Bacterial & Fungal Infections

of
Blood &
Cardiovascular System
Prof. Dr. Amany Tharwat Abd El Rhman
Dr. Ragda Hussain
Medical Microbiology & Immunology Department,
MUST
By the end of this chapter students should be able to:
 Distinguish among septicemia, bacteremia, and toxemia.
 Describe the signs, symptoms, causes, diagnosis, treatment, and
prevention of septicemia and toxemia.
 Compare between action of endotoxin and exotoxins.
 Describe the signs, symptoms, causes, diagnosis, treatment, and
prevention of endocarditis, myocarditis, pericarditis and rheumatic
fever.
 Compare and contrast the causative agents, vectors, reservoirs,
symptoms, treatments, and preventive measures for vector-borne
diseases of cardiovascular system.
 Definitions:
blood is normally sterile,

 Bacteremia:
presence of small number of bacteria in the blood which do not multiply significantly.

 Septicemia (blood stream infection- blood poisoning)

Presence of rapidly multiplying highly pathogenic bacteria, progress to
Septic shock

 Toxemia:
When bacteria remain fixed at a site of infection but release toxins into the blood, the
condition is toxemia Toxic sock

the Greek word for "blood" (haima).

Greek word, sepsin, which literally means "poison in blood."
 Septic shock is different from toxic shock.

 In septic shock, the bacteria are in the bloodstream,

 whereas in toxic shock, it is the toxin that is circulating in the blood

 Fungimia: the presence of fungi in the blood.

 Viremia: the presence of viruses in the blood.

 Pathogenesis of Blood Stream Infections
Source of infection :

 In hospital settings; direct inoculation of the organism into the blood as a

result of invasive procedures e.g. Intravenous catheterization.

 Via non-sterile needle use by drug users.

 From an infection elsewhere in the body e.g urinary tract infection

, pneumonia, abdominal area, and surgical wound infections.

 Through small abrasions in the respiratory or digestive tracts.

 Common Causal Agents
of blood stream infection
 Gram positive cocci: S. aureus, S. epidermidis (most common cause among Gram
positive cocci), S. pyogenes and S. pneumoniae.
 Gram negative cocci: Neisseria meningitides.
 Gram-positive bacilli: Clostridium causing gas gangrene, Bacillus anthracis.
 Gram negative bacilli: as E. coli, Klebsiella species (most common cause among
enterobacteriaceae), Salmonella spp., Yersinia pestis, brucellae, Pseudomonas
aeruginosa.
 Spirochete e.g Borrelia burgdorferi (Lyme disease), Borrelia causing relapsing fever.
 Rickettsiae.

 Fungi : e.g Candida, Dimorphic fungi e.g hispoplasma capsulatum .

 8.virus Epstein-Barr virus, and parvovirus
 Pathogenesis
 Septicemia:
is due to the excessive activation of the inflammatory immune
response to molecules from the microorganism that have caused the
infection.

Depending on the type of bacterium, these molecules may be,

lipopolysaccharide (LPS) ( Lipid A) molecules of Gram negative
bacteria, or lipoteichoic acid of Gram positive bacteria.

 a serious complication of septicemia is septic shock .

 Mode of action of endotoxin

Clinical finding Mechanism

fever activating macrophages to

produce:
interleukin-1 (IL-1), tumor
necrosis factor (TNF),

Hypotension (shock) tumor necrosis factor (TNF),

Inflammation Complement activation: C3a

and C5a
Disseminated activating tissue factor
intravascular Coagulation
 Septicemia can lead to an infection of the
lymphatic system in which inflamed lymphatic
vessels become visible as red streaks under the
skin, a condition known as lymphangitis.

 Lymphocytes, particularly in lymph nodes,

act to limit infection of lymphatic vessels
and lymph nodes.
 Signs & symptoms
 Septicemia: is characterized by :
 fever (over 38°C), chills, malaise,
 nausea, vomiting, diarrhea,
 shortness of breath, petechiae (minute hemorrhagic skin lesions) and
 changes in mental status such as confusion and anxiety.

 These signs and symptoms can progress rapidly to septic shock.

 Septic shock: is characterized by :

 Extremely low blood pressure resulting from dilation of blood vessels,
 Decrease in body temperature,
 Decrease in or absence of urine output,
 Rapid breathing.
 Extremities become cool and pale.
 Bluish discoloration of the digits or lips (cyanosis)
 Increased heart rate, anxiety, and death.
 Laboratory Diagnosis of septiceamia:

Blood culture: for isolation of causative organism from blood.

 Treatment:
Treatment generally involves prompt diagnosis and treatment with appropriate
antimicrobial drugs against the specific bacterial cause;
 Toxemia:

 manifests differently according to the exotoxins produced by the

organism

 a serious complication of toxemia is toxic shock .

ANTHRAX
Causative organism

Bacillus anthracis
Bacillus anthracis derives from the Greek word for coal, anthrakis, because the
disease causes black, coal-like skin lesions.
 Bacillus anthracis

 Large aerobic, non motile, Gram-positive bacilli occurring in chains.

 Spores are formed only outside the body; oval & central.
 The bacilli form a polypeptide capsule in infected tissue.
 Anthrax disease

Anthrax is primarily a disease of herbivorous

animals, such as cattle, sheep, goat.
Humans become infected accidentally when brought
into contact with diseased animals, or their bodies.
It is a zoonotic disease.
 Mode of transmission

Humans are infected by :

 Inhalation of spores or
Traumatic implantation, or
Ingestion of undercooked food containing
anthrax endospores (zoonotic disease).
 Pathogenesis:
 Infections by B. anthracis are initiated by
endospores. Once introduced into the body,
they are taken up by alveolar macrophages.
 Spores are transported through lymph system
to mediastinal lymph nodes where
Germination of spores occurs and toxin
production Pulmonary edema
death
 The organisms are not killed, but multiply,
eventually killing the macrophage.

 The released bacteria then enter the

bloodstream, replicate rapidly, and secrete
toxins Shock Death
 Lymphatic or hematogenous spread to C.N.S
occurs causing meningitis Death
 Virulence factors:
1. Capsule (formed of polypeptides):
It is anti-phagocytic, not stimulate immune system.

2. Anthrax toxin: (A-B subunit):

-A subunit; formed of two toxins : has enzymatic activity.
 Lethal factor (protease): Kill cells; specially targets and kill
macrophages, and causes tissue necrosis.
 Edema factor: is an adenylate cyclase; which causes
elevation of intracellular cAMP, this causes an outpouring of
fluid from the cell into the extracellular space, resulting in
severe edema.
-B-subunit : binding subunit ; protective antigen
 Clinical forms of anthrax
 Cutaneous anthrax (malignant pustule).

 Inhalational anthrax (Wool sorters disease):begins with nonspecific respiratory tract

influenza –like symptoms , especially fever, a dry cough, chest discomfort.
After being inhaled into the lung, the organism moves rapidly to the mediastinal lymph
nodes, where it causes hemorrhagic mediastinitis, bloody pleural effusions,, septic shock,
and death.

 Gastrointestinal anthrax (a rare clinical form) leads to abdominal pain and bloody
diarrhea.
 If untreated ; usually kills the patient within 24 to 36 hours. The mortality rate is exceptionally
high, approaching 100%.
 Cutaneous anthrax
Malignant pustule

Hide porters.
Farmers,
butchers,
veterinarians .
black eschar, a necrotic lesion
covered by a crust
 Laboratory Diagnosis

 Specimen :blood, respiratory secretions or cutaneous lesion

 Gram stain: Gram-positive rods in chains.
 Culture on blood agar: large, non-hemolytic colonies.
 Direct IF antibody test: that detects antigens of the organism in the lesion.
 Serology: ELISA test for antibodies.
 PCR.
Treatment: ciprofloxacin or doxycycline.

 Prevention of anthrax:
 Destroy animal carcasses by incineration or deep burial in quick lime.
 Active immunization of animals by live attenuated vaccine.
 Human anthrax vaccines: cell-free vaccine containing purified protective
antigen (B –subunit of anthrax toxin ) as immunogen.
 Brucellosis
(undulant fever- Malta fever)
 Causative agent: Brucellae

Small Gram-negative rods (coccobacilli),

non capsulate.

Facultative intracellular pathogen:

that can survive and multiply within host phagocytic cells.
 Reservoir:

 Brucellosis is a true zoonotic disease. It is primarily pathogens of

animals and transmitted from animals to humans.

 Brucellae are shed in large numbers in the animal's urine, milk,

placental fluid, and other body fluids.

 The three major human pathogens and their animal reservoirs are
Brucella melitensis (goats and sheep), Brucella abortus (cattle), and
Brucella suis (pigs).
 Mode of Transmission:

• Ingestion of raw milk and unpasteurized milk products

like fresh cheese.

• Direct contact: of skin abrasions/ mucosal surfaces with

tissues or organs of infected animals.

• Inhalation of contaminated aerosols or dried remnants

of infected animal tissues or secretions.

• No human to human infection.

 Virulence Factors:

 Endotoxin.

 Facultative intracellular pathogens: that can survive and

multiply within host phagocytic cells.
 Pathogenesis:
 Acute stage: From the portal of entry the organisms
reach the blood stream via lymphatics and cause
bacteremia.

 From blood the organisms reach organs that are

involved in the reticuloendothelial system, including the
liver, spleen, kidneys, bone marrow, and other lymph
nodes ; where they multiply inside phagocytic cells.

 Chronic stage: The organisms stimulate cell mediated

immunity with the formation of granulomatous nodules,
which can progress to form focal abscesses.
Granulomatous
nodules in liver
 Granulometous nodule
Accumulation of epithelioid cells, giant cells
(macrophages), and T lymphocytes
surrounded by fibrous tissue.
 Clinical Findings

 : I.P 1 to 3 weeks . Acute or gradual onset;

 Nonspecific symptoms such as fever, chills, fatigue, malaise, anorexia, and
weight loss occur.
 Undulating (rising-and-falling) fever pattern that gives the disease its name
(like a wave) (often in evening), in untreated patients.
 Enlarged lymph nodes, liver, and spleen are frequently found.
 Osteomyelitis is the most frequent complication.
 Laboratory Diagnosis of Brucellosis

 Brucella is difficult to culture in a laboratory,

 diagnosis is confirmed by serological tests showing a rising level of

antibodies against Brucellae.
Laboratory Diagnosis of Brucellosis

Direct methods Indirect methods

(Acute stage) (Acute & chronic stage)

1. Specimen: blood, bone

marrow sample.

Serum Agglutination test:

2. Blood Culture: Castaneda
medium; Trypticase-soy broth & ( four fold increase in
agar , 5-10 % CO2 (for 3 weeks). antibody titer; or
>1:160 considered
3. Colonies are identified by: positive)
- Gram stained film
- B.R
 Treatment

As the organism is intracellular pathogen, a combined

prolonged course of treatment with:

Deoxycycline and rifampicin (for at least 6 weeks) for

adults.
Cotrimoxazole and rifampicin for children.
 Prevention And Control:

 Pasteurization of milk is the most important measure.

 Health education for farmers, veterinarians and

slaughterhouse workers for occupational hazards.

 Active immunization of animals with live-attenuated

strains.
Plague (Black Death)

the plague, which peaked in Europe between 1346 and 1353, referred to the
event as the “Great Mortality” or the “Great Plague.” It is estimated to have
killed 30–60% of Europe's total population
 Causative agent :
Yersinia pestis (Y. pestis)
 Small Gram-negative rods
 Facultative intracellular parasite.
 Non-lactose fermenting members of
the enterobacteriaceae.
 Transmission:

 Plague is enzootic in wild rodents (e.g. rats).

Transmitted among them by fleas (Xenopsylla
cheopis) (urban plague).

 Infection is transmitted from infected rats to

humans by flea bites mainly.

 In case of pneumonic plague spread can

occur from human to human by respiratory
droplets (epidemic plague).
 Virulence Factors:

 It is one of the most virulent bacteria known (i.e., 1 to 10

organisms are capable of causing disease).
 Polypeptide capsule :It is anti-phagocytic
 Endotoxin.
 Exotoxin.
 Yersinia outer proteins: inhibit phagocytosis.
 V and W antigens: allow the organism to survive and
grow intracellularly.
 Clinical diseases:
 Bubonic plague, the most frequent form, begins with pain and
swelling of the lymph nodes draining the site of the flea bite.
Buboes are typically located in the groin but may also occur in
axillae or on the neck.
 They started red and as the patient's condition worsened they
would become a dark purple or black colour - and leak blood
and pus.
(A bubo (Greek βουβών, boubôn, "groin") is defined
as adenitis or inflammation of the lymph nodes)

 Septicemic plague: The endotoxin-related symptoms, including

disseminated intravascular coagulation and cutaneous
hemorrhages.

Swelling of the lymph glands
 Pneumonic plague: From blood, the bacilli reach many organs on the neck
especially the lungs causing secondary pneumonic plague.
Bubonic plague in axilla Bubonic plague in groin
 Laboratory Diagnosis of plague

Direct methods Indirect methods

Clinical specimens and cultures are hazardous
Detection of antibodies
1. Specimen : blood, L.N aspirate, sputum.
to the capsular antigen
by:
2. Stained film with :
- Gram’s: Gram negative coccobacilli.
- IF. ELISA
(titer of ≥ 16)
3. Isolation and identification by:
Culture at 270C for 2-3 days on:
blood, or selective medium.
4. The organism is identified by: B.R
Treatment
A combination of streptomycin and doxycycline.

 Prevention & Control:

 Anti-rats measures and Anti-fleas measures (insecticides).
 strict isolation (quarantine) of patient for 72 hours after
antibiotic therapy is started.
 Chemoprophylaxis :for contacts with cases of pneumonic
plague e.g. Tetracyclines.
 Formalin killed vaccine: for persons at risk. provides partial
protection against bubonic but not pneumonic plague
Relapsing Fever
 Causative organism:

 Borrelia recurrentis, and Borrelia hermsii

 Borreliae are Gram negative, large irregular wide spirals, highly flexible, and
motile.
 Relapsing fever
 Relapsing fever occurs in 2 forms: Epidemic and Endemic.

 B.recurrentis is transmitted from person to person by the human body louse;

Humans are the only hosts.

 While B.hermsii are transmitted to humans by soft ticks (Ornithodoros),
Rodents are the main reservoirs (Zoonosis).

Epidemic Endemic Relapsing

Relapsing Fever Fever
Causative Borrelia Borrelia hermsii
organism recurrentis
Vector lice ticks
Natural hosts Obligate human Rodents
pathogens
 Infection started by the arthropod bite that introduces spirochetes to
blood; where it multiply and spread to many tissues, producing fever, chills,
headaches, myalgia, and multiple-organ dysfunction.
 Relapsing fever is characterized
by several cycles of apparent
recovery, each followed by a
relapse.

 A most important property of

the organism is its ability to
change surface protein
antigens.
Clinical stages of relapsing fever.
 As antibodies appear,
organisms disappear from the
blood and are replaced by a
different antigenic variant within
a few days.
 Laboratory diagnosis
 Blood smears stained by Giemsa’s stain :diagnosis is usually based on the
appearance of loosely coiled spirochetes in the blood during the febrile
stage of the disease.
 Treatment
 Tetracycline may be beneficial early in the illness and may prevent
relapses.

 Prevention:
 Maintain good personal hygiene and delousing.
 Insecticides for eradication of ticks.