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SummaryBackgroundMalaria is a major cause of morbidity and mortality in Africa. International effort and funding for control has been stepped up, with substantial increases from 2003 in the delivery of malaria interventions to pregnant women and children younger than 5 years in The Gambia. We investigated the changes in malaria indices in this country, and the causes and public-health significance of these changes.MethodsWe undertook a retrospective analysis of original records to establish numbers and proportions of malaria inpatients, deaths, and blood-slide examinations at one hospital over 9 years (January, 1999–December, 2007), and at four health facilities in three different administrative regions over 7 years (January, 2001–December, 2007). We obtained additional data from single sites for haemoglobin concentrations in paediatric admissions and for age distribution of malaria admissions.FindingsFrom 2003 to 2007, at four sites with complete slide examination records, the proportions of malaria-positive slides decreased by 82% (3397/10861 in 2003 to 337/6142 in 2007), 85% (137/1259 to 6/368), 73% (3664/16932 to 666/11333), and 50% (1206/3304 to 336/1853). At three sites with complete admission records, the proportions of malaria admissions fell by 74% (435/2530 to 69/1531), 69% (797/2824 to 89/1032), and 27% (2204/4056 to 496/1251). Proportions of deaths attributed to malaria in two hospitals decreased by 100% (seven of 115 in 2003 to none of 117 in 2007) and 90% (22/122 in 2003 to one of 58 in 2007). Since 2004, mean haemoglobin concentrations for all-cause admissions increased by 12 g/L (85 g/L in 2000–04 to 97 g/L in 2005–07), and mean age of paediatric malaria admissions increased from 3·9 years (95% CI 3·7–4·0) to 5·6 years (5·0–6·2).InterpretationA large proportion of the malaria burden has been alleviated in The Gambia. Our results encourage consideration of a policy to eliminate malaria as a public-health problem, while emphasising the importance of accurate and continuous surveillance.FundingUK Medical Research Council.

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Artemether is as effective as quinine in the treatment of cerebral malaria in children.

Tumor necrosis factor (TNF) is thought to playa key role in the pathogenesis of cerebral malaria. A double-blind, placebo-controlled trial of an anti-TNF monoclonal antibody (B-C7) comprised 610 Gambian children with cerebral malaria, with mortality and residual neurologic sequelae as primary study end points. Sixty (19.9%) of 302 children who received B-C7 died compared with 64 (20.8%) of 308 children who received placebo (adjusted odds ratio [OR], 0.90; 95% confidence interval [CI], 0.57-1.42). Residual neurologic sequelae were detected in 15 (6.8%) of 221 survivors from the B-C7 group and in 5 (2.2%) of 225 survivors of the placebo group (adjusted OR, 3.35; 95% CI, 1.08-10.4). The monoclonal antibody used in this study did not improve survival in cerebral malaria and was associated with a significant increase in neurologic sequelae. A possible explanation of the latter observation is that the antibody acts to retain TNF within the circulation and thereby prolongs its effects on vascular endothelium. Cerebral malaria in children has a case fatality rate of 10%-30% despite effective antimalarial treatment [1, 2]. Deaths in cases of cerebral malaria occur frequently in the first hours after admission, before antimalarial therapy has become effective. Recently, it has been shown that a fast-acting antimalarial agent, artemether, did not change this pattern, nor did it improve outcome [3]. Thus, there is a need to develop new forms of therapy for cerebral malaria. These should have antidisease properties and a fast onset of action and be given in conjunction with conventional antimalarial treatment. Recent studies strongly suggest that tumor necrosis factor (TNF) plays a key role in the pathogenesis of cerebral malaria. In clinical studies, an association has been found between plasma TNF levels and disease severity and outcome [4, 5], and it has been shown that children homozygous for the TNF2 allele, which has been associated with high TNF production, are more likely to develop cerebral malaria and die as a conse

Little empirical evidence from field-based studies exists on the relative magnitude or duration of clinical protection from Plasmodium falciparum malaria in infancy. A prospective study was undertaken to examine the age distribution of hospital admissions in four geographically and demographically well-defined areas with differing intensities of P. falciparum transmission. Where transmission was perennial, significant clinical protection from severe morbidity was observed up to the third month of life; in the seasonal transmission area, disease rates rose after the sixth month of life. Infants exposed to the highest rates of P. falciparum exposure demonstrated significant declines in the risks of severe malaria from 6 months of age. These data provide direct evidence for the very early acquisition of clinical immunity and for the existence of a period of clinical protection, which together may explain why, in these communities, the cumulative risk of malarial disease throughout childhood appears to decline with increasing transmission intensity.

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SummaryAdmission records from two paediatric units in The Gambia were used to explore the relationship between admission weight and different diseases. In total 13579 hospitalized children were analysed. For comparison, 7399 children were recruited from several surveys of well subjects to provide anthropometric values for healthy Gambian children. Compared to the control children, mean admission weights were lower for malaria (weight for age z-score: Ϫ 1.602), cerebral malaria (Ϫ 1.547), transfused malarial anaemia (Ϫ 1.764), pneumonia (Ϫ 1.725), meningitis (Ϫ 1.362), gastro-enteritis (Ϫ 2.497) and malnutrition (Ϫ 3.786). Children with bronchiolitis did not have a significantly different weight for age than the controls. Outcome of the hospital admission was recorded and related to the weight on admission. In all disease categories the death rate rose with decreasing admission weight with the exception of bronchiolitis. For all diseases taken together, case fatality was 7.2% for children with a weight for age z-score above -2 Standard Deviations (SD), 9.3% between Ϫ 2 and Ϫ 3 SD, 15.6% between Ϫ 3 and Ϫ 4 SD and 22.7% for children with weight for age SD z-scores less than -4. Malnourished children are more susceptible to several infectious diseases frequently seen in developing countries and nutritional interventions, as well as standard treatment, may improve outcome.