PfHRP2 and PfLDH antigen detection for monitoring the efficacy of artemisinin-based combination therapy (ACT) in the treatment of uncomplicated falciparum malaria

Malar J. 2009 Sep 7:8:211. doi: 10.1186/1475-2875-8-211.

Abstract

Background: An assessment of the accuracy of two malaria rapid diagnostic tests (RDT) for the detection of Plasmodium falciparum histidine-rich protein 2 (PfHRP2) or Pf lactate dehydrogenase (PfLDH) was undertaken in children aged between six and 59 months included in an anti-malarial efficacy study in Benin.

Methods: In Allada (Benin), 205 children aged 6-59 months with falciparum malaria received either artesunate-amodiaquine (ASAQ), artemether-lumefantrine (AL), or sulphadoxine-pyrimethamine (SP). Children included in the study were simultaneously followed by both RDT and high-quality microscopy for up to 42 days.

Results: At the time of inclusion, PfHRP2-based tests were positive in 203 children (99%) and PfLDH-based tests were positive in 204 (99.5%). During follow-up, independent of the treatment received, only 17.3% (28/162) of children effectively cured were negative with the PfHRP2 RDT at day 3, with a gradual increase in specificity until day 42. The specificity of antigen detection with the PfLDH test was 87% (141/162) on day 3, and between 92% and 100% on days 7 to 42. A statistical difference was observed between the persistence of PfHRP2 and PfLDH antigenaemia during follow-up in children treated with artemisinin-based combination therapy (ACT) but not with SP.

Conclusion: Although both RDTs are as sensitive as microscopy in detecting true malaria cases, the PfHRP2 RDT had very low specificity during follow-up until day 28. On the other hand, the PfLDH test could be used to detect failures and, therefore, to assess anti-malarial efficacy.

Publication types

  • Comparative Study
  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amodiaquine / therapeutic use
  • Antigens, Protozoan / blood*
  • Antimalarials / therapeutic use*
  • Artemether, Lumefantrine Drug Combination
  • Artemisinins / therapeutic use*
  • Benin
  • Blood / parasitology
  • Child, Preschool
  • Drug Combinations
  • Drug Monitoring / methods*
  • Drug Therapy, Combination
  • Ethanolamines / therapeutic use
  • Fluorenes / therapeutic use
  • Follow-Up Studies
  • Humans
  • Infant
  • L-Lactate Dehydrogenase / blood*
  • Malaria, Falciparum / diagnosis*
  • Malaria, Falciparum / drug therapy*
  • Malaria, Falciparum / parasitology
  • Microscopy / methods
  • Molecular Diagnostic Techniques
  • Protozoan Proteins / blood*
  • Pyrimethamine / therapeutic use
  • Sensitivity and Specificity
  • Sulfadoxine / therapeutic use
  • Treatment Outcome

Substances

  • Antigens, Protozoan
  • Antimalarials
  • Artemether, Lumefantrine Drug Combination
  • Artemisinins
  • Drug Combinations
  • Ethanolamines
  • Fluorenes
  • HRP-2 antigen, Plasmodium falciparum
  • Protozoan Proteins
  • amodiaquine, artesunate drug combination
  • Amodiaquine
  • fanasil, pyrimethamine drug combination
  • Sulfadoxine
  • artemisinin
  • L-Lactate Dehydrogenase
  • Pyrimethamine