Comparison of antibody responses and parasite clearance in artemisinin therapeutic efficacy studies in Democratic Republic of Congo and Asia.
Cutts JC., O'Flaherty K., Zaloumis SG., Ashley EA., Chan JA., Onyamboko MA., Fanello C., Dondorp AM., Day NP., Phyo AP., Dhorda M., Imwong M., Fairhurst RM., Lim P., Amaratunga C., Pukrittayakamee S., Hien TT., Htut Y., Mayxay M., Abdul Faiz M., Takashima E., Tsuboi T., Beeson JG., Nosten F., Simpson JA., White NJ., Fowkes FJI.
BACKGROUND: Understanding the effect of immunity on P. falciparum clearance is essential for interpreting therapeutic efficacy studies designed to monitor emergence of artemisinin drug resistance. In low transmission areas of Southeast Asia, where resistance has emerged, P. falciparum antibodies confound parasite clearance measures. However, variation in naturally acquired antibodies across Asian and sub-Saharan African epidemiological contexts and their impact on parasite clearance, is yet to be quantified. METHODS: In an artemisinin therapeutic efficacy study, antibodies to twelve pre-erythrocytic and erythrocytic P. falciparum antigens were measured in 118 children with uncomplicated P. falciparum malaria in Democratic Republic of Congo (DRC) and compared to responses in patients from Asian sites, described previously. RESULTS: Parasite clearance half-life was faster in DRC patients (median 2 hours) compared to most Asian sites (median ranged from 2-7 hours), but P. falciparum antibody levels and seroprevalences were similar. There was no evidence for an association between antibody seropositivity and parasite clearance half-life (mean difference between seronegative and seropositive ranged from -0.14 and +0.40 h) in DRC patients. CONCLUSIONS: In DRC, where artemisinin remains highly effective, the substantially faster parasite clearance time compared with Asia was not explained by differences in the P. falciparum antibody responses studied.