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Linking time-varying symptomatology and intensity of infectiousness to patterns of norovirus transmission.

Zelner JL, Lopman BA, Hall AJ, Ballesteros S, Grenfell BT - PLoS ONE (2013)

Bottom Line: Model 2 assumes infectiousness decays exponentially as a function of time since onset, while Model 3 is discontinuous, with a spike concentrating 50% of transmissibility at onset.We also show that these results are robust to the presence of asymptomatic infections.Explicitly representing explosive NoV infectiousness at onset should be considered when developing models and interventions to interrupt and prevent outbreaks of norovirus in the community.

View Article: PubMed Central - PubMed

Affiliation: Department of Ecology and Evolutionary Biology, Princeton University, Princeton, New Jersey, United States of America. jzelner@princeton.edu

ABSTRACT

Background: Norovirus (NoV) transmission may be impacted by changes in symptom intensity. Sudden onset of vomiting, which may cause an initial period of hyper-infectiousness, often marks the beginning of symptoms. This is often followed by: a 1-3 day period of milder symptoms, environmental contamination following vomiting, and post-symptomatic shedding that may result in transmission at progressively lower rates. Existing models have not included time-varying infectiousness, though representing these features could add utility to models of NoV transmission.

Methods: We address this by comparing the fit of three models (Models 1-3) of NoV infection to household transmission data from a 2009 point-source outbreak of GII.12 norovirus in North Carolina. Model 1 is an SEIR compartmental model, modified to allow Gamma-distributed sojourn times in the latent and infectious classes, where symptomatic cases are uniformly infectious over time. Model 2 assumes infectiousness decays exponentially as a function of time since onset, while Model 3 is discontinuous, with a spike concentrating 50% of transmissibility at onset. We use Bayesian data augmentation techniques to estimate transmission parameters for each model, and compare their goodness of fit using qualitative and quantitative model comparison. We also assess the robustness of our findings to asymptomatic infections.

Results: We find that Model 3 (initial spike in shedding) best explains the household transmission data, using both quantitative and qualitative model comparisons. We also show that these results are robust to the presence of asymptomatic infections.

Conclusions: Explicitly representing explosive NoV infectiousness at onset should be considered when developing models and interventions to interrupt and prevent outbreaks of norovirus in the community. The methods presented here are generally applicable to the transmission of pathogens that exhibit large variation in transmissibility over an infection.

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Fitted infectivity profiles for Models 2 & 3.The figure shows infectiousness as a function of time since symptom onset for the estimated values of the exponential decay model (Model 2; solid line) and burst model (Model 3; dashed line).
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pone-0068413-g003: Fitted infectivity profiles for Models 2 & 3.The figure shows infectiousness as a function of time since symptom onset for the estimated values of the exponential decay model (Model 2; solid line) and burst model (Model 3; dashed line).

Mentions: Across all three models, estimates of the probability of infection at the point source are similar, with a 55% probability of infection for non-index cases exposed to the point source ( =  0.55, 95% CI  = 0.38, 0.71. Estimates of a secondary attack rate of approximately 15% are also consistent across models. To test the validity of the assumption in Model 3 that  =  0.5, i.e. that 50% of infectiousness occurs during the burst at onset and 50% occurs afterwards, we re-fit Model 3 while allowing to vary. We found that the estimated value was close to the assumed value ( =  0.46, 95% CI: 0.19, 0.75), while other parameter estimates listed in Table 2 were unchanged. Sensitivity analysis using Bayes factors was also performed in which the duration of the burst at onset was varied from 12 to 24 hours, and both burst durations were supported equally by the data with no impact on estimated parameter values. Figure 3 illustrates the fitted infectivity profiles for Models 2 and 3.


Linking time-varying symptomatology and intensity of infectiousness to patterns of norovirus transmission.

Zelner JL, Lopman BA, Hall AJ, Ballesteros S, Grenfell BT - PLoS ONE (2013)

Fitted infectivity profiles for Models 2 & 3.The figure shows infectiousness as a function of time since symptom onset for the estimated values of the exponential decay model (Model 2; solid line) and burst model (Model 3; dashed line).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3722229&req=5

pone-0068413-g003: Fitted infectivity profiles for Models 2 & 3.The figure shows infectiousness as a function of time since symptom onset for the estimated values of the exponential decay model (Model 2; solid line) and burst model (Model 3; dashed line).
Mentions: Across all three models, estimates of the probability of infection at the point source are similar, with a 55% probability of infection for non-index cases exposed to the point source ( =  0.55, 95% CI  = 0.38, 0.71. Estimates of a secondary attack rate of approximately 15% are also consistent across models. To test the validity of the assumption in Model 3 that  =  0.5, i.e. that 50% of infectiousness occurs during the burst at onset and 50% occurs afterwards, we re-fit Model 3 while allowing to vary. We found that the estimated value was close to the assumed value ( =  0.46, 95% CI: 0.19, 0.75), while other parameter estimates listed in Table 2 were unchanged. Sensitivity analysis using Bayes factors was also performed in which the duration of the burst at onset was varied from 12 to 24 hours, and both burst durations were supported equally by the data with no impact on estimated parameter values. Figure 3 illustrates the fitted infectivity profiles for Models 2 and 3.

Bottom Line: Model 2 assumes infectiousness decays exponentially as a function of time since onset, while Model 3 is discontinuous, with a spike concentrating 50% of transmissibility at onset.We also show that these results are robust to the presence of asymptomatic infections.Explicitly representing explosive NoV infectiousness at onset should be considered when developing models and interventions to interrupt and prevent outbreaks of norovirus in the community.

View Article: PubMed Central - PubMed

Affiliation: Department of Ecology and Evolutionary Biology, Princeton University, Princeton, New Jersey, United States of America. jzelner@princeton.edu

ABSTRACT

Background: Norovirus (NoV) transmission may be impacted by changes in symptom intensity. Sudden onset of vomiting, which may cause an initial period of hyper-infectiousness, often marks the beginning of symptoms. This is often followed by: a 1-3 day period of milder symptoms, environmental contamination following vomiting, and post-symptomatic shedding that may result in transmission at progressively lower rates. Existing models have not included time-varying infectiousness, though representing these features could add utility to models of NoV transmission.

Methods: We address this by comparing the fit of three models (Models 1-3) of NoV infection to household transmission data from a 2009 point-source outbreak of GII.12 norovirus in North Carolina. Model 1 is an SEIR compartmental model, modified to allow Gamma-distributed sojourn times in the latent and infectious classes, where symptomatic cases are uniformly infectious over time. Model 2 assumes infectiousness decays exponentially as a function of time since onset, while Model 3 is discontinuous, with a spike concentrating 50% of transmissibility at onset. We use Bayesian data augmentation techniques to estimate transmission parameters for each model, and compare their goodness of fit using qualitative and quantitative model comparison. We also assess the robustness of our findings to asymptomatic infections.

Results: We find that Model 3 (initial spike in shedding) best explains the household transmission data, using both quantitative and qualitative model comparisons. We also show that these results are robust to the presence of asymptomatic infections.

Conclusions: Explicitly representing explosive NoV infectiousness at onset should be considered when developing models and interventions to interrupt and prevent outbreaks of norovirus in the community. The methods presented here are generally applicable to the transmission of pathogens that exhibit large variation in transmissibility over an infection.

Show MeSH
Related in: MedlinePlus