Modelling to explore the potential impact of asymptomatic human infections on transmission and dynamics of African sleeping sickness
Authors: Aliee Maryam , Keeling Matt J. , Rock Kat S. 
Published: May 2021

AbstractGambiense human African trypanosomiasis (gHAT, sleeping sickness) is one of several neglected tropical diseases (NTDs) where there is evidence of asymptomatic human infection but there is uncertainty of the role it plays in transmission and maintenance. To explore possible consequences of asymptomatic infections, particularly in the context of elimination of transmission – a goal set to be achieved by 2030 – we propose a novel dynamic transmission model to account for the asymptomatic population. This extends an established framework, basing infection progression on a number of experimental and observation gHAT studies. Asymptomatic gHAT infections include those in people with blood-dwelling trypanosomes, but no discernible symptoms, or those with parasites only detectable in skin. Given current protocols, asymptomatic infection with blood parasites may be diagnosed and treated, based on observable parasitaemia, in contrast to many other diseases for which treatment (and/or diagnosis) may be based on symptomatic infection. We construct a model in which exposed people can either progress to either asymptomatic skin-only parasite infection, which would not be diagnosed through active screening algorithms, or blood-parasite infection, which is likely to be diagnosed if tested. We add extra parameters to the baseline model including different self-cure, recovery, transmission and detection rates for skin-only or blood infections. Performing sensitivity analysis suggests all the new parameters introduced in the asymptomatic model can impact the infection dynamics substantially. Among them, the proportion of exposures resulting in initial skin or blood infection appears the most influential parameter.For some plausible parameterisations, an initial fall in infection prevalence due to interventions could subsequently stagnate even under continued screening due to the formation of a new, lower endemic equilibrium. Excluding this scenario, our results still highlight the possibility for asymptomatic infection to slow down progress towards elimination of transmission. Location-specific model fitting will be needed to determine if and where this could pose a threat.Author summaryGambiense African sleeping sickness is an infectious disease targeted for elimination of transmission by 2030. Despite this there is still some uncertainty how frequently some infected people who may not have symptoms could “self-cure” without ever having disease and whether some types of infections, such as infections only in the skin, but not the blood, could still contribute to transmission, yet go undiagnosed.To explore how problematic these asymptomatic infections could be in terms of the elimination goal, we use a mathematical model which quantitatively describes changes to infection and transmission over time and includes these different types of infection. We use results of published experimental or field studies as inputs for the model parameters governing asymptomatic infections.We examined the impact of asymptomatic infections when control interventions are put in place. Compared to a baseline model with no asymptomatics, including asymptomatic infection using plausible biological parameters can have a profound impact on transmission and slow progress towards elimination. In some instances it could be possible that even after initial decline in sleeping sickness cases, progress could stagnate without reaching the elimination goal at all, however location-specific modelling will be needed to determine if and where this could pose a threat.