BackgroundThe causative agent of Chagas disease, Trypanosoma cruzi, is divided into 6 Discrete Typing Units (DTU): Tc I, IIa, IIb, IIc, IId and IIe. In order to assess the relative pathogenicities of different DTUs, blood samples from three different clinical groups of chronic Chagas disease patients (indeterminate, cardiac, megacolon) from Bolivia were analyzed for their circulating parasites lineages using minicircle kinetoplast DNA polymorphism.Methods and FindingsBetween 2000 and 2007, patients sent to the Centro Nacional de Enfermedades Tropicales for diagnosis of Chagas from clinics and hospitals in Santa Cruz, Bolivia, were assessed by serology, cardiology and gastro-intestinal examinations. Additionally, patients who underwent colonectomies due to Chagasic magacolon at the Hospital Universitario Japonés were also included. A total of 306 chronic Chagas patients were defined by their clinical types (81 with cardiopathy, 150 without cardiopathy, 100 with megacolon, 144 without megacolon, 164 with cardiopathy or megacolon, 73 indeterminate and 17 cases with both cardiopathy and megacolon). DNA was extracted from 10 ml of peripheral venous blood for PCR analysis. The kinetoplast minicircle DNA (kDNA) was amplified from 196 out of 306 samples (64.1%), of which 104 (53.3%) were Tc IId, 4 (2.0%) Tc I, 7 (3.6%) Tc IIb, 1 (0.5%) Tc IIe, 26 (13.3%) Tc I/IId, 1 (0.5%) Tc I/IIb/IId, 2 (1.0%) Tc IIb/d and 51 (25.9%) were unidentified. Of the 133 Tc IId samples, three different kDNA hypervariable region patterns were detected; Mn (49.6%), TPK like (48.9%) and Bug-like (1.5%). There was no significant association between Tc types and clinical manifestations of disease.ConclusionsNone of the identified lineages or sublineages was significantly associated with any particular clinical manifestations in the chronic Chagas patients in Bolivia.

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We report a patient with congenital Chagas disease in Japan. This report reemphasizes the role of neglected and emerging tropical diseases in the era of globalization. It also indicates the need for increased vigilance for detecting Chagas disease in non–disease-endemic countries.

Background There are no reports on the prevalence of Chagas disease in Japan. Furthermore, screening programs and access to diagnosis and treatment have not been established. This study aimed to clarify the prevalence of Chagas disease among suspected cases in Japan and provide the reference data required for disease control. Methods Seventeen patients with suspected Chagas disease in Japan between 2012 and 2017 were included in the study. Patients were diagnosed with Chagas disease based on the two different serological tests for antibodies to Trypanosoma cruzi . Real-time polymerase chain reaction assay and blood culture techniques were performed to confirm T. cruzi parasitemia. Results Of the 17 patients, 11 (64.7%) were immigrants from Latin America. Ultimately, 6 patients (35.3%) were diagnosed with Chagas disease. Of these 6 patients, median age was 53.5 years, 5 patients were immigrants from Latin American, and 1 was Japanese who had a congenital infection. T. cruzi parasitemia was confirmed in 4 patients (66.7%), and 5 (83.3%) were in the chronic phase (Chagas cardiomyopathy, 4; megacolon, 1). Two patients (33.3%) commenced benznidazole treatment. Conclusion Our study showed that some patients of Chagas disease living in Japan are already in the chronic phase at diagnosis because of substantial diagnostic delays. Further epidemiological studies on the prevalence of Chagas disease and systematic screening programs for the Latin American population are needed.

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BackgroundChagas disease, caused by the flagellate parasite Trypanosoma cruzi affects 8–10 million people in Latin America. The mechanisms that underlie the development of complications of chronic Chagas disease, characterized primarily by pathology of the heart and digestive system, are not currently understood. To identify possible host genetic factors that may influence the clinical course of Chagas disease, Human Leucocyte Antigen (HLA) regional gene polymorphism was analyzed in patients presenting with differing clinical symptoms.MethodologyTwo hundred and twenty nine chronic Chagas disease patients in Santa Cruz, Bolivia, were examined by serological tests, electrocardiogram (ECG), and Barium enema colon X-ray. 31.4% of the examinees showed ECG alterations, 15.7% megacolon and 58.1% showed neither of them. A further 62 seropositive megacolon patients who had undergone colonectomy due to acute abdomen were recruited. We analyzed their HLA genetic polymorphisms (HLA-A, HLA-B, MICA, MICB, DRB1 and TNF-alpha promoter region) mainly through Sequence based and LABType SSO typing test using LUMINEX Technology.Principal FindingsThe frequencies of HLA-DRB1*01 and HLA-B*14:02 were significantly lower in patients suffering from megacolon as well as in those with ECG alteration and/or megacolon compared with a group of patients with indeterminate symptoms. The DRB1*0102, B*1402 and MICA*011 alleles were in strong Linkage Disequilibrium (LD), and the HLA-DRB1*01-B*14-MICA*011haplotype was associated with resistance against chronic Chagas disease.ConclusionsThis is the first report of HLA haplotype association with resistance to chronic Chagas disease.

Fifty-eight stocks of Trypanosoma cruzi from Latin America were genetically characterized using the methods of the polymerase chain reaction (PCR) and the single-stranded conformation DNA polymorphism (SSCP) with four genes, mini-exon, 24Salpha rRNA, 18Sr RNA, cruzipain, and a RAPD fragment DNA region, P7-P8. All the isolates examined were assigned to T. cruzi I or subgroups of T. cruzi II by these methods. From these results, the SSCP analysis, which was simple to perform and highly sensitive to sequence variation, seemed to be a good modality for characterizing T. cruzi, particularly for subgroups of T. cruzi II. However, in several isolates of T. cruzi II, the subgroups determined with the SSCP of 24Salpha rRNA were not consistent with those determined with other genes, the SSCP of 18S rRNA and cruzipain, and the PCR of P7-P8, possibly because of the occurrence of rare genetic exchanges or mutations or both in natural populations of this parasite. The SSCP patterns of 24Salpha rRNA and 18S rRNA were highly variable in the T. cruzi I isolates; therefore, analyses using both genes are considered to be one possible method for the characterization of isolates within T. cruzi I.

Molecular phylogenetic analysis was carried out for 21 strains of Trypanosoma cruzi, nine of which were obtained from Guatemala and 12 from South America. Phylogenetic trees were constructed using the nucleotide sequences of two nuclear gene regions, dihydrofolate reductase-thymidylate synthase (DHFR-TS) and trypanothione reductase (TR), and contiguous portions of two mitochondrial genes, cytochrome oxidase subunit II (COII) and reduced nicotinamide adenine dinucleotide dehydrogenase subunit 1 (ND1). Possible genetic exchange between the rather divergent lineages of T. cruzi II from South America was suggested in the trees of the two nuclear genes. T. cruzi I strains obtained from Guatemala and Colombia were identical in all the genes examined, but other T. cruzi I isolates from South America were rather polymorphic in the DHFR-TS and mitochondrial genes. No genetic exchange was identified between T. cruzi I populations from Central and South America in the present study.