Trypanosoma cruzi IV Causing Outbreaks of Acute Chagas Disease and Infections by Different Haplotypes in the Western Brazilian Amazonia

Abstract

BackgroundChagas disease is an emergent tropical disease in the Brazilian Amazon Region, with an increasing number of cases in recent decades. In this region, the sylvatic cycle of Trypanosoma cruzi transmission, which constitutes a reservoir of parasites that might be associated with specific molecular, epidemiological and clinical traits, has been little explored. The objective of this work is to genetically characterize stocks of T. cruzi from human cases, triatomines and reservoir mammals in the State of Amazonas, in the Western Brazilian Amazon.Methodology/Principal FindingsWe analyzed 96 T. cruzi samples from four municipalities in distant locations of the State of Amazonas. Molecular characterization of isolated parasites from cultures in LIT medium or directly from vectors or whole human blood was performed by PCR of the non-transcribed spacer of the mini-exon and of the 24 S alfa ribosomal RNA gene, RFLP and sequencing of the mitochondrial cytochrome c oxidase subunit II (COII) gene, and by sequencing of the glucose-phosphate isomerase gene. The T. cruzi parasites from two outbreaks of acute disease were all typed as TcIV. One of the outbreaks was triggered by several haplotypes of the same DTU. TcIV also occurred in isolated cases and in Rhodnius robustus. Incongruence between mitochondrial and nuclear phylogenies is likely to be indicative of historical genetic exchange events resulting in mitochondrial introgression between TcIII and TcIV DTUs from Western Brazilian Amazon. TcI predominated among triatomines and was the unique DTU infecting marsupials.Conclusion/SignificanceDTU TcIV, rarely associated with human Chagas disease in other areas of the Amazon basin, is the major strain responsible for the human infections in the Western Brazilian Amazon, occurring in outbreaks as single or mixed infections by different haplotypes.

Characteristics of Triatomine infestation and natural Trypanosoma cruzi infection in the State of Rio Grande do Norte, Brazil

“…Trypanosoma cruzi isolates were typed using three different parasite genomic sequences as reported (39) , with the 24Sα ribosomal (rRNA) gene D7 domain (40) , mitochondrial cytochrome oxidase subunit 2 gene (COII) (41) , and the spliced leader genes intergenic region (42) as markers for six discrete typing units (DTUs) (43) , using T. cruzi reference strains (15) (44) (45) and clones (46) (47) as DTU controls.…”

Chagas disease in the State of Amazonas: history, epidemiological evolution, risks of endemicity and future perspectives

“…Studies in Amazonas have demonstrated the presence of DTUs TcI, TcIII and TcIV in the parasite sylvatic transmission cycle (33) (34) (35) (38) . TcIV predominates among orally transmitted acute human cases (34) , and TcI predominates among the isolated and chronic cases (35) (38) , suggesting their association with different transmission profiles. The T. cruzi isolates showed variable behavior in experimental infections in mice, promoting low parasitemia, virulence and pathogenicity, which is compatible with the low parasitemia and morbidity profi le of CD in humans and with the poor performance of diagnostic methods in the region (43) .…”

Impact of Benznidazole on Infection Course in Mice Experimentally Infected with Trypanosoma cruzi I, II, and IV

“…A total of 18 T. cruzi strains were studied; 14 were isolated from patients during the acute phase of infection, vectors and wild reservoirs from the State of Amazonas and were classified as TcI (6) and TcIV (8), 13 and four strains were isolated from chronically infected patients residing in the State of Paraná and were genotyped as TcII 20 (Table 1). Parasites were maintained in culture in liver infusion tryptose (LIT) medium by successive subculturing with alternating mouse-LIT-mouse passages and in blood passages in mice at the Chagas Disease Laboratory (Laborató rio de Doença de Chagas), Maringá State University (Universidade Estadual de Maringá ; UEM).…”

“…To date, knowledge about these T. cruzi DTUs in the Amazon region is scarce, and pioneer studies from our group present a detailed understanding of the genetic, biological, and histopathological characteristics of parasites belonging to TcI and IV DTUs. [13][14][15][16][17] The goal of etiologic treatment of CD is the parasite elimination from the infected individual, thereby inhibiting clinical evolution and breaking the disease transmission chain. 18 Histologically, the acute phase of trypanosomiasis is a systemic infection, and intracellular forms of the parasite can be found in all organs.…”