Effectiveness of Seasonal Malaria Chemoprevention in Children under Ten Years of Age in Senegal: A Stepped-Wedge Cluster-Randomised Trial

Abstract

BackgroundSeasonal Malaria Chemoprevention (SMC) with sulfadoxine-pyrimethamine (SP) plus amodiaquine (AQ), given each month during the transmission season, is recommended for children living in areas of the Sahel where malaria transmission is highly seasonal. The recommendation for SMC is currently limited to children under five years of age, but, in many areas of seasonal transmission, the burden in older children may justify extending this age limit. This study was done to determine the effectiveness of SMC in Senegalese children up to ten years of age.Methods and FindingsSMC was introduced into three districts over three years in central Senegal using a stepped-wedge cluster-randomised design. A census of the population was undertaken and a surveillance system was established to record all deaths and to record all cases of malaria seen at health facilities. A pharmacovigilance system was put in place to detect adverse drug reactions. Fifty-four health posts were randomised. Nine started implementation of SMC in 2008, 18 in 2009, and a further 18 in 2010, with 9 remaining as controls. In the first year of implementation, SMC was delivered to children aged 3–59 months; the age range was then extended for the latter two years of the study to include children up to 10 years of age. Cluster sample surveys at the end of each transmission season were done to measure coverage of SMC and the prevalence of parasitaemia and anaemia, to monitor molecular markers of drug resistance, and to measure insecticide-treated net (ITN) use. Entomological monitoring and assessment of costs of delivery in each health post and of community attitudes to SMC were also undertaken. About 780,000 treatments were administered over three years. Coverage exceeded 80% each month. Mortality, the primary endpoint, was similar in SMC and control areas (4.6 and 4.5 per 1000 respectively in children under 5 years and 1.3 and 1.2 per 1000 in children 5-9 years of age; the overall mortality rate ratio [SMC: no SMC] was 0.90, 95% CI 0.68–1.2, p = 0.496). A reduction of 60% (95% CI 54%–64%, p < 0.001) in the incidence of malaria cases confirmed by a rapid diagnostic test (RDT) and a reduction of 69% (95% CI 65%–72%, p < 0.001) in the number of treatments for malaria (confirmed and unconfirmed) was observed in children. In areas where SMC was implemented, incidence of confirmed malaria in adults and in children too old to receive SMC was reduced by 26% (95% CI 18%–33%, p < 0.001) and the total number of treatments for malaria (confirmed and unconfirmed) in these older age groups was reduced by 29% (95% CI 21%–35%, p < 0.001). One hundred and twenty-three children were admitted to hospital with a diagnosis of severe malaria, with 64 in control areas and 59 in SMC areas, showing a reduction in the incidence rate of severe disease of 45% (95% CI 5%–68%, p = 0.031). Estimates of the reduction in the prevalence of parasitaemia at the end of the transmission season in SMC areas were 68% (95% CI 35%–85%) p = 0.002 in 2008, 84% (95% CI 58%–94%, p < 0.001) in 2...

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“…Nonetheless, our results are indicative of the potential value of extending the target age range of seasonal malaria chemoprevention to include older school-aged children. 32 …”

Prevalence of asymptomatic malaria parasitaemia following mass testing and treatment in Pakro sub-district of Ghana

“…Attempts to implement mass treatment in endemic communities SMC are presently limited to children under 5 in the Sahelian region of Africa. SMC has been shown to reduce the burden of malaria in children below 5 years in Senegal, Mali and Burkina Faso and has further been proven to be affordable if extended to 10 year old children [29,[37][38][39][40]. While SMC has targeted the Sahelian region with marked seasonal transmission, strategies for reducing malaria parasitaemia towards elimination in other endemic transmission areas of Africa, which cover the broader population are needed.…”

Seasonal Malaria Chemoprevention: An Evolving Research Paradigm

“…They found a 60% reduction in malaria incidence [1]. This empirical evidence demonstrates the benefits that can be gained by increasing the age window of targeted SMC in areas where transmission intensity is either already moderately low or brought down by vector control.…”

“…Milligan and colleagues used a step-wedged design to incrementally test the effects of monthly distribution of SP+AQ to children under the age of ten years during the short malaria season in Senegal [1]. They found a 60% reduction in malaria incidence [1].…”

“…In this issue, Paul Milligan and colleagues [1] provide evidence of the dramatic impact on the incidence of malaria of seasonal malaria chemoprevention (SMC) among children aged older than five years, the current recommended upper age limit for SMC. Research on drugs to prevent malaria in Africa among nonpregnant populations has a long history with surprisingly little sustainable policy impact.…”