NEW YORK (Reuters Health) – The high case mortality rate associated with H5N1 avian influenza in humans can be significantly reduced with oseltamivir therapy, even when started a week after symptom onset, according to an analysis of a global patient registry.
“While interest in avian influenza has been eclipsed by the widespread concern about swine flu, it is important to remember that there is a large reservoir of the H5N1 (avian influenza) virus in birds,” Dr. Nancy A. Dreyer pointed out in emailed comments. “Untreated, human infection with H5N1 carries a high mortality, and death comes quickly.”
Furthermore, she added, “The threat remains that avian influenza could become more adept at human-to-human transmission and could still become a pandemic.”
Dr. Dreyer of Outcome Sciences in Cambridge, Massachusetts, and an international team describe their study in the October 15th issue of The Journal of Infectious Diseases.
To examine the efficacy of antiviral therapy for H5N1 influenza, the researchers compiled data on 308 cases from 12 countries, mostly in Asia. “To our knowledge, this is the first pooled, systematic analysis of multi-country data and the largest series of human cases of confirmed H5N1 infection analyzed,” the authors state.
Among the cohort, 150 patients were treated with oseltamivir alone while 134 did not receive any antiviral agents. The other 24 were treated with other antivirals.
Crude overall survival rates were 60% for patients who received at least one dose of oseltamivir compared with only 24% among those not given any antiviral therapy, according to the report.
Survival was 83% when oseltamivir was given within 2 days of symptom onset, and a survival advantage was apparent with treatment started up to 6-8 days after symptom onset. “No statistically significant benefit was seen when the first dose of oseltamivir was administered >8 days after symptom onset.”
The mortality hazard ratio with oseltamivir was 0.51 after adjustment for propensity score, and the benefit was seen in all age groups.
Summing up, Dr. Dreyer said: “The main contribution of this large observational study is the strong evidence it reveals about the benefits of treatment with oseltamivir, and perhaps most important, that even when treatment is delayed as much as 6-8 days after symptom onset, there is still a meaningful life-sparing benefit.”
She added, “This study also shows one of the benefits of large observational studies — that is, their ability to detect previously unknown risks and benefits. In this situation, the effectiveness of oseltamivir even with delayed initiation may not have been otherwise detected.”
F. Hoffmann-La Roche, the manufacturer of Tamiflu, provided funding to create and conduct the registry study.
In an editorial Dr. Robert B. Couch of Baylor College of Medicine and Dr. Barry R. Davis of The University of Texas School of Public Health, Houston, ask, “Has Oseltamivir Been Shown to Be Effective for Treatment of H5N1 Influenza?”
They conclude that it has, but say that better treatment is needed. “Available data suggest oral therapy with a higher dosage (150 mg twice daily) and a longer duration (7-10 days) or parenteral therapy with peramivir or zanamivir are likely to improve on the standard oral oseltamivir treatment regimen.”
Reference:
Effectiveness of Antiviral Treatment in Human Influenza A(H5N1) Infections: Analysis of a Global Patient Registry
J Infect Dis 2010;202:1154–1160.
