Abstract

Trypanosoma cruzi, the causative agent of human Chagas disease, is endemic to the southern region of the United States where it routinely infects many host species. The indoor/outdoor housing configuration used in many non-human primate research and breeding facilities in the southern of the USA provides the opportunity for infection by T. cruzi and thus provides source material for in-depth investigation of host and parasite dynamics in a natural host species under highly controlled and restricted conditions. For cynomolgus macaques housed at such a facility, we used a combination of serial blood quantitative PCR (qPCR) and hemoculture to confirm infection in >92% of seropositive animals, although each method alone failed to detect infection in >20% of cases. Parasite isolates obtained from 43 of the 64 seropositive macaques were of 2 broad genetic types (discrete typing units, (DTU's) I and IV); both within and between these DTU groupings, isolates displayed a wide variation in growth characteristics and virulence, elicited host immune responses, and susceptibility to drug treatment in a mouse model. Likewise, the macaques displayed a diversity in T cell and antibody response profiles that rarely correlated with parasite DTU type, minimum length of infection, or age of the primate. This study reveals the complexity of infection dynamics, parasite phenotypes, and immune response patterns that can occur in a primate group, despite being housed in a uniform environment at a single location, and the limited time period over which the T. cruzi infections were established.

Highlights

  • This study reveals the complexity of infection dynamics, parasite phenotypes, and immune response patterns that can occur in a primate group, despite being housed in a uniform environment at a single location, and the limited time period over which the T. cruzi infections were established

  • Trypanosoma cruzi is the agent of human Chagas disease, the highest impact parasitic disease in the Americas, affecting 10–20 million individuals

  • The misconceptions surrounding T. cruzi infection and Chagas disease emanate in part from the largely anecdotal nature of investigations of human infections, the remarkable genetic variability among individual isolates of T. cruzi, and the limited number of these genetic variants that have been extensively studied in naturally infected hosts, especially humans

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Summary

Introduction

Trypanosoma cruzi is the agent of human Chagas disease, the highest impact parasitic disease in the Americas, affecting 10–20 million individuals. T. cruzi infection has been studied for over a century in its numerous mammalian hosts, including humans, there remain many unanswered questions and misconceptions concerning the factors that determine the control of the infection and the progression and severity of, and the tissues affected by, the disease. Irrespective of the host species, T. cruzi is nearly always a persistent infection and disease development is progressive in the absence of effective treatment. Such treatments exist, few individuals benefit from them for a variety of reasons, including the justifiable concerns of side effects, the documented failure in some cases to cure the infection and the shortage of drugs [1,2,3,4]. The identification of a large cohort of cynomolgus macaques (Macaca fascicularis) with naturally acquired T. cruzi infection at the Southwest National Primate Research Center (SNPRC) provided a unique opportunity to study, in a relatively large primate population, the parasitological and immunological parameters associated with the infection and disease

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