Supply of neuraminidase inhibitors related to reduced influenza A (H1N1) mortality during the 2009-2010 H1N1 pandemic: an ecological study

PLoS One. 2012;7(9):e43491. doi: 10.1371/journal.pone.0043491. Epub 2012 Sep 11.

Abstract

Background: The 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.

Methods: Country-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.

Results: After 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).

Conclusion: While 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.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Antiviral Agents / pharmacology
  • Antiviral Agents / supply & distribution
  • Antiviral Agents / therapeutic use
  • Enzyme Inhibitors / supply & distribution*
  • Enzyme Inhibitors / therapeutic use*
  • Geography
  • Humans
  • Influenza A Virus, H1N1 Subtype / drug effects
  • Influenza A Virus, H1N1 Subtype / physiology*
  • Influenza, Human / drug therapy*
  • Influenza, Human / mortality*
  • Neuraminidase / antagonists & inhibitors*
  • Neuraminidase / metabolism
  • Oseltamivir / supply & distribution
  • Oseltamivir / therapeutic use
  • Pandemics / prevention & control*
  • Poisson Distribution
  • Regression Analysis
  • Socioeconomic Factors
  • World Health Organization
  • Zanamivir / supply & distribution
  • Zanamivir / therapeutic use

Substances

  • Antiviral Agents
  • Enzyme Inhibitors
  • Oseltamivir
  • Neuraminidase
  • Zanamivir

Grants and funding

This work was supported in part by National Science Foundation Grant # DMS-0354308. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. No additional external funding was received for this study.