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, Domtila Kimani, Patricia Njuguna, Mainga Hamaluba, Edward Otieno, Rinter Kimathi, James Tuju, B. Kim Lee Sim, CHMI-SIKA Study Team, Abdirahman I. Abdi, Yonas Abebe, Philip Bejon, Peter F. Billingsley, Peter C. Bull, Zaydah R. de Laurent, Stephen L. Hoffman, Eric R. James, Silvia N. Kariuki, Samson Kinyanjui, Cheryl Kivisi, Johnstone Makale, Kevin Marsh, Khadija Said Mohammed, Moses Mosobo, Janet Musembi, Jennifer Musyoki, Michelle K. Muthui, Jedidah Mwacharo, Kennedy Mwai, Joyce Ngoi, Omar Ngoto, Irene N. Nkumama, Francis M. Ndungu, Dennis Odera, Bernhards Ogutu, Fredrick Olewe, Donwilliams O. Omuoyo, John Michael Ong’echa, Faith Osier, Thomas L. Richie, Jimmy Shangala, Juliana Wambua, Thomas N. Williams
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.