Household Transmission of the 2009 Pandemic A/H1N1 Influenza Virus: Elevated Laboratory‐Confirmed Secondary Attack Rates and Evidence of Asymptomatic Infections

Papenburg, Jesse; Baz, Mariana; Hamelin, Marie‐Ève; Rhéaume, Chantal; Carbonneau, Julie; Ouakki, Manale; Rouleau, Isabelle; Hardy, Isabelle; Skowronski, Danuta M.; Roger, Michel; Charest, Hugues; Serres, Gaston De; Boivin, Guy

doi:10.1086/656582

Cited by 105 publications

(118 citation statements)

References 36 publications

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“…Our estimates of the effectiveness of trivalent influenza vaccine for sH1N1 and sH3N2 were consistent with findings reported elsewhere [18]. We estimated that almost all secondary infections (97%) were acquired from the household, and this findings was also consistent with other studies (see Supplementary Appendix) [37][38][39]. In particular, our analysis of the homology in virus sequences between infections in index case patients and household contacts confirmed that almost all infections in household contacts were acquired within the household [39].…”

Section: Discussionsupporting

confidence: 92%

Influenza A Virus Shedding and Infectivity in Households

Tsang¹,

Cowling²,

Fang³

et al. 2015

J Infect Dis.

103

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Background. Viral shedding is often considered to correlate with the infectivity of influenza, but the evidence for this is limited.Methods. In a detailed study of influenza virus transmission within households in 2008-2012, index case patients with confirmed influenza were identified in outpatient clinics, and we collected nose and throat swab specimens for testing by reverse-transcription polymerase chain reaction from all household members regardless of illness. We used individual-based hazard models to characterize the relationship between viral load (V ) and infectivity.Results. Assuming that infectivity was proportional to viral load V gave the worst fit, because it strongly overestimated the proportion of transmission occurring at symptom onset. Alternative models assuming that infectivity was proportional to a various functions of V provided better fits, although they all overestimated the proportion of transmission occurring >3 days after symptom onset. The best fitting model assumed that infectivity was proportion to V γ , with estimates of γ = 0.136 and γ = 0.156 for seasonal influenza A(H1N1) and A(H3N2) respectively.Conclusions. All the models we considered that used viral loads to approximate infectivity of a case imperfectly explained the timing of influenza secondary infections in households. Identification of more accurate correlates of infectivity will be important to inform control policies and disease modeling.

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Section: Discussionsupporting

confidence: 92%

Influenza A Virus Shedding and Infectivity in Households

Tsang¹,

Cowling²,

Fang³

et al. 2015

J Infect Dis.

103

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“…This may be because our study includes a number of additional middle and low countries who conducted serologic studies because this analysis was published and because we excluded studies which focused on specialized populations17). Additionally, the age‐specific trends we found in our cumulative incidence results are consistent with studies which measured cumulative incidence as a fourfold increase in titers among paired sera36, 42, 57 and similar to studies which measured age‐specific secondary attack rates using RT‐PCR 58, 59…”

Section: Discussionsupporting

confidence: 90%

Estimating age‐specific cumulative incidence for the 2009 influenza pandemic: a meta‐analysis of A(H1N1)pdm09 serological studies from 19 countries

Kerkhove¹,

Hirve

Koukounari

et al. 2013

Influenza Resp Viruses

164

139

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BackgroundThe global impact of the 2009 influenza A(H1N1) pandemic (H1N1pdm) is not well understood.ObjectivesWe estimate overall and age‐specific prevalence of cross‐reactive antibodies to H1N1pdm virus and rates of H1N1pdm infection during the first year of the pandemic using data from published and unpublished H1N1pdm seroepidemiological studies.MethodsPrimary aggregate H1N1pdm serologic data from each study were stratified in standardized age groups and evaluated based on when sera were collected in relation to national or subnational peak H1N1pdm activity. Seropositivity was assessed using well‐described and standardized hemagglutination inhibition (HI titers ≥32 or ≥40) and microneutralization (MN ≥ 40) laboratory assays. The prevalence of cross‐reactive antibodies to the H1N1pdm virus was estimated for studies using sera collected prior to the start of the pandemic (between 2004 and April 2009); H1N1pdm cumulative incidence was estimated for studies in which collected both pre‐ and post‐pandemic sera; and H1N1pdm seropositivity was calculated from studies with post‐pandemic sera only (collected between December 2009–June 2010).ResultsData from 27 published/unpublished studies from 19 countries/administrative regions – Australia, Canada, China, Finland, France, Germany, Hong Kong SAR, India, Iran, Italy, Japan, Netherlands, New Zealand, Norway, Reunion Island, Singapore, United Kingdom, United States, and Vietnam – were eligible for inclusion. The overall age‐standardized pre‐pandemic prevalence of cross‐reactive antibodies was 5% (95%CI 3–7%) and varied significantly by age with the highest rates among persons ≥65 years old (14% 95%CI 8–24%). Overall age‐standardized H1N1pdm cumulative incidence was 24% (95%CI 20–27%) and varied significantly by age with the highest in children 5–19 (47% 95%CI 39–55%) and 0–4 years old (36% 95%CI 30–43%).ConclusionsOur results offer unique insight into the global impact of the H1N1 pandemic and highlight the need for standardization of seroepidemiological studies and for their inclusion in pre‐pandemic preparedness plans. Our results taken together with recent global pandemic respiratory‐associated mortality estimates suggest that the case fatality ratio of the pandemic virus was approximately 0·02%.

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“…All subjects had detectable memory B cells reactive against pH1N1 2009 HA before vaccination (median 0.4%, range 0.01-1.98%). However, subclinical infections with influenza that induce seroconversion without symptoms do occur and go unreported (13). It was therefore possible that some of the vaccinees had been exposed to pH1N1 2009 virus between its emergence (March 2009) and their vaccination (October 2009).…”

Section: Pandemic H1n1 2009 Vaccine Induces Monoclonal Antibodies Withmentioning

confidence: 99%

Pandemic H1N1 influenza vaccine induces a recall response in humans that favors broadly cross-reactive memory B cells

Chiu

Wrammert

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

371

431

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We have previously shown that broadly neutralizing antibodies reactive to the conserved stem region of the influenza virus hemagglutinin (HA) were generated in people infected with the 2009 pandemic H1N1 strain. Such antibodies are rarely seen in humans following infection or vaccination with seasonal influenza virus strains. However, the important question remained whether the inactivated 2009 pandemic H1N1 vaccine, like the infection, could also induce these broadly neutralizing antibodies. To address this question, we analyzed B-cell responses in 24 healthy adults immunized with the pandemic vaccine in 2009. In all cases, we found a rapid, predominantly IgGproducing vaccine-specific plasmablast response. Strikingly, the majority (25 of 28) of HA-specific monoclonal antibodies generated from the vaccine-specific plasmablasts neutralized more than one influenza strain and exhibited high levels of somatic hypermutation, suggesting they were derived from recall of B-cell memory. Indeed, memory B cells that recognized the 2009 pandemic H1N1 HA were detectable before vaccination not only in this cohort but also in samples obtained before the emergence of the pandemic strain. Three antibodies demonstrated extremely broad cross-reactivity and were found to bind the HA stem. Furthermore, one stem-reactive antibody recognized not only H1 and H5, but also H3 influenza viruses. This exceptional cross-reactivity indicates that antibodies capable of neutralizing most influenza subtypes might indeed be elicited by vaccination. The challenge now is to improve upon this result and design influenza vaccines that can elicit these broadly cross-reactive antibodies at sufficiently high levels to provide heterosubtypic protection.

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Household Transmission of the 2009 Pandemic A/H1N1 Influenza Virus: Elevated Laboratory‐Confirmed Secondary Attack Rates and Evidence of Asymptomatic Infections

Abstract: Household transmission of pH1N1 may be substantially greater than previously estimated, especially in association with clinical presentations that include gastrointestinal complaints. Approximately 10% of pH1N1 infections acquired in the household may be asymptomatic.

Cited by 105 publications

References 36 publications

Influenza A Virus Shedding and Infectivity in Households

Influenza A Virus Shedding and Infectivity in Households

Estimating age‐specific cumulative incidence for the 2009 influenza pandemic: a meta‐analysis of A(H1N1)pdm09 serological studies from 19 countries

Pandemic H1N1 influenza vaccine induces a recall response in humans that favors broadly cross-reactive memory B cells

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