AVIAN INFLUENZA H5N1

BIRD FLU
Dr Sanjay Shrestha
IM resident, NAMS
INTRODUCTION
 Influenza is an acute, usually self-limited, febrile illness
caused by infection with influenza type A or B virus that
occurs in outbreaks of varying severity almost every
winter.
 Influenza virus has caused recurrent epidemics of febrile
respiratory disease every 1 to 3 years for at least the
past 400 years.
INTRODUCTION
 Influenza viruses belong to the family Orthomyxoviridae
 4 types of influenza viruses, based on major antigenic differences.
 Influenza A viruses infect humans and many different animals.
The emergence of a new and very different influenza A virus
infect people and have sustained human to human
transmission, can cause an influenza pandemic.
 Influenza B viruses circulates among humans and cause
seasonal epidemics. Recent data showed seals also can be
infected.
 Influenza C viruses can infect both humans and pigs but
infections are generally mild and are rarely reported.
 Influenza D viruses primarily affect cattle and are not known to
infect or cause illness in people.
INFLUENZA TYPE A VIRUSES 

 Most significant to public health

 potential to cause an influenza pandemic.
 Influenza type A viruses are classified into subtypes
according to the combinations of different virus surface
proteins hemagglutinin (HA) and neuraminidase (NA).
 So far , 18 different hemagglutinin and 11 different
neuraminidase subtypes.
 Humans can be infected with avian, swine and other
zoonotic influenza viruses, such as avian influenza virus
subtypes A(H5N1), A(H7N9), and A(H9N2) and swine
influenza virus subtypes A(H1N1), A(H1N2) and A(H3N2).
 Depending on the origin host, influenza A viruses can be
classified as avian influenza, swine influenza, or other
types of animal influenza viruses.
 Examples include
 avian influenza "bird flu" virus subtypes A(H5N1) and
A(H9N2)
 swine influenza "swine flu" virus subtypes A(H1N1)
and A(H3N2). 
 The virus that causes bird flu is influenza A type with
eight RNA strands that make up its genome.
 The highly lethal H5N1 viruses have become well
established in migratory waterfowl throughout Asia and
have undergone considerable diversification, with the
development of at least 10 antigenically distinct clades
and multiple subclades, as defined with phylogeny of HA
gene sequences.
ANTIGENIC VARIATION
CHANGES IN ANTIGENICITY

 Antigenic variation involves principally the two external

glycoproteins of the virus, HA and NA, and is referred to
as
 antigenic shifts - large RNA segments are
interchanged between different influenza virus type
 antigenic drifts - small RNA sequences are changed.
 The antigenic shifts are usually responsible for
developing new strains
 New mutations can allow the virus to evade the body's
immune system and makes older vaccines ineffective
AVIAN INFLUENZA A
 Avian influenza A viruses are classified into the following two
categories:
 low pathogenic avian influenza (LPAI) A viruses
 Infection of poultry with LPAI viruses may cause no

disease or mild illness (such as ruffled feathers and a

drop in egg production) and may not be detected.
 highly pathogenic avian influenza (HPAI) A viruses.
 Infection of poultry with HPAI viruses can cause severe

disease with high mortality.

 Both HPAI and LPAI viruses can spread rapidly through poultry
flocks. However, some ducks can be infected without any signs
of illness
AVIAN INFLUENZA IN BIRDS
 Avian influenza Type A viruses
 occur naturally among wild aquatic birds worldwide
 can infect domestic poultry and other bird and animal
species.
 Wild aquatic birds
 can be infected with avian influenza A viruses in their
intestines and respiratory tract
 but usually do not get sick.
 Domesticated bird
 avian influenza A viruses are very contagious among
birds
 viruses can sicken and even kill certain domesticated
bird species including chickens, ducks, and turkeys.
 Infected birds can shed avian influenza A viruses in their
saliva, nasal secretions, and feces.
 Susceptible birds become infected when they have
contact with the virus as it is shed by infected birds.
 They also can become infected through contact with
surfaces that are contaminated with virus from infected
birds.
EPIDEMIOLOGY
  The first human case of illness from highly pathogenic
avian influenza (termed HPAI in older literature) was
identified in 1997.
 Since that time, H5N1 has infected 784 individuals with
429 deaths.
 Patients with symptomatic H5N1 infections have ranged
in age from 3 months to 75 years, with a median age of
20 years
 The case fatality rates have been highest for those in the
10 to 19 year age group, lowest for people 50 years or
older, and in between for children aged less than 10
years, with an overall rate of 58%.
AVIAN INFLUENZA H7N9
 The identification of H7N9 bird flu strain is worrisome.
 Health officials worldwide are concerned because of the
possibility of a bird flu type that could develop easy
transmission from birds to humans.
 A(H7N9) virus had not previously been seen in either
animals or people until it was found in March 2013 in
China. 
 As of 29 March 2018, a total of 1,625 laboratory-
confirmed human infections and 623 deaths with avian
influenza A(H7N9) virus have been reported to WHO
since early 2013.
AVIAN INFLUENZA A(H5N1) VIRUS
INFECTIONS IN HUMANS
 Human infections are primarily acquired through direct
contact with infected animals or contaminated
environments, but do not result in efficient transmission
of these viruses between people.
 Almost all cases of H5N1 infection in people have been
associated with close contact with infected live or dead
birds, or H5N1-contaminated environments.
 The virus does not infect humans easily, and spread
from person to person appears to be unusual.
RISK FACTORS FOR HUMAN
INFECTIONS
 The primary risk factor for human infection appears to be
 Direct or indirect exposure to infected live or dead
poultry or contaminated environments, such as live
bird markets.
 Slaughtering, defeathering, handling carcasses of
infected poultry, and preparing poultry for
consumption, especially in household settings
 No evidence to suggest that the A(H5), A(H7N9) or other
avian influenza viruses can be transmitted to humans
through properly prepared poultry or eggs.
 Influenza A(H5N1) human cases have been linked to
consumption of dishes made with raw, contaminated
poultry blood.
 EWARS
HIGH RISK GROUPS
 Children playing with or taking care of infected poultry and/or
asymptomatic infected ducks
 Poultry handlers in live animal markets / wet markets
 Cullers without using proper PPE precautions
 Persons involved in defeathering and preparing of sick birds in
wet markets / backyard poultry / kitchens
 People consuming undercooked poultry products
 Hospital functionaries managing human cases of AI without
using proper PPE precautions
 Veterinarians exposed to avian influenza infected poultry
 Human or animal laboratory personnel or other staff who
handle animal or human samples from persons / patients
suspected of or known to contain H5N1 virus in a laboratory
or field setting
CLINICAL PRESENTATION
 Current data indicate an incubation period averaging 2
to 5 days and ranging up to 17 days.
 For human infections with the A(H7N9) virus,
incubation period ranges from 1 to 10 days, with an
average of 5 days.
 For both viruses, the average incubation period is longer
than that for seasonal influenza (2 days).
 For human infections with swine influenza viruses, an
incubation period of 2–7 days has been reported.
CLINICAL PRESENTATION
 Avian, swine and other zoonotic influenza infections in
humans may cause
 disease ranging from mild upper respiratory infection
(fever and cough) to rapid progression to severe
pneumonia, acute respiratory distress syndrome,
shock and even death.
 Gastrointestinal symptoms such as nausea, vomiting and
diarrhea has been reported more frequently in A(H5N1)
infection.
 Conjunctivitis has also been reported in influenza A(H7).
  Common initial symptoms are
 high fever (greater than or equal to 38°C)
 chilliness or frank shaking chills, headaches, myalgia,
malaise, and anorexia.
 Usually, myalgia or headache is the most troublesome
symptom,
 Severity is related to the height of the fever.
 Myalgia may involve the extremities or the long
muscles of the back.
 In children, calf muscle myalgia may be particularly
prominent.
 Severe pain in the eye muscles can be elicited with
lateral gazing, and arthralgia but not frank arthritis is
commonly observed.
 Other ocular symptoms include tearing and burning.
 Cough followed by symptoms of lower respiratory tract
involvement including dyspnoea or difficulty breathing.
 Upper respiratory tract symptoms such as sore throat or
coryza are less common
 Atypical symptoms like nausea, vomiting,
encephalopathy, and bleeding gums and nose have been
reported.
 Watery diarrhea may be present before the onset of
respiratory symptoms.
SIGNS
 FEVER
 The temperature usually rises rapidly to a peak of 100°F to
104°F, and occasionally to 106°F, within 12 hours of onset,
concurrent with the development of systemic symptoms.
 Fever is usually continuous but may be intermittent,
 On the second and third days of illness, the temperature
elevation usually 0.5°F to 1.0°F lower than on the first day,
 as fever subsides, the systemic symptoms diminish.
 Typically, the duration of fever is 3 days, but it may last 4 to
8 days.
 Small, tender cervical lymph nodes are often present.
 Transient scattered rhonchi or localized areas of rales
are found in less than 20% of cases.
EWARS
CASE DEFINITIONS
 Influenza Like illness (ILI):
 A case with:
 Sudden onset of a fever over 38°C
 AND - Cough or sore throat
 AND –An absence of other diagnoses.
 Severe acute Respiratory Infection (SARI):
 A case with:
 Sudden onset of fever over 38°C
 AND - Cough or sore throat
 AND - Shortness of breath or difficulty breathing
 AND - Requiring hospital admission
SUSPECTED CASE OF HUMAN AI
 A person presenting with
 unexplained acute lower respiratory illness with fever (>38 ºC)
 and cough, shortness of breath or difficulty breathing.
 and One or more of the following epidemiological linkage or exposures in the 14
days prior to onset of the symptoms:
 Close contact (< 1 m) with a person who is a suspected, probable, or

confirmed H5N1
 Exposure to poultry or wild birds or animals or their remains or to

environments contaminated by their faeces in an area where H5N1 infections

in animals or humans have been suspected or confirmed in the last month
 Consumption of raw or undercooked poultry products in an area where H5N1

infections in animals or humans have been suspected or confirmed in the last

month
 Travel to an area where H5N1 infections in animals or humans have been

suspected or confirmed in the last one month

 Handling samples (animal or human) suspected of containing H5N1 virus in a

laboratory or other setting

INVESTIGATION
 Significant lymphopenia and leucopenia
 Severe leukopenia has been described in overwhelming
viral or bacterial infection, whereas leukocytosis with
>15,000 cells/μL raises the suspicion of secondary
bacterial infection.
 Mild to moderate thrombocytopenia

 Elevated transaminase levels.

 Most patients have abnormal chest radiographic results

with diffuse and multifocal or patchy infiltration, but
pleural effusions are rare.
PATHOLOGIC CHANGES
 Diffuse alveolar damage in the lungs,
 Reactive hemophagocytosis in the marrow

 Lymphoid depletion with atypical lymphocytosis in the

spleen and lymphoid tissues
DIAGNOSIS
 Laboratory tests are required to diagnose
human infection with zoonotic influenza.
 Avian influenza A virus infection is usually
diagnosed by collecting a swab from the
upper respiratory tract (nose or throat) of
the sick person. (Testing is more accurate
when the swab is collected during the first
few days of illness.)
 DIAGNOSIS
 Virus isolation
 from nasal swab specimens, throat swab specimens, nasal
washes, or combined nose and throat swab specimens.
 Rapid influenza diagnostic tests (RIDTs)
 are based on immunologic detection of viral antigen in
respiratory secretions
 have lower sensitivity, sensitivities of each test in comparison
with cell culture have ranged between 40% and 80%,
 dependent on the nature of the samples tested and the
patients from whom they were derived.
 Nucleic acid hybridization and PCR amplification.
 PCR in particular has the advantage of being
potentially more sensitive than cell culture
 may allow detection of virus in samples in which the
virions have lost viability.
 Reverse-transcriptase polymerase chain reaction (RT-
PCR) is the most sensitive and specific technique for
detection of influenza viruses.
 RT-PCR can differentiate among influenza subtypes
and is used for detection of avian influenza viruses.
SPECIMEN COLLECTION
 Specimens should be obtained for novel influenza A
virus testing as soon as possible after illness onset,
ideally within 7 days of illness onset.
 However, Infected persons are known to shed virus for
longer periods (e.g., children and immunocompromised
persons),
 specimens should be tested for novel influenza A
virus even if obtained after 7 days from illness onset.
 The following should be collected as soon as possible
after illness onset:
 a nasopharyngeal swab, or
 a nasal aspirate or wash, or
 two swabs combined into one viral transport media
vial (e.g., nasal or nasopharyngeal swab combined
with an oropharyngeal swab)
 Swab specimens should be collected using swabs with a
synthetic tip (e.g., polyester or Dacron®) and an
aluminum or plastic shaft.
 Swabs with cotton tips and wooden shafts are not
recommended.
CONFIRMED CASE OF HAI
A person meeting the criteria for a suspected or probable case
AND meets one of the following positive results at a laboratory
whose H5N1 test results are accepted by WHO as confirmatory:
 Isolation of a HAI A (H5N1) virus
 Positive H5 PCR results from tests using two different PCR
targets, e.g. primers specific for influenza A and H5 HA
 A fourfold or greater rise in neutralization antibody titre for
H5N1 based on testing of an acute serum specimen and a
convalescent serum specimen
 A micro-neutralization antibody titre for H5N1 of 1:80 or
greater in a single serum specimen collected on Day 14 or
later after symptom onset
TREATMENT
 In suspected and confirmed cases,
 neuraminidase inhibitors should be prescribed as soon as
possible (ideally, within 48 hours following symptom onset)
to maximize therapeutic benefits.
 However, given the significant mortality and prolonged viral
replication, administration of the drug should also be
considered in patients presenting later in the course of illness.
 Treatment is recommended for a minimum of 5 days, but can
be extended until there is satisfactory clinical improvement.
 The standard dose of oseltamivir
 75 mg twice daily for 5 days.
 optimal duration and dose uncertain for severe or
complicated influenza.
 Influenza A (H5N1) and A (H7N9) viruses
 associated with higher virus loads and
 more sustained viral replication (particularly in the lower
respiratory tract) than seasonal influenza
 longer courses of treatment (e.g., 10 days) considered for
severely ill hospitalized patients with infections with novel
influenza A viruses.
INFLUENZA ANTIVIRAL MEDICATIONS FOR TREATMENT OR CHEMOPROPHYLAXIS
 Corticosteroids should not be used routinely, unless
indicated for other reasons
 associated with prolonged viral clearance
 immunosuppression leading to bacterial or fungal
superinfection.
 Antibiotics for secondary bacterial infections

 Supportive management

 Most recent A(H5) and A(H7N9) viruses

 resistant to adamantane antiviral drugs (e.g.
amantadine and rimantadine)
 not recommended for monotherapy.
COMPLICATIONS OF INFECTION

 Pulmonary complications:
 Two manifestations of pneumonia associated with
influenza are well recognized: primary influenza
viral pneumonia and secondary bacterial infection.
 Severe pneumonia,
 Hypoxemic respiratory failure,
 multi-organ dysfunction,septic shock, and
secondary bacterial and fungal infections.
 Primary influenza viral pneumonia
 presents as acute influenza that does not resolve
 but instead progresses relentlessly, with persistent
fever, dyspnea, and eventual cyanosis.
 Sputum production is generally scanty, but the
sputum can contain blood.
 imaging findings consistent with diffuse interstitial
infiltrates and/or acute respiratory distress syndrome
may be present.
 Secondary bacterial pneumonia
 Follows acute influenza.
 Improvement of the patient’s condition over 2–3 days
is followed by a reappearance of fever along with
clinical signs and symptoms of bacterial pneumonia,
including cough, production of purulent sputum, and
physical and x-ray signs of consolidation.
NON PULMONARY COMPLICATIONS
 Myositis and myoglobinuria
 with tender leg muscles and elevated serum creatine phosphokinase
(CPK) levels have been reported, mostly in children
 Cardiac Complications.
 Myocarditis and Pericarditis have been rarely associated with influenza
A or B virus infection.
 In patients with cardiac disease, the acquisition of influenza provides a
significant risk of death.
 Toxic Shock Syndrome.
 In recent outbreaks of influenza A or B, toxic shock–like syndrome has
occurred in previously healthy children or adults, presumably because
viral infection changed colonization and replication characteristics of
the toxin-producing staphylococcus.
 Central Nervous Complications.
 Guillain-Barre syndrome
 transverse myelitis and encephalitis
 Reye’s Syndrome.
PREVENTION
 Controlling the circulation of avian influenza viruses in
poultry is essential to reducing the risk of human
infection.
 Given the persistence of the A(H5) and A(H7N9) viruses
in some poultry populations, control will require long-
term commitments from countries and strong
coordination between animal and public health
authorities.
PREVENTION
 Apart from antiviral treatment, the public health
management includes personal protective
measures like:
 Regular hand washing with proper drying of the
hands
 Good respiratory hygiene – covering mouth and nose
when coughing or sneezing, using tissues and
disposing of them correctly
 Early self-isolation of those feeling unwell, feverish
and having other symptoms of influenza
 Avoiding close contact with sick people
 Avoiding touching one’s eyes, nose or mouth
 Available studies indicate that highly pathogenic viruses,
including the H5N1 virus, spread to virtually all parts of
an infected bird, including meat.
 Proper handling of poultry and poultry products during
food preparation and proper cooking are extremely
important .
 Juices from raw poultry or poultry products should
never be allowed, during food preparation, to touch or
mix with items eaten raw. 
 Consumers need to be sure that
 all parts of the poultry are fully cooked (no “pink” parts)
 Eggs are properly cooked (no “runny” yolks).
 The H5N1 virus can survive for at least one month at low
temperatures.
 common food preservation measures, such as freezing
and refrigeration, will not substantially reduce the
concentration of virus in contaminated meat or kill the
virus.
 Refrigerated or frozen meat to be handled and prepared
with the same precautions as fresh products.
VACCINATION

 Candidate vaccines to prevent H5N1 infection have been

developed, but they are not ready for widespread use.
 Seasonal influenza vaccination does not appear to
protect against H5N1 infection.
REFERENCE
 Mandell, Douglas, and Bennett’s principles and practice
of infectious diseases seventh edition
 Early Warning and Reporting System (EWARS) Guidelines

 CDC guidelines on Avian Influenza

 WHO- Avian influenza: guidelines, recommendations &

descriptions
 Harrison’s Principles of Internal medicine 19th edition

 Uptodate
THANK YOU