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

Abstract

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.

Trial registration: ClinicalTrials.gov NCT00712374.

Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1. Trial profile, showing the number of children in each zone in the stepped-wedge trial.

Fig 2. Map of the study area showing health facilities involved in SMC delivery and pharmacovigilance.

Fig 3. Adverse drug reactions notified by health facilities within 10 days of SMC administration.

The incidence as the percentage of children who were treated is indicated on the left hand axis) and number of cases on the right hand axis). In 2009, the total number of adverse event reports was 33% (95% CI 19%,45%) lower in October than in September and 69% (95% CI 61%,76%) lower in November than in September. In 2010 the number of adverse events was 35% (95% CI 25%,44%) lower in October than in September, and in 70% (95% CI 64%,75%) lower in November.

Fig 4. Age distribution of cases (upper left); time from the first SMC dose to onset of symptoms (upper right); duration of symptoms (lower left) and frequency of vomiting (lower right) in 108 children who presented at the clinic with symptoms of vomiting within 1 week of SMC administration.