Modelling to explore the potential impact of asymptomatic human infections on transmission and dynamics of African sleeping sickness

Abstract

Gambiense 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.

A modelling assessment of short- and medium-term risks of programme interruptions for gambiense human African trypanosomiasis in the DRC

“…Other modelling work comparing the model variant used in this study with a variant including possible animal transmission found that, in some health zones in the former Bandundu province, EoT may occur later if animal transmission is occurring [14]. Similarly, if frequent self-curing asymptomatic transmission exists, this may result in more pessimistic predictions for EoT [33]. Although the impacts of interruptions on delays to EoT and additional DALYs accrued in models with animal transmission or self-curing asymptomatic infections are unknown, we speculate that results would not be qualitatively dissimilar to those presented here.…”

Modelling to infer the role of animals in gambiense human African trypanosomiasis transmission and elimination in the DRC

“…The model variants in the present paper already allow for long-term parasite carriage for a small proportion of individuals via their exponentially distributed infection periods, however not for self-cure or for skin-only parasite infection which would be missed in current screening algorithms. A few models considering potential self-curing asymptomatic transmission have been previously developed [ 23 , 34 , 35 ] and show that such a reservoir could hinder progress towards EoT. However, as with animal data, data on frequency and duration of such infections is sparse.…”

Enhancing research integration to improve One Health actions: learning lessons from neglected tropical diseases experiences

“…For, instance, it has been recently demonstrated that the emergence of animal reservoirs of Dracunculus medinensis , particularly in fish-consuming domestic dogs (93% of all Guinea worms detected worldwide in 2020 were in dogs in Chad), has become the major impediment to eradication of this human disease 3 4. For human African trypanosomiasis, the importance of latent infections in seropositive asymptomatic individuals,5 the identification of domestic pigs as reservoirs of Trypanosoma brucei gambiense 6 and the probable role of skin-dwelling trypanosomes in transmission maintenance7 8 are active research areas that may be crucial for reaching the elimination goal 9. Actually, the lack of fundamental scientific knowledge about the natural reservoirs and even the transmission of Mycobacterium ulcerans, that still remain elusive in most endemic areas,10 is also pointing to the crucial need for more fundamental knowledge on NTDs.…”