BIRD FLU [AVIAN & HUMAN INFLUENZA (H5N1) INFECTION]
Dr Ira Shah
Medical Sciences Department, Pediatric Oncall, Mumbai, India
Influenza virus is known to cause epidemics every several years. There is now a threat to human kind by an infection with Influenza A (H5N1) virus. The virus is predominantly known to infect birds (avians) causing death even in a day of infection but now due to high infectivity, humans are known to get affected. Human Influenza infection by this virus is known to be highly fatal.

History:-
First reported in 1997 in Hong Kong, this infection has now affected over 20 countries around the globe. Recent outbreaks in Kazakhstan, Mongolia, Russia and India indicate that humans are now at risk to this disease. Largest numbers of cases have occurred in Vietnam and 20 human deaths have been reported with the recent from Indonesia (1 - 3) .

Transmission:-
Human influenza is transmitted by inhalation of infectious droplets, by direct contact or by fomite transmission (4, 5) . Bird-to-human, environment-to-human transmission is known with H5N1 virus however, evidence of human-to-human transmission is lacking. Exposure to live infected poultry is a risk to transmission. There is no risk related to eating or preparing poultry products (6) .

Pathogenesis :-
It is a highly pathogenic virus and possesses the poly basic amino acid sequence at the hemagglutinin-cleavage site that is associated with visceral dissemination in birds (7) . In humans, too invasive disease is seen. The virus continues to evolve with change in antigenicity and is able to affect wide range of birds and felids (8) . These genetic and biologic changes may lead to different affection in humans and may have effect on response to therapy as well as case fatality. However, despite wide spread exposure to infected poultry, the H5N1 virus affects humans with relatively low frequency and genetic factors may be also contributory.

Pathology:-
This avian influenza virus (H5N1) leads to pneumonia with histology of alveolar spaces showing fibrinous exudates, hyaline-membrane formation, vascular congestion, infiltration of lymphocytes into the interstitial space and proliferation of reactive fibroblasts. Reactive histiocytosis with hemophagocytosis is known and atypical lymphocytes are seen in lymphoid tissue and spleen. Centrilobular hepatic necrosis and acute tubular necrosis (ATN) can also occur (9) .

Clinical features :-
The possibility of influenza A (H5N1) should be considered in all patients with severe acute respiratory illness in countries or areas with animal influenza A (H5N1) particularly in patients who have been exposed to poultry (1) . Sub-clinical and atypical presentations such as gastroenteritis may occur. After an incubation period of 2 to 8 days, most patients present with high fever, myalgia, cough with expectoration, sore throat and breathlessness (10-12) . Diarrhea, vomiting, abdominal pain, pleuritic pain and bleeding from gums and nose has been reported early in the course of the disease. Lower respiratory tract manifestations in form of respiratory distress, tachypnea and inspiratory crepitations are seen with 1-16 days of presentation (10) . Progression to adult respiratory distress syndrome (ARDS), multi organ failure in form of renal failure and cardiac dilation is common.

Laboratory findings: -
Common hematological abnormalities that are seen are lymphopenia, thrombocytopenia and elevated liver enzymes. With renal failure, elevated creatinine levels occur. Radiographic changes include diffuse, multifocal or patchy infiltrates; interstitial infiltrates or segmental consolidation with air bronchograms. Progression to ARDS leads to diffuse bilateral ground glass appearance.

Diagnosis:-
Virus isolation or RNA PCR specific for H5 virus from pharyngeal samples are the investigation of choice to confirm the diagnosis.

Management :-
Whenever feasible, patients with suspected or proven influenza A virus should be hospitalized in isolation. Supportive care with oxygen and ventilators may be essential. Patients with suspected H5N1 influenza A should receive a neuraminidase inhibitor pending the result of diagnostic test. Oral Oseltamivir and topical Zanamivir have been found to be useful in animals with good in vitro susceptibility (13, 14) . Approved doses of Oseltamivir (75 mg twice daily for five days in adults, children < 15 kg - 30 mg twice a day, children between 15-23 kg - 45 mg twice a day, those between 23-40 kg - 60 mg twice a day and those above 40 kg - 75 mg twice a day) are good for treating early, mild cases. However higher doses and longer duration of treatment may be required in patients with severe disease.

High-level antiviral resistance to Oseltamivir by substitution of a single amino acid in N1 neuraminidase (His 274 Tyr) has been found recently and hence one needs to use this drug with caution to prevent drug resistance (14) . Amantadine and Rimantidine have no therapeutic effect on the recent influenza A (H5N1) isolates. Role of corticosteroids is uncertain.

Prevention :-
No influenza A (H5) vaccines are currently commercially available for human. However now several candidate vaccines and live attenuated intranasal vaccines are under study (15, 16) . Chemoprophylaxis with 75 mg of Oseltamivir once daily for 7 to 10 days to recommended for persons who have had a possible exposure to infected poultry (17) . Travelers to areas with avian influenza activity should be immunized with the available trivalent human vaccine preferably at least 2 weeks before traveling. Direct contact with poultry and touching surfaces contaminated with poultry feces or secretions should be avoided. Avoid ingestion of undercooked eggs or poultry foods. Health care workers should wear masks, long-sleeved cuffed gowns, eye goggles and gloves when taking care of affected patient.
References :
  1. The Writing Committee of the World Health Organization (WHO) Consultation on Human Influenza A/H5. Avian Influenza A (H5N1) Infections in Humans. New Engl J Med 2005;353:1374-1385.
  2. Liu J, Xiao H, Lei F et al. Highly pathogenic H5N1 influenza virus infection in migratory birds. Science 2005;309:1206.
  3. Chen H, Smith JD, Zhang SY et al. Avian flu : H5N1 virus outbreak in migratory waterfowl. Nature 2005;436:191-2.
  4. Salgado CD, Farr BM, Hall KK, Hayden FG. Influenza in the acute hospital setting. Lancet Infect Dis 2002;2:145-55.
  5. Bridges CB, Kuehnert MJ, Hall CB. Transmission of influenza : implications for control in health care settings. Clin Infect Dis 2003;37:1094-104.
  6. Mounts AW, Kwong H, Izurieta HS et al. Case Control Study of risk factors for avian influenza A (H5N1) disease, Hong Kong, 1997. J Infect Dis 1999;180:505-8.
  7. Hatta M, Gao P, Halfmann P, Kawaoka Y. Molecular basis for high virulence of Hong Kong H5N1 influenza A viruses. Science 2001;293:1840-2.
  8. Horimoto T, Fuku da N, Iwatsuki-Horimoto K et al. Antigenic differences between H5N1 human influenza viruses isolated in 1997 and 2003. J Vet Med Sci 2004;66:303-5.
  9. To KF, Chan PK, Chan KF et al. Pathology of fatal human infection associated with avian influenaza A (H5N1 virus. J Med Virol 2001;63:242-6.
  10. Hien TT, Liem NT, Dung NT et al. Avian influenza A (H5N1) in 10 patients in Vietnam. N Engl J Med 2004;350:1179-88.
  11. Yuen KY, Chan PK, Peiris M et al. Clinical features and rapid viral diagnosis of human disease associated with avian influenza A H5N1 virus. Lancet 1998;351:467-71.
  12. Chotpitayasunondh T, Ung Vhusak K, Hanshaoworakul W et al. Human disease from influenza A (H5N1), Thailand, 2004, Emerg Infect Dis 2005;11:201-9.
  13. Govorkova EA, Leneva IA, Goloubeva OG, Bush K, Webster RG. Comparison of efficacies of RWJ-270201, Zanamivir and Oseltamivir against H5N1, H9N2 and other avian influenza viruses. Antimicrob Agents. Chemother 8001;45:2723-32.
  14. Treanor JJ, Hayden FG, Vrooman PS et al. Efficacy and safety of the oral neuraminidase inhibitor Oseltamivir in treating acute influenza : a randomized controlled trial. JAMA 2000;283:1016-24.
  15. Webby RJ, Perez DR, Coleman JS et al. Responsiveness to a pandemic alert: use of reverse genetics for rapid development of influenza vaccines. Lancet 2004;363:1099-103.
  16. Belshe RB, Mendelman PM, Treanor J et al. The efficacy of live attenuated, cold adapted, trivalent intranasal influenza virus vaccine in children. N Engl J Med 1998;338:1405-12.
  17. Hayden FG, Belshe R, Villanueva C et al. Management of influenza in households : a prospective, randomized comparison of Oseltamivir treatment with or without post exposure prophylaxis. J Infect Dis 2004;189:440-9.
Last Updated : Wednesday, March 01, 2006 Vol 3 Issue 3 Art #
How to Cite URL :
Shah I. BIRD FLU [AVIAN & HUMAN INFLUENZA (H5N1) INFECTION]. Pediatric Oncall [serial online] 2006[cited 2006 January 1];3. Art #. Available From : http://www.pediatriconcall.com/Journal/Article/FullText.aspx?artid=762&type=J&tid=&imgid=&reportid=414&tbltype=
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