Simulation-guided design of serological surveys of the cumulative incidence of influenza infection

BMC Infectious Diseases

Steven Riley¹  Kendra M Wu² 

[1] Medical Research Council Centre for Outbreak Analysis and Modelling, Department of Infectious Disease Epidemiology, School of Public Health, Imperial College London, London, UK;School of Public Health, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China

关键词: Mathmatical modelling;    Longitudinal study design;    Cross-sectional study design;    Serological survey;    Influenza;    Seroprevalence;    Cumulative incidence;    Infection attack rate;   

Others  :  1125546
DOI  :  10.1186/1471-2334-14-505

 received in 2014-02-10, accepted in 2014-09-02,  发布年份 2014

【 摘 要 】

Background

Influenza infection does not always cause clinical illnesses, so serological surveillance has been used to determine the true burden of influenza outbreaks. This study investigates the accuracy of measuring cumulative incidence of influenza infection using different serological survey designs.

Methods

We used a simple transmission model to simulate a typical influenza epidemic and obtained the seroprevalence over time. We also constructed four illustrative scenarios for baseline levels of antibodies prior and levels of boosting following infection in the simulated studies. Although illustrative, three of the four scenarios were based on the most detailed empirical data available. We used standard analytical methods to calculate estimated seroprevalence and associated confidence intervals for each of the four scenarios for both cross-sectional and longitudinal study designs. We tested the sensitivity of our results to changes in the sampled size and in our ability to detect small changes in antibody levels.

Results

There were substantial differences between the background antibody titres and levels of boosting within three of our illustrative scenarios which were based on empirical data. These differences propagated through to different and substantial patterns of bias for all scenarios other than those with very low background titre and high levels of boosting. The two survey designs result in similar seroprevalence estimates in general under these scenarios, but when background immunity was high, simulated cross-sectional studies had higher biases. Sensitivity analyses indicated that an ability to accurately detect low levels of antibody boosting within paired sera would substantially improve the performance of serological surveys, even under difficult conditions.

Conclusions

Levels of boosting and background immunity significantly affect the accuracy of seroprevalence estimations, and depending on these levels of immunity responses, different survey designs should be used to estimate seroprevalences. These results suggest that under current measurement criteria, cumulative incidence measured by serological surveys might have been substantially underestimated by failing to include all infections, including mild and asymptomatic infections, in certain scenarios. Dilution protocols more highly resolved than serial 2-fold dilution should be considered for serological surveys.

【 授权许可】

   
2014 Wu and Riley; licensee BioMed Central Ltd.

【 图 表 】

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