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

BACKGROUND: Seasonal 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 FINDINGS: SMC 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 2009, and 30% (95% CI -130%-79%, p = 0.56) in 2010. SMC was well tolerated with no serious adverse reactions attributable to SMC drugs. Vomiting was the most commonly reported mild adverse event but was reported in less than 1% of treatments. The average cost of delivery was US$0.50 per child per month, but varied widely depending on the size of the health post. Limitations included the low rate of mortality, which limited our ability to detect an effect on this endpoint. CONCLUSIONS: SMC substantially reduced the incidence of outpatient cases of malaria and of severe malaria in children, but no difference in all-cause mortality was observed. Introduction of SMC was associated with an overall reduction in malaria incidence in untreated age groups. In many areas of Africa with seasonal malaria, there is a substantial burden in older children that could be prevented by SMC. SMC in older children is well tolerated and effective and can contribute to reducing malaria transmission. TRIAL REGISTRATION: ClinicalTrials.gov NCT00712374

Management of pituitary adenoma: Preliminary experience with endoscopic endonasal transphenoidal surgery in a developing country. Example of Senegal about 180 cases

Introduction: Endoscopic endonasal transsphenoidal surgery is currently the gold-standard therapeutic approach for pituitary adenomas. Although being spread worldwide, the endoscopic endonasal approach for pituitary adenomas is recently implemented in Senegal.This study aimed to report our results and the complications observed in the context of an under-equipped facility. Materials and methods: We conducted a retrospective study including all patients with a pituitary adenoma treated who underwent endonasal transsphenoidal resection under a single endoscopic approach from January 2014 to May 2022, in the Neurosurgery Department of Fann National Hospital Centre, Dakar. All patients were assessed according to clinical, radiological, and endocrinological criteria. They all were operated by the same team with an average follow-up of 24 months. Results: In this series of 180 patients, including 57.7 % women and 42.3% men with a mean age of 44.8 years (extremes of 18 and 76 years), the visual deficit was the most frequent onset symptom (69.4 %), followed by clinical forms of hormone hypersecretion (30.5 %). Twelve cases of pituitary apoplexy and 1 case of incidentaloma were reported. The most frequent tumors were non-functional tumors (61.6 %). Among the functional adenomas, the most frequent was prolactinoma (15.5 %). Regarding tumor size, 75 % were macroadenomas, 15.5 % were microadenomas, and 9.5 % were giants. Cavernous sinus invasion (Knosp grade ≥ 3) and suprasellar extension were noted in 14.4 % and 53.3 %, respectively. The resection was total in 80 % of cases, subtotal in 18.8 %, and partial in 1.2 %. Partial improvement of sight was observed in 91.1% and endocrine hypersecretion remission in 76.6 %. As for complications, the most frequent was transient diabetes insipidus (32.7 %). Conclusion: Despite the scanty resources, our results are similar to the best-reported series and strengthen scientific evidence on the efficacy and safety of performing this technique in an under-equipped setting context

Prevalence of <i>P</i>. <i>falciparum</i> parasitaemia in children under five years old (2008) and under ten years old (2009 and 2010)^* in SMC and control areas at the end of the malaria transmission season.

<p>Prevalence of <i>P</i>. <i>falciparum</i> parasitaemia in children under five years old (2008) and under ten years old (2009 and 2010)^{<a href="http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.1002175#t003fn001" target="_blank">*</a>} in SMC and control areas at the end of the malaria transmission season.</p

Trial profile.

<p>Trial profile.</p

Characteristics of the randomised intervention zones.

<p>Characteristics of the randomised intervention zones.</p

Stepped-wedge introduction of SMC in 45 health post areas over three years.

<p>The upper maps show the health district boundaries (the district of Fatick was subdivided in 2010 to create a new district of Niakhar); land cover and water bodies; and the location of villages and health facilities. In the lower maps, the polygons show the catchment areas of the 54 health posts (drawn as the convex hull of the village coordinates). ^# Each zone comprised nine health post areas. The nine health post areas in Zone 6 remained untreated. * In 2008, SMC was delivered to children aged 3–59 months; in other years, SMC was provided for children aged 3–119 months.</p

The malaria incidence rate ratio after to before introduction of SMC is shown for five study zones (1–5) where SMC was introduced, and the control area (Zone 6) that remained without SMC.

<p>The <i>y</i>-axis is the rate ratio comparing the years 2010:2008. Rate ratios for each age group are shown.</p