African animal trypanocide resistance: A systematic review and meta-analysis
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Date
2023-01-04
Journal Title
Journal ISSN
Volume Title
Publisher
Frontiers in Veterinary Science
Abstract
Background: African animal trypanocide resistance (AATr) continues
to undermine global efforts to eliminate the transmission of African
trypanosomiasis in endemic communities. The continued lack of new
trypanocides has precipitated drug misuse and overuse, thus contributing
to the development of the AATr phenotype. In this study, we investigated
the threat associated with AATr by using the major globally available
chemotherapeutical 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; I2 = 46%, P = 0.05), DA vs. HB (SMD =
0.96, 95% CI: 0.47, 1.45; I2 = 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.
Conclusion: AATr is a threat that requires a shift in the current disease control
strategies in most developing nations due to inter-species transmission. Multi-
drug cross-resistance against the only accessible trypanocides is a major publichealth risk, justifying the need to revise the policy in developing countries to
promote control of African trypanosomiasis
Description
Keywords
African animal trypanosomiasis, Trypanosoma brucei brucei, Trypanocide resistance, Drug resistance, T. evansi, T. congolense, T. vivax, Bovine trypanosomiasis