Drug resistance in African trypanosomiasis: the melarsoprol and pentamidine story

Melarsoprol and pentamidine represent the two main classes of drugs, the arsenicals and diamidines, historically used to treat the diseases caused by African trypanosomes: sleeping sickness in humans and Nagana in livestock. Cross-resistance to these drugs was first observed over 60 years ago and re...

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Bibliographic Details
Published in:Trends in parasitology 2013-03, Vol.29 (3), p.110-118
Main Authors: Baker, Nicola, de Koning, Harry P, Mäser, Pascal, Horn, David
Format: Article
Language:English
Subjects:
African trypanosomiasis
Animals
AQP2
Aquaglyceroporins - genetics
Aquaglyceroporins - metabolism
arsenicals
AT1
bovine trypanosomiasis
cross resistance
drug resistance
Drug Resistance - genetics
drugs
Gastroenterology and Hepatology
Humans
Infectious Disease
livestock
Melarsoprol - therapeutic use
MIP
MRPA
parasites
parasitology
Pentamidine - therapeutic use
Phylogeny
Trypanocidal Agents - pharmacology
Trypanocidal Agents - therapeutic use
Trypanosoma brucei
Trypanosoma brucei brucei - classification
Trypanosoma brucei brucei - drug effects
Trypanosoma brucei brucei - genetics
Trypanosomiasis, African - drug therapy
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Summary:Melarsoprol and pentamidine represent the two main classes of drugs, the arsenicals and diamidines, historically used to treat the diseases caused by African trypanosomes: sleeping sickness in humans and Nagana in livestock. Cross-resistance to these drugs was first observed over 60 years ago and remains the only example of cross-resistance among sleeping sickness therapies. A Trypanosoma brucei adenosine transporter is well known for its role in the uptake of both drugs. More recently, aquaglyceroporin 2 (AQP2) loss of function was linked to melarsoprol–pentamidine cross-resistance. AQP2, a channel that appears to facilitate drug accumulation, may also be linked to clinical cases of resistance. Here, we review these findings and consider some new questions as well as future prospects for tackling the devastating diseases caused by these parasites.
ISSN:1471-4922
1471-5007
DOI:10.1016/j.pt.2012.12.005