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Changing Antimalarial Drug Sensitivities in Uganda.

Stephanie A Rasmussen1, Frida G Ceja1, Melissa D Conrad2

  • 1Department of Natural Sciences and Mathematics, Dominican University of California, San Rafael, California, USA.

Antimicrobial Agents and Chemotherapy
|September 20, 2017
PubMed
Summary

Antimalarial drug sensitivity in Uganda is shifting. While dihydroartemisinin-piperaquine (DP) shows promise, resistance is a concern. Studies reveal changing sensitivities to key malaria drugs, with some improving and others decreasing.

Keywords:
Plasmodium falciparumUgandaartemether-lumefantrinedihydroartemisinin-piperaquinedrug resistanceex vivok13pfcrtpfmdr1plasmepsin 2

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Area of Science:

  • Malariology
  • Infectious Diseases
  • Pharmacology

Background:

  • Dihydroartemisinin-piperaquine (DP) is effective for malaria in Uganda, but resistance is emerging globally.
  • Artemether-lumefantrine, Uganda's first-line treatment, faces potential reduced sensitivity to lumefantrine.
  • Monitoring antimalarial drug sensitivity is crucial for effective malaria control.

Purpose of the Study:

  • To assess current *ex vivo* antimalarial drug sensitivities in Ugandan malaria isolates.
  • To characterize genotypes associated with drug resistance in these isolates.
  • To compare drug sensitivities between community isolates and those from a DP chemoprevention trial.

Main Methods:

  • Collected 58 malaria isolates from Tororo, Uganda, in 2016.
  • Performed *ex vivo* drug sensitivity assays for various antimalarials.
  • Genotyped isolates for known drug resistance-associated mutations.

Main Results:

  • Isolates from DP trial subjects showed lower sensitivity to aminoquinolines (chloroquine, amodiaquine, piperaquine) and higher sensitivity to lumefantrine and mefloquine.
  • Community isolates in 2016 demonstrated improved sensitivity to chloroquine, amodiaquine, and piperaquine compared to 2010-2013 data.
  • Sensitivity to lumefantrine decreased, while dihydroartemisinin sensitivity remained unchanged in community isolates.
  • Prevalence of transporter mutations for aminoquinoline resistance decreased; novel artemisinin/piperaquine resistance genotypes were rare.

Conclusions:

  • Antimalarial drug sensitivity patterns in Uganda are evolving.
  • DP selection pressure may influence drug sensitivity profiles.
  • Current resistance markers for artemisinins and piperaquine are not prevalent in Uganda, but declining lumefantrine sensitivity warrants monitoring.