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Clinical microbiology reviews
10, 2018;31 (4):

Recent Development of Visceral Leishmaniasis Treatments: Successes, Pitfalls, and Perspectives.

Fabiana Alves, Graeme Bilbe, Séverine Blesson, Vishal Goyal, Séverine Monnerat, Charles Mowbray, Gina Muthoni Ouattara, Bernard Pécoul, Suman Rijal, Joelle Rode, Alexandra Solomos, Nathalie Strub-Wourgaft, Monique Wasunna, Susan Wells, Eduard E Zijlstra, Byron Arana, Jorge Alvar
Author Information
  1. Fabiana Alves: Drugs for Neglected Diseases initiative (DNDi), Geneva, Switzerland.
  2. Graeme Bilbe: Drugs for Neglected Diseases initiative (DNDi), Geneva, Switzerland.
  3. Séverine Blesson: Drugs for Neglected Diseases initiative (DNDi), Geneva, Switzerland.
  4. Vishal Goyal: Drugs for Neglected Diseases initiative (DNDi), Geneva, Switzerland.
  5. Séverine Monnerat: Drugs for Neglected Diseases initiative (DNDi), Geneva, Switzerland.
  6. Charles Mowbray: Drugs for Neglected Diseases initiative (DNDi), Geneva, Switzerland.
  7. Gina Muthoni Ouattara: Drugs for Neglected Diseases initiative (DNDi), Geneva, Switzerland.
  8. Bernard Pécoul: Drugs for Neglected Diseases initiative (DNDi), Geneva, Switzerland.
  9. Suman Rijal: Drugs for Neglected Diseases initiative (DNDi), Geneva, Switzerland.
  10. Joelle Rode: Drugs for Neglected Diseases initiative (DNDi), Geneva, Switzerland.
  11. Alexandra Solomos: Drugs for Neglected Diseases initiative (DNDi), Geneva, Switzerland.
  12. Nathalie Strub-Wourgaft: Drugs for Neglected Diseases initiative (DNDi), Geneva, Switzerland.
  13. Monique Wasunna: Drugs for Neglected Diseases initiative (DNDi), Geneva, Switzerland.
  14. Susan Wells: Drugs for Neglected Diseases initiative (DNDi), Geneva, Switzerland.
  15. Eduard E Zijlstra: Drugs for Neglected Diseases initiative (DNDi), Geneva, Switzerland.
  16. Byron Arana: Drugs for Neglected Diseases initiative (DNDi), Geneva, Switzerland.
  17. Jorge Alvar: Drugs for Neglected Diseases initiative (DNDi), Geneva, Switzerland jalvar@dndi.org.
PMID: 30158301 DOI: 10.1128/CMR.00048-18

Abstract

Research in visceral leishmaniasis in the last decade has been focused on how better to use the existing medicines as monotherapy or in combination. Systematic research by geographical regions has shown that a universal treatment is far from today's reality. Substantial progress has been made in the elimination of kala-azar in South Asia, with a clear strategy on first- and second-line therapy options of single-dose liposomal amphotericin B and a combination of paromomycin and miltefosine, respectively, among other interventions. In Eastern Africa, sodium stibogluconate (SSG) and paromomycin in combination offer an advantage compared to the previous SSG monotherapy, although not exempted of limitations, as this therapy requires 17 days of painful double injections and bears the risk of SSG-related cardiotoxicity. In this region, attempts to improve the combination therapy have been unsuccessful. However, pharmacokinetic studies have led to a better understanding of underlying mechanisms, like the underexposure of children to miltefosine treatment, and an improved regimen using an allometric dosage. Given this global scenario of progress and pitfalls, we here review what steps need to be taken with existing medicines and highlight the urgent need for oral drugs. Furthermore, it should be noted that six candidates belonging to five new chemical classes are reaching phase I, ensuring an optimistic near future.

Keywords

new chemical entities treatment visceral leishmaniasis

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MeSH Term

Antiprotozoal Agents
Biomedical Research
Drug Discovery
Humans
Leishmaniasis, Visceral

Chemicals

Antiprotozoal Agents
Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Review
Article has an altmetric score of 32

Word Cloud

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