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Updated: Aug 23, 2025
Purification of Extracellular Trypanosomes, Including African, from Blood by Anion-Exchangers Diethylaminoethyl-cellulose Columns
Published on: April 6, 2019
Systematic Review and Meta-Analysis on Human African Trypanocide Resistance
Keneth Iceland Kasozi1,2, Ewan Thomas MacLeod1, Susan Christina Welburn1,3
1Infection Medicine, Deanery of Biomedical Sciences, Edinburgh Medical School, College of Medicine and Veterinary Medicine, The University of Edinburgh, Edinburgh EH8 9JZ, UK.
Human African trypanocide resistance (HATr) threatens HAT eradication, with drug failures linked to genetic changes in Trypanosoma brucei. Developing new treatments and targets is crucial to combat resistance and meet WHO elimination goals.
Area of Science:
- Parasitology
- Molecular Biology
- Drug Resistance Studies
Background:
- Human African Trypanosomiasis (HAT) eradication is challenged by widespread drug resistance.
- Treatment failures are increasing for both Trypanosoma brucei gambiense and T. b. rhodesiense.
- Resistance is associated with genetic alterations in parasite receptors.
Purpose of the Study:
- To systematically review and analyze the literature on human African trypanocide resistance (HATr).
- To identify the molecular mechanisms and clinical implications of HATr.
- To inform strategies for combating drug resistance in HAT.
Main Methods:
- Conducted comprehensive electronic searches across 12 databases and 3 Google search websites.
- Included 51 publications identified using the PRISMA checklist.
- Analyzed data using RevMan with random effect sizes and 95% confidence intervals.
Main Results:
- Cross-resistance to pentamidine, melarsoprol, and nifurtimox linked to loss of TbAT1/P2, TbAQP 2/3, and HAPT1.
- Eflornithine resistance associated with loss of amino acid transporter 6 (AAT6).
- Nifurtimox/eflornithine combination therapy resistance linked to AAT6 and nitroreductase loss; melarsoprol showed highest failure rates (41.49%).
Conclusions:
- Emerging drug resistance to trypanocidal agents poses a major threat to the WHO's 2030 HAT elimination target.
- T. brucei strains exhibit significant resistance to diamidines, and high drug concentrations can be fatal.
- Novel chemotherapeutic agents and alternative protein targets are needed to mitigate HATr.
