A Rapid Review on the Efficacy and Safety of Pharmacological Treatments for Chagas Disease
Bibliographic record
Abstract
Chagas disease remains a neglected tropical disease, causing significant burden in the Americas and countries that receive immigrants from endemic nations. Current pharmaceutical treatments are suboptimal, not only varying drastically in efficacy, depending on the stage of disease, but also presenting significant risk of adverse events. The objective of this review is to provide a timely update on the efficacy and safety of current trypanocidals. Eligible studies published from January 2015 to December 2020 were retrieved by one reviewer from six electronic databases. Ana-lysis was done with review management software and risk of bias was assessed using tools appropriate for the type of study (i.e., experimental or observational). Thirteen studies (10 observational and three RCTs) were included in the analysis. All 13 studies tested Benznidazole (BNZ) or Nifurtimox (NFX), and two studies also tested Posaconazole (POS) or E1224 (Ravucanazole). BNZ was found to be the most efficacious trypanocidal drug compared to Nifurtimox, POS, and E1224; it also resulted in the highest percentage of adverse effects (AEs) and treatment discontinuation due to its toxicity. Adults experienced higher frequency of neurological AEs while taking BNZ or NFX compared to children. Children had a higher frequency of general AEs compared to adults while taking BNZ. Overall, BNZ is still the most efficacious, but development of new, less toxic drugs is paramount for the quality of life of patients. Studies testing combination therapies and shorter regimens are needed, as is the devising of better clinical parameters and laboratory biomarkers to evaluate treatment efficacy. Considering the variability in methodology and reporting of the studies included in the present analysis, we offer some recommendations for the improvement and replicability of clinical studies investigating pharmacological treatment of Chagas disease. These include full disclosure of methodology, standardization of outcome measures, and always collecting and reporting data on both the efficacy of trypanocidals and on safety outcomes.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.007 | 0.025 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.005 | 0.005 |
| Bibliometrics | 0.009 | 0.008 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.002 | 0.003 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.002 | 0.001 |
| Insufficient payload (model declined to judge) | 0.008 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".