Inference of the generalized-growth model via maximum likelihood estimation: A reflection on the impact of overdispersion.

Recently, the generalized-growth model was introduced as a flexible approach to characterize growth dynamics of disease outbreaks during the early ascending phase. In this work, by using classical maximum likelihood estimation to obtain parameter estimates, we evaluate the impact of varying levels of overdispersion on the inference of the growth scaling parameter through comparing Poisson and Negative binomial models. In particular, under exponential and sub-exponential growth scenarios, we evaluate, via simulations, the error rate of making an incorrect characterization of early outbreak growth patterns. Simulation results show that the ability to correctly identify early outbreak growth patterns can be affected by overdispersion even when accounted for using the Negative binomial model. We exemplify our findings using data on five different outbreaks. Overall, our results show that estimates should be interpreted with caution when data are overdispersed.

Estimating the generation interval for coronavirus disease (COVID-19) based on symptom onset data, March 2020.

BackgroundEstimating key infectious disease parameters from the coronavirus disease (COVID-19) outbreak is essential for modelling studies and guiding intervention strategies.AimWe estimate the generation interval, serial interval, proportion of pre-symptomatic transmission and effective reproduction number of COVID-19. We illustrate that reproduction numbers calculated based on serial interval estimates can be biased.MethodsWe used outbreak data from clusters in Singapore and Tianjin, China to estimate the generation interval from symptom onset data while acknowledging uncertainty about the incubation period distribution and the underlying transmission network. From those estimates, we obtained the serial interval, proportions of pre-symptomatic transmission and reproduction numbers.ResultsThe mean generation interval was 5.20 days (95% credible interval (CrI): 3.78-6.78) for Singapore and 3.95 days (95% CrI: 3.01-4.91) for Tianjin. The proportion of pre-symptomatic transmission was 48% (95% CrI: 32-67) for Singapore and 62% (95% CrI: 50-76) for Tianjin. Reproduction number estimates based on the generation interval distribution were slightly higher than those based on the serial interval distribution. Sensitivity analyses showed that estimating these quantities from outbreak data requires detailed contact tracing information.ConclusionHigh estimates of the proportion of pre-symptomatic transmission imply that case finding and contact tracing need to be supplemented by physical distancing measures in order to control the COVID-19 outbreak. Notably, quarantine and other containment measures were already in place at the time of data collection, which may inflate the proportion of infections from pre-symptomatic individuals.

Assessing inference of the basic reproduction number in an SIR model incorporating a growth-scaling parameter.

The standard mass action, which assumes that infectious disease transmission occurs in well-mixed populations, is popular for formulating compartmental epidemic models. Compartmental epidemic models often follow standard mass action for simplicity and to gain insight into transmission dynamics as it often performs well at reproducing disease dynamics in large populations. In this work, we formulate discrete time stochastic susceptible-infected-removed models with linear (standard) and nonlinear mass action structures to mimic varying mixing levels. Using simulations and real epidemic data, we demonstrate the sensitivity of the basic reproduction number to these mathematical structures of the force of infection. Our results suggest the need to consider nonlinear mass action in order to generate more accurate estimates of the basic reproduction number although its uncertainty increases due to the addition of one growth scaling parameter.

Assessing the relationship between epidemic growth scaling and epidemic size: The 2014-16 Ebola epidemic in West Africa.

We assess the relationship between epidemic size and the scaling of epidemic growth of Ebola epidemics at the level of administrative areas during the 2014-16 Ebola epidemic in West Africa. For this purpose, we quantify growth scaling parameters from the ascending phase of Ebola outbreaks comprising at least 7 weeks of epidemic growth. We then study how these parameters are associated with observed epidemic sizes. For validation purposes, we also analyse two historic Ebola outbreaks. We find a high monotonic association between the scaling of epidemic growth parameter and the observed epidemic size. For example, scaling of growth parameters around 0.3-0.4, 0.4-0.6 and 0.6 are associated with epidemic sizes on the order of 350-460, 460-840 and 840-2500 cases, respectively. These results are not explained by differences in epidemic onset across affected areas. We also find the relationship between the scaling of epidemic growth parameter and the observed epidemic size to be consistent for two past Ebola outbreaks in Congo (1976) and Uganda (2000). Signature features of epidemic growth could become useful to assess the risk of observing a major epidemic outbreak, generate improved diseases forecasts and enhance the predictive power of epidemic models. Our results indicate that the epidemic growth scaling parameter is a useful indicator of epidemic size, which may have significant implications to guide control of Ebola outbreaks and possibly other infectious diseases.

Spatiotemporal Evolution of Ebola Virus Disease at Sub-National Level during the 2014 West Africa Epidemic: Model Scrutiny and Data Meagreness.

BACKGROUND: The Ebola outbreak in West Africa has infected at least 27,443 individuals and killed 11,207, based on data until 24 June, 2015, released by the World Health Organization (WHO). This outbreak has been characterised by extensive geographic spread across the affected countries Guinea, Liberia and Sierra Leone, and by localized hotspots within these countries. The rapid recognition and quantitative assessment of localised areas of higher transmission can inform the optimal deployment of public health resources. METHODS: A variety of mathematical models have been used to estimate the evolution of this epidemic, and some have pointed out the importance of the spatial heterogeneity apparent from incidence maps. However, little is known about the district-level transmission. Given that many response decisions are taken at sub-national level, the current study aimed to investigate the spatial heterogeneity by using a different modelling framework, built on publicly available data at district level. Furthermore, we assessed whether this model could quantify the effect of intervention measures and provide predictions at a local level to guide public health action. We used a two-stage modelling approach: a) a flexible spatiotemporal growth model across all affected districts and b) a deterministic SEIR compartmental model per district whenever deemed appropriate. FINDINGS: Our estimates show substantial differences in the evolution of the outbreak in the various regions of Guinea, Liberia and Sierra Leone, illustrating the importance of monitoring the outbreak at district level. We also provide an estimate of the time-dependent district-specific effective reproduction number, as a quantitative measure to compare transmission between different districts and give input for informed decisions on control measures and resource allocation. Prediction and assessing the impact of control measures proved to be difficult without more accurate data. In conclusion, this study provides us a useful tool at district level for public health, and illustrates the importance of collecting and sharing data.