Abstract

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.

Highlights

  • Many infections only occur as isolated cases, short chains of transmission, or as small infection clusters

  • The apparent trend towards decreased human-to-human transmission of MERS-CoV during the second half of 2013 may be a reflection of stochasticity rather than a true decrease in Reff Since 2011, there have been over 500 confirmed cases of MERS-CoV, and over 140 associated deaths, suggesting a case fatality rate of 28% [32]

  • Human-to-human transmission has been relatively limited so far, with Reff likely less than one, there is concern that future adaptation that could lead to spread similar to sudden acute respiratory syndrome (SARS) in 2003

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Summary

Introduction

Many infections only occur as isolated cases, short chains of transmission, or as small infection clusters (i.e. intertwined transmission chains). Examples include zoonotic infections with relatively weak human-to-human transmission as well as vaccinepreventable infections in settings of high vaccination coverage [1,2,3,4,5,6,7]. Even though transmission is limited, these diseases are an important public health concern. Zoonotic infections can adapt for increased human-to-human transmission and cause greater or even pandemic spread [8,9,10]. Self-limited (or subcritical) transmission characterizes diseases that are on the brink of elimination such as smallpox during its worldwide eradication campaign or polio today [12,13,14]

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