African animal trypanocide resistance: A systematic review and meta-analysis
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...
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Frontiers in Veterinary Science
2023
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| Online Access: | http://hdl.handle.net/20.500.12493/1144 |
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| author | Keneth Iceland, Kasozi Ewan, Thomas MacLeod Susan, Christina Welburn |
| author_facet | Keneth Iceland, Kasozi Ewan, Thomas MacLeod Susan, Christina Welburn |
| author_sort | Keneth Iceland, Kasozi |
| collection | KAB-DR |
| description | 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 |
| format | Article |
| id | oai:idr.kab.ac.ug:20.500.12493-1144 |
| institution | KAB-DR |
| language | English |
| publishDate | 2023 |
| publisher | Frontiers in Veterinary Science |
| record_format | dspace |
| spelling | oai:idr.kab.ac.ug:20.500.12493-11442024-01-17T04:48:37Z African animal trypanocide resistance: A systematic review and meta-analysis Keneth Iceland, Kasozi Ewan, Thomas MacLeod Susan, Christina Welburn African animal trypanosomiasis Trypanosoma brucei brucei Trypanocide resistance Drug resistance T. evansi T. congolense T. vivax Bovine trypanosomiasis 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 Kabale University 2023-04-20T13:08:08Z 2023-04-20T13:08:08Z 2023-01-04 Article http://hdl.handle.net/20.500.12493/1144 en Attribution-NonCommercial-NoDerivs 3.0 United States http://creativecommons.org/licenses/by-nc-nd/3.0/us/ application/pdf Frontiers in Veterinary Science |
| spellingShingle | African animal trypanosomiasis Trypanosoma brucei brucei Trypanocide resistance Drug resistance T. evansi T. congolense T. vivax Bovine trypanosomiasis Keneth Iceland, Kasozi Ewan, Thomas MacLeod Susan, Christina Welburn African animal trypanocide resistance: A systematic review and meta-analysis |
| title | African animal trypanocide resistance: A systematic review and meta-analysis |
| title_full | African animal trypanocide resistance: A systematic review and meta-analysis |
| title_fullStr | African animal trypanocide resistance: A systematic review and meta-analysis |
| title_full_unstemmed | African animal trypanocide resistance: A systematic review and meta-analysis |
| title_short | African animal trypanocide resistance: A systematic review and meta-analysis |
| title_sort | african animal trypanocide resistance a systematic review and meta analysis |
| topic | African animal trypanosomiasis Trypanosoma brucei brucei Trypanocide resistance Drug resistance T. evansi T. congolense T. vivax Bovine trypanosomiasis |
| url | http://hdl.handle.net/20.500.12493/1144 |
| work_keys_str_mv | AT kenethicelandkasozi africananimaltrypanocideresistanceasystematicreviewandmetaanalysis AT ewanthomasmacleod africananimaltrypanocideresistanceasystematicreviewandmetaanalysis AT susanchristinawelburn africananimaltrypanocideresistanceasystematicreviewandmetaanalysis |