Abstract
BackgroundThe influenza A (H1N1) pandemic swept across the globe from April 2009 to August 2010 affecting millions. Many WHO Member States relied on antiviral drugs, specifically neuraminidase inhibitors (NAIs) oseltamivir and zanamivir, to treat influenza patients in critical condition. Such drugs have been found to be effective in reducing severity and duration of influenza illness, and likely reduced morbidity during the pandemic. However, it is less clear whether NAIs used during the pandemic reduced H1N1 mortality.MethodsCountry-level data on supply of oseltamivir and zanamivir were used to predict H1N1 mortality (per 100,000 people) from July 2009 to August 2010 in forty-two WHO Member States. Poisson regression was used to model the association between NAI supply and H1N1 mortality, with adjustment for economic, demographic, and health-related confounders.ResultsAfter adjustment for potential confounders, each 10% increase in kilograms of oseltamivir, per 100,000 people, was associated with a 1.6% reduction in H1N1 mortality over the pandemic period (relative rate (RR) = 0.84 per log increase in oseltamivir supply). While the supply of zanamivir was considerably less than that of oseltamivir in each Member State, each 10% increase in kilogram of active zanamivir, per 100,000, was associated with a 0.3% reduction in H1N1 mortality (RR = 0.97 per log increase).ConclusionWhile there are limitations to the ecologic nature of these data, this analysis offers evidence of a protective relationship between antiviral drug supply and influenza mortality and supports a role for influenza antiviral use in future pandemics.
Highlights
The 2009 influenza A (H1N1) pandemic provoked large-scale public health responses and implementation of pandemic preparedness plans throughout the world
Clinical trials have shown that neuraminidase inhibitors (NAIs), a class of antiviral drugs including oseltamivir and zanamivir, are efficacious in lowering morbidity related to influenza, reducing both the duration of symptoms from influenza and the overall severity of the illness [1,2,3,4]
A retrospective analysis of patients seen during the H1N1 pandemic in Beijing found that 80% of the inpatients evaluated received antiviral treatment and found oseltamivir to be beneficial [13]
Summary
Data for total kilograms of neuraminidase inhibitors (NAIs) distributed and lab-confirmed deaths attributed to pandemic H1N1 from July 2009 to August 2010 were available for 62 WHO Member States in all WHO regions. Twelve were significantly associated with both pandemic H1N1 mortality rate and NAI rates, and kept as potential confounders for evaluation in multivariable adjusted models These twelve potential confounders included under five mortality, life expectancy at birth, percent of obese males over the age of 15, percent of population using improved sanitation, percent of population with access to improved water quality standards, derived pregnancy rate, adult literacy rate, percentage of population over the age of 65, per capita gross domestic product (GDP), per capita health spending, physician density, and hospital bed density. The final model considered pregnancy rate, life expectancy, hospital bed density, per capita health spending, percentage of the population over 65 years old, under-five mortality rate, adult literacy rate, the rate of male obesity, and physician density. The statistical program R (http://www.r-project.org/) was used for all analysis and pvalues#0.05 were considered statistically significant
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