Life-threatening malaria in African children: a prospective study in a mesoendemic urban setting.

BACKGROUND: The population exposed to malaria within African cities has steadily increased. However, comprehensive data on life-threatening malaria features and risk factors in children from urban areas with seasonal malaria transmission, such as in Bamako (Mali), are lacking. METHODS: Children admitted to the Gabriel Touré Hospital in Bamako with severe malarial anemia (SMA) and/or cerebral malaria (CM) were prospectively included in the study. Indicators of either SMA or CM were analyzed using logistic regression; and death hazard ratios (HRs) were estimated through survival analysis. RESULTS: The study included 455 children: 66% presented with CM, 34% with SMA, 3% with hypoglycemia (HG); 5% with dehydration; 17% with respiratory distress (RD); 25% with splenomegaly; and 92% with hepatomegaly. The children with CM were older than those with SMA. CM was more often associated with dehydration, HG, and RD, whereas SMA was more often associated with splenomegaly. The overall case fatality rate was 16%, and 94% of the children who died had CM. HG [HR: 2.37; 95% confidence interval (CI): 1.04-5.39; P = 0.040], RD (HR: 4.23; 95% CI: 2.46-7.30; P < 10(-6)) and a deep coma with a Blantyre score of less than 3 (HR: 6.78, 95% CI: 2.43-18.91; P < 10(-3)), were all independent predictors of death. CONCLUSIONS: These findings delineate the patterns of severe malaria in children in a West African mesoendemic urban setting. They validate practicable prognostic indicators of life-threatening malaria for use in the limited facilities available in African health centers and provide a frame of reference for further research addressing life-threatening malaria in this setting.

Risk factors for severe malaria in Bamako, Mali: a matched case-control study.

The aim of this case-control study was to identify epidemiological risk factors for severe malaria among children living in Bamako, a malaria-endemic area. For this, 260 healthy community controls were matched to 130 patients with severe malaria. Conditional multiple logistic regression analysis indicated that all examined independent factors associated with severe malaria are directly related to characteristics of the child's mother, with the exception of the child's own yellow fever vaccination history (odds ratio (OR): 1.93, 95% confidence intervals (CI(95%)) [1.10-3.37]). The following characteristics were all associated with a decreased risk of severe malaria in the child: maternal education (OR: 0.52, CI(95%) [0.31-0.86]), the mother's adequate knowledge about malaria (OR: 0.46, 95% CI(95%) [0.25-0.86]), her use of mosquito bed nets (OR: 0.53, CI(95%) [0.30-0.92]) and breast-feeding for at least 2 years (OR: 0.57, CI(95%) [0.33-0.94]). Conversely, chronic maternal disease (OR: ?3.16, CI(95%) [1.31-7.61]) was associated with an increased risk of severe malaria. These findings strongly support the hypothesis that maternal factors are central to the development of severe malaria in children. Programmes aiming to improve both maternal health and maternal education may reduce the incidence of severe malaria in children and should therefore be advocated in Bamako and in areas with similar epidemiological patterns for malaria.

Alleles 308A and 238A in the tumor necrosis factor alpha gene promoter do not increase the risk of severe malaria in children with Plasmodium falciparum infection in Mali.

The hypothesis that tumor necrosis factor (TNF) aggravates malaria in children is supported by observations that TNF polymorphisms and high TNF levels have been associated with cerebral malaria. Nevertheless, severe malaria was not associated with polymorphisms located at positions -308A and -238A in the TNF alpha gene promoter or with a high TNF level in plasma in children from Bamako, Mali.

Familial aggregation of cerebral malaria and severe malarial anemia.

BACKGROUND: The predominant manifestations of severe malaria in African children are cerebral malaria (CM) and severe malarial anemia (SMA). As a first step toward a family-based approach to identify the environmental and genetic pathways that contribute to severe malaria, we tested whether it aggregates within families. METHODS: Family history of severe malaria was explored during face-to-face interviews with parents. Logistic regression was used to determine whether CM and SMA aggregate within individuals and within families. The pattern of familial aggregation was then expressed as familial odds ratios that were adjusted for relevant risk factors. RESULTS: This study was of 2811 inhabitants of Bamako, Mali, clustered in 407 nuclear families. The probands were 136 children with severe malaria and 271 healthy children from the community. Within-person association of CM and SMA was significant (odds ratio, 6.15 [95% confidence interval (CI), 2.62-14.41]). Over a lifetime, with each additional affected relative, the odds of a person contracting CM increased by 1.98 times (95% CI, 1.59-2.45), and the odds of having SMA increased by 1.91 times (95% CI, 1.05-3.47). Over a lifetime, for a child whose sibling had a history of CM, the odds of having CM were 2.49 times greater (95% CI, 1.51-4.10) than the odds for a child whose sibling had no such history; for a child whose sibling had a history of SMA, the odds of having SMA were 4.92 times greater (95% CI, 1.21-19.9) than the odds for a child whose sibling had no such history. CONCLUSION: Our data suggest strong familial aggregation of CM and SMA.