Funding for Chagas Disease: A 10-Year (2009–2018) Survey

Sangenito, Leandro S.; Branquinha, Marta H.; Santos, André Luis Souza dos

doi:10.3390/tropicalmed5020088

Cited by 17 publications

(19 citation statements)

References 25 publications

(53 reference statements)

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“…This systematic review has several limitations. As a neglected tropical disease, scarce investment over time has limited the generation of high-quality evidence ( 51 ). A significant risk of bias has been detected among most of the studies resulting from small sample sizes, differences among study designs, differences not reporting on basal characteristics, different CCC assessments, and PCR methods along with the fact that most of the studies were not even designed for this purpose.…”

Section: Discussionmentioning

confidence: 99%

Association Between Trypanosoma cruzi DNA in Peripheral Blood and Chronic Chagasic Cardiomyopathy: A Systematic Review

Bosch-Nicolau

Espinosa-Pereiro

Salvador

et al. 2022

Front. Cardiovasc. Med.

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Chronic chagasic cardiomyopathy (CCC) is the most important complication of patients with Chagas disease (CD). The role of persistent detection of DNA in peripheral blood and its association to CCC is unknown. We performed a systematic review up to July 2021, including studies that reported ratios of CCC and PCR positivity among non-treated adult patients. We identified 749 records and selected 12 for inclusion corresponding to 1,686 patients. Eight studies were performed in endemic countries and 4 in non-endemic countries. Only two studies showed an association between CCC and Trypanosoma cruzi parasitemia by means of PCR detection. Six studies reported greater positive PCR ratios among patients with CCC than in the patients with indeterminate chagas disease (ICD) with no statistical significance. A significant risk of bias has been detected among most of the studies. Therefore, while we performed a meta-analysis, wide inter-study heterogeneity impeded its interpretation.ConclusionsWith the available information, we could not establish a correlation between PCR-detectable parasitemia and CCC.Systematic Review Registration:https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020216072, identifier: CRD42020216072.

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Section: Discussionmentioning

confidence: 99%

Association Between Trypanosoma cruzi DNA in Peripheral Blood and Chronic Chagasic Cardiomyopathy: A Systematic Review

Bosch-Nicolau

Espinosa-Pereiro

Salvador

et al. 2022

Front. Cardiovasc. Med.

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“…It is a serious health problem in many countries in Latin America, and it has spread to North America, Europe, and Asia. It is estimated that 8 million people are infected worldwide, with 6 to 7 million in 21 countries in Latin America ( Sangenito et al., 2020 ). In recent years, oral transmission of the disease has been a major contributor to the increased number of acute new cases.…”

Section: Introductionmentioning

confidence: 99%

Air Pollution’s Impact on Cardiac Remodeling in an Experimental Model of Chagas Cardiomyopathy

Fonseca

Pessoa²,

Ribeiro³

et al. 2022

Front. Cell. Infect. Microbiol.

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BackgroundChagas disease is characterized by intense myocardial fibrosis stimulated by the exacerbated production of inflammatory cytokines, oxidative stress, and apoptosis. Air pollution is a serious public health problem and also follows this same path. Therefore, air pollution might amplify the inflammatory response of Chagas disease and increase myocardial fibrosis.MethodsWe studied groups of Trypanosoma cruzi infected Sirius hamsters (Chagas=CH and Chagas exposed to pollution=CH+P) and 2 control groups (control healthy animals=CT and control exposed to pollution=CT+P). We evaluated acute phase (60 days post infection) and chronic phase (10 months). Echocardiograms were performed to assess left ventricular systolic and diastolic diameter, in addition to ejection fraction. Interstitial collagen was measured by morphometry in picrosirius red staining tissue. The evaluation of inflammation was performed by gene and protein expression of cytokines IL10, IFN-γ, and TNF; oxidative stress was quantified by gene expression of NOX1, MnSOD, and iNOS and by analysis of reactive oxygen species; and apoptosis was performed by gene expression of BCL2 and Capsase3, in addition to TUNEL analysis.ResultsChagas groups had increased collagen deposition mainly in the acute phase, but air pollution did not increase this deposition. Also, Chagas groups had lower ejection fraction in the acute phase (p = 0.002) and again air pollution did not worsen ventricular function or dilation. The analysis of the inflammation and oxidative stress pathways were also not amplified by air pollution. Apoptosis analysis showed increased expression of BCL2 and Caspase3 genes in chagasic groups in the acute phase, with a marginal p of 0.054 in BCL2 expression among infected groups, and TUNEL technique showed amplified of apoptotic cells by pollution among infected groups.ConclusionsA possible modulation of the apoptotic pathway was observed, inferring interference from air pollution in this pathway. However, it was not enough to promote a greater collagen deposition, or worsening ventricular function or dilation caused by air pollution in this model of Chagas cardiomyopathy.

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“…5 The Disability-Adjusted Life-Years (DALYs) attributed to CD is about 700,000 DALYs, resulting in an overall economic impact of more than impressive US$ 7.2 billion. 6 , 7 , 8 …”

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confidence: 99%

Repositioning drug strategy against Trypanosoma cruzi: lessons learned from HIV aspartyl peptidase inhibitors

Sangenito

d’Avila-Levy

Branquinha

et al. 2022

Mem. Inst. Oswaldo Cruz

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Chagas disease (CD) is an old neglected problem that affects more than 6 million people through 21 endemic countries in Latin America. Despite being responsible for more than 12 thousand deaths per year, the disease disposes basically of two drugs for its treatment, the nitroimidazole benznidazole and the nitrofuran nifurtimox. However, these drugs have innumerous limitations that greatly reduce the chances of cure. In Brazil, for example, only benznidazole is available to treat CD patients. Therefore, some proof-of-concept phase II clinical trials focused on improving the current treatment with benznidazole, also comparing it with repositioned drugs or combining them. Indeed, repositioning already marketed drugs in view of combating neglected tropical diseases is a very interesting approach in the context of decreased time for approval, better treatment options and low cost for development and implementation. After the introduction of human immunodeficiency virus aspartyl peptidase inhibitors (HIV-PIs) in the treatment of acquired immune deficiency syndrome (AIDS), the prevalence and incidence of parasitic, fungal and bacterial co-infections suffered a marked reduction, making these HIV-PIs attractive for drug repositioning. In this line, the present perspective presents the promising and beneficial data concerning the effects of HIV-PIs on the clinically relevant forms of Trypanosoma cruzi (i.e., trypomastigotes and amastigotes) and also highlights the ultrastructural and physiological targets for the HIV-PIs on this parasite. Therefore, we raise the possibility that HIV-PIs could be considered as alternative treatment options in the struggle against CD.

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Funding for Chagas Disease: A 10-Year (2009–2018) Survey

Cited by 17 publications

References 25 publications

Association Between Trypanosoma cruzi DNA in Peripheral Blood and Chronic Chagasic Cardiomyopathy: A Systematic Review

Association Between Trypanosoma cruzi DNA in Peripheral Blood and Chronic Chagasic Cardiomyopathy: A Systematic Review

Air Pollution’s Impact on Cardiac Remodeling in an Experimental Model of Chagas Cardiomyopathy

Repositioning drug strategy against Trypanosoma cruzi: lessons learned from HIV aspartyl peptidase inhibitors

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