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-control
studies (2185 cases of confirmed malaria and 4370 controls). In Burkina Faso and The Gambia, implementation of
SMC was associated with reductions in the number of malaria deaths in hospital during the high transmission
period, of 42·4% (95% CI 5·9 to 64·7) in Burkina Faso and 56·6% (28·9 to 73·5) in The Gambia. Over 2015–16, the
estimated reduction in confirmed malaria cases at outpatient clinics during the high transmission period in the seven
countries ranged from 25·5% (95% CI 6·1 to 40·9) in Nigeria to 55·2% (42·0 to 65·3) in The Gambia. Molecular
markers of resistance occurred at low frequencies. In individuals aged 10–30 years without SMC, the combined
mutations associated with resistance to amodiaquine (pfcrt CVIET haplotype and pfmdr1 mutations [86Tyr and
184Tyr]) had a prevalence of 0·7% (95% CI 0·4–1·2) in 2016 and 0·4% (0·1–0·8) in 2018 (prevalence ratio 0·5 [95% CI
0·2–1·2]), and the quintuple mutation associated with resistance to sulfadoxine–pyrimethamine (triple mutation in
pfdhfr and pfdhps mutations [437Gly and 540Glu]) had a prevalence of 0·2% (0·1–0·5) in 2016 and 1·0% (0·6–1·6)
in 2018 (prevalence ratio 4·8 [1·7–13·7]). The weighted average economic cost of administering four monthly SMC
treatments was US$3·63 per child.
Interpretation SMC at scale was effective in preventing morbidity and mortality from malaria. Serious adverse
reactions were rarely reported. Coverage varied, with some areas consistently achieving high levels via doorto-
door campaigns. Markers of resistance to sulfadoxine–pyrimethamine and amodiaquine remained uncommon,
but with some selection for resistance to sulfadoxine–pyrimethamine, and the situation needs to be carefully
monitored. These findings should support efforts to ensure high levels of SMC coverage in west and central
Africa.