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Avian Influenza: High Mortality but Inefficient Person-to-Person Spread -- So Far

Probable person-to-person transmission of avian influenza: An early warning of a pandemic to come?

Avian influenza A (H5N1) virus has spread in bird populations in Asia; in 2004, it infected at least 44 humans, killing 32. Three recent studies provide new information about its spread in human populations and about clinical findings.

Ungchusak and colleagues' investigation of a cluster of three cases (2 fatal) in Thailand showed probable person-to-person transmission of H5N1. The 11-year-old index patient, who had played and slept in an area where sick and dying chickens were sometimes present, was hospitalized with pneumonia in September 2004. Her mother and aunt, who had had no recent exposure to poultry or poultry products, each provided >12 hours of unprotected bedside care for her before she died. Both developed pneumonia. The mother died; the aunt, in whom oseltamivir was initiated 7 days after symptom onset, survived. Specimens from the mother (lung tissue) and aunt (nasopharyngeal and throat swabs) tested positive for H5N1 by reverse-transcriptase (RT) PCR. Genetic sequencing showed that all the viral genes were of avian origin and were closely related to other H5N1 sequences from Thailand. No additional cases were identified among contacts.

In December 2003, Thailand began countrywide surveillance for H5N1 to identify patients with influenzalike illnesses or pneumonia who had been exposed to sick poultry or lived in areas with abnormal poultry deaths. Nasopharyngeal or throat swabs and serum samples were collected from such patients. H5N1 was diagnosed by positive viral culture, immunofluorescence assay, or RT-PCR. Out of 610 possible cases reported from January through March 2004, Chotpitayasunondh and colleagues identified 12 confirmed (8 fatal), 12 suspected, and 577 excluded cases. Confirmed-case patients were younger than suspected case-patients and were significantly more likely to die than were excluded patients. In confirmed cases, fever preceded dyspnea; myalgia and diarrhea each occurred in 42%. Lymphopenia, found in 58%, was associated with acute respiratory distress syndrome and with death. Fifty-eight percent of confirmed-case patients received oseltamivir; survival tended to be associated with earlier therapy.

Liem and colleagues conducted a cross-sectional seroprevalence survey among workers at a Hanoi hospital who had been exposed to patients with confirmed or probable H5N1 infection or to their clinical specimens. Testing for antibodies to H5N1 by microneutralization (single specimen, 29 days after exposure) was completed on 95% of employees with possible exposure. Most had used personal protective equipment while providing clinical care; none had taken oseltamivir prophylactically. No evidence of transmission was found among the 83 employees tested.

Comment: Although the first study provides convincing evidence for person-to-person H5N1 transmission after close contact, spread among humans has been inefficient thus far. As pointed out in editorial comments, the eight Asian countries with recent H5N1 outbreaks in poultry contain about 30% of the world's population, and contact with poultry is common among rural residents. Recent studies provide evidence of heightened potential for a pandemic (e.g., increased pathogenicity in poultry, an expanded mammalian range [see Journal Watch Infectious Diseases Dec 10 2004], excretion of highly pathogenic forms of the virus by apparently healthy ducks). Mutation, or reassortment of avian and human genes, could lead to a virus that retains its virulence but is more transmissible among humans -- a reason for grave concern. Scientists and policymakers must explore ways to control the virus, assuming both genetic change and expansion into other regions.

— Mary E. Wilson, MD

Published in Journal Watch Infectious Diseases February 11, 2005

Citation(s):

Ungchusak K et al. Probable person-to-person transmission of avian influenza A (H5N1). N Engl J Med 2005 Jan 27; 352:333-40.

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Chotpitayasunondh T et al. Human disease from influenza A (H5N1), Thailand, 2004. Emerg Infect Dis 2005 Feb; 11:201-9.

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Liem NT et al. Lack of H5N1 avian influenza transmission to hospital employees, Hanoi, 2004. Emerg Infect Dis 2005 Feb; 11:210-5.

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Monto AS. The threat of an avian influenza pandemic. N Engl J Med 2005 Jan 27; 352:323-5.

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Stöhr K. Avian influenza and pandemics -- Research needs and opportunities. N Engl J Med 2005 Jan 27; 352:405-7.

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• Medline abstract (Free)