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Mass Drug Administration of Ivermectin and Dihydroartemisinin-piperaquine as an Additional Intervention for Malaria Elimination

Phase 3
Completed
Conditions
Malaria
Interventions
Drug: dihydroartemisinin-piperaquine (DP)
Other: standard malaria control interventions only
Registration Number
NCT03576313
Lead Sponsor
London School of Hygiene and Tropical Medicine
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?

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
4939
Inclusion Criteria

Not provided

Exclusion Criteria
  • Exclusion criteria for both IVM and DP will include the following:
  • Known chronic illness (eg HIV, TB, hepatitis and severe malnutrition).

Additionally for IVM:

  1. Pregnancy (any trimester) and breast feeding
  2. Hypersensitivity to IVM
  3. Travel to Loa loa endemic countries (e.g. Central Africa)

Additionally for DP:

  1. First trimester pregnancy
  2. Hypersensitivity to DP
  3. Taking drugs that influence cardiac function or prolong QTc interval

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
intervention: IVM and DPivermectin (IVM)Mass Drug Administration with ivermectin (IVM) and dihydroartemisinin-piperaquine (DP) will be given to participants in the intervention villages plus the NMCP standard malaria control intervention
intervention: IVM and DPdihydroartemisinin-piperaquine (DP)Mass Drug Administration with ivermectin (IVM) and dihydroartemisinin-piperaquine (DP) will be given to participants in the intervention villages plus the NMCP standard malaria control intervention
intervention: IVM and DPstandard malaria control interventions onlyMass Drug Administration with ivermectin (IVM) and dihydroartemisinin-piperaquine (DP) will be given to participants in the intervention villages plus the NMCP standard malaria control intervention
control: standard malaria control intervetionsstandard malaria control interventions onlyParticipants in the control clusters will receive only standard malaria control interventions such as Artemether Lumefantrine, LLINs, IRS, SMC and IPTp as implemented by the National Malaria Control Program (NMCP) of the Gambia
Primary Outcome Measures
NameTimeMethod
prevalence of malaria infectionat 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

Vector's parous rate7-14 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

Secondary Outcome Measures
NameTimeMethod
malaria prevalenceat 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

incidence of clinical (laboratory confirmed) malaria casesafter 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

serological markers of recent malariaafter 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 exposureafter 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 densityover 24 months after MDA

Total number of mosquitoes collected during the study period across both intervention and control villages

mosquito mortality21 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

sporozoite rates in field-caught mosquitoesover 24 months after MDA

Number of P. falciparum circumsporozoite antibody (CSP) positive mosquitoes divided by the total number of mosquitoes caught

Trial Locations

Locations (1)

Basse Villages

🇬🇲

Basse Santa Su, Gambia

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