guanos dropings
Mold: tuberculate macroconidia
Yeast: intracellular yeast cell (Macrophage)
Histoplasma duboisii Double cell
African histoplasmosis
Grows in increased nitrogen environment
Figure of 8
Coccidioides immitis San Joaquin Valley Fever
Desert Fever
Mold: barrel-shaped arthroconidia
Yeast: spherule with endospores
Send to Reference Laboratory
Laboratory Diagnosis:
Wright’s/Giemsa – Histoplasma
KOH: Blastomyces, Paracoccidioides, Coccidioides
Exoantigen Test:
A – B. dermatitidis
HS, HL, F – C. immitis
H, M – H. capsulatum
1, 2, 3 – P. brasiliensis
OPPORTUNISTIC MYCOSES
C. albicans Normal flora: skin, mucous membrane, GIT

Produce yeast and hyphae in vivo
Screening: Germ tube: forms at 35’C (Organisms + Serum ---(35’C for 2-3 hours))
Confirmatory: Chlamydospore: Corn Meal Tween 80 Agar (RT’ for 48-72 hours)
Blastoconidia, Pseudohyphae, True hyphae
Oral Thrush, Diaper rash
-Candidiasis (Old: Moniliasis): cutaneous, oropharyngeal (white patches), esophagitis,
cheilitis, onchomycosis, vulvovaginitis, invasive infection (CNS, blood)
Vaginal discharge = 10% KOH (Whiff’s test)
Mannan Antigen
Other Candida spp C. tropicalis = infection on immunocompromised host
C. krusei = hematological disorders
C. parapsilosis = endocarditis
C. dubliniensis = double conidia
Cryptococcus (Filobasidiella) Found in pigeon droppings and soil
neoformans Meningitis, Torulosis (Old: Cryptococcosis), Pneumonia
MOT: inhalation of airborne organism
Old: India ink preparation = Encapsulated yeast
New: Latex agglutination (Ag): capsule
Phenoloxidase = makes the colonies black
Staibs Nigerseed Agar / Birdseed
Colonies: Yeastlike, mucoid, cream to brown
SDA w/o cycloheximide
Rhodotorula Resemble C. neoformans
Encapsulated
To differentiate: Rhodotorula = pink colonies
Aspergillus fumigatus Fungus ball, Aspergilloma
Septate hyphae
Found in nature: soil, plant, air
Vesicles: swollen conidiophores
Czapek’s Medium
Ag detection (serum) = Galactomannan
Other Aspergillus spp.
A. flavus Aflatoxin (toxicoses) = HCC
Brown to black spore

A. niger
Zygomycosis/ Agents: Zygomycetes
Rhizopus, Absidia, Mucor
Mucormycosis
MOT: inhalation of airborne conidia
Rhinocerebral: Rhino-facial-cranial, involves Lungs, GIT, skin
Fusarium Sickle or canoe shaped, multiseptate macroconidia
Colony: Cottony white to pink or purple colony
Phaeohyphomycosis Alternaria, Bipolaris, Curvularia, Dreschlera, Exophiala
Pneumocystis jiroveci Fungi because of DNA homology

Masson-Fontana silver stain
(Old: P. carinii)
Mucicarmine: stain for spherule
Mycology- medically important fungi that can cause human diseases
Fungi- is actually harmless unless the individual is immunocompromised.
Thallophytes- loves to thrive in wet/moist environment
- NO true roots
Saprophytes- organisms that live on dead or decaying matter, they get their food from dad organic matter.
pH Temperature
FUNGI BACTERIA
Low pH Neutral to alkaline/ to acid
(Acidic)
Has sterol specifically NO ergosterol
ERGOSTEROL in cell
membrane
Q: Does fungi & bacteria go well together in nature?

NO! Because some fungi produces antibacterial substances such as penicillin produced by a mold “penicillium
notatum” which targets the bacterial cell wall and destroys/kills the bacteria.
THERMAL DIMORPHISM (dimorphic) – the capability of an organism to change/transform morphology depending

on the temperature it is currently in.
MONOMORPHISM/MONOMORPHIC – Grows only in one form
MOLDS YEASTS
25°c – 30°c 36°c – 37°c
Close to room temp.(20°C-24°C) Body temp.
2 fundamental structures
HYPHAE – main body of fungi
SPORES – little ovulations responsible for reproduction.
AGAR – nutrient-filled substance used for artificial growing of microorganism

(lab:bacteria/fungi, virus is rarely/not cultured)
MYCELLIUM – grouped hyphae
VEGETATIVE/SUBSTRATE HYPHAE – responsible of NUTRIENT ABSORPTION & MOUNTING FUNGI to one place
AERIAL/REPRODUCTIVE HYPHAE – grows out of the air, grows upwards; responsible for reproduction.
CANDIDA ALBICANS – no.1 cause of non-bacterial UTI
ESCHERICHIA COLI – no. 1 cause of bacterial UTI
SPOROTHRIX SCHENKII – cause of Rose-Gardener’s Disease; found in the bushes of roses and on the ground.
AMAN MEDIUM – is a special medium for mycotic growth; stain used: LACTOPHENOL COTTON BLUE
LACTOPHENOL COTTON BLUE - combination of:
LACTOPHENOL – mountant; keeps the fungi intact on the slide.
METHYL BLUE – gives color/ coloring agent
OPPORTUNISTIC MYCOSES:
EXOGENOUS – microorganism is from an outside source ( not a normal flora )
ENDOGENOUS – microorganism already found inside the body before the initial infection occurred.
PERFECT FUNGI – Fungi that can sexually & asexually reproduce.

IMPERFECT FUNGI – Fungi that is only capable of asexual reproduction.
NEUTROPENIA – decrease of WBC especially neutrophils.

CADIDEMIA – Candida in blood
INTERSTITIAL PNEUMONITIS – there is water in the linings of our lungs.
CRYPTOCOCCUS NEOFORMANS - stain used: INDIA INK ( negative type of staining )
- to view prominent feature
- Thick polysaccharide capsule would serve as the virulent factor of
C. neoformans and acts as a protective mechanism against phagocytosis
ASPERGILLUS SPP. – is usually found on farms or drylands
PAS – PERIODIC ACID SCHIFF
OPPORTUNISTIC FUNGAL INFECTIONS

FUNGI
EUCARIOTIC ORGANISMS
TWO BASIC FORMS:- YEASTS- MOLDS
MYCOSES
1. SUPERFICIAL
2. CUTANEOUS
3. SUBCUTANEOUS
4. ENDEMIC (PRIMARY, SYSTEMIC):
Histoplasma capsulatum, Coccidioides immitis, Blastomyces dermatitidis, Paracoccidioides brasiliensis
5. OPPORTUNISTIC
MAIN DEFENSE MECHANISMS AGAINST CANDIDA II.
 Phagocytosis
 killing, mostly in polymorphonuclear cells, less in macrophages
 T-cells (CD4)
THE MOST IMPORTANT RISK FACTORS
1. Neutropenia
2. Diabetes mellitus
3. AIDS
4. SCID
5. Myeloperoxidase defects
6. Broad-spectrum antibiotics
7. Indwelling catethers
8. Major surgery
9. Organ transplantation
10. Neonates
11. Severity of any illness

12. Intravenous drug addicts
CLINICAL FORMS OF CANDIDIASIS
1. Cutaneous and mucosal candidiasis

2. Invasive (systemic, disseminated, hematogenous) candidiasis (most dangerous form of candidiasis)
 Usually begins with candidemia (but in only about 50% of cases candidemia can be proven)
 If phagocytic system is normal, invasive infection stops here
 If phagocytic system is compromised, infection spreads to many organs and causes focal infection in these organs
 mortality of candidemia is 30-40%
DIAGNOSIS OF INVASIVE CANDIDIASIS
 Gram stain and isolation from blood, CSF or peritoneal fluid

 isolation and/or pathology positive of organ involved other tests are of lower significance for the diagnosis
EPIDEMIOLOGY
Although candidiasis is endogenous in most cases, cross infections are described, especially in intensive care unit patients.
Pneumocystis carinii
 Present in lungs of many mammals, including humans, in persistent but harmless infection
 Main defense mechanism is T-cell mediated
 causes interstitial pneumonitis in compromised patients

 treatment and prevention: cotrimoxasole or pentamidine
 Occurs worldwide in soil and in bird droppings

 Prominent feature: thick polysaccharide capsule, which causes evasion from phagocytosis
MAIN DEFENSE MECHANISMS AND PATHOGENESIS
• T-cells responsible for defense

• Cryptococcus reaches humans by inhalation of aerosolized yeast cells
CHRONIC MENINGITIS IN AIDS-PATIENTS
 The most important clinical syndrome

 treatment: amphotericin B+/-flucytosine
 recurrence prevention: fluconazole
EPIDEMIOLOGY OF CRYPTOCOCCOSIS
Infection is always exogenous, is not transmitted from human to human
Aspergillus species
 Aspergilli are worldwide occurring saprophytes, living in soil and on plants; they have small conidia that form
aerosols
 Main defense mechanism is phagocytosis
 Main risk factors are hematological malignancy, bone marrow transplantation and corticosteroid therapy
 The most frequent syndromes are: - aspergilloma
- invasive aspergillosis (high mortality rate)
 Treatment: amphotericin B, itraconazole, flucytosine and surgery
 Prevention: avoid exposure to conidia (new buildings in the hospital!)
ZYGOMYCETES
 Zygomycetes are ubiquitous saprophytes

 main host defense is phagocytosis
 main risk factors are diabetes, hematological malignancies, corticosteroid therapy.
Major clinical syndrome is:

 Rhinocerebral mucormycosis (infection of nasal passages, sinuses, eyes, cranial bones and brain)
 Treatment: surgery and amphotericin B
 Prognosis: very poor
OPPORTUNISTIC FUNGAL INFECTIONS ARE:

 difficult to diagnose
 difficult to treat
 difficult to prevent
 more and more frequent
 a great challenge for a future work in all fields
VIROLOGY
Virus: Obligate intracellular parasite Blood components: WBC ( with nucleus )
- need nucleated cell to multiply
Viral Structure: Either DNA or RNA
Virus particle: Virion
Capsid: protein coat (Icosahedral) (Helical) (Complex) - coats the nucleic acid genome
Envelope: lipid derived from host cell membrane
DNA: Nucleus
RNA: Cytoplasm
Diagnostic Virology:
1. Electron Microscopy – Morphology
2. Phase contrast – Inclusion bodies on tissue smear
3. Viral Genome – PCR
4. Cell Culture – CPE (Inverted Phase Contrast)
- Cytopathic effect (virus is out of the cell)
- Glycoprotein (attachment)
* Grading of CPE
INFLUENZA PMKC, MDCK, Embryonated Egg Negative Uninfected monolayer
CMV(cytomegalovirus) Human Embryonic Fibroblast 1+ 1-25% of monolayer exhibits CPE
2+ 26-50% of monolayer exhibits CPE
RSV (respiratory Hep-2 cells 3+ 51-75% of monolayer exhibits CPE
synctial virus)
4+ 76-100% of monolayer exhibits CPE
Syncytium (contain RSV, Measles, Rubella

multiple nucleus) Transport Medium:
Heme adsorption Para/Influenza 1. Stuart’s Medium (moist)
Refractile, round Rhinovirus Transport: 4’C ; Storage: -70’C (not -20’C = Crystal
Koilocyte (halo) HPV (Papillomavirus) formation)
Negri bodies Rabies 2. Leibovitz-Emory Medium
3. Hanks Balance Salt Solution
Multiplication Cycle
Receptors:
Naked virus Enveloped virus
- Directly - host cell to diffusion
- Cell will lyse - budding
 Needs lipid
Acetylcholine: Rabies
Sialic acid: Influenza
CD4: HIV
C3d: EBV
Largest virus: Pox virus

Smallest: poliovirus
Rules for DNA Viruses:

1. All are DS-DNA except PARVOVIRUS
2. All are Icosahedral except POX VIRUS
3. All are enveloped except PAPOVA, PARVO and ADENOVIRUS
4. All multiply in Nucleus except POX VIRUS
Rules for RNA Viruses:

1. All are SS-RNA except REOVIRUS
2. All are enveloped except PICORNA, CALICI and REOVIRUS
3. Positive Sense: Call Pico and Flavi To Come in Retro
4. Negative Sense: Pair Of Rabbits at Bunny’s Area
DNA VIRUSES
1. POX VIRUS
A. Largest Virus
B. Molluscum contagiosum – wart-like tumors
C. Variola virus: small pox – last case Somalia 1977 -causative agent for polio? Similar to cow virus
2. PARVOVIRIDAE
A. Strain B-19 causes Aplastic crisis (Parvovirus B19 – most common )
bone marrow not producing RBC, WBC, & Platelets
B. Smallest DNA Virus
C. Fifth childhood disease
D. Erythema infectiosum (Slapped-cheek appearance)
3. HERPESVIRIDAE
A. HSV-1: Common cause of Viral Encephalitis, Intraoral mucosal vesicles – border of the lips
B. HSV-2: Genital herpes (vesicles on the mucosa of the labia and vagina)
C. Tzanck Smear: multinucleated giant cells with cow dry type A inclusion
4. VARICELLA ZOSTER VIRUS
A. Primary: chicken pox
B. Shingles or Herpes Zoster (Dorsal root of ganglia: latency)
5. EPSTEIN BARR VIRUS
A. B cells, CD 21, C3d containing spikes
B. Infectious Mononucleosis
C. 80-90% positive with Anti-EBNA
6. CYTOMEGALOVIRUS
A. Number 1 Congenital Infection 40 days fever
B. Owl-eye Inclusion
7. HUMAN HERPES VIRUS 6
A. Roseola Infantum Rosy cheeks
th
B. 6 Childhood disease
8. HUMAN HERPES VIRUS 8
A. Detected in all forms of Kaposis Sarcoma (Bluish purple)
- Seen with AIDS patients
9. BK virus – Kidney, Cystitis
10. JC (John Cunningham) Virus – Progressive Multifocal Leukoencephalopathy (seen in brain,sample : CSF)
11. PAPILLOMAVIRUS
A. Tropism for Squamous Epithelial Cell
B. Condylomata acuminate – Anogenital warts (anus/genital)
12. ADENOVIRUS
A. Number 1 Viral Conjunctivitis (grapelike appearance)
B. Hexon– cross reactive protein (covers the virus)
C. Infantile gastroenteritis
13. HEPADNAVIRUS
A. Dane particle -Infectious Particle
B. Number 1 blood borne viral pathogen
-Hepa B
Other neonatal infection
Test for neonatal Cytomegalovirus

TORCH HSV
Toxoplasma Rubella
gondi
RNA VIRUSES
1. PICORNAVIRIDAE
ENTEROVIRUS POE: Mouth (resistant to acid)
A. Coxsackie A – FMHD (Foot Mouth Hand Disease)
B. Coxsackie B – Pericarditis (Pleurodynia-Devil’s Grip)
C. ECHO Virus – Enteric Cytopathic Human Orphan
D. Enterovirus 72 – Hepatitis A Virus
E. Enterovirus 71 – Encephalitis (aseptic meningitis)
F. Polio Virus – Flaccid Paralysis. Anterior Horn Cell of the Spinal Cord Caused by destroyed neuron
RHINOVIRUS – Labile at 33’C, common cause of Common Colds (nose only)
2. ORTHOMYXOVIRIDAE
A. Segmented, SS-RNA
B. Influenza A & B: 8 segments of RNA; Influenza C: 7 segments of RNA
C. 16 H Antigens (1, 2 & 3); 9 N Antigens (1 & 2) virulent H= Heme agglutination, N= neuraminidase
D. Influenza A – associated with antigenic shift
E. Drift: change in antigenic structure
F. Shift: genetic reassortment (pig: human and avian receptor)
G. AH1N1 – Spanish flu (Dominant strain) , antigenic shift in influenza A
H. AH2N2 – Asian flu
I. AH3N2 – Hongkong flu (Dominant strain)
J. AH5N1 – Avian
K. Hemagglutination Inhibition – Reference Test
L. RT-PCR – Definitive Test (for orthomyxoxiridae)
3. PARAMYXOVIRIDAE
A. Non-segmented
B. Hemagglutinin, Neuraminidase and Fusion Ag
C. Parainfluenza 1 – CROUP (laryngotracheobronchitis)
D. Mumps virus – Parotitis, bull neck appearance (C. diphtheria) Testes: orchitis, Parotid: Parotitis
E. Rubeola Virus – Measles, Koplik spots: red spots w/ bluish white speck in the center, 2nd Infection: SSPE, 3C’s
- 1 cause of cell multiple nucleus
4. Respiratory Syncytial Virus – Bronchiolitis in children, Viral Pneumonia in Adult, multiple infection Encephalitis
TOGAVIRIDAE
A. Togavirus – Chikungunya virus-like Dengue
B. Rubella virus – German measles, erythematous rash (face -> trunk and limbs)
-grape appearance, war then
5. RHABDOVIRIDAE
A. Rabies virus – Lyssavirus, Bullet, Seller’s stain for Negri bodies, excessive salivation, hydrophobia
6. FILOVIRIDAE
Ebola zire-most virulent ebola
Ebola R- Reston virginia, less virulent
A. Lake Victoria Marburg – Shepherd’s hook
B. Ebola (Ebola river) – Most lethal hemorrhagic fever (EBO-Zaire: most virulent)
C. Flavivirus – Dengue virus, Saddleback/Break bone fever (bone pain) Aedes aegyptius & Aedes albopictus
DHF: exposure to 2 different types of dengue virus
D. Yellow fever – jaundice (too much RBC, liver)
E. Bunya virus – Hemorrhagic fever
F. Hanta virus- Hantaan virus/Seoul Virus/ Dobrava virus: Hemorrhagic Fever with renal syndrome (OWHV)
Canned good virus
G. Puumala virus: nephropathia epidemica (OWHV)
Old world
H. Sin Nombre – hantavirus pulmonary syndrome (NWHV)
New world, -no name-
7. REOVIRIDAE
A. DS-RNA, segmented
8. Rotavirus – wagon wheel-like, Infantile diarrhea, Gastroenteritis in children, Winter Diarrhea RETROVIRUS
-norwalk virus
A. Reverse transcriptase
B. Lentevirus – HIV
9. CORONAVIRUS
A. Enveloped helical viruses with ssRNA
B. Club-shaped projections -SARS-
C. Summer Diarrhea
10. CALICIVIRUS
A. Norwalk – Adult Diarrhea
11. ARENAVIRIDAE
A. Hemorrhagic fever
B. Arena (Sandy)
12. HEPATOTROPIC VIRUS
A. Hepatitis A – Infectious hepatitis, Picornavirus
B. Hepatitis B – Serum hepatitis, Hepadnavirus
C. Hepatitis C – Post-transfusion hepatitis, Flavivirus
D. Hepatitis D – viroid-like
E. Hepatitis E – Waterborne, Calicivirus
F. Hepatitis G – blood-borne hepatitis
MYCOLOGY&VIROLOGY MODULE NOTES
Fungi
- Are multicellular members of the plant kingdom, and are referred to as thallophytes
- Usually filamentous – branched -somatic structure surrounded by the true cell wall.
Characteristics of a Fungi:
- 1. They are achlorophyllous ( can not manufacture its own food)
- 2. Ubiquitous ( present everywhere)
- 3. Exists in nature as saprophytes
- 4. Grow In the presence of acid and large amount of sugar (SDA- with pH of 5.6) which inhibits bacteria
- 5. Resistant to cold and are easily killed by high temperature
COMPARISON OF FUNGI AND BACTERIA
STRUCTURE AND GROWTH OF FUNGI
2 Basic Fundamental Structures: 1. hyphae 2. Spores
2 Morphologic Forms of Fungi: 1. Yeast 2. Molds

Yeast:
- They produce moist, creamy, opaque or pasty colonies 0.5-3.0 mm in dm on culture media
- Single-celled/ unicellular structures with a thick cell wall
- Most reproduce by asexual budding, few by binary fission
Mold
- Produces multicellular filamentous colonies: Fluffy, cottony, wooly or powdery
Structure of Molds:
- 1. Hyphae : the basic structural unit of mold which can be divided in to:
Septate ( with septum)
Aseptate/ Coenocytic ( without septum)
Mycelium (when hyphae overlaps one from the other), hyphae forms a mass of intertwining strands
Which can be divided into 2:

a. Vegetative or Substrate
b. Aerial or Reproductive mycelium

ILLUSTRATION OF THE MORPHOLOGIC FORM OF FUNGI
FORMS OF HYPHAE:
1. Antler Hyphae/Favic Chandelier : Hyphae that are curved, freely branching and antler in appearance( like that of a
2. Racquet Hyphae: enlarged, club-shaped with the smaller end attached to the large end of the adjacent club-shaped
strands.
3. Spiral Hyphae: Coiled or corkscrew seen within hyphal strands; Frequently found in dermatophytes
ILLUSTRATION IF THE DIFFERENT FORMS OF HYPHAE
Dimorphism
- The capability of an organism to grow in more than one form under different environment
- Example. Sporothrix schenkii
Monomorphic
- An organism that grows only in one form ( mold/ Sparobic/ hyphal)may it be at room temperature or at a higher temp
REPRODUCTIVE AND MULTIPLICATION OF FUNGI
- Multicellular fungi reproduce by conversion of a spore into a vegetative fungus
- Spores are functionally similar to a seeds of a higher plant

METHODS OF REPRODUCTION
1. Sexual (Teleomorph)= perfect fungus; is associated with the formation of specialized structures that facilitates
fertilization and nuclear fission resulting in the formation of specialized spores
Zygospores/Zygomycetes = derived from fusion of identical cells from the same hyphae
Ascospores/Ascomycetes = enclosed in a specific sac called ascus (asci)
Basidiospores/Basidiomycetes = enclosed in a club-shaped structures called basidia or basidium
Oospores = derived from fusion of non-identical cells from the same hyphae
ILLUSTRATIONS:
2. Asexual (anamorph) = imperfect fungus (Fungus imperfecti) ; a new colony is formed without the involvement of a
gamete and without nuclear fusion; a type of sporulation seen in most fungi encountered I the clinical laboratory and
occurs strictly by mitosis
A. Thalospores = derived from the cells of the thallus or body of the fungi
A.1.Blastospores = buds formed by budding process, sprouting from the surface of the parent Cell
Ex. Yeast: Candida albicans
A.2. Arthrospores/Arthroconidia = arise by fragmentation of the ends of hyphae at the point of septation; square
rectangular barrel-shaped thick walled cells
A.2.1. Oidia = when hyphal cells separate from one another to form flat ended spores
Ex. Geotrichum candidum
A.3. Chlamydospores/Chlamydoconidia = enlarged, round unicellular thick-walled structures
that are formed during unfavorable conditions; formed by the enlargement of a hyphal cells
Ex. Candida albicans
Types of Chlamydoconidia
A.3.1. Terminal = Chlamydia found at the hyphal tip
A.3.2 Intercallary = Chlamydia found within the hyphal strand
A.3.3. Sessile =Chlamydoconida found at the side of the hyphal strands

A.4. Sporangiospores = borne internally within a sac called sporangium . which develops at the
tip of the sporangipore
Conidia = asexual spores produces singly or in groups (en-grape) by specialized vegetative strands/branch
called Conidiphore (borne externally not with in)
NOTE: Some conidiophore terminate into swollen structure called VESICLE;
From the surface of the vesicle are formed secondary flask-shaped or bottle called PHIALIDES or STERIGMA
which in turn give rise to long chains of conidia as seen in Aspergillus
 In Penicillium, the structure known as Penicillus (brush-like structure) whereas each branch terminates in
secondary branches(metulae) and phialides from which chains of conidia are borne.
2 Sized of Conidia
1. Microconidia/Microaleuriospores
- Small, unicellular conidia, maybe round, elliptical or pyriform (pear-shaped)
- Usually born directly on the side of the hyphal strands or at the end of a long or short conidiophore
2. Macroconidia/Macroaleriospores
- Large, multicellular conidia; multi-septate, clavate or spindle-shaped
- Usually borne on a short to long conidiophore
- Echinulate-rough and spiny
- Catenate-conidia in chain
DIAGNOSTIC METHODS USED FOR FUNGAL IDENTIFICATION
1. Direct Examination:
A. Wet Mount ( Temporary Mounts)
A.1. KOH (10-20%)
• Used to clear and dissolve debris making fungal elements prominent
• For direct examination of infected materials
• Specimen: skin, nails, skin scrapings, sputum, bone marrow, pus, exudates from draining sinus
tract
• Gentle heat increases the rate of clearing to enable one to see fungal elements better
• Observe for: hyphae, budding yeast cells or any mycelial filaments
• KOH is recommended in the following:

A.2. India Ink
Cryptococcus neoformans .
CSF (meningeal form)
Sputum (pulmonary form)
encapsulated yeast cells
A.3. Lactophenol Cotton Blue
AMAN Medium
Preserves and stains fungi( shades of blue)
lactic acid, phenol and cotton blue which is excellent for mounting most fungi
Skin scrapings, hair and nails
Observe for spores, yeast cells and hyphae
B. Fluorescence
B.1. Calcoflour White Stain
fluorescence under fluorescent microscope
B.2. Wood’s lamp
Infected hair fluorescence bright yellow green under UV light
C. Staining
C.1. Gram Staining (Permanent Mounts)
see if fungus is a contaminant with a bacterium
All fungi are gram (+)
C.2. PAS
visualizing fungi skin scraping or tissue
dematiaceous, appears as dark brow/black

C.3. Wright’s or Giemsa
Gridley,Gomori-Methenamine Silver)
staining yeast cells of H. capsulatum in tissue
C.4. Papanicolau Method
stain for B. dermatitidis
C.5. Acridine Orange
Ideal for T. vesicolor
Produce green fluorescent and orange epithelial cells
C.6. Acid Fast Stain (Kinyoun)
differentiation of Nocardia from Actinomyces
Hyphae of Nocardia steroids and Nocardia brasilliensis are partially acid fast
Recommendation for Fungal Culture Media
- 1. Media with or without enrichment should be used (5-10%) sheep's RBC
- 2. Media with or without cyclohexmide (inhibits growth of fungi) should be used
- 3. All should contain antibacterial agents like chloramphenicol
NOTE:
• Culture should be incubated at RT for 30 days before reporting negative
• Culture should be examined at least 3 times a week during incubation
• Recommended to use agar plates or screw capped tubes for the recovery of fungi
Disadvantage of Culture Tubes:
• This will lead to poor isolation of colonies
• Reduce surface area of culture
• Tendency to promote anaerobiasis
• Cotton plugged tubes with culture media are not ideal or unsatisfactory for fungal cultures
Serologic Test:
• A significant rise in antibody titer to confirm the diagnosis
1. Complement fixation= for Cocciioidomycosis, Histoplasmosis, Blastomycosis
2. Latex Agglutination= for Cryptococcosis
3.Precipitation test
SUPERFICIAL MYCOSES
- Limited or confined to the outermost layer of the skin, hair and nails
- Does not invade living tissue
- Causes
Profuse sweating
Poor hygiene
Poor immunity
DISEASES ASSOCIATED WITH SUPERFICIAL MYCOSES
1. Keratomycosis (Keratitis/ Keratomycosis/ Keratitis)
- First described by Leber (Aspergillus species) in 1879
- Major cause of blindness in Asia
- Incidence low in Britain & North USA
- 6-53% of all cases of ulcerative keratitis in Asia
- Can occur alone or coexist with a bacterial infection (14.1%)
(Basak et al. India J. Ophthalmol.2005 Jun;53(2):143)
- Earlier phaeoid fungi (Dematiaceous) not considered to be significant but now are important cause of
keratomycosis.
- Clinical picture:
White corneal plaques with the development of satellite lesions and endothelial plaques
- Etiologic agent:
- Pathogenesis:
a defect in epithelial barrier.

e cornea so fungi continues
to grow & persists (i.e. why conjunctival flap help in control of fungal infection)
- Risk Factors:
– filamentous
Therapeutic lens – Yeasts
Overall bacterial infection more common with contact lens users
Broad spectrum antibiotics
- penetrating keratoplasty, LASIK
– in cases of Herpes simplex, Herpes zoster, Vernal/Allergic keratitis
tate – in cases of HIV, Leprosy
- Laboratory Diagnosis:
Giemsa stain
Grocott’s Methamine silver
PAS stain
Lectins
Calcoflour white
-20% KOH)
yeast cells with strands of pseudohyphae
For Keratitis Work up: Sheep blood agar
Chocolate agar
Saboraud’s Dextrose agar
Thioglycollate broth
Brain Heart Infusion broth/solid media

Within 1 week 97% cases
Electron microscopy
Polymerase Chain Reaction (PCR)
Advantages: Provide initial debridement of organisms
Improve penetration of drugs
Diamond tipped motorized burr
Diagnostic Superficial Keratectomy/Corn Biopsy
Femtosecond Laser
27 guage hypodermic needle ( 6-0 silk culture)
Anterior chamber tap: Hypopyon or endothelial plaque
Note: It is done in minor OT with topical anaesthesia
2-3 mm dermatologic trephine on anterior corneal stroma incorporating both clinically
infected
And adjacent clear cornea. (avoiding visual axis).
- Management:
Mode of action : binds to ergosterol in fungal cell membrane & cause the membrane to
become leaky.)
Mode of action: inhibits CYP P450 14 a-demethylase enzyme involved in conversion of
lanosterol to ergosterol
Mode of action: causes faulty RNA synthesis & non competitive inhibitor of Thymidylate
synthesis
Mode of action: Ergosterol Biosynthesis inhibitor

Mode of action: Cell wall synthesis inhibitors, D-glucan synthesis inhibitors
2. Otomycosis/ Mycotic Otitis Externa
- Clinical picture: Chronic fungal infection of the outer ear canal
- Filamentous fungi: Aspergillus, Mucor, Penicillium and Rhizopus
- Microscopic ID: Presence of hyphae or yeast cells
- Organism responsible: Candida albicans, Candida tropicalis
Aspergillus fumigatus, Aspergillus niger
- Symptoms of otomycosis includes: pain, itchiness, redness, hearing loss, discharge from ears, swelling,
physical narrowing of ear canal
3. Piedras (Chignon disease, Tinea nodosa, Biegel’s Disease)

4. Tinea nigra/ Keratomycosis nigricans palmaris/ Tinea nigra palmaris/Pytyriasis nigra/Microsporis nigra
- Clinical picture: Superficial infection on the palm of the hands or the sole of the foot
- Etiologic agent: Clasdosporium wernickii or Hortae or Exophiala or Phaeoannellomyces werneckii
- Outstanding Characteristics: 10-20% KOH: Strongly dematiaceous septate hyphae
5. Pityriasis versicolor
- Clinical picture: Patchy brown desquamating rash involving mainly the trunk, arms, shoulder and face “ blotchy
appearance
- Characteristic microscopic appearance: in 10-20% KOH
Clusters of short angular hyphae along with some yeast cells “spaghetti
and meatballs appearance”

CUTANEOUS MYCOSES/ DERMATOMYCOSES
Ringworm
tissues
ungal infection of human and are usually referred to as Tinea
Endothrix = dermatophytes grow inside the hair shaft
Ringworm:
ot)
Note: For nails and Skin: observes hyaline, septate hyphae
The specimen for culture is taken from the center of the lesion
Hair, skin and nail cultures use mycosel or mycobiotic medium and incubate at RT 4-6 weeks before
reporting
The infections maybe characterized by another latin noun to design the area of the body involved
Jock Itch (Tinea cruris)
- To treat jock itch, follow these steps:
ters
Athlete’s Foot ( Tinea pedis)
- Treatment:
tree oil
Scalp Ringworm (Tinea capitis)
- Treatment:
Barber’s Itch (Tinea barbae)
- Treatment:
Ringworm of the body (Tinea corporis)
- Treatment:
sulconazole, serconazole)
lanosterol 14-alpha-demethylase, a cytochrome P-450-dependent enzyme that
converts lanosterol to ergosterol.
The weakened dermatophyte is unable to produce and is slowly killed by fungistatic action.
Onchomycosis(Nail) (Tinea unguium)
- is most often due to Trichophyton rubrum and T. interdigitale.
- is increasingly prevalent with increased age and spreads from tinea pedis or less often, tinea manuum
- It is often confused with non-infected nail dystrophy due to skin disease, particularly psoriasis
Onchomycosis can be present as several different patterns:
- Lateral onychomycosis. A white or yellow opaque streak appears at one side of the nail.
- Subungual hyperkeratosis. Scaling occurs under the nail.
- Distal onycholysis. The end of the nail lifts up. The free edge often crumbles.
- Superficial white onychomycosis. Flaky white patches and pits appear on the top of the nail plate.
- Proximal onychomycosis. Yellow spots appear in the half-moon (lunula).
- Complete destruction of the nail.
Tinea axillaris
- Treatment with itraconazole over 4 weeks led to complete clearing of all lesions on glabrous skin.
3 GENERA CAUSING RINGWORM
1. Microscporum
• Ectothrix infection hair
• Yellow green fluorescence except M. gypseum
• Causes 2% of cutaneous mycoses in man
Microsporum audonii
- Lesions: T. capitis; T. corporis
- Anthropophilic
- Causes T. capitis among lower age group
- Growth rate; 2 weeks
- MICROSCOPIC ID:
- Sterile hyphae, terminal chlamydospore, favic chandelier and pectinate bodies
- Macroconidia: Rare, if present “spindle-shaped”
- Microconidia: Rare, “leaf-like” or absent
- Colony: Downy white to salmon pink
Microsporum canis
- Lesions: T. capitis, T. barbae, T. corporis
- Zoophilic
- Common caused of ringworm in dogs and cats
- Growth rate; 1 week
- Characteristic colony: white and fluffy; reverse canary yellow pigment, large thick walled, spindle shaped “boat-
shaped”
- Macroconidia: 8-12 septa
- Microconidia: Rarely seen
Microsporum gypseum
- Rarely caused human infection
- Geophilic
- Growth rate: 1 week
- Microconidia: Thick walled rough elliptical multisptate
- Macroconidia: Few or absent, with echinulate surface (4-6 cell with rounded terminal ends)
- Characteristic colony: Mold and cottony light brown “cinnamon powdery color”
- Rice medium: differential medium supporting the growth of M. canis and M. gypseum
Microsporum ferrugineum
- Lesions: T. capitis
- Anthropophilic
- Growth rate: 1 week
- Charateristic; thik septa, “bamboo” hyphae
- Macroconidia: rare
- Microconidia: none
2. Tricophyton
• Anthropophilic except T. verrucosum
• Ectothrix or endothrix infection on hair
• No fluorescence on wood’s lamp
Tricophyton mentagrophytes
- Lesions: T. pedis; t. corporis; T. unguium
- Worldwide cause of athletes foot
- Produces urease within 2-3 days or in 7 days after inoculation to Christensen medium
- Growth rate: 7-10 days
- Characteristic Microscopic appearance
Macroconidia: “cigar-shaped” 2-5 cells
Microconidia: “grape-like clusters” or “engrappe” lateraly along the hyphae
- Spiral hyphae seen in 30% of isolates
- Colony: White to pinkish granular and fluffy varieties
Tricpohyton rubrum
- Lesions; T. pedis; T. corporis; T. unguium; T. cruris
- Caused of long established foot and toe nail infections
- Fastest growing drmatophytes
- Growth rate: 2 days
- Does not produce urease
- Hair baiting Technique:
V-shaped penetration on hair shaft
• T. rubrum (-)
• T. mentagrophyes (+)
Characteristic microscopic appearance:
• Macroconidia: usually absent; if present “pencil-shaped” 3-8 septa
• Microconidia: “tear-drop” most commonly borne along the ides of hyphae
- Colony: Vary from white down to pink granular; ugal folds are common;
- Reverse= yellow when young however WINE RED color develops with age
- Dexrose-Cornmeal Agar: Differential medium which aids in the identification of T. rubrum nd T. mentagrophytes
on the basis of pigment production
Tricophyton concentricum
- Lesions: T. corporis
- Tinea imbracata;
- Characteristic of skin lesion is CONCENTRIC/RING-SHAPED in appearance
- Balloon shaped chlamydoconidia
Tricophyton tonsurans
- Lesions: T. capitis; T. corporis; T. pedis; T. unguium
- Caused of adult ringworm of the scalp( Alopecia)
- Characteristic Microscopic Appearance:
Macroconidia: “balloon” forms are seen
Microconidia: “tear-drop/ club-shaped” with flat bottons
- Colony: white, tan to yellow or rust, suede-like to powdery
Tricophyton verrucosum
- Lesions: T. corporis; T.barbae;T.capitis
- Usually found in cattles
- Grows better at 35˚C than at RT
- Growth rate; 2-3 days
- Macroconidia: rare; but form “rat-tail” type, 3-5 cell, thin walled
- Microconidia: rare; large and “tear-drop” when seen
Tricophyton violaceum
- Lesions: T. capitis; T. corporis; T. barbae
- Growth rate; 2-3 weeks
- Microscopic ID:
- Branched tortuous hyphae
- Chlamydospore are usually aligned in chains
- Colony; Portwine to deep violet colony
- Macroconidia and microcondia are generally not present
Tricophyton shoenleinii
- Slowest growing dermatophyte
- Growth rate: 2-3 weeks
- Microscopic ID:
- Hyphae seen as “favic-chandeliers”
- Colony: Irregular heaped, smooth white to cream colony with radiating grooves
3. Epidermophyton
• Antrophophilic
• No fluorescence
Epidermophyton floccosum
- Lesions: t. bilateral; T. cruris; T. pedis; T. unguium; T. capitis
- Microscopic characteristics:“club-shaped macroconidia” usually formed singly or in clusters
- No microconidia
- Colony: Center of the colony tends to be folded and is khaki green, periphery is yellow
SUBCUTANEOUS MYCOSES/ DERMATOMYCOSES
- Infections that involve the skin and subcutaneous tissue
- Affected areas: hands, arms and legs, feet
- Portal of entry: skin puncture/abrasions; thorns of the skin through traumatic inoculation
Sporothricossis/Rose Gardener’s Disease
- Only fungus disease that can almost be diagnosed by clinical picture alone
- Etiologic aent: Sporothrix schenkii
- A dimorphic fungus
- Microscopic Morphologic Feature:
-37˚C on BHIA) spherical/oval Cigar-shaped- Bodies singly or multiple budding on
gram stain
Stain
-like arrangement e conidia borne along the sides of hdaisy-like “Rossette”
clusters or “boquet”-like
-Mold Cultures: Sleeve-formation= single conidia borne along the sides of hyphae
Chromomycosis/Chromoblastomycosis/Verrucous dermatitidis
- Characterized by the development of papule which spreads to form warty tumor-like lesions characterized as
“ cauliflower-like” Etiologic agent: Dematiaceous fungi; (based on the type of conidiophore)
- 1. Cladosporium type: Cladosporium type:

- 2.Phialophora type
-like or vase-like or tube-like conidiophore” each with distinct
Collarette
3. Acrotheca type:
-shaped ends of conidiophore”
Brown “fission bodies” or “sclerotic bodies ”which appears brown, rounded and resemble
“copper pennies” as seen in tissue either in 10% KOH preparations or sectioned tissues
Mycetuma/Madura foot/Maduramycosis
- Chronic granulomatous infection which produces tumor-like lesions and sinus tract formation with the
presence of granules usually of the foot
- Etiologic agent:
- Actinomycotic mycetoma
-like bacteria
Granules contain very fine delicate filaments to bacilliary to coccoid forms
-like” colony
sis;caviae)
- Eumycotic mycetoma
B. Madurella (M. mycetoma; M. grisea)
Lobomycosis
- Initial lesions are small, hard and subcutaneous nodules appearing on the extremities, face or ear
- Lymhp nodes are not involved
- Etiologic agent: Loboa loboi
- Characteristics:
thick-walled
Rhinosporidiosis
- Tumor-like polyp usually on the nose
- Etiologic agent: Rhinosporidium seeberi
- Acquired from stagnant water
- Characteristics:
-30 microns in dm filled with SPORANGIOSPORES
Systemic Mycoses
- May involved any of the internal organs of the body as well as lymph nodes.
- Bones and subcutaneous tissues and skin.
- Dimorphic
- Transmitted via inhalation of spores
- Source of specimen: Sputum and body fluids
- Exoantigen test: Is now considered by most laboratories to be the most conclusive method for making a definitive
identification of dimorphic fungi
- Serologic confirmation for systemic fungi
- Acquired through inhalation from bird droppings
- Etiologic agent: Histoplasma capsulatum
- Smallest yeast cells
- Emmonsiella capsulatum
-sexual stage
- Colony Characteristics:
- Microscopic feature from Culture:
TUBERCULATE with age
infectious
Microscopic features of tissue form:
-5 um small; oval to spherical budding cells often seen inside mononuclear cells (phagocytic
cells)
- Confirmatory Test for Identification:
N bands
- Histoplasma capsulatum var. duboisii
Coccidiodomycosis/Cocci/ Desert Fever/Valley fever/ Desert Rheumatism/ “The Bumps”/ San Joaquin Valley
Fever/ Posadas Werneckii
- Acquired through inhalation of arthrospores
- Etiologic agent: Coccidiodes immitis
- Major biohazard to health
- Colony Characteristics
fy white but may be pigmented gray, orange, brown or
yellow
-web” like growth
- Microscopic features from Culture
-SHAPED ARTHROCONIDIA
small and often arranged in rope-like strands and racquet forms are seen in young
cultures
- Microscopic Features of Tissue Form
-60 um in diameter containing 2-5 um ENDOSPORES
F and TP bands
- Diagnostic procedure for detecting active infection with C. immitis:

Blastomycosis/ Gilcrhrist’s Disease/Chicago Disease/ North American Blastomycosis
- Chronic granulomatous disease of skin, mucous membrane, lymph nodes and internal organs
- Etiologic agent: Blastomyces dermatitidis, Ajellomyces dermatitidis( perfect-sexual stage )
- Clinical characteristics of the cutaneous skin lesion:
- Colony Characteristics
to glabrous and adherent to the surface with tufts of hyphae projecting upwards (“PRICKY
STATE”) on medium with blood
Microscopic features from Cultures:
-2um in dm are present, single pyriform oidia are produced on shorth to long
conidiopohores (“LOLLIPOP conidia”)
-15 um BROAD-BASED BUDDING thick walled yeast cells
- Confirmatory test or ID:Broad-based budding cells
- Microscopic features from Cultures:
-2um in dm are present, single pyriform onidia are producedon shorth to long
conidiopohores (“LOLLIPOP conidia”)
-15 um BROAD-BASED BUDDING thick walled yeast cells
- Confirmatory test or ID:Broad-based budding cells
PARACOCCIDIOIDOMYCOSIS/SOUTH AMERICAN BLASTMYCOSIS/ “PARA” or “PARACOCCI”/ ALMEIDA”S
DISEASE/ LUTZ SPLENDORE ALMEIDA’S DISEASE
- Etiologic agent: Paracoccidioides brasiliensis
- Growth rate:21-28 days
- Colony Characteristic:
Colonies heaped, wrinkled, moist and yeast like with age

brown
- Microscopic features from Culture:
-2 um in dm are present
milar to B. dermatitisis chlamydospores maybe numerous and
MULTIPLE BUDDING YEAST maybe present
- Microscopic Features of Tissue Form:
for 1,2 and 3
OPPORTUNISTIC MYCOSES
- are infections due to fungi with low inherent virulence which means that these pathogens constitute an almost
limitless number of fungi. These organisms are common in all environments.
- The disease equation:
Number of organisms x Virulence = Disease
- With opportunistic infections, the equation is tilted in favor of "disease" because resistance is lowered when
the host is immunocompromised. In fact, for the immunocompromised host, there is no such thing as a non-
pathogenic fungus.
- The fungi most frequently isolated from immunocompromised patients are saprophytic (i.e. from the
environment) or endogenous (a commensal). The most common species
are Candida species, Aspergillus species, and Mucor species.
- The upward trend in the diagnoses of opportunistic mycoses reflects increasing clinical awareness by
physicians, improved clinical diagnostic procedures and better laboratory identification techniques. Another
important factor contributing to the increasing incidence of infections by fungi that have not been previously
known to be pathogenic has been the rise in the number of immunocompromised patients who are
susceptible hosts for the most uncommon agents. Patients with primary immunodeficiencies are susceptible
to mycotic infections particularly when cell-mediated immunity is compromised. In addition, several types
of secondary immunodeficiencies may be associated with an increased frequency of fungal infections. (Dr Art
DiSalvo,OPPORTUNISTIC MYCOSES, microbiology and Immunology On-Line, University of South caroloina
School of Medicine)
When a fungus is isolated from an immunocompromised patient, the attending physician has to distinguish between:
- Colonization (which is of no major concern)
- Transient fungemia (often involving C. albicans)
- Systemic infection
The diagnosis of opportunistic infections requires a high index of suspicious. Without this curiosity, the clinician may not
consider mycotic infections in the compromised patient because:
- Patients present with atypical signs and symptoms
- Unusual histopathology
- The fungus may have an unusual organ affinity
- The etiological agent may be considered a saprophyte or contaminant
- The systemic mycoses may occur outside the known endemic area
- The serologic response may be suppressed
Causes of Immunodeficiency commonly encountered are:
- Malignancies (Leukemias, lymphomas, Hodgkin's Disease).
- In one study of cancer patients, fungal septicemia and pneumonias accounted for almost a third of deaths.
- Drug therapies. Anti-neoplastic substances, steroids, immunosuppressive drugs.
- Antibiotics. Over-use or inappropriate use of antibiotics can also contribute to the development of fungal
infections by altering the normal flora of the host and facilitating fungal overgrowth or by selecting for resistant
organisms.
Therapeutic Procedures can predispose for fungal infections;
- Solid Organ and Bone Marrow transplantation
- Open heart surgery
- Indwelling catheters (urinary, I.V. drugs or parenteral hyperalimentation). In cases of fungemia, the
contaminated catheter must be removed before starting anti-fungal therapy.
- Artificial heart valves can be colonized by a variety of infectious agents, including Candida species. In a case
of infection of an artificial heart valve, antifungal treatment is only efficient if the infected valve is replaced.
- Radiation therapy.
Other Factors Associated with increasing frequency of Mycotic infections is:
- Severe burns
- Diabetes
- Tuberculosis
- I.V. Drug use

- AIDS. Virtually all AIDS patients will have a fungal infections sometimes during the course of disease.
NOTE: Certain fungi may be frequently associated with some of the predisposing factors listed above. However any one
of the ubiquitous saprophytes (most of which do not cause disease in immunocompetent hosts) aw well as occasional
pathogens may cause disease in these patients.
BIOFILM
- It has long been recognized that in patients with a microbial infection, any artificial device such as an
indwelling catheter or prosthetic valve, must be removed before antibiotic therapy is effective. The foreign
body will act as a nidus, seeding the infection if it remains present. The exact mechanism is not clear. A
biofilm is a microcolony of organisms which adhere to a surface (catheter, implant, or dead tissue) and which
resist removal by fluid movement and have a decreased susceptibility to antimicrobials (figure 1). This biofilm
phenomenon, which occurs on the rocks in a stream, was first recognized as a public health problem in water
pipes and was regarded as a source of coliform contamination of drinking water. Recent work in clinical
microbiology has shown that these organisms develop a resistance to therapy because they are contained in
a matrix which acts like a tissue to and becomes a barrier to antibodies, macrophages and antimicrobial
agents.
- Candida species readily form biofilms and are the most prevalent organism isolated from catheters.
In Immunocompromised patients, common fungal infections may have an unusual presentation because of:
- Atypical signs and symptoms.
-limited disease in normal hosts
(Tinea versicolor) (figure 3), but in immunocompromised patients may show a rash with disseminated
disease and sepsis. This organism requires long-chain fatty acids for growth. Patients receiving
parenteral fat emulsions for nutrition become a walking petri plate.
- Unusual Organ affinity.
may invade liver, heart valves; Oral thrush (figure 4) occurs in people who are
relatively immunocompetent while esophageal candidiasis occurs in those patients who are
immunologically compromised. Cryptococcus may cause pulmonary, cutaneous and cardiac (figure
5A) infections.
- Infections with systemic dimorphic fungi occurring outside endemic areas. These factors complicate the
diagnosis and management of these disease.
- Unusual Histopathology.
iopsy specimens. The normal host reaction to

fungal invasion is usually pyogenic or granulomatous. In the immunodeficient host, the inflammatory
reaction is necrotic.
Immunocompromised Patients are at risk for:
- Systemic Invasive Aspergillosis
- Candidiasis
- Cryptoccocal meningitis
- Rhinocerebral/Horacic mucormycosis
1. Aspergillosis
• Acquired through inhalation of spores
• Common laboratory contaminant
• Growth rate: 3-10 days
• Clinical forms:
• Allergic forms ( allergic bronchopulmonary)
• The fungus grows in the bronchial tree
Granulomatous (Pulmonary)
- Necrotizing disease of the lungs which often disseminates hematogenusly to various organs (GIT, brain,
kidney, heart, skin, eye)
Fungus ball (or aspergilloma)
- Most common form f Pulmonary Aspergillosis
- Fungus taken u residence in an old lug cavity which are usually the result of old TB lesions
- Organisms remain in these cavities. It grows huge ass of mycellium -> FUNGUS BALL
Etiologic agent:
- A. Aspergillus fumigatus = most often seen in clinical laboratory
- B. Aspergilus flavus = causes oncomycosis
- C. Aspergilllus niger = major cause of otomycosis
- In tissue or sputum ( 10-20% KOH): HYALINE, DICHOTOMOUSLY BRANCHED, SEPTATE
HYPHAE
NOTE: A and B are clinically significant among o hosts who have undergone organ transplantation( bone marrow
transplant) and chemotherapy.
PAS = recommended to visualize the fungus on smear from internal organs
- Cultures are MONOMORPHIC on SDA at RT or at 35-37˚C

- Confirmatory test for ID: Based on microscopic morphology
Allergic Disease
Fungal Sinusitis:
- Previously, Aspergillus was thought to be the most common fungus responsible for allergic sinusitis, but it is
now appreciated that disease due to dematiaceous fungi actually comprises the majority of cases. The most
common are Bipolaris spp, Curvularia spp., Exserohilum spp. and Alternaria spp. This is a hypersensitivity
phenomenon and does not involve invasive disease. Diagnosis generally depends on demonstration of
allergic mucin, with or without actual culture of the organism. Therapy consists of surgery to remove the
mucin, which is often tenacious, and systemic steroids. Antifungal therapy, usually in the form of itraconazole,
may play a role in reducing the requirement for steroids, but this is not routinely recommended. Other azoles
have only rarely been used for this disease. Immunotherapy with weekly injections of fungal antigens have
shown promise in preliminary studies.
Allergic Bronchopulmonary Mycosis (ABPM):
- This is a fairly recent concept, similar in presentation to allergic bronchopulmonary aspergillosis (ABPA),
which is typically seen in patients with asthma or cystic fibrosis. The most common fungi are Bipolaris spp.
andCurvularia spp.Therapy is primarily systemic steroids, usually prednisone at 0.5 mg/kg/day for 2 weeks,
followed by a slow taper over 2-3 months or longer, if necessary. Itraconazole has been used as a steroid
sparing agent, but its efficacy is not clear and routine use of itraconazole is not generally recommended.
Sinus Fungus Balls
- Black fungi are also commonly responsible for sinus fungus balls,
including Bipolaris spp, Curvularia spp., Exserohilum spp., and Alternaria spp. Therapy consisting of surgical
resection of the fungus ball, and aeration of the sinus is generally curative. Unless invasion of the surrounding
mucosa or bone is demonstrated, antifungal agents do not appear to be of additional benefit.
Pneumonia
- Non-allergic pulmonary disease usually occurs in immunocompromised patients, and may be due to a wide
variety of species (including Bipolaris spp., Ochroconis, Galloparum, and Chaetomium spp.); in contrast to
allergic disease. However, cases in immunocompetent patients may also be seen. It is unclear what specific
risk factors may contribute to pulmonary infection with these fungi, which are commonly found in the
environment. Therapy usually consists of intravenous amphotericin B or oral itraconazole initially, followed by
itraconazole for a more prolonged period. Mortality rates are high in immunocompromised patients.
Experience with voriconazole and posaconazole is accumulating.
2. Candidiasis/ Monilliasis/ Mycotic vulvovginitis/ Candida endocarditis

- is a type of fungal infection due to any type of Candida.
Candida
- Normal flora of the skin, mouth, GIT and vagina
- It is not transmitted
- When local or host defense are impaired, disease may result
- Most frequently encountered opportunistic fungal infection
Clinical Formation:
- 1.Thrush = a disease of the oral mucous membrane
- 2. Nail infection (PARONYCHIA)
- 3. Mycotic Volvuvaginitis
Systemic Candidiasis (acute disseminated candidiasis)
is an infection of blood or other normally sterile site (e.g., pleural and peritoneal fluid) with Candida species,
usually in association with fever, hypotension, and/or leukocytosis. Candida organisms may be disseminated to multiple
sites, notably retina, kidney, liver and spleen, bones, and the central nervous system. Chronic disseminated candidiasis
usually implies involvement of liver and/or spleechronicn in association with recovery from chemotherapy-induced
neutropenia.(
sobel, J.D.,et.al.,2020.; Systemic Candidiasis. https://bestpractice.bmj.com/topics/en-us/1062)
- May caused pulmonary disease or endocarditis or may even evolved the meninge
- Etioloic agent:
- Microscopic features of Tissue forms:
0-20% KOH:
- Microscopic features from Culture:

Tween 80 for 24-72 hrs at RT
-Candida species = budding yeast cells only
- Confirmatory test on ID:
-37˚C 2 hrs.
= (+)A
-)
- Urine culture:
colony count of 104-105 colonies/ml indicates SYSTEMIC INFECTION
3. Zygomysis/ Phycomysis/ Mucormysis
- A systematic disease caused by a number of closely isolated fungi belonging to class phycomycetes
- 3 genera:
1. Rhizopus
NOTE: Mucor spp: No rhizoids or stolons
Rhizopus spp. : Unbranched sporangiophores with rhizoids where stolon arises
Absidia spp.: Rhizoids originates between sporangiophores
- Confirmatory test for ID:
characteristic morphological features
4. Cryptococcosis/ Torulosis/ European Blastomycosis
- Acute/ chronic pulmonary systemic or meningeal mycosis

- Transmitted through inhalation of spores from bird droppings (excreta of pigeons)
- Etiologic agent: Cryptococcus neoformans
Filobasidiella neoformans (sexual stage)
- Characteristic microscopic appearance: India Ink Wet mount:
-off” bud present on parent cell
- Most widely used method for rapid detection of C. neoformans in clinical specimen
mucoid colony (resembles Klebsiella)
- Confirmatory test for ID:
C. neoformans
-) = C. albicans
-)
- Final ID:
- Other Test for ID:
-DOPA Ferric Citrate Test
Result:
Indicates (+) for C. neoformans
SAPHROPHYTIC FUNGI COMMONLY ENCOUNTERED IN THE CLINICAL LABORATORY
1. HYALINE MOLD
- Characteristic Microscopic Appearance:
ube-like phialides,”conidia in clusters” at the tip of phialides
-like conidiophores”
– shaped macroconidia”
– like” structure
2. DEMATIACEOUS MOLD
- Over 100 species and 60 genera of dematiaceous, or pigmented fungi have been implicated in human
disease (Matsumoto T, Ajello L, Matsuda T, Szaniszlo PJ, Walsh TJ. Developments in hyalohyphomycosis and
phaeohyphomycosis. J Med Vet Mycol 1994; 32 Suppl 1:329-349.).
- The vast majority are filamentous fungi or moulds, though a few yeast species are also important pathogens.
Though they represent a very heterogeneous group of fungi, the distinguishing characteristic common to all
these various species is the presence of melanin in their cell walls, which imparts the dark color to their
conidia or spores and hyphae (Rinaldi MG. Phaeohyphomycosis. Dermatol Clin 1996; 14:147-153. [PubMed]).
- The colonies are typically brown to black in color as well. As the number of patients immunocompromised
from diseases and medical therapy increases, additional species are being reported as causes of human
disease, expanding an already long list of potential pathogens. As many of these are rarely seen clinically,
referral to a mycology reference lab may be needed to accurately identify isolates to species level.
EPIDEMIOLOGY
- Dematiaceous fungi are generally found in soil or associated with plants and distributed worldwide. Those causing the
specific conditions of mycetoma and chromoblastomycosis are primarily found in tropical regions. Occasionally, species
appear to be geographically restricted, such as Ramichloridium mackenzei, which has only been seen in patients from the
Middle East. Exposure is thought to be from inhalation or minor trauma, which may not even be noticed by the patient.
Surveys of outdoor air for fungal spores routinely observe dematiaceous fungi. As these are widespread in the
environment, individuals are constantly exposed to them, though they remain uncommon causes of disease
(http://www.antimicrobe.org/new/f05.asp).
CLINICAL MANIFESTATION
- A variety of infectious syndromes are attributed to dematiaceous fungi. Two unique conditions, mycetoma and
chromoblastomycosis, are caused by a small number of species and are usually seen in tropical regions . Mycetoma may
be caused by a variety of other pathogens as well, including Nocardia and non-dematiaceous fungi, though they will not
be discussed here. It is commonly associated with chronic swelling and draining sinus tracts, usually of the lower
extremities. It can be debilitating and difficult to treat. Chromoblastomycosis often presents with verrucous lesions that
may occur anywhere on the body, but usually on the lower extremities. This is a chronic, slowly progressive subcutaneous
mycosis. Minor trauma typically precedes the lesions. Initially, nodular lesions are present, which may progress over years
to form large, verrucous plaques. In contrast, phaeohyphomycosis is a catch-all term that encompasses many clinical
syndromes due to a wide variety of fungi. Conditions include superficial infections such as keratitis and subcutaneous
nodules, allergic diseases, and invasive infections such as brain abscess and disseminated disease. In general, these
diseases have been reported worldwide(http://www.antimicrobe.org/new/f05.asp).
LABORATORY DIAGNOSIS
- Unlike other more common fungal infections, there are no simple diagnostic tests to identify these fungi, particularly to
the
species level. No routine serologic, antigen or polymerase chain reaction (PCR) methods are available, which is at least
partly due to the tremendous diversity of these pathogens. However, studies have begun to examine the potential of
identifying species within this diverse group of fungi using PCR of highly conserved regions of ribosomal DNA (1).
Currently, the diagnosis of infection due to dematiaceous fungi relies on pathologic examination of clinical specimens and
careful gross and microscopic examination of cultures, occasionally requiring the expertise of a mycology reference lab for
unusual or newly described pathogens. In the case of mycetoma and chromoblastomycosis, pathognomonic histologic
findings are very useful. The presence of black mycotic granules or grains can establish the diagnosis of mycetoma due to
dematiaceous fungi. Histologically, they appear to be composed of fungal cells surrounded by a dense extracellular matrix
composed primarily of a melanin compound, which gives it a dark color. Chromoblastomycosis is characterized by the
production of characteristic dark sclerotic bodies in tissue, which are thick walled with septae. Phaeohyphomycosis does
not have such pathognomonic features, though the histologic appearance is often characterized by irregular hyphal
elements and beaded, yeast-like forms. However, it may still be difficult to differentiate this pathologically from infection
due to other moulds such as Aspergillus. In such cases, the Fontana-Masson stain, which is specific for melanin, can
usually be used to confirm the presence of dematiaceous hyphae (Rinaldi MG. Phaeohyphomycosis. Dermatol Clin 1996;
14:147-153. [PubMed]).
PATHOGENESIS
- Relatively little is known regarding the pathogenic mechanisms by which many of these fungi cause disease,
particularly in immunocompetent individuals. One of the likely candidate virulence factors is the presence of
melanin in the cell wall, which is common to all dematiaceous fungi. Melanin has been found to be an
important virulence factor in certain fungi, including Cryptococcus (C.) neoformans and Wangiella
(W.) dermatitidis, which is a dematiaceous yeast . In these fungi, disruption of specific genes involved in
melanin production leads to markedly reduced virulence in animal models.There are several mechanisms
proposed by which melanin may act as a virulence factor. It is thought to confer a protective advantage by
scavenging free radicals and hypochlorite that are produced by phagocytic cells in their oxidative burst that
would normally kill most organisms. In addition, melanin may bind to hydrolytic enzymes, thereby preventing
their action on the plasma membrane . These multiple functions may help explain the pathogenic potential of
some dematiaceous fungi, even in immunocompetent hosts. Another pathogenic mechanism is the production
of allergic disease. It is interesting to note that most allergic disease and eosinophilia is caused by two
genera, Bipolaris andCurvularia. These organisms are very common in the environment, so exposure is
practically universal. The virulence factors in these fungi that are responsible for eliciting allergic reactions are
unclear at present, though certain HLA-types have been associated
(http://www.antimicrobe.org/new/f05.asp).
SUSCETIBILITY IN VITRO AND IN VIVO
Single Drugs
- In vitro antifungal testing has only recently become standardized, and the first standardized method for
filamentous fungi was not available until 2002. As such, the available in vitro data for dematiaceous fungi is
relatively sparse, and often relies on small numbers of isolates per species. The past several years have seen
an increased interest in dematiaceous fungi, and reports of in vitro testing. An important caveat is that much
of the older literature is often inconsistent with regards to methodology, leading to difficulties in comparing
data. In addition, interpretive breakpoints are not available for most drugs and any of the dematiaceous
fungi, and clinical correlation data is practically non-existent. Therefore, suggestions regarding susceptibility are guidelines
only. Compared with in vitro data, animal studies with dematiaceous pathogens are even
more scarce, and only a few species have been studied(http://www.antimicrobe.org/new/f05.asp).
Amphotericin B
- Amphotericin B has in vitro activity against many clinically important dematiaceous fungi. However, some
species have been consistently resistant (minimum inhibitory concentration (MIC) ≥2 μg/mL),
including Scedosporium (S.) prolificans and Scopulariopsis (S.) brumptii. Other species have occasionally
found to be resistant, including Chaetomium spp., Curvularia spp., Phialemonium spp.,Exophiala spp.
and Ramichloridium (R.) mackenzei . However, use of lipid AmB preparations allows for much higher doses
than possible with standard AmB, which may improve their efficacy against these fungi. The
pharmacodynamics of these formulations are different from standard AmB and may also affect their overall
efficacy for specific infections . Animal studies have also suggested that amphotericin B is active against
some species, including murine models of infection with W. dermatitidis, F. pedrosoi C. bantiana,
andOchroconis (O.) gallopavum . In a study of murine infection with S. prolificans, use of liposomal
amphotericin B with granulocyte colony stimulating factor (G-CSF) was found to significantly prolong
survival. (http://www.antimicrobe.org/new/f05.asp).
Flucytosine (5- fluorocytosine; 5-FC)

- 5-FC is unique in its mechanism of action, inhibiting DNA and RNA synthesis. Concerns over the development
of resistance during monotherapy have resulted in its almost exclusive use in combination therapy for
systemic mycoses, most notably cryptococcal meningitis . Resistance is suggested with MICs ≥32 μg/mL. In
vitro studies with dematiaceous fungi are limited, though activity has been shown against C. bantiana,
Exophiala spp., and W. dermatitidis. In particular, good activity is present againstFonsecaea (F.) pedrosoi,
the major etiologic agent of chromoblastomycosis. Early animal studies demonstrated activity in murine
models of infection with W. dermatitidis, C. bantiana, Ochroconis (O.) gallopavum and F.
pedrosoi http://www.antimicrobe.org/new/f05.asp)..
Azoles
- Azoles were the first oral, broad spectrum antifungal agents available, and are widely used. As a group, they
are well-tolerated, but often have multiple drug interactions. Fluconazole will not be discussed below, as it
has negligible activity against dematiaceous moulds, and essentially no role in therapy given the variety of
other options available. http://www.antimicrobe.org/new/f05.asp).
Ketoconazole:
- Sparse in vitro data are available for this agent against dematiaceous fungi, but good activity is noted for the
most common fungi causing chromoblastomycosis and mycetoma. However, side-effects have significantly
limited its current use compared with the availability of newer agents that are much better tolerated. In
certain areas, due to the expense and lack of availability of newer agents, ketoconazole remains a useful
drug. http://www.antimicrobe.org/new/f05.asp).
Itraconazole:
- There has been extensive experience with itraconazole, though it is currently only available in oral
formulations in the U.S. Of the oral preparations, the capsules require an acidic environment for absorption,
while the suspension with cyclodextrin does not, being more consistently absorbed. Clinical use has declined
due lack of the intravenous form and an FDA black box warning regarding congestive heart failure and
significant drug interactions. Itraconazole has in vitro activity against the vast majority of dematiaceous
fungi, with MICs generally ≤0.125 μg/mL. Almost all the recent in vitro data with dematiaceous fungi includes
itraconazole. S. prolificans and S. brumptii are resistant http://www.antimicrobe.org/new/f05.asp).
Voriconazole:
- Voriconazole is one of the most widely used azoles due to its indication for aspergillosis, and is available in
both oral and IV forms. Similar to itraconazole, it has a broad spectrum of activity that includes most
dematiaceous fungi . Recently it has supplanted itraconazole as the drug of choice for these infections.
However, MICs for these fungi are usually slightly higher for voriconazole than itraconazole, though the
clinical significance of this is unclear. S. prolificans is generally resistant.
http://www.antimicrobe.org/new/f05.asp).
Posaconazole:
- Posaconazole is a broad spectrum azole similar in structure to itraconazole, though with more activity,
particularly against Aspergillus and other moulds. The published in vitro data is limited for dematiaceous
fungi, but good activity is demonstrated against most species tested, including Bipolaris spp., C.
bantiana, Phialophora spp. and R. mackenzei . As with other azoles, S. prolificans and S. brumptii are
resistant . Murine models have shown activity of posaconazole against R. mackenzei and Wangiellainfection.
http://www.antimicrobe.org/new/f05.asp).Ravuconazole: Ravuconazole is an investigational, broad-spectrum
azole with activity against a wide variety of moulds. In vitro activity is demonstrated
against Chaetomium spp., F. pedrosoi, and Phialophora spp. S. prolificans is resistant.
Isavuconazole:
- Isavuconazole is another investigational azole for which limited data have been published regarding
dematiaceous fungihttp://www.antimicrobe.org/new/f05.asp).
Terbinafine
- Terbinafine also inhibits ergosterol synthesis, but acts on squalene epoxidase, an enzyme two steps before
the target of azoles. It is also considered fungistatic, and its clinical role has been relegated to treatment of
dermatophyte infections. However, in vitro activity is quite broad and includes many non-dermatophyte
moulds There has been recent interest in potentially expanding its clinical spectrum However, its extensive
binding to serum proteins and distribution into skin and adipose tissue have diminished enthusiasm for its
use in treating serious systemic fungal infections In vitro studies against dematiaceous fungi are emerging
and fairly broad spectrum activity is seen. Genera affected include Alternaria, Curvularia, Phialophora,
and Bipolaris . C. bantiana, Ochroconis (O.) gallopavum, and W. dermatitidis were studied in mice though
terbinafine was found to be inactive in vivo, despite good in vitro activity
http://www.antimicrobe.org/new/f05.asp).
Echinocandins
- The echinocandins are the latest group of antifungals agents to be developed and have a unique mechanism
of action, inhibiting β-1,3 glucan synthesis and thereby disrupting the fungal cell wall . They are generally
well-tolerated.
Caspofungin:
- Caspofungin was the first of the class available for clinical use. In vitro studies with dematiaceous fungi are
limited, though some activity is demonstrated against Curvularia, Bipolaris, and F. pedrosoi C. bantiana has
higher MICs and S. prolificans appears resistant In general, MICs for dematiaceous fungi are higher than
for Aspergillus sp.
Micafungin:
- Micafungin has been evaluated against only a few species in vitro, with activity shown against C. bantiana, F.
pedrosoi, andExophiala (E.) spinifera . MICs may be somewhat lower than for caspofungin.
Anidulafungin:
- Anidulafungin is the most recently approved echinocandin and little in vitro data is available. There appears
to be some activity against Bipolaris and C. bantiana http://www.antimicrobe.org/new/f05.asp).
Combination Drugs
- This is a potentially useful strategy for refractory infections, though it has not been studied extensively in
dematiaceous fungi. The combination of itraconazole or voriconazole with terbinafine was found to be
synergistic against S. prolificans, which is otherwise generally resistant to all agents). The mechanism is
presumably potent inhibition of ergosterol synthesis at two different steps of the pathway by these agents.
However, this should be interpreted with caution, as terbinafine is not generally used for systemic
infections. Another report suggested synergy for S. prolificans with voriconazole and caspofungin . Animal
studies with C. bantiana show benefit with combination antifungal therapy over monotherapy, though it is
unclear which is the optimal combination. Older literature also suggests additive activity and synergy with 5-
FC and ketoconazole or amphotericin B for a variety of dematiaceous fungi.This may be applicable to other
azoles as well. http://www.antimicrobe.org/new/f05.asp).
Drug of Choice
- Voriconazole, posaconazole and itraconazole demonstrate the most consistent in vitro activity against this
group of fungi. Oral itraconazole had been considered the drug of choice for most situations, given its
extensive clinical experience . However, voriconazole is now preferred due to better tolerability, safety and
the availability of an intravenous formulation, and may have advantages for central nervous system
infections due to its ability to achieve good cerebrospinal fluid levels, unlike itraconazole. Posaconazole is a
broad-spectrum alternative that is well-tolerated, though with less clinical experience. All likely achieve
adequate brain tissue levels. http://www.antimicrobe.org/new/f05.asp).
- Alternaria sp.
e brown conidia resembling “drumstick”
- B. Cladosporium sp.
- C. Dreschlera (Helminthosporium)
MLS 0289 (Mycology and Virology-

Lecture)
STUDENT ACTIVITY SHEET BS MLS / THIRD YEAR
Session # 7
Materials:
Book, pen and notebook, index card/class list
LESSON TITLE: INTRODUCTION TO
References:
VIROLOGY LEARNING OUTCOMES:
1. Beneke, Everett (1999). Smith, Ph.D. Scope of
Upon completion of this lesson, the student shall be able to: Monograph on Human Mycoses, Kalamazoo, Michigan;
Upjohn Company
1. discuss the basic concepts and general features of DNA and 2. Bulmer, glenn(1995). Fungus Disease in the
RNA viruses, Orient,3rd ed. Manila: Rex Bookstore
2. classify different types of viruses as to DNA or RNA based on 3. McPherson and Pincus. (2018). HENRY’s Clinical
taxonomy and characteristics, Diagnosis and Management by Laboratory Methods
3. restate the replication and multiplication process of DNA and 23rd ed.,Singapore: Elsevier Pte.Ltd
RNA virueses.
MAIN LESSON (50 minutes)

BRIEF HISTORY
- 1884 = Chamberland –Pasteur Filter

- 1886 = Edward Mayer(Mosaic disease of Tobacco)
- 1892 = Dmitri Ivanovski( Tobacco sap)
- 1898 = Martinus Beijerinck (contigum vivum fluidum)
= Friedrich Loeffler and Paul Frosch.(1st animal virus;FMD)
= G. Sanarelli ( Smallpox virus and myxoma virus of rabbits)
- 1901 = Walter Reed ( 1st human virus reported ; yellow fever)
- 1881 = Carlos Finlay ( hypothesis on disease caused by Mosquito bite; Aedes aegyptii)
Chamberland-Pasteur Filter
TERMS/TERMINOLOGIES
- VIRION
 Virus particle
 complete infectious unit of a virus particle
 structurally mature, extracellular virus particle
- CAPSID
 protein which coats the nucleic acid genome
- NUCLEOCAPSID
 capsid + genome
- CAPSOMERES
 the individual sub units of a capsid
 can be an icosahedral or irregular in shape
DISTINGUISHING CHARACTERISTIC OF A VIRUS

- 1. Obligate intracellular parasites
- 2. Extreme genetic simplicity
- 3. Contain DNA or RNA
- 4. Replication involves disassembly and reassembly
- 5. Replicate by one-step growth
HOW VIRUSES ARE NAMED?

BASED ON!
- 1. the disease they cause;

 Ex. Poliovirus, rabies virus
- 2. the type of disease
 Ex. Murine leukemia virus
- 3. the geographic location
 Ex. Sendai virus, Coxsackie virus
- 4. their discoverer
 Ex. Epsteinn- Barr virus
- 5.how they were originally thought to be contracted
 Ex. Dengue virus( "evil spirit"); influenza virus ("the influence of bad air")
- 6.combination of the above
 Ex. Rous sarcoma virus
VIRAL
REPLICATION
TRANSMISSION OF VIRUS
- Respiratory transmission
Ex. Influenza
- Faecal-Oral transmission
Ex. Enterovirus
- Blood-borne transmission
Ex. Hepatitis B
- Sexual Transmission
Ex. HIV
- Animal or insect transmission
Ex. Rabies virus
Bacteriophage
- A bacteriophage is any one of a number of viruses that infect bacteria.
- They do this by injecting genetic material, which they carry enclosed in an outer protein capsid.
- The genetic material can be ssRNA, dsRNA, ssDNA, dsDNA (‘ss’- or ‘ds’- prefix denotes singles-strand or double- strand)
along with either circular or linear arrangement.
Sub-Viral - Viroids
Agents
- Satellite
 May be encapsidated (satellite virus)
 Mostly in plants, can be human e.g. hepatitis delta virus
 Contain nucleic  If nucleic acid only-virusoid
acid
 Depend on co-  Unencasidated , small circular ssRNA molecules that replicate autonomously
infection with a  Only in plants, e.g. potato spindle tuber viroid
helper virus  Depend on host cell poll for replication, no protein or mRNA
 ssRNA genome and the smallest known pathogens
- Prions
 No nucleic acid
 Infectious protein e.g. BSE
 Infectious particle that are entirely protein
 Highly heat resistant
 Animal disease that affect nervous tissue
 Are rather ill-defined infectious agents believed to consist of a single type of protein molecule with no
nucleic acid component.
 Confusion arises from the fact that the prion protein & gene which encodes it are also found in normal
“uninfected cells”.
 Affects nervous tissue and results in
 Bovine Spongiform Encephalitis (BSE) “mad cow disease”
 Scrapie in sheep
 Kuri & Creutzfeld-Jacob Disease (CJD) in humans
- Dependovirus/ Virusoids
 Virusoids are small (200-400nt), circular RNA molecules with a rod-like secondary structure which possess
no capsid or envelope which are associated with certain plant diseases.
 Their replication strategy like that of viruses- they are obligate intracellular parasites.
CHECK FOR UNDERSTANDING (25 minutes)
Answer the following questions:
1. The purified form of RNA negative sense is noninfectious by itself: TRUE or FALSE
2. A viral genome which can be automatically considered as mRNA
3. Who coined the term Virus?
4. what is the Swahili term for “Dengue” and what is it’s meaning?
5. Illustrate and label the complete viral structure
Lesson Wrap Up:
Viruses enters the body of the host in a variety of ways:

- The commonest form of viral transmission are via:
1. Inhaled droplets (in sneezing or coughing) – ex. Common colds or influenza , COVID 19
2. Drinking water or eating raw foods - ex. Hepatitis A, Polio virus
3. Sexual intercourse - ex. HIV, Hepatitis B
4. Vertical Transmission 9 mother to fetus) - ex. HIV, Hepatitis B, Rubella
5. Vector bites (arthropods/mosquitoes) - ex. Yellow fever, Rift Valley fever, Dengue.
Most viral infections no not lead to such serious complications and the host:
- 1. Get well after a period of sickness to be immune for the rest of their lives:
Ex. Measles infection, Rubella or German Measles, Mumps, etc.
MLS 0289 (Mycology and Virology- Lecture)
BS MLS / THIRD YEAR
STUDENT ACTIVITY SHEET Session # 8
LESSON TITLE: RNA CONTAINING VIRUS ( RABIES Materials:

VIRUS)
Book, pen and notebook, index card/class list
LEARNING OUTCOMES:
References:
Upon completion of this lesson, the student shall be able to:
1. Kasper, Dennis L. et al. “Harrison’s Principle of
1. identify the mode of transmission of RNA containing Internal Medicine” 19th ed.
virus (RABIES VIRUS).
2. summarize different laboratory diagnosis both virolocal and 2. McPherson and Pincus. (2018). HENRY’s Clinical
serological method. Diagnosis and Management by Laboratory Methods
3. practice consistently the ways and means on how to prevent 23rd ed.,Singapore: Elsevier Pte.Ltd.
control viral infection.
4. discuss the epidemiology, clinical stages and
pathogenesis of rabies virus. Internet Source: RITM, ‘Escaping Rabies’ Death
5. illustrate viral structure of rabies virus. Crawl: PH’s Combat against the deadly disease.
6. know the ways and means on treatment, prevention and Volume 1, Issue 2 (July -Sept. 2014).
control of rabies virus infection. http://ritm.gov.ph/escaping-rabies-death-crawl-
7. know the established facts about rabies cases in the phs-combat-against-the-deadly-disease/.
Philippines.
RABIES
- is a rapidly progressive, acute infectious disease of the CENTRAL NERVOUS SYSTEM (CNS) in humans and animals that is caused
by infection with rabies virus
- 2 FORMS:
 encephalitic (80%)
 paralytic (20%)
- The infection is normally transmitted from animal vectors. Rabies has encephalitic and paralytic forms that progress to death.
- SYNAPSES - sites of functional apposition where signals are transmitted from one neuron to another or from a neuron to
another type of cell
-
- CLASSIFICATION
 Site of synaptic contact
 Axodendritic synapses
 Axosomatic synapses
 Axoaxonic synapses
 Dendrodendritic synapses
- CLASSIFICATION
 Method of Signal Transmission
 Chemical synapse (neurotransmitter)
 Neuron-neuron; neuron-muscle
 Delay by 0.5 ms
 Electrical synapse
 Gap junctions; nearly instantaneous transmission
 Less common
- ETIOLOGIC AGENT
- Rabies virus is a member of the family Rhabdo viridae. Two genera in this family, Lyssavirus and Vesiculovirus, contain species that
cause human disease. Six other non–rabies virus species in the Lyssavirus genus have been reported to cause a clinical picture
similar to rabies. Vesicular stomatitis virus, a vesiculo virus, causes vesiculation and ulceration in cattle, horses, and other animals
and causes a self-limited, mild, systemic illness in humans.
RABIES VIRUS STRUCTURE
- Rabies virus is a lyssavirus that infects a broad range of animals and causes serious neurologic disease when transmitted to
humans. Rhabdo virions are enveloped, with bullet shaped and bacilliform geometries. This single- strand RNA virus has a non
segmented, negative sense (antisense) genome that consists of 11,932 nucleotides and encodes 5 proteins: nucleocapsid protein,
phosphoprotein, matrix protein, glycoprotein, and a large polymerase protein.
EPIDEMIOLOGY
- Rabies is present on all continents with the exception of Antarctica, but more than 95% of human deaths occur in
ASIA and AFRICA
- DOGS are the source of the vast majority of human rabies deaths, contributing up to 99% of all rabies transmissions to humans.
However bats, raccoons, skunks, foxes, and coyotes are also known to be important reservoirs of the disease.
- 40% of people who are bitten by suspect rabid animals are children under 15 years of age.
TRANSMISSION
- Rabies is a ZOONOTIC DISEASE.
- Rabies is usually transmitted through the SALIVA of the host animal (or person), usually via a BITE OR SCRATCH.
- All WARM-BLOODED species, including humans, may become infected with the rabies virus and develop symptoms.
- Human-to-human transmission is extremely rare.
NOTE: Transmission of rabies virus usually begins when infected saliva of a host is passed to an uninfected animal. The
most common mode of rabies virus transmission is through the bite and virus-containing saliva of an infected host.
Transmission has resulted from corneal transplantation and also from solid organ transplantation and a vascular conduit
(for a liver transplant) from undiagnosed donors with rabies in Texas, Florida,
and Germany.
PATHOGENESIS:
- The incubation period of rabies (defined as the interval between exposure and the onset of clinical disease) is usually 20–90 days
but in rare cases is as short as a few days or >1 year. During most of the incubation period, rabies virus is thought to be present at
or close to the site of inoculation.
- In muscles, the virus is known to bind to nicotinic acetylcholine receptors on postsynaptic membranes at neuromuscular junctions,
but the exact details of viral entry into the skin and SC tissues have not yet been clarified.
- Rabies virus spreads centripetally along peripheral nerves toward the CNS at a rate of up to ~250 mm/d via retrograde fast
axonal transport to the spinal cord or brainstem.
- Once the virus enters the CNS, it rapidly disseminates to other regions of the CNS via fast axonal transport along neuroanatomic
connections. Neurons are prominently infected in rabies; infection of astrocytes is unusual.
- After CNS infection becomes established, there is centrifugal spread along sensory and autonomic nerves to other tissues,
including the salivary glands, heart, adrenal glands, and skin.
- Rabies virus replicates in acinar cells of the salivary glands and is secreted in the saliva of rabid animals that serve as vectors of
the disease.
- There is no well-documented evidence for hematogenous spread of rabies virus. Pathologic studies show mild inflammatory
changes in the CNS in rabies, with mononuclear inflammatory infiltration in the leptomeninges, perivascular regions, and
parenchyma, including microglial nodules called Babes nodules.
- Degenerative neuronal changes usually are not prominent, and there is little evidence of neuronal death; neuronophagia is
observed occasionally.
- The pathologic changes are surprisingly mild in light of the clinical severity and fatal outcome of the disease. The most
characteristic pathologic finding in rabies is the Negri body. Negri bodies are eosinophilic cytoplasmic inclusions in brain neurons
that are composed of rabies virus proteins and viral RNA.
- These inclusions occur in a minority of infected neurons, are commonly observed in Purkinje cells of the cerebellum and in
pyramidal neurons of the hippocampus, and are less frequently seen in cortical and brainstem neurons. Negri bodies are not
observed in all cases of rabies.
- The lack of prominent degenerative neuronal changes has led to the concept that neuronal dysfunction—rather than neuronal
death—is responsible for clinical disease in rabies.
- The basis for behavioral changes, including the aggressive behavior of rabid animals, is not well understood.
CLINICAL STAGES
- The clinical features of rabies begin with nonspecific prodromal manifestations, including fever, malaise, headache, nausea, and
vomiting. Anxiety or agitation may also occur. The earliest specific neurologic symptoms of rabies include paresthesias, pain, or
pruritus near the site of the exposure, one or more of which occur in 50–80% of patients and strongly suggest rabies. The wound
has usually healed by this point, and these symptoms probably reflect infection with associated inflammatory changes in local
dorsal root or cranial sensory ganglia.
- Two Acute Neurologic Forms:
 1. Encephalitic (furious) in 80% rabies
 Automatic dysfunction is commn and may result in episodes of hyperexcitability, gooseflesh, cardiac
arrhytmia,priapism, hydrophobia, aerophobia. The combination of hypersalivation and pharyngeal dysfunction is
also responsible for the classic appearance of “foaming at the mouth.”
 Episodes including fever, confusion, hallucinations, combativeness, and seizures
 Rabies encephalitis is distinguished by early brainstem involvement, which results in the classic features of
hydrophobia (involuntary, painful contraction of the diaphragm and accessory respiratory, laryngeal, and pharyngeal
muscles in response to swallowing liquids) and aerophobia (the same features caused by stimulation from a draft of
air). These symptoms are probably due to dysfunction of infected brainstem neurons that normally inhibit inspiratory
neurons near the nucleus ambiguous, resulting in exaggerated defense reflexes that protect the respiratory tract.
The combination of hypersalivation and pharyngeal dysfunction is also responsible for the classic appearance of
“foaming at the mouth”. Brainstem dysfunction progresses rapidly, and coma—followed within days by death—is
the rule unless the course is prolonged by supportive measures. With such measures, late complications can include
cardiac and/or respiratory failure, disturbances of water balance (syndrome of inappropriate antidiuretic hormone
secretion or diabetes insipidus), noncardiogenic pulmonary edema, and gastrointestinal hemorrhage. Cardiac
arrhythmias may be due to dysfunction affecting vital centers in the brainstem or to myocarditis. Multiple-organ
failure is common in patients treated aggressively in critical care units.
 2. Paralytic Rabies
 ( About 20% of patients have paralytic rabies in which muscle weakness predominates and cardinal features
of encephalitic rabies (hyperexcitability, hydrophobia, and aerophobia) are lacking.
 There is early and prominent flaccid muscle weakness, often beginning in the bitten extremity and spreading
to produce quadriparesis and facial weakness. Sphincter involvement is common, sensory
involvement is usually mild, and these cases are commonly misdiagnosed as Guillain-Barre
syndrome.
 Patients with paralytic rabies generally survive a few days longer than those with encephalitic rabies, but
multiple-organ failure nevertheless ensues.
NOTE  Brainstem dysfunction progresses rapidly, and coma-followed within days by death-is the rule
unless the course is prolonged by supportive measures.
:  The perivascular cuff composed of primarily lymphocytes. This is typical of the nonsuppurative inflammation
seen in many viral infections.
 Typically there is a mild cellular infiltrate of mainly lymphocytes admixed with plasma cells in the
leptomeninges
 Remember that the glial nodule is an accumulation of microglial cells (possible admixed with other cell types).
 Negri bodies round or oval inclusion bodies seen in the cytoplasm and sometimes in the processes of neurons
of rabid animals after death. Negri bodies are eosinophilic, sharply outlined, pathognomonic inclusion bodies
(2-10 um in diameter) found in the cytoplasm of certain nerve.
LABORATORY INVESTIGATION AND DIAGNOSIS
TREATMENT
- There is no established treatment for rabies. There have been many recent treatment failures with the combination of antiviral
drugs, ketamine, and therapeutic (induced) coma—measures that were used in a healthy survivor in whom antibodies to rabies
virus were detected at presentation. Expert opinion should be sought before a course of experimental therapy is embarked upon.
A palliative approach may be appropriate for some patients.
PREVENTION
- Postexposure Prophylaxis - Since there is no effective therapy for rabies, it is extremely important to prevent the disease
after an animal exposure.
- Since there is no effective therapy for rabies, it is extremely important to prevent the disease after an animal exposure.
- On the basis of the history of the exposure and local epidemiologic information, the physician must decide whether initiation of
PEP is warranted. Healthy dogs, cats, or ferrets may be confined and observed for 10 days. PEP is not necessary if the animal
remains healthy.
- If the animal develops signs of rabies during the observation period, it should be euthanized immediately; the head should be
transported to the laboratory under refrigeration, rabies virus should be sought by DFA testing, and viral isolation should be
attempted by cell culture and/or mouse inoculation.
- Any animal other than a dog, cat, or ferret should be euthanized immediately and the head submitted for laboratory examination.
In high-risk exposures and in areas where canine rabies is endemic, rabies prophylaxis should be initiated without waiting for
laboratory results. If the laboratory results prove to be negative, it may safely be concluded that the animal’s saliva did not contain
rabies virus, and immunization should be discontinued.
- If an animal escapes after an exposure, it must be considered rabid, and PEP must be initiated unless information from public
health officials indicates otherwise (i.e., there is no endemic rabies in the area).
- Although controversial, the use of PEP may be warranted when a person (e.g., a small child or a sleeping adult) has been present
in the same space as a bat and an unrecognized bite cannot be reliably excluded. PEP includes local wound care and both active
and passive immunization.
- Local wound care is essential and may greatly decrease the risk of rabies virus infection. Wound care should not be delayed, even
if the initiation of immunization is postponed pending the results of the 10-day observation period. All bite wounds and scratches
should be washed thoroughly with soap and water. Devitalized tissues should be debrided, tetanus prophylaxis given, and
antibiotic treatment initiated whenever indicated.
- All previously unvaccinated persons (but not those who have previously been immunized) should be passively immunized with
rabies immune globulin (RIG). If RIG is not immediately available, it should be administered no later than 7 days after the first
vaccine dose. After day 7, endogenous antibodies are being produced, and passive immunization may actually be
counterproductive. If anatomically feasible, the entire dose of RIG (20 IU/kg) should be infiltrated at the site of the bite; otherwise,
any RIG remaining after infiltration of the bite site should be administered IM at distant site. With multiple or large wounds, the
RIG preparation may need to be diluted in order to obtain a sufficient volume for adequate infiltration of all wound sites.
- If the exposure involves a mucous membrane, the entire dose should be administered IM. Rabies vaccine and RIG should never
be administered at the same site or with the same syringe.
- Commercially available RIG in the United States is purified from the serum of hyperimmunized human donors. These human RIG
preparations are much better tolerated than are the equine-derived preparations still in use in some countries. Serious adverse
effects of human RIG are uncommon.
- Local pain and low-grade fever may occur. Two purified inactivated rabies vaccines are available for rabies PEP in the United
States. They are highly immunogenic and remarkably safe compared with earlier vaccines. Four 1-mL doses of rabies vaccine
should be given IM in the deltoid area. (The anterolateral aspect of the thigh also is acceptable in children.) Gluteal injections,
which may not always reach muscle, should not be given and have been associated with rare vaccine failures. Ideally, the first dose
should be given as soon as possible after exposure; failing that, it should be given without further delay.
- The three additional doses should be given on days 3, 7, and 14; a fifth dose on day 28 is no longer recommended. Pregnancy is
not a contraindication for immunization. Glucocorticoids and other immunosuppressive medications may interfere with the
development of active immunity and should not be administered during PEP unless they are essential. Routine measurement of
serum neutralizing antibody titers is not required, but titers should be measured 2– 4 weeks after immunization in
immunocompromised persons. Local reactions (pain, erythema, edema, and pruritus) and mild systemic reactions (fever, myalgias,
headache, and nausea) are common; anti-inflammatory and antipyretic medications may be used, but immunization shouldnot be
discontinued. Systemic allergic reactions are uncommon, but anaphylaxis does occur rarely and can be treated with epinephrine
and antihistamines.
- The risk of rabies development should be carefully considered before the decision is made to discontinue vaccination because of
an adverse reaction. Most of the burden of rabies PEP is borne by persons with the fewest resources. In addition to the rabies
vaccines discussed above, vaccines grown in either primary cell lines (hamster or dog kidney) or continuous cell lines (Vero cells)
are satisfactory and are available in many countries outside the United States. Less expensive vaccines derived from neural tissues
are still used in a diminishing number of developing countries;
however, these vaccines are associated with serious neuroparalytic complications, including postinfectious
encephalomyelitis and Guillain-Barre syndrome.
- The use of these vaccines should be discontinued as soon as possible, and progress has been made in this regard. Worldwide, >10
million individuals receive postexposure rabies vaccine each year. If human RIG is unavailable, purified equine RIG can be used in
the same manner at a dose of 40 IU/kg. Before the administration of equine RIG, hypersensitivity should be assessed by
intradermal testing with a 1:10 dilution.
- The incidence of anaphylactic reactions and serum sickness has been low with recent equine RIG products.
- Preexposure Rabies vaccination

 should be considered for people with an occupational or recreational risk of rabies exposures, including certain travelers
to rabies-endemic areas. The primary schedule consists of three doses of rabies vaccine given on days 0, 7, and 21 or 28.
Serum neutralizing antibody tests help determine the need for subsequent booster doses. When a previously immunized
individual is exposed to rabies, two booster doses of vaccine should be administered on days 0 and 3. Wound care
remains essential. As stated above, RIG should not be administered to previously vaccinated persons.
RABIES CASES IN THE PHILIPPINES (AN IMPORTANT FACT)

- Rabies continues to be a prevalent public threat in the Philippines. The Philippines ranks among the highest in the world in terms
of rabies prevalence. The DOH accounts that around 200 to 300 Filipinos die of rabies every year. The Philippine government aims
to bring these figures down to zero. In 2007, the government passed the Anti-Rabies Act (RA 9482), a law that calls for the control
and elimination of human and animal rabies. It mandated the creation of the National Rabies Prevention and Control Program
(NRPCP), a multi- agency/multi-sector initiative that targets to eliminate human rabies by 2016, and declare a rabies-free
Philippines by 2020.
- The main component activities of this program are:
 Mass vaccination of dogs;
 Establishment of a central database system or registration and vaccinated dogs;
 Impounding field control and disposition of unregistered, stray and unvaccinated dogs;
 Information and education campaign on the prevention and control of rabies;
 Provision of pre-exposure treatment to high-risk personnel and Post Exposure Treatment to animal bite victims;
 Provision of free immunization or Pre-Exposure Prophylaxis of school children aged five to fourteen in areas where
there is high incidence of rabies;
 Encouragement of the practice of responsible pet ownership
 Provides support services in the form of capacity-building.
- Since the launch of the NRPCP, the number of deaths due to rabies has slowly dropped. From 257 deaths in 2010, it went down
to 187 last year. The number of human rabies cases has also dropped by 27 percent from 2010-2013.
- SOURCE: RITM, ‘Escaping Rabies’ Death Crawl: PH’s Combat against the deadly disease. Volume 1, Issue 2 (July - Sept. 2014).
http://ritm.gov.ph/escaping-rabies-death-crawl-phs-combat-against-the-deadly-disease/.
-
1. What are the 2 forms of Rabies infection:

2. Is rabies infection curable?
3. Why is RA 9482 limits only the provision of free immunization or Pre-Exposure Prophylaxis of school children aged five to fourteen
in areas where there is high incidence of rabies?
4. Illustrate and label the complete viral structure OF Rabies virus
Lesson Wrap Up 10 Minutes:

- Rabies claims a person’s life every 10 minutes, according to the United States Centers for Disease Control and Prevention (CDC).
- Most of these death incidents happen in Asia and Africa with children aged below 15 years old comprising more than half of the
deaths.
- Rabies is a viral disease that attacks the central nervous system. It is transmitted to a person through a bite of an infected animal.
- All warm blooded mammals may carry the rabies virus, but dogs account for the most number of reported rabies cases. Other
animals such as cats also contribute to the virus transmission.
- Once a person is bitten by a rabid animal and the victim was not vaccinated, the rabies virus will travel from the site of the bite to
the victim’s brain. As it reaches the human nervous system, it becomes 100% fatal.
- As the rabies virus goes on a death crawl to the brain, the victim will feel the initial symptoms such as a high temperature of 38ºC,
chiils, fatigue, irritability, anxiety and vomiting. After 2 to 10 days, more severe symptoms will start to manifest
including aggressive behavior such as biting, excessive salivation, hallucination, hydrophobia, aerophobia and muscles
spasm.
- When these symptoms start, death is fast approaching.

- Rabies is tagged by the Global Alliance for Rabies Control as the “Deadliest Disease on Earth”. Although extensive
research has been done on rabies, scientist have not yet developed a cure once the virus reaches the human nervous
system RITM, ‘Escaping Rabies’ Death Crawl: PH’s Combat against the deadly disease. Volume 1, Issue 2 (July -Sept. 2014).
http://ritm.gov.ph/escaping-rabies-death-crawl-phs-combat-against- the-deadly-disease/
MLS 0289 (Mycology and Virology-
Lecture)
BS MLS / THIRD YEAR
STUDENT ACTIVITY SHEET
Session # 9
LESSON TITLE: RNA CONTAINING VIRUS Materials:

(PARAMYXOVIRUSES VIRUS) Book, pen and notebook, index card/class list
LEARNING OUTCOMES:
References:
1. identify the mode of transmission of RNA containing Internet Source:

virus (PARAMYXOVIRUES VIRUS). https://www.ncbi.nlm.nih.gov/books/NBK8461/
2. summarize different laboratory diagnosis both virolocal and
serological method. 1. Anderson LJ, Heilman CA. Protective and disease-
3. practice consistently the ways and means on how to prevent enhancing immune responses to respiratory
control viral infection. syncytial virus. J Infect Dis. 1995;171:1. [PubMed]
4. discuss the epidemiology, clinical stages and 2. Baron, D. (1996).Medical Microbiology, 4th ed.
pathogenesis of rabies virus. University of Texas Medical Branch at Galveston 3.CDC
5. illustrate viral structure of rabies virus. Measles-United States, 1994. MMWR.
6. know the ways and means on treatment, prevention and 1995;44(26):486. [PubMed]
control of paramyxoviruses virus infection.
SUBJECT INTRODUCTION (10 minutes)

The teacher will start the lesson by introducing to the students the general concepts of paramyxoviruses.
Paramyxoviruses
- The family Paramyxoviridae consists of three genera: Paramyxovirus, which includes the parainfluenza viruses and mumps
virus; Pneumovirus, which includes respiratory syncytial virus; and Morbillivirus, which includes the measles virus.
- The family Paramyxoviridae consists of three genera: Paramyxovirus, Pneumovirus, and Morbillivirus .
- All members of the genus Paramyxovirus share similar properties. Pneumoviruses lack hemagglutinin and neuraminidase
activity. They also differ from other paramyxoviruses in morphology (diameter of nucleocapsid and surface projections).
Morbillivirus is distinguished by the absence of neuraminidase in the virions and by the presence of common envelope and
nucleocapsid antigens
VIRAL STRUCTURE
- All paramyxoviruses are enveloped particles 150 to 300 nm in diameter.
 The tubelike, helically symmetrical nucleocapsid contains a monopartite, single-stranded, negative-sense RNA
genome and an RNA-directed RNA polymerase.
 The nucleocapsid associates with the matrix protein (M) at the base of a double-layered lipid envelope.
 The spikes on the envelope contain two glycoproteins, a viral attachment protein, and a fusion protein.
- The paramyxoviruses can be distinguished by the gene order for the viral proteins and by the biochemical properties for
their viral attachment proteins.
 In parainfluenza viruses, the viral protein spikes have hemagglutinating and neuraminidase activities (HN). –
 Respiratory syncytial virus lacks both these activities and measles virus lacks neuraminidase but has
hemagglutinating activity.
- All paramyxoviruses are labile to very labile and quickly inactivated, e.g. by heat, organic solvents, detergents, ultraviolet, or
visible light, and low pH value.
ILLUSTRATION
SOURCE: Lamb, R.A., et.al. Paramyxoviridae . https://basicmedicalkey.com/paramyxoviridae/
- Paramyxoviruses contain nonsegmented single-stranded RNA genomes of negative polarity and replicate entirely in the
cytoplasm. Their genomes are 15 to 19 kB in length, and the genomes contain 6 to 10 tandemly linked genes. A lipid envelope
containing two surface glycoproteins (F and a second glycoprotein variously referred to as HN, or H or G) surrounds the virions.
Inside the envelope lies a helical nucleocapsid core containing the RNA genome and the nucleocapsid (N), phospho- (P), and
large (L) proteins, which initiate intracellular virus replication. Residing between the envelope and the core lies the viral matrix
(M) protein that is important in virion architecture, and which is released from the core during virus entry. In addition to the
genes encoding structural proteins, paramyxoviruses contain “accessory” genes that are found mostly as additional
transcriptional units interspersed with the tandemly linked invariant genes. For the Paramyxovirinae, the accessory genes are
found mostly as open reading frames (ORFs) that overlap within the P gene transcriptional unit Lamb, R.A., et.al.
Paramyxoviridae . https://basicmedicalkey.com/paramyxoviridae/.
Multiplication
- The multiplication of all paramyxoviruses is similar to that of orthomyxoviruses except that the paramyxovirus genome is
monopartite.
EXAMPLES OF THE MEMBERS OF THE FAMILY PARAMYXOVIRIDAE

- Family Paramyxoviridae : Subfamily Paramyxovirinae
 Genus Rubulavirus
 Mumps virus (Mu V)
 Parainfluenza virus type 5 (previously called simian virus 5 [SV5] (PIV5))
 Human parainfluenza virus type 2, types 4a and 4b (HPIV2/4a/4b)
 Genus Mapuera virus
 Porcine rubulavirus (La-Piedad-Michoacan-Mexico virus)
 Genus Avulavirus
 Newcastle disease virus (avian paramyxovirus 1) (NDV)
 Genus Respirovirus
 Sendai virus (mouse parainfluenza virus type 1) (SeV)
 Human parainfluenza virus type 1 and type 3 (HPIV1/3)
 Bovine parainfluenza virus type 3(bPIV3)
 Genus Henipaviruses
 Hendra virus (HeV)
 Nipah virus (NiV)
 Genus Ferlavirus
 Fer-de-Lance virus (FDLV)
 Genus Aquaparamyxovirus
 Atlantic salmon paramyxovirus
 Genus Morbillivirus
 Measles virus (MeV)
 Cetacean morbillivirus
 Canine distemper virus (CDV)
 Peste-des-petits-ruminants virus
 Phocine distemper virus
 Rinderpest virus
- Family Paramyxoviridae: Subfamily Pneumovirinae
 Genus Pneumovirus
 Human respiratory syncytial virus A2, B1, S2 (HRSV)
 Bovine respiratory syncytial virus (BRSV)
 Pneumonia virus of mice (PVM)
 Genus Metapneumovirus
 Human metapneumovirus (HMPV)
 Avian metapneumovirus
- Unclassified paramyxoviruses
 Tupaia paramyxovirus (TPMV)
 Menangle virus (MenV)
 Tioman virus (TiV)
 Beilong virus
 J virus
 Mossman virus (MoV)
 Salem virus (SaV)
 Nariva virus
NOTE: Of all the virus listed above, in this module emphasis will be given to the clinically significant/ often encountered
paramyxoviruses
PARAINFLUENZA VIRUS
Clinical Manifestation
- Parainfluenza viruses cause approximately 30 to 40 percent of all acute respiratory infections in infants and children. The
spectrum of disease ranges from a mild, febrile common cold to severe, potentially life-threatening croup, bronchiolitis, and
pneumonia. Types 1 to 3 are the most common identifiable agents of croup and are surpassed only by respiratory syncytial
virus as the cause of severe lower respiratory tract disease in infants. Reinfection, causing milder upper respiratory illness, is
common in older children and adults. Type 4 causes usually only mild upper respiratory infection in children and adults, but
severe symptoms can occur in infants.
Structure
- The virions are enveloped particles with an average diameter of 120 to 300 nm. The complete virion consists of a nucleocapsid
and an envelope. The 12-18-nm-wide nucleocapsid is a tubelike structure with helical symmetry. It contains one molecule of
single-stranded generally negative-sense RNA (molecular weight 5-8 × 106), the major nucleoprotein (NP), the
phosphoprotein P and the L protein. The L protein is the RNA polymerase which is necessary for transcription of viral RNA.
The P protein facilitates RNA synthesis and the NP protein helps to maintain genome structure. The envelope is a double-
layered membrane covered with spikes. It contains lipoproteins and glycoproteins, as well as lipids derived mainly from the
host cell. The nonglycosylated matrix protein (M) is attached to the inner side of the envelope, the two glycoproteins that
form the spikes contain the hemagglutinin and neuraminidase (HN) and the cell fusion protein (F), which is activated by
proteolytic cleavage.
Classification and Antigenic Type
- Among the paramyxoviruses four human parainfluenza serotypes are now recognized: 1, 2, 3, and 4. Type 4 occurs in two
subtypes (A and B), which possess common internal but different capsid antigens.
Multiplication
- Parainfluenza viruses attach to the host cell by the hemagglutinin, which binds to the host cell neuraminic acid receptor, and
then penetrate the cell by fusion with the cell membrane mediated by the F1 and F2 glycopeptides. The viral particles contain
single-stranded negative-sense RNA, which cannot serve as a messenger. The virion transcriptase initiates transcription into
5-8 complementary messenger positive-sense RNA strands. They direct the viral protein synthesis and are copied into
negative-sense RNA strands which are integrated in the new virions. For envelopment, the virus-specific glycoproteins
accumulate in the cell membrane. Assembly is completed by budding of the nucleocapsid through the cell membrane studded
with glycoproteins.
Pathogenesis
- The parainfluenza viruses generally initiate localized infections in the upper and lower respiratory tracts without causing
systemic infection, although viremia may occur. Local and serum antibodies develop after primary infection. The resulting
immunity is not adequate to prevent reinfection, but does provide some protection against disease.
- These viruses first infect the ciliated epithelial cells of the nose and throat. Infection may extend to the paranasal sinuses, the
middle ear, and occasionally to the lower respiratory tract. Progeny viruses spread among cells both extracellularly and
intracellularly. Virus is shed in the respiratory secretions for 3 to 16 days following primary infection and for 1 to 4 days
following reinfection. Shedding starts shortly before the onset of disease and ends with development of local antibody. The
main pathogenic change is an inflammatory response in the superficial layers of the mucous membranes.
- The most characteristic and important clinical syndromes associated with parainfluenza virus infection are croup,
bronchiolitis, and pneumonia. The development of croup is linked to IgE antibodies and the release of histamine. The most
severe manifestation of infection with types 1 and 2 viruses is croup, whereas type 3 virus causes all three syndromes.
Parainfluenza type 3 can also cause meningitis. Type 4 infections usually cause mild symptoms but cases with symptoms of
bronchiolitis, pneumonia or aseptic meningitis have been reported. Parainfluenza virus infection with all 4 types can cause
serious illness in immunosuppressed individuals.Croup caused by parainfluenza virus is not distinguishable from that caused
by other viruses such as respiratory syncytial virus or measles virus.
Host Defense
- Nonspecific defenses (including interferon) may contribute to resistance against human parainfluenza viruses. The
immunologic events during and after natural infection with parainfluenza viruses in infants and children are not well
understood. Type-specific secretory and humoral immune responses occur, but protection does not last, since reinfection
with the same serotype may occur within 3 months to several years after primary infection. The degree of resistance to
reinfection and, even more, to clinical disease seems to depend mainly on the concentration of secretory IgA antibodies that
possess neutralizing activity. Neutralizing IgA is found in infants and young children only for a short time after primary
infection. Serum antibodies usually are not significant in resistance to reinfection with the nonsystemic respiratory viruses,
but their presence in high titers may restrict local virus multiplication and disease manifestation. Passive maternal antibodies
do not totally protect against infection; however they appear to influence disease manifestations with types 1 and 2 virus.
Also maternal antibodies may suppress the immune response following primary infection.
Epidemiology
- The parainfluenza viruses are distributed worldwide, causing infection and illness in young children. These virus infections
are endemic, sometimes reaching epidemic proportions. Infections with parainfluenza virus types 1 and 2 peak in the winter
months, whereas parainfluenza virus type 3 appears throughout the year. The source of human parainfluenza virus infection
is the respiratory tract of humans; the incubation period ranges from 2 to 6 (to
10) days.In primary infection virus is shed in the respiratory secretions for 3 to 16 days and 1 to 4 days following reinfection.
Parainfluenza viruses are transmitted by direct person-to-person contact and by the airborne route through large droplets.
Only a small inoculum is required to infect. However, parainfluenza viruses are labile and do not persist in the environment.
They are spread mainly by infants and preschool children with only mild signs of infection.
Diagnosis
- Diagnosis based on clinical manifestations is not possible. Laboratory diagnosis is made by detection of viral antigens by
fluorescent-antibody staining of nasopharyngeal cells or the enzyme-linked immunosorbent assay in sonicated
nasopharyngeal specimens. A reverse transcription PCR enzyme immunoassay is available for rapid detection of parainfluenza
type 3 RNA in respiratory specimens.
- Serologic evidence of infection may be obtained by demonstrating a significant rise in antibody titer between two serum
samples. Serodiagnosis by this means is clouded by the heterotypic anamnestic responses to previous parainfluenza infection.
An early and usually reliable serodiagnosis of infection can be made by the demonstration
of significant levels of IgA or IgM antibodies in a single-serum sample. Infections are not always recognizable
serologically due to the insufficient induction of antibodies.
Control
- Cross-infection with parainfluenza virus types 1 and 3 is common in hospital wards and day care centers. It can be prevented
by strict isolation. Recent techniques that allow rapid diagnosis facilitate such control.
- Active immunization against parainfluenza viruses is desirable but not yet available. Experimental killed vaccines are not
effective. A live attenuated bovine para influenza virus type 3 vaccine seems to be safe, infectious, immunogenic and
phenotypical stable in infants and children. Passive prophylaxis with human immunoglobulin in exposed infants is not
indicated, because it may dampen an active serum antibody response. Ribavirin may be effective but it also has toxic side
effects.
RESPIRATORY SYNCYTIAL VIRUS

- Most respiratory syncytial virus infections lead to illnesses ranging from mild upper respiratory disease to life- threatening
lower respiratory tract illness (e.g., bronchiolitis and pneumonitis) in infants and young children, among whom respiratory
syncytial virus is the most important serious lower respiratory tract pathogen. It is also an important cause of otitis media in
young children. It can infect the middle ear directly or predispose individuals to bacterial superinfection. Older children and
adults usually have common cold symptoms. In the elderly patients, respiratory syncytial virus can again be a significant lower
respiratory tract pathogen.
- Morbidity and mortality are greatest in the very young infants (less than 6 months of age, in preterm infants with underlying
pulmonary or cardiac disease and in immunodeficient children.
Structure
- Respiratory syncytial virus has a linear single-stranded RNA of about 5 × 106 daltons, which encodes at least 10 proteins (7-8
structural and 2 nonstructural proteins). The RNA is surrounded by a helical nucleocapsid, which in turn is surrounded by an
envelope of pleomorphic structure. Virions range from 120 to 300 nm in diameter. Protective antibody appears to be evoked
only by the F and G protein, F elicits a cell mediated as well as a humoral response. Respiratory syncytial virus has neither
hemagglutinin nor neuraminidase activity.

- Respiratory syncytial virus belongs to a separate genus, Pneumovirus, because of its distinctive surface projections,
nucleocapsid diameter, molecular weight of the N and P proteins, lack of hemagglutinin and neuraminidase activity, and
differences in number and order of its genes. RSV is divided in two subgroups A and B based on the G protein
antigen.
Multiplication
- After absorption, penetration, and uncoating, the respiratory syncytial virus genome serves as a template for the production
of 10 different mRNA species and a full-length, positive-sense complementary RNA (cRNA). The mRNAs serve as the template
for translation of viral proteins. The full-length, cRNA serves as a template for
transcription of virion RNA. Within 10 to 24 h after infection, projections of viral proteins appear on the cell surface, and virions
bud through the cell membrane incorporating part of the cell membrane into their envelope.
Pathogenesis
- Respiratory syncytial virus generally initiates a localized infection in the upper or lower respiratory tract or both.
The degree of illness varies with the age and immune status of the host.
- Initially, the virus infects the ciliated mucosal epithelial cells of the nose, eyes, and mouth. Infection generally is confined to
the epithelium of the upper respiratory tract, but may involve the lower respiratory tract. The virus spreads both
extracellularly and by fusion of cells to form syncytia. Thus, humoral antibodies that do not penetrate intracellularly cannot
completely restrict infection. The virus is shed in respiratory secretions usually for about 5 days and sometimes for as long as
3 weeks. Shedding begins with the onset of symptoms and declines with the appearance of local antibody.
- The most important clinical syndromes caused by respiratory syncytial virus are bronchiolitis and pneumonia in infants, croup
and tracheobronchitis in young children, and tracheobronchitis and pneumonia in the elderly. Conjunctivitis, otitis media,
and various exanthems involving the trunk or face, or both, are occasionally seen in primary and secondary infections.
- Bronchiolitis is inflammatory, and pneumonia is interstitial. The pathogenesis of bronchiolitis may be immunologic or directly
due to viral cytopathology. Respiratory syncytial virus bronchiolitis during the first year of life may be a risk factor for the later
development of asthma and sensitization to common allergens.
Host Defense
- Nonspecific defenses such as virus-inhibitory substances in secretions probably contribute to resistance to and recovery from
respiratory syncytial virus infection. Age, immunologic competence, and physical condition also appear to be important. Data
on the development, persistence, and effectiveness of specific cell-mediated and secretory immunity in first and repeat
infections are still fragmentary. Although secretory and serum antibody responses occur, immunity does not protect
completely against reinfection and repeat illness, which may occur as early as a few weeks after recovery from the first
infection. Protective immunity is mainly elicited by the F and G proteins.
- Resistance to reinfection and repeat illness seems to depend mainly on the presence of neutralizing antibody activity on the
mucosal surfaces. There is increasing evidence that humoral antibody contributes to protection from lower but not upper
respiratory tract infection.
- Bronchiolitis is inflammatory, and pneumonia is interstitial. The pathogenesis of bronchiolitis may be immunologic or directly
due to viral cytopathology. Respiratory syncytial virus bronchiolitis during the first year of life may be a risk factor for the later
development of asthma and sensitization to common allergens.
Host Defense
- Nonspecific defenses such as virus-inhibitory substances in secretions probably contribute to resistance to and recovery from
respiratory syncytial virus infection. Age, immunologic competence, and physical condition also appear to be important. Data
on the development, persistence, and effectiveness of specific cell-mediated and secretory immunity in first and repeat
infections are still fragmentary. Although secretory and serum antibody responses occur, immunity does not protect
completely against reinfection and repeat illness, which may occur as early as a few weeks after recovery from the first
infection. Protective immunity is mainly elicited by the F and G proteins.
- Resistance to reinfection and repeat illness seems to depend mainly on the presence of neutralizing antibody activity on the
mucosal surfaces. There is increasing evidence that humoral antibody contributes to protection from lower but not upper
respiratory tract infection.
Epidemiology
- Respiratory syncytial virus is distributed worldwide, causing infection and illness in infants and young children. The infection
is endemic, reaching epidemic proportions every year. In temperate climates, these epidemics occur each winter and last 4
to 5 months, with peaks mainly from January to March. Both RSV subgroups A and B circulate during these epidemics.
Estimates for urban settings suggest that about one-half of the susceptible infants undergo primary infection in each
epidemic. The infection is almost universal by the second birthday. Reinfection may occur as early as a few weeks after
recovery, but usually takes place during subsequent annual outbreaks, with a rate of 10 to 20 percent per epidemic
throughout childhood. In adults, the frequency of reinfection is lower.
- The source of human respiratory syncytial virus infection is the respiratory tract of humans. The incubation period for the
disease is about 4 days. As noted above, primary infections are contagious from about 5 days to 3 weeks, with greatest virus
shedding in the first 4 to 5 days after onset of symptoms. The contagious periods become progressively shorter during
reinfections. The virus is transmitted by direct person-to-person contact and by the airborne route through droplet spread.
It is probably introduced into families by schoolchildren undergoing reinfection. Secondary spread is to younger siblings and
parents. In hospital and institutional settings, mildly symptomatic infected adults also spread the infection. Respiratory
syncytial virus readily infects infants during the first few months of life despite the presence of maternal serum antibodies.
Thus, the age at which first infection takes place depends primarily on the opportunity for exposure. Sex and socioeconomic
factors appear also to influence the outcome of infection.
Diagnosis
- In infants with lower respiratory tract disease, respiratory syncytial virus infection can be strongly suspected on the basis of
the time of year, the presence of a typical outbreak, and the family epidemiology. Aside from this virus, only parainfluenza
virus type 3 attacks infants with any frequency during the first few months of life.
- Definite diagnosis of infection (of practical importance in ruling out bacterial involvement) rests on the virology laboratory.
Rapid diagnosis can be made within hours by using fluorescent antibody staining of infected nasal epithelial cells or by antigen
detection in the nasopharyngeal secretion by enzyme-linked immunosorbent assay
and by detecting viral RNA polymerase chain reaction (PCR). Isolation of virus in various types of cell culture takes 3-6 days
for recognition of the characteristic cytopathic effect. Serologic diagnosis can be made by detecting a significant rise of antibody
in 2-3 weeks or by detecting specific IgM antibodies in a single serum.
- Serological response in young infants following primary infection may be poor. After repeated infection an anamnestic
response generally occurs.
Control
- It is nearly impossible to prevent respiratory syncytial virus transmission in the home setting. In hospital wards, cross-
infection may be restricted by isolation and sanitation. Despite its tremendous clinical and economic impact, therapy and
prevention of respiratory syncytial virus illness remains problematic. As yet, there is no safe and effective vaccine against RSV.
- A promising means of protection is the administration of RSV-enriched polyclonal immunoglobulin (RSVIG) with monthly high-
dose infusion. The maintenance of high-titer RSV neutralizing antibodies seems to significantly decrease the incidence and
severity of respiratory syncytial virus illness in children at high risk.
- The only approved antiviral agent for the treatment of RSV illness, e.g. in the USA, is ribavirin. It has been in use since 1986.
However, the safety and clinical efficacy remain controversial.
MUMPS VIRUS
- Without widespread vaccination, mumps is a common acute disease of children and young adults that is characterized by a
nonpurulent inflammation of the salivary glands, especially the parotids. Severe manifestations may include pancreatitis,
meningitis and encephalitis with hearing loss or deafness at any age and orchitis or oophoritis in young adults. Most disease
manifestations are benign and self-limiting. Both symptomatic and asymptomatic mumps virus infections usually induce
lifelong immunity. Rarely, reinfections with wild-type virus leading to typical mumps may occur.
Sructure
- Mumps virus shares many structural properties with the other paramyxoviruses.

- Mumps virus belongs to the genus Paramyxovirus and exhibits most characteristics of the Paramyxoviridae. It occurs only in
a single serotype and shares minor common envelope antigens with other Paramyxovirus species. The nucleotide-sequence
homology between various mumps virus isolates is 90 to 99 percent.
Multiplication
- Like other paramyxoviruses, mumps virus initiates infection by attachment of the HN protein to sialic acid on the cell-
surface glycolipids and works together with the F protein to promote fusion with the plasma membrane.
Following uncoating, the negative-sense viral RNA is transcribed by the RNA-dependent RNA polymerase to mRNAs followed
by the synthesis of viral proteins which are essential for the continuation of the replication process. After assembly of the
nucleocapsids (RNA, N, L, and P protein) in the cytoplasm, the maturation of the virus is completed by budding.
Pathogenesis
- Mumps virus causes a systemic generalized infection that is spread by viremia with involvement of glandular and nervous
tissues as target organs. The infecting virus probably enters the body through the pharynx or the conjunctiva. Local
multiplication of the virus in epithelial cells at the portal of entry and a primary viremia precede a secondary viremia, lasting
2 to 3 days. The incubation period usually is 18 to 21 days, but may extend from 12 to 35 days. Recognizable symptoms do
not appear in 35 percent of infected individuals. The virus is carried to the main target organs (various salivary glands, testes,
ovaries, pancreas, and brain). Viral replication takes place in the ductal cells of the glands. It is not known how the virus
spreads to the central nervous system. Studies in experimental animals suggest that indirect spread occurs by passage of
infected mononuclear cells across the epithelium of the plexus to the epithelial cells of the plexus choroideus. Alternatively,
direct spread of virus is possible.
- Shedding of the virus in salivary gland secretions begins about 6 days before onset of symptoms and continues for another 5
days, even though local secretory IgA and humoral antibodies become detectable during that time. Shedding occurs also in
conjunctival secretions and urine. During the first 2 days of illness, the virus may be recovered from blood. In cases of
meningitis or early-onset encephalitis, virus can be detected in cerebrospinal fluid and cells during the first 6 days after onset
of disease. The virus may persist in tissues for 2 to 3 weeks after the acute stage, despite the presence of circulating antibodies.
The main pathogenic changes induced by mumps virus infection in the salivary glands and the pancreas are inflammatory
reactions. When the testes are involved, swelling, interstitial hemorrhage, and focal infarcts (leading to atrophy of the
germinal epithelium) may occur. Infection of the pancreas disturbs endocrine and exocrine functions, leading to diabetic
manifestations and increased serum amylase levels. Mumps virus infection of the pancreas has been reported to be a
triggering mechanism for onset of juvenile insulin-dependent diabetes mellitus (IDDM); however, a causal relationship has
not been established.
- The pathologic reaction to mumps virus infection of brain tissues is generally an aseptic meningitis. Less often, the infection
involves the brain neurons (as in early-onset mumps encephalitis). Histopathologic findings are widespread and include
neuronolysis and ependymitis, which may lead to deafness and obstructive hydrocephalus in children. One human case of
chronic central nervous system mumps virus infection has been described. The late-onset (postinfectious) type of mumps
encephalitis is attributed to autoimmune reactions. Histopathologic findings are characterized by perivascular accumulation
of mononuclear leukocytes, demyelinization, and overgrowth of glial cells, with relative sparing of the neurons. These findings
resemble those seen in postinfectious measles, rubella, and varicella encephalitis.
- The most characteristic clinical feature of mumps virus infection is the edematous, painful enlargement of one or both of the
parotid glands. Commonly, the submandibular salivary glands are involved and, less frequently, the sublingual glands.
Pancreatitis is uncommon as a severe illness. Epididymo-orchitis develops in 23 percent of infected postpubertal males and
may lead to atrophy of the affected testicles, although rarely to total sterility. Oophoritis develops in 5 percent of infected
postpubertal women. Mumps meningitis occurs in up to 10 percent of patients with or without parotitis. Encephalitis has
been reported to occur in 1 in 400 cases of mumps. Transient high frequency deafness is the most common complication (4
percent), and permanent unilateral deafness occurs infrequently (0.005 percent). Primary mumps virus infection in early
pregnancy may lead to abortion, but there is no convincing evidence of an increased risk of congenital defects in humans.
Host Defense
- Mumps virus infection is followed rapidly by interferon production and then by specific cellular and humoral immune
responses. Interferon limits virus spread and multiplication, and its production ceases as virus levels decrease and humoral
antibodies and cell-mediated immunity appear. Little is known about cell-mediated immunity to mumps virus; in contrast,
the humoral antibody response is well understood.
- IgM class-specific antibodies to mumps antigens develop rapidly within the first 3 days after onset of symptoms and persist
for approximately 2 to 3 months. The IgG antibodies appear a few days later and persist for life. Circulating antibodies are
responsible for the lifelong protection against recurrent disease, but reinfection may occur. Parainfluenza virus infections,
particularly with type 3 virus, cause a rise of mumps antibody titers, contributing to the lifelong stability of the mumps
antibody. Protective mumps antibody of the IgG class is transplacentally transferred to the newborn and persists in declining
titers during the first 6 months of life.
Epidemiology
- Mumps occurs worldwide. In urban areas the infection is endemic with a peak incidence between January and May. Local
outbreaks are common wherever large numbers of children and young adults are concentrated (institutions, boarding
schools, and military camps). Epidemics occur every 2 to 3 years. In rural areas, mumps tends to die out until enough
susceptible individuals have accumulated and the virus is reintroduced which may lead to large outbreaks. Humans are the
only known hosts.
- Infection is transmitted by salivary gland secretions, mainly just before and shortly after clinical onset. In asymptomatic
infections, peak contagion occurs within a similar period. Mumps virus is transmitted usually by direct and close person-to-
person contact and less often by the airborne route. School children (6 to 14 years old) are the main source of spread. Mumps
infection is acquired later in childhood than are other paramyxovirus infections; 95 percent of individuals have antibody by
age 15. As already mentioned, 35 percent of these infections are subclinical. In remote areas, a much lower percentage of
children may be infected.
- Active vaccination in the United States has reduced the incidence of reported mumps and mumps complications by more
than 90 percent.
Diagnosis
- Typical cases of mumps involving the salivary glands can usually be diagnosed without laboratory tests. An etiologic diagnosis
of other clinical manifestations without parotitis (e.g., meningitis, encephalitis, orchitis, and oophoritis) requires laboratory
confirmation. Acute infections can be diagnosed by isolating the virus from saliva, cerebrospinal fluid or urine in cell culture.
Serologic evidence of acute infection is obtained e.g. with the ELISA or an immunofluorescence test early after onset of
symptoms by demonstrating IgM antibodies in the first serum and later by detecting a significant IgG antibody rise in paired
sera. Reinfection after previous vaccination is recognized by high titers of mumps-specific IgG antibody, mostly in the absence
of specific IgM. An alternative to antibody detection in serum is the detection of IgM and IgA antibody in saliva which in the
acute phase of mumps compares satisfactorily with IgM antibody detection in serum.
Control
- In view of the long period of virus shedding and the 35 percent rate of subclinical infection, isolating patients with typical
symptoms does little to prevent spread. Passive prophylaxis with mumps immunoglobulin prior to viremia is used for
individuals at high risk, such as children with underlying disease, those in hospital wards, postpubertal males, and pregnant
women. With the enzyme-linked immunosorbent assay (EIA), the immune status can be assessed in 3 hours so that
immunoglobulin is given only to exposed seronegative (susceptible) individuals.
- Active immunization against mumps is recommended for all children at 12 to 18 months of age in many countries. A combined
live virus vaccine is available for mumps, measles, and rubella (MMR). The mumps component contains attenuated virus
grown in chick embryo tissue culture. The vaccine containing Jeryl Lynn strain is well tolerated and safe in contrast to another
strain (Urabe Am9). Usually it is effective only when maternal antibodies are absent. The seroconversion rate with the Jeryl
Lynn vaccine strain used in the USA is >90 percent. The vaccine-induced antibody titers are lower than those following natural
infection. This antibody protects generally against clinical disease but not against reinfection. Long-term vaccine-induced
immunity seems to be maintained by inapparent (and sometimes also by apparent) reinfection with mumps wild-type virus
and infections with other parainfluenza viruses. In spite of this, antibody may decline to very low or undetectable levels.
- Mumps vaccination (two doses) has been responsible, e.g. in the USA for a 95 percent decrease in the annual incidence of
reported mumps and mumps complications. To close vaccination gaps and to enhance antibody levels in previous vaccines,
a second dose of vaccine is recommended either at 6 or 12 to 13 years of age.
MEASLES VIRUS
- Measles virus usually causes, in the nonvaccinated population, an acute childhood disease characterized by coryza,
conjunctivitis, fever, and rash. The disease usually is benign but can be dangerous, causing pneumonia and acute encephalitis.
In immunocompromised patients, giant-cell pneumonia and measles inclusion body encephalitis (MIBE) may occur. Defective
measles virus may persist in the central nervous system after natural infection and may later cause subacute sclerosing
panencephalitis (SSPE). The live vaccine has dramatically reduced the incidence of disease in developed countries, but measles
still remains a major health problem in developing countries causing the death of 1.5 million children per year.
Structure
- Measles virus has the structure of the family Paramyxoviridae, consisting of spherical, enveloped particles with a central
helical nucleocapsid. The diameter of the pleomorphic particles varies between 120 and 250 nm. The nucleocapsid contains
a monopartite, single-stranded, negative-sense RNA genome (molecular weight 7 × 106). It is surrounded by the nucleocapsid
protein N and associated with the enzymatically active phosphoprotein P and the large protein L, both of which are
involved in viral transcription and replication. The P gene also gives rise to nonstructural proteins C and V. The
bilayered lipid envelope is partly of cellular origin with the matrix protein M inside and bears a fringe of spike-like
projections containing the hemagglutination (H) and the hemolytic and cell fusion (F) activities.
- Virion infectivity is lost readily when the envelope is disrupted spontaneously and when the virus is treated with lipid solvents.
- Measles virus is a member of the genus Morbillivirus. It differs from other paramyxoviruses in lacking neuraminidase and in
having hemagglutination activity restricted to monkey and some human red blood cells. Measles virus and the other
morbilliviruses occur only as one cross-reactive antigenic type. The natural disease is limited to humans and monkeys.
Multiplication
- Measles virus multiplies like the other members of the family Paramyxoviridae. Attachment of particles to the cell surface is
followed by fusion of the virus envelope and the cytoplasmic membranes and penetration of the nucleocapsid structures into
the cytoplasm. The negative-sense RNA is transcribed by the nucleocapsid- associated enzymatically active P and L proteins.
The order of genes in terms of their products is N, P, M, F, H and L. The virion RNA serves not only as a template for production
of mRNA, but also for replication of intact RNA via a positive-stranded intermediate. After accumulation of genomic RNA and
the different structural proteins in the cell cytoplasm, maturation takes place by budding of the virus from the cell. The cell
membrane is modified by attachment of N-linked carbohydrate chains of cellular origin before virus transmembranous
proteins appear at the cell surface.
- The release of viral particles from single cells varies from a few hours, if the cells succumbs rapidly to cytopathology, to an
unlimited time in chronic, steady-state infections. Development of chronic infection and diseases in the central nervous
system (CNS), such as in subacute sclerosing panencephalitis may be caused by a variety of mutations. These result in a lack
of viral budding, reduced expression of the viral envelope proteins, and spread of ribonucleoprotein (RNP) through the CNS
in spite of massive immune response.
Pathogenesis
- Measles virus causes a systemic infection, disseminated by viremia, with acute disease manifestations involving the lymphatic
and respiratory systems, the skin, and sometimes the brain (Fig. 59-4). Inapparent infections are rare. Measles virus may
persist silently for years (with constant replication of the ribonucleoprotein at very low levels) and occasionally causes
subacute sclerosing panencephalitis (SSPE) and autoimmune chronic hepatitis. In immunocompromised patients, measles
inclusion body encephalitis (MIBE) may occur after a shorter persistence.
- Measles virus enters the host through the oropharynx and possibly through the conjunctiva. Local virus multiplication in the
respiratory tract and the regional lymph nodes is followed by primary viremia with virus spread to the rest of the
reticuloendothelial system, where extensive replication takes place. A second viremia, which occurs 5 to 7 days later,
disseminates virus to the mucosa of the respiratory, gastrointestinal, and urinary tracts, to the skin, and to the central nervous
system. In these organs the virus replicates in epithelial cells, endothelial cells, and in monocytes and macrophages. With
development of serum antibodies, free virus is quickly cleared from the blood and body fluids, but virus persists for
various periods in lymphoid, lung, bladder tissue, and in polymorphonuclear leucocytes.
- The main pathologic change attributable to viral replication in the main target organs is an inflammatory response. Virus-
infected cells contain virus antigens and inclusions in the cytoplasm and nuclei. Infected cells may fuse to form giant cells.
The pathology and pathogenesis of postinfectious (allergic) measles encephalitis are the same as those of other
exanthematous viral diseases.
- In subacute sclerosing panencephalitis patients, mainly noninfectious viral ribonucleoprotein (RNP) inclusion bodies occur in
different cell types in the gray and white matter with a strong inflammatory response and some demyelination. RNA can be
detected in brain biopsies.
- The temporary loss of delayed skin hypersensitivity during acute measles may be due to virus multiplication in T and B
lymphocytes. The maculopapular rash is a consequence of the interaction between virus-infected endothelial cells and
immune T cells. The simultaneous onset of rash and appearance of serum antibodies suggests an antibody-dependent cellular
cytotoxic cause of the exanthem. In cases of dysfunction of T cells, no rash is seen and relentless progression of the infection
may lead to giant-cell pneumonia with fatal outcome. Abnormal encephalograms are common during measles, suggesting
frequent viral invasion of the brain.
- Clinically, measles is characterized by upper respiratory tract symptoms during the prodromal stage and by the maculopapular
rash during the eruptive phase. After an incubation period of 9 to 12 days, the prodromal stage starts with malaise, fever,
coryza, cough, and conjunctivitis. At the end of this stage, the pathognomonic Koplik spots (red spots with bluish-white specks
in their centers) appear in the oral mucosa opposite the second molars. The rash appears 1 or 2 days later, first on the head
and then spreading down the body and limbs, including the palms and soles. Initially it is erythematous and maculopapular
and later becomes confluent. Uncomplicated illness lasts 7 to 10 days. Otitis media caused by bacterial superinfection is the
most frequent complication. Primary viral or secondary bacterial pneumonia is the most common complication responsible
for hospitalization and death. Purely viral complications are croup, bronchiolitis, and the fatal giant-cell pneumonia; these
often occur without rash in immunocompromised children.
- A severe but infrequent atypical measles syndrome consists of high fever, atypical pneumonia and an urticarial, purpuric rash
that begins peripherally and spreads centripetally. This syndromeis an allergic response to measles infection in adolescents
and young adults who were inadequately immunized (mainly with killed measles vaccine) in childhood.
- The acute postinfectious measles encephalitis, one of the main reason for introducing measles vaccination, has a frequency
of 0.1 to 0.2 percent with a mortality of 20 percent. Permanent neurologic sequelae occur in 20 to 40 percent of cases. Rare
complications may be myocarditis, pericarditis, hepatitis, appendicitis, mesenteric lymphadenitis and ileocolitis.
- Mild (modified) measles develops in children who possess low levels of maternally derived or injected antibodies.
If measles infection occurs during pregnancy spontaneous abortion or stillbirth and preterm delivery may occur.
Host Defense
- Little natural resistance to measles virus infection exists. Nonspecific substances, such as interferon, appear to contribute to
early limitation of virus spread. Interferon may be detected until virus-specific antibodies appear. The cell-mediated immune
response is associated with recovery from primary infection and also with resistance to reinfection at the portal of entry. The
humoral immune response helps to eliminate extracellular virus during primary infection and to prevent systemic spread at
reinfection .
- The humoral immune response occurs in the three immunoglobulin classes. Lifelong persistence of serum antibodies may be
due to persistence of viral antigen. Maternal IgG antibodies completely protect the infant for 6 months; between 6 and 12
months of age, subclinical infection or modified disease may occur.
- In patients with subacute sclerosing panencephalitis, strikingly high titers of measles oligoclonal antibody (IgG) are present in
serum and cerebrospinal fluid. Antibodies are directed against the viral proteins.
Epidemiology
- In the pre-vaccine era measles occurred throughout the world, in all races and all climates, with humans as the only host. The
main factors accounting for the epidemiological pattern are universal susceptibility to infection in the absence of antibody,
extreme contagiousness, population density, and standard of living.
- Sporadic cases occur throughout the year, with peak incidence in the late winter and early summer months. Epidemics occur
every 2 to 4 years in developed urban areas with a nonimmunized population and every 4 to 8 years in rural areas, when the
number of susceptible persons reaches about 40 percent of the population. The epidemics last 3 to 4 months, until the
number of susceptible persons falls below 20 percent. Local outbreaks occur in crowded institutional settings, even when less
than 2 percent of the population is susceptible.
- The source of infection is the virus-containing respiratory tract secretions, either airborne or transmitted by fomites. The
contagious period lasts about 6 days, beginning with the prodromal symptoms and persisting until about 2 days after rash
develops, at which time antibodies first appear.
- In developed societies, measles infects children between 4 and 7 years of age. In underdeveloped societies, measles occurs
before age 4. By age 7 to 12 years, in all but the most isolated areas, nearly all children have had measles and possess specific
antibodies. In countries such as the United States, in which vaccine is used extensively, the incidence of reported disease and
its complications have dropped more than 95 percent. As a result of this decreased transmission, a transitory shift to older
teenagers has occurred. The incidence of measles encephalitis is almost twice as great in teenagers as in younger children.
Subacute sclerosing panencephalitis follows natural measles at an estimated rate of 6 to 20 cases for every 106 children
developing measles.
- The risk of subacute sclerosing panencephalitis from live measles vaccine is 1/10 of that of natural infection. Most recent
studies suggest a perinatal and early postnatal measles virus infection or vaccination as a presumable cause of Crohn's
disease.
Diagnosis
- Clinical diagnosis of measles is easy when the characteristic symptomatology is present. Laboratory diagnosis is indicated in
cases with uncharacteristic exanthems, atypical measles, pneumonia, or encephalitis after a rash, as well as in suspected
cases of giant-cell pneumonia, measles inclusion body encephalitis (MIBE) and of subacute sclerosing panencephalitis. It may
also be indicated in previously vaccinated persons who show symptoms and signs of measles.
- Laboratory diagnosis of acute measles can be made until about 2 days after onset of rash by demonstrating multinucleated
giant cells or fluorescent antibody-staining cells in nasal secretions, urine, and skin biopsies. Isolation of measles virus is
difficult and therefore not suitable for routine diagnosis. The detection of RNA by polymerase chain reaction (Rt-PCR) can also
be used in complications and unusual manifestations of measles.
- Routinely, measles infection is diagnosed serologically by demonstration of IgM antibodies in the first serum sample, taken 2
to 3 days after onset of rash. Rising IgG antibodies are detectable in the 2nd serum within 5 to 8 days. The antibody index
(between CSF and serum titer values) when >3 is indicative of intrathecal antibody synthesis, thereby implying intrathecal
viral antigens. In surveillance studies, saliva specimens can be tested instead of serum for the presence of IgM antibodies.
- A serologic diagnosis of subacute sclerosing panencephalitis can be made by demonstrating extremely high IgG antibody
levels without IgM in serum and cerebrospinal fluid. Such extremely high IgG antibodies without IgM are also diagnostic for
the atypical measles syndrome.
Control
- Quarantine is futile, because by the time the rash signals the disease, shedding has been in progress for 2 or 3 days. Passive
prophylaxis with measles immunoglobulin is recommended for exposed, susceptible individuals, especially those at high risk
(e.g., patients with cancer, immunosuppressed and immunodeficient patients, infants younger than 1 year of age, and
pregnant women). To completely prevent measles infection, viremia must be prevented by an appropriate dose of
immunoglobulin given within 3 days of exposure. Administration of immunoglobulin between days 5 and 9 after exposure
cannot prevent the secondary viremia, but will modify the disease and allow immunity to develop. Disease also can be
modified within 3 days of exposure by reducing the dose of immunoglobulin. Immunoglobulin may protect recipients for
about 4 weeks.
- Active immunization with the combined measles-mumps-rubella live-virus vaccine is recommended for all healthy
12 to 18-month-old children. Vaccine-induced antibody develops in about 94 percent of the seronegative recipients and usually
persists in declining titers for more than 18 years. Natural exposure to virus may cause an antibody booster response.
Revaccination is recommended in some countries at the age of 6 and in others at the age of 12 years to reach primary vaccine
failures (6-7 percent) and to boost low levels of antibody. Vaccination is also emphasized in the USA for adolescents entering
college. Furthermore, live-virus vaccine should be given to anyone who does not have a history of measles or has not received
live virus vaccine after the age of 15 months.
- Efforts are being made for elimination of indigenous measles in the USA using strategies successful in 17 Caribbean countries,
in Finland and in England. The World Health Organization (WHO) lists measles as one of the pathogens to be eradicated
worldwide
- No specific treatment for measles, measles encephalitis, or subacute sclerosing panencephalitis is available. Management is
symptomatic and supportive. Bacterial superinfection should be treated with appropriate antimicrobial agents, but
prophylactic antibiotics to prevent superinfection have no known value and are contraindicated.

1. What is the morphologic distinguishing feature among enveloped viruses of the subfamily Paramyxoviridae.
ANSWER/RATIONALIZATION: The morphologic distinguishing feature among enveloped viruses for the subfamily
Paramyxovirinae is the size and shape of the nucleocapsids (diameter 18 nm, 1 μm in length, a pitch of 5.5 nm), which have a left-handed
helical symmetry.
2. What are the biological criteria for the classification of Paramyxoviruses?
ANSWER/RATIONALIZATION: The biological criteria are (a) antigenic cross-reactivity between members of a genus and (b) the
presence (Respirovirus and Rubulavirus) or absence (Morbillivirus and Henipavirus) of neuraminidase (NA) activity. In addition, the
differing coding potentials of the P genes are considered, and there is the presence of an extra gene (SH) in some rubulaviruses as well
as J virus and Beilong virus.
3. How can you distinguish Pneumoviridae from Paramyxoviridae?
ANSWER/RATIONALIZATION: he pneumoviruses can be distinguished from Paramyxovirinae morphologically, as they contain

narrower nucleocapsids. In addition, the Pneumovirinae have major differences in the number of encoded proteins and an attachment
protein that is very different from that of Paramyxovirinae.
4. Illustrate and label the complete viral structure OF PARAMYXOVIRUS

- The Paramyxoviridae include some of the great and ubiquitous disease-causing viruses of humans and animals,
including one of the most infectious viruses known (measles virus), some of the most prevalent viruses known
(measles virus, parainfluenza viruses [PIVs], mumps virus, respiratory syncytial virus [RSV], and
metapneumovirus), a virus that has been targeted by the World Health Organization for eradication (measles
virus; however, to date, eradication has failed), a virus that has been eradicated (rinderpest virus), viruses that
have a major economic impact on poultry rearing (Newcastle disease virus [NDV]), and many recently identified
viruses (pinniped morbilliviruses, Hendra virus, Nipah virus, J virus and Beilong virus), some of which cause deadly
diseases (Hendra and Nipah viruses).
- The Paramyxoviridae are enveloped negative-stranded RNA viruses that have special relationships with two other
families of negative-strand RNA viruses, namely the Orthomyxoviridae (for the biological properties of the envelope
glycoproteins) and the Rhabdoviridae (for the similarity of organization of the nonsegmented genome and its
expression). The Paramyxoviridae are defined by having a protein (F) that causes viral–cell membrane fusion, in most
cases at neutral pH.
- The genomic RNA of all negative-strand RNA viruses has to serve two functions: first as a template for synthesis
of messenger RNAs (mRNAs) and second as a template for synthesis of the antigenome positive strand. Negative-
strand RNA viruses encode and package their own RNA polymerase (RNAP); however, mRNAs are only synthesized
once the virus has been uncoated in the infected cell. Viral replication occurs after synthesis of the mRNAs and
requires the continuous synthesis of viral proteins.
- The newly synthesized antigenome positive strand serves as the template for further copies of the negative-strand
genomic RNA.
PARAINFLUENZA VIRUSES
Clinical manifestation
- Parainfluenza viruses cause mild or severe upper and lower respiratory tract infections, particularly in children.
Classification and Antigenic Types
- Human parainfluenza viruses are divided into types 1, 2, 3, and 4; type 4 consists of A and B subtypes.
Pathogenesis
- Transmission is by droplets or direct contact. The virus disseminates locally in the ciliated epithelial cells of the respiratory
mucosa.
Host defense
- Nonspecific defenses, including interferon, are followed by the appearance of secretory and humoral antibodies and cell-
mediated immune responses.
Epidemiology
- Parainfluenza virus diseases occur worldwide; they are usually endemic but sometimes epidemic. Primary infections occur
in young children; reinfection is common but results in milder disease.
Diagnosis
- Clinical symptoms are nonspecific. Laboratory diagnosis is made by detecting viral antigen, by isolating the virus, or by
detecting a rise in antibody titer or elevated IgG- and IgA- (IgM-) antibodies in a single serum.
Control
- No vaccine is available.
RESPIRATORY SYNCYTIAL VIRUS

- Respiratory syncytial viruses are divided into types A and B.
Pathogenesis
- Transmission is by droplets or direct contact. The virus infects the ciliated epithelial cells of the respiratory mucosa and
disseminates locally. Disease is caused partly by immunopathologic antibody-dependent cellular cytotoxicity.
Host Defense
- Nonspecific immune defenses, including interferon, are followed by the appearance of secretory and serum antibody and
cell-mediated responses. Reinfection occurs, but the frequency and severity of disease decrease with age.
Epidemiology
- T his disease is found worldwide; in temperate climates, epidemics occur in winter and early spring and affect mainly
infants and young children.
Diagnosis
- Clinical symptoms are nonspecific; laboratory diagnosis is made by detecting viral antigen, by isolating the virus or by
detecting RNA with polymerase chain reaction (PCR), or by detecting a rise in antibody titer or elevated IgM antibodies in a
single serum.
Control
- There is no vaccine. Aerosolized ribavirin can be used for treatment if necessary. In hospital wards, infected patients may be
isolated.
MUMPS VIRUS
- Mumps is a systemic febrile infection of children and young adults. Swelling of the salivary glands, especially the parotid
glands, is characteristic; meningitis is common; and pancreatitis, encephalitis, and hearing loss may occur. In young adults,
orchitis or oophoritis is not uncommon.
- The single serotype of mumps virus shares antigens with parainfluenza viruses, particularly type 1.
Pathogenesis
- The virus is spread in droplets. Primary infection consists of viremia and involvement of glandular and nervous tissue,
resulting in inflammation and cell death.
Host Defense
- Interferon and other initial defenses are followed by specific cellular and humoral immune responses, which confer lifelong
immunity.
Epidemiology
- Mumps is found worldwide. Without extensive vaccination it is endemic in cities with epidemic variations in 2 to 3 years
intervals. In rural areas it is intermittent, reappearing there every 5 to 7 years, and may reach epidemic proportions. In
temperate climates, the incidence peaks from January to May.
Diagnosis
- In typical cases, the clinical picture is diagnostic. Atypical cases are diagnosed by isolating the virus in cell culture, or by
detecting viral antigen or RNA, and most easily by detecting specific IgM in the first serum sample soon after onset of
symptoms or by a rise of IgG antibodies.
Control
- Vaccination with live attenuated mumps virus vaccine gives long-lasting immunity, but reinfection may occur
MEASLES
- Measles sets in abruptly with coryza, conjunctivitis, fever, and rash. The typical maculopapular rash appears 1 to 3 days later.
Complications include otitis, pneumonia, and encephalitis. Subacute sclerosing panencephalitis is a rare late sequela.
- There is only single antigenic type
Pathogenesis
- The virus causes viremia with wide dissemination and multiplies in cells of the lymphatic, respiratory, intestinal and urinary
system, the skin, and sometimes the brain.
Host Defense
- Interferon and other initial defenses are followed by specific cellular and humoral immune responses, which confer long-
lasting immunity.
Epidemiology
- Prior to the vaccine era measles occurred worldwide in an endemic or epidemic pattern and disease was inevitable. In
temperate climates, the incidence peaks in the late winter and early summer.
Diagnosis
- In typical cases, the clinical picture is diagnostic. Atypical cases or cases following previous vaccination are diagnosed by
isolating the virus in cell culture by direct smear of cell-containing specimen, by detection of RNA with the polymerase chain
reaction (Rt-PCR) or detecting specific IgM in the first serum at the time of rash with a rising titer of IgG antibodies in the
second serum.
Control
- Active vaccination with a live attenuated virus vaccine gives long-lasting protection. Passive prophylaxis with measles
immunoglobulin is used to prevent disease in susceptible, exposed individuals.
BS MLS / THIRD YEAR
LESSON TITLE: RNA CONTAINING VIRUS Materials:

(ORTHOMYXOVIRUSES VIRUS) Book, pen and notebook, index card/class list
LEARNING OUTCOMES: References:
Internet Source:
1. identify the mode of transmission of RNA containing
virus (ORTHOMYXOVIRUES VIRUS). (https://www.ncbi.nlm.nih.gov/books/NBK8611/]
serological method. https://en.wikipedia.org/wiki/Orthomyxoviridae.
3. practice consistently the ways and means on how to prevent
control viral infection.
4. discuss the epidemiology, clinical stages and International Committee on Taxonomy of
pathogenesis of rabies virus. Viruses Index of Viruses —
5. illustrate viral structure of rabies virus.
Orthomyxovirus (2006). In: ICTVdB—The
6. know the ways and means on treatment, prevention and
control of paramyxoviruses virus infection. Universal Virus Database, version 4.
Büchen-Osmond, C (Ed), Columbia
University, New York

The teacher will start the lesson by introducing to the students the general concepts of paramyxoviruses and some
examples of orthomyxoviruses.
Orthomyxoviridae
- From Greek work “orthos” meaning straight; and “myxa” meaning mucus;
- Is a family of negative -sense RNA viruses.
- It includes seven genera:
 Alpha influenza virus
 Beta influenza virus
 Delta influenza virus
 Gamma influenza virus
 Isavirus
 Thogoto virus
 Quanranja virus
- NOTE: The first four (4) genera contain viruses that cause influenza in vertebrates, including birds (you may also read on avian
influenza), humans and other mammals. Isaviruses infects salmon; Thogotoviruses are arboviruses infecting vertebrates and
invertebrates such as ticks & mosquitoes, while the Quaranja viruses infects arthropods as well as birds.
- The four (4) genera of influenza virus that infect vertebrates, which are identified by antigenic differences in their
nucleoprotein and matrix protein, are as follows;
 Alpha influenza virus = infects humans, other mammals, and birds, and causes all flu pandemics
 Beta influenza virus = infects humans and seals
 Delta influenza virus = infects pigs and cattle
 Gamma influenza virus= infects humans, and pigs, and dogs. .
MAIN LESSON (50 minutes) Othromyxoviruses
(Influenza viruses)
- The orthomyxoviruses (influenza viruses) constitute the genus Orthomyxovirus, which consists of three types
(species): A, B, and C. These viruses cause influenza, an acute respiratory disease with prominent systemic
symptoms. Pneumonia may develop as a complication and may be fatal, particularly in elderly persons with
underlying chronic disease. Type A viruses cause periodic worldwide epidemics (pandemics); both types A and B
cause recurring regional and local epidemics. Influenza epidemics have been recorded throughout history. In
temperate climates, the epidemics typically occur in the winter and cause considerable morbidity in all age groups.
An epidemic with associated mortality has occurred in most of the past 100 years. The worst of these was the 1918
pandemic, which caused about 20 million deaths worldwide and about 500,000 deaths in the United States.
The Influenza virus virion:
- Is pleomorphic, the viral envelope can occur in spherical and filamentous forms. In general the virus’s morphology is
ellipsoidal with particles 80-120 nm in diameter, or filamentous with particles 80-120 nm in diameter and up to 20um long
(Noda T (2012-01-03). "Native morphology of influenza virions; https://en.wikipedia.org/wiki/Orthomyxoviridae.
-
- There are some 500 distinct spike-like surface projections I the envelope each projecting 10 to 14 nm from the surface with
varying surface densities.
- The major glycoprotein (HA) spike is interposed irregularly by clusters of Neuraminidase (NA) spikes, with a ratio of HA to
NA of about 4.5 to 1.
- The best-characterised of the influenzavirus proteins are hemagglutinin and neuraminidase,
two large glycoproteins found on the outside of the viral particles.
 Neuraminidase is an enzyme involved in the release of progeny virus from infected cells, by cleaving sugars
that bind the mature viral particles.
 hemagglutinin is a lectin that mediates binding of the virus to target cells and entry of the viral genome into
the target cell.
NOTE: The hemagglutinin (H) and neuraminidase (N) proteins are targets for antiviral drugs. These proteins are also recognised
by antibodies, i.e. they are antigens. The responses of antibodies to these proteins are used to classify the
different serotypes of influenza A viruses, hence
the H and N in H5N1(https://en.wikipedia.org/wiki/Orthomyxoviridae)
- The viral envelop composed of a lipid bilayer membrane in which the glycoprotein spikes are anchored encloses the
nucleocapsids; nucleoproteins of different size classes with a loop at each end; the arrangement within the virion is
uncertain. The ribonuclear proteins are filamentous and fall in the range of 50 to 130 nm long and 9 to 15 nm in
diameter. They have a helical symmetry.
-
Classification
NOTE: Flu viruses are named by the type of surface proteins:
 Hemagglutinin= trimer (HA)
 Helps virus enter cell
 Neuraminidase = tetramer (NA)
 Helps virus exit cell
 9 subtypes
Influenza (Flu)
- “La malatia per I’influenza della stella”( the disease caused by the influence of the stars”
- In French: grippe, from French verb “ agrippe” (clinging)
- Localized infection of the respiratory tract (Severe Respiratory Disease).
- 20-50 Million respiratory illnesses each year in the U.S.
 30 million to physicians, 200,000 hospitalizations
 20,000 deaths
Influenza A
- (-) ss RNA; 8 segments (pieces); one gene per segment; with nucleoprotein and matrix protein
- NS (nonstructural proteins, that are not incorporated into viral particles) gene encodes two different non-structural
proteins
- Flu viruses currently infecting : Human = H1N1, H1N2, H3N2
Avian flue = H5N1
- Sub-units of RNA polymerase, has spikes (about 500)
- Is the most virulent human pathogens among the three (3) influenza types and caused the most severe disease.
- The serotypes that have been confirmed in humans, ordered by the number of known human pandemic deaths are:
H1N1 caused "Spanish flu" in 1918 and "Swine flu" in 2009.
 H2N2 caused "Asian Flu".
 H3N2 caused "Hong Kong Flu"
 H5N1, "avian" or "bird flu".
 H7N7 has unusual zoonotic potential
 H1N2 is endemic in humans and pigs.
 H9N2, H7N2, H7N3, H10N7.
Influenza B

- Is almost exclusively a human pathogen, and is less common than influenza A. The only other animal known to be
susceptible to influenza B infection is the seal. This type of influenza mutates at a rate 2–3 times lower than type A and
consequently is less genetically diverse, with only one influenza B serotype. As a result of this lack of antigenic diversity,
a degree of immunity to influenza B is usually acquired at an early age. However, influenza B mutates enough that
lasting immunity is not possible. This reduced rate of antigenic change, combined with its limited host range (inhibiting
cross species antigenic shift), ensures that pandemics of influenza B do not occur.
https://en.wikipedia.org/wiki/Orthomyxoviridae .
- Virion enveloped, contains about 500 spikes, the nucleocapsid enclosed within lipoprotein membrane
- Virion contains 8 segments of linear negative-sense single stranded RNA.
- Infect much man and causes human disease but generally not as severe as Type A.
- Believed to be epidemiologically important-reassortment with Type A leads to epidemics.
Influenza C
- The influenza C virus infects humans and pigs, and can cause severe illness and local epidemics.[44]
However, influenza C is less common than the other types and usually causes mild disease in children.
https://en.wikipedia.org/wiki/Orthomyxoviridae.
- Virion enveloped
- Contains many spikes, the nucleocapsid enclosed with in lipoprotein membrane
- Virion contain 7 segments of linear negative – sense single stranded RNA.
Influenza D
- This is a genus that was classified in 2016, the members of which were first isolated in 2011. This genus appears to be
most closely related to Influenza C, from which it diverged several hundred years ago. There are at least two extant
strains of this genus. The main hosts appear to be cattle, but the virus has been known to infect pigs as well.
Replication
Multiplication
- Orthomyxovirus replication takes about 6 hours and kills the host cell. The viruses attach to permissive cells via the
hemagglutinin subunit, which binds to cell membrane glycolipids or glycoproteins containing N- acetylneuraminic acid, the
receptor for virus adsorption. The virus is then engulfed by pinocytosis into endosomes. The acid environment of the
endosome causes the virus envelope to fuse with the plasma membrane of the endosome, uncoating the nucleocapsid and
releasing it into the cytoplasm. A transmembrane protein derived from the matrix gene (M2) forms an ion channel for protons
to enter the virion and destabilize protein binding allowing the nucleocapsid to be transported to the nucleus, where the
genome is transcribed by viral enzymes to yield viral mRNA. Unlike replication of other RNA viruses, orthomyxovirus
replication depends on the presence of active host cell DNA. The virus scavenges cap sequences from the nascent mRNA
generated in the nucleus by transcription of the host DNA and attaches them to its own mRNA. These cap sequences allow
the viral mRNA to be transported to the cytoplasm, where it is translated by host ribosomes. The nucleocapsid is
assembled in the nucleus.
- Virions acquire an envelope and undergo maturation as they bud through the host cell membrane. During budding, the viral
envelope hemagglutinin is subjected to proteolytic cleavage by host enzymes. This process is necessary for the released
particles to be infectious. Newly synthesized virions have surface glycoproteins that contain N acetylneuraminic acid as a part
of their carbohydrate structure, and thus are vulnerable to self- agglutination by the hemagglutinin. A major function of the
viral neuraminidase is to remove these residues(https://www.ncbi.nlm.nih.gov/books/NBK8611/).
Gene Reassortment
- Because the influenza virus genome is segmented, genetic reassortment can occur when a host cell is infected simultaneously
with viruses of two different parent strains. If a cell is infected with two strains of type A virus, for example, some of the
progeny virions will contain a mixture of genome segments from the two strains. This process of genetic reassortment
probably accounts for the periodic appearance of the novel type A strains that cause influenza pandemics
(https://www.ncbi.nlm.nih.gov/books/NBK8611/).
Antigenic Drift
- Repeated minor antigenic changes, which generate strains that retain a degree of serologic relationship with the currently
prevailing strain.
- occurs in both type A and type B influenza viruses and is responsible for the strains that cause yearly influenza epidemics.
Antigenic Shift
- A major change in one or both of the surface antigens—a change that yields an antigen showing no serologic relationship
with the antigen of the strains prevailing at the time.
- Changes of this magnitude have been demonstrated in type A virus only and produce the strains responsible for influenza
pandemics.
Pathogenesis
- Influenza virus is transmitted from person to person primarily in droplets released by sneezing and coughing. Some of the
inhaled virus lands in the lower respiratory tract, and the primary site of disease is the tracheobronchial tree, although the
nasopharynx is also involved
- The neuraminidase of the viral envelope may act on the N-acetylneuraminic acid residues in mucus to produce liquefaction.
In concert with mucociliary transport, this liquified mucus may help spread the virus through the respiratory tract. Infection
of mucosal cells results in cellular destruction and desquamation of the superficial mucosa. The resulting edema and
mononuclear cell infiltration of the involved areas are accompanied by such symptoms as nonproductive cough, sore throat,
and nasal discharge. Although the cough may be striking, the most prominent symptoms of influenza are systemic: fever,
muscle aches, and general prostration. Viremia is rare, so these systemic symptoms are not caused directly by the virus.
Circulating interferon is a possible cause: administration of therapeutic interferon causes systemic symptoms resembling
those of influenza.
- Current evidence indicates that the extent of virus-induced cellular destruction is the prime factor determining the
occurrence, severity, and duration of clinical illness. In an uncomplicated case, virus can be recovered from respiratory
secretions for 3 to 8 days. Peak quantities of 104 to 107 infectious units/ml are detected at the time of maximal illness. After
1 to 4 days of peak shedding, the titer begins to drop, in concert with the progressive abatement of disease.
- Occasionally—particularly in patients with underlying heart or lung disease—the infection may extensively involve the alveoli,
resulting in interstitial pneumonia, sometimes with marked accumulation of lung hemorrhage and edema. Pure viral
pneumonia of this type is a severe illness with a high mortality. Virus titers in secretions are high, and viral shedding is
prolonged. In most cases, however, pneumonia associated with influenza is caused by bacteria, principally pneumococci,
staphylococci, and Gram-negative bacteria. These bacteria can invade and cause disease because the preceding viral infection
damages the normal defenses of the lung(https://www.ncbi.nlm.nih.gov/books/NBK8611/).
Host Defense
- The immune mechanisms responsible for recovery from influenza have not been clearly delineated. Several mechanisms
probably act in concert. Interferon appears in respiratory secretions shortly after viral titers reach their peak level, and may
play a role in the subsequent reduction in viral shedding. Antibody usually is not
detected in serum or secretions until later in recovery or during convalescence; nevertheless, local antibody appears
responsible for the final clearing of virus from secretions. T cells and antibody-dependent cell-mediated cytotoxicity
also participate in clearing the infection.
- Antibody is the primary defense in immunity to reinfection. IgG antibody, which predominates in lower respiratory secretions,
appears to be the most important. The IgG in these secretions is derived from the serum, which accounts for the close
correlation between serum antibody titer and resistance to influenza. IgA antibody, which predominates in upper respiratory
secretions, is less persistent than IgG but also contributes to immunity.
- Only antibody directed against the hemagglutinin is able to prevent infection. A sufficient titer of anti- hemagglutinin antibody
will prevent infection. Lower titers of anti-hemagglutinin antibody lessen the severity of infection. Anti-hemagglutinin
antibody administered after an infection is under way reduces the number of infectious units released from infected cells,
presumably because the divalent antibody aggregates many virions into a single infectious unit. Antibody directed against the
neuraminidase also reduces the number of infectious units (and thus the intensity of disease), presumably by impairing the
action of neuraminidase against N- acetylneuraminic acid residues in the virion envelope and thus promoting virus
aggregation. Antibody directed against nucleoprotein has no effect on virus infectivity or on the course of disease.
- Immunity to an influenza virus strain lasts for many years. Recurrent cases of influenza are caused primarily by antigenically
different strains(https://www.ncbi.nlm.nih.gov/books/NBK8611/).
Diagnosis
- A diagnosis of influenza is suggested by the clinical picture of sudden onset of fever, malaise, headache, marked muscle aches,
sore throat, nonproductive cough, and coryza. When a syndrome resembling influenza occurs in the winter in an adult (the
etiologies of illnesses of this type are more complex in children), an influenza virus is a likely cause. If an epidemic of febrile
respiratory disease is known to be under way in the community, the diagnosis is yet more likely. Definitive diagnosis, however,
relies on detecting either the virus or a significant rise in antibody titer between acute phase and convalescent-phase sera.
- A rapid specific diagnosis of influenza may be obtained by demonstrating viral antigens in cells obtained from the nasopharynx
in immunostaining tests such as immunofluorescence or in enzyme immunoassays (ELISA) employing respiratory secretions.
Influenza virus is usually isolated from respiratory secretions by being grown in tissue cultures or chick embryos. Virus growth
in tissue cultures is detected by testing for hemadsorption: red cells are added to the culture and adhere to virus budding
from infected cells. If the culture tests positive, serologic tests with specific antisera may be used to identify the virus. In the
chick embryo culture method, fluid from the amniotic or allantoic cavity of chick embryos is tested for the presence of newly
formed viral hemagglutinin; the virus in positive fluids is then identified by hemagglutination inhibition tests with specific
antisera. Finally, a rise in serum antibody titer between acute-phase and convalescent-phase sera can be identified by various
tests, of which complement fixation, hemagglutination inhibition, and immunodiffusion (using specific viral antigens) are the
most common. None of these techniques will identify all
infections((https://www.ncbi.nlm.nih.gov/books/NBK8611/).
Prevention
- Inactivated influenza virus vaccines have been used for about 40 years to prevent influenza. The viruses for the vaccine are
grown in chick embryos, inactivated by formalin, purified to some extent, and adjusted to a dosage known to elicit an antibody
response in most individuals. A given vaccine contains the strains of types A and B viruses that are judged most likely to
produce epidemics during the following winter. The vaccine is administered parenterally in the fall; one or two doses are
required, depending on the immune experience of the population with related antigens. Protection against illness has varied
from 50 to 90 percent in civilian populations and from 70 to 90 percent in military populations. Local and systemic reactions
to the vaccine are minor and occur in the first day or two after vaccination. During the national swine flu immunization of
1976 in the United States, an increased risk of developing Guillain-Barre syndrome accompanied vaccination; however, this
correlation has not been detected since. Annual use of inactivated influenza virus vaccine is currently recommended in the
United States for persons at risk of developing pneumonia from the disease and for their close associates. Live attenuated
vaccines are being developed as alternatives to inactivated vaccine.
- The synthetic drugs amantadine and rimantadine hydrochloride effectively prevent infection and illness caused by type A,
but not by type B, viruses. The drugs interfere with virus uncoating and transport by blocking the transmembrane M2 ion
channel (see multiplication). Drugs prevent about 50 percent of infections and about 67 percent of illnesses under natural
conditions. When administered for 10 days to household contacts of a person with influenza, drugs protect up to 80 percent
of the persons from illness. Side effects are greater for amantadine and limited primarily to the central nervous system ( CDC.
Prevention and Control of Influenza.MMWR, 44:No. RR 3:1-22, 1995 . [PubMed]) .
Treatment
- Amantadine and rimantadine are the only specific antiviral treatments available for influenza. As in the case of prophylaxis,
they are effective only against type A virus. When administration is started early in the course of illness, drugs hasten the
disappearance of fever and other symptoms. Emergence of viral resistance can occur during
treatment((https://www.ncbi.nlm.nih.gov/books/NBK8611/).
1. If antibody to the HA and NA are protective. Why we continually get epidemics of flu, with fever, chills, arthralgia, myalgias and
other miseries?
ANSWER: Antigenic Drift
RATIONALIZATION: Gradual accumulation of mutations that allow the hemagglutinin to escape neutralizing antibodies.
Epidemic strains thought to have changes in three or more antigenic sites. Repeated minor antigenic changes, which
generate strains that retain a degree of serologic relationship with the currently prevailing strain. Antigenic drift occurs in
both type A and type B influenza viruses and is responsible for the strains that cause yearly influenza epidemics. When
persons are reinfected with drift viruses, the serum antibody responses to the surface antigens that are shared with earlier
strains to which the person has been exposed are frequently stronger and of greater avidity than are the responses to the
new antigens. This phenomenon, is called “original antigenic sin,”
2. When all thinks that flu is just a pesky mild self-limiting disease; but truth be told that it can cause pneumonia and more serious
disease in the elderly, and still resolves without complications in 3-7 days. So why there have been a devastating pandemic of influenza
(1981)?
ANSWER: Antigenic shift
RATIONALIZATION: Antigenic shift is a complete change in HA and NA. A major change in one or both of the surface
antigens—a change that yields an antigen showing no serologic relationship with the antigen of the strains prevailing at the
time. Changes of this magnitude have been demonstrated in type A virus only and produce the strains responsible for
influenza pandemics.
3. Where does influenza came from?
ANSWER/ RATIONALIZATION: Type A constantly circulates in natural reservoirs. Birds are the natural reservoirs of all
subtypes of Influenza viruses ( migratory waterfowl, chickens, turkeys, ducks, geese)while humans, pigs, horses can be a
reservoir host too.
5. Why does influenza can recur despite the development of immunity?
ANSWER/RATIONALIZATION: Because influenza Type A and Type B viruses are proficient at altering their surface
antigens and thus generating strains that evade the existing immunity. Influenza strains are constantly appearing to which
part or all of the human population is susceptible.
4. Illustrate and label the complete viral structure of Orthomyxovirus
- Classic influenza is a febrile illness of the upper and lower respiratory tract, characterized by sudden onset of fever, cough,
myalgia, malaise, and other symptoms. Many patients do not exhibit the full syndrome. Pneumonia is the most common
serious complication.
Structure
- Influenza viruses are spherical or filamentous enveloped particles 80 to 120 nm in diameter. The helically symmetric
nucleocapsid consists of a nucleoprotein and a multipartite genome of single-stranded antisense RNA in seven or eight
segments. The envelope carries a hemagglutinin attachment protein and a neuraminidase.
Classification and Antigenic Types

- Influenza viruses are divided into types A, B, and C on the basis of variation in the nucleoprotein antigen. In types A and B the
hemagglutinin and neuraminidase antigens undergo genetic variation, which is the basis for the emergence of new strains;
type C is antigenically stable.
Multiplication/replication
- The virus binds to host cells via the hemagglutinin. Transcription and nucleocapsid assembly take place in the nucleus.
Progeny virions are assembled in the cytoplasm and bud from the cell membrane, killing the cell. In cells infected
simultaneously with more than one parent virion, the genome segments may undergo reassortment.
Pathogenesis
- The virus is transmitted in aerosols of respiratory secretions. It multiplies in the respiratory mucosa, causing cellular
destruction and inflammation.
Host Defense
- Both a cell-mediated response and antibody develop after infection. Antibody provides long-lasting immunity against the
infecting strain.
Epidemiology
- Influenza epidemics involving all age groups occur each winter; worldwide pandemics appear irregularly. Changes in the
hemagglutinin and neuraminidase surface antigens are responsible for the appearance of antigenically novel strains that
evade host immunity and cause reinfections.
Diagnosis
- The diagnosis is suggested by the symptoms, particularly if an influenza epidemic is under way. Definitive diagnosis depends
on detecting the virus or a rise in antibody titer.
Control
- An inactivated virus vaccine is developed each year against the strains most likely to cause disease the next winter. The drugs
amantadine and rimantadine can be used for prophylaxis and treatment of influenza A infections.
BS MLS / THIRD YEAR
Materials:
LESSON TITLE: RNA CONTAINING VIRUS ( SARS- Book, pen and notebook, index card/class list
CoV2/COVID-19)
References:
LEARNING OUTCOMES:
https://www.who.int/healthtopics/coronavirus#t
ab=tab_1.
1. identify the mode of transmission of RNA containing
(Yuefei, Jin et.al., 2020: Virology, Epidemiology,
virus ().SARS-COV2/COVID-19
Pathogenesis, and Control of COVID-19,
serological method. Department of Epidemiology, College of Public
3. practice consistently the ways and means on how to prevent Health, Zhengzhou University, Zhengzhou 450001,
and control viral infection. China School of Public Health, Xinxiang Medical
4. discuss the epidemiology, clinical stages and University, Xinxiang 453003, China Department of
pathogenesis of SARS-COV2/ COVID-19 virus. Immunology, Duke University Medical Center,
5. illustrate viral structure of SARS-COV2/COVID-19virus.
Durham, NC 27710, USA,
6. know the ways and means on treatment, prevention and
control of SARS-COV2/COVID-19virus infection.
https://www.mdpi.com/1999-
4915/12/4/372/htm).

Introduction
- At the end of 2019, a cluster of pneumonia patients with an unidentified cause emerged in Wuhan, Hubei Province, China (i,
Q.; Guan, X.; Wu, P.; Wang, X.; Zhou, L.; Tong, Y.; Ren, R.; Leung, K.S.M.; Lau, E.H.Y.; Wong, J.Y.; et al. Early Transmission
Dynamics in Wuhan, China, of Novel Coronavirus–Infected Pneumonia. N. Engl. J. Med. 2020. [Google Scholar] [CrossRef]
[PubMed].
- Since then, outbreaks and sporadic human infections have resulted in more than 80,000 laboratory confirmed cases (update
on March 23, 2020) across mainland China. Through the analysis of sequence, this unidentified pneumonia was considered
to be caused by a novel coronavirus (CoV) named 2019-nCoV (Zhu, N.; Zhang, D.; Wang, W.; Li, X.; Yang, B.; Song, J.; Zhao,
X.; Huang, B.; Shi, W.; Lu, R.; et al. A Novel Coronavirus from Patients with Pneumonia in China, 2019. N. Engl. J. Med.
2020. [Google Scholar] [CrossRef] [PubMed].
- Subsequently, the World Health Organization (WHO) announced a standard format of Coronavirus Disease-2019 (COVID-19),
according to its nomenclature, for this novel coronavirus pneumonia on February 11, 2020 ( World Health Organization Press
Conference. The World Health Organization (WHO) Has Officially Named the Disease Caused by the Novel
Coronavirus as COVID-19. Available online: https://www.who.int/emergencies/diseases/novel-coronavirus-
2019 (accessed on 11 February 2020).
- . On the same day, the International Committee on Taxonomy of Viruses (ICTV) named this novel coronavirus as SARS-CoV-2
(Gorbalenya, A.E.; Baker, S.C.; Baric, R.S.; de Groot, R.J.; Drosten, C.; Gulyaeva, A.A.; Haagmans, B.L.; Lauber, C.;
Leontovich, A.M.; Neuman, B.W.; et al. Severe acute respiratory syndrome-
related coronavirus: The species and its viruses—A statement of the Coronavirus Study Group. bioRxiv 2020.
[Google Scholar] [CrossRef].
- So far, the SARS-CoV-2 infection is still spreading, and this virus poses a serious threat to public health, though joint
prevention and quarantine mechanisms in almost all provinces of mainland China have been confirmed to be enacted. Due
to a lack of specific antiviral treatments and pressure of clinical treatment, thousands of severe cases have died every day
worldwide.
Virology, Origin and Classification

- At the end of 2019, COVID-19 emerged in several local hospitals of Wuhan, Hubei Province, China. Based on clinical
manifestations, blood tests, and chest radiographs, this disease was diagnosed as virus-induced pneumonia by
clinicians. Initial epidemiological investigation suggested that a majority of suspected cases were associated with their
presence (exposure) in a local Huanan seafood market. Notably, not just seafood, but many kinds of live wild animals
were available for sale in this market all year round before it was forced to close on January 1, 2020. As expected,
SARS-CoV-2 was isolated in environmental samples of the Huanan Seafood Market by China Center for Disease
Control and Prevention (CDC), implying the origin of the outbreak. However, such a decisive conclusion was disputed
because the earliest case had had no reported link connection to the mentioned market. In addition, it was found
that at least two different strains of SARS-CoV-2 had occurred a few months earlier before COVID-19 was officially
reported. A recently phyloepidemiologic analysis suggests that SARS-CoV-2 at the Huanan Seafood Market could have
been imported from other places. To date, it remains inconsistent with regard to the origin of SARS-CoV-2, and
epidemiologic and etiologic investigations are being conducted by Chinese health authorities (Yuefei, Jin et.al., 2020:
Virology, Epidemiology, Pathogenesis, and Control of COVID-19, Department of Epidemiology, College of Public
Health, Zhengzhou University, Zhengzhou 450001, China School of Public Health, Xinxiang Medical University, Xinxiang
453003, China Department of Immunology, Duke University Medical Center, Durham, NC 27710, USA,
https://www.mdpi.com/1999-4915/12/4/372/htm).
- Geographic location of Wuhan, Hubei Province in China. Hubei Province is located in the central area of China, and the
provincial capital is Wuhan.
- SARS-CoV-2 was first isolated in the bronchoalveolar lavage fluid (BALF) of three COVID-19 patients from Wuhan
Jinyintan Hospital on December 30, 2019. After sequence and evolutionary tree analysis, SARS- CoV-2 was
considered as a member of β-CoVs. The CoVs family is a class of enveloped, positive-sense single-stranded RNA
viruses having an extensive range of natural roots. These viruses can cause respiratory, enteric, hepatic, and
neurologic diseases. The CoVs are genotypically and serologically divided into four subfamilies: α, β, γ, and δ-CoVs.
Human CoV infections are caused by α- and β-CoVs]. SARS coronavirus (SARS-CoV) and MERS coronavirus (MERS-
CoV) are members of β-CoVs . Genome-wide phylogenetic analysis indicates that SARS-CoV-2 shares 79.5% and 50%
sequence identity to SARS-CoV and MERS-CoV, respectively. However, there is 94.6% sequence identity between the
seven conserved replicase domains in ORF1ab of SARS-CoV-2 and SARS-CoV, and less than 90% sequence identity
between those of SARS-CoV-2 and other β-CoVs, implying that SARS-CoV-2 belongs to the lineage B (Sarbecovirus) of
β-CoVs ((Yuefei, Jin et.al., 2020: Virology, Epidemiology, Pathogenesis, and Control of COVID-19, Department of
Epidemiology, College of Public Health, Zhengzhou University, Zhengzhou 450001, China School of Public Health,
Xinxiang Medical University, Xinxiang 453003, China Department of
Immunology, Duke University Medical Center, Durham, NC 27710, USA, https://www.mdpi.com/1999-
4915/12/4/372/htm).
VIRUS STRUCTURE
- As shown in the figure below(A), similar to other β-CoVs, the SARS-CoV-2 virion with a genome size of 29.9 kb possesses a
nucleocapsid composed of genomic RNA and phosphorylated nucleocapsid (N) protein. The nucleocapsid is buried inside
phospholipid bilayers and covered by two different types of spike proteins: the spike glycoprotein trimmer (S) that exists in
all CoVs, and the hemagglutinin-esterase (HE) only shared among some CoVs. The membrane (M) protein and the
envelope (E) protein are located among the S proteins in the viral envelope.
- The SARS-CoV-2 genome has 5′ and 3′ terminal sequences (265 nt at the 5′ terminal and 229 nt at the 3′ terminal region),
which is typical of β-CoVs, with a gene order 5′-replicase open reading frame (ORF) 1ab-S-envelope(E)- membrane(M)-N-3′
9FigureB).
- The predicted S, ORF3a, E, M, and N genes of SARS-CoV-2 are 3822, 828, 228, 669, and 1260 nt in length, respectively.
Similar to SARS-CoV, SARS-CoV-2 carries a predicted ORF8 gene (366 nt in length) located between the M and N ORF genes
(Yuefei, Jin et.al., 2020: Virology, Epidemiology, Pathogenesis, and Control of COVID-19, Department of Epidemiology,
College of Public Health, Zhengzhou University, Zhengzhou 450001, China School of Public Health, Xinxiang Medical
University, Xinxiang 453003, China Department of Immunology, Duke University Medical Center, Durham, NC 27710,
USA, https://www.mdpi.com/1999- 4915/12/4/372/htm).
- β-coronavirus particle and genome (A) The β-coronavirus particle. β-coronavirus is an enveloped, nonsegmented,
positive-sense single-stranded RNA virus genome in a size ranging from 29.9 kb. The virion has a nucleocapsid composed
of genomic RNA and phosphorylated nucleocapsid (N) protein, which is buried inside phospholipid bilayers and covered
by the spike glycoprotein trimmer (S).
- The membrane (M) protein hemagglutinin-esterase (HE) and the envelope (E) protein are located among the S proteins in
the virus envelope. (B) 5′ and 3′ terminal sequences of the SARS-CoV-2 genome. The gene order is 5′-replicase ORF1ab-S-
envelope(E)-membrane(M)-N-3′. ORF3ab, ORF6, ORF7ab, ORF8, ORF9ab, and ORF10 are located at the predicted positions
shown in the picture. 1a, 1b, 3a, 3b, 6, 7a, 7b, 8, 9a, 9b, 10 in the picture represent different ORF genes (Yuefei, Jin et.al.,
2020: Virology, Epidemiology, Pathogenesis, and Control of COVID-19, Department of Epidemiology, College of Public
Health, Zhengzhou University, Zhengzhou 450001, China School of Public Health, Xinxiang Medical University,
Xinxiang 453003, China Department of Immunology, Duke University Medical Center, Durham, NC 27710, USA,
https://www.mdpi.com/1999- 4915/12/4/372/htm).
Physicochemical Properties
- The virus particle has a diameter of 60~100 nm and appears round or oval. Most of the knowledge about the
physicochemical properties of CoVs comes from SARS-CoV and MERS-CoV. SARS-CoV-2 can be inactivated by UV or heated
at 56 °C 30 min, and also sensitive to most disinfectants such as diethyl ether, 75% ethanol, chlorine, peracetic acid, and
chloroform. It has been reported that SARS-CoV-2 was more stable on plastic and
stainless steel than on copper and cardboard, and viable virus was detected up to 72 h after application to these surfaces.
On cardboard, the half-life of SARS-CoV-2 was longer than that of SARS-CoV and the longest viability of both viruses was on
stainless steel and plastic ((Yuefei, Jin et.al., 2020: Virology, Epidemiology, Pathogenesis, and Control of COVID-19,
Department of Epidemiology, College of Public Health, Zhengzhou University, Zhengzhou 450001, China School of
Public Health, Xinxiang Medical University, Xinxiang 453003, China Department of Immunology, Duke University
Medical Center, Durham, NC 27710, USA, https://www.mdpi.com/1999-4915/12/4/372/htm).
Receptor Interactions and Cell Entry

- Human angiotensin-converting enzyme 2 (ACE2) is a functional receptor hijacked by SARS-CoV-2 for cell entry, similar to
SARS-CoV. ACE2 is a type I membrane protein expressed in lung, heart, kidney, and intestine mainly associated with
cardiovascular diseases. The full-length ACE2 consists of an N-terminal peptidase domain (PD) and a C terminal Collectrin-
like domain (CLD) that ends with a single transmembrane helix and an~40-residue intracellular segment. In addition to
cleavage of angiotensin (Ang) I to produce Ang-(1-9), ACE2 also provides a direct binding site for the S proteins of CoVs. The
S protein of CoVs exists in a metastable pre-fusion conformation that undergoes a dramatic structural rearrangement to
fuse the viral membrane with the host cell membrane. This process is triggered by the S1 subunit and a host–cell receptor
binding, which destabilizes the pre-fusion trimer, resulting in the S1 subunit shedding and the S2 subunit transition to a
highly stable post-fusion conformation. To engage a host–cell receptor, the receptor-binding domain (RBD) of S1 undergoes
hinge-like conformational movements that transiently hide or expose the determinants of receptor binding. In order to
figure out the potential of SARS-CoV-2 to infect humans, the receptor-binding domain (RBD) of its S protein, which is in
contact with ACE2, was analyzed. The biophysical and structural evidence suggests that SARS-CoV-2 S protein likely binds to
human ACE2 with 10–20 fold higher affinity than SARS-CoV . Another structural evidence suggests that the ACE2-B0AT1
complex can bind two S proteins simultaneously ((Yuefei, Jin et.al., 2020: Virology, Epidemiology, Pathogenesis, and
Control of COVID-19, Department of Epidemiology, College of Public Health, Zhengzhou University, Zhengzhou
450001, China School of Public Health, Xinxiang Medical University, Xinxiang 453003, China Department of
4915/12/4/372/htm).
Genomic Variation
- The initial 10 genomic sequences of SARS-CoV-2 obtained from the nine COVID-19 patients were extremely similar,
exhibiting more than 99.98% sequence identity, implying that not much variation has taken place. A recent study
indicates that 120 substitution sites were evenly distributed in eight coding regions, without evident recombination
events. However, Tang et al. found that SARS-CoV-2 had evolved into two major types of L and S, based on analyses
of 103 genomes. Due to severe selective pressure on the L type, the L type might be more aggressive and spread
more quickly, while the S type might remain milder due to relatively weaker selective pressure. Due to the unstable
nature of RNA viruses, the continuous surveillance of SARS-CoV-2 from humans or animals is extremely important
for disease control (Yuefei, Jin et.al., 2020: Virology, Epidemiology, Pathogenesis, and Control of COVID-19,
Department of Epidemiology, College of Public Health, Zhengzhou University, Zhengzhou 450001, China School of
Public Health, Xinxiang Medical University, Xinxiang 453003, China Department of Immunology, Duke University
EPIDEMIOLOGY
- Highlights
 The basic reproductive number (R0) of 2019-nCoV is higher than (R0) of Severe Acute Respiratory Syndrome Coronavirus
(SARS-CoV) and Middle East Respiratory Syndrome Coronavirus (MERS-CoV). COVID-19 presents with asymptomatic
infections, with potential to propagate and perpetuate this pandemic.
 2019- nCoV isolated from patients shows limited sequence diversity, suggesting that the interspecies transmission event
was very recent and that the source of the virus was focused, possibly a point-source event.
 The amino acid sequence in the ACE2 receptor responsible for 2019-nCoV binding in farm animals and cats has only a
few exchanges compared with the human receptor, suggesting that the species barrier for virus transmission is small (
Jiumeng Sun, et.al., 2020: COVID-19 Epidemiology, Evolution and Cross-Disciplinary Perspective
https://www.sciencedirect.com/science/article/abs/pii/S1471491420300654).
- Originated in bats, 2019-nCoV/ severe acute respiratory syndrome coronavirus (SARS-CoV)-2 likely experienced adaptive evolution
in intermediate hosts before transfer to humans at a concentrated source of transmission. Similarities of receptor sequence
binding to 2019-nCoV between humans and animals suggest a low species barrier for transmission of the virus to farm
animals(Jiumeng Sun, et.al., 2020: COVID-19 Epidemiology, Evolution and Cross-Disciplinary Perspective
https://www.sciencedirect.com/science/article/abs/pii/S1471491420300654).).
Source of Infection
- Currently, COVID-19 patients are the main source of infection, and severe patients are considered to be more contagious
than mild ones. Asymptomatically infected persons or patients in incubation who show no signs or symptoms of respiratory
infection proven to shed infectious virus, may also be potential sources of infection. Additionally, samples taken from
patients recovered from COVID-19 continuously show a positive RT-PCR test, which has never been seen in the history of
human infectious diseases. In other words, asymptomatically infected persons and patients in incubation or recovered from
COVID-19 may pose serious challenges for disease prevention and control(Yuefei, Jin et.al., 2020: Virology, Epidemiology,
Pathogenesis, and Control of COVID-19, Department of Epidemiology, College of Public Health, Zhengzhou University,
Zhengzhou 450001, China School of Public Health, Xinxiang Medical University, Xinxiang 453003, China Department of
4915/12/4/372/htm). .
Spectrum of Infection
- COVID-19 has been considered as a type of self-limiting infectious disease, and most cases with mild symptoms can recover
in 1–2 weeks. SARS-CoV-2 infection can cause five different outcomes: asymptomatically infected persons (1.2%); mild to
medium cases (80.9%); severe cases (13.8%); critical case (4.7%); and death (2.3% in all reported cases). The latest study
indicates that the proportion of asymptomatic infection in children under 10- years old is as high as 15.8%. Therefore, the
proportion of asymptomatic infection should be further uncovered in the future(Yuefei, Jin et.al., 2020: Virology,
Epidemiology, Pathogenesis, and Control of COVID-19, Department of Epidemiology, College of Public Health, Zhengzhou
University, Zhengzhou 450001, China School of Public Health, Xinxiang Medical University, Xinxiang 453003, China
Department of Immunology, Duke University Medical Center, Durham, NC 27710, USA, https://www.mdpi.com/1999-
4915/12/4/372/htm).
Regions Affected
- According to the WHO data updated on March 23, 2020, 190countriesor areas have reported 332,218 laboratory confirmed
cases including 14,510 deaths. The total case-fatality rate of global cases outside China is 4.5%. More attention should be
paid to Italy, Spain, the USA, Germany, France, and Iran with more severe outbreaks. The top five countries with the highest
cumulative confirmed cases in the world are China (24.6%), Italy (17.8%), USA (9.5%), Spain (8.6%), and Germany (7.5%).
Higher case-fatality rates were found in Italy (9.3%), Iran (7.8%), and Spain (6.0%)(Yuefei, Jin et.al., 2020: Virology,
Epidemiology, Pathogenesis, and Control of COVID- 19, Department of Epidemiology, College of Public Health, Zhengzhou
4915/12/4/372/htm).
Herd Susceptibility
- A s an emerging infectious disease, the population of all races and ages is generally susceptible. In mainland China, 30~65-
year-old persons account for 71.45% and children under 10-years-old account for 0.35%. Elderly people and persons with
underlying basic disorders such as asthma, diabetes, cardiovascular diseases, and cancer may be more susceptible to SARS-
CoV-2. Smoking and obesity are also susceptible factors(Yuefei, Jin et.al., 2020: Virology, Epidemiology, Pathogenesis, and
Control of COVID-19, Department of Epidemiology, College of Public Health, Zhengzhou University, Zhengzhou 450001, China
School of Public Health, Xinxiang Medical University, Xinxiang 453003, China Department of Immunology, Duke University
High-Risk Population
- Persons who are in close contact with patients or subclinically symptomatic infected persons are part of the high-risk
population. High infection risk is also considered in healthcare workers and the family members of patients(Yuefei, Jin et.al.,
2020: Virology, Epidemiology, Pathogenesis, and Control of COVID-19, Department of Epidemiology, College of Public
Health, Zhengzhou University, Zhengzhou 450001, China School of Public
Health, Xinxiang Medical University, Xinxiang 453003, China Department of Immunology, Duke University Medical Center,
Durham, NC 27710, USA, https://www.mdpi.com/1999-4915/12/4/372/htm).
TRANSMISSION
- The COVID-19 virus spreads primarily through droplets of saliva or discharge from the nose when an infected person coughs or
sneezes, so it’s important that you also practice respiratory etiquette (for example, by coughing into a flexed elbow)
https://www.who.int/health-topics/coronavirus#tab=tab_1.
Route of transmission
- Currently, respiratory droplets and contact transmission are considered to be the main transmission routes. Recent reports
indicate that SARS-CoV-2 can be detected in the urine and stool of laboratory confirmed patients, implying a risk of fecal–
oral transmission. However, it is not yet certain that the consumption of virus- contaminated foods will cause infection and
transmission. There is still no evidence that SARS-CoV-2 can be transmitted through aerosols or from mother to baby during
pregnancy or childbirth(Yuefei, Jin et.al., 2020: Virology, Epidemiology, Pathogenesis, and Control of COVID-19, Department
of Epidemiology, College of Public Health, Zhengzhou University, Zhengzhou 450001, China School of Public Health, Xinxiang
Medical University, Xinxiang 453003, China Department of Immunology, Duke University Medical Center, Durham, NC 27710,
USA, https://www.mdpi.com/1999-4915/12/4/372/htm).
PATHOGENESIS:
Viral Entry and Spread
- SARS-CoV-2 is transmitted predominantly via respiratory droplet, contact, and potential in fecal-oral. Primary viral
replication is presumed to occur in mucosal epithelium of upper respiratory tract (nasal cavity and pharynx), with further
multiplication in lower respiratory tract and gastrointestinal mucosa, giving rise to a mild viremia. Few infections are
controlled at this point and remain asymptomatic. Some patients have also exhibited non- respiratory symptoms such as
acute liver and heart injury, kidney failure, diarrhea, implying multiple organ involvement. ACE2 is broadly expressed in
nasal mucosa, bronchus, lung, heart, esophagus, kidney, stomach, bladder, and ileum, and these human organs are all
vulnerable to SARS-CoV-2. Recently, potential pathogenicity of the SARS-CoV-2 to testicular tissues hasalso been proposed
by clinicians, implying fertility concerns in young patients. The postulated pathogenesis of SARS-CoV-2 infection is graphed
in the figure below(Yuefei, Jin et.al., 2020: Virology, Epidemiology, Pathogenesis, and Control of COVID-19, Department of
Epidemiology, College of Public Health, Zhengzhou University, Zhengzhou 450001, China School of Public Health, Xinxiang
- Postulated pathogenesis of SARS-CoV-2 infection. Antibody-dependent enhancement (ADE); ACE2: angiotensin-converting

enzyme 2; RAS: renin-angiotensin system; ARDS: acute respiratory distress syndrome. Red words represent the important
turning points in SARS-CoV-2 infection.
- COVID-19 affects different people in different ways. Most infected people will develop mild to moderate illness and
recover without hospitalization.
- Most common symptoms:
 Fever
 Dry cough
 Tireness
- Less common symptoms:
 Aches and pains
 Sore throat
 Diarrhoea
 Conjuctivitis
 Headache
 Loss of taste or smell
 A rash on skin, or discoloration of fingers or toes
- Serious symptoms:
 Difficulty in breathing or shortness of breath
 Chest pain or pressure
 Loss of speech or movement
NOTE:
- It is advice to seek immediate medical attention if serious symptoms occur. Always call before visiting the physician or health
facility.
- People with mild symptoms who are otherwise healthy should manage their symptoms at home.
- On average , it takes 5-6 days from when someone is infected with the virus for symptoms to show, however it can take up to 14
days.
LABORATORY INVESTIGATION AND DIAGNOSIS
Nucleic Acid Test
- Viral diagnostics is one important part of our armamentarium against COVID-19. After initial outbreak, diagnostic tests
based on the detection of the viral sequence by RT-PCR or next generation sequencing platforms soon became available.
Subsequently, many biotechnology companies have successfully developed nucleic acid detection kits, and the China Food
and Drug Administration (CFDA) has urgently approved a batch of fluorescent quantitative kits and sequencing systems.
- The main concern related to the nucleic acid test is false negatives. To solve the problem of low detection efficiency, some
improved rapid viral nucleic acid diagnostic tests have been invented. Particularly, a nucleic acid test paper, which can be
used for the rapid detection of SARS-CoV-2 with the naked eye observation within three minutes, has been successfully
developed(Yuefei, Jin et.al., 2020: Virology, Epidemiology, Pathogenesis, and Control of COVID-19, Department of
RT-PCR (REAL-TIME POLYMERASE CHAIN REACTION)
- The COVID-19 RT-PCR test is a real-time reverse transcription polymerase chain reaction (rRT-PCR) test for the qualitative
detection of nucleic acid from SARS-CoV-2 in upper and lower respiratory specimens (such as nasopharyngeal or oropharyngeal
swabs, sputum, lower respiratory tract aspirates, bronchoalveolar lavage, and nasopharyngeal wash/aspirate) collected from
individuals suspected of COVID 19 by their healthcare provider (HCP), as well as upper respiratory specimens (such as
nasopharyngeal or oropharyngeal swabs, nasal swabs, or mid- turbinate swabs) collected from any individual, including from
individuals without symptoms or other reasons to suspect COVI-19 infection.
- The COVID-19 RT-PCR test is also for the qualitative detection of nucleic acid from the SARS-CoV-2 in pooled samples, using a
matrix pooling strategy (i.e., group pooling strategy), containing up to five individual upper respiratory swab specimens
(nasopharyngeal, mid-turbinate, anterior nares or oropharyngeal swabs) per pool and 25 specimens per matrix, where each
specimen is collected under observation or by a HCP using individual vials containing transport media. Negative results from
pooled testing should not be treated as definitive. If a patient’s clinical signs and symptoms are inconsistent with a negative result
or results are necessary for patient management, then the patient should be considered for individual testing. Specimens included
in pools where the positive sample cannot be identified using the matrix must be tested individually prior to reporting a result.
Specimens with low viral loads may not be detected in sample pools due to the decreased sensitivity of pooled testing.
- Results are for the identification of SARS-CoV-2 RNA. The SARS-CoV-2 RNA is generally detectable in respiratory specimens
during the acute phase of infection. Positive results are indicative of the presence of SARS-CoV-2 RNA; clinical correlation with
patient history and other diagnostic information is necessary to determine patient infection status. Positive results do not rule
out bacterial infection or co-infection with other viruses. The agent detected may not be the definite cause of disease.
Laboratories within the United States and its territories are required to report all positive results to the appropriate public
health authorities.
- Negative results do not preclude SARS-CoV-2 infection and should not be used as the sole basis for patient management decisions.
Negative results must be combined with clinical observations, patient history, and epidemiological information.
- Testing with the COVID-19 RT-PCR test is intended for use by trained clinical laboratory personnel specifically instructed and
trained in the techniques of real-time PCR and in vitro diagnostic procedures. The COVID-19 RT-PCR is only for use under the Food
and Drug Administration’s Emergency Use Authorization.
NOTE: FOR MORE UNDERSTANDING ON THE DIFFERENT MACHINES USED FOR DETECTION OF COVID-19
INFECTION USING RT – PCR REFER TO THE FF:
 LabCorp COVID-19 RT-PCR test EUA Summary – 7/24/2020
 Novel Coronavirus (2019-nCoV) Nucleic Acid Diagnostic Kit (PCR-Fluorescence Probing) USINF SANSURE
NATCH /MA 6000
 Qualitative assay for use on the QX200™ and QXDx™ Droplet Digital™ PCR Systems
Serologic Diagnosis
- It has been shown that patients with SARS-CoV-2 infection possess acute serological responses. Combined with
immunochromatography, colloidal gold, and other technologies, relevant detection reagents have been developed
rapidly(Yuefei, Jin et.al., 2020: Virology, Epidemiology, Pathogenesis, and Control of COVID-19, Department of Epidemiology,
College of Public Health, Zhengzhou University, Zhengzhou 450001, China School of Public Health, Xinxiang Medical
University, Xinxiang 453003, China Department of Immunology, Duke University Medical Center, Durham, NC 27710, USA,
CRISPR/Cas13 System
- The Cas13-based SHERLOCK (specific high-sensitivity enzymatic reporter unlocking) platform has been widely used to detect
Zika virus (ZIKV) and dengue virus (DENV) in patient samples at concentrations as low as 1 copy per microliter. Recently,
Zhang et al. released a CRISPR/Cas13-based SHERLOCK technology to detect SARS- CoV-2. However, this CRISPR/Cas13
system remains to be verified because it has not been tested on clinical samples from COVID-19 patients(Yuefei, Jin et.al.,
2020: Virology, Epidemiology, Pathogenesis, and Control of COVID-19, Department of Epidemiology, College of Public Health,
Zhengzhou University, Zhengzhou 450001, China School of Public Health, Xinxiang Medical University, Xinxiang 453003,
China Department of Immunology, Duke University Medical Center, Durham, NC 27710, USA,
https://www.mdpi.com/1999- 4915/12/4/372/htm).
Imaging Technology
- Chest radiograph or CT is an important tool for COVID-19 diagnosis in clinical practice. The majority of
COVID- 19 cases have similar features on CT images including bilateral distribution of patchy shadows and
ground glass
opacity. The great value of using the deep learning machine to extract radiological graphical features for COVID- 19 diagnosis
has been introduced. Artificial Intelligence (AI) can accurately interpret the CT images of the suspected cases of the new
crown within 20 s, and the accuracy rate of the analysis results reached 96%, greatly improving the diagnostic efficiency.
This technique is already being used in clinical practice(Yuefei, Jin et.al., 2020: Virology, Epidemiology, Pathogenesis, and
TREATMENT
- At this time, there are no specific vaccines or treatments for COVID-19. However, there are many ongoing clinical trials evaluating
potential treatments. WHO will continue to provide updated information as soon as clinical findings become
available(https://www.who.int/health-topics/coronavirus#tab=tab_1).
Potential Therapeutics
- Currently, there are no specificantiviral drugs or vaccines for the control of SARS-CoV-2. Symptomatic treatment strategies
are recommended for clinical practice. Here, we summarize potential therapeutics available for the treatment of SARS-CoV-
2.
Type I IFNs
- Type I IFNs are antiviral cytokines that induce a large range of proteins that can impair viral replication in targeted cells.
Previous studies have reported that IFN-β was superior against SARS-CoV compared to IFN-α. Synergistic effects of
leukocytic IFN-α with ribavirin and IFN-β with ribavirin against SARS-CoV were demonstrated in vitro(Yuefei, Jin et.al., 2020:
Virology, Epidemiology, Pathogenesis, and Control of COVID-19, Department of Epidemiology, College of Public Health,
Zhengzhou University, Zhengzhou 450001, China School of Public Health, Xinxiang Medical University, Xinxiang 453003,
China Department of Immunology, Duke University Medical Center, Durham, NC 27710, USA,
https://www.mdpi.com/1999-4915/12/4/372/htm). .
Potential Antiviral Compounds
- Ribavirin. During the outbreak of SARS in Hong Kong, ribavirin was broadly used for patients with or without
concomitant use of steroids. Ribavirin and IFN-β could synergistically inhibit SARS-associated CoV replication
in vitro.Due to adverse reactions, the proper dose of ribavirin in clinical application should be given carefully.
- Lopinavir/ritonavir. The combination of lopinavir/ritonavir is widely used in the treatment of HIV infection. It has been
reported that the use of lopinavir/ritonavir with ribavirin has a good therapeutic effect in SARSand MERS. Lopinavir/ritonavir
has been recommended for clinical treatment for COVID-19(Yuefei, Jin et.al., 2020: Virology, Epidemiology, Pathogenesis,
and Control of COVID-19, Department of Epidemiology, College of Public Health, Zhengzhou University, Zhengzhou 450001,
China School of Public Health, Xinxiang Medical University, Xinxiang 453003, China Department of Immunology, Duke
University Medical Center, Durham, NC 27710, USA, https://www.mdpi.com/1999-4915/12/4/372/htm). .
- Remdesivir. Remdesivir (RDV) was previously reported to restrain SARS-CoV in vivo, and the antiviral
protection of RDV and IFN-β was found to be superior to that of lopinavir/ritonavir-IFN-β against MERS-CoV in vitro and in
vivo. In addition, remdesivir was used in the treatment of the first COVID-19 patient in the United Statesand was shown to
have antiviral activity against SARS-CoV-2 in vitro]. However, its effectiveness and safety have not been verified in clinical
trials yet(Yuefei, Jin et.al., 2020: Virology, Epidemiology, Pathogenesis, and Control of COVID-19, Department of
USA, https://www.mdpi.com/1999-4915/12/4/372/htm). .
- Nelfinavir. Nelfinavir is a selective inhibitor of HIV protease, which has been shown to have a strong inhibition
of SARS-CoV implying a possible therapeutic for COVID-19.
- Arbidol. Arbidol, a broad-spectrum antiviral compound, is able to block viral fusion against influenza viruses. In
addition, arbidol and its derivative, arbidolmesylate, have been reported to have antiviral activity against SARS- CoV in vitro].
The ntiviral activity of arbidol against SARS-CoV-2 has been confirmed in vitro and recommended for clinical
treatment(Yuefei, Jin et.al., 2020: Virology, Epidemiology, Pathogenesis, and Control of COVID-19, Department of
Epidemiology, College of Public Health, Zhengzhou University, Zhengzhou 450001, China School
of Public Health, Xinxiang Medical University, Xinxiang 453003, China Department of Immunology, Duke University Medical
Center, Durham, NC 27710, USA, https://www.mdpi.com/1999-4915/12/4/372/htm). .
- Chloroquine. Chloroquine has many interesting biochemical properties including antiviral effect. It has been found to be a
potent inhibitor of SARS-CoV through interfering with ACE2. Chloroquine can effectively inhibit SARS-CoV-2 in vitro, and is
recommended for the clinical control of viral replication(Yuefei, Jin et.al., 2020: Virology, Epidemiology, Pathogenesis, and
Convalescent Plasma
- Recently, convalescent plasma has been widely recommended to be used for COVID-19, but the effect of convalescent
plasma cannot be discerned from the effects of patient comorbidities, stage of illness, or effect of other treatments(Yuefei,
Jin et.al., 2020: Virology, Epidemiology, Pathogenesis, and Control of COVID-19, Department of Epidemiology, College of
Public Health, Zhengzhou University, Zhengzhou 450001, China School of Public Health, Xinxiang Medical University, Xinxiang
453003, China Department of Immunology, Duke University Medical Center, Durham, NC 27710, USA,
Protective Monoclonal Antibody

- It has been reported that the monoclonal antibody (mAb) can efficiently neutralize SARS-CoV and inhibit syncytia formation
between cells expressing the S protein and those expressing the SARS-CoV receptor ACE2. However, mAbs can only
recognize a single epitope, and the anti-infective effect may be limited. In addition, the development of mAbs requires a
certain period of time, which is difficult to achieve in clinical application in a short time(Yuefei, Jin et.al., 2020: Virology,
4915/12/4/372/htm).
Others
- Based on the virology of SARS-CoV-2, blocking the binding of S protein to ACE2 is important for the treatment of virus
infection. ACE2 is an important component of the renin-angiotensin system (RAS). RAS inhibitors, ACEI and AT1R, may be
potential therapeutic tools for COVID-19. Additionally, intravenous transplantation of ACE2- mesenchymal stem cells
(MSCs), blocking of FcR with immunoglobulin (IVIG), and systemic anti-inflammatory drugs to reduce cytokine storm are
also potential therapeutic strategies for severe COVID-19. (Yuefei, Jin et.al., 2020: Virology, Epidemiology, Pathogenesis, and
PREVENTION
- To prevent infection and to slow transmission of COVID-19, do the following:

 1. Wash your hands regularly with soap and water, or clean them with alcohol-based hand rub.
 2. Maintain at least 1 metre distance between you and people coughing or sneezing.
 3. Avoid touching your face.
 4. Cover your mouth and nose when coughing or sneezing.
 5. Stay home if you feel unwell.
 6. Refrain from smoking and other activities that weaken the lungs.
 7. Practice physical distancing by avoiding unnecessary travel and staying away from large groups of people.
Vaccine Development
- accination probably offers the best option for COVID-19 control. Epitopes, mRNA, and S protein-RBD structure- based
vaccines have been widely proposed and started. Rapid reconstruction of SARS-CoV-2 using a synthetic genomics platform
has been reported, and this technical advance is helpful for vaccine development. Human ACE2 transgenic mouse and rhesus
monkey models of COVID-19 have been well established for vaccine development, and someSARS-CoV-2 vaccines are
already under clinical trial(Yuefei, Jin et.al., 2020: Virology,
4915/12/4/372/htm). .
1. What is COVID-19 and how is it related to SARS-CoV and MERS-CoV?
ANSWER: _
2. Is convalescent plasma effective in treating COVID-19 patient?
ANSWER:

SARS-COV2/ COVID-19
- Coronavirus disease (COVID-19) is an infectious disease caused by a newly discovered coronavirus.
- Most people infected with the COVID-19 virus will experience mild to moderate respiratory illness and recover without
requiring special treatment. Older people, and those with underlying medical problems like cardiovascular disease, diabetes,
chronic respiratory disease, and cancer are more likely to develop serious illness.
- The best way to prevent and slow down transmission is be well informed about the COVID-19 virus, the disease it causes and
how it spreads. Protect yourself and others from infection by washing your hands or using an alcohol based rub frequently
and not touching your face (https://www.who.int/health-topics/coronavirus#tab=tab_1).
You will now mark (encircle) the session you have finished today in the tracker below. This is simply a visual to help you
track how much work you have accomplished and how much work there is left to do.
You are done with the session! Let’s track your progress.
AL Strategy: Illustration and Discussion and Analysis (through questions and rationalization of answer). Something to think
about?
1. What important lesson you learned from this topic?
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MYCOLOGY&VIROLOGY

The branching filaments of molds and mushrooms *

Mass of hyphae constructing the thallus *

It is used to demonstrate germ tube production by the yeast Candida albicans *

It is used for growth of Cryptococcus neoformans *

It is used to recover dermatophytes. *

Infection of the scalp Caused by Microsporum and Trichophyton *

Tinea is a mycotic organism? *

Histoplasma capsulatum and Sporothrix schenckii are both dimorphic. *

Which of the following organism below is considered to be achlorophyllous. *

Which pair below is correctly matched: *

BACTERIA : 4um in dm.

Both H. capsulatum and C. neoformans can be acquired via bird droppings. *

Opportunistic fungi usually have hyaline hyphae. *

Causative agent of AIDS:

Causative agent of HEPATITIS B: *

Causative agent of HEPATITIS A: *

Causative agent of DENGUE: *

Causative agent of MUMPS: *

Causative agent of Influenza type A: *

Causative agent of Influenza type B: *

It causes a primary disease (chicken pox) and a recurrent disease (shingles) *

Varicella zoster virus

The preferred pH range for bacterial growth *

The preferred pH range for Mycotic/fungal growth *

The pH range/value which is considered to be Neutral is *

The pH range/value which is considered to be Acidic. *

The pH range/value which is considered to be Alkaline. *

Do some fungi produce substances that may kill bacteria? *

1. Which of the following organism below is considered to be achlorophyllous. *

2. Which statement below is not true regarding fungi. *

They exist in nature as saprophytic.

4. Fungi are much closely associated to _______ in terms of structure. *

5. Which pair below is correctly matched: *

FUNGI : APPROX 7um in dm.

7. The cell wall content of a bacteria is mostly composed of: *

Spore in fungi is primarily used for reproduction.

9. What type of hyphae is responsible for nutrient absorption and stability. *

16. 1porothrix schenkii is a dimorphic fungus, same as Candida albicans. *

17. Madura's foot is a condition caused by a fungal specie only. *

18. JOCK ITCH IS otherwise known : *

1. HALLMARK: MACROCONIDIA WITH TUBERCULATE-FINGER LIKE PROJECTIONS.

2. HALLMARK: INTRACELLULAR YEAST CELLS, MOSTLY RESISTANT TO PHAGOCYTIC ACTION OF MACROPHAGES. *

3. HALLMARK: COB-WEB LIKE GROWTH OF MYCELIUM.

4. HALLMARK: INTRACELLULAR YEAST CELLS, MOSTLY RESISTANT TO PHAGOCYTIC ACTION OF MACROPHAGES.

5. HALLMARK: MULTINUCLEATED YEAST CELLS WITH MLTIPLE BUDDING.

8. Spelunker's disease is otherwise known as histoplasmosis. What is Spelunking?

10. Which of the ff. Opportunistic fungi is strictly exogenous in nature:

12. Darling's disease is otherwise known as Histoplasmosis. Who is Darling?

13. Histoplasma capsulatum and Sporothrix schenckii are both dimorphic.

15. Histoplasma capsulatum does not have any capsule.

17. Most systemic mycoses affects primarily the lungs.

MYCOLOGY&VIROLOGY ONLINE QUIZLETS

Yeasts Unicellular fungi

Systemic mycosisMultiorgan infection caused by fungi

Opportunistic mycosisFungal disease that occur primarily in immunocompromised

Dimorphic fungiFungi that show both a yeast and mold phase

SaprophyteOrganism capable of living on decaying organic material

HyphaeBasic structural unit of molds

MyceliumHyphae come together to form: