WHO panel offers clinical profile of H1N1

May 5, 2010 (CIDRAP News) – A panel of experts assembled by the World Health Organization (WHO) has published a clinical profile of pandemic H1N1 influenza, using data from scores of studies to fill in details of the broad picture that has emerged over the past year.

The report, released today by the New England Journal of Medicine, affirms that the disease has taken its heaviest toll on young adults and children but otherwise generally resembles seasonal flu.

The international team of 15 authors writes that the overall estimated case-fatality rate (CFR) has been less than 0.5%, with estimates ranging all the way from 0.0004% to 1.47%, reflecting uncertainty about the true number of cases. The US CFR has been estimated at 0.048%, a bit higher than the United Kingdom's estimate of 0.026%.

About 90% of those who have died of the virus were younger than 65, while hospitalization rates have been highest in children under 5 years old and lowest in the elderly, the report notes.

The virus seems to be about as contagious as seasonal flu or slightly more so, with estimates of the basic reproduction number (the number of secondary cases caused by the primary case in a susceptible population) ranging from 1.3 to 1.7. But in school outbreaks the number may be about twice as high: 3.0 to 3.6.

The report says that about 25% to 50% of H1N1 patients who were hospitalized or died had no coexisting medical condition. Risk factors for complications are generally the same as those for complications in seasonal flu, including age under 5 years, pregnancy, cardiovascular disease, asthma, diabetes, immunosuppression, and several other conditions. Obesity is "suggested but not yet proved to be an independent risk factor" for severe disease or death.

The virus's incubation period is about 1.5 to 3 days, similar to that of seasonal flu, the report says. But viral replication may persist longer in H1N1, as some studies have found that patients with uncomplicated cases still carried infectious virus 8 days after illness onset.

A mild illness with no fever has been reported in 8% to 32% of cases, the article says. It affirms that gastrointestinal symptoms have been more common in H1N1 than in seasonal flu, especially in adults.

The most common clinical syndrome leading to hospitalization and intensive care, the experts write, is "diffuse viral pneumonitis associated with severe hypoxemia, ARDS [acute respiratory distress syndrome], and sometimes shock and renal failure." This has been seen in about 49% to 72% of intensive care unit (ICU) cases.

Other syndromes seen in severe cases include severe exacerbation of chronic obstructive pulmonary disease (COPD) and asthma. About 24% to 50% of hospitalized patients have had a history of asthma, and COPD has been reported in about 36% of hospitalized adults.

Secondary bacterial pneumonia has been suspected or confirmed in 20% to 24% of ICU patients and found in 26% to 38% of patients who died. The most common pathogens are Staphylococucs aureus (often methicillin-resistant), Streptococcus pneumoniae, and S pyogenes.

The article affirms the established advice about early treatment with oseltamivir (Tamiflu) or zanamivir (Relenza) for high-risk patients and adds that doubling the dose and duration of oseltamivir therapy is reasonable in patients with pneumonia or evidence of disease progression.

The report notes that antiviral resistance has been seen sporadically, mainly in treated patients. The His275Tyr mutation confers resistance to oseltamivir (and to peramivir, a drug that is used intravenously under an emergency use authorization) but does not cause resistance to zanamivir.

Writing Committee of the WHO Consultation on Clinical Aspects of Pandemic 2009 Influenza A (H1N1). Clinical aspects of pandemic 2009 influenza A (H1N1) virus infection. N Engl J Med 2010 May 6;362(18):1708-19 [Full text]

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