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Safety of Seasonal Malaria Chemoprevention (SMC) with Sulfadoxine-Pyrimethamine plus Amodiaquine when Delivered to Children under 10 Years of Age by District Health Services in Senegal: Results from a Stepped-Wedge Cluster Randomized Trial
Open accessAbstract
BACKGROUND: It is recommended that children aged 3 months to five years of age living in areas of seasonal transmission in the sub-Sahel should receive Seasonal Malaria Chemoprevention (SMC) with sulfadoxine-pyrimethamine plus amodiaquine (SPAQ) during the malaria transmission season. The purpose of this study was to evaluate the safety of SMC with SPAQ in children when delivered by community health workers in three districts in Senegal where SMC was introduced over three years, in children from 3 months of age to five years of age in the first year, then in children up to 10 years of age. METHODS: A surveillance system was established to record all deaths and all malaria cases diagnosed at health facilities and a pharmacovigilance system was established to detect adverse drug reactions. Health posts were randomized to introduce SMC in a stepped wedge design. SMC with SPAQ was administered once per month from September to November, by nine health-posts in 2008, by 27 in 2009 and by 45 in 2010. RESULTS: After three years, 780,000 documented courses of SMC had been administered. High coverage was achieved. No serious adverse events attributable to the intervention were detected, despite a high level of surveillance. CONCLUSIONS: SMC is being implemented in countries of the sub-Sahel for children under 5 years of age, but in some areas the age distribution of cases of malaria may justify extending this age limit, as has been done in Senegal. Our results show that SMC is well tolerated in children under five and in older children. However, pharmacovigilance should be maintained where SMC is implemented and provision for strengthening national pharmacovigilance systems should be included in plans for SMC implementation. TRIAL REGISTRATION: ClinicalTrials.gov NCT 00712374.
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Ndiaye et al. (2016) chose the stepped wedge design to allow phased implementation and rigorous evaluation while ensuring all clusters eventually received the intervention, and because it was logistically feasible.
“The stepped wedge design was chosen to allow phased implementation and rigorous evaluation of the intervention's safety and effectiveness while ensuring all clusters eventually received the intervention. This design was logistically feasible and allowed for the evaluation of SMC's impact on a large scale”
From Applications and implementation considerations for stepped-wedge designs in sub-Saharan Africa: a systematic review (2026) · cites this paper as [61]
The Study design section (page unavailable) confirms that SMC was introduced in phases, but directly contradicts the claim that all clusters eventually received it: nine health posts remained without the intervention. The paper does not state that logistical feasibility was a reason for choosing the design. (LLM, conf=0.86)
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Experimental — accuracy not yet measuredNdiaye et al. (2016) randomized 54 health posts to implement SMC in either 2008, 2009, or 2010, with nine health posts remaining without the intervention each year for comparison.
“Fifty-four health posts were randomized to implement SMC in either 2008, 2009, or 2010. Nine health posts remained without the intervention each year for comparison purposes.”
From Applications and implementation considerations for stepped-wedge designs in sub-Saharan Africa: a systematic review (2026) · cites this paper as [61]
The Study design section confirms that 54 health posts were randomized to introduce SMC in 2008, 2009, or 2010. It does not support nine posts remaining without SMC each year: nine were untreated in 2010, but 45 were untreated in 2008 and, from the reported rollout, 27 in 2009. (LLM, conf=0.91)
Experimental — accuracy not yet measuredNdiaye et al. (2016) had a duration of 3 years.
“3 years”
From Applications and implementation considerations for stepped-wedge designs in sub-Saharan Africa: a systematic review (2026) · cites this paper as [61]
Ndiaye et al. (2016) included 54 clusters (health posts).
“54”
From Applications and implementation considerations for stepped-wedge designs in sub-Saharan Africa: a systematic review (2026) · cites this paper as [61]
Ndiaye et al. (2016) used three steps in the stepped wedge design.
“3”
From Applications and implementation considerations for stepped-wedge designs in sub-Saharan Africa: a systematic review (2026) · cites this paper as [61]
Pharmaceutical and biomedical interventions, including PrEP and SMC, were commonly evaluated using SWD, supporting its utility for phased implementation of large-scale public health strategies in low- and middle-income settings.
“Pharmaceutical and biomedical interventions, including PrEP (93) and SMC (61), were also commonly evaluated using SWD, supporting its utility for phased implementation of large-scale public health strategies in low- and middle-income settings (34, 40, 113).”
From Applications and implementation considerations for stepped-wedge designs in sub-Saharan Africa: a systematic review (2026) · cites this paper as [61]
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References 20 · Cited by 60
Research works printed but not linked: 19
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Metadata
- Authors
- NDiaye, J. L., Cissé, B., Ba, E. H., Gomis, J. F., Ndour, C. T., Molez, J. F., Fall, F. B., Sokhna, C., Faye, B., Kouevijdin, E., Niane, F. K., Cairns, M., Trape, J. F., Rogier, C., Gaye, O., Greenwood, B. M., & Milligan, P. J. M.
- Affiliations
- Cheikh Anta Diop University (SN)
- Institut Pasteur de Madagascar (MG)
- Institut de Recherche pour le Développement (SN)
- London School of Hygiene & Tropical Medicine (GB)
- Corresponding author
- Milligan, P. J. M.
- ORCID
- Venue
- PLOS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2016-10-20
- Volume
- 11
- Issue
- 10
- Pages
- e0162563
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC5072628
- OpenAlex
- W2536894942
- Cited by
- 60
- References
- 20
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 8 · 2023: 8 · 2022: 11 · 2021: 9 · 2020: 6 · 2019: 2 · 2018: 5 · 2017: 2 · 2016: 2
- FWCI
- 3.64
- Type
- journal article
- Language
- en
- Update notices
- correction (2016-12-08)
- Open access
- gold
- doi.org
- Licence
- Locations
- PLoS ONE (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- LSHTM Research Online (London School of Hygiene and Tropical Medicine) (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Figshare (submittedVersion, cc-by)
- Funders
- Bill and Melinda Gates Foundation (40099)
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Malaria Research and Control
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Toxicology › Pharmacovigilance and Adverse Drug Reactions
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Travel-related health issues
- Keywords
- seasonal malaria chemoprevention, sulfadoxine-pyrimethamine, amodiaquine, drug safety, adverse drug reactions, pharmacovigilance, children under five, community health workers, pediatric malaria, Senegal, sub-Saharan Africa
- MeSH terms
- Amodiaquine, Antimalarials, Child, Child, Preschool, Drug Combinations, Drug Therapy, Combination, Female, Health Services, Hospitalization, Humans, Infant, Jaundice, Malaria, Male, Pyrimethamine, Seasons, Senegal, Sulfadoxine, Survival Analysis, Chemoprevention
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