Malaria
Conditions
Keywords
transmission, reduction
Brief summary
This is a community-based cluster-randomized trial in which a novel approach to interrupt residual malaria transmission by mass drug administration (MDA) with ivermectin (IVM) combined with dihydroartemisinin-piperaquine (DP) will be tested. 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. This trial aims at establishing whether MDA with IVM and DP can reduce or interrupt malaria transmission in medium to low transmission settings by reducing vector survival and the human reservoir of infection. MDA with IVM and DP will be implemented in the intervention villages and all human settlements in the buffer zone, with the aim of minimizing spillover effects. Control clusters will receive standard malaria control interventions as implemented by the National Malaria Control Program. The primary outcomes will be the prevalence of malaria infection determined by molecular methods in all age groups at the peak of the second transmission season (November-December 2019) and the vector's parous rate 7-14 days after MDA.
Detailed description
The hypothesis of this project is that mass drug administration (MDA) with ivermectin (IVM) and dihydroartemisinin-piperaquine (DP) can reduce or interrupt malaria transmission in medium to low transmission settings by reducing vector survival and the human reservoir of infection. The research questions include the following: 1. Will MDA with IVM plus DP (3 rounds per transmission season) in communities with high coverage of vector control interventions further reduce malaria transmission (up to local elimination)? 2. Will MDA with IVM suppress the vector population? 3. What is the most socially acceptable and sustainable way of achieving and maintaining high coverage of MDA with IVM and DP, and of embedding it within local communities and stakeholders? 4. What is the impact of MDA with IVM on prevalence of ectoparasites and helminths 5. What is the cost and cost-effectiveness of this intervention compared to standard malaria control measures?
Interventions
DP will be available as tablets of 320/40mg and 160/20mg piperaquine/ dihydroartemisinin per tablet. Administration of a full course of DP will be done as per manufacturer's guidelines once daily for 3 days and according to body weight. DP will be taken orally with water and without food
DRUGivermectin (IVM)
IVM will be available as tablets of 3mg or 6mg strength. It will be given at 300-400μg/kg/day over 3 days (to the nearest whole tablet). IVM will also be taken on an empty stomach with water
OTHERstandard malaria control interventions only
this is the standard malaria control interventions in the Gambia
Sponsors
Institute of Tropical Medicine, Belgium
National Malaria Control Programme, The Gambia
Liverpool School of Tropical Medicine
Radboud University Medical Center
University of Durham
Imperial College London
London School of Hygiene and Tropical Medicine
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
SINGLE (Outcomes Assessor)
Masking description
Malaria prevalence will be determined by technicians blinded to the treatment arm
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
Eligibility
Sex/Gender
ALL
Age
6 Months to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Age/anthropometry 1. For IVM: weight ≥ 15kg or height ≥90 cm; 2. For DP: age \> 6 months * Willingness to comply with trial procedures * Individual written informed consent obtained at the beginning of the study
Exclusion criteria
*
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Vector's parous rate | 7-14 days after mass drug administration (MDA) | Malaria prevalence will be used as an indicator of on-going malaria transmission, while vector's parous rate will quantify the effect of IVM on vector survival and mosquito population age structure. Proportion: number of parous vectors divided by the total number of collected vectors |
| prevalence of malaria infection | at 12 months | Prevalence of malaria infection determined by molecular methods number of participants with a positive varATS quantitative PCR divided by the total number of participants sampled |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| serological markers of recent malaria | after MDA over 6 months period | serological markers of recent malaria infection by Mean Fluorescent Intensity of the different antigens will be determined and presented as a geometric mean |
| serological markers of recent Anopheles exposure | after MDA over 6 months period | serological markers of recent Anopheles exposure by Mean Fluorescent Intensity of the different antigens will be determined and presented as a geometric mean |
| mosquito density | over 24 months after MDA | Total number of mosquitoes collected during the study period across both intervention and control villages |
| malaria prevalence | at 6 months | malaria prevalence at the peak of the first transmission season of number of participants with a positive varATS quantitative PCR divided by the total number of participants sampled |
| sporozoite rates in field-caught mosquitoes | over 24 months after MDA | Number of P. falciparum circumsporozoite antibody (CSP) positive mosquitoes divided by the total number of mosquitoes caught |
| mosquito mortality | 21 days post treatment | mosquito mortality after feeding on IVM treated individuals Number of mosquitoes that die after a blood meal 21 days post-treatment divided by total number of mosquitoes blood fed |
| incidence of clinical (laboratory confirmed) malaria cases | after MDA over 6 months period | incidence of clinical (laboratory confirmed) malaria cases at health facilities of Number of clinical malaria cases observed divided by person-years of follow-up |
Other
| Measure | Time frame | Description |
|---|---|---|
| drug resistance markers | after MDA 6 months | prevalence of drug resistance markers in the number of malaria parasites with drug-resistance markers divided by the total number of samples tested |
Countries
The Gambia
Outcome results
None listed