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Trypanosomiases are diseases caused by various species of protozoan parasite in the genus Trypanosoma, each presenting with distinct clinical manifestations and prognoses. Infections can affect multiple organs, with Trypanosoma cruzi predominantly affecting the heart and digestive system, leading to American trypanosomiasis or Chagas disease, and Trypanosoma brucei primarily causing a disease of the central nervous system known as human African trypanosomiasis or sleeping sickness. In this Review, we discuss the effects of these infections on the heart, with particular emphasis on Chagas disease, which continues to be a leading cause of cardiomyopathy in Latin America. The epidemiology of Chagas disease has changed substantially since 1990 owing to the emigration of over 30 million Latin American citizens, primarily to Europe and the USA. This movement of people has led to the global dissemination of individuals infected with T. cruzi. Therefore, cardiologists worldwide must familiarize themselves with Chagas disease and the severe, chronic manifestation - Chagas cardiomyopathy - because of the expanded prevalence of this disease beyond traditional endemic regions.

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Background: There is a lack of up-to-date estimates about the prevalence of Chagas disease (ChD) clinical presentations and, therefore, we aimed to assess the prevalence of clinical forms of ChD among seropositive adults, pooling available data. Methods: A systematic review was conducted in Medline, Embase, Biblioteca Virtual em Saúde and Cochrane databases looking for studies published from 1990 to August 2023, which investigated the prevalence of ChD clinical forms among seropositive adults, including: (i) indeterminate phase, (ii) chronic Chagas cardiomyopathy (CCM), (iii) digestive and (iv) mixed (CCM + digestive) forms. Pooled estimates and 95% confidence intervals (CI) were calculated using random-effects models. Studies quality and risk of bias was assessed with the Leboeuf-Yde and Lauritsen tool. Heterogeneity was assessed with the I2 statistic. The study was registered in the PROSPERO database (CRD42022354237). Findings: 1246 articles were selected for screening and 73 studies were included in the final analysis (17,132 patients, 44% men). Most studies were conducted with outpatients (n = 50), followed by population-based studies (n = 15). The pooled prevalence of the ChD clinical forms was: indeterminate 42.6% (95% CI: 36.9-48.6), CCM 42.7% (95% CI: 37.3-48.3), digestive 17.7% (95% CI: 14.9-20.9), and mixed 10.2% (95% CI: 7.9-13.2). In population-based studies, prevalence was lower for CCM (31.2%, 95% CI: 24.4-38.9) and higher for indeterminate (47.2%, 95% CI: 39.0-55.5) form. In meta-regression, age was inversely associated with the prevalence of indeterminate (ß = -0.05, P < 0.001) form, and directly associated with CCM (ß = 0.06, P < 0.001) and digestive (ß = 0.02, P < 0.001) forms. Heterogeneity was overall high. Interpretation: Compared to previous publications, our pooled estimates show a higher prevalence of CCM among ChD seropositive patients, but similar rates of the digestive form. Funding: This study was funded by the World Heart Federation, through a research collaboration with Novartis Pharma AG.

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Chagas disease affects approximately 7 million people worldwide in Latin America and is a neglected tropical disease. Twenty to thirty percent of chronically infected patients develop chronic Chagas cardiomyopathy decades after acute infection. Identifying biomarkers of Chagas disease progression is necessary to develop better therapeutic and preventive strategies. Circulating microRNAs are increasingly reliable biomarkers of disease and therapeutic targets. To identify new circulating microRNAs for Chagas disease, we performed exploratory small RNA sequencing from the plasma of patients and performed de novo miRNA prediction, identifying potential new microRNAs. The levels of the new microRNAs temporarily named miR-Contig-1519 and miR-Contig-3244 and microRNAs that are biomarkers for nonchagasic cardiomyopathies, such as miR-148a-3p and miR-224-5p, were validated by quantitative reverse transcription. We found a specific circulating microRNA signature defined by low miR-Contig-3244, miR-Contig-1519, and miR-148a-3 levels but high miR-224-5p levels for patients with chronic Chagas disease. Finally, we predicted in silico that these altered circulating microRNAs could affect the expression of target genes involved in different cellular pathways and biological processes, which we will explore in the future.

Assuntos

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Chagas disease (ChD), a Neglected Tropical Disease, has witnessed a transformative epidemiological landscape characterized by a trend of reduction in prevalence, shifting modes of transmission, urbanization, and globalization. Historically a vector-borne disease in rural areas of Latin America, effective control measures have reduced the incidence in many countries, leading to a demographic shift where most affected individuals are now adults. However, challenges persist in regions like the Gran Chaco, and emerging oral transmission in the Amazon basin adds complexity. Urbanization and migration from rural to urban areas and to non-endemic countries, especially in Europe and the US, have redefined the disease's reach. These changing patterns contribute to uncertainties in estimating ChD prevalence, exacerbated by the lack of recent data, scarcity of surveys, and reliance on outdated models. Besides, ChD's lifelong natural history, marked by acute and chronic phases, introduces complexities in diagnosis, particularly in non-endemic regions where healthcare provider awareness is low. The temporal dissociation of infection and clinical manifestations, coupled with underreporting, has rendered ChD invisible in health statistics. Deaths attributed to ChD cardiomyopathy often go unrecognized, camouflaged under alternative causes. Understanding these challenges, the RAISE project aims to reassess the burden of ChD and ChD cardiomyopathy. The project is a collaborative effort of the World Heart Federation, Novartis Global Health, the University of Washington's Institute for Health Metrics and Evaluation, and a team of specialists coordinated by Brazil's Federal University of Minas Gerais. Employing a multidimensional strategy, the project seeks to refine estimates of ChD-related deaths, conduct systematic reviews on seroprevalence and prevalence of clinical forms, enhance existing modeling frameworks, and calculate the global economic burden, considering healthcare expenditures and service access. The RAISE project aspires to bridge knowledge gaps, raise awareness, and inform evidence-based health policies and research initiatives, positioning ChD prominently on the global health agenda.

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BACKGROUND: Chagas disease (CD) is a neglected disease affecting millions worldwide, yet little is known about its economic burden. This systematic review is part of RAISE project, a broader study that aims to estimate the global prevalence, mortality, and health and economic burden attributable to chronic CD and Chronic Chagas cardiomyopathy. The objective of this study was to assess the main costs associated with the treatment of CD in both endemic and non-endemic countries. METHODS: An electronic search of the Medline, Lilacs, and Embase databases was conducted until 31st, 2022, to identify and select economic studies that evaluated treatment costs of CD. No restrictions on place or language were made. Complete or partial economic analyses were included. RESULTS: Fifteen studies were included, with two-thirds referring to endemic countries. The most commonly investigated cost components were inpatient care, exams, surgeries, consultation, drugs, and pacemakers. However, significant heterogeneity in the estimation methods and presentation of data was observed, highlighting the absence of standardization in the measurement methods and cost components. The most common component analyzed using the same metric was hospitalization. The mean annual hospital cost per patient ranges from $25.47 purchasing power parity US dollars (PPP-USD) to $18,823.74 PPP-USD, and the median value was $324.44 PPP-USD. The lifetime hospital cost per patient varies from $209,44 PPP-USD for general care to $14,351.68 PPP-USD for patients with heart failure. DISCUSSION: Despite the limitations of the included studies, this study is the first systematic review of the costs of CD treatment. The findings underscore the importance of standardizing the measurement methods and cost components for estimating the economic burden of CD and improving the comparability of cost components magnitude and cost composition analysis. Finally, assessing the economic burden is essential for public policies designed to eliminate CD, given the continued neglect of this disease.

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OBJECTIVE: To describe clinical, epidemiological and management information on cases of acute Chagas disease (ACD) by oral transmission in the state of Amazonas in western Amazon. METHODS: Manual and electronic medical records of patients diagnosed with ACD at the Fundação de Medicina Tropical Doutor Heitor Vieira Dourado (FMT-HVD) were included. RESULTS: There were 147 cases of acute CD registered from 10 outbreaks that occurred in the state of Amazonas between 2004 and 2022. The transmission pathway was through oral route, with probable contaminated palm fruit juice (açaí and/or papatuá), and involved people from the same family, friends or neighbours. Of 147 identified cases, 87 (59%) were males; cases were aged 10 months to 82 years. The most common symptom was the febrile syndrome (123/147; 91.8%); cardiac alterations were present in 33/100 (33%), (2/147; 1.4%) had severe ACD with meningoencephalitis, and 12 (8.2%) were asymptomatic. Most cases were diagnosed through thick blood smear (132/147; 89.8%), a few (14/147; 9.5%) were diagnosed by serology and (1/147; 0.7%) by polymerase chain reaction (PCR) and blood culture. In all these outbreaks, 74.1% of the patients were analysed by PCR, and Trypanosoma cruzi TcIV was detected in all of them. No deaths were recorded. The incidence of these foci coincided with the fruit harvest period in the state of Amazonas. CONCLUSION: The occurrence of ACD outbreaks in the Amazon affected individuals of both sexes, young adults, living in rural and peri-urban areas and related to the consumption of regional foods. Early diagnosis is an important factor in surveillance. There was a low frequency of cardiac alterations. Continuous follow-up of most patients was not carried out due to difficulty in getting to specialised centres; therefore, little is known about post-treatment.

Assuntos

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BACKGROUND: COVID-19 has become a major public health problem after the outbreak caused by SARS-CoV-2 virus. Great efforts to contain COVID-19 transmission have been applied worldwide. In this context, accurate and fast diagnosis is essential. METHODS: In this prospective study, we evaluated the clinical performance of three different RNA-based molecular tests - RT-qPCR (Charité protocol), RT-qPCR (CDC (USA) protocol) and RT-LAMP - and one rapid test for detecting anti-SARS-CoV-2 IgM and IgG antibodies. RESULTS: Our results demonstrate that RT-qPCR using the CDC (USA) protocol is the most accurate diagnostic test among those evaluated, while oro-nasopharyngeal swabs are the most appropriate biological sample. RT-LAMP was the RNA-based molecular test with lowest sensitivity while the serological test presented the lowest sensitivity among all evaluated tests, indicating that the latter test is not a good predictor of disease in the first days after symptoms onset. Additionally, we observed higher viral load in individuals who reported more than 3 symptoms at the baseline. Nevertheless, viral load had not impacted the probability of testing positive for SARS-CoV-2. CONCLUSION: Our data indicates that RT-qPCR using the CDC (USA) protocol in oro-nasopharyngeal swabs samples should be the method of choice to diagnosis COVID-19.

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OBJECTIVES: To determine the comparative efficacy and safety of a fixed dose of benznidazole (BZN) with an adjusted-dose for Trypanosoma cruzi-seropositive adults without cardiomyopathy. METHODS: We conducted a systematic review and individual participant data (IPD) meta-analysis following Cochrane methods, and the PRISMA-IPD statement for reporting. Randomised controlled trials (RCTs) allocating participants to fixed or adjusted doses of BZN for T. cruzi-seropositive adults without cardiomyopathy were included. We searched (December 2021) Cochrane, MEDLINE, EMBASE, LILACS and trial registries and contacted Chagas experts. Selection, data extraction, risk of bias assessment using the Cochrane tool, and a GRADE summary of finding tables were performed independently by pairs of reviewers. We conducted a random-effects IPD meta-analysis using the one-stage strategy, or, if that was impossible, the two-stage strategy. RESULTS: Five RCTs (1198 patients) were included, none directly comparing fixed with adjusted doses of BZN. Compared to placebo, BZN therapy was strongly associated with negative qPCR and sustainable parasitological clearance regardless of the type of dose and subgroup analysed. For negative qPCR, the fixed/adjusted rate of odds ratios (RORF/A ) was 8.83 (95% CI 1.02-76.48); for sustained parasitological clearance, it was 4.60 (95% CI 0.40-52.51), probably indicating at least non-inferior effect of fixed doses, with no statistically significant interactions by scheme for global and most subgroup estimations. The RORF/A for treatment interruption due to adverse events was 0.44 (95% CI 0.14-1.38), probably indicating no worse tolerance of fixed doses. CONCLUSIONS: We found no direct comparison between fixed and adjusted doses of BZN. However, fixed doses versus placebo are probably not inferior to weight-adjusted doses of BZN versus placebo in terms of parasitological efficacy and safety. Network IPD meta-analysis, through indirect comparisons, may well provide the best possible answers in the near future. REGISTRATION: The study protocol was registered in PROSPERO (CRD42019120905).

Assuntos

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Increasing numbers of travellers returning from Cuba with dengue virus infection were reported to the GeoSentinel Network from June to September 2022, reflecting an ongoing local outbreak. This report demonstrates the importance of travellers as sentinels of arboviral outbreaks and highlights the need for early identification of travel-related dengue.

Assuntos