@article{fdi:010081127,
  title = {{I}n vitro susceptibility of {T}rypanosoma cruzi discrete typing units ({DTU}s) to benznidazole : a systematic review and meta-analysis},
  author = {{V}ela, {A}. and {C}oral-{A}lmeida, {M}. and {S}ereno, {D}enis and {C}ostales, {J}. {A}. and {B}arnab{\'e}, {C}hristian and {B}reni{\`e}re, {S}imone {F}r{\'e}d{\'e}rique},
  editor = {},
  language = {{ENG}},
  abstract = {{B}ackground {C}hagas disease, a neglected tropical disease endemic to {L}atin {A}merica caused by the parasite {T}rypanosoma cruzi, currently affects 6-7 million people and is responsible for 12,500 deaths each year. {N}o vaccine exists at present and the only two drugs currently approved for the treatment (benznidazole and nifurtimox), possess serious limitations, including long treatment regimes, undesirable side effects, and frequent clinical failures. {A} link between parasite genetic variability and drug sensibility/efficacy has been suggested, but remains unclear. {T}herefore, we investigated associations between {T}. cruzi genetic variability and in vitro benznidazole susceptibility via a systematic article review and meta-analysis. {M}ethodology/{P}rincipal findings {I}n vitro normalized benznidazole susceptibility indices ({LC}50 and {IC}50) for epimastigote, trypomastigote and amastigote stages of different {T}. cruzi strains were recorded from articles in the scientific literature. {A} total of 60 articles, which include 189 assays, met the selection criteria for the meta-analysis. {M}ean values for each discrete typing unit ({DTU}) were estimated using the meta and metaphor packages through {R} software, and presented in a rainforest plot. {S}ubsequently, a meta-regression analysis was performed to determine differences between estimated mean values by {DTU}/parasite stage/drug incubation times. {F}or each parasite stage, some {DTU} mean values were significantly different, e.g. at 24h of drug incubation, a lower sensitivity to benznidazole of {T}c{I} vs. {T}c{II} trypomastigotes was noteworthy. {N}evertheless, funnel plots detected high heterogeneity of the data within each {DTU} and even for a single strain. {C}onclusions/{S}ignificance {S}everal limitations of the study prevent assigning {DTU}s to different in vitro benznidazole sensitivity groups; however, ignoring the parasite's genetic variability during drug development and evaluation would not be advisable. {O}ur findings highlight the need for establishment of uniform experimental conditions as well as a screening of different {DTU}s during the optimization of new drug candidates for {C}hagas disease treatment. {A}uthor summary {A}lthough a century has elapsed since {C}hagas disease discovery, only two drugs, benznidazole and nifurtimox, are approved for its treatment. {T}hese drugs have significant safety and efficacy limitations and their specific modes of action are still poorly understood. {M}oreover, the causative agent, the protozoan parasite {T}rypanosoma cruzi, displays high genetic variability, which is suspected to affect clinical manifestations and disease outcome. {W}ith these facts in mind, we aimed to elucidate the role of the parasite's genetic background in benznidazole treatment efficacy. {O}ur results unveiled interesting differences in the sensitivity to benznidazole between some {T}. cruzi genotypes, which suggests genetic variability could influence patient cure rates. {A}dditionally, they show the need for uniformity in experimental conditions during laboratory analysis of new drug candidates for {C}hagas disease treatment, and they highlight the importance of screening diverse {T}. cruzi strains from different genetic background as part of the process of drug evaluation and optimization.},
  keywords = {{AMERIQUE} {LATINE}},
  booktitle = {},
  journal = {{PL}o{S} {N}eglected {T}ropical {D}iseases},
  volume = {15},
  numero = {3},
  pages = {e0009269 [16 p.]},
  ISSN = {1935-2735},
  year = {2021},
  DOI = {10.1371/journal.pntd.0009269},
  URL = {https://www.documentation.ird.fr/hor/fdi:010081127},
}