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The NHEPACHA Iberoamerican Network, founded on the initiative of a group of researchers from Latin American countries and Spain, aims to establish a research framework for Chagas disease that encompasses diagnosis and treatment. For this purpose, the network has created a questionnaire to gather relevant data on epidemiological, clinical, diagnostic, and therapeutic aspects of the disease. This questionnaire was developed based on a consensus of expert members of the network, with the intention of collecting high-quality standardized data, which can be used interchangeably by the different research centers that make up the NHEPACHA network. Furthermore, the network intends to offer a clinical protocol that can be embraced by other researchers, facilitating comparability among published studies, as well as the development of therapeutic response and progression markers. Author summary: In this work, we present a new clinical questionnaire for the standardized evaluation and collection of clinical data from patients with acute or chronic Trypanosoma cruzi infection, as well as a uniformed database to collect it. The questionnaire has been produced after consensus from clinical experts belonging to the NHEPACHA network, a coalition of clinical research institutions in Latin America and Spain. This tool will facilitate the collection and sharing of high-quality clinical and paraclinical data useful to annotate sample collections, and allow clinically meaningful comparisons between different cohorts. [ABSTRACT FROM AUTHOR]

Chagas disease (CD) is recognized as one of the 20 neglected tropical diseases by the World Health Organization (WHO), posing a significant global health challenge. The objective of this work was to conduct a systematic methodology review to explore the different classifications used to describe the presence and degree of organ involvement in patients with CD since the disease's description in 1909. We searched relevant electronic medical databases from their inception dates to July 2023. We also delved into historical variations and revisions of each classification, the necessary diagnostic methods, their prognostic value, and their uptake. Our study underscores the conspicuous absence of a universally accepted CD classification system for cardiac and digestive involvement, both in the context of clinical trials and within current clinical guidelines. This endeavour will facilitate cross-population comparisons if clinical manifestations and complementary test results are available for each patient, constituting a pivotal stride toward identifying precise prognoses and establishing a minimum data set requisite for a fitting CD classification, tailored to the test availability in both endemic and non-endemic regions. Author summary: Chagas disease (CD) is a serious global health issue, and in our research, we aimed to investigate how doctors classify the impact of this disease on different organs. CD is one of the neglected tropical diseases recognized by the World Health Organization. It is important for us to understand how this disease affects people because it can lead to severe health problems. To conduct our study, we reviewed the various ways doctors have classified CD since it was first described in 1909. We looked at how these classifications have changed over time, the tests used to diagnose CD, and how these classifications are applied in clinical practice and research. One crucial discovery we made during our research is that there isn't a universally accepted classification system for CD, especially when it comes to assessing its impact on the heart and digestive system. This absence of a standard classification system makes it difficult to compare CD cases across different regions and to predict the disease's progression in individual patients. We believe that establishing a standardized classification system for CD is of utmost importance. Such a system would greatly assist doctors and researchers in gaining a better understanding of the disease, making more accurate predictions about how it will affect patients, and improving CD diagnosis and treatment, both in regions where the disease is prevalent and in areas where it's not. In summary, our study highlights the urgent need for a standardized method to classify Chagas disease, which is a significant global health concern. Establishing a common classification system would simplify the study and treatment of the disease, benefiting people worldwide. [ABSTRACT FROM AUTHOR]

Anti‐severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) seroprevalence is used to estimate the proportion of individuals within a population previously infected, to track viral transmission, and to monitor naturally and vaccine‐induced immune protection. However, in sub‐Saharan African settings, antibodies induced by higher exposure to pathogens may increase unspecific seroreactivity to SARS‐CoV‐2 antigens, resulting in false positive responses. To investigate the level and type of unspecific seroreactivitiy to SARS‐CoV‐2 in Africa, we measured immunoglobulin G (IgG), IgA, and IgM to a broad panel of antigens from different pathogens by Luminex in 602 plasma samples from African and European subjects differing in coronavirus disease 2019, malaria, and other exposures. Seroreactivity to SARS‐CoV‐2 antigens was higher in prepandemic African than in European samples and positively correlated with antibodies against human coronaviruses, helminths, protozoa, and especially Plasmodium falciparum. African subjects presented higher levels of autoantibodies, a surrogate of polyreactivity, which correlated with P. falciparum and SARS‐CoV‐2 antibodies. Finally, we found an improved sensitivity in the IgG assay in African samples when using urea as a chaotropic agent. In conclusion, our data suggest that polyreactive antibodies induced mostly by malaria are important mediators of the unspecific anti‐SARS‐CoV‐2 responses, and that the use of dissociating agents in immunoassays could be useful for more accurate estimates of SARS‐CoV‐2 seroprevalence in African settings. [ABSTRACT FROM AUTHOR]

Background: Chagas disease, caused by the parasite Trypanosoma cruzi, is a neglected infectious disease that exerts the highest public health burden in the Americas. There are two anti-parasitic drugs approved for its treatment–benznidazole and nifurtimox—but the absence of biomarkers to early assess treatment efficacy hinders patients´ follow-up. Methodology/Principal findings: We conducted a longitudinal, observational study among a cohort of 106 chronically T. cruzi-infected patients in Cochabamba (Bolivia) who completed the recommended treatment of benznidazole. Participants were followed-up for five years, in which we collected clinical and serological data, including yearly electrocardiograms and optical density readouts from two ELISAs (total and recombinant antigens). Descriptive and statistical analyses were performed to understand trends in data, as well as the relationship between clinical symptoms and serological evolution after treatment. Our results showed that both ELISAs documented average declines up to year three and slight inclines for the following two years. The recorded clinical parameters indicated that most patients did not have any significant changes to their cardiac or digestive symptoms after treatment, at least in the timeframe under investigation, while a small percentage demonstrated either a regression or progression in symptoms. Only one participant met the "cure criterion" of a negative serological readout for both ELISAs by the final year. Conclusions/Significance: The study confirms that follow-up of benznidazole-treated T. cruzi-infected patients should be longer than five years to determine, with current tools, if they are cured. In terms of serological evolution, the single use of a total antigen ELISA might be a more reliable measure and suffice to address infection status, at least in the region of Bolivia where the study was done. Additional work is needed to develop a test-of-cure for an early assessment of drugs´ efficacy with the aim of improving case management protocols. Author summary: Chagas disease is a neglected parasitic disease prevalent throughout the Americas, with approximately seven million people infected. The highest infection rates have been identified in Bolivia. There, we followed for five years a cohort of chronically T. cruzi-infected patients attending the Platform for Integral Care of Chagas disease Patients in Cochabamba. With the aim to understand clinical and serological responses after completing treatment with benznidazole, we recorded clinical symptomatology and collected serum samples to run two ELISAs based on total and recombinant antigens in each yearly follow-up visit. Upon analyzing clinical and serological data, we found there were no major changes in the patients´ clinical status while serological reactivity generally declined until the third year of follow-up, particularly with the total antigen test. Remarkably, only one participant met the cure criterion of negative serological reversion for both ELISAs at the final visit. Our findings confirm that, using currently available tools, the appropriate time to address treatment efficacy is longer than five years. Additional studies are needed to find biomarkers for the early assessment of treatment efficacy. [ABSTRACT FROM AUTHOR]

Background Chagas disease (CD) has significant global health impact, but safe, effective treatments remain elusive. The nitroimidazole fexinidazole is a potential treatment. Methods This double-blind, randomized, placebo-controlled, dose-finding, proof-of-concept study was conducted in Bolivia. Adults with serologically confirmed chronic indeterminate CD and positive PCR were randomly assigned to 1 of 6 fexinidazole regimens (1200 or 1800 mg/day for 2, 4, or 8 weeks) or placebo. Target recruitment was 20 patients/arm. The primary endpoint was sustained parasitological clearance by serial negative qPCR from end of treatment (EOT) until 6 months follow-up in the intention-to-treat (ITT) population. Follow-up was extended to 12 months. Results Enrollment was interrupted after 4/47 patients presented with transient asymptomatic grade 3 and 4 neutropenia. Treatment of ongoing patients was stopped in all patients administered >2 weeks. A total of 40 patients received treatment with fexinidazole from 3 days to 8 weeks. Delayed-onset neutropenia (n = 8) and increased liver enzymes (n = 8) were found in fexinidazole patients vs none in the placebo arm. In the ITT analysis, sustained parasitological clearance from EOT to 12 months follow-up varied between 66.7% (1200 mg–2 week) and 100.0% (1800 mg–2 week). Rapid, sustained clearance of parasitemia was observed in all treated patients with available data, but not in any patients in the placebo group, at 12 months (P =.0056). Further exploratory exposure-response analysis suggested low dosages of fexinidazole may be safe and effective. Conclusions Further evaluation is needed to establish fexinidazole's minimum effective dosage and risk–benefit relationship. Results suggest potential for effective treatment regimens <10 days. Clinical Trials Registration NCT02498782. [ABSTRACT FROM AUTHOR]

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). [ABSTRACT FROM AUTHOR]