Chagas' disease, a neglected tropical illness for which current therapy is unsatisfactory, is caused by the intracellular parasite Trypanosoma cruzi. The goal of this work is to investigate the in vitro and in vivo effects of the arylimidamide (AIA) DB766 against T. cruzi. This arylimidamide exhibits strong trypanocidal activity and excellent selectivity for bloodstream trypomastigotes and intracellular amastigotes (Y strain), giving IC 50 s (drug concentrations that reduce 50% of the number of the treated parasites) of 60 and 25 nM, respectively. DB766 also exerts striking effects upon different parasite stocks, including those naturally resistant to benznidazole, and displays higher activity in vitro than the reference drugs. By fluorescent and transmission electron microscopy analyses, we found that this AIA localizes in DNA-enriched compartments and induces considerable damage to the mitochondria. DB766 effectively reduces the parasite load in the blood and cardiac tissue and presents efficacy similar to that of benznidazole in mouse models of T. cruzi infection employing the Y and Colombian strains, using oral and intraperitoneal doses of up to 100 mg/kg/day that were given after the establishment of parasite infection. This AIA ameliorates electrocardiographic alterations, reduces hepatic and heart lesions induced by the infection, and provides 90 to 100% protection against mortality, which is similar to that provided by benznidazole. Our data clearly show the trypanocidal efficacy of DB766, suggesting that this AIA may represent a new lead compound candidate to Chagas' disease treatment.

No abstract

Traditional molecular and biochemical methods, such as schizodeme analysis, karyotyping, DNA fingerprinting, and enzyme electrophoretic profiles, have shown a large variability among Trypanosoma cruzi isolates. In contrast to those results, polymerase chain reaction (PCR) amplification of sequences from the 24S␣ ribosomal RNA gene and from the mini-exon gene nontranscribed spacer indicated a dimorphism among T. cruzi isolates, which enabled the definition of two major parasite lineages. In the present study, 86 T. cruzi field stocks (68 isolated from humans with defined presentations of Chagas' disease and 18 from triatomines) derived from four Brazilian geographic areas were typed by the PCR assay based on the DNA sequences of the mini-exon and 24S␣ rRNA genes. These stocks were ordered into the two major T. cruzi lineages. Lineage 1 was associated mainly with human isolates and lineage 2 with the sylvatic cycle of the parasite.

AIAs represent promising new chemical entities against T. cruzi and are also potential trypanocidal agents to prevent transfusion-associated Chagas' disease.

We refer to Oswaldo Cruz's reports dating from 1913 about the necessities of a healthcare system for the Brazilian Amazon Region and about the journey of Carlos Chagas to 27 locations in this region and the measures that would need to be adopted. We discuss the risks of endemicity of Chagas disease in the Amazon Region. We recommend that epidemiological surveillance of Chagas disease in the Brazilian Amazon Region and Pan-Amazon region should be implemented through continuous monitoring of the human population that lives in the area, their housing, the environment and the presence of triatomines. The monitoring should be performed with periodic seroepidemiological surveys, semi-annual visits to homes by health agents and the training of malaria microscopists and healthcare technicians to identify Trypanosoma cruzi from patients' samples and T. cruzi infection rates among the triatomines caught. We recommend health promotion and control of Chagas disease through public health policies, especially through sanitary education regarding the risk factors for Chagas disease. Finally, we propose a healthcare system through base hospitals, intermediate-level units in the areas of the Brazilian Amazon Region and air transportation, considering the distances to be covered for medical care.

This paper reports a study on the mycobiota in the digestive tract of four important species of triatomines: Rhodnius prolixus, R. neglectus, Diptelanogaster maximus and Panstrongylus megistus. The digestive tracts of 90 adults and 425 nymphs of these four triatomine species were studied and 365 fungal strains were isolated. The genera with the greatest number of species were Aspergillus, Penicillium (14 species in each genus), Acremonium and Cladosporium (three species in each genus), and the most frequent species, in decreasing order, were Aspergillus awamori, Penicillium corylophilum, Cladosporium herbarum and Aspergillus niger. It was concluded that, among the isolated fungi, Aspergillus niger and Penicillium corylophilum might be part of the natural flora of the digestive tract of triatomines.

Trypanosoma cruzi, the etiologic agent of Chagas disease, presents considerable heterogeneity between isolated populations within the wild and domestic cycles. By using multiplex polymerase chain reaction based on the mini-exon gene, characterization was performed on seven samples isolated from specimens of Triatoma vitticeps that had been collected from the locality of Triunfo in the municipality of Santa Maria Madalena, state of Rio de Janeiro, Brazil. The samples SMM10, SMM53, SMM88, and SMM98 (area A) and SMM36 and SMM82 (area B) revealed the presence of 150 base pairs, corresponding to the zymodeme III (Z3). Our study suggested that one isolate (SMM1) presents a mixed genotype associated with Z3 and TcII. The typing of isolates of T. cruzi has the main aim of identifying strains with different epidemiological and/or clinical characteristics of Chagas disease. Our results corroborate other descriptions in the literature and contribute towards the knowledge and records of the profile of some additional wild isolates of T. cruzi in regions not yet affected by the disease.

A study of the mycobiota in the digestive tract of 5 important species of triatomines, Triatoma brasiliensis, T infestans, T. sordida, T. pseudomaculata and T. vitticeps, was made. The digestive tracts of 164 adults and 535 nymphs of those triatomines were studied and 393 fungal strains were isolated. The genera with the greatest number of species were Penicillium (19 species), Aspergillus (17 species) and Acremonium (5 species) and the most frequent species, in decreasing order, were Penicillium corylophilum, Aspergillus niger, Penicillium felluttanum, Cladosporium herbarum, Penicillium waksmanii, Aspergillus awamori and Paecilomyces variotii. Among the isolated fungi, we found species that are recognized as entomopathogenic and pathogenic for humans and animals.