Avian Influenza (Bird Flu, Including H5N1): Clinical Features, Diagnosis and Management

Clinical Medicine Year 3 • zoonotic influenza at the human–animal interface and its pandemic potential

Learning outcomes

• Explain influenza A subtypes, haemagglutinin/neuraminidase nomenclature and avian influenza ecology.
• Recognise the exposure history and clinical spectrum of human H5N1/H7N9 infection.
• Plan testing, isolation, antiviral treatment and monitoring of contacts.
• Identify respiratory, ocular, gastrointestinal and neurologic complications.
• Explain how reassortment, mutation and poultry control influence pandemic risk.

Influenza virology

Influenza A viruses are enveloped, segmented, negative-sense RNA viruses in the family Orthomyxoviridae. Their surface proteins are haemagglutinin (H) and neuraminidase (N), which define subtypes such as H5N1, H7N9 and H1N1. The segmented genome allows reassortment when two influenza viruses infect the same cell. Gradual mutation is called antigenic drift; abrupt reassortment can produce a virus to which humans have little immunity.

“Highly pathogenic” and “low pathogenic” refer primarily to disease severity in poultry, not automatically to severity in humans. A low-pathogenic avian virus in birds may still cause serious human illness.

Animal reservoirs and human exposure

Wild aquatic birds are important reservoirs. Poultry, wild birds and some mammals can become infected. Human infections are uncommon and usually follow close exposure to infected animals or contaminated environments rather than efficient human-to-human spread.

• Handling sick or dead poultry, wild birds, cats or other infected animals.
• Slaughtering, defeathering, butchering, cleaning cages or handling droppings and secretions.
• Working on farms, in live-bird markets, veterinary services or culling teams.
• Contact with infected dairy cattle or raw milk in settings where H5 viruses are circulating in mammals.
• Unprotected contact with contaminated surfaces, equipment or aerosols.

Human infection is not acquired by eating properly cooked poultry or pasteurised milk. The primary concern is exposure during handling, slaughter, milking or preparation of infected animals and contaminated materials.

Pathogenesis and pandemic risk

1. Virus enters through the eye, nose, mouth or lower respiratory tract.
2. Avian influenza viruses preferentially bind receptors in the respiratory tract, but some strains can infect conjunctival, gastrointestinal or neurologic tissues.
3. Viral replication and an exaggerated inflammatory response can damage alveoli, causing diffuse pneumonitis and ARDS.
4. Gastrointestinal and neurologic involvement may occur in severe or unusual presentations.
5. Pandemic risk would rise if a novel avian virus acquired sustained, efficient human-to-human transmission through mutation or reassortment. That is a surveillance concern—not evidence that every human case spreads readily.

Clinical presentations

1. Conjunctivitis

Red, watery, painful or gritty eyes may be the first or only symptom after ocular exposure. Conjunctivitis in a person who handled infected birds, cattle or contaminated equipment should prompt avian-influenza testing and public-health notification.

2. Upper-respiratory and systemic illness

• Fever, chills, headache, myalgia, malaise and anorexia.
• Sore throat, cough, rhinorrhoea and shortness of breath.
• Diarrhoea, nausea, vomiting or abdominal pain—particularly described with H5N1.

3. Severe lower-respiratory disease

Viral pneumonia can progress rapidly to hypoxaemic respiratory failure, ARDS, shock, secondary bacterial infection, acute kidney injury and multiorgan failure. Findings include tachypnoea, hypoxaemia, crackles, cyanosis, confusion, chest pain and increasing work of breathing.

4. Neurologic complications

Encephalitis, encephalopathy, seizures, ataxia and altered consciousness have been reported. Consider neurologic disease particularly when respiratory findings do not fully explain the level of altered mental status.

History and examination

Investigations

Specific virologic testing

• Collect respiratory specimens in consultation with the reference laboratory: nasopharyngeal/oropharyngeal swabs for upper-respiratory illness and lower-respiratory specimens when severe pneumonia is present.
• Collect conjunctival swabs when conjunctivitis is present.
• Use real-time RT-PCR with assays that detect influenza A and differentiate avian subtypes. Routine seasonal influenza rapid tests may be negative or cannot subtype the virus.
• Do not delay public-health notification while waiting for a result.
• Use appropriate PPE and specimen packaging; laboratory workers require trained procedures for potentially high-consequence pathogens.

Severity assessment

• Pulse oximetry, arterial/venous blood gas, chest radiograph or CT when indicated.
• Full blood count, electrolytes, renal/liver tests, glucose, CRP and lactate.
• Blood cultures and tests for bacterial coinfection when pneumonia or sepsis is suspected.
• ECG/troponin and neurologic imaging/CSF only when clinically indicated and safe.

Differential diagnosis

Management

Antiviral therapy

• Oseltamivir: commonly started as soon as possible, often 75 mg orally twice daily in adults with normal renal function; adjust for renal impairment, age and local guidance. Severe novel-influenza cases may require specialist decisions about duration, absorption and combination therapy.
• Do not wait for a positive PCR when epidemiology and clinical illness are concerning.
• Consider inhaled zanamivir or other agents only with specialist/public-health advice because lower-respiratory disease, resistance and delivery limitations matter.

Supportive and critical care

• Oxygen, careful fluid management, fever control, nutrition and monitoring of respiratory effort.
• Early high-flow oxygen, non-invasive ventilation or mechanical ventilation when indicated, with aerosol precautions.
• Manage ARDS using lung-protective ventilation and intensive-care protocols.
• Investigate and treat bacterial coinfection; avoid routine corticosteroids unless another indication exists.
• Manage shock, renal failure, myocarditis, encephalitis and secondary complications.
• Use isolation and cohorting based on public-health assessment; restrict visitors and protect staff from respiratory and ocular exposure.

Prevention and public health

• Avoid contact with sick/dead birds or mammals; do not touch carcasses with bare hands.
• Use gloves, eye protection, protective clothing and fit-tested respiratory protection for high-risk animal work.
• Wash hands and disinfect equipment; separate work clothing and shower after high-risk exposure.
• Cook poultry, eggs and meat thoroughly; avoid raw milk and unpasteurised animal products.
• Monitor exposed people for symptoms for the period set by the national/public-health protocol, commonly 10 days after the last exposure.
• Provide post-exposure antiviral prophylaxis only when recommended by public health; do not self-medicate contacts.
• Vaccination against seasonal influenza does not protect against H5N1, but it can reduce confusion with seasonal influenza and supports routine prevention. Candidate or stockpiled avian-influenza vaccines are used only under national/regulatory programmes.
• Animal surveillance, rapid culling/vaccination decisions, safe disposal and One Health coordination reduce human risk.

Exam-focused pearls

• Ask about birds, poultry, wild animals, dairy cattle, raw milk and contaminated environments.
• Conjunctivitis can be a key presentation of H5N1 infection.
• Human avian-influenza disease ranges from mild eye/upper-respiratory illness to ARDS and encephalitis.
• Routine rapid influenza tests do not reliably exclude or subtype H5N1.
• Start oseltamivir promptly when suspicion is significant; coordinate with public health.
• Most avian influenza viruses do not spread efficiently between humans, but surveillance is essential because reassortment could change pandemic risk.

References and further reading

• SlideShare: Bird flu / avian influenza
• WHO: Avian and other zoonotic influenza
• CDC: Clinical guidance for evaluating and treating H5N1
• CDC: Prevention and exposure-control recommendations
• WOAH: Avian influenza in animals