Melarsoprol Resistance in African Trypanosomiasis

Alan Fairlamb, David Horn (Lead / Corresponding author)

Research output: Contribution to journalReview article

13 Citations (Scopus)
83 Downloads (Pure)

Abstract

Arsenicals were introduced as monotherapies for the treatment of human African trypanosomiasis, or sleeping sickness, over 100 years ago. Toxicity has always been an issue but these drugs have proven to be both effective and quite durable. Unfortunately, melarsoprol-resistant parasites emerged as early as the 1970s and were widespread by the late 1990s. Resistance was due to mutations affecting an aquaglyceroporin (AQP2), a parasite solute and drug transporter. This is the only example of widespread drug resistance in trypanosomiasis patients for which the genetic basis is known. This link between melarsoprol and AQP2 illustrates how a drug transporter can improve drug selectivity but, at the same time, highlights the risk of resistance when the drug uptake mechanism is dispensable for parasite viability and virulence.
Original languageEnglish
Pages (from-to)481-492
Number of pages12
JournalTrends in Parasitology
Volume34
Issue number6
Early online date25 Apr 2018
DOIs
Publication statusPublished - Jun 2018

Fingerprint

Melarsoprol
African Trypanosomiasis
Parasites
Drug Resistance
Pharmaceutical Preparations
Aquaglyceroporins
Arsenicals
Trypanosomiasis
Virulence
Mutation

Keywords

  • AQP2
  • AT1
  • Trypanosoma brucei
  • adenosine transporter
  • aquaglyceroporin
  • arsenic
  • pentamidine

Cite this

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Melarsoprol Resistance in African Trypanosomiasis. / Fairlamb, Alan; Horn, David (Lead / Corresponding author).

In: Trends in Parasitology, Vol. 34, No. 6, 06.2018, p. 481-492.

Research output: Contribution to journalReview article

TY - JOUR

T1 - Melarsoprol Resistance in African Trypanosomiasis

AU - Fairlamb, Alan

AU - Horn, David

N1 - WT Grant (203134/Z/16/Z), WT Grant (1003200/Z/12/Z), MRC (K000500/1)

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KW - arsenic

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