Detecting Presymptomatic Infection Is Necessary to Forecast Major Epidemics in the Earliest Stages of Infectious Disease Outbreaks

Abstract

We assess how presymptomatic infection affects predictability of infectious disease epidemics. We focus on whether or not a major outbreak (i.e. an epidemic that will go on to infect a large number of individuals) can be predicted reliably soon after initial cases of disease have appeared within a population. For emerging epidemics, significant time and effort is spent recording symptomatic cases. Scientific attention has often focused on improving statistical methodologies to estimate disease transmission parameters from these data. Here we show that, even if symptomatic cases are recorded perfectly, and disease spread parameters are estimated exactly, it is impossible to estimate the probability of a major outbreak without ambiguity. Our results therefore provide an upper bound on the accuracy of forecasts of major outbreaks that are constructed using data on symptomatic cases alone. Accurate prediction of whether or not an epidemic will occur requires records of symptomatic individuals to be supplemented with data concerning the true infection status of apparently uninfected individuals. To forecast likely future behavior in the earliest stages of an emerging outbreak, it is therefore vital to develop and deploy accurate diagnostic tests that can determine whether asymptomatic individuals are actually uninfected, or instead are infected but just do not yet show detectable symptoms. Emerging epidemics pose a significant challenge to human health worldwide. Accurate real-time forecasts of whether or not initial reports will be followed by a major outbreak are necessary for efficient deployment of control. For all infectious diseases, there is a delay between infection and the appearance of symptoms, i.e. an initial period following first infection during which infected individuals remain presymptomatic. We use mathematical modeling to evaluate the effect of presymptomatic infection on predictions of major epidemics. Our results show rigorously, for the first time, that precise estimates of the current number of infected individuals—and consequently the chance of a major outbreak in future—cannot be inferred from data on symptomatic cases alone. This is the case even if the values of epidemiological parameters, such as the average infection and death or recovery rates of individuals in the population, can be estimated accurately. Accurate prediction is in fact impossible without additional data from which the number of currently infected but as yet presymptomatic individuals can be deduced.