Detecting Differential Transmissibilities That Affect the Size of Self-Limited Outbreaks

Our ability to respond appropriately to infectious diseases is enhanced by identifying differences in the potential for transmitting infection between individuals. Here, we identify epidemiological traits of self-limited infections (i.e. infections with an effective reproduction number satisfying ) that correlate with transmissibility. Our analysis is based on a branching process model that permits statistical comparison of both the strength and heterogeneity of transmission for two distinct types of cases. Our approach provides insight into a variety of scenarios, including the transmission of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) in the Arabian peninsula, measles in North America, pre-eradication smallpox in Europe, and human monkeypox in the Democratic Republic of the Congo. When applied to chain size data for MERS-CoV transmission before 2014, our method indicates that despite an apparent trend towards improved control, there is not enough statistical evidence to indicate that has declined with time. Meanwhile, chain size data for measles in the United States and Canada reveal statistically significant geographic variation in , suggesting that the timing and coverage of national vaccination programs, as well as contact tracing procedures, may shape the size distribution of observed infection clusters. Infection source data for smallpox suggests that primary cases transmitted more than secondary cases, and provides a quantitative assessment of the effectiveness of control interventions. Human monkeypox, on the other hand, does not show evidence of differential transmission between animals in contact with humans, primary cases, or secondary cases, which assuages the concern that social mixing can amplify transmission by secondary cases. Lastly, we evaluate surveillance requirements for detecting a change in the human-to-human transmission of monkeypox since the cessation of cross-protective smallpox vaccination. Our studies lay the foundation for future investigations regarding how infection source, vaccination status or other putative transmissibility traits may affect self-limited transmission.
Author Summary The goal of this paper is to identify epidemiological factors that correlate with either an increased or decreased risk of transmitting a particular disease. We are particularly interested in identifying such factors for diseases that are self-limited (meaning that infections tend to occur in isolated clusters), because targeted control of these diseases can facilitate public health goals for minimizing the risk of disease emergence or promoting disease elimination. For example, we show that there is a significant difference in the transmission of measles between the United States and Canada. In contrast, we find that an observed decrease in the transmission of Middle East respiratory syndrome coronavirus during the latter half of 2013 cannot be ascertained with sufficient confidence. We then quantify the degree to which control was effective in eradicating smallpox in Europe. We also consider how the transmission of monkeypox in humans depends on whether the infection source is an animal or a human. Finally, we demonstrate how our approach can be used by surveillance programs to detect changes in transmission that may occur over time.