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PARTNERSHIPS FOR ENHANCED ENGAGEMENT IN RESEARCH (PEER) HEALTH
Cycle 1


Principal Investigator: Alassane Dicko, University of Bamako
NIH-Supported Collaborator: Patrick Duffy, National Institute of Allergy and Infectious Disease (NIAID)
Title of NIH Award: Malaria Immunology and Pathogenesis in Pregnant Women and Young Children
Project Dates: February 2014 - April 2019

Project Overview
 
Malaria is the leading cause of morbidity and mortality in Mali. Despite effective implementation of usual control measures such as insecticide treated nets (ITN) and artemisinin combination therapy (ACT) malaria remains the number one killer in Mali. We recently showed that Seasonal Malaria Chemoprevention (SMC), previously known as Intermittent Preventive Treatment of Malaria in children, reduces malaria infection and disease by more 80% in Malian children, prompting the WHO to approve SMC as policy for 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. An optimal SMC delivery approach will make a substantial contribution toward the achievement of the goals of the US President’s Malaria Initiative (PMI) and the Millenium Development Goals. The objectives of the study are to identify the most effective method to deliver SMC, and to obtain information on the long term impact of SMC on malaria immunity. The design is a cluster-randomized trial over three years. By using a step-wedge design, the investigators aim to i) 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 anticipated outcome of the study will be a qualified optimal approach to deliver SMC in Mali, and an expanded understanding of its impact on health outcomes and antimalarial immunity. The results will be shared with stakeholders, and will be used at the end of each year to guide the implementation of SMC in Mali.
 
PH 1-85 Mali photo 2PH 1-85 Mali photo 1

Summary of Overall Activities:

The initial key objectives of the project were all achieved. These include:
  1. Determination of the optimal delivery method for SMC. The team demonstrated that a door-to-door delivery method provides higher coverage than the fixed-point delivery method that was used in Mali. Project results prompted the government to change the SMC delivery method from fixed-point to door-to-door, leading to higher coverage and protection of children against malaria. The team has also demonstrated that direct observation of the second and third day treatment does not improve the SMC coverage compared to when these treatments were given to the care givers for administration. The results were published in PloS One (Barry et al 201).
     
  2. Assessment of the long-term impact of SMC on malaria immunity. Project results indicated that three or four years of SMC was not associated with a decrease to the IgG levels of AMA1, MSP1 and CSP. Part of these results were published in Malaria J (Mahamar et al 2017, Mahamar et al, manuscript in preparation). Four years of antimalarial administration through SMC was not associated with a decrease to the IgG levels of AMA1, MSP1 and CSP.
     
  3. Assessment of the long-term impact of SMC on resistance of P. falciparum to SMC drugs. The analysis of molecular markers associated with the resistance of P. falciparum to Sulfadoxine- pyrimethamine and amodiaquine (the drugs used for SMC) indicated that two and three years of SMC implementation were not associated with an increase in frequency of the molecular markers of the resistance to SP, although the presence of the dhps 581G mutation for the first time, although at very low frequency, warrant further surveillance in the longer term (Mahamar et al, manuscript in preparation).
All these results have implications for policy and were presented in various meetings at national and international levels including: i) annual meetings of the national malaria control program in Mali on SMC; ii) the regional meetings such as annual SMC meeting for ECOWAS countries; and iii) International meeting such as the meeting of the Multilateral Initiative on Malaria (MIM) and the annual meetings of the American Society of Tropical Medicine and Hygiene.


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