Abstract
BackgroundNaturally acquired immunity (NAI), which is characterized by protection against overt clinical disease and high parasitaemia, is acquired with age and transmission intensity. The role of NAI on the efficacy of anti-malarial drugs, including artemisinin-based combinations used as the first-line treatment for uncomplicated Plasmodium falciparum, has not been fully demonstrated. This study investigated the role of NAI in response to artemisinin-based combination therapy (ACT), in symptomatic patients living in western Kenya, a high malaria transmission area.MethodsSera samples from malaria immune participants (n = 105) in a therapeutic efficacy study were assessed for in vitro growth inhibitory activity against the 3D7 strain of P. falciparum using a fluorescent-based growth inhibition assay (GIA). Participants’ age and parasite clearance parameters were used in the analysis. Pooled sera from malaria naïve participants (n = 6) with no Plasmodium infection from malaria non-endemic regions of Kenya was used as negative control.ResultsThe key observations of the study were as follows: (1) Sera with intact complement displayed higher GIA activity at lower (1%) serum dilutions (p < 0.0001); (2) there was significant relationship between GIA activity, parasite clearance rate (p = 0.05) and slope half-life (p = 0.025); and (3) age was a confounding factor when comparing the GIA activity with parasite clearance kinetics.ConclusionThis 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.
Highlights
Acquired immunity (NAI), which is characterized by protection against overt clinical disease and high parasitaemia, is acquired with age and transmission intensity
The percentage growth inhibition of P. falciparum at 10 and 1% serum concentration from the study participants was significantly higher than for the non-immune controls (p < 0.0001) (Fig. 1), indicating parasite growth inhibition was due to the immune status
Age and Growth inhibition assays (GIA) activity To determine whether age or parasitaemia were confounding factors in GIA, the GIA data were stratified based on individuals younger than 5 years (< 5 years) or 5 years and older (≥ 5 years)
Summary
Acquired immunity (NAI), which is characterized by protection against overt clinical disease and high parasitaemia, is acquired with age and transmission intensity. People living in malaria endemic areas acquire natural immunity with age, with faster rates of acquisition occurring in high compared to low transmission settings [1] Both humoral and cell-mediated immune responses are involved in generating effective immunity [2], with individuals who possess greater breadth of immunological responses being at a lower risk of developing overt clinical symptoms [3]. Artemisinin-based combination therapy (ACT) is still highly efficacious in sub-Saharan Africa (sSA) [5], but as malaria transmission reduces, and malaria immunity at population level wanes [6], the efficacy of ACT is likely to be impacted It is, important to monitor and assess the effect of pre-existing acquired immunity on the efficacy of ACT as part of therapeutic efficacy studies (TESs). Using GIA, the present study aimed to assess the role of complement and pre-existing immunity in the response to malaria drug treatment in symptomatic patients living in a malaria high-transmission area of western Kenya
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