Last Updated

12 Nov 2019

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

Objectives

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:

  1. To evaluate the impact on malaria transmission of mass drug administration with ivermectin plus dihydroartemisinin-piperaquine (3 rounds per transmission season) in communities with high coverage of vector control interventions;
  2. To evaluate the impact of mass drug administration with ivermectin in suppressing the vector population density;
  3. To identify the most socially acceptable and sustainable way of achieving and maintaining high coverage of mass drug administration with ivermectin and dihydroartemisinin-piperaquine, and of embedding it within local communities and stakeholders
  4. To determine the cost and cost-effectiveness of this intervention compared to standard malaria control measures
Principal Investigator
Funding Information
Joint Global Health Trial Scheme. 2,057,637.72 GBP
Rationale and Abstract

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:

  1. Prevalence of malaria infection determined by molecular methods (ultrasensitive varATS quantitative PCR) in all age groups at the peak of the second transmission season (November-December 2019);
  1. Vector’s parous rate. 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.

Secondary outcomes are:

  1. Malaria prevalence at the peak of the first transmission season (Nov-Dec 2018)
  2. Incidence of clinical (laboratory confirmed) malaria cases as detected at health facilities
  3. Prevalence of drug-resistance markers
  4. Serological markers of recent malaria infection
  5. Serological markers of recent Anopheles exposure
  6. Mosquito density and sporozoite rates in field-caught mosquitoes
  7. Mosquito mortality after feeding on IVM treated individuals until 21 days post-treatment
  8. Intervention coverage at the village level
  9. Individual compliance with treatment regimens
  10. MDA acceptability
  11. MDA costs and cost-effectiveness

Tertiary outcomes are:

  1. Bedbug prevalence
  2. Headlice prevalence
  3. Prevalence of scabies
  4. Prevalence of soil-transmitted helminths

Dose: Ivermectin will be available as tablets of 3mg or 6mg strength. It will be given at 300-400μg/kg/day over 3 days

Outcome measures: 

  • 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 Design
Study Type  : Interventional  (Clinical Trial)
Allocation: Randomized
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
Primary Purpose: Prevention