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Controlled human malaria infection (CHMI) is a powerful tool to evaluate the efficacy of malaria vaccines and pharmacologics. Investigators at the University of Maryland, Baltimore, Center for Vaccine Development (UMB-CVD) pioneered the technique in the 1970s and continue to advance the frontiers of CHMI research. We reviewed the records of 338 malaria-naive volunteers who underwent CHMI at UMB-CVD with Plasmodium falciparum from 1971 until 2017. These 338 volunteers underwent 387 CHMI events, including 60 via intradermal injection or direct venous inoculation (DVI) of purified, cryopreserved sporozoites. No volunteer suffered an unplanned hospitalization or required intravenous therapy related to CHMI. Median prepatency period was longer in challenges using NF54 (9 days) than in those using 7G8 (8 days), P = 0.0006 by the log-rank test. With dose optimization of DVI, the prepatent period did not differ between DVI and mosquito bite challenge (log-rank test, P = 0.66). Polymerase chain reaction (PCR) detected P. falciparum infection 3 days earlier than thick smears (P < 0.001), and diagnosis by ultrasensitive PCR was associated with less severe symptoms than smear-based diagnosis (39% versus 0%, P = 0.0003). Historical studies with NF54 showed a shorter median prepatency period of 10.3 days than more recent studies (median 11.0 days, P = 0.02) despite significantly lower salivary gland scores in earlier studies, P = 0.0001. The 47-year experience of CHMI at UMB-CVD has led to advancements in sporozoite delivery, diagnostics, and use of heterologous challenge. Additional studies on new challenge strains and genomic data to reflect regional heterogeneity will help advance the use of CHMI as supporting data for vaccine licensure.
Financial support: K. E. L. is supported by the National Institutes of Health (NIH) (U19 AI110820, U01 AI089342, and R01AI110852), the Vaccine Research Center of NIH and the EMMES Corporation (HHSN272201000049I), the Office of the Surgeon General, Department of the Army (W81XWH-15-R-0034), and the Joint Warfighter Medical Research Program and Sanaria, Inc. (W81XWH-JW14843). This publication was made possible by an NIH-funded postdoctoral fellowship to D. J. F. K. (T32 AI007524). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Authors’ addresses: DeAnna J. Friedman-Klabanoff, Matthew B. Laurens, Andrea A. Berry, Mark A. Travassos, Matthew Adams, Kathy A. Strauss, Biraj Shrestha, Myron M. Levine, Robert Edelman, and Kirsten E. Lyke, Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, MD, E-mails: firstname.lastname@example.org, email@example.com, firstname.lastname@example.org, email@example.com, firstname.lastname@example.org, email@example.com, firstname.lastname@example.org, email@example.com, firstname.lastname@example.org, and email@example.com.