Project Title: Adaptation of blood-stage CHMI for Evaluation of Transmission Blocking Malaria Intervention in Endemic Countries
Project Description: Plasmodium falciparum (Pf) malaria still remains a disease of public health significance affecting millions across the globe. Controlled Human Malaria Infection (CHMI) is the tool that has been used widely used to evaluate candidate malaria vaccines and drugs providing a more cost-effective way to down-select potential candidate interventions before large Phase II and III trials are conducted. To date, approximately 200 malaria naïve individuals have safely participated in blood-stage CHMI, and several candidate blood-stage CHMI... Plasmodium falciparum (Pf) malaria still remains a disease of public health significance affecting millions across the globe. Controlled Human Malaria Infection (CHMI) is the tool that has been used widely used to evaluate candidate malaria vaccines and drugs providing a more cost-effective way to down-select potential candidate interventions before large Phase II and III trials are conducted. To date, approximately 200 malaria naïve individuals have safely participated in blood-stage CHMI, and several candidate blood-stage CHMI and several candidate blood-stage malaria vaccine candidates have been evaluated using the model. Very few adverse events have been reported following blood-stage CHMI compared to sporozoite CHMI. However, this model has not been used in Africa, among other things due to difficulty in accessing viable PfiRbc, lack of necessary technical expertise and infrastructure, and safety concerns. This study, therefore, aims to achieve the following primary and secondary objectives. Primary Objectives • To determine the safety of two different P.falciparum blood-stage CHMI models adapted for transmission studies in semi-immune healthy adults residing in Bagamoyo, Tanzania. • To select the most effective P.Falciparum blood-stage CHMI model adapted for transmission studies for induction of stable gametocytaemia at densities detectable by qRT-PCR. Secondary Objectives: • To investigate the dynamics of gametocyte development, maturation, and sex ratio by molecular markers of sexual stage development in semi-immune healthy adults residing in Bagamoyo Tanzania • To determine time profit of peak density of gametocytaemia in the P.falciparum blood-stage CHMI model adapted for transmission studies in semi-immune healthy adults residing in Bagamoyo, Tanzania • To determine the effects of naturally acquired antibody and cellular immune responses to blood-stage and gametocyte antigens on gametocyte development, dynamics, and their infectivity following challenge with viable Plasmodium Falciparum infected human erythrocytes in healthy semi-immune adults residing in Bagamoyo, Tanzania. The project will take place at the IHI Clinical Trial Facility located at Bagamoyo town (about 60 km north of Dar es Salaam). Participants will be recruited from around Bagamoyo town in the Bagamoyo district. The study will enroll students (aged 18 to 35 years) from higher learning institutions located in Bagamoyo town whose intellectual capability enables them appropriately and will assess the risk-benefit ratio before consenting. The PI will first interact with the community advisory committee in the study area, the scientific community, and ethical and regulatory authorities in Tanzania to discuss the blood-stage challenge model, safety experience from previous studies in malaria naïve adults, and procedures to mitigate any potential safety concerns. As part of this fellowship, clinical experts from the University of Oxford will first train the team in Tanzania on the blood-stage CHMI protocol currently being used at the University of Oxford. The training will include the necessary laboratory and clinical setup, managing the P.falciparum infected erythrocytes, its administration, safety follow-ups, and treatment criteria. Potential risks to volunteers, staff, and the environment (transmission to the local mosquitoes) will be discussed, and necessary measures to mitigate them identified. All participants will receive a course of Artemether/Lumefantrine and a single dose of Primaquine (at 0.25/kg) to clear all parasites on day C+28 before discharge from the in-house observation on C+31. Before discharge confirmatory of parasite clearance by PCR will be done. The results of the research work will be published in an open-access peer-reviewed and presented at International scientific meetings. We will communicate the findings of the study to research scientists in IHI through seminars and annual scientific retreat meetings. Seminars and scientific presentations will also be used to communicate information about the study and the outcome. Also, one Ph.D. student will be funded by the EDCTP fellowship. The data generated by the study is however sufficient to support an additional Master Student.
Principal Investigator : Ally Olotu
Department Name : BRCT
Time frame: (2019-12-18) - (2025-03-31)
European and Developing Countries Clinical Trials Partnership Programme (EDCTP) (Normal)
External Collaborating Partners
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