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

Abstract

People living in areas with active vector-borne transmission of Chagas disease have multiple contacts with its causative agent, Trypanosoma cruzi. Reinfections by T. cruzi are possible at least in animal models leading to lower or even hardly detectable parasitaemia. In humans, although reinfections are thought to have major public health implications by increasing the risk of chronic manifestations of the disease, there is little quantitative knowledge about 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 re-inoculation in humans and ii) to assess how frequent are reinfections during the acute and chronic stages of the disease according to alternative hypotheses on the adaptive immune response following a primary infection. By using a hybrid genetic algorithm, the models were fitted to epidemiological data of Argentinean rural villages where mixed infections by different genotypes of T. cruzi reach 56% in humans. To explain this percentage, the best model predicted 0.032 (0.008–0.042) annual reinfections per individual with 98.4% of them occurring in the chronic phase. In addition, the parasite escapes to the adaptive immune response mounted after the primary infection in at least 20% of the events of re-inoculation. With these low annual rates, the risks of reinfection during the typically long chronic stage of the disease stand around 14% (4%-18%) and 60% (21%-70%) after 5 and 30 years, with most individuals being re-infected 1–3 times overall. These low rates are better explained by the weak efficiency of the stercorarian mode of transmission than a highly efficient adaptive immune response. Those estimates are of particular interest for vaccine development and for our understanding of the higher risk of chronic disease manifestations suffered by infected people living in endemic areas.

Detailed ecological associations of triatomines revealed by metabarcoding and next-generation sequencing: implications for triatomine behavior and Trypanosoma cruzi transmission cycles

“…Overall, our results are in agreement with the large diversity of T. cruzi strains and DTUs observed in T. dimidiata in Veracruz, Mexico 13 , and Guatemala 17 , as well as in vertebrate hosts from the Yucatan 89 , even though these studies only documented the dominant genotypes as mentioned above. Our observations raise the questions of the nature of the interactions among parasite haplotypes within vectors, which may play an important role in shaping parasite transmission and the epidemiology of T. cruzi infection 97 , 98 . In any case, it is clear that future studies should take into account the multiclonality of T. cruzi infections to further understand parasite transmission networks and the epidemiology of Chagas disease.…”

Treatment with Fenofibrate plus a low dose of Benznidazole attenuates cardiac dysfunction in experimental Chagas disease

“…Furthermore, we couldn't reproduce the cardiac dysfunction characteristic of human Chagas disease, using single population infections. Besides, in the context of active vector-driven transmission in rural and some suburban areas, an individual may be exposed to reinfection by several T. cruzi populations ( Tomasini et al, 2017 ), some of which may differ in their virulence, tropism, immunogenicity and genetics. This, of course, may be conditioned by the diversity of genotypes present in a specific geographic area.…”

A voluntary use of insecticide treated nets can stop the vector transmission of Chagas disease

“…However, for the other values of the parameters, most notably the vector birth rate β and death rate μ such a high value of ω would result in no bugs in the plantation area. Consequently, we adapted the value 0.01 from [ 56 ]. Moreover, as seen from the sensitivity analysis, the results are not overly sensitive to values of ω .…”