Optimal Delivery of Seasonal Malaria Chemoprevention and Its Effects on the Acquisition of Malaria Immunity
Trial Snapshot
- Phase
- Not Applicable
- Sponsor
- University of Bamako
- Enrollment
- 10,000
- Locations
- 1
- Primary Endpoint
- Coverage of SMC
Study Overview
Brief Summary
Based in part on the pivotal studies conducted in Mali, SMC was approved by WHO as a policy for malaria control in countries with seasonal malaria transmission such as Mali in March 2012. The goals are to identify the most effective method to deliver SMC, and to obtain more information on the long term impact of SMC on malaria immunity. Our specific aims are 1) to determine the optimal mode (fixed-point (FPD) vs door-to-door delivery (DDD); directly observed treatment (DOT) vs non-DOT (NDOT)) and frequency (3 vs 4 doses per season) of SMC delivery; 2) to compare quantitative measures of immunity in children who do and do not receive SMC. A cluster-randomized design will be sued. The target population will be children aged 3-59 months old in Ouelessebougou district, Mali. In Year 1, villages in four sub-districts will be randomized into four groups (FPD+DOT; FPD+NDOT; DDD+DOT; DDD+NDOT). The optimal mode of delivery will be selected based on the SMC coverage during the first year, and will then be implemented in villages of two additional sub-districts. Villages in these two newly selected sub-districts will be randomized in two groups. Children in the first group will received three rounds of SMC and those in the second group will receive four rounds of SMC to determine the optimal frequency of SMC based on the incidence rate of clinical malaria as measured by passive surveillance. In Year 3, children in the selected sub-districts will received SMC by the optimal delivery system determined in Years 1 -2. A survey will be conducted collect data on mortality and hospital admission and compare these outcomes in areas where SMC was implemented and areas where SMC was not implemented.
Detailed Description
Based in part on the pivotal studies conducted in Mali, SMC was approved by WHO as a policy for malaria control in countries with seasonal malaria transmission such as Mali in March 2012. The strategy is a highly cost-effective approach to reduce childhood mortality in these areas. Despite the huge benefit of the SMC on malaria infection and disease, the optimal approach to deliver SMC remains to be determined and there is no data on the long term effect of this strategy on the development of immunity to malaria. While fixed-point delivery (FPD) combined with non directly observed treatment (NDOT) by community health workers is attractive for the SMC implementation, it is need to be evaluated and compared to other mode of delivery. The objectives are to identify the most effective method to deliver SMC, and to obtain information on the long term impact of SMC on malaria immunity. Specifically, i) to determine the optimal mode (fixed-point (FPD) vs door-to-door delivery (DDD); directly observed treatment (DOT) vs. non-DOT (NDOT)) and frequency (3 vs. 4 doses per season) of SMC delivery; ii) to compare quantitative measures of immunity in children who do and do not receive SMC over a three year period.
The design is a cluster-randomized trial over three years. The target population is children aged 3-59 months old living in Ouelessebougou district, Mali. In Year 1, villages in four sub-districts will be randomized into four groups (FPD+DOT; FPD+NDOT; DDD+DOT; DDD+NDOT). The optimal mode of delivery will be selected based on the SMC coverage during the first year, and will then be implemented in villages of two additional sub-districts. Villages in these two newly selected sub-districts will be randomized in two groups. Children in the first group will received three rounds of SMC and those in the second group will receive four rounds of SMC to determine the optimal frequency of SMC based on the incidence rate of clinical malaria as measured by passive surveillance. Children in the four sub-districts selected in Year 1 will continue to receive three rounds of SMC in Year 2 using the optimal mode of delivery. In Year 3, children in the randomly selected sub-districts will received SMC by the optimal delivery system determined in Years 1 -2. Immune responses will be measured and compared between the children receiving SMC to a cohort of children not receiving SMC, to assess the impact of SMC on key antimalarial antibody responses over the three year period using cross-sectional surveys at the beginning and the end of the transmission season.
In Year 3, 4 and 5 surveys will be conducted to collect data on mortality and hospital admissions and compare these outcomes in areas where SMC was implemented and areas where SMC was not implemented.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Factorial
- Primary Purpose
- Prevention
- Masking
- None
Eligibility Criteria
- Ages
- 3 Months to 59 Months (Child)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •Age >= 3 months & < 60 months
Exclusion Criteria
- •severe, chronic illness
- •known allergy to one of the study drugs (SP or AQ)
- •known HIV positive subjects using Cotrimoxazole.
Outcomes
Primary Outcomes
Coverage of SMC
Time Frame: 1-5 weeks after last round of SMC in Year1
SMC coverage will be defined as proportion of the children who have received the three treatments doses at each of the three rounds of SMC.
Hospital admission
Time Frame: 1, 2, 3, 4 years of the intervention
Hospitalization
Mortality rate
Time Frame: 1, 2, 3, 4 years of the intervention
death
Incidence of clinical malaria in Year 2
Time Frame: up to 4 weeks after the last round of SMC
Clinical malaria defined as signs and symptoms suggestive of malaria with positive RDT and/or positive blood smear.
Secondary Outcomes
- malaria parasitemia(one week before the first round of SMC and 4-6 weeks after the last round of SMC)
- moderate anemia(one week before the first round of SMC and 4-6 weeks after the last round of SMC)
- immune response to malaria parasite(one week before the first round of SMC and 4-6 weeks after the last round of SMC)
- molecular markers of resistance to SP + AQ(one week before the first round of SMC and 4-6 weeks after the last round of SMC)
- Clinical malaria in Year 1(up to 4 weeks after the last round of SMC)
- nutritional status(one week before the first round of SMC and 4-6 weeks after the last round of SMC)
Investigators
Alassane Dicko
Professor
University of Bamako