Towards a paradigm shift in the treatment of chronic Chagas disease.

Treatment for Chagas disease with currently available medications is recommended universally only for acute cases (all ages) and for children up to 14 years old. The World Health Organization, however, also recommends specific antiparasite treatment for all chronic-phase Trypanosoma cruzi-infected individuals, even though in current medical practice this remains controversial, and most physicians only prescribe palliative treatment for adult Chagas patients with dilated cardiomyopathy. The present opinion, prepared by members of the NHEPACHA network (Nuevas Herramientas para el Diagnóstico y la Evaluación del Paciente con Enfermedad de Chagas/New Tools for the Diagnosis and Evaluation of Chagas Disease Patients), reviews the paradigm shift based on clinical and immunological evidence and argues in favor of antiparasitic treatment for all chronic patients. We review the tools needed to monitor therapeutic efficacy and the potential criteria for evaluation of treatment efficacy beyond parasitological cure. Etiological treatment should now be mandatory for all adult chronic Chagas disease patients.

Presence of Rhodnius ecuadoriensis in sylvatic habitats in the southern highlands (Loja Province) of Ecuador.

The main vectors of Chagas disease in Ecuador are Triatoma dimidiata and Rhodnius ecuadoriensis. The latter species occupies domestic and peridomestic habitats, as well as sylvatic ecotopes--particularly associated with Phytelephas aequatorialis palm trees--in the western coastal region of Ecuador. In the southern highlands, however, such palm tree habitats are uncommon, and sylvatic populations of R. ecuadoriensis have not previously been reported to date. This study was carried out in five rural communities in Loja Province in southern Ecuador, where manual triatomine searches were conducted in various sylvatic habitats. A total of 81 squirrel nests (Sciurus stramineus) and > 200 bird nests and other habitats were searched. One hundred three R. ecuadoriensis individuals were found in 11 squirrel nests (infestation index = 13.6%, density = 2 bugs per nest searched, crowding = 9.5 bugs per infested nest, colonization index = 72.7% of infested nests with nymphs). No triatomines were found in bird nests or other sylvatic habitats. The presence of sylvatic R. ecuadoriensis in the southern highlands of Ecuador has important implications for the long-term control of Chagas disease in the region because of the possibility of reinfestation of dwellings after insecticide-based control interventions.

High household infestation rates by synanthropic vectors of Chagas disease in southern Ecuador.

Entomological surveys were conducted in five rural communities (138 domiciliary units [DUs]) in the southern Andes of Ecuador. Adobe walls and ceramic tile roofs were predominant construction materials. A 35% house infestation rate with Panstrongylus chinai (Del Ponte, 1929) (0.7%), Panstrongylus rufotuberculatus (Champion, 1899) (0.7%), Rhodnius ecuadoriensis (Lent & León, 1958) (27%), and/or Triatoma carrioni (Larrousse, 1926) (7%) was found. Adults and nymphs of R. ecuadoriensis and T. carrioni were found in intradomiciliary and peridomiciliary areas. Breeding triatomine colonies were present in 85% of infested DUs, and the average insect crowding was 52+/-113 triatomine bugs per infested house. T. cruzi-like organisms were found by microscopic examination in the feces or hindgut but not the salivary glands of 4% of examined R. ecuadoriensis and 12% T. carrioni. Serological tests detected a general anti-T. cruzi antibody seroprevalence of 3.9% (n = 1136). Only 2% of individuals had heard of Chagas disease, and although triatomines were reported as a major nuisance by the population they were not considered vectors of disease. Additional baseline field research is needed for the design and implementation of a Chagas disease control program in the region.

Mouse model for Chagas disease: immunohistochemical distribution of different stages of Trypanosoma cruzi in tissues throughout infection.

Different stages of Trypanosoma cruzi are seen during mammalian infection. Histologic sections of infected hearts have shown amastigotes and, when using immunohistochemistry (IHC), parasite antigens; however, demonstration of trypomastigotes in these tissues has proven elusive. Using a mouse strain that develops chagasic cardiomyopathy (histologically similar to human infection) 70 days after injecting T. cruzi-Brazil strain, we studied the distribution of parasite stages and the extent of inflammation. All organs had varying amounts of mononuclear inflammation by day 10, which peaked between day 20 and day 30, and decreased by day 50. Amastigotes were detected in myocytes, histiocytes, acinar pancreatic cells, astrocytes and ependymal cells by day 10, and the number of amastigotes peaked on day 30. Immunohistochemistry demonstrated trypomastigotes in sinusoids, vessels and interstitial tissues of several organs between day 15 and 50. Abundant parasite antigens (granular staining) were detected in connective tissues throughout the infection. The burden of amastigotes and trypomastigotes during the acute phase seems to correlate with the degree of inflammation and granular staining in the chronic stage.

Use of polymerase chain reaction to diagnose the fifth reported US case of autochthonous transmission of Trypanosoma cruzi, in Tennessee, 1998.

In July 1998, the mother of an 18-month-old boy in rural Tennessee found a triatomine bug in his crib, which she saved because it resembled a bug shown on a television program about insects that prey on mammals. The gut contents of the Triatoma sanguisuga were found, by light microscopy and polymerase chain reaction (PCR), to be infected with Trypanosoma cruzi; PCR products hybridized with T. cruzi-specific oligonucleotide probes. Whole-blood specimens obtained from the child in July and August were negative by buffy-coat examination and hemoculture but positive by PCR and DNA hybridization, suggesting that he had low-level parasitemia. Specimens obtained after treatment with benznidazole were negative. He did not develop anti-T. cruzi antibody; 19 relatives and neighbors also were seronegative. Two of 3 raccoons trapped in the vicinity had positive hemocultures for T. cruzi. The child's case of T. cruzi infection-the fifth reported US autochthonous case-would have been missed without his mother's attentiveness and the availability of sensitive molecular techniques.

Immunological characterization of antigens released by Trypanosoma cruzi-infected cells.

Chagas' disease, caused by Trypanosorna cruzi, is characterized by the appearance of pathological lesions in the heart and other tissues during the chronic phase. The mechanisms responsible for such damage are still unclear. In the vertebrate host, T. cruzi replicates intracellularly before transforming from amastigotes into trypomastigotes. The infected host cell then lyses, releasing the cytoplasmic contents and the parasites that shed membrane glycoproteins soon after release. The sum of all these components we have termed released antigen (Rag). We characterized antigens, released in vitro by fibroblasts infected with T. cruzi, obtained by concentrating conditioned serum-free culture media. The results demonstrate that Rag contains a complex protein mixture including stage-specific T. cruzi antigens (Ssp-1, -2, -4), glucose-regulated protein (Grp) 78h, and peptides recognized by the monoclonal antibody 2B10. These peptides exhibit neuraminidase activity and are expressed by intracellular and 10-20% of released trypomastigotes. Additionally, Rag is recognized by sera from T. cruzi-infected mice and human chagasic patients. Rag also stimulates in vitro production of interferon-gamma by splenocytes from resistant C57B1/6 and susceptible BALB/c infected mice and interleukin-4 by splenocytes from BALB/c infected mice. Altogether these results indicate that Rag is immunologically relevant and could contribute to pathogenesis of T. cruzi infection.

Short report: screening for Trypanosoma cruzi in the blood supply by the Red Cross blood bank in Quito, Ecuador.

The status of Chagas' disease in Ecuador is not clear. In response to reports suggesting the possibility of transfusion-associated transmission of Chagas' disease in the blood bank in Quito, the Ecuadorian Red Cross in collaboration with the Instituto Nacional de Higiene, Zona Norte and the Tropical Disease Institute of Ohio University implemented a pilot Chagas' disease screening of the donated blood in the Quito blood bank. The results of the screening showed a low incidence of seropositivity among the donors (0.01% in 1994, 0.04% in 1995, and 0.02% in 1996) to the Quito blood bank and a higher seropositivity in samples donated to smaller blood banks (0.4% in 1994, 0.28% in 1995, and 0.13% in 1996) located in areas considered endemic, as well as from at least two areas previously considered nonendemic for Chagas' disease. This report highlights the need for a comprehensive evaluation of the prevalence and distribution of Chagas' disease in Ecuador.

Blood donors in a vector-free zone of Ecuador potentially infected with Trypanosoma cruzi.

Chagas' disease is a serious health problem for the population of South and Central America. Blood transfusion is the second most common way in which this disease is transmitted. Several studies have reported finding Trypanosoma cruzi-infected blood in blood banks in endemic areas. Serum samples were taken from the Red Cross blood bank in Quito, a nonendemic and vector free zone of Ecuador, in December 1992 and May 1993 and analyzed by enzyme-linked immunosorbent assay using crude epimastigote extract from the Brazil strain of T. cruzi. Of 162 samples examined in December 1992, 12.1%, 13.9%, and 74% were seropositive, indeterminate, and seronegative, respectively. Of 173 samples taken in May 1993, 6.2%, 17.9%, 75.9% were seropositive, indeterminate, and seronegative, respectively. Western blot analysis of these sera using sodium dodecyl sulfate-polyacrylamide gel electrophoresis with 7.5% gels separated T. cruzi epimastigote antigen proteins, and revealed a reaction with a 205-kD doublet antigen with most of the seropositive samples. These results indicate the necessity for long-term screening of blood bank donors to reduce the risk of transfusion transmission of the disease even in areas of endemic countries where the vector is not present.