Molecular Epidemiology of Human Oral Chagas Disease Outbreaks in Colombia

Abstract

Background

Trypanosoma cruzi, the causative agent of Chagas disease, displays significant genetic variability revealed by six Discrete Typing Units (TcI-TcVI). In this pathology, oral transmission represents an emerging epidemiological scenario where different outbreaks associated to food/beverages consumption have been reported in Argentina, Bolivia, Brazil, Ecuador and Venezuela. In Colombia, six human oral outbreaks have been reported corroborating the importance of this transmission route. Molecular epidemiology of oral outbreaks is barely known observing the incrimination of TcI, TcII, TcIV and TcV genotypes.

Methodology and Principal Findings

High-throughput molecular characterization was conducted performing MLMT (Multilocus Microsatellite Typing) and mtMLST (mitochondrial Multilocus Sequence Typing) strategies on 50 clones from ten isolates. Results allowed observing the occurrence of TcI, TcIV and mixed infection of distinct TcI genotypes. Thus, a majority of specific mitochondrial haplotypes and allelic multilocus genotypes associated to the sylvatic cycle of transmission were detected in the dataset with the foreseen presence of mitochondrial haplotypes and allelic multilocus genotypes associated to the domestic cycle of transmission.

Conclusions

These findings suggest the incrimination of sylvatic genotypes in the oral outbreaks occurred in Colombia. We observed patterns of super-infection and/or co-infection with a tailored association with the severe forms of myocarditis in the acute phase of the disease. The transmission dynamics of this infection route based on molecular epidemiology evidence was unraveled and the clinical and biological implications are discussed.

Author Summary

Chagas disease represents a serious health problem affecting more than 10 million people in the Americas. The oral transmission route has emerged as a new epidemiological scenario that needs to be considered in prevention and control strategies. Herein was developed a high-resolution molecular characterization using mtMLST and MLMT tools in order to unravel the molecular epidemiology and transmission dynamics drivers in six well-characterized human oral outbreaks in Colombia. We observed the majority of clones typed as TcI and one clone as TcIV. The analysis of mitochondrial haplotypes allowed us to observe a high frequency of sylvatic haplotypes and a low proportion of domestic haplotypes. Likewise, a tailored allelic profile by each outbreak was observed. Our results suggest that sylvatic populations of T. cruzi are the causative agents of Chagas disease oral outbreaks and these findings should help to pursue new initiatives of control and prevention in those areas where domiciliated vectorial transmission has been interrupted.