New pre-print! A Controlled Human Malaria Infection model for relapsing Plasmodium vivax
We are excited to share our latest pre-print, a collaborative project between the University of Oxford and Radboud University Medical Center as part of the OptiViVax consortium, where we demonstrate the safety and feasibility of a Controlled Human Malaria Infection (CHMI) model for relapsing Plasmodium vivax malaria.1
P. vivax is a major cause of malaria globally, and the majority of cases are caused by relapse infections.2,3 Relapses arise from the reactivation of dormant forms of the P. vivax parasite, called hypnozoites. However, the mechanisms underlying hypnozoite formation and reactivation are poorly understood, and current available anti-relapse therapies are sub-optimal. Although P. vivax relapse infections pose a major challenge to malaria elimination efforts, they also present an opportunity, as effectively tackling the hypnozoite reservoir of infection could significantly reduced P. vivax disease burden.
CHMI studies, in which healthy volunteers are deliberately infected with malaria in a controlled research setting, allow the study of host-pathogen interactions in detail and accelerate the development of vaccines and drug therapies.4 In our paper, we report the first CHMI study of relapsing P. vivax, and the first CHMI study in the modern era to administer a well-characterised clonal isolate of P. vivax (called PvW1) by mosquito bite.
Five participants, carefully screened for eligibility, were recruited in Oxford. The mosquito-bite CHMI was administered at Radboud University Medical Center before follow-up continued in Oxford. Anti-relapse treatment (primaquine) was delayed for six months and participants were carefully monitored for relapse infections. All participants in the study developed P. vivax infection and experienced at least one relapse infection in a six-month follow-up period (two participants experienced two relapses). All participants were effectively treated at the end of follow-up. We demonstrate that CHMI of relapsing P. vivax is safe and feasible. Our study creates a platform for future drug and vaccine efficacy studies, and presents an opportunity for improved knowledge of the mechanisms underlying P. vivax relapse infections.
We thank all the study participants without whom this research would not be possible. Find the pre-print online at medRxiv here.
References
1. Duncan ADS, Geraedts TJM, Manlutac D, et al. A Controlled Human Malaria Infection model for relapsing Plasmodium vivax. medRxiv 2026: 2026.06.18.26355868.
2. Commons RJ, Simpson JA, Watson J, White NJ, Price RN. Estimating the Proportion of Plasmodium vivax Recurrences Caused by Relapse: A Systematic Review and Meta-Analysis. Am J Trop Med Hyg 2020; 103(3): 1094–9.
3. Adekunle AI, Pinkevych M, McGready R, et al. Modeling the dynamics of Plasmodium vivax infection and hypnozoite reactivation in vivo. PLoS Negl Trop Dis 2015; 9(3): e0003595.
4. Roestenberg M, Hoogerwerf MA, Ferreira DM, Mordmuller B, Yazdanbakhsh M. Experimental infection of human volunteers. Lancet Infect Dis 2018; 18(10): e312–e22.
OptiViVax is co-funded from the European Union Horizon Europe programme under grant agreement No. 101080744. The project also receives funding from UK Research and Innovation (UKRI) under the UK government’s Horizon Europe funding guarantee (grant No. 10077974) and Swiss Government’s State Secretariat for Education, Research, and Innovation (SERI No. 23.00182). Views and opinions expressed are those of the author(s) only and do not necessarily reflect those of the European Union, UK Research and Innovation or Swiss Government’s State Secretariat for Education, Research, and Innovation. Neither the European Union, UK Research and Innovation or Swiss Government’s State Secretariat for Education, Research, and Innovation nor the granting authority can be held responsible for them. The study was also funded in part by the UK National Institute for Health and Care Research (NIHR) Biomedical Research Centre: Oxford. The views expressed are those of the authors and not necessarily those of the National Health Service, the NIHR, or the Department of Health.