Controlled human malaria infection (CHMI) outcomes in Kenyan adults is associated with prior history of malaria exposure and anti-schizont antibody response

Abstract

Background: Individuals living in endemic areas acquire immunity to malaria following repeated parasite exposure. We sought to assess the controlled human malaria infection (CHMI) model as a means of studying naturally acquired immunity in Kenyan adults with varying malaria exposure.

Methods: We analysed data from 142 Kenyan adults from three locations representing distinct areas of malaria endemicity (Ahero, Kilifi North and Kilifi South) enrolled in a CHMI study with Plasmodium falciparum sporozoites NF54 strain (Sanaria® PfSPZ Challenge). To identify the in vivo outcomes that most closely reflected naturally acquired immunity, parameters based on qPCR measurements were compared with anti-schizont antibody levels and residence as proxy markers of naturally acquired immunity.

Results: Time to endpoint correlated more closely with anti-schizont antibodies and location of residence than other parasite parameters such as growth rate or mean parasite density. Compared to observational field-based studies in children where 0.8% of the variability in malaria outcome was observed to be explained by anti-schizont antibodies, in the CHMI model the dichotomized anti-schizont antibodies explained 17% of the variability.

Conclusions: The CHMI model is highly effective in studying markers of naturally acquired immunity to malaria. Trial registration Clinicaltrials.gov number NCT02739763. Registered 15 April 2016.

Keywords: Anti-schizont antibody response; Controlled human malaria infection; Malaria exposure; Plasmodium falciparum.

Fig. 1

Time to treatment survival analysis. Kaplan–Meier curves comparing time to treatment with location of residence (left panel) and anti-schizont antibody response (right panel). Shown are survival curves for location of residence is low transmission (blue) vs. high transmission (red). For anti-schizont antibody responses shown is low antibodies (blue) vs. high antibodies (red)

Fig. 2

Survival analysis of CHMI vs. field-based observational study. Kaplan–Meier curves comparing of the CHMI cohort (left panel) and field-based cohort (right panel) in relation to requirement for treatment and anti-schizont antibody responses. Antibody responses are shown as low (red) vs. high (blue)