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.

Protective actions of melatonin against heart damage during chronic Chagas disease

Chronic cardiomyopathy is the most important clinical form of Chagas disease, and it is characterised by myocarditis that is associated with fibrosis and organ dysfunction. Alternative treatment options are important tools to modulate host immune responses. The main goal of this work was to evaluate the anti-inflammatory actions of melatonin during the chronic phase of Chagas disease. TNF-α, IL-10 and nitrite concentrations were evaluated as predictive factors of immune modulation. Creatine phosphokinase-MB (CK-MB), cardiac inflammatory foci and heart weight were assessed to evaluate the efficacy of the melatonin treatment. Male Wistar rats were infected with 1 × 105 blood trypomastigotes of the Y strain of Trypanosoma cruzi and kept untreated for 60 days to mimic chronic infection. After this period, the rats were orally treated with melatonin 50 mg/kg/day, and the experiments were performed 90, 120, and 180 days post-infection. Melatonin treatment significantly increased the concentration of IL-10 and reduced the concentrations of NO and TNF-α produced by cardiomyocytes. Furthermore, it led to decreased heart weight, serum CK-MB levels and inflammatory foci when compared to the untreated and infected control groups. We conclude that melatonin therapy is effective at protecting animals against the harmful cardiac inflammatory response that is characteristic of chronic T. cruzi infection. © 2013 Elsevier B.V. All rights reserved.

A novel association between Rhodnius neglectus and the Livistona australis palm tree in an urban center foreshadowing the risk of Chagas disease transmission by vectorial invasions in Monte Alto City, Sao Paulo, Brazil

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

The enigmatic role of cholinergic reflex in the pathogenesis of Chagas disease

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

Laparoscopic Heller Myotomy and Fundoplication in Patients with Chagas' Disease Achalasia and Massively Dilated Esophagus

Laparoscopic Heller myotomy and fundoplication is considered today the treatment of choice for achalasia. The optimal treatment for end-stage achalasia with esophageal dilation is still controversial. This multicenter and retrospective study aims to evaluate the outcome of laparoscopic Heller myotomy in patients with a massively dilated esophagus. Eleven patients (mean age, 56 years; 6 men) with massively dilated esophagus (esophageal diameter greater than 10 cm) underwent a laparoscopic Heller myotomy and anterior fundoplication between 2000 and 2009 at three different institutions. Preoperative workup included upper endoscopy, esophagram, and esophageal manometry in all patients. Average follow-up was 31.5 months (range, 3 to 60 months). Two patients (18%) had severe dysphagia, four patients (36%) had mild and occasional dysphagia to solid food, and five patients (45%) were asymptomatic. All patients gained or kept body weight, except for the two patients with severe dysphagia. Of the two patients with severe dysphagia, one underwent esophageal dilatation and the other a laparoscopic esophagectomy. They are both doing well. Heller myotomy relieves dysphagia in the majority of patients even when the esophagus is massively dilated.

Challenges and perspectives of Chagas disease: a review

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

Entoepidemiology of Chagas disease in northwest Sao Paulo and cytogenetic analysis of its main vector, Triatoma sordida (Hemiptera: Triatominae)

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

Genetic Variability and Geographical Diversity of the Main Chagas' Disease Vector Panstrongylus megistus (Hemiptera: Triatominae) in Brazil Based on Ribosomal DNA Intergenic Sequences

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Pharmacokinetics of Hydroxymethylnitrofurazone, a Promising New Prodrug for Chagas' Disease Treatment

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

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)

De novo transcriptome assembly for a non-model species, the blood-sucking bug Triatoma brasiliensis, a vector of Chagas disease

High throughput sequencing (HTS) provides new research opportunities for work on non-model organisms, such as differential expression studies between populations exposed to different environmental conditions. However, such transcriptomic studies first require the production of a reference assembly. The choice of sampling procedure, sequencing strategy and assembly workflow is crucial. To develop a reliable reference transcriptome for Triatoma brasiliensis, the major Chagas disease vector in Northeastern Brazil, different de novo assembly protocols were generated using various datasets and software. Both 454 and Illumina sequencing technologies were applied on RNA extracted from antennae and mouthparts from single or pooled individuals. The 454 library yielded 278 Mb. Fifteen Illumina libraries were constructed and yielded nearly 360 million RNA-seq single reads and 46 million RNA-seq paired-end reads for nearly 45 Gb. For the 454 reads, we used three assemblers, Newbler, CAP3 and/or MIRA and for the Illumina reads, the Trinity assembler. Ten assembly workflows were compared using these programs separately or in combination. To compare the assemblies obtained, quantitative and qualitative criteria were used, including contig length, N50, contig number and the percentage of chimeric contigs. Completeness of the assemblies was estimated using the CEGMA pipeline. The best assembly (57,657 contigs, completeness of 80 %, < 1 % chimeric contigs) was a hybrid assembly leading to recommend the use of (1) a single individual with large representation of biological tissues, (2) merging both long reads and short paired-end Illumina reads, (3) several assemblers in order to combine the specific advantages of each.

Characterization of Trypanosoma cruzi Sirtuins as Possible Drug Targets for Chagas Disease

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

Molecular identification of food sources in triatomines in the Brazilian northeast: roles of goats and rodents in Chagas disease epidemiology

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

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.