Drug resistance in African trypanosomiasis: the melarsoprol and pentamidine story

• 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
• ISSN: 1471-4922; 1471-5007
• DOI: 10.1016/j.pt.2012.12.005

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.