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Transmission of novel influenza A(H1N1) in households with post-exposure antiviral prophylaxis.

ABSTRACT: BACKGROUND:Despite impressive advances in our understanding of the biology of novel influenza A(H1N1) virus, little is as yet known about its transmission efficiency in close contact places such as households, schools, and workplaces. These are widely believed to be key in supporting propagating spread, and it is therefore of importance to assess the transmission levels of the virus in such settings. METHODOLOGY/PRINCIPAL FINDINGS:We estimate the transmissibility of novel influenza A(H1N1) in 47 households in the Netherlands using stochastic epidemic models. All households contained a laboratory confirmed index case, and antiviral drugs (oseltamivir) were given to both the index case and other households members within 24 hours after detection of the index case. Among the 109 household contacts there were 9 secondary infections in 7 households. The overall estimated secondary attack rate is low (0.075, 95%CI: 0.037-0.13). There is statistical evidence indicating that older persons are less susceptible to infection than younger persons (relative susceptibility of older persons: 0.11, 95%CI: 0.024-0.43. Notably, the secondary attack rate from an older to a younger person is 0.35 (95%CI: 0.14-0.61) when using an age classification of 12 years, and 0.28 (95%CI: 0.12-0.50) when using an age classification of 18 years. CONCLUSIONS/SIGNIFICANCE:Our results indicate that the overall household transmission levels of novel influenza A(H1N1) in antiviral-treated households were low in the early stage of the epidemic. The relatively high rate of adult-to-child transmission indicates that control measures focused on this transmission route will be most effective in minimizing the total number of infections.

SUBMITTER: van Boven M

PROVIDER: S-EPMC2898802 | biostudies-literature | 2010 Jul

REPOSITORIES: biostudies-literature

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Transmission of novel influenza A(H1N1) in households with post-exposure antiviral prophylaxis.

van Boven Michiel M Donker Tjibbe T van der Lubben Mariken M van Gageldonk-Lafeber Rianne B RB te Beest Dennis E DE Koopmans Marion M Meijer Adam A Timen Aura A Swaan Corien C Dalhuijsen Anton A Hahné Susan S van den Hoek Anneke A Teunis Peter P van der Sande Marianne A B MA Wallinga Jacco J

PloS one 20100707 7

<h4>Background</h4>Despite impressive advances in our understanding of the biology of novel influenza A(H1N1) virus, little is as yet known about its transmission efficiency in close contact places such as households, schools, and workplaces. These are widely believed to be key in supporting propagating spread, and it is therefore of importance to assess the transmission levels of the virus in such settings.<h4>Methodology/principal findings</h4>We estimate the transmissibility of novel influenz ...[more]

PMID: 20628642

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Project description:With the rise of the second pandemic wave of the novel influenza A (H1N1) virus in the current season in the Northern Hemisphere, pandemic plans are being carefully re-evaluated, particularly for the strategic use of antiviral drugs. The recent emergence of oseltamivir-resistant in treated H1N1 patients has raised concerns about the prudent use of neuraminidase inhibitors for both treatment of ill individuals and post-exposure prophylaxis of close contacts.We extended an established population dynamical model of pandemic influenza with treatment to include post-exposure prophylaxis of close contacts. Using parameter estimates published in the literature, we simulated the model to evaluate the combined effect of treatment and prophylaxis in minimizing morbidity and mortality of pandemic infections in the context of transmissible drug resistance.We demonstrated that, when transmissible resistant strains are present, post-exposure prophylaxis can promote the spread of resistance, especially when combined with aggressive treatment. For a given treatment level, there is an optimal coverage of prophylaxis that minimizes the total number of infections (final size) and this coverage decreases as a higher proportion of infected individuals are treated. We found that, when treatment is maintained at intermediate levels, limited post-exposure prophylaxis provides an optimal strategy for reducing the final size of the pandemic while minimizing the total number of deaths. We tested our results by performing a sensitivity analysis over a range of key model parameters and observed that the incidence of infection depends strongly on the transmission fitness of resistant strains.Our findings suggest that, in the presence of transmissible drug resistance, strategies that prioritize the treatment of only ill individuals, rather than the prophylaxis of those suspected of being exposed, are most effective in reducing the morbidity and mortality of the pandemic. The impact of post-exposure prophylaxis depends critically on the treatment level and the transmissibility of resistant strains and, therefore, enhanced surveillance and clinical monitoring for resistant mutants constitutes a key component of any comprehensive plan for antiviral drug use during an influenza pandemic.

Project description:BackgroundAntiviral post-exposure prophylaxis with neuraminidase inhibitors can reduce the incidence of influenza and the risk of symptomatic influenza, but the efficacy of the other classes of antiviral remains unclear. To support an update of WHO influenza guidelines, this systematic review and network meta-analysis evaluated antiviral drugs for post-exposure prophylaxis of influenza.MethodsWe systematically searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Cumulative Index to Nursing and Allied Health Literature, Global Health, Epistemonikos, and ClinicalTrials.gov for randomised controlled trials published up to Sept 20, 2023 that evaluated the efficacy and safety of antivirals compared with another antiviral or placebo or standard care for prevention of influenza. Pairs of reviewers independently screened studies, extracted data, and assessed the risk of bias. We performed network meta-analyses with frequentist random effects model and assessed the certainty of evidence using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. The outcomes of interest were symptomatic or asymptomatic infection, admission to hospital, all-cause mortality, adverse events related to antivirals, and serious adverse events. This study is registered with PROSPERO, CRD42023466450.FindingsOf 11 845 records identified by our search, 33 trials of six antivirals (zanamivir, oseltamivir, laninamivir, baloxavir, amantadine, and rimantadine) that enrolled 19 096 individuals (mean age 6·75-81·15 years) were included in this systematic review and network meta-analysis. Most of the studies were rated as having a low risk of bias. Zanamivir, oseltamivir, laninamivir, and baloxavir probably achieve important reductions in symptomatic influenza in individuals at high risk of severe disease (zanamivir: risk ratio 0·35, 95% CI 0·25-0·50; oseltamivir: 0·40, 0·26-0·62; laninamivir: 0·43, 0·30-0·63; baloxavir: 0·43, 0·23-0·79; moderate certainty) when given promptly (eg, within 48 h) after exposure to seasonal influenza. These antivirals probably do not achieve important reductions in symptomatic influenza in individuals at low risk of severe disease when given promptly after exposure to seasonal influenza (moderate certainty). Zanamivir, oseltamivir, laninamivir, and baloxavir might achieve important reductions in symptomatic zoonotic influenza in individuals exposed to novel influenza A viruses associated with severe disease in infected humans when given promptly after exposure (low certainty). Oseltamivir, laninamivir, baloxavir, and amantadine probably decrease the risk of all influenza (symptomatic and asymptomatic infection; moderate certainty). Zanamivir, oseltamivir, laninamivir, and baloxavir probably have little or no effect on prevention of asymptomatic influenza virus infection or all-cause mortality (high or moderate certainty). Oseltamivir probably has little or no effect on admission to hospital (moderate certainty). All six antivirals do not significantly increase the incidence of drug-related adverse events or serious adverse events, although the certainty of evidence varies.InterpretationPost-exposure prophylaxis with zanamivir, oseltamivir, laninamivir, or baloxavir probably decreases the risk of symptomatic seasonal influenza in individuals at high risk for severe disease after exposure to seasonal influenza viruses. Post-exposure prophylaxis with zanamivir, oseltamivir, laninamivir, or baloxavir might reduce the risk of symptomatic zoonotic influenza after exposure to novel influenza A viruses associated with severe disease in infected humans.FundingWorld Health Organization.

Project description:BackgroundWhen an outbreak of a novel pathogen occurs, some of the most pressing questions from a public-health point of view relate to its transmissibility, and the probabilities of different clinical outcomes following infection, to allow an informed response. Estimates of these quantities are often based on household data due to the high potential for transmission in this setting, but typically a rich spectrum of individual-level outcomes (from uninfected to serious illness) are simplified to binary data (infected or not). We address the added benefit from retaining the heterogeneous outcome information in the case of the 2009-10 influenza pandemic, which posed particular problems for estimation of key epidemiological characteristics due to its relatively mild nature and hence low case ascertainment rates.MethodsWe use mathematical models of within-household transmission and case ascertainment, together with Bayesian statistics to estimate transmission probabilities stratified by household size, the variability of infectiousness of cases, and a set of probabilities describing case ascertainment. This novel approach was applied to data we collected from the early "containment phase" stage of the epidemic in Birmingham, England. We also conducted a comprehensive review of studies of household transmission of influenza A(H1N1)pdm09.ResultsWe find large variability in the published estimates of within-household transmissibility of influenza A(H1N1)pdm09 in both model-based studies and those reporting secondary attack rates, finding that these estimates are very sensitive to how an infected case is defined. In particular, we find that reliance on laboratory confirmation alone underestimates the true number of cases, while utilising the heterogeneous range of outcomes (based on case definitions) for household infections allows a far more comprehensive pattern of transmission to be elucidated.ConclusionsDifferences in household sizes and how cases are defined could account for an appreciable proportion of the reported variability of within-household transmissibility of influenza A(H1N1)pdm09. Retaining and statistically analysing the full spectrum of individual-level outcomes (based on case definitions) rather than taking a potentially arbitrary threshold for infection, provides much-needed additional information. In a future pandemic, our approach could be used as a real-time analysis tool to infer the true number of cases, within-household transmission rates and levels of case ascertainment.

Dataset Information

Transmission of novel influenza A(H1N1) in households with post-exposure antiviral prophylaxis.

Publications

Transmission of novel influenza A(H1N1) in households with post-exposure antiviral prophylaxis.

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