The View From Here

Geoffrey Pasvol

New and ‘old’ drugs for malaria

Geoffrey Pasvol, PhDThis editor’s choice expands on the multiplicity of approaches, new and old, in the pharmacological assault on malaria. These approaches are outlined here:

  • New inhibitors of folate synthesis or folate conversion (antifolates) are being sought, particularly those that inhibit dihydrofolate reductase (DHFR) and that are active in the nanomolar range (see reviews by Anderson and Nzila).
  • New and old antimalarials like chloroquine and artemisinins, repectively, inhibit haem detoxification and lead to parasite death. High throughput screening should identify new targets in this pathway that can bind to haem (review by Rathore et al.).
  • Production of artemisinins previously required laborious extraction from the plant Artemisia annua. Now, Escherichia coli have been genetically engineered to produce an artemisinin precursor (see Martin et al.).
  • Artemisinins should make a considerable contribution in the fight against drug-resistant malaria (Huatalung et al.) and eradication in low transmission areas, probably related to its antigametocytocidal activity (see Barnes et al.).
  • Closer to the bedside, the water-soluble artemisinin artesunate, rather than lipid-soluble artemether, has been shown to reduce mortality in severe malaria when given parenterally (Dondorp et al.). Artesunate has a far more reliable pharmacokinetic profile (Hien et al.) and can also be used rectally (Barnes et al.).
  • Malaria could provide current licensed drugs with a new lease of life. The macrolide azithromycin is efficacious in combination with artesunate or quinine (Noedl et al.); even chloroquine, formerly one of our best antimalarials (and made apparently redundant because of resistance), might yet make a comeback (see Laufer et al.).
  • Meanwhile, on the non-pharmacological front, production of a successful malarial vaccine continues to frustrate the most determined scientists (see Pinzon-Charry et al.).

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Geoffrey Pasvol MA, MB ChB, D Phil, FRCP, FRCPE
Professor of Infection & Tropical Medicine
Imperial College London

Geoffrey Pasvol is Professor of Infection & Tropical Medicine at Imperial College London, based at Northwick Park and St Mary’s Hospitals London. His main research interests are severe malaria and the immunology, diagnosis, treatment and prevention of tuberculosis. He is Director of the Imperial College Wellcome Centre for Clinical Tropical Medicine.