ABSTRACT
Chagas disease (CD) is a neglected tropical disease caused by the parasitic protozoan Trypanosoma cruzi. However, only 20% to 30% of infected individuals will progress to severe symptomatic cardiac manifestations. Current treatments are benznidazole and nifurtimox, which are poorly tolerated regimens. Developing a biomarker to determine the likelihood of patient progression would be helpful for doctors to optimize patient treatment strategies. Such a biomarker would also benefit drug discovery efforts and clinical trials. In this study, we combined untargeted and targeted metabolomics to compare serum samples from T. cruzi-infected individuals who progressed to severe cardiac disease, versus infected individuals who remained at the same disease stage (non-progressors). We identified four unannotated biomarker candidates, which were validated in an independent cohort using both untargeted and targeted analysis techniques. Overall, our findings demonstrate that serum small molecules can predict CD progression, offering potential for clinical monitoring.
ABSTRACT
Background: Chagas disease is an endemic protozoan disease with high prevalence in Latin America. Of those infected, 20-30% will develop chronic Chagas cardiomyopathy (CCC) however, prediction using existing clinical criteria remains poor. In this study, we investigated the utility of left ventricular (LV) echocardiographic speckle-tracking global longitudinal strain (GLS) for early detection of CCC. Methods and results: 139 asymptomatic T. cruzi seropositive subjects with normal heart size and normal LV ejection fraction (EF) (stage A or B) were enrolled in this prospective observational study and underwent paired echocardiograms at baseline and 1-year follow-up. Progressors were participants classified as stage C or D at follow-up due to development of symptoms of heart failure, cardiomegaly, or decrease in LVEF. LV GLS was calculated as the average peak systolic strain of 16 LV segments. Measurements were compared between participants who progressed and did not progress by two-sample t-test, and the odds of progression assessed by multivariable logistic regression. Of the 139 participants, 69.8% were female, mean age 55.8 ± 12.5 years, with 12 (8.6%) progressing to Stage C or D at follow-up. Progressors tended to be older, male, with wider QRS duration. LV GLS was -19.0% in progressors vs. -22.4% in non-progressors at baseline, with 71% higher odds of progression per +1% of GLS (adjusted OR 1.71, 95% CI 1.20-2.44, p = 0.003). Conclusion: Baseline LV GLS in participants with CCC stage A or B was predictive of progression within 1-year and may guide timing of clinical follow-up and promote early detection or treatment.
ABSTRACT
Background : People with tuberculosis disease and their household members may suffer direct out-of-pocket expenses and indirect costs of lost income. These tuberculosis-related costs can worsen poverty, make tuberculosis treatment completion unaffordable, impair quality of life and increase the risk of death. Costs due to tuberculosis are usually defined as catastrophic if they exceed 20% of the pre-disease annual household income. The World Health Organisation strategy to "End TB" and the United Nations Sustainable Development Goals include the target that no households should face catastrophic costs due to tuberculosis. However, there is limited evidence and policy concerning how this global priority of eliminating catastrophic costs due to tuberculosis should be achieved. This systematic review and meta-analysis aims to address this knowledge gap. Methods : Publications assessing interventions that aimed to eliminate catastrophic costs will be identified by searching three electronic databases (PubMed, Scopus and Web of Science) together with reference lists from pertinent publications. We will screen eligible studies, extract data, and assess the risk of bias with the quality assessment tool from the National Heart, Lung, and Blood Institute. Discrepancies will be resolved by discussion between the reviewers. If we find sufficient comparable studies quantifying strategies to eliminate catastrophic costs then a meta-analysis will be performed. This systematic review and meta-analysis is registered with the PROSPERO database (CRD42022292410). Conclusion : This systematic review and meta-analysis aims to rigorously assess the evidence for strategies to eliminate catastrophic costs due to tuberculosis.
