Influenza A Virus Shedding and Infectivity in Households

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.

Keywords: infectiousness; influenza; isolation; public health.

Figure 1.

Viral shedding patterns from observed data and predicted from the fitted random effects log-linear censored regression model. A, B, Observed and predicted viral shedding pattern for children with polymerase chain reaction (PCR)–confirmed seasonal influenza A(H1N1) virus infection. C, D, Observed and predicted viral shedding pattern for adults with PCR-confirmed seasonal influenza A(H1N1) virus infection. E, F, Observed and predicted viral shedding pattern for children with PCR-confirmed seasonal influenza A(H3N2) virus infection. G, H, Observed and predicted viral shedding pattern for adults with PCR-confirmed seasonal influenza A(H3N2) virus infection.

Figure 2.

The estimated infectivity profile since symptom onset from the Epi-only and the viral shedding model for seasonal influenza A(H1N1) virus (A) and seasonal influenza A(H3N2) virus (B). It showed proportion of infectivity in an illness episode. In the viral shedding model, infectivity was assumed to be proportional to viral load V^γ (model A, γ estimated; model B, γ = 1) or to logarithm of viral loads (log V)^γ (model C, γ estimated; model D, γ = 1).

Figure 3.

Estimated distribution of time of infection in secondary case patients from the Epi-only and viral shedding models for seasonal influenza A(H1N1) virus (A) and seasonal influenza A(H3N2) virus (B). Circles represent the observed proportion of infections that occurred since symptom onset in index case patients; triangles and diamonds, the estimated proportions of secondary infections that occurred since symptom onset in index case patients from the Epi-only and viral shedding model, respectively; vertical lines, 95% credible intervals for the estimated proportions of infectivity. The observed infection times were estimated under the assumption that the incubation period was 1 day.