Avian Flu: Do You Need to Be Prepared?

January 1, 2007

Avian influenza primarily affects wild birds and domesticated poultry. Humans acquire avian influenza viruses chiefly through direct contact of the mucous membranes with secretions or excreta from infected birds or contaminated poultry products. The upper respiratory tract and conjunctivae appear to be the main portals of entry. Influenza pandemics occur when new virus subtypes emerge and become readily transmissible among humans. On average, pandemics occur about 3 or 4 times per century. Avian influenza is not a pandemic influenza. It is not easily transmitted among humans, and it has not been found in the United States. Therefore, at present, the risk to persons in this country is considered low.

Avian influenza primarily affects wild birds and domesticated poultry. Humans acquire avian influenza viruses chiefly through direct contact of the mucous membranes with secretions or excreta from infected birds or contaminated poultry products. The upper respiratory tract and conjunctivae appear to be the main portals of entry.

Influenza pandemics occur when new virus subtypes emerge and become readily transmissible among humans. On average, pandemics occur about 3 or 4 times per century. Avian influenza is not a pandemic influenza. It is not easily transmitted among humans, and it has not been found in the United States.1 Therefore, at present, the risk to persons in this country is considered low.

However, the spread of avian influenza A subtype H5N1 worldwide and the outbreak in Southeast Asia are warning signs. Since influenza viruses have the ability to change, there is concern that the H5N1 virus could mutate and become more easily transmitted among humans.

WHY WORRY?
More than 200 laboratory-confirmed cases of human infection with H5N1 viruses have been reported since 2003.2 Mortality has been about 55%.2 Another alarming observation is that most cases have occurred in previously healthy children and young adults. Most cases have been associated with direct or close contact with infected poultry or contaminated surfaces.

So far, human-to-human transmission of avian influenza viruses has been inefficient. In the 1997 outbreak in Hong Kong, only one household contact of an infected patient and 3.7% of involved health care workers were subsequently seropositive.3,4 However, the changing epidemiology and pathogenicity of avian influenza viruses underscore the potential for a severe epidemic.5

Several avian influenza A virus subtypes, such as H5N1, H9N2, H7N3, and H7N7, have been shown to cross the species barrier from wild migratory birds or poultry to humans.6 Since its emergence in 1997, the H5N1 virus (Figure) has undergone multiple genetic reassortment events with avian viruses and could mutate further, potentially becoming more efficient with respect to transmission.6,7



PRESENTATION AND DIAGNOSIS
There are no pathognomonic symptoms or signs of avian influenza. Patients often present with the typical influenza symptoms, such as fever, cough, sore throat, and myalgia; conjunctivitis is fairly common as well. The patient's history is particularly important--recent travel to an area where avian influenza is endemic and a history of contact with poultry are major diagnostic clues.

Symptoms seem to occur 2 to 4 days after exposure to infected birds.8 Compared with typical influenza illness, avian influenza has a more aggressive course, with progression to pneumonia and severe respiratory failure within a few days of the onset of symptoms.8-10 Most patients who have died of avian influenza had multiorgan failure and acute respiratory distress syndrome.5 Leukopenia on presentation also appears to be a significant prognostic indicator.8,9

The diagnosis of avian influenza can be confirmed by viral culture or reverse transcriptase polymerase chain reaction (PCR) assay of throat swabs or nasopharyngeal aspirates. Reverse transcriptase PCR may be the most promising method of rapid testing.5

PREVENTION AND TREATMENT
The US Department of Agriculture has implemented measures to help prevent an outbreak of avian influenza. These measures include surveillance of bird populations, restrictions on bird importation, and regulation of agricultural practices.11

There is no commercially available vaccine to prevent avian influenza. However, vaccines are being developed and clinical trials are under way.

In vitro data and animal studies suggest that oseltamivir (Tamiflu) and zanamivir (Relenza) might be effective in treating avian influenza in humans.1,5,12,13 The World Health Organization preferentially recommends oseltamivir.14,15 However, the development of resistance to oseltamivir has been reported in Vietnamese patients who were infected with H5N1.16 Amantadine and rimantadine are not considered to be the antivirals of choice, partly because of the emergence of resistance.5

References:

REFERENCES:1. Centers for Disease Control and Prevention. Key facts about avian influenza (bird flu) and avian influenza A (H5N1) virus. Available at: http://www.cdc.gov/flu/avian/gen-info/facts.htm. Accessed December 1, 2006.
2. World Health Organization. Cumulative number of confirmed human cases of avian influenza A/(H5N1) reported to WHO. Available at: http://www.who.int/csr/disease/avian_influenza/country/cases_table_2006_11_13/en/index.html. Accessed December 1, 2006.
3. Katz JM, Lim W, Bridges CB, et al. Antibody response in individuals infected with avian influenza A (H5N1) viruses and detection of anti-H5 antibody among household and social contacts. J Infect Dis. 1999;180:1763-1770.
4. Buxton Bridges C, Katz JM, Seto WH, et al. Risk of influenza A (H5N1) infection among health care workers exposed to patients with influenza A (H5N1), Hong Kong. J Infect Dis. 2000;181:344-348.
5. Wong SS, Yuen KY. Avian influenza virus infections in humans. Chest. 2006; 129:156-168.
6. Whitley RJ, Monto AS. Seasonal and pandemic influenza preparedness: a global threat. J Infect Dis. 2006;194(suppl 2):S65-S69.
7. Li KS, Guan Y, Wang J, et al. Genesis of a highly pathogenic and potentially pandemic H5N1 influenza virus in eastern Asia. Nature. 2004;430:209-213.
8. Tran TH, Nguyen TL, Nguyen TD, et al. Avian influenza A (H5N1) in 10 patients in Vietnam. N Engl J Med. 2004;350:1179-1188.
9. Centers for Disease Control and Prevention. Cases of influenza A (H5N1)--Thailand 2004. MMWR. 2004;53:100-103.
10. Chan PK. Outbreak of avian influenza A (H5N1) virus infection in Hong Kong in 1997. Clin Infect Dis. 2002;34(suppl 2):S58-S64.
11.Morgan A. Avian influenza: an agricultural perspective. J Infect Dis. 2006; 194(suppl 2):S139-S146.
12. Leneva IA, Roberts N, Govorkova EA, et al. The neuraminidase inhibitor GS4104 (oseltamivir phosphate) is efficacious against A/Hong Kong/156/97 (H5N1) and A/Hong Kong/1074/99 (H9N2) influenza viruses. Antiviral Res. 2000;48:101-115.
13. Yen HL, Monto AS, Webster RG, Govorkova EA. Virulence may determine the necessary duration and dosage of oseltamivir treatment for highly pathogenic A/Vietnam/1203/04 influenza virus in mice. J Infect Dis. 2005;192:665-672.
14. Butler D. WHO urges regional offices to stockpile flu drug for staff. Nature. 2005;436:899.
15. Coombes R. UK stocks up on antiviral drug to tackle flu outbreak. BMJ. 2005;330:495.
16. de Jong MD, Tran TT, Truong HK, et al. Oseltamivir resistance during treatment of influenza A (H5N1) infection. N Engl J Med. 2005;353:2667-2672.