Serological response in RT-PCR confirmed H1N1-2009 influenza a by hemagglutination inhibition and virus neutralization assays: an observational study.
BACKGROUND
We describe the serological response following H1N1-2009 influenza A infections confirmed by reverse-transcriptase polymerase chain reaction (RT-PCR).


RESULTS
The study included patients admitted to hospital, subjects of a seroepidemiologic cohort study, and participants identified from outbreak studies in Singapore. Baseline (first available blood sample) and follow-up blood samples were analyzed for antibody titers to H1N1-2009 and recently circulating seasonal influenza A virus strains by hemagglutination inhibition (HI) and virus micro-neutralization (VM) assays. 267 samples from 118 cases of H1N1-2009 were analyzed. Geometric mean titers by HI peaked at 123 (95% confidence interval, CI 43-356) between days 30 to 39. The chance of observing seroconversion (four-fold or greater increase of antibodies) was maximized when restricting analysis to 45 participants with baseline sera collected within 5 days of onset and follow-up sera collected 15 or more days after onset; for these participants, 82% and 89% seroconverted to A/California/7/2009 H1N1 by HI and VM respectively. A four-fold or greater increase in cross-reactive antibody titers to seasonal A/Brisbane/59/2007 H1N1, A/Brisbane/10/2007 H3N2 and A/Wisconsin/15/2009 H3N2 occurred in 20%, 18% and 16% of participants respectively.


CONCLUSIONS
Appropriately timed paired serology detects 80-90% RT-PCR confirmed H1N1-2009; Antibodies from infection with H1N1-2009 cross-reacted with seasonal influenza viruses.
Chen
Mark I
MI
Clinical Epidemiology, Tan Tock Seng Hospital, Singapore, Singapore. Mark_IC_Chen@ttsh.com.sg
Barr
Ian G
IG
Koh
Gerald C H
GC
Lee
Vernon J
VJ
Lee
Caroline P S
CP
Shaw
Robert
R
Lin
Cui
C
Yap
Jonathan
J
Cook
Alex R
AR
Tan
Boon Huan
BH
Loh
Jin Phang
JP
Barkham
Timothy
T
Chow
Vincent T K
VT
Lin
Raymond T P
RT
Leo
Yee-Sin
YS
D000328:Adult; D000914:Antibodies, Viral / Q000032:analysis / Q000276:immunology; D015331:Cohort Studies; D003429:Cross Reactions; D005260:Female; D006385:Hemagglutination Inhibition Tests / Q000379:methods*; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000502:physiology*; D007251:Influenza, Human / Q000175:diagnosis* / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009500:Neutralization Tests / Q000379:methods*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055815:Young Adult
D000914:Antibodies, Viral
PLoS One. 2010 Apr 14;5(4):e10036
20418945
N Engl J Med. 2010 Jun 10;362(23):2175-2184
20558368
N Engl J Med. 2009 Jun 18;360(25):2605-15
19423869
Wkly Epidemiol Rec. 2010 Jun 11;85(24):229-35
20545056
Lancet. 2010 Mar 27;375(9720):1100-8
20096450
Science. 2009 Jun 19;324(5934):1557-61
19433588
Emerg Infect Dis. 2010 Oct;16(10):1554-61
20875280
J Infect Dis. 2010 Nov 1;202(9):1319-26
20863233
Arch Intern Med. 2001 Sep 24;161(17):2116-22
11570941
Virus Res. 2004 Jul;103(1-2):125-32
15163500
Ann Acad Med Singap. 2010 Apr;39(4):313-12
20473458
N Engl J Med. 2009 Dec 17;361(25):2405-13
19745216
JAMA. 2010 Apr 14;303(14):1383-91
20388894
J Infect Dis. 2006 Jan 1;193(1):49-53
16323131
PLoS Curr. 2010 Feb 24;2:RRN1148
20191082
Singapore Med J. 1970 Mar;11(1):33-7
5448708
N Engl J Med. 2009 Nov 12;361(20):1945-52
19745214
JAMA. 2010 Jan 6;303(1):37-46
20026597
Wkly Epidemiol Rec. 2010 Mar 5;85(10):81-92
20210260
PLoS Curr. 2009 Dec 24;1:RRN1140
20043034
Emerg Infect Dis. 2010 Jan;16(1):103-5
20031051