In 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.
Anthropometric 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.
Both 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 < or = -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.
Child 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.
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.
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.
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.
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.
Available data on the long-term consequences of preschool stunting are scarce and conflicting. The objective of this study was to assess the amount of catch-up growth from preschool stunting and the ...effect of migration (change in environment) during adolescence. A cohort study from preschool age (1-5 y) to adulthood (18-23 y) was conducted among 2874 subjects born in a rural area of Senegal. The subjects were divided into 3 groups of preschool stunting: none, mild, and marked, with height-for-age Z-scores of >-1, -2 to -1, and <-2, respectively. At follow-up, the history of migration was recalled. Mean height was 161.3 cm for girls and 174.0 cm for boys (>=20 y). Stunted subjects remained smaller than the others: the age-adjusted height deficit between the 2 extreme categories was 6.6 and 9.0 cm in girls and boys, respectively. However, their height increment from early childhood to adulthood differed (69.3, 70.5, and 72.0 cm, P = 0.0001, and 78.9, 80.0, and 80.3 cm, P < 0.01, for nonstunted, mildly stunted, and markedly stunted girls and boys, respectively). The duration of labor migration to the city was associated with height increment in girls only in a nonlinear relation (adjusted means: 67.2, 69.3, 67.4, and 67.7 cm for 4 groups of increasing duration, P < 0.01). In conclusion, Senegalese children caught up in height prior to adulthood, with the adult means ~2 cm below the WHO/NCHS reference. However, this global catch up did not reduce height differences between formerly stunted and nonstunted children to any greater extent and it was not enhanced by labor migration.
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.
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.
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/microL, 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.
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.
ClinicalTrials.gov NCT00529620.
In sub-Saharan Africa, malaria and malnutrition are major causes of morbidity and mortality in children less than five years of age. To explore the impact of malnutrition on subsequent susceptibility ...to malaria, a cohort of 874 rural preschool children in Senegal was followed-up during one malaria transmission season from July through December. Data on nutritional status and Plasmodium falciparum parasitemia were collected at baseline. Malaria morbidity was monitored through weekly home visits. Wasted children (weight-for-height z-score < -2) were at lower risk of having at least one subsequent clinical malaria attack (odds ratio = 0.33; 95% confidence interval = 0.13-0.81, P = 0.02), whereas stunting (height-for-age z-score < -2) or being underweight (weight-for-age z-score < -2) was not associated with clinical malaria. Although non-biological explanations such as overprotection of wasted children by their mothers should be considered, immunomodulation according to nutritional status could explain the lower risk of malaria attack among wasted children.
Summary
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.
Methods We analysed two birth cohorts, comprising 7796 and 3573 persons who had received either BCG and DTP (diphtheria‐tetanus‐pertussis) simultaneously or neither of these vaccines, and who had been followed from birth to 2 years of age. The association between vaccinations and mortality was assessed by Cox proportional hazards model.
Results Mortality ratios for recipients of the BCG/DTP combination were 0.59 (95% CI: 0.46–0.74) for the first cohort and 0.70 (0.50–0.97) for the second cohort. Mortality ratios for measles vaccine recipients were 0.98 (0.75–1.27) for the first cohort and 0.87 (0.57–1.30) for the second cohort.
Conclusions The BCG/DTP combination was associated with a reduction in mortality whereas measles vaccination was not associated with mortality.
Ruel and Menon recently published a young child feeding index based on characteristics taken from 24-h and 7-d recalls. A strong positive association was found in 7 Latin American Demographic and ...Health Surveys for 12- to 36-mo-old children (1). The aim of this study was to test for associations of this index with height-for-age and linear growth in African children. Children (n = 500), aged 12-42 mo, living in a rural area of Senegal were visited in their homes in April-May, and 24-h and 7-d food recalls were conducted with their mothers. Height was measured, and measurements taken 7 mo earlier were used to compute linear growth rates. General linear models were used to adjust for potential confounders (child age and sex, maternal height, BMI, and socioeconomic status). The feeding index was not associated with either height-for-age (adjusted means: -1.01, -1.06, and -1.20 Z-scores for the 1st, 2nd, and 3rd tercile, respectively) or with linear growth (6.2, 6.0, and 6.3 cm/7 mo for the 3 terciles, respectively). Continuing breast-feeding was negatively associated with height-for-age (P < 0.05) and positively associated with linear growth (P < 0.01). Frequent consumption of fruit was positively associated with both (P = 0.059 and P = 0.027, respectively, in adjusted models), whereas food consumption from an animal source was not. In conclusion, the composite feeding index was independent of height and linear growth in these rural African children, due in part to reverse causality between breast-feeding duration and stunting.
Although infections contribute to growth faltering in preschool children, malaria prevention seems to have limited impact on height status. In 2002-2003, a malaria intermittent preventive treatment ...(IPT) trial was conducted in Senegal, including randomly selected preschool children from 11 villages. A rapid decrease in stunting prevalence (from 28.3 to 16.3%; P < 0.0001) was reported in both intervention and placebo groups. During this 15-mo period, both groups of children benefited from active detection and prompt treatment of malaria attacks. In this study, we investigated whether management of malaria morbidity could explain the improvement of height status. An anthropometric survey, conducted in September 2004 in the area, included 929 2- to 5-y-old children. Some 539 children, previously included in the 2002-2003 IPT trial, benefited from active malaria morbidity management and formed the malaria trial group. The remaining 390 children constituted the control group. Mean height-for-age and stunting prevalence in September 2004 were compared between groups adjusting for age and mother's activity. Mean height-for-age Z-scores did not differ between trial (-1.17 +/- 0.93) and control children (-1.24 +/- 1.00; P = 0.25). Only 36- to 47-mo-old malaria trial children had a lower prevalence of stunting than controls of similar age (19.4 vs. 28.7%; P = 0.044). Compared with the usually slow progression of height status related to better living conditions, it seems very likely that the rapid improvement observed among IPT study children resulted from the trial. These findings suggest that improved health services provided by the trial may also have benefited children not included living in study villages.
Negative consequences of malaria might account for seasonality in nutritional status in children in the Sahel. We report the impact of a randomized, double-blind, placebo-controlled trial of seasonal ...intermittent preventive anti-malarial treatment on growth and nutritional status in 1,063 Senegalese preschool children. A combination of artesunate and sulfadoxine-pyrimethamine was given monthly from September to November. In the intervention arm, mean weight gain was significantly greater (122.9 +/- 340 versus 42.9 +/- 344 SD g/mo, P < 0.0001) and losses in triceps and subscapular skinfold measurements were less (-0.39 +/- 1.01 versus -0.66 +/- 1.01 mm/mo, and -0.15 +/- 0.64 versus -0.36 +/- 0.62 mm/mo, respectively, P < 0.0001 for both). There was no difference in height increments. The prevalence of wasting increased significantly in the control arm (4.6% before versus 9.5% after, P < 0.0001), but remained constant in intervention children: 5.6% versus 7.0% (P = 0.62). The prevention of malaria would improve child nutritional status in areas with seasonal transmission.
Background Evidence suggests that intrauterine growth restriction followed by rapid post-natal growth is associated with high blood pressure. We assessed the effect of early size and post-natal ...growth on blood pressure in a population from West Africa, where fetal growth retardation and childhood malnutrition are common. Methods A total of 1288 Senegalese subjects were followed from infancy to young adulthood (mean age 17.9 years). Adult systolic blood pressure (SBP) was regressed on infant and adult anthropometric characteristics. Results In unadjusted analyses, infant size was positively associated with adult SBP (1.1 ± 0.3; P = 0.001 for weight; 0.7 ± 0.3; P = 0.04 for length). With adjustment for current size, the regression coefficients for infant size were reversed (−0.2 ± 0.3; P = 0.51 for weight; −0.3 ± 0.3; P = 0.35 for length). SBP increased by 4.1 and 2.9 mmHg for 1 standard deviation (SD) increase in current weight or height, respectively. No interaction between infant size and current size was found in the overall models (P = 0.11 for weight, P = 0.95 for height), but this term interacted with sex for weight effect. A negative interaction was found in males (−0.9 ± 0.4; P = 0.02) but not in females (0.3 ± 0.4; P = 0.46). The association of current weight with SBP was stronger in lighter weight male infants. Conclusions These findings support the hypothesis that subjects who were small in early life and experienced enhanced post-natal growth have higher levels of SBP, even in low-income settings.
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