Systematic Review and Meta-Analysis of Seasonal Malaria Chemoprevention

Abstract

Seasonal malaria chemoprevention (SMC) for children under 5 years of age for up to four monthly cycles during malaria transmission season was recommended by the WHO in 2012 and has been implemented in 13 countries in the Sahel, reaching more than 30 million children annually. Malaria control programs implementing SMC have asked the WHO to consider expanding the age range or number of monthly cycles. We conducted a systematic review and meta-analysis of SMC among children up to 15 years of age and up to six monthly cycles. Twelve randomized studies were included, with outcomes stratified by age (< 5/≥ 5 years), by three or four versus five or six cycles, and by drug where possible. Drug regimens included sulfadoxine-pyrimethamine + amodiaquine, amodiaquine-artesunate, and sulfadoxine-pyrimethamine + artesunate. Included studies were all conducted in Sahelian countries in which high-grade resistance to sulfadoxine-pyrimethamine was rare and in zones with parasite prevalence ranging from 1% to 79%. Seasonal malaria chemoprevention resulted in substantial reductions in uncomplicated malaria incidence measured during that transmission season (rate ratio: 0.27, 95% CI: 0.25-0.29 among children < 5 years; rate ratio: 0.27, 95% CI: 0.25-0.30 among children ≥ 5 years) and in the prevalence of malaria parasitemia measured within 4-6 weeks from the final SMC cycle (risk ratio: 0.38, 95% CI: 0.34-0.43 among children < 5 years; risk ratio: 0.23, 95% CI: 0.11-0.48 among children ≥ 5 years). In high-transmission zones, SMC resulted in a moderately reduced risk of any anemia (risk ratio: 0.77, 95% CI: 0.72-0.83 among children < 5 years; risk ratio: 0.70, 95% CI: 0.52-0.95 among children ≥ 5 years [one study]). Children < 10 years of age had a moderate reduction in severe malaria (risk ratio: 0.53, 95% CI: 0.37-0.76) but no evidence of a mortality reduction. The evidence suggests that in areas in which sulfadoxine-pyrimethamine and amodiaquine remained efficacious, SMC effectively reduced malaria disease burden among children both < 5 and ≥ 5 years old and that the number of cycles should be commensurate with the length of the transmission season, up to six cycles.

Figure 1.

Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) diagram. AL = artemether–lumefantrine; AQ = amodiaquine; AS = artesunate; AZ = azithromycin; DP = dihydroartemisinin–piperaquine; IPTi = intermittent preventive treatment in infancy; SMC = seasonal malaria chemoprevention; SP = sulfadoxine–pyrimethamine.

Figure 2.

Location of eligible seasonal malaria chemoprevention studies. Zones: Sahel—mean annual precipitation 200–700 mm; Sudan—mean annual precipitation 700–900 mm; Guinean—mean annual precipitation 900–1,600 mm; and Guineo–Congolian—mean annual precipitation 1,600–2,000 mm.

Figure 3.

Risk of bias summary: review authors’ judgments about each risk of bias item for each included study by malaria outcomes, randomized studies. Revised risk of bias (RoB 2) tool: Domain 1a. Risk of bias arising from randomization; Domain 1b. Risk of bias from timing of identification/recruitment; Domain 2. Risk of bias due to deviations from intended intervention; Domain 3. Missing outcome data; Domain 4. Risk of bias in measurement of the outcome; Domain 5. Risk of bias in selection of reported result. Color code: green—low risk of bias; yellow—some concern for bias; red—high risk of bias.

Figure 4.

Incidence among children < 5 years of age by drug regimen, three or four cycles versus five or six cycles. AS–AQ = artesunate–amodiaquine; df = degrees of freedom; SE = standard error; SMC = seasonal malaria chemoprevention; SP+AQ = sulfadoxine–pyrimethamine + amodiaquine; SP+AS = sulfadoxine–pyrimethamine + artesunate.

Figure 5.

Incidence among children ≥ 5 years of age by drug regimen, three or four cycles versus five or six cycles, randomized studies. AS–AQ = artesunate–amodiaquine; SE = standard error; SP+AQ = sulfadoxine–pyrimethamine + amodiaquine.

Figure 6.

Prevalence among children < 5 years of age by drug regimen, three or four cycles versus five or six cycles, randomized studies. AS–AQ = artesunate–amodiaquine; SE = standard error; SMC = seasonal malaria chemoprevention; SP+AQ = sulfadoxine–pyrimethamine + amodiaquine; SP+AS = sulfadoxine–pyrimethamine + artesunate.