Systematic Review and Meta-Analysis on Human African Trypanocide Resistance

Simple item page
dc.contributor.authorKeneth Iceland, Kasozi
dc.contributor.authorEwan Thomas, MacLeod
dc.contributor.authorSusan Christina, Welburn
dc.date.accessioned2023-02-02T05:16:28Z
dc.date.available2023-02-02T05:16:28Z
dc.date.issued2022-09-25
dc.description.abstractBackground Human African trypanocide resistance (HATr) is a challenge for the eradica- tion of Human African Trypansomiaisis (HAT) following the widespread emergence of increased monotherapy drug treatment failures against Trypanosoma brucei gambiense and T. b. rhodesiense that are associated with changes in pathogen receptors. Methods: Electronic searches of 12 databases and 3 Google search websites for human African trypanocide resistance were performed using a keyword search criterion applied to both laboratory and clinical studies. Fifty-one publications were identified and included in this study using the PRISMA checklist. Data were analyzed using RevMan and random effect sizes were computed for the statistics at the 95% confidence interval. Results: Pentamidine/melarsoprol/nifurtimox cross-resistance is associated with loss of the T. brucei adenosine transporter 1/purine 2 gene (TbAT1/P2), aquaglyceroporins (TbAQP) 2 and 3, followed by the high affinity pentamidine melarsoprol transporter (HAPT) 1. In addition, the loss of the amino acid transporter (AAT) 6 is associated with eflornithine resistance. Nifurtimox/eflornithine combination therapy resistance is associated with AAT6 and nitroreductase loss, and high resistance and parasite regrowth is responsible for treatment relapse. In clinical studies, the TbAT1 proportion of total random effects was 68% (95% CI: 38.0–91.6); I2 = 96.99% (95% CI: 94.6–98.3). Treatment failure rates were highest with melarsoprol followed by eflornithine at 41.49% (95% CI: 24.94–59.09) and 6.56% (3.06–11.25) respectively. HATr-resistant phenotypes used in most laboratory experiments demonstrated significantly higher pentamidine resistance than other trypanocides. Conclusion: The emergence of drug resistance across the spectrum of trypanocidal agents that are used to treat HAT is a major threat to the global WHO target to eliminate HAT by 2030. T. brucei strains were largely resistant to diamidines and the use of high trypanocide concentrations in clinical studies have proved fatal in humans. Studies to develop novel chemotherapeutical agents and identify alternative protein targets could help to reduce the emergence and spread of HATr.en_US
dc.description.sponsorshipKabale Universityen_US
dc.identifier.citationKasozi, K.I.; MacLeod, E.T.; Welburn, S.C. Systematic Review and Meta-Analysis on Human African Trypanocide Resistance. Pathogens 2022, 11, 1100. https://doi.org/ 10.3390/pathogens11101100en_US
dc.identifier.urihttp://hdl.handle.net/20.500.12493/926
dc.language.isoenen_US
dc.publisherMDPI.en_US
dc.rightsAttribution-NonCommercial-NoDerivs 3.0 United States*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/3.0/us/*
dc.subjectHuman African trypanosomiasisen_US
dc.subjectTrypanosomesen_US
dc.subjectDrug resistanceen_US
dc.subjectPentamidinesen_US
dc.subjectNifurtimox/eflornithine combination therapy;en_US
dc.subjectExinidazole;en_US
dc.subjectNECTen_US
dc.subjectTbATen_US
dc.subjectAmino-aquapurine trans- portersen_US
dc.subjectAmino acid transportersen_US
dc.subjectTrypanosoma brucei rhodesienseen_US
dc.subjectTrypanosoma brucei gambienseen_US
dc.subjectNeglected tropical diseasesen_US
dc.titleSystematic Review and Meta-Analysis on Human African Trypanocide Resistanceen_US
dc.typeArticleen_US

Files

Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
pathogens-11-01100.pdf
Size:
760.34 KB
Format:
Adobe Portable Document Format
Description:
Systematic Review and Meta-Analysis on Human African Trypanocide Resistance
Download
License bundle
Now showing 1 - 1 of 1
No Thumbnail Available
Name:
license.txt
Size:
1.71 KB
Format:
Item-specific license agreed upon to submission
Description:
Download

Collections

School of Medicine (KABSOM)