Tim K Tsang1, Benjamin J Cowling1, Vicky J Fang1, Kwok-Hung Chan2, Dennis K M Ip1, Gabriel M Leung1, J S Malik Peiris3, Simon Cauchemez4. 1. WHO Collaborating Centre for Infectious Disease Epidemiology and Control, School of Public Health. 2. Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China. 3. WHO Collaborating Centre for Infectious Disease Epidemiology and Control, School of Public Health Centre of Influenza Research, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China. 4. Mathematical Modelling of Infectious Diseases Unit, Institut Pasteur, Paris.
Abstract
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.
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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