Abstract
BackgroundInfluenza cohort studies, in which participants are monitored for infection over an epidemic period, are invaluable in assessing the effectiveness of control measures such as vaccination, antiviral prophylaxis and non-pharmaceutical interventions (NPIs). Influenza infections and illnesses can be identified through a number of approaches with different costs and logistical requirements.Methodology and Principal FindingsIn the context of a randomized controlled trial of an NPI with a constrained budget, we used a simulation approach to examine which approaches to measuring outcomes could provide greater statistical power to identify an effective intervention against confirmed influenza. We found that for a short epidemic season, the optimal design was to collect respiratory specimens at biweekly intervals, as well as following report of acute respiratory illness (ARI), for virologic testing by reverse transcription polymerase chain reaction (RT-PCR). Collection of respiratory specimens only from individuals reporting ARI was also an efficient design particularly for studies in settings with longer periods of influenza activity. Collection of specimens only from individuals reporting a febrile ARI was less efficient. Collection and testing of sera before and after influenza activity appeared to be inferior to collection of respiratory specimens for RT-PCR confirmation of acute infections. The performance of RT-PCR was robust to uncertainty in the costs and diagnostic performance of RT-PCR and serological tests.Conclusions and SignificanceOur results suggest that unless the sensitivity or specificity of serology can be increased RT-PCR will remain as the preferable outcome measure in NPI studies. Routine collection of specimens for RT-PCR testing even when study participants do not report acute respiratory illness appears to be the most cost efficient design under most scenarios.
Highlights
Influenza is a major cause of mortality and morbidity worldwide [1]
Our results suggest that unless the sensitivity or specificity of serology can be increased RTPCR will remain as the preferable outcome measure in nonpharmaceutical interventions (NPIs) studies
In Scenario I in which expected rates of acute respiratory illness (ARI) and febrile ARI (FARI) noise matched actual rates, biweekly reverse transcription polymerase chain reaction (RT-PCR) plus ARI trigger followed by RT-PCR upon ARI trigger were the most powerful study designs
Summary
Influenza is a major cause of mortality and morbidity worldwide [1]. Field studies of influenza have been invaluable for understanding influenza epidemiology [2,3]. Because acute upper respiratory tract infections (URTIs) associated with different pathogens can have similar clinical presentation, the sensitivity and specificity of syndromic classifications of influenza infection, or proxy measures such as absenteeism, tend to be poor when compared to laboratory-based outcomes [26]. Respiratory specimens, such as nasal swabs or aspirates, can be collected from patients with acute URTI for virologic testing. Influenza infections and illnesses can be identified through a number of approaches with different costs and logistical requirements
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