Effectiveness of seasonal malaria chemoprevention at scale in west and central Africa: an observational study

Abstract

Summary Background Seasonal malaria chemoprevention (SMC) aims to prevent malaria in children during the high malaria transmission season. The Achieving Catalytic Expansion of SMC in the Sahel (ACCESS-SMC) project sought to remove barriers to the scale-up of SMC in seven countries in 2015 and 2016. We evaluated the project, including coverage, effectiveness of the intervention, safety, feasibility, drug resistance, and cost-effectiveness. Methods For this observational study, we collected data on the delivery, effectiveness, safety, influence on drug resistance, costs of delivery, impact on malaria incidence and mortality, and cost-effectiveness of SMC, during its administration for 4 months each year (2015 and 2016) to children younger than 5 years, in Burkina Faso, Chad, The Gambia, Guinea, Mali, Niger, and Nigeria. SMC was administered monthly by community health workers who visited door-to-door. Drug administration was monitored via tally sheets and via household cluster-sample coverage surveys. Pharmacovigilance was based on targeted spontaneous reporting and monitoring systems were strengthened. Molecular markers of resistance to sulfadoxine–pyrimethamine and amodiaquine in the general population before and 2 years after SMC introduction was assessed from community surveys. Effectiveness of monthly SMC treatments was measured in case-control studies that compared receipt of SMC between patients with confirmed malaria and neighbourhood-matched community controls eligible to receive SMC. Impact on incidence and mortality was assessed from confirmed outpatient cases, hospital admissions, and deaths associated with malaria, as reported in national health management information systems in Burkina Faso and The Gambia, and from data from selected outpatient facilities (all countries). Provider costs of SMC were estimated from financial costs, costs of health-care staff time, and volunteer opportunity costs, and cost-effectiveness ratios were calculated as the total cost of SMC in each country divided by the predicted number of cases averted. Findings 12 467 933 monthly SMC treatments were administered in 2015 to a target population of 3 650 455 children, and 25 117 480 were administered in 2016 to a target population of 7 551 491. In 2015, among eligible children, mean coverage per month was 76·4% (95% CI 74·0–78·8), and 54·5% children (95% CI 50·4–58·7) received all four treatments. Similar coverage was achieved in 2016 (74·8% [72·2–77·3] treated per month and 53·0% [48·5–57·4] treated four times). In 779 individual case safety reports over 2015–16, 36 serious adverse drug reactions were reported (one child with rash, two with fever, 31 with gastrointestinal disorders, one with extrapyramidal syndrome, and one with Quincke's oedema). No cases of severe skin reactions (Stevens-Johnson or Lyell syndrome) were reported. SMC treatment was associated with a protective effectiveness of 88·2% (95% CI 78·7–93·4) over 28 days in case-c...

Genetic surveillance for monitoring the impact of drug use on Plasmodium falciparum populations

“…There is general evidence that SMC is effective in reducing the episodes of P. falciparum malaria, with a Cochrane review ( Meremikwu et al, 2012 ) reporting that SMC was effective in reducing the incidence of malaria by approximately 75 % in children under 6 years of age during the transmission season in areas with seasonal malaria transmission. Another study ( Access-SMC-Partnership, 2020 ) also reported reduced mortality. Subsequent reviews concurred on the benefits of SMC ( Ashley and Poespoprodjo, 2020 ; Gutman et al, 2017 ; McCann et al, 2020 ), with reports of prevalence reduction by 65 % and incidence reduction by 80 % following SMC ( Greenwood, 2017 ; York, 2017 ).…”

“…Challenges to evaluating the statistical and clinical impact of population-level drug-based interventions like SMC and MDA include monitoring impact on malaria burden, evaluating the clinical benefit of these interventions, and addressing whether these interventions can interrupt transmission ( WHO, 2013 , 2015 , 2017 ). Historically, the impact of SMC or MDA has been assessed based on epidemiological metrics like prevalence or incidence ( Access-SMC-Partnership, 2020 ) ( Supplemental Table 1 ); however, these indicators may not reveal important changes to the parasite population and become more challenging to assess in certain contexts such as very low transmission settings. Measuring the impact of these interventions on clinical metrics like anemia or childhood mortality requires careful study designs that are powered to evaluate these outcomes ( Cohee et al, 2020 ).…”

Geographical and temporal variation in reduction of malaria infection among children under 5 years of age throughout Nigeria

“…Community-based trials in diverse areas of West Africa where malaria is highly seasonal have demonstrated that the effect of intensively-delivered SMC on clinical incidence and parasite prevalence should be substantial. [24][25][26] Although there are many challenges to optimal implementation in northern Nigeria where malaria is most seasonal, it is notable that SMC has been safely and effectively delivered to children up to the age of 10 years in trials in Senegal, 27 so potential benefits of expanding the age coverage in Nigeria should be considered, while continuing efforts to establish effective delivery to younger children as currently intended.…”

Geographical and temporal variation in reduction of malaria infection among children under five years of age throughout Nigeria

“…In addition to established methods, seasonal malaria chemoprevention (SMC) targeted to children under five years of age became a policy from 2014 onwards in several of the northern states where malaria prevalence has remained high, but only very limited implementation occurred in a few states before the 2018 survey. Community-based trials in diverse areas of West Africa where malaria is highly seasonal have demonstrated that the effect of intensively-delivered SMC on clinical incidence and parasite prevalence should be substantial 24-26 . Although there are many challenges to optimal implementation in northern Nigeria where malaria is most seasonal, it is notable that SMC has been safely and effectively delivered to children up to the age of 10 years in trials in Senegal 27 , so potential benefits of expanding the age coverage in Nigeria should be considered, while continuing efforts to establish effective delivery to younger children as currently intended.…”