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. 2022 Jan 24;22(1):86.
doi: 10.1186/s12879-022-07044-8.

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

Melissa C Kapulu  1   2 , Domtila Kimani  3 , Patricia Njuguna  3 , Mainga Hamaluba  3   4 , Edward Otieno  3 , Rinter Kimathi  3 , James Tuju  3 , B Kim Lee Sim  5 ; CHMI-SIKA Study Team
Collaborators, Affiliations

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

Melissa C Kapulu et al. BMC Infect Dis. .

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.

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Conflict of interest statement

B. K. L. S. is a salaried, full-time employee of Sanaria Inc., the manufacturer of Sanaria PfSPZ Challenge. Thus, all authors associated with Sanaria Inc. have potential conflicts of interest. All other authors declare no competing interests.

Figures

Fig. 1
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
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)
See this image and copyright information in PMC

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