Mass Drug Administration of Ivermectin and Dihydroartemisinin-piperaquine as an Additional Intervention for Malaria Elimination (MASSIV)
The general objective of this proposal is to determine whether MDA combining an antimalarial treatment (dihydroartemisinin-piperaquine) with ivermectin can substantially reduce and possibly interrupt malaria transmission in an area with high coverage of standard malaria control interventions. This will be done by carrying out a cluster-randomized controlled trial with an intervention (MDA with dihydroartemisinin-piperaquine and ivermectin) and control (standard malaria control interventions) arm.
Specific objectives are as follows:
- To compare, after 2 years of MDA with dihydroartemisinin-piperaquine and ivermectin, the prevalence of malaria (all age groups) between intervention and control clusters;
- To compare, after 2 years of MDA with dihydroartemisinin-piperaquine and ivermectin, the vector parous rate between intervention and control clusters, and other entomological variables (density and sporozoite rates);
- To quantify the mosquitocidal effect of ivermectin until 21 days after treatment;
- To determine the coverage and compliance of MDA with dihydroartemisinin-piperaquine and ivermectin in intervention clusters and related socio-cultural factors;
- To estimate the incremental cost and cost-effectiveness of MDA using the trial outcome measures.
This project aims to evaluate a novel approach to decrease and possibly stop residual malaria transmission; it consists of mass drug administration (MDA) with an artemisinin-based combination treatment, dihydroartemisinin-piperaquine (DP), and a systemic endectocidal drug, ivermectin (IVM), toxic to Anopheles mosquitoes when biting treated individuals. This intervention will be tested through a community-based, cluster-randomized trial to be implemented in the Upper River Region of The Gambia where there is still residual malaria transmission despite high coverage of standard malaria control activities.
Thirty two villages (clusters) at least 3-4 km apart and with 200-600 inhabitants will be randomized to either the intervention or the control arm. MDA with IVM and DP will be implemented in 16 intervention villages and a buffer zone of 2 km around each of them, and will consist of 3-monthly rounds per year during the malaria transmission season for two years.
At the peak of each transmission season, a cross-sectional survey to determine malaria prevalence (200 individuals per cluster) will be carried out in both study arms. The vector population will be monitored throughout the transmission season. In addition, qualitative social science data on coverage, potential bottlenecks for the intervention, adherence and acceptability will be collected; a health economics study on the cost-effectiveness of the intervention will be carried out.
The primary outcomes will be malaria prevalence (by molecular methods) in all age groups and vector's parous rates after 2 MDA seasonal cycles (3 rounds each). Secondary outcomes will include incidence of clinical malaria, serological markers of recent infection or recent exposure to the vector, other entomological variables, intervention coverage, and cost-effectiveness of the intervention.
Dose: Ivermectin will be available as tablets of 3mg or 6mg strength. It will be given at 300-400μg/kg/day over 3 days
- Primary outcomes: prevalence of malaria infection at 12 months, vector's parous rate at 7-14 days after MDA
- Secondary outcomes: malaria prevalence at 6 months, incidence of clinical (laboratory confirmed) malaria cases after MDA over a 6 months period, serological markers of recent malaria, serological markers of recent Anopheles exposure, mosquito density, mosquito mortality and sporozoite rates in field-caught mosquitoes.
- Other outcomes: drug resistance markers
Clinicaltrials.gov ID: NCT03576313
|Study Type :||Interventional (Clinical Trial)|
|Intervention Model:||Parallel Assignment|
|Intervention Model Description:||This cluster-randomized trial will involve 32 villages in the Upper River Region of The Gambia that will be randomized to MDA with IVM and DP or to standard of care in a ratio 1:1|
|Masking:||Single (Outcomes Assessor)|
|Masking Description:||Malaria prevalence will be determined by technicians blinded to the treatment arm|