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

Nicolás Tomasini,Sébastien Gourbière,Juan Pablo Aparicio,Paula Gabriela Ragone,Patricio Diosque,Roland R Regoes

doi:10.1371/journal.pcbi.1005532

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.

Highlights

Chagas disease (American trypanosomiasis) is a vector-borne disease primarily transmitted by a broad range of ecologically and evolutionary diversified triatomine species (e.g. [1])
Chagas disease is caused by a unicellular parasite mainly transmitted by blood-feeding bugs
The immune system is activated and almost clears the parasites before the host enters the chronic phase of the disease

Summary

Introduction

Chagas disease (American trypanosomiasis) is a vector-borne disease primarily transmitted by a broad range of ecologically and evolutionary diversified triatomine species (e.g. [1]). The disease enters a chronic stage where parasite persistence is associated with chronic manifestations of the disease [3,4,5,6,7,8] This parasite persistence triggers a constant activation of the immune system that is thought to exert a resistance to reinfections. This condition of non-sterile immunity, known as premunition or premunity [9], has been described for several diseases like malaria [10,11,12] and infections by helminthes [13,14,15,16,17]. Since reinfections in humans cannot be experimentally evaluated for obvious ethical concerns, mathematical and computational models of Chagas disease transmission are Reinfection dynamics of Chagas disease critically needed to infer on the rate and timing of T. cruzi reinfections from epidemiological field data

Methods

Results

Discussion

Conclusion