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Open Access Highly Accessed Research article

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

Vernon J Lee1234*, Jonathan Yap1, Joshua K Tay1, Ian Barr5, Qiuhan Gao1, Hanley J Ho1, Boon Huan Tan6, Paul M Kelly4, Paul A Tambyah7, Anne Kelso5 and Mark I Chen8

Author Affiliations

1 Biodefence Centre, Ministry of Defence, Transit Road, Singapore 778910, Singapore

2 Centre for Health Services Research, National University of Singapore, Medical Drive, Singapore 117597, Singapore

3 Department of Epidemiology and Public Health, National University of Singapore, Medical Drive, Singapore 117597, Singapore

4 National Centre for Epidemiology and Population Health, Australian National University, Canberra, ACT 0200, Australia

5 WHO Collaborating Center for Reference and Research for Influenza, Wreckyn Street, North Melbourne, Victoria 3051, Australia

6 Detection and Diagnostics Laboratory, Defence Medical and Environmental Research Institute, DSO National Laboratories, Medical Drive, Singapore 117510, Singapore

7 Division of Infectious Diseases, National University of Singapore, Lower Kent Ridge Road, Singapore 119074, Singapore

8 Department of Clinical Epidemiology, Tan Tock Seng Hospital, Jalan Tan Tock Seng, Singapore 308433, Singapore

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BMC Infectious Diseases 2010, 10:164  doi:10.1186/1471-2334-10-164

Published: 10 June 2010

Abstract

Background

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.

Methods

Between 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.

Results

237 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.

Conclusions

Post-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.