On an acute case of Chagas disease in a region under vector control in the state of São Paulo, Brazil

Desde a década de 1970 não se notificavam casos autóctones de doença de Chagas aguda em São Paulo. em março de 2006 a Vigilância Epidemiológica registrou óbito por doença de Chagas aguda, em Itaporanga, de paciente de seis anos de idade. Exame histopatológico post mortem realizado no Hospital das Clínicas da Faculdade de Medicina de Botucatu confirmou o diagnóstico. Consultamos prontuários de hospitais e entrevistamos profissionais de saúde envolvidos além de familiares do paciente. Descrevemos medidas adotadas in loco para identificar a via de transmissão, reservatórios e vetores. Discutimos as possíveis fontes de infecção. Na região não foram identificados outros casos humanos, vetores ou reservatórios vertebrados infectados por Trypanosoma cruzi. Salientamos a importância de manter a vigilância, mesmo em áreas onde a transmissão de doença de Chagas está interrompida e naquelas ainda infestadas por triatomíneos. Deve-se admitir a hipótese diagnóstica de doença de Chagas quando observados: edema palpebral (uni ou bilateral), insuficiência cardíaca, miocardite, pericardite, anasarca, quadros similares aos de síndrome nefrótica ou glomerulonefrite sem causas outras aparentes, em pacientes com dados epidemiológicos positivos. Encontro, mesmo em raras ocasiões, de triatomíneos na região ou ainda contato com alimento contaminável com formas infectantes de T. cruzi.

Chagas disease and triatomine biology (Heteroptera, Triatominae), with emphasis on aspects of spermatogenesis

A century after the discovery of Chagas disease, it is still one of the most important parasitic diseases affecting humans. The subfamily Triatominae is important in medical health, because these insects are vectors of Trypanosoma cruzi, the etiologic agent of Chagas disease. These insects are also of important cytological relevance because they have particular cell characteristics, such as persistence of nucleolar material in spermatogenesis. The germ cells of the animal kingdom have chromatoid bodies (CBs) in their cytoplasm that can originate from nucleolar material that is fragmented in the early stages of spermatogenesis and plays an important role in cellular communication between the spermatids during spermiogenesis. Currently, there are few studies on the function and formation of the CB in nucleologenesis, especially with emphasis on the ultrastructure of the cells involved in spermatogenesis of insects. Considering the importance of knowledge about the triatomine fauna, we conducted a study of the biogeography and reports of these insects and a survey of patients with Chagas disease in the northwestern region of São Paulo State. Data collected from 1995 to 2009 indicated 700 individuals with Chagas disease, demonstrating a range of 0 to 40 years, which shows that the disease may be active in this region. Moreover, of the 1150 patients treated for cardiomyopathy, 44% were chagasic. Regarding the triatomines noted and captured in the period from 2004 to 2009, the species were Triatoma sordida and Rhodnius neglectus, with T. sordida being the most abundant. In addition, some triatomines were infected by T. cruzi in various developmental stages. We also analyzed the nucleolar cycle and fibrillarin nucleolar protein expression in CB of spermatogenic cells of T. infestans and T. sordida, using histological, ultrastructural and immunocytochemical techniques. The results revealed fibrillarin nucleolar protein expression in the nucleus and in some cytoplasmic spots of germ cells during spermatogenesis in triatomines. These data suggest that fibrillarin could be a constituent of CB, which was most likely derived from nucleolar fragmentation. This is the first time that fibrillarin protein expression has been shown in CB during spermatogenesis progression in triatomines. Knowledge about the biology of triatomines was deepened in this study and, in particular, the structural and ultrastructural aspects of spermatogenesis in triatomines. This study showed that the disease may be active in the northwestern region of São Paulo and expanded our knowledge of the biology of triatomines, the main vectors of Chagas disease. © FUNPEC-RP.

Biologic and genetics aspects of chagas disease at endemic areas

The etiologic agent of Chagas Disease is the Trypanosoma cruzi, transmitted through blood-sucking insect vectors of the Triatominae subfamily, representing one of the most serious public health concerns in Latin America. There are geographic variations in the prevalence of clinical forms and morbidity of Chagas disease, likely due to genetic variation of the T. cruzi and the host genetic and environmental features. Increasing evidence has supported that inflammatory cytokines and chemokines are responsible for the generation of the inflammatory infiltrate and tissue damage. Moreover, genetic polymorphisms, protein expression levels, and genomic imbalances are associated with disease progression. This paper discusses these key aspects. Large surveys were carried out in Brazil and served as baseline for definition of the control measures adopted. However, Chagas disease is still active, and aspects such as host-parasite interactions, genetic mechanisms of cellular interaction, genetic variability, and tropism need further investigations in the attempt to eradicate the disease. Copyright 2012 Marilanda Ferreira Bellini et al.

Entoepidemiology of Chagas disease in the Western region of the State of Sao Paulo from 2004 to 2008, and cytogenetic analysis in Rhodnius neglectus (Hemiptera, Triatominae)

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Study on Chagas disease occurrence in the municipality of Monte Negro, State of Rondônia, Brazilian Amazon

Introduction: Studies on Chagas disease deal with the perspective of its occurrence in the Amazon region, which is directly correlated to the population growth and the spread of the bug biotope. The state of Rondônia has an immense source of vectors (Triatomine) and reservoirs of Trypanosoma cruzi. Environmental changes brought forth by the deforestation in the region may cause vector behavior changes and bring these vectors to a closer contact with humans, increasing the probability of vector infection. Methods: This study was carried out to check the occurrence of Chagas disease in the municipality of Monte Negro, Rondônia, Brazil, based on a random sampling of the farms and people wherein blood collection from the population and capturing triatomines were done. The blood samples were submitted to serologic tests to detect antibodies of the IgG class against T. cruzi. The triatomines that were collected had their digestive tract checked for the presence of trypanosomatidae with morphology resembling that of the T. cruzi. Results: The population examined was mostly from other states. From the 322 bugs examined on the microscope, 50% showed parasites with morphology compatible with T. cruzi. From the serology of 344 random samples of human blood, 1.2% was found positive, 6% showed inconclusive results, and 92.8% were negative. Conclusions: Monte Negro shows low prevalence of human infection by T. cruzi and none active vector transmission; however, preventive and surveying measures, which are not performed until now, shall be taken due to the abundance of vectors infected by trypanosomatidae.

(-)-Hinokinin-loaded poly(d,l-lactide-co-glycolide) microparticles for Chagas disease

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Immunosensor for the diagnosis of Chagas' disease

Trypanosoma cruzi proteins from epimastigote membranes, herein referred as antigens, have been used for the construction of an amperometric immunosensor for serological diagnosis of Chagas' disease. The proteins used had a molecular mass ranging from 30 to 100 kDa. The gold electrode was treated with cysteamine and glutaraldehyde prior to antigen immobilization. Antibodies present in the serum of patients with Chagas' disease were captured by the immobilized antigens and the affinity interaction was monitored by chronoamperometry at a potential of -400 mV (versus Ag pseudo-reference electrode) using peroxidase-labeled IgG conjugate and hydrogen peroxide, iodide substrate. The incubation time to allow maximum antigen-antibody and antibody-peroxidase-labeled IgG interactions was 20 min with a reactivity threshold at -0.104 mu A. (c) 2004 Elsevier B.V. All rights reserved.

Hydroxymethylnitrofurazone Is Active in a Murine Model of Chagas' Disease

The addition of a hydroxymethyl group to the antimicrobial drug nitrofurazone generated hydroxymethylnitrofurazone (NFOH), which had reduced toxicity when its activity against Trypanosoma cruzi was tested in a murine model of Chagas' disease. Four groups of 12 Swiss female mice each received 150 mg of body weight/kg/day of NFOH, 150 mg/kg/day of nitrofurazone (parental compound), 60 mg/kg/day of benznidazole (BZL), or the solvent as a placebo. Treatments were administered orally once a day 6 days a week until the completion of 60 doses. NFOH was as effective as BZL in keeping direct parasitemia at undetectable levels, and PCR results were negative. No histopathological lesions were seen 180 days after completion of the treatments, a time when the levels of anti-T. cruzi antibodies were very low in mice treated with either NFOH or BZL. Nitrofurazone was highly toxic, which led to an overall rate of mortality of 75% and necessitated interruption of the treatment. In contrast, the group treated with its hydroxymethyl derivative, NFOH, displayed the lowest mortality (16%), followed by the BZL (33%) and placebo (66%) groups. The findings of histopathological studies were consistent with these results, with the placebo group showing the most severe parasite infiltrates in skeletal muscle and heart tissue and the NFOH group showing the lowest. The present evidence suggests that NFOH is a promising anti-T. cruzi agent.

Dysautonomia and ventricular dysfunction in the indeterminate form of Chagas disease

Background: the associations between autonomic function and biventricular function in patients with the indeterminate form of Chagas disease remains to be elucidated.Methods: In 42 asymptornatic patients and 19 healthy volunteers, the autonomic function was assessed by time domain indices of heart rate variability (HRV), analyzed for 24 h; the right ventricular function was assessed by fraction area change, right ventricle shortening, and systolic excursion of the tricuspid valve; and the left ventricular function was assessed by ejection fraction and transmittal flow velocities. Data were expressed as mean SD or medians (including the lower quartile and upper quartile). Groups were compared by Student's t or Mann-Whitney U test. Autonomic and ventricular function were correlated by Pearson's or Spearman's correlation coefficient. The level of significance was 5%.Results: Right and left ventricular systolic function indexes were comparable between groups. Transmittal flow velocities were decreased in the Chagas disease group (p < 0.05). The patients presented impaired HRV as indicated by the values of SDNN-day (80 (64-99) ms vs. 98 (78-127) ms; p = 0.045), SDNNI-24 It (54 (43-71) vs. 65 (54-105) ms; p = 0.027), SDNNI-day (49 (42-64) vs. 67 (48-76) ms; p = 0.045), pNN50-day (2.2 (0.7-5)% vs. 10 (3-11)%; p = 0.033); and pNN50-24 It (3 (1-7)% vs. 12 (8-19)%; p = 0.013). There were no correlations between the left ventricular diastolic indices and autonomic dysfunctional indices (p > 0.05).Conclusion: Patients with the indeterminate form of Chagas disease have both dysautonomia, and left ventricular diastolic dysfunction. However, the right ventricular function is preserved. Importantly, ventricular diastolic dysfunction and dysautonomia. are independent phenomena. (c) 2005 Elsevier B.V.. All rights reserved.

Definition of a diagnostic routine in individuals with inconclusive serology for chagas disease

Despite the existence of highly sensitive tests, inconclusive serological results are frequent in chronic chagasic infection. This study aimed to define a diagnostic conduct for 30 individuals with inconclusive serology (G3) for chagasic infection assisted at the Outpatient Unit for Infectious and Parasitic Diseases of the Botucatu School of Medicine. Twenty-one individuals with negative serology (G1) and 33 with positive serology (G2) were also studied. Serological methods ELISA, HAI, IFI and immunoblotting TESA-cruzi were used for G1, G2 and G3, and parasitological methods xenodiagnosis, hemoculture and PCR-LIT were used for G2 and G3 individuals. ELISA, HAI and IFI were performed in 5 different blood samples in G2 and G3. TESA-cruzi was carried out only once in G1, G2 and G3 and, since it is the most sensitive, it was utilized as standard. In G3, positivity for ELISA reached 86% in the fifth blood sample; the ELISA+HAI+IFI combination showed a maximum of 44.8% in the second sample; and TESA-cruzi, 76% in one single sample. Xenodiagnosis positivity was 9.4%; hemoculture showed 15.2%; and PCR-LIT exhibited 22% positivity in G2. Nevertheless, in G3, positivity percentage was 3.4% for xenodiagnosis, 6.7% for PCR-LIT, and no positive result was found for hemoculture. In G3, PCR-LIT resolved one case which was still inconclusive according to serology tests. In order to define inconclusive diagnoses, the results suggest the combined use of ELISA+HAI+IFI in 2 blood samples, decreasing the occurrence of false positive/negative results. If results remain inconclusive, the performance of TESA-cruzi and PCR-LIT, if necessary, is recommended.

A critical evaluation of the expression of parasitemia in experimental Chagas' disease

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Serum uric acid levels in Chagas' disease

A uricemia foi estudada em uma amostra de 192 indivíduos de uma região altamente endêmica para a doença de Chagas (Bambuí, Estado de Minas Gerais, Brasil). A amostra continha 50 indivíduos sorologicamente negativos (controles) e os positivos foram classificados na base da presença de alterações eletrocardiográficas (63), esvaziamento esofagiano alterado (16), ou ausência de sinais ou sintomas da doença (76). Somente os indivíduos com a forma digestiva da doença de Chagas crônico mostraram hiperuricemia, quando comparados com controles adequados. Dados familiares sugerem que a hiperuricemia é um efeito da patologia digestiva em vez de causa, uma vez que os irmãos não afetados dos pacientes com megaesôfago não apresentaram níveis elevados de ácido úrico sérico. São postulados alguns mecanismos possivelmente responsáveis pelos achados.

Gene Mutations in Esophageal Mucosa of Chagas Disease Patients

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

p53, p16 and Fhit Proteins Expressions in Chronic Esophagitis and Chagas Disease

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)