Seroconversion and asymptomatic infections during oseltamivir prophylaxis against Influenza A H1N1 2009.
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.
Lee
Vernon J
VJ
Biodefence Centre, Ministry of Defence, Transit Road, Singapore 778910, Singapore. vernonljm@hotmail.com
Yap
Jonathan
J
Tay
Joshua K
JK
Barr
Ian
I
Gao
Qiuhan
Q
Ho
Hanley J
HJ
Tan
Boon Huan
BH
Kelly
Paul M
PM
Tambyah
Paul A
PA
Kelso
Anne
A
Chen
Mark I
MI
D000328:Adult; D000914:Antibodies, Viral / Q000097:blood*; D000998:Antiviral Agents / Q000008:administration & dosage*; D018890:Chemoprevention / Q000379:methods*; D015331:Cohort Studies; D004196:Disease Outbreaks; D006385:Hemagglutination Inhibition Tests; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D007251:Influenza, Human / Q000175:diagnosis* / Q000517:prevention & control*; D008297:Male; D008889:Military Personnel; D009305:Nasopharynx / Q000821:virology; D053139:Oseltamivir / Q000008:administration & dosage*; D012367:RNA, Viral / Q000302:isolation & purification; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012846:Singapore / Q000453:epidemiology; D011795:Surveys and Questionnaires; D055815:Young Adult
D000914:Antibodies, Viral; D000998:Antiviral Agents; D012367:RNA, Viral; D053139:Oseltamivir