Serological Evidence of Subclinical Transmission of the 2009 Pandemic H1N1 Influenza Virus Outside of Mexico

Abstract

BackgroundRelying on surveillance of clinical cases limits the ability to understand the full impact and severity of an epidemic, especially when subclinical cases are more likely to be present in the early stages. Little is known of the infection and transmissibility of the 2009 H1N1 pandemic influenza (pH1N1) virus outside of Mexico prior to clinical cases being reported, and of the knowledge pertaining to immunity and incidence of infection during April–June, which is essential for understanding the nature of viral transmissibility as well as for planning surveillance and intervention of future pandemics.Methodology/Principal FindingsStarting in the fall of 2008, 306 persons from households with schoolchildren in central Taiwan were followed sequentially and serum samples were taken in three sampling periods for haemagglutination inhibition (HI) assay. Age-specific incidence rates were calculated based on seroconversion of antibodies to the pH1N1 virus with an HI titre of 1∶40 or more during two periods: April–June and September–October in 2009. The earliest time period with HI titer greater than 40, as well as a four-fold increase of the neutralization titer, was during April 26–May 3. The incidence rates during the pre-epidemic phase (April–June) and the first wave (July–October) of the pandemic were 14.1% and 29.7%, respectively. The transmissibility of the pH1N1 virus during the early phase of the epidemic, as measured by the effective reproductive number R0, was 1.16 (95% confidence interval (CI): 0.98–1.34).ConclusionsApproximately one in every ten persons was infected with the 2009 pH1N1 virus during the pre-epidemic phase in April–June. The lack of age-pattern in seropositivity is unexpected, perhaps highlighting the importance of children as asymptomatic transmitters of influenza in households. Although without virological confirmation, our data raise the question of whether there was substantial pH1N1 transmission in Taiwan before June, when clinical cases were first detected by the surveillance network.

2009 A(H1N1) Seroconversion Rates and Risk Factors among the General Population in Vientiane Capital, Laos

“…Serological analysis provided a picture consistent with what has been reported in other countries: whichever HI threshold was considered, the highest prevalence levels and HI titres were identified in ( i ) individuals under 20 yo, reflecting the fact that this age group was the primary target of the pandemic virus [7], [8], [12], [17]–[19], [30]–[38], and ( ii ) the elderly. Elderly individuals were paradoxically poorly impacted by the first wave, most probably because of pre-existing cross-reactive antibodies.…”

“…They may have been infected with Spanish flu-related A(H1N1) strains prior to the major antigenic drift of A(H1N1) viruses that occurred at the end of the 1940s [39]. These antibodies had been detected in individuals over 60 yo in most previous sero-epidemiological studies [7], [8], [17], [30], [32], [38], [40]–[52], with the exception of three studies in China [53], Taiwan [19], and Singapore [54], where none of the participants over 60 yo was seropositive for pandemic 2009 A(H1N1) antibodies.…”

Molecular Evolutionary Analysis of pH1N1 2009 Influenza Virus in Reunion Island, South West Indian Ocean Region: A Cohort Study

“…A similar conclusion was also drawn from Australian sequences [44]. A study reported from Taiwan [45] showed evidence of pre-epidemic subclinical community transmission as proved by seroconversion occurring several weeks before report of the first documented case in the island.…”

Transmissibility and temporal changes of 2009 pH1N1 pandemic during summer and fall/winter waves

“…It was also lower than that of the winter outbreak in the Southern Hemisphere around the same time [19,32,33], perhaps attributable to the fact that it was the winter influenza season in the Southern Hemisphere. Moreover, It is lower than the final size estimate of R 0 (1.87; 95% CI: 1.68-2.06) obtained from serological study of a cohort household population in central Taiwan during the same period of time [1]. However, we note that this disparity is reasonable since the serologic data used for this estimate accounts for the asymptomatic cases among the cohort group.…”

“…Serological evidence has indicated that approximately one in every ten persons was infected with the 2009 pH1N1 virus in central Taiwan by April-June [1,27]; hence the estimates using data after July does not yield, and can reasonably be expected to be lower than, the more commonly known basic reproduction number R 0 .…”