African animal trypanocide resistance: A systematic review and meta-analysis
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Date
2024-02
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Abstract
African animals resistance ( AATr) continues to undermine global efforts to eliminate the transmission
of africa intrypanosomiasis in endemic communities. the continued lack of new trypanocides has participated
drug misuse and over use, thus contributing to the devlopment of the AADr phenotype. in this study, we investigated
the threate associated with AAtr by using the major globally available chemotherapeutic agents.
Methods: A total of seven electronic databases were screened for an article
on trypanocide resistance in AATr by using keywords on preclinical and clinical
trials with the number of animals with treatment relapse, days taken to relapse,
and resistant gene markers using the PRISMA checklist. Data were cleaned
using the SR deduplicator and covidence and analyzed using Cochrane
RevMan®. Dichotomous outputs were presented using risk ratio (RR), while
continuous data were presented using the standardized mean difference (SMD) at a 95% confidence interval.
Results: A total of eight publications in which diminazene aceturate (DA),
isometamidium chloride (ISM), and homidium chloride/bromide (HB) were
identified as the major trypanocides were used. In all preclinical studies, the
development of resistance was in the order of HB > ISM > DA. DA vs. ISM
(SMD = 0.15, 95% CI: −0.54, 0.83; I
2 = 46%, P = 0.05), DA vs. HB (SMD =
0.96, 95% CI: 0.47, 1.45; I
2 = 0%, P = 0.86), and HB vs. ISM (SMD = −0.41,
95% CI: −0.96, 0.14; I2 = 5%, P = 0.38) showed multiple cross-resistance.
Clinical studies also showed evidence of multi-drug resistance on DA and ISM
(RR = 1.01, 95% CI: 0.71–1.43; I2 = 46%, P = 0.16). To address resistance,
most preclinical studies increased the dosage and the treatment time, and this
failed to improve the patient’s prognosis. Major markers of resistance explored
include TbAT1, P1/P2 transporters, folate transporters, such as F-I, F-II, F-III,
and polyamine biosynthesis inhibitors. In addition, immunosuppressed hosts
favor the development of AATr.