Epidemiological modeling of Trypanosoma cruzi: Low stercorarian transmission and failure of host adaptive immunity explain the frequency of mixed infections in humans

TOMASINI, NICOLÁS; RAGONE, PAULA GABRIELA; GOURBIÈRE, SÉBASTIEN; APARICIO, JUAN PABLO; DIOSQUE, PATRICIO

PLOS Computational Biology

PLOS computacional Biology

Año: 2017 vol. 13

People living in areas with active vector-borne transmission of Chagas disease have multiplecontacts with its causative agent, Trypanosoma cruzi. Reinfections by T. cruzi are possibleat least in animal models leading to lower or even hardly detectable parasitaemia. Inhumans, although reinfections are thought to have major public health implications byincreasing the risk of chronic manifestations of the disease, there is little quantitative knowledgeabout their frequency and the timing of parasite re-inoculation in the course of the disease.Here, we implemented stochastic agent-based models i) to estimate the rate of reinoculationin humans and ii) to assess how frequent are reinfections during the acute andchronic stages of the disease according to alternative hypotheses on the adaptive immuneresponse following a primary infection. By using a hybrid genetic algorithm, the models werefitted to epidemiological data of Argentinean rural villages where mixed infections by differentgenotypes of T. cruzi reach 56% in humans. To explain this percentage, the best modelpredicted 0.032 (0.008?0.042) annual reinfections per individual with 98.4% of them occurringin the chronic phase. In addition, the parasite escapes to the adaptive immune responsemounted after the primary infection in at least 20% of the events of re-inoculation. Withthese low annual rates, the risks of reinfection during the typically long chronic stage of thedisease stand around 14% (4%-18%) and 60% (21%-70%) after 5 and 30 years, with mostindividuals being re-infected 1?3 times overall. These low rates are better explained by theweak efficiency of the stercorarian mode of transmission than a highly efficient adaptiveimmune response. Those estimates are of particular interest for vaccine development andfor our understanding of the higher risk of chronic disease manifestations suffered byinfected people living in endemic areas.