Clearance dynamics of lactate dehydrogenase and aldolase following antimalarial treatment for Plasmodium falciparum infection

Lingering post-treatment parasite antigen in blood complicates malaria diagnosis through antigen detection. Characterization of antigen clearance dynamics is important for interpretation of positive antigen detection tests. We used a bead-based serological assay to measure lactate dehydrogenase (LDH), aldolase (Aldo), and histidine-rich protein 2 (HRP2) levels in 196 children with Plasmodium falciparum malaria treated with effective antimalarials and followed for 28 to 42 days as part of therapeutic efficacy studies in Angola. Compared to pre-treatment levels, antigen concentrations two days after treatment declined by 99.7% for LDH, 96.3% for Aldo, and 54.6% for HRP2. After Day 2, assuming a first-order kinetics clearance model, half-lives of the antigens were 1.8 days (95% CI: 1.5–2.3) for LDH, 3.2 days (95% CI: 3.0–3.4) for Aldo, and 4.8 days (95% CI: 4.7–4.9) for HRP2. LDH and Aldo show substantially different clearance rates than HRP2, and their presence is largely indicative of active infection.