Ex-vivo Sensitivity of Plasmodium falciparum to Common Anti-malarial Drugs: The Case of Kéniéroba, a Malaria Endemic Village in Mali

Drugs R D. 2020 Sep;20(3):249-255. doi: 10.1007/s40268-020-00313-4.

Abstract

Background: In 2006, the National Malaria Control Program in Mali recommended artemisinin-based combination therapy as the first-line treatment for uncomplicated malaria. Since the introduction of artemisinin-based combination therapy, few reports are available on the level of resistance of Plasmodium falciparum to the most common anti-malarial drugs in Mali.

Methods: From 2016 to 2017, we assessed the ex-vivo drug sensitivity of P. falciparum isolates in Kéniéroba, a village located in a rural area of southern Mali. We collected P. falciparum isolates from malaria-infected children living in Kéniéroba. The isolates were tested for ex-vivo sensitivity to commonly used anti-malarial drugs, namely chloroquine, quinine, amodiaquine, mefloquine, lumefantrine, dihydroartermisinin, and piperaquine. We used the 50% inhibitory concentration determination method, which is based on the incorporation of SYBR® Green into the parasite's genetic material.

Results: Plasmodium falciparum isolates were found to have a reduced ex-vivo sensitivity to quinine (25.7%), chloroquine (12.2%), amodiaquine (2.7%), and mefloquine (1.3%). In contrast, the isolates were 100% sensitive to lumefantrine, dihydroartermisinin, and piperaquine. A statistically significant correlation was found between 50% inhibitory concentration values of quinine and amodiaquine (r = 0.80; p < 0.0001).

Conclusions: Plasmodium falciparum isolates were highly sensitive to dihydroartermisinin, lumefantrine, and piperaquine and less sensitive to amodiaquine (n = 2), mefloquine (n = 1), and quinine (n = 19). Therefore, our data support the previously reported increasing trend in chloroquine sensitivity in Mali.

MeSH terms

  • Adolescent
  • Amodiaquine / pharmacology
  • Antimalarials / pharmacology*
  • Artemisinins / pharmacology
  • Child
  • Child, Preschool
  • Chloroquine / pharmacology
  • Drug Resistance
  • Endemic Diseases
  • Humans
  • Infant
  • Inhibitory Concentration 50
  • Lumefantrine / pharmacology
  • Malaria, Falciparum / epidemiology
  • Malaria, Falciparum / parasitology
  • Mali / epidemiology
  • Mefloquine / pharmacology
  • Plasmodium falciparum / drug effects*
  • Plasmodium falciparum / isolation & purification
  • Quinine / pharmacology
  • Quinolines / pharmacology

Substances

  • Antimalarials
  • Artemisinins
  • Quinolines
  • Amodiaquine
  • artenimol
  • Chloroquine
  • piperaquine
  • Quinine
  • Lumefantrine
  • Mefloquine