PfHRP2 and PfLDH 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 (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.


CONCLUSIONS
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.
Houzé
Sandrine
S
Parasitology Laboratory EA209, AP-HP, Bichat-C, Bernard Hospital, Paris-Descartes University, 75018 Paris, France. sandrine.houze@bch.aphp.fr
Boly
Mainoumata Dicko
MD
Le Bras
Jacques
J
Deloron
Philippe
P
Faucher
Jean-François
JF
D000655:Amodiaquine / Q000627:therapeutic use; D000953:Antigens, Protozoan / Q000097:blood*; D000962:Antimalarials / Q000627:therapeutic use*; D000077611:Artemether, Lumefantrine Drug Combination; D037621:Artemisinins / Q000627:therapeutic use*; D001541:Benin; D001769:Blood / Q000469:parasitology; D002675:Child, Preschool; D004338:Drug Combinations; D016903:Drug Monitoring / Q000379:methods*; D004359:Drug Therapy, Combination; D004983:Ethanolamines / Q000627:therapeutic use; D005449:Fluorenes / Q000627:therapeutic use; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D007770:L-Lactate Dehydrogenase / Q000097:blood*; D016778:Malaria, Falciparum / Q000175:diagnosis* / Q000188:drug therapy* / Q000469:parasitology; D008853:Microscopy / Q000379:methods; D025202:Molecular Diagnostic Techniques; D015800:Protozoan Proteins / Q000097:blood*; D011739:Pyrimethamine / Q000627:therapeutic use; D012680:Sensitivity and Specificity; D013413:Sulfadoxine / Q000627:therapeutic use; D016896:Treatment Outcome
D000953:Antigens, Protozoan; D000962:Antimalarials; D000077611:Artemether, Lumefantrine Drug Combination; D037621:Artemisinins; D004338:Drug Combinations; D004983:Ethanolamines; D005449:Fluorenes; C514457:HRP-2 antigen, Plasmodium falciparum; D015800:Protozoan Proteins; C515299:amodiaquine, artesunate drug combination; D000655:Amodiaquine; C001205:fanasil, pyrimethamine drug combination; D013413:Sulfadoxine; C031327:artemisinin; D007770:L-Lactate Dehydrogenase; D011739:Pyrimethamine