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Diagnosis and antiviral intervention strategies for mitigating an influenza epidemic.

ABSTRACT: BACKGROUND:Many countries have amassed antiviral stockpiles for pandemic preparedness. Despite extensive trial data and modelling studies, it remains unclear how to make optimal use of antiviral stockpiles within the constraints of healthcare infrastructure. Modelling studies informed recommendations for liberal antiviral distribution in the pandemic phase, primarily to prevent infection, but failed to account for logistical constraints clearly evident during the 2009 H1N1 outbreaks. Here we identify optimal delivery strategies for antiviral interventions accounting for logistical constraints, and so determine how to improve a strategy's impact. METHODS AND FINDINGS:We extend an existing SEIR model to incorporate finite diagnostic and antiviral distribution capacities. We evaluate the impact of using different diagnostic strategies to decide to whom antivirals are delivered. We then determine what additional capacity is required to achieve optimal impact. We identify the importance of sensitive and specific case ascertainment in the early phase of a pandemic response, when the proportion of false-positive presentations may be high. Once a substantial percentage of ILI presentations are caused by the pandemic strain, identification of cases for treatment on syndromic grounds alone results in a greater potential impact than a laboratory-dependent strategy. Our findings reinforce the need for a decentralised system capable of providing timely prophylaxis. CONCLUSIONS:We address specific real-world issues that must be considered in order to improve pandemic preparedness policy in a practical and methodologically sound way. Provision of antivirals on the scale proposed for an effective response is infeasible using traditional public health outbreak management and contact tracing approaches. The results indicate to change the transmission dynamics of an influenza epidemic with an antiviral intervention, a decentralised system is required for contact identification and prophylaxis delivery, utilising a range of existing services and infrastructure in a "whole of society" response.

SUBMITTER: Moss R

PROVIDER: S-EPMC3033893 | biostudies-literature | 2011 Feb

REPOSITORIES: biostudies-literature

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Diagnosis and antiviral intervention strategies for mitigating an influenza epidemic.

Moss Robert R McCaw James M JM McVernon Jodie J

PloS one 20110204 2

<h4>Background</h4>Many countries have amassed antiviral stockpiles for pandemic preparedness. Despite extensive trial data and modelling studies, it remains unclear how to make optimal use of antiviral stockpiles within the constraints of healthcare infrastructure. Modelling studies informed recommendations for liberal antiviral distribution in the pandemic phase, primarily to prevent infection, but failed to account for logistical constraints clearly evident during the 2009 H1N1 outbreaks. Her ...[more]

PMID: 21346794

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Project description:BackgroundNeuraminidase inhibitors were used to reduce the transmission of pandemic influenza A/H1N1 2009 at the early stages of the 2009/2010 pandemic. Policies for diagnosis of influenza for the purposes of antiviral intervention differed markedly between and within countries, leading to differences in the timing and scale of antiviral usage.Methodology/principal findingsThe impact of the percentage of symptomatic infected individuals who were diagnosed, and of delays to diagnosis, for three antiviral intervention strategies (each with and without school closure) were determined using a simulation model of an Australian community. Epidemic characteristics were based on actual data from the A/H1N1 2009 pandemic including reproduction number, serial interval and age-specific infection rate profile. In the absence of intervention an illness attack rate (AR) of 24.5% was determined from an estimated R(0) of 1.5; this was reduced to 21%, 16.5% or 13% by treatment-only, treatment plus household prophylaxis, or treatment plus household plus extended prophylaxis antiviral interventions respectively, assuming that diagnosis occurred 24 hours after symptoms arose and that 50% of symptomatic cases were diagnosed. If diagnosis occurred without delay, ARs decreased to 17%, 12.2% or 8.8% respectively. If 90% of symptomatic cases were diagnosed (with a 24 hour delay), ARs decreased to 17.8%, 11.1% and 7.6%, respectively.ConclusionThe ability to rapidly diagnose symptomatic cases and to diagnose a high proportion of cases was shown to improve the effectiveness of all three antiviral strategies. For epidemics with R(0)< = 1.5 our results suggest that when the case diagnosis coverage exceeds ∼70% the size of the antiviral stockpile required to implement the extended prophylactic strategy decreases. The addition of at least four weeks of school closure was found to further reduce cumulative and peak attack rates and the size of the required antiviral stockpile.

Project description:BackgroundAs seen during past pandemic influenza outbreaks, pharmaceutical interventions (PHIs) with vaccines and antivirals are the most effective methods of mitigation. However, availability of PHIs is unlikely to be adequate during the early stages of a pandemic. Hence, for early mitigation and possible containment, non-pharmaceutical interventions (NPIs) offer a viable alternative. Also, NPIs may be the only available interventions for most underdeveloped countries. In this paper we present a comprehensive methodology for design of effective NPI strategies.MethodsWe develop a statistical ANOVA-based design approach that uses a detailed agent-based simulation as an underlying model. The design approach obtains the marginal effect of the characteristic parameters of NPIs, social behavior, and their interactions on various pandemic outcome measures including total number of contacts, infections, and deaths. We use the marginal effects to establish regression equations for the outcome measures, which are optimized to obtain NPI strategies. Efficacy of the NPI strategies designed using our methodology is demonstrated using simulated pandemic influenza outbreaks with different levels of virus transmissibility.ResultsOur methodology was able to design effective NPI strategies, which were able to contain outbreaks by reducing infection attack rates (IAR) to below 10% in low and medium virus transmissibility scenarios with 33% and 50% IAR, respectively. The level of reduction in the high transmissibility scenario (with 65% IAR) was also significant. As noted in the published literature, we also found school closure to be the single most effective intervention among all NPIs.ConclusionsIf harnessed effectively, NPIs offer a significant potential for mitigation of pandemic influenza outbreaks. The methodology presented here fills a gap in the literature, which, though replete with models on NPI strategy evaluation, lacks a treatise on optimal strategy design.

Project description:BackgroundAntivirals (eg, oseltamivir) are important for mitigating influenza epidemics. In 2007, an oseltamivir-resistant influenza seasonal A H1N1 strain emerged and spread to global fixation within 1 year. This event showed that antiviral-resistant (AVR) strains can be intrinsically more transmissible than their contemporaneous antiviral-sensitive (AVS) counterpart. Surveillance of AVR fitness is therefore essential. Our objective was to develop a simple method for estimating AVR fitness from surveillance data.MethodsWe defined the fitness of AVR strains as their reproductive number relative to their co-circulating AVS counterparts. We developed a simple method for real-time estimation of AVR fitness from surveillance data. This method requires only information on generation time without other specific details regarding transmission dynamics. We first used simulations to validate this method by showing that it yields unbiased and robust fitness estimates in most epidemic scenarios. We then applied this method to two retrospective case studies and one hypothetical case study.FindingsWe estimated that the oseltamivir-resistant A H1N1 strain that emerged in 2007 was 4% (95% credible interval [CrI] 3-5) more transmissible than its oseltamivir-sensitive predecessor and the oseltamivir-resistant pandemic A H1N1 strain that emerged and circulated in Japan during 2013-14 was 24% (95% CrI 17-30) less transmissible than its oseltamivir-sensitive counterpart. We show that in the event of large-scale antiviral interventions during a pandemic with co-circulation of AVS and AVR strains, our method can be used to inform optimal use of antivirals by monitoring intrinsic AVR fitness and drug pressure on the AVS strain.InterpretationWe developed a simple method that can be easily integrated into contemporary influenza surveillance systems to provide reliable estimates of AVR fitness in real time.FundingResearch Fund for the Control of Infectious Disease (09080792) and a commissioned grant from the Health and Medical Research Fund from the Government of the Hong Kong Special Administrative Region, Harvard Center for Communicable Disease Dynamics from the National Institute of General Medical Sciences (grant number U54 GM088558), Area of Excellence Scheme of the Hong Kong University Grants Committee (grant number AoE/M-12/06).

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Diagnosis and antiviral intervention strategies for mitigating an influenza epidemic.

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Diagnosis and antiviral intervention strategies for mitigating an influenza epidemic.

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