The challenges of managing severe dehydrating diarrhoea in a resource-limited setting.

Diarrhoea remains one of the most common causes of childhood deaths worldwide despite the widespread use of oral rehydration solution (ORS). The vast majority of the nearly 2 million diarrhoeal deaths occurring annually in children under five years of age are in south Asia and sub-Saharan Africa. Signs of critical illness in severely dehydrated children are poorly recognised, and although considerable efforts have gone into establishing the management of diarrhoeal disease in general, there is surprisingly little understanding of the aetiology, metabolic processes and risk factors for the very high mortality associated with severe dehydrating diarrhoea (SDD). We suggest that in many resource-poor settings, the degree of fluid requirement as well as the prevalence of electrolyte disturbances are seriously under-recognised and may be contributing significantly to mortality. The heterogeneity of children with SDD renders the generic 'one size fits all' approach to fluid and electrolyte management in these critically ill children inadequate. In this review we will highlight SDD as an important target for research in resource-limited settings, and emphasise the need to re-evaluate the efficacy of prevailing intravenous fluid protocols in well conducted multi-centre interventional trials.

Prognostic value of circulating pigmented cells in African children with malaria.

BACKGROUND: Plasmodium falciparum malaria is a common cause of morbidity in African children, but identifying those who are likely to die is problematic. Previous studies suggested that circulating malarial pigment might be a useful predictor of severity, but none were large enough to detect any association with mortality. METHODS: We used thick blood smears performed on admission for 26,296 children hospitalized with P. falciparum at 1 of 6 hospitals in the Severe Malaria in African Children network to assess the prognostic value of pigment-containing granulocytes, monocytes, and parasites. RESULTS: Although at all but one of the study sites the risk of mortality for subjects presenting with >5 pigmented granulocytes per 200 white blood cells was higher than in subjects with no pigmented granulocytes, adjusted odds ratios estimated through logistic regression, which included other established markers of severe malaria, suggested that associations between pigmented cells and mortality were moderate to nonexistent in most sites. The predictive ability of pigmented cells was low, as measured by the change in the area under the receiver operating characteristic curve of logistic regression models. CONCLUSIONS: Although high levels of pigmented cells were associated with a fatal outcome in some study sites, they were not useful predictors of outcome across Africa.

Bacteremia in Malawian children with severe malaria: prevalence, etiology, HIV coinfection, and outcome.

BACKGROUND: Previous prospective studies of bacteremia in African children with severe malaria have mainly included children with cerebral malaria, and no study has examined the impact of human immunodeficiency virus (HIV) infection. We examined the prevalence and etiology of bacteremia and the impact of HIV infection on bacteremia in Malawian children with severe malaria, as well as the impact of bacteremia and HIV infection on outcome. METHODS: From 1996 until 2005, blood for culture was obtained on admission from all children admitted with severe malaria during the rainy season to the Paediatric Research Ward at the Queen Elizabeth Central Hospital in Blantyre, Malawi. HIV testing was performed prospectively from 2001 to 2005 and retrospectively for those admitted from 1996 to 2000. Multivariate regression analysis examined independent risk factors for bacteremia and death. RESULTS: Sixty-four (4.6%) of 1388 children with severe malaria had bacteremia; nontyphoidal Salmonellae (NTS) accounted for 58% of all bacteremias. The prevalence of any bacteremia and of NTS bacteremia was highest in children with severe malarial anemia (11.7% and 7.6%), compared with the prevalence in children with cerebral malaria and severe anemia (4.7% and 3.8%) and in those with cerebral malaria alone (3.0% and 0.9%). HIV infection status was determined in 1119 patients. HIV prevalence was 16% (and was highest in those with severe malaria anemia, at 20.4%), but HIV infection was not significantly associated with bacteremia. Neither bacteremia nor HIV infection was associated with death. CONCLUSIONS: Antibiotics are not routinely indicated for children with severe malaria in this region, in which HIV is endemic. However, antibiotic therapy should be used to treat NTS infection if bacteremia is suspected in children with severe malarial anemia.

Metabolites of the kynurenine pathway of tryptophan metabolism in the cerebrospinal fluid of Malawian children with malaria.

A retrospective study of 100 Malawian children (87 with malaria and 13 with a diagnosis other than malaria) was conducted to determine the relationship between levels of metabolites of the kynurenine pathway in cerebrospinal fluid (CSF) and disease outcome. Three metabolites were measured: quinolinic acid (QA), an excitotoxin; kynurenic acid (KA), a neuroprotective receptor antagonist; and picolinic acid (PA), a proinflammatory mediator. Elevated levels of QA and PA in CSF were associated with a fatal outcome in Malawian children with cerebral malaria (CM). QA was associated with a history of convulsions. An increase in the QArcolon;KA ratio, which favors neurotoxicity, was observed only in the 3 patients with tuberculosis meningitis. Compared with Vietnamese adults with malaria, Malawian children with malaria had higher concentrations of KA. Elevated levels of KA in children with CM may serve to contain injury in the developing brain, which is more susceptible to excitotoxic damage than is the adult brain.