Human African trypanosomiasis: Potential therapeutic benefits of an alternative suramin and melarsoprol regimen

Frank W. Jennings, Jean Rodgers, Barbara Bradley, G. Gettinby, Peter G.E. Kennedy, M. Murray

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Treatment of late-stage human African trypanosomiasis is complicated by the presence of trypanosomes within the central nervous system (CNS). The regimen commonly prescribed to treat CNS-stage disease involves the use of the trypanocidal drugs suramin and melarsoprol. Suramin does not cross the blood-brain barrier efficiently and therefore, at normal dosages, will not cure CNS-stage infections. An initial treatment with suramin is given to eliminate the parasites from the peripheral tissues. This is followed by a course of intravenous melarsoprol, which can enter the CNS. However, melarsoprol not only produces severe adverse reactions but also is extremely painful to administer. One possible method to help alleviate these problems is to reduce the total amount of melarsoprol in the treatment regimen. This study indicates a synergism between suramin and melarsoprol and demonstrates that experimental murine CNS-trypanosomiasis can be cured with a single intraperitoneal dose of 20 mg/kg suramin followed almost immediately by 0.05 ml (4.5 μmol) topical melarsoprol. These dosages will not cure the infection when administered as monotherapies. Moreover, the timing of the drug administration appears to be crucial to the successful outcome of the regimen. If the interval between injection of suramin and application of topical melarsoprol is extended from 15 min to 3 or 7 days, the infections are not cured. Although extended relapse times occur following these regimens when compared with monotherapy approaches. Thus, there is strong evidence that injected suramin and topical melarsoprol should be given almost simultaneously to achieve the most effective combination of the two drugs.
Original languageEnglish
Pages (from-to)381-388
Number of pages7
JournalParasitology International
Volume51
Issue number4
DOIs
Publication statusPublished - Dec 2002

Fingerprint

Melarsoprol
African Trypanosomiasis
Suramin
Trypanosomiasis
Central Nervous System
Therapeutics
Trypanocidal Agents
Central Nervous System Infections
Central Nervous System Diseases
Drug Combinations
Infection
Blood-Brain Barrier
Parasites

Keywords

  • melarsoprol
  • suramin
  • combination chemotherapy
  • human African trypanosomiasis
  • mouse-model

Cite this

Jennings, Frank W. ; Rodgers, Jean ; Bradley, Barbara ; Gettinby, G. ; Kennedy, Peter G.E. ; Murray, M. / Human African trypanosomiasis: Potential therapeutic benefits of an alternative suramin and melarsoprol regimen. In: Parasitology International. 2002 ; Vol. 51, No. 4. pp. 381-388.
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Human African trypanosomiasis: Potential therapeutic benefits of an alternative suramin and melarsoprol regimen. / Jennings, Frank W.; Rodgers, Jean; Bradley, Barbara; Gettinby, G.; Kennedy, Peter G.E.; Murray, M.

In: Parasitology International, Vol. 51, No. 4, 12.2002, p. 381-388.

Research output: Contribution to journalArticle

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