Kirsten Simondon

Seasonal intermittent preventive treatment with artesunate and sulfadoxine-pyrimethamine for prevention of malaria in Senegalese children: a randomised placebo-controlled double-blind trial.

BACKGROUND In the Sahel and sub-Sahelian regions of Africa, malaria transmission is highly seasonal. During a short period of high malaria transmission, mortality and morbidity are high in children under age 5 years. We assessed the efficacy of seasonal intermittent preventive treatment-a full dose of antimalarial treatment given at defined times without previous testing for malaria infection. METHODS We did a randomised, placebo-controlled, double-blind trial of the effect of intermittent preventive treatment on morbidity from malaria in three health-care centres in Niakhar, a rural area of Senegal. 1136 children aged 2-59 months received either one dose of artesunate plus one dose of sulfadoxine-pyrimethamine or two placebos on three occasions during the malaria transmission season. The primary outcome was a first or single episode of clinical malaria detected through active or passive case detection. Primary analysis was by intention-to-treat. This study is registered with , number NCT00132561. FINDINGS During 13 weeks of follow-up, the intervention led to an 86% (95% CI 80-90) reduction in the occurrence of clinical episodes of malaria. With passive case detection, protective efficacy against malaria was 86% (77-92), and when detected actively was 86% (78-91). The incidence of malaria in children on active drugs was 308 episodes per 1000 person-years at risk, whereas in those on placebo it was 2250 episodes per 1000 person-years at risk. 13 children were not included in the intention-to-treat analysis, which was restricted to children who received a first dose of antimalarial or placebo. There was an increase in vomiting in children who received the active drugs, but generally the intervention was well tolerated. INTERPRETATION Intermittent preventive treatment could be highly effective for prevention of malaria in children under 5 years of age living in areas of seasonal malaria infection.

A trial of the efficacy, safety and impact on drug resistance of four drug regimens for seasonal intermittent preventive treatment for malaria in Senegalese children.

Summary In the Sahel, most malaria deaths occur among children 1–4 years old during a short transmission season. A trial of seasonal intermittent preventive treatment (IPT) with sulfadoxine-pyrimethamine (SP) and a single dose of artesunate (AS) showed an 86% reduction in the incidence of malaria in Senegal but this may not be the optimum regimen. We compared this regimen with three alternatives. Methods 2102 children aged 6–59 months received either one dose of SP plus one dose of AS (SP+1AS) (the previous regimen), one dose of SP plus 3 daily doses of AS (SP+3AS), one dose of SP plus three daily doses of amodiaquine (AQ) (SP+3AQ) or 3 daily doses of AQ and AS (3AQ+3AS). Treatments were given once a month on three occasions during the malaria transmission season. The primary end point was incidence of clinical malaria. Secondary end-points were incidence of adverse events, mean haemoglobin concentration and prevalence of parasites carrying markers of resistance to SP. Findings The incidence of malaria, and the prevalence of parasitaemia at the end of the transmission season, were lowest in the group that received SP+3AQ: 10% of children in the group that received SP+1AS had malaria, compared to 9% in the SP+3AS group (hazard ratio HR 0.90, 95%CI 0.60, 1.36); 11% in the 3AQ+3AS group, HR 1.1 (0.76–1.7); and 5% in the SP+3AQ group, HR 0.50 (0.30–0.81). Mutations associated with resistance to SP were present in almost all parasites detected at the end of the transmission season, but the prevalence of Plasmodium falciparum was very low in the SP+3AQ group. Conclusions Monthly treatment with SP+3AQ is a highly effective regimen for seasonal IPT. Choice of this regimen would minimise the spread of drug resistance and allow artemisinins to be reserved for the treatment of acute clinical malaria. Trial Registration Clinicaltrials.gov NCT00132548

Preschool stunting, age at menarche and adolescent height: a longitudinal study in rural Senegal

Objective: To study the impact of preschool stunting on adolescent height and age at menarche in rural West Africa.Design: A longitudinal, population-based study.Setting: The Niakhar study area in Central Senegal.Subjects: 1650 children aged 12–17 y with known height-for-age at the age of 2–5 y.Main outcome measures: Adolescent height; mean age at menarche of girls estimated by the status quo method.Results: The subjects were divided into three groups of preschool height-for-age: <−2, −2 to −1 and >−1 z-score of the NCHS reference. The mean height during adolescence differed significantly according to preschool height-for-age for both boys and girls (P<0.001). Relative risk of adolescent stunting according to preschool stunting varied from 2.0–4.0 depending on age and sex. Estimated mean age at menarche was 17.2 (95% fiducial confidence interval: 16.6–18.7), 16.5 (16.1–17.2) and 15.6 (15.2–16.0) y, respectively, for the three groups of preschool height-for-age (P<0.001). Mean increment from age 5 y to adolescence did not differ significantly among the boys according to preschool stunting, but among the girls aged 16–17 y, the increment was higher for those who had been stunted during preschool life (P<0.01).Conclusion: Some evidence of catch-up growth between the ages of 5 and 17 y was found for stunted girls. The significant delay in sexual maturation of the stunted girls suggests that stunted children of both sexes have a possibility of catch-up growth after the age of 17 y.Sponsorship: The preschool study was supported by the EEC (TSD-036).

Relationship between stunting in infancy and growth and fat distribution during adolescence in Senegalese girls.

Objective: To study the long-term impact of stunting during infancy on maturation, growth and fat distribution in adolescence.Design: A cohort of 406 Senegalese adolescent girls of rural origin underwent clinical and growth assessments every year from 1995 to 1999.Subjects: Mean coverage rate was 82% at each round. Adolescent girls were 11.4±0.5 y of age in 1995 and 15.5±0.5 y of age in 1999. Their growth status during infancy was known. About 20% of the girls had a height–age (H–age) below −2 Z-scores (chronic malnutrition or stunting) when they were 6–18 months of age. As adolescents, the girls were divided into two groups on the basis of H–age: those stunted and those non-stunted during infancy.Measurements: Sexual maturation was assessed by stage of breast development and menarche. Height, body mass, sitting height, bi-iliac and bi-acromial diameters, and six skinfolds were measured.Results: Differences in sexual maturation between previously stunted and non-stunted girls were not significant. Girls stunted at infancy caught up in body weight and subcutaneous fat mass during puberty, but they did not catch up on stature, sitting height or skeletal breadths (bi-acromial and bi-iliac diameters) until the final observation in 1999. Stunted girls did not have less subcutaneous fat (sum of six skinfolds) or a lower BMI. Regional variation in subcutaneous fat distribution (Z-score profile) indicated greater accretion at the biceps and subscapular sites in stunted compared to the non-stunted girls. Regional fat distribution was also assessed by principal component analysis (PCA) performed on the residuals of the six skinfolds measured during the final round (1999). PCA identified three components. Stunted and non-stunted girls were similar for the first (trunk–extremity contrast) and second (anterior–posterior contrast) components. However, there was a difference for the third component: stunted girls tended to accumulate more subcutaneous fat on the upper part of the body (trunk or arms) than non-stunted girls.Conclusion: Stunted Senegalese girls have a potential for catching up in growth during puberty. The greater accumulation of subcutaneous fat on the upper body in stunted girls may be a consequence of complex hormonal adjustments at the onset of puberty.Sponsorship: Institut de Recherche pour le Développement (IRD anciennement ORSTOM) and the Nestlé Foundation.European Journal of Clinical Nutrition (2001) 55, 50–58

Impact of child malnutrition on the specific anti-Plasmodium falciparum antibody response

BackgroundIn sub-Saharan Africa, preschool children represent the population most vulnerable to malaria and malnutrition. It is widely recognized that malnutrition compromises the immune function, resulting in higher risk of infection. However, very few studies have investigated the relationship between malaria, malnutrition and specific immunity. In the present study, the anti-Plasmodium falciparum IgG antibody (Ab) response was evaluated in children according to the type of malnutrition.MethodsAnthropometric assessment and blood sample collection were carried out during a cross-sectional survey including rural Senegalese preschool children. This cross-sectional survey was conducted in July 2003 at the onset of the rainy season. Malnutrition was defined as stunting (height-for-age <-2 z-scores) or wasting (weight-for-height <-2 z-scores). The analysis was performed on all malnourished children in July (n = 161, either stunted, n = 142 or wasted, n = 19), pair-matched to well-nourished controls. The IgG Ab response to P. falciparum whole extracts (schizont antigens) was assessed by ELISA in sera of the included children.ResultsBoth the prevalence of anti-malarial immune responders and specific IgG Ab levels were significantly lower in malnourished children than in controls. Depending on the type of malnutrition, wasted children and stunted children presented a lower specific IgG Ab response than their respective controls, but this difference was significant only in stunted children (P = 0.026). This down-regulation of the specific Ab response seemed to be explained by severely stunted children (HAZ ≤ -2.5) compared to their controls (P = 0.03), while no significant difference was observed in mildly stunted children (-2.5 < HAZ <-2.0). The influence of child malnutrition on the specific anti-P. falciparum Ab response appeared to be independent of the intensity of infection.ConclusionChild malnutrition, and particularly stunting, may down-regulate the anti-P. falciparum Ab response, both in terms of prevalence of immune responders and specific IgG Ab levels. This study provides further evidence for the influence of malnutrition on the specific anti-malarial immune response and points to the importance of taking into account child malnutrition in malaria epidemiological studies and vaccine trials.

Lipodystrophy and metabolic disorders in HIV-1-infected adults on 4- to 9-year antiretroviral therapy in Senegal: a case-control study.

Objective:To assess adverse effects of long-term highly active antiretroviral therapy (HAART), that is, lipodystrophy and metabolic disorders, in a cohort of African patients. Methods:One hundred eighty HIV-1-infected patients treated with HAART for 4-9 years in Dakar and 180 age-matched and sex-matched controls were enrolled. Regional subcutaneous fat changes were assessed by physicians, and fasting blood samples were drawn. Centralization of body fat was estimated using skinfold ratio, waist circumference, and waist to hip ratio (WHR). Results:Mean duration of HAART was 5.4 years. Main drugs received were zidovudine, stavudine, and protease inhibitors. The prevalence of moderate-severe lipodystrophy was 31.1% (95% confidence interval: 24.3 to 37.9), with 13.3%, 14.5%, and 3.3% for lipoatrophy, lipohypertrophy, and mixed forms, respectively. Mild-severe lipodystrophy affected 65.0% (58.0; 72.0) of patients. Stavudine was the only independent risk factor (any vs. none: odds ratio = 2.8; 1.4 to 5.5). Patients had lower body mass index and skinfolds but greater centralization of body fat (WHR, P < 0.0001 and skinfold ratio, P < 0.001), fasting glucose (P < 0.0001), homeostasis model assessment insulin resistance, and triglyceride levels (P < 0.01 for both) than controls. Moderately-severely lipodystrophic patients had higher triglyceride and low-density lipoprotein cholesterol than other patients (P < 0.001 and P < 0.05, respectively). Conclusions:Moderate-severe lipodystrophy affected one third of West African patients on long-term HAART and was associated with a less favorable metabolic profile.

Randomized trial of piperaquine with sulfadoxine-pyrimethamine or dihydroartemisinin for malaria intermittent preventive treatment in children.

Background The long terminal half life of piperaquine makes it suitable for intermittent preventive treatment for malaria but no studies of its use for prevention have been done in Africa. We did a cluster randomized trial to determine whether piperaquine in combination with either dihydroartemisin (DHA) or sulfadoxine-pyrimethamine (SP) is as effective, and better tolerated, than SP plus amodiaquine (AQ), when used for intermittent preventive treatment in children delivered by community health workers in a rural area of Senegal. Methods Treatments were delivered to children 3–59 months of age in their homes once per month during the transmission season by community health workers. 33 health workers, each covering about 60 children, were randomized to deliver either SP+AQ, DHA+PQ or SP+PQ. Primary endpoints were the incidence of attacks of clinical malaria, and the incidence of adverse events. Results 1893 children were enrolled. Coverage of monthly rounds and compliance with daily doses was similar in all groups; 90% of children received at least 2 monthly doses. Piperaquine combinations were better tolerated than SP+AQ with a significantly lower risk of common, mild adverse events. 103 episodes of clinical malaria were recorded during the course of the trial. 68 children had malaria with parasitaemia >3000/µL, 29/671 (4.3%) in the SP+AQ group, compared with 22/604 (3.6%) in the DHA+PQ group (risk difference 0.47%, 95%CI −2.3%,+3.3%), and 17/618 (2.8%) in the SP+PQ group (risk difference 1.2%, 95%CI −1.3%,+3.6%). Prevalences of parasitaemia and the proportion of children carrying Pfdhfr and Pfdhps mutations associated with resistance to SP were very low in all groups at the end of the transmission season. Conclusions Seasonal IPT with SP+PQ in children is highly effective and well tolerated; the combination of two long-acting drugs is likely to impede the emergence of resistant parasites. Trial Registration ClinicalTrials.gov NCT00529620

Non-specific effects of vaccination on child survival? A prospective study in Senegal

Objectives  Several studies have shown an association between vaccination and child mortality in developing countries. The present paper examines this issue using data from a Senegalese rural area which has been monitored from 1983 to the present.

Impact of the health and living conditions of migrant and non-migrant Senegalese adolescent girls on their nutritional status and growth

OBJECTIVE To describe the living conditions of Senegalese adolescent girls according to their migration status, and to define the main socio-economic and biological determinants of their nutritional and growth status. DESIGN Health and living conditions, sexual maturation, and nutritional and growth status of adolescent girls were determined within the framework of a longitudinal study on growth. SETTINGS The capital city of Senegal (Dakar) and a rural community (Niakhar), 120 km south-east of Dakar. SUBJECTS Three hundred and thirty-one girls, 14.5-16.6 years of age, were recruited from the same villages. Thirty-six per cent of the sample remained in the villages to attend school and/or to help with household subsistence tasks (non-migrants). The remaining (64%) migrated to cities to work as maids (migrants) and lived in two different socio-economic environments: at the home of a guardian during the night and in the house of the employer during the daytime. RESULTS Family rural environment and guardian and employer urban environments were socio-economically different (P < 0.001). Living conditions in urban areas were better than in rural areas and the employers environment was socio-economically more favourable. Migrants had more advanced sexual maturation and higher body mass index (BMI), fat mass index (FMI) and mid-upper arm circumference than non-migrants. However, migrants were smaller than non-migrants. BMI, FMI and weight-for-age were related to socio-economic levels and duration of migration. Schooling was positively related to height and negatively related to BMI. CONCLUSIONS Migrants enjoyed better living conditions than non-migrants. This could be partly due to the better socio-economic environment of the employer. It was associated with earlier puberty and better nutritional status, but not with a better growth.

Early breastfeeding cessation in rural Senegal: causes modes and consequences.

OBJECTIVES We studied reasons for cessation of breastfeeding before the age of 15 months, replacement feeding modes, and child mortality in West Africa. METHODS Data were gathered for 12208 children born between 1987 and 1997 in a rural area of Senegal. Interviews were conducted with caregivers of early-weaned children, and child mortality risks were assessed. RESULTS Fewer than 1% of children had been weaned early. The main reasons for early weaning were maternal death and new pregnancy (in 41% and 27% of cases, respectively). Twenty percent of children had been relactated by a wet nurse, and 16% had received formula. Many early-weaned children died before the age of 2 years (26%), particularly those weaned early as a result of the mothers death (hazard ratio = 5.1; 95% confidence interval [CI] = 1.74, 15.0). Girls had a lower hazard ratio than boys (0.16; 95% CI=0.05, 0.41). CONCLUSIONS Our results showed that early cessation of breastfeeding was rare but that associated mortality was high, especially when the mother had died.