P. falciparum malaria Infections and Infestations
Conditions
Interventions
Current interventions as of 28/03/2025:
We will recruit 25-27 participants for three study groups.
Group 2 participants will receive the yellow fever vaccination first. Approximately four months af
Sponsors
University of Oxford
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Participant inclusion criteria as of 30/04/2024: 1. Healthy, malaria-naïve adult aged 18 to 45 years old 2. Able and willing (in the Investigator’s opinion) to comply with all study requirements 3. Willing to allow the Investigators to access the volunteer’s electronic medical records or discuss the volunteer’s medical history with their GP 4. Participants of childbearing potential only: must practice continuous effective contraception for the duration of the study 5. Able and willing to provide written informed consent to participate in the trial 6. Negative haemoglobinopathy screen (including sickle cell disease and alpha and beta thalassaemia) and normal G6PD levels 7. Agreement to permanently refrain from blood donation during and after the study, as per current UK Blood Transfusion and Tissue Transplantation Services guidelines 8. Reachable (24 hours a day) by mobile phone during the period between CHMI and completion of anti-malarial treatment 9. Willing to take a curative anti-malarial treatment regimen following CHMI 10. Able to answer all questions on the informed consent questionnaire correctly at the first or second attempt 11. Able to travel to CCVTM 12. Willingness to be registered on the TOPS database (The Overvolunteering Prevention System; www.tops.org.uk). _____ Previous participant inclusion criteria: 1. Healthy, malaria-naïve, CMV-seropositive adult aged 18 to 45 years old 2. Able and willing (in the Investigator’s opinion) to comply with all study requirements 3. Willing to allow the Investigators to access the volunteer’s electronic medical records or discuss the volunteer’s medical history with their GP 4. Participants of childbearing potential only: must practice continuous effective contraception for the duration of the study 5. Able and willing to provide written informed consent to participate in the trial 6. Negative haemoglobinopathy screen (including sickle cell disease and alpha and beta thalassaemia) and normal G6PD levels 7. Agreement to permanently refrain from blood donation during and after the study, as per current UK Blood Transfusion and Tissue Transplantation Services guidelines 8. Reachable (24 hours a day) by mobile phone during the period between CHMI and completion of anti-malarial treatment 9. Willing to take a curative anti-malarial treatment regimen following CHMI 10. Able to answer all questions on the informed consent questionnaire correctly at the first or second attempt 11. Able to travel to CCVTM 12. Willingness to be registered on the TOPS database (The Overvolunteering Prevention System; www.tops.org.uk).
Exclusion criteria
Exclusion criteria: Participant exclusion criteria as of 30/04/2024: 1. Red blood cells negative for the Duffy antigen/chemokine receptor (DARC) (this exclusion criterion is for Group 2 only) 2. Body weight = 5% at screening, as determined by the Systematic Coronary Risk Evaluation (SCORE) shown in Appendix B in the protocol 25. Use of medications known to have a potentially clinically significant interaction with Riamet 26. Any other contraindications/known hypersensitivities to Riamet or Malarone 27. History of sickle cell anaemia, sickle cell trait, thalassaemia or thalassaemia trait, G6PD deficiency or any haematological condition that could affect susceptibility to malaria infection 28. Pregnancy, lactation or intention to become pregnant during the study 29. History of cancer (except basal cell carcinoma of the skin and cervical carcinoma in situ) 30. History of serious psychiatric condition that may affect participation in the study 31. Any other serious chronic illness requiring hospital specialist supervision 32. Suspected or known current alcohol misuse as defined
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. Parasite growth rate measured using plasmodium falciparum-specific 18S rRNA qPCR assay and linear modelling for parasite multiplication rate (PMR) 2. Proliferation rate and half-life of total and Yellow fever vaccine (YFV)-specific memory T cells measured using flow cytometry with cell sorting and mass spectrometry analysis of deuterium incorporation | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Pan-Plasmodium 18S rRNA qPCR assay for confirmation of successful infection together with active and passive detection of (S)AE 2. Anti-PvDBPII total IgG standardised ELIS Exploratory Immunology Objectives Any other immunological analyses performed will be reported as not pre-specified in the study protocol. Other analyses may be detailed in the BIO-004 laboratory plan. Some assays may be duplicated at different laboratory sites. Some of these will involve analysis of frozen samples, and others analysis of fresh samples. For any exploratory endpoints not completed prior to the end of the study, where appropriate consent is received, samples will be registered under the University of Oxford HTA licence 12217 and analysed under the University of Oxford’s Central University Research Ethics Committee (CUREC) ethical approval. Exploratory immunology objectives include (but are not limited to): 1. Assessing whether T cell activation is pathogenic during a first-in-life malaria episode 2. Identifying the cellular and molecular adaptations that reprogram activated T cells 3. Measuring the functional capacity of T cells to provide essential B cell help Exploratory Immunology Outcome Measures Possibilities for exploratory immunology include (but are not limited to): 1. Tetramer and intracellular cytokine staining of memory T cells (ex vivo) by CyTOF. 2. Flow sorting and mass spectrometry of activated T cells. 3. IgG+/IgM+ memory B cell differentiation in organoid cultures. 4. Bead-based plasma protein arrays. 5. ChIP-sequencing and culture-based assays (such as cytoadherence and cytotoxicity) using cryopreserved PBMC. 6. High dimensional imaging mass cytometry of bone marrow biopsies. Other established and exploratory immunology assays may be carried out, which may include collaboration with other specialist laboratories within or beyond Europe. This would involve the transfer of samples, but samples would be pseudonymised. Volunteers will provide consent for this. | — |
Countries
England, United Kingdom
Contacts
Public ContactRachel Cowan
Outcome results
None listed