High prevalence of persistent residual parasitemia on days 3 and 14 after artemether-lumefantrine or pyronaridine-artesunate treatment of uncomplicated Plasmodium falciparum malaria in Nigeria

Parasitol Res. 2023 Feb;122(2):519-526. doi: 10.1007/s00436-022-07753-8. Epub 2022 Dec 13.

Abstract

Background: Microscopic evaluation of parasite clearance is the gold standard in antimalarial drug efficacy trials. However, the presence of sub-microscopic residual parasitemia after artemisinin-based combination therapy (ACT) needs to be investigated.

Methods: One hundred and twenty (AL: n = 60, PA: n = 60) days 3 and 14 dried blood spots, negative by microscopy were analysed for residual parasitemia using nested PCR. Isolates with residual parasitemia on days 3 and 14 were further genotyped with their corresponding day-0 isolates using merozoite surface proteins msp-1, msp-2, and glurp genes for allelic similarity.

Results: Persistent PCR-determined sub-microscopic residual parasitemia at day 3 post ACT treatment was 83.3 (AL) and 88.3% (PA), respectively (ρ = 0.600), while 63.6 and 36.4% (ρ = 0.066) isolates were parasitemic at day 14 for AL and PA, respectively. Microscopy-confirmed gametocytemia persisted from days 0 to 7 and from days 0 to 21 for AL and PA. When the alleles of day 3 versus day 0 were compared according to base pair sizes, 59% of parasites shared identical alleles for glurp, 36% each for 3D7 and FC27, while K1 was 77%, RO33 64%, and MAD20 23%, respectively. Similarly, day 14 versus day 0 was 36% (glurp), 64% (3D7), and 32% (FC27), while 73% (K1), 77% (RO33), and 41% (MAD20), respectively.

Conclusion: The occurrence of residual parasitemia on days 3 and 14 following AL or PA treatment may be attributable to the presence of either viable asexual, gametocytes, or dead parasite DNAs, which requires further investigation.

Keywords: Gametocytes; Nigeria; P. falciparum malaria; PCR-determined residual parasitemia; Sub-microscopy.

MeSH terms

  • Antimalarials* / therapeutic use
  • Artemether / therapeutic use
  • Artemether, Lumefantrine Drug Combination / therapeutic use
  • Humans
  • Malaria, Falciparum* / drug therapy
  • Malaria, Falciparum* / epidemiology
  • Malaria, Falciparum* / parasitology
  • Merozoite Surface Protein 1 / genetics
  • Nigeria / epidemiology
  • Parasitemia / drug therapy
  • Parasitemia / epidemiology
  • Parasitemia / parasitology
  • Plasmodium falciparum
  • Prevalence

Substances

  • pyronaridine tetraphosphate, artesunate drug combination
  • Antimalarials
  • Artemether
  • Artemether, Lumefantrine Drug Combination
  • Merozoite Surface Protein 1