Pf HRP2 and Pf LDH antigen detection for monitoring the efficacy of artemisinin-based combination therapy (ACT) in the treatment of uncomplicated falciparum malaria

Background An assessment of the accuracy of two malaria rapid diagnostic tests (RDT) for the detection of Plasmodium falciparum histidine-rich protein 2 ( Pf HRP2) or Pf lactate dehydrogenase ( Pf LDH) 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, Pf HRP2-based tests were positive in 203 children (99%) and Pf LDH-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 Pf HRP2 RDT at day 3, with a gradual increase in specificity until day 42. The specificity of antigen detection with the Pf LDH 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 Pf HRP2 and Pf LDH 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 Pf HRP2 RDT had very low specificity during follow-up until day 28. On the other hand, the Pf LDH test could be used to detect failures and, therefore, to assess anti-malarial efficacy.