Evidence map›Paper›PMID 38904688›Full record

SynthesisParasitology research2024

Listen to what the animals say: a systematic review and meta-analysis of sterol 14-demethylase inhibitor efficacy for in vivo models of Trypanosoma cruzi infection.

Margarita María Catalina Bisio, Laura Smeldy Jurado Medina, Facundo García-Bournissen, Julián Ernesto Nicolás Gulin

Abstract readSystematic ReviewMeta-Analysis
PubMed Publisher
In one paragraph

Synthesis in Parasitology research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Review
  2. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors.

Margarita María Catalina BisioInstituto Nacional de Parasitología (INP) 'Dr. Mario Fatala Chaben'-ANLIS 'Dr. Carlos G. Malbrán', Buenos Aires, Argentina. Av. Paseo Colón 568, C1097, Buenos Aires, Argentina.
Laura Smeldy Jurado MedinaDipartimento Di Scienze Mediche E Chirurgiche, Alma Mater Studiorum, Università Di Bologna, Via San Giacomo 12, 2 Floor, 55. 40126, BO. Bologna, Italy.
Facundo García-BournissenDivision of Paediatric Clinical Pharmacology, Department of Paediatrics, Schulich School of Medicine & Dentistry, University of Western Ontario, 800 Commissioners Rd. E., Rm. B1-437., London, ON, Canada.
Julián Ernesto Nicolás GulinInstituto de Biología y Medicina Experimental (IBYME), CONICET, Vuelta de Obligado 2490 (C1428ADN), Buenos Aires, Argentina. jgulin@fvet.uba.ar.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Sterol 14-demethylase (CYP51) inhibitors, encompassing new chemical entities and repurposed drugs, have emerged as promising candidates for Chagas disease treatment, based on preclinical studies reporting anti-Trypanosoma cruzi activity. Triazoles like ravuconazole (RAV) and posaconazole (POS) progressed to clinical trials. Unexpectedly, their efficacy was transient in chronic Chagas disease patients, and their activity was not superior to benznidazole (BZ) treatment. This paper aims to summarize evidence on the global activity of CYP51 inhibitors against T. cruzi by applying systematic review strategies, risk of bias assessment, and meta-analysis from in vivo studies. PubMed and Embase databases were searched for original articles, obtaining fifty-six relevant papers meeting inclusion criteria. Characteristics of animal models, parasite strain, treatment schemes, and cure rates were extracted. Primary outcomes such as maximum parasitaemia values, survival, and parasitological cure were recorded for meta-analysis, when possible. The risk of bias was uncertain in most studies. Animals treated with itraconazole, RAV, or POS survived significantly longer than the infected non-treated groups (RR = 4.85 [3.62, 6.49], P < 0.00001), and they showed no differences with animals treated with positive control drugs (RR = 1.01 [0.98, 1.04], P = 0.54). Furthermore, the overall analysis showed that RAV or POS was not likely to achieve parasitological cure when compared with BZ or NFX treatment (OD = 0.49 [0.31, 0.77], P = 0.002). This systematic review contributes to understanding why the azoles had failed in clinical trials and, more importantly, how to improve the animal models of T. cruzi infection by filling the gaps between basic, translational, and clinical research.

Indexed as

14-alpha Demethylase InhibitorsChagas DiseaseDisease Models, AnimalTrypanosoma cruziAnimalsHumansSterol 14-DemethylaseThiazolesTreatment OutcomeTriazolesTrypanocidal Agents14-alpha Demethylase InhibitorsER 30346posaconazoleSterol 14-DemethylaseThiazolesTriazolesTrypanocidal AgentsAnimal modelsChagas diseaseMeta-analysisSterol 14-demethylase inhibitorsSystematic reviewTrypanosoma cruzi

Identifiers

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.