Biosecurity Briefing Subscribe | About | Current Issue | RSS | Archive WHO Update on Human H5N1 Infections By Eric Toner, January 18, 2008 On January 17, 2008, the Writing Committee of the Second World Health Organization (WHO) Consultation on Clinical Aspects of Human Infection with Avian Influenza A (H5N1) Virus published a review article in the New England Journal of Medicine providing updated information on human cases of highly pathogenic avian influenza A (H5N1) infection.1 Overview
The article indicates that H5N1 viruses continue to evolve and that eight distinct clades, or subgroups, of H5N1 are now recognized. Clade 1 viruses caused the 2004 outbreaks in Southeast Asia; and Clade 2 viruses have caused outbreaks in Indonesia, western China, Europe and Africa (Clade 2 is now recognized to have 5 subclades). Although the introduction of H5N1 into new geographic regions may occur as a result of migratory wild birds, the authors conclude that the principal spread of H5N1 has been associated with movement of domesticated poultry and poultry products. The authors judge that the risk of H5N1 being introduced to North America by migratory birds through Alaska is low.1 Human Infections
Although human cases of H5N1 continue to occur, primarily in Indonesia and Egypt, they remain rare relative to poultry infections. Ninety percent of human cases occur in individuals younger than age 40. Although the overall case fatality rate remains at approximately 60%, it is highest in individuals aged 10-19 and lowest in those older than 50 years. The reason for the difference in fatality rates by age is unclear. Most human cases continue to be associated with recent and close poultry exposure. Usually, but not always, the birds were ill or had died. The consumption of raw or undercooked poultry products also has been associated with some cases. The source of infection in approximately one quarter of cases is unclear, and there continues to be little evidence of mild or asymptomatic human infections. Many clusters (i.e., two or more cases that are linked) of human H5N1 infections have been identified in 10 different countries. Although most clusters probably represent common-source exposures (i.e. exposure to the same infected poultry), several appear to have resulted from non-sustained person-to-person transmission within a family. Despite new knowledge about H5N1, understanding of poultry-to-human and human-to-human transmission of the virus remains incomplete.1 Symptoms
Evidence indicates that, as in birds but in contrast to other human influenza infections, H5N1 can infect many systems of the body. However, to date, pneumonia continues to be the predominant clinical symptom of H5N1 infection. Since respiratory infection is a symptom common to many other diseases, approximately 90% of H5N1 patients are initially misdiagnosed. The most commonly mistaken diagnoses are community acquired pneumonia, dengue, and simply upper respiratory infection.1 Antivirals and Vaccines
According to the article, most Clade 1 and Clade 2 viruses from Indonesia are resistant to the antiviral drug amantadine; however, Clade 2 viruses from other countries are usually susceptible. Early treatment with oseltamivir (brand name Tamiflu®) appears to improve human survival. However, Clade 1 viruses are 15-30 times more sensitive to oseltamivir than Clade 2 viruses. There have been instances where H5N1 virus variants that are highly resistant to oseltamivir have emerged during the course of therapy and have been associated with subsequent death.1 Continued advances in vaccine research hold promise for more effective vaccines. However, the vaccines produced thus far have limited utility due to the continual changes in the H5N1 virus and because two large doses of the vaccine are required to induce an adequate immune response. The New England Journal article does suggest that “priming” a person’s immune system with a pre-pandemic vaccine may consequently reduce the needed amount of pandemic-specific vaccine to a single dose.1 References - Writing Committee of the Second World Health Organization Consultation on Clinical Aspects of Human Infection with Avian Influenza A (H5N1) Virus. Update on avian influenza A (H5N1) virus infection in humans. NEJM 2008;358:261-273. http://content.nejm.org/cgi/content/full/358/3/261. Accessed January 17, 2008
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