Pandemic Influenza Due to pH1N1/2009 Virus: Estimation of Infection Burden in Reunion Island through a Prospective Serosurvey, Austral Winter 2009

International audienceBACKGROUND: To date, there is little information that reflects the true extent of spread of the pH1N1/2009v influenza pandemic at the community level as infection often results in mild or no clinical symptoms. This study aimed at assessing through a prospective study, the attack rate of pH1N1/2009 virus in Reunion Island and risk factors of infection, during the 2009 season.METHODOLOGY/PRINCIPAL FINDINGS: A serosurvey was conducted during the 2009 austral winter, in the frame of a prospective population study. Pairs of sera were collected from 1687 individuals belonging to 772 households, during and after passage of the pandemic wave. Antibodies to pH1N1/2009v were titered using the hemagglutination inhibition assay (HIA) with titers ≥ 1/40 being considered positive. Seroprevalence during the first two weeks of detection of pH1N1/2009v in Reunion Island was 29.8% in people under 20 years of age, 35.6% in adults (20-59 years) and 73.3% in the elderly (≥ 60 years) (P<0.0001). Baseline corrected cumulative incidence rates, were 42.9%, 13.9% and 0% in these age groups respectively (P<0.0001). A significant decline in antibody titers occurred soon after the passage of the epidemic wave. Seroconversion rates to pH1N1/2009 correlated negatively with age: 63.2%, 39.4% and 16.7%, in each age group respectively (P<0.0001). Seroconversion occurred in 65.2% of individuals who were seronegative at inclusion compared to 6.8% in those who were initially seropositive.CONCLUSIONS: Seroincidence of pH1N1/2009v infection was three times that estimated from clinical surveillance, indicating that almost two thirds of infections occurring at the community level have escaped medical detection. People under 20 years of age were the most affected group. Pre-epidemic titers ≥ 1/40 prevented seroconversion and are likely protective against infection. A concern was raised about the long term stability of the antibody responses

Synoptic view of CoPanFlu protocol implementation.

<p>Green and violet lines represent the number of blood samples collected from the cohort, on inclusion (weeks 30–44) and at the end of the study (weeks 45–52) respectively (Y axis at the left: number of samples collected). Shaded area represents the profile of the epidemic wave in Reunion Island according to the local epidemiology surveillance unit (Y axis at the right: estimated number of symptomatic influenza cases occurring in the island); X axis: calendar weeks.</p

Seroconversion rates according to age and baseline-proxy HIA titers in 249 individuals enrolled in pre-pandemic phase, CoPanFlu-RUN cohort, Reunion Island, 2009.

<p>Data are numbers, percentages (100 * number seroconverters/number tested (95% confidence intervals)) and ALR parameter test <i>P</i> value for comparison of seroconversion proportions between baseline-proxy HIA titer (<1/40 versus ≥1/40), in each age, after controlling for household selection. In the group “All ages” seroconversion rates were standardized according to age structure of the community.</p><p>*HIA titer: hemagglutination inhibition assay titer. Seroconversion was defined as a shift from seronegative at inclusion (i.e. HIA titer <1/40) to seropositive on follow-up sample, or as a 4-fold increase of reciprocal HIA titer between first and second paired samples for sera tested seropositive on inclusion (i.e. HIA titer ≥1/40).</p

Socio-demographic and space-time characteristics of the COPanFlu-RUN cohort subjects compared to the community, Reunion Island, 2009.

<p>Data are numbers (percentages);</p><p>*paired sera;</p><p>**French National Institute for Statistics and Economical Studies (INSEE) source.</p

Probability of seroconversion according to age and to baseline pre-epidemic HIA titer.

<p>Probability of seroconversion according to age and to baseline pre-epidemic HIA titer.</p

The cohort profile and major outcomes.

<p><a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0025738#pone-0025738-g001" target="_blank">Figure 1</a> details the three phases of the protocol: i) inclusion (weeks 30–44) and serum samples S1 collection; ii) follow up for detection of ILI in households, qRT-PCR on nasal swabs and estimation of cumulative seroincidence rates; iii) end of the study (weeks 45–52) and samples S2 collection. HIA on paired sera (S1+S2) allowed estimating seroconversion rates.</p

Seroconversion rates to 2009 pandemic influenza A H1N1 virus (pH1N1/2009) according to age and time of first sample (S1) collection, CoPanFlu-RUN cohort, Reunion Island, 2009.

<p>Data are numbers, percentages (95% confidence intervals) and ALR parameter test <i>P</i> value for comparison of seroconversion proportions according to time of first sample (S1) collection at inclusion, in each age group, after controlling for household selection. In the group “All ages”, rates of seroconversion were standardized according to age structure of the community. NA: not assessed. Seroconversion was defined as a shift from seronegative at inclusion (i.e. HIA titer <1/40) to seropositive on follow-up sample, or as a 4-fold increase of reciprocal HIA titer between first and second paired samples for sera tested seropositive on inclusion (i.e. HIA titer ≥1/40). W30–31: first sample collected in early epidemic phase (baseline-proxy); W32–39: first sample collected during the full development of the epidemic wave; W40–44: first sample collected in the immediate post- epidemic phase; W30–44: whole inclusion period.</p