A Cluster-randomised, Open-label Trial to Compare the Impact of Combined Mass Vaccine and Drug Administrations, Mass Drug Administration, Mass Vaccinations, or no Intervention on Plasmodium Falciparum Malaria Transmission
Overview
- Phase
- Phase 4
- Intervention
- DHA/piperaquine and a SLD-PQ
- Conditions
- Plasmodium Falciparum Malaria
- Sponsor
- University of Oxford
- Enrollment
- 10000
- Locations
- 2
- Primary Endpoint
- Falciparum malaria prevalence by study groups
- Status
- Recruiting
- Last Updated
- 4 months ago
Overview
Brief Summary
This is an open i.e. not blinded, cluster-randomised, controlled intervention study. The study will use a factorial design to estimate the protective effectiveness of mass drug administrations, mass vaccinations, combined mass vaccinations and drug administrations versus the current standard of care.
Detailed Description
Trial Activities: The investigators are most interested in the combined effect of mass administration of vaccines and drugs on malaria transmission. Can Mass Vaccine and Drug Administrations (MVDA) reduce the parasite prevalence in intervention villages compared to control villages which did not receive the intervention? The entire village population will be enrolled at study start and followed for two years after D0, the first day of the interventions in the intervention villages. The village population is a dynamic cohort with new members entering the cohort by birth or immigration and other members leaving the cohort due to emigration or death. Newcomers entering villages will receive MVDA as soon as feasible and as appropriate (dependent on age). Secondly, the investigators want to know how effective the individual components of the intervention, mass vaccinations and mass drug administrations are in relation to MVDA? Hanako Foundation funded this study. Grant reference number: B9R05700
Investigators
Eligibility Criteria
Inclusion Criteria
- •Current residence in a study village irrespective of permanence
- •Age 6 months and above (no upper age limit)
- •Written informed consent provided by participants (or a parent/guardian in case the participant is under 18 years old)
Exclusion Criteria
- •Pregnancy, plan to get pregnant, or breastfeeding.
- •Acute illness requiring intervention
- •A history of an adverse reaction to study drugs/vaccine and prior receipt of any other malaria vaccine or enrolment in another intervention trial.
Arms & Interventions
MDA + Vaccine
The participants in MVDA villages will receive R21/Matrix M at M0, M1, M2, and a booster M12 plus DHA/piperaquine and a SLD-PQ at M0, M1, and M2
Intervention: DHA/piperaquine and a SLD-PQ
MDA + Vaccine
The participants in MVDA villages will receive R21/Matrix M at M0, M1, M2, and a booster M12 plus DHA/piperaquine and a SLD-PQ at M0, M1, and M2
Intervention: Study vaccine R21/Matrix-M™
MDA only
The participants in MDA only villages will receive DHA/piperaquine and a SLD-PQ at M0, M1, and M2
Intervention: DHA/piperaquine and a SLD-PQ
Vaccine only
The participants in vaccine only villages will receive R21/Matrix M at M0, M1, M2, and a booster M12
Intervention: Study vaccine R21/Matrix-M™
Outcomes
Primary Outcomes
Falciparum malaria prevalence by study groups
Time Frame: PCR for malaria detection from DBS will be collected at 6th month intervals until two years following baseline intervention (Month 0, Month 6, Month 12, Month 18 and Month 24)
Falciparum malaria prevalence will be determined by the number of positive falciparum confirmed by dried blood spots (DBS) polymerase chain reaction (PCR) malaria detection method during cross-sectional surveys to determine the overall protective efficacy against subclinical P. falciparum among study groups. * The investigators will collect dried blood spots to detect malaria during cross-sectional surveys from the healthy participants. * Those who have axillary temperature ≥37.5°C AND P. falciparum positive RDT or microscopy will receive treatment according to national treatment guidelines.
Falciparum malaria incidence by study groups
Time Frame: Data will be collected for two years following baseline intervention (Month 0 to Month 24)
Falciparum malaria incidence will be determined by the number of clinical falciparum malaria cases confirmed by Rapid diagnostic test (RDT) or microscopy to determine the overall protective efficacy against clinical falciparum malaria among study groups. The investigators will look for the presence of axillary temperature ≥37.5°C AND P. falciparum positive RDT or microscopy as a primary case definition of clinical falciparum malaria.
Overall percentage of falciparum malaria positivity by study groups
Time Frame: DBS: Month 0, Month 6, Month 12, Month 18 and Month 24 and Clinical malaria data for two year following intervention
The percentage of falciparum malaria positivity will be determined by the number of falciparum positives detected by PCR, RDT or microscopy to determine overall protective efficacy against clinical and subclinical falciparum malaria among study groups. Dried blood spots to detect malaria from by PCR will be collected at baseline and every six months until two years. Clinical malaria data detected by rapid diagnostic test or microscopy will be collected for two years following intervention. * The investigators will look for the presence of axillary temperature ≥37.5°C AND P. falciparum positive RDT or microscopy as a primary case definition of clinical malaria. * The investigators will collect dried blood spots to detect malaria during cross-sectional surveys from the healthy participants.
Secondary Outcomes
- The incidence of Deaths related to falciparum malaria among study groups(Data will be collected for two years following baseline intervention (Month 0 to Month 24))
- The incidence of severe anaemia among study groups(Data will be collected for two years following baseline intervention (Month 0 to Month 24))
- The incidence of adverse events(All adverse events which occur after administration of the first dose of the study drugs until one month after last dose of drugs or vaccine will be recorded. This data will be collected from Month 0 to month 24.)
- The incidence of clinical falciparum malaria confirmed by RDT or microscopy among vaccinated and drug administered participants in compare to unvaccinated and no drug-administered participants living in standard-of-care villages.(Data will be collected for two years following baseline intervention (Month 0 to Month 24))
- Vivax malaria prevalence by study groups(PCR for malaria detection from DBS will be collected at 6th month intervals until two years following baseline intervention (Month 0, Month 6, Month 12, Month 18 and Month 24))
- The acceptability of the intervention will be assessed by coverage (The number of residents participating in the interventions) reported as percentage of the target population participating in the intervention.(Month 3 and Month 13)
- The incidence of clinical falciparum malaria confirmed by RDT or microscopy among vaccinated participants in compare to unvaccinated participants living in standard-of-care villages.(Data will be collected for two years following baseline intervention (Month 0 to Month 24))
- The concentration of antibodies against Plasmodium falciparum circumsporozoite (anti-NANP total IgG antibody) among subset of randomly selected participants from vaccinated and no intervention group.(One month after the completion of the third dose (at Study month 3), and one month after the booster dose (at Study Month 13))
- The acceptability of the intervention will be assessed by mixed social science methods, in depth interviews and Focus group discussions.(Data will be collected for two years following baseline intervention (Month 0 to Month 24))
- The incidence of severe malaria disease among study groups(Data will be collected for two years following baseline intervention (Month 0 to Month 24))
- Vivax malaria incidence by study groups(Data will be collected for two years following baseline intervention (Month 0 to Month 24))
- Overall percentage of vivax malaria positivity by study groups(DBS: Month 0, Month 6, Month 12, Month 18 and Month 24 and Clinical malaria data for two year following intervention)
- Prevalence of molecular markers for drug resistant P. falciparum(Data will be collected for two years following baseline intervention (Month 0 to Month 24))
- The incidence of clinical falciparum malaria confirmed by RDT or microscopy among drug administered participants in compare to no drug-administered participants living in standard-of-care villages.(Data will be collected for two years following baseline intervention (Month 0 to Month 24))
- The incidence of clinical falciparum malaria confirmed by RDT or microscopy among unvaccinated and no drug-administered people living in intervention clusters relative to unvaccinated and no drug-administered people living in standard-of-care villages.(Data will be collected for two years following baseline intervention (Month 0 to Month 24))
- The incidence of clinical falciparum malaria confirmed by RDT or microscopy among unvaccinated people living in intervention clusters relative to unvaccinated people living in standard-of-care villages.(Data will be collected for two years following baseline intervention (Month 0 to Month 24))
- The incidence of clinical falciparum malaria confirmed by RDT or microscopy among no drug-administered people living in intervention clusters relative to no drug-administered people living in standard-of-care villages.(Data will be collected for two years following baseline intervention (Month 0 to Month 24))