The Role of Complement Immune Response on Artemisinin Combination Therapy in a Population from Malaria Endemic Region of Western Kenya

Abstract

BACKGROUND: Naturally acquired immunity which is characterized by protection against overt clinical disease and high parasitemia is acquired with age and transmission intensity. The role of naturally acquired immunity on the efficacy of antimalarial drugs including artemisinin combination therapies (ACTs), the first-line treatments for uncomplicated Plasmodium falciparum has been demonstrated. This study investigated the role of naturally acquired immunity in the response to malaria ACT drug treatment in symptomatic patients living in a malaria high-transmission area of Western Kenya. METHODS:This study used samples obtained from a therapeutic efficacy study conducted in western Kenya, an areas of high transmission which assessed ACTs. Sera samples from malaria immune (n = 105) and naïve participants (n = 6) were assessed for in vitro growth inhibitory activity against 3D7 P. falciparum using a fluorescent-based Growth Inhibition Assay (GIA). Participants' age and parasite clearance parameters were used in the analysis. RESULTS:The key observations of the study are: (1) Sera with intact complement displayed higher GIA activity at lower serum dilutions; (2) there was significant relationship between GIA activity, parasite clearance rate, and slope half-life; (3) Age was a confounding factor when comparing the GIA activity with parasite clearance kinetics. CONCLUSION:Taken together, this study demonstrates for the first time there is synergy of complement, pre-existing immunity, and drug treatment in younger patients with symptomatic malaria in a high-transmission area.

Towards identification and development of alternative vaccines against pregnancy-associated malaria based on naturally acquired immunity

“…New evidence suggests that these mechanisms may also contribute to vaccine-induced immunity. For example, the RTS,S vaccine can induce complement-fixing antibodies against the central repeat and C-terminal regions of CSP (49).…”