Establishing a blood-stage controlled human malaria infection model with Plasmodium falciparum in healthy semi-immune Tanzanian adults
- 1Department of Paediatrics, Department of Biochemistry and Kavli Institute for Nanoscience Discovery, University of Oxford, Oxford, United Kingdom
Abstract
Controlled human malaria infection (CHMI) studies are a critical tool for the assessment and down-selection of potential malaria interventions, allowing detailed characterisation and understanding of host-parasite responses to inform both malaria vaccine and antimalarial drug development in humans. Blood-stage CHMI offers a specific means for proof-of-concept testing of blood-stage malaria vaccines, bypassing the pre-erythrocytic stages of malaria infection. Here, we establish a blood-stage CHMI model in an endemic region in a clinical study involving 12 healthy semi-immune male adult participants residing in Bagamoyo district, Tanzania. Participants were enrolled into relatively 'low' (n=6) and 'high' (n=6) malaria pre-exposure groups as defined by serum anti-schizont IgG levels. Participants were challenged with approximately 1000 erythrocytes infected with a chloroquine-sensitive Plasmodium falciparum 3D7 clone and closely monitored for 28 days at the Ifakara Health Institute clinical trial facility in Bagamoyo. Blood samples were collected for safety and immunology assessments, with venous blood samples for P. falciparum quantitative polymerase chain reaction (qPCR) taken once on day after challenge (C+1) and twice daily from two to 28 days after challenge (C+2 to C+28). Participants were treated once pre-defined diagnostic criteria were met or at day 28 (if criteria not met). The challenge inoculum was found to be safe with the severity grading of adverse events (AEs) in keeping with previous challenge studies. Overall, fewer AEs were reported as compared to malaria-naive UK adults previously challenged with the same inoculum dose, despite a 50-fold higher treatment threshold being used in Tanzanian adults. Nine of 11 participants developed parasitaemia detectable by qPCR and one participant was retrospectively excluded from parasitaemia endpoint analysis due to non-3D7 type infection. The two participants who remained qPCR negative were both in the 'high' pre-exposure group. Higher anti-schizont baseline serology status was associated with later median time to parasitaemia detection and time to pre-defined treatment criteria. These data demonstrate that blood-stage CHMI is safe and feasible in semi-immune adults in a malaria-endemic setting.
Related
- Controlled human infection with Plasmodium falciparum-infected mosquito bites elicits antibodies against mosquito salivary protein SG1L3
- Severe Plasmodium falciparum infection with multi-organ involvement in an asplenic patient: a case report.
- First report of severe Plasmodium vivax malaria with sub-microscopic co-infection of Plasmodium vivax and Plasmodium falciparum and their clinicodemographic correlates: a study from hyperendemic areas of Tripura
- Hierarchy of immunogenicity of Plasmodium falciparum merozoite antigens and vaccine candidates in first human infection
- Identifying shared and parasite-specific determinants of Plasmodium falciparum and Schistosoma mansoni co-infection in a large-scale community-based study in rural Uganda
BibTeX
@misc{silk2026establishing,
title = {{Establishing a blood-stage controlled human malaria infection model with Plasmodium falciparum in healthy semi-immune Tanzanian adults}},
author = {S. E. Silk and J. Salkeld and O. Hassan and N. Balige and L. Mohamed and F. Milando and J. R. Barrett and S. Ahmed and A.-E. Kahatano and E. Kessy and P. Kweyamba and D. Quinkert and O. Juma and B. Mwalimu and M. Mohamed and N. G. Marchevsky and L. M. Hofer and M. Mohamed and B. B. Tarimo and H. Msami and T. G. Mwamlima and W. F. Kalinga and I. A. Sasamalo and I. M. Mtaka and N. S. Lilolime and F. R. Donnellan and M. Bardelli and A. Diouf and A. M. Lawrie and R. Roberts and F. L. Nugent and C. A. Long and S. Mswata and M. Kasubi and J.-S. Cho and C. M. Nielsen and S. J. Draper and A. M. Minassian and A. I. Olotu},
howpublished = {medRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.25.26366323},
url = {https://www.medrxiv.org/content/10.64898/2026.10.25.26366323v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Establishing a blood-stage controlled human malaria infection model with Plasmodium falciparum in healthy semi-immune Tanzanian adults
AU - S. E. Silk
AU - J. Salkeld
AU - O. Hassan
AU - N. Balige
AU - L. Mohamed
AU - F. Milando
AU - J. R. Barrett
AU - S. Ahmed
AU - A.-E. Kahatano
AU - E. Kessy
AU - P. Kweyamba
AU - D. Quinkert
AU - O. Juma
AU - B. Mwalimu
AU - M. Mohamed
AU - N. G. Marchevsky
AU - L. M. Hofer
AU - M. Mohamed
AU - B. B. Tarimo
AU - H. Msami
AU - T. G. Mwamlima
AU - W. F. Kalinga
AU - I. A. Sasamalo
AU - I. M. Mtaka
AU - N. S. Lilolime
AU - F. R. Donnellan
AU - M. Bardelli
AU - A. Diouf
AU - A. M. Lawrie
AU - R. Roberts
AU - F. L. Nugent
AU - C. A. Long
AU - S. Mswata
AU - M. Kasubi
AU - J.-S. Cho
AU - C. M. Nielsen
AU - S. J. Draper
AU - A. M. Minassian
AU - A. I. Olotu
PY - 2026
DA - 2026/10/25
PB - medRxiv
DO - 10.64898/2026.10.25.26366323
UR - https://www.medrxiv.org/content/10.64898/2026.10.25.26366323v1
AB - Controlled human malaria infection (CHMI) studies are a critical tool for the assessment and down-selection of potential malaria interventions, allowing detailed characterisation and understanding of host-parasite responses to inform both malaria vaccine and antimalarial drug development in humans. Blood-stage CHMI offers a specific means for proof-of-concept testing of blood-stage malaria vaccines, bypassing the pre-erythrocytic stages of malaria infection. Here, we establish a blood-stage CHMI model in an endemic region in a clinical study involving 12 healthy semi-immune male adult participants residing in Bagamoyo district, Tanzania. Participants were enrolled into relatively 'low' (n=6) and 'high' (n=6) malaria pre-exposure groups as defined by serum anti-schizont IgG levels. Participants were challenged with approximately 1000 erythrocytes infected with a chloroquine-sensitive Plasmodium falciparum 3D7 clone and closely monitored for 28 days at the Ifakara Health Institute clinical trial facility in Bagamoyo. Blood samples were collected for safety and immunology assessments, with venous blood samples for P. falciparum quantitative polymerase chain reaction (qPCR) taken once on day after challenge (C+1) and twice daily from two to 28 days after challenge (C+2 to C+28). Participants were treated once pre-defined diagnostic criteria were met or at day 28 (if criteria not met). The challenge inoculum was found to be safe with the severity grading of adverse events (AEs) in keeping with previous challenge studies. Overall, fewer AEs were reported as compared to malaria-naive UK adults previously challenged with the same inoculum dose, despite a 50-fold higher treatment threshold being used in Tanzanian adults. Nine of 11 participants developed parasitaemia detectable by qPCR and one participant was retrospectively excluded from parasitaemia endpoint analysis due to non-3D7 type infection. The two participants who remained qPCR negative were both in the 'high' pre-exposure group. Higher anti-schizont baseline serology status was associated with later median time to parasitaemia detection and time to pre-defined treatment criteria. These data demonstrate that blood-stage CHMI is safe and feasible in semi-immune adults in a malaria-endemic setting.
ER -