Oct 11, 2005 (CIDRAP News) – A recent and extensive review of research on H5N1 avian influenza in humans shows the illness differs from ordinary flu in several ways, besides the most obvious fact that it is far more deadly.
The report by a World Health Organization (WHO) committee says avian flu may have a longer incubation period and is more likely to cause diarrhea than typical flu viruses are, among other differences.
Published in the Sep 29 New England Journal of Medicine, the review was written by experts from several countries, including Vietnam, Cambodia, Thailand, the United States, the United Kingdom, Hong Kong, and Myanmar. They reviewed 71 published studies and reports, including details on 41 confirmed human cases from Vietnam, Thailand, Cambodia, and Hong Kong.
The H5N1 virus first jumped from birds to humans in Hong Kong in 1997, infecting 18 people and causing 6 deaths. In late 2003 the virus began sweeping through poultry flocks in East Asia, and since then it has struck at least 116 people and killed at least 60, by the WHO's official count.
The new report says the virus may incubate longer than other human flu viruses before causing symptoms. Incubation periods in ordinary flu range from 1 to 4 days, with an average of 2 days, according to the Centers for Disease Control and Prevention (CDC). In H5N1 cases, the incubation time has mostly been from 2 to 4 days but has stretched to 8 days, the WHO report says. In household clusters of cases, the time between cases has generally ranged from 2 to 5 days but sometimes has been as long as 17 days.
Initial symptoms are more likely to include diarrhea in avian flu than in ordinary flu, the report says. The problem can appear up to a week before any respiratory symptoms. That feature, combined with the detection of viral RNA in stool samples, suggests that the virus grows in the gastrointestinal tract.
Lower respiratory tract symptoms such as shortness of breath appear early in the course of the illness, whereas upper respiratory symptoms such as runny nose are less common, the article says. Also, unlike in ordinary flu cases, the virus may be found in larger amounts in the throat than in the nose.
Most cases so far have been linked with exposure to poultry. Specific activities that have been implicated include plucking and preparation of diseased birds; handling fighting cocks; playing with poultry, especially asymptomatic infected ducks; and consumption of duck's blood or possibly undercooked poultry, the report says.
Blood tests of people in contact with H5N1 patients in Vietnam and Thailand have shown no evidence of asymptomatic infections. However, surveillance involving polymerase chain reaction (PCR) tests has revealed mild cases, more infections in older adults, and an increase in family clusters of cases in northern Vietnam—"findings suggesting that the local virus strains may be adapting to humans," the article says. (The WHO first reported these findings in May; see link to more information below.)
But it adds that more work is needed to confirm these findings, and so far the disease has rarely spread to healthcare workers, even when appropriate isolation measures were not used.
The article says the relatively low number of human cases amid widespread infection in birds suggests that the species barrier to human cases of H5N1 is "substantial." The authors add that family clusters of cases may be caused by common exposures rather than by person-to-person transmission.
The report also discusses the "severe" lung injury found in autopsies of H5N1 victims, whose lungs become choked with debris resulting from the body's intense response to the infection. The authors say the body's innate immune response to the virus, involving heavy release of proteins that trigger inflammation, may contribute to the severity of the disease.
Most patients hospitalized for H5N1 infection have received antiviral drugs, usually oseltamivir, the report says. This treatment appears to be helpful only when started early in the illness.
Recent experiments on mice suggest that the virus has become less susceptible to oseltamivir since 1997, the article notes. To reap a similar benefit, mice infected with a 2004 strain of the virus needed a higher dosage and longer course of oseltamivir than mice infected with a 1997 strain did. Hence, the report suggests that physicians treating severe infections should consider doubling the approved dose.
Oseltamivir is one of the two neuraminidase inhibitors used for flu. The other one, zanamivir, has not been studied in H5N1 cases, the report says. The two older antivirals used for flu, amantadine and rimantadine, no longer work against H5N1.
Writing committee of the World Health Organization (WHO) Consultation on Human Influenza A/H5. Avian influenza A (H%N1) infection in humans. N Engl J Med 2005 Sep 29;353(13):1374-85 [Full text]
May 18, 2005, CIDRAP News story "WHO: Pandemic threat may be growing"