Seroconversion and asymptomatic infections during oseltamivir prophylaxis against Influenza A H1N1 2009

Vernon J Lee,Qiuhan Gao,Anne Kelso,Boon Huan Tan,Joshua K Tay,Hanley J Ho,Mark I Chen,Paul M Kelly,Jonathan Yap,Paul A Tambyah,Ian Barr

doi:10.1186/1471-2334-10-164

Abstract

BackgroundAnti-viral prophylaxis is used to prevent the transmission of influenza. We studied serological confirmation of 2009 Influenza A (H1N1) infections during oseltamivir prophylaxis and after cessation of prophylaxis.MethodsBetween 22 Jun and 16 Jul 09, we performed a cohort study in 3 outbreaks in the Singapore military where post-exposure oseltamivir ring chemoprophylaxis (75 mg daily for 10 days) was administered. The entire cohort was screened by RT-PCR (with HA gene primers) using nasopharyngeal swabs three times a week. Three blood samples were taken for haemagglutination inhibition testing - at the start of outbreak, 2 weeks after completion of 10 day oseltamivir prophylaxis, and 3 weeks after the pandemic's peak in Singapore. Questionnaires were also administered to collect clinical symptoms.Results237 personnel were included for analysis. The overall infection rate of 2009 Influenza A (H1N1) during the three outbreaks was 11.4% (27/237). This included 11 index cases and 16 personnel (7.1%) who developed four-fold or higher rise in antibody titres during oseltamivir prophylaxis. Of these 16 personnel, 8 (3.5%) were symptomatic while the remaining 8 personnel (3.5%) were asymptomatic and tested negative on PCR. Post-cessation of prophylaxis, an additional 23 (12.1%) seroconverted. There was no significant difference in mean fold-rise in GMT between those who seroconverted during and post-prophylaxis (11.3 vs 11.7, p = 0.888). No allergic, neuropsychiatric or other severe side-effects were noted.ConclusionsPost-exposure oseltamivir prophylaxis reduced the rate of infection during outbreaks, and did not substantially increase subsequent infection rates upon cessation. Asymptomatic infections occur during prophylaxis, which may confer protection against future infection. Post-exposure prophylaxis is effective as a measure in mitigating pandemic influenza outbreaks.

Highlights

Anti-viral prophylaxis is used to prevent the transmission of influenza
There were no increases of influenza-like illness or respiratory illness cases in these units, nor were there any confirmed cases of 2009 Influenza A (H1N1)
The final study population consisted of 237 personnel of which 11 personnel were index cases of the outbreaks

Summary

Introduction

Anti-viral prophylaxis is used to prevent the transmission of influenza. We studied serological confirmation of 2009 Influenza A (H1N1) infections during oseltamivir prophylaxis and after cessation of prophylaxis. Anti-viral prophylaxis has been used as a strategy to prevent the transmission and spread of influenza. Post-exposure prophylaxis with oseltamivir, a commonly used neuraminidase-inhibitor, has been shown to be effective in preventing the development of clinical disease against seasonal influenza when used against household contacts [1,2]. One mathematical model showed that premature cessation of prophylaxis before the pandemic's peak resulted in higher peak infection rates compared to no prophylaxis use [7]. Prophylaxis may delay the spread of the virus such that the overall infection rate in the affected group is reduced, and may spread out the burden of disease, reducing the strain on resources and disruption of services. There is little evidence on the actual outcome of prophylaxis in such situations

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Conclusion