Abstract. Thrombocytopenia is a common finding in malaria, but its prognostic value has not been addressed in children. The relationship between thrombocytopenia (platelet count < 100,000/mm 3 on admission) and severity and outcome was investigated prospectively in children hospitalized with falciparum malaria in Dakar, Senegal, an area that is hypoendemic for malaria. Of 288 falciparum cases, 215 matched the 2000 World Health Organization definition of severe malaria. Median platelet counts were lower (98,000/mm 3 versus 139,000/mm 3 ; P < 0.02) among severe cases than in mild cases, and in children who died than among those who recovered (68,500/mm 3 versus 109,000/mm 3 ; P < 0.002). In severe cases, children presenting with a platelet count < 100,000/mm 3 were more likely to die (odds ratio [OR] ס 6.31, 95% confidence interval [CI] ס 2.0-26.0). Moreover, multivariate analysis identified thrombocytopenia as an independent predictor of death (OR ס 13.3, 95% CI ס 3.2-55.1). Our data show an association between thrombocytopenia and either severity or prognosis in childhood falciparum malaria.
To our knowledge, this is the largest study of patients with SUCLA2 and SUCLG1 deficiency. The most important findings were a significantly longer survival in patients with SUCLA2 mutations compared to SUCLG1 mutations and a trend towards longer survival in patients with missense mutations compared to loss-of-function mutations. Hypertrophic cardiomyopathy and liver involvement was exclusively found in patients with SUCLG1 mutations, whereas epilepsy was much more frequent in patients with SUCLA2 mutations compared to patients with SUCLG1 mutations. The mutation analysis revealed a number of novel mutations, including a homozygous deletion of the entire SUCLA2 gene, and we found evidence of two founder mutations in the Scandinavian population, in addition to the known SUCLA2 founder mutation in the Faroe Islands.
The relevance of WHO criteria for severe and complicated malaria has been debated for a while, especially as regards children. Recent data led WHO experts to modify the definition of severe malaria. The objective of this study was to evaluate retrospectively the significance of the new definition on severity, lethality and intensive care distribution in children admitted with falciparum malaria (in 1997-99) to Hôpital Principal de Dakar, Senegal. We used the paediatric risk of mortality score (PRISM) to compare the 2 definitions, WHO 2000 and WHO 1990. Finally, we evaluated the impact of the new definition in terms of major therapeutic interventions (MTIs): mechanical ventilation, haemodynamic support, transfusion, haemodialysis, and the use of sedatives. Among 311 patients, the frequencies of severe malaria cases and case-fatality rates thereof were 52% (n = 161) and 17% (n = 28) respectively using the 1990 WHO criteria, and 75% (n = 233) and 12% (n = 28) using the 2000 WHO criteria. Mean PRISM score among severe cases decreased with the new definition (6.5 versus 8.6). Both definitions predicted neurological sequelae and deaths with 100% sensitivity. One or more MTIs were required in severe malaria cases in 86% (n = 139) under the 1990 criteria and 73% (n = 170) under the 2000 criteria. In this area of low and seasonal transmission, the 2000 WHO definition of severe malaria proved broader and less specific, but was easier to apply and retained the high sensitivity of the earlier definition in identifying life-threatening infections.
This discrepancy observed in five classes of expected mortality (Hosmer-Lemeshow chi-square test, p < .001) may have been due to chance (sample size too small for a valid test), to a lower standard of care in Dakar than in the American hospitals where PRISM was designed, or to a failure of PRISM to classify risk in severe malaria.
Impaired lung development has been demonstrated in neonatal animals exposed to hyperoxia. High lung cys-leukotriene levels may be a contributing factor towards the increase in oxygen toxicity. We investigated the effect of cysteinyl-leukotriene inhibition using the receptor antagonist, montelukast (MK, Singulair), on hyperoxia-induced changes in lung parenchymal structure in neonatal rat pups. Rat pups were exposed to 21% O(2) (air) or 50% O(2) (moderate hyperoxia) from days 1-14 after birth, and were administered the cys-leukotriene receptor antagonist MK (1 mg/kg/day) or normal saline from days 4-14. Somatic growth and morphometric measurements were done on day 15. There was a significant increase in bronchoalveolar lavage fluid cysteinyl-leukotriene levels (+61.9%) when animals were exposed to hyperoxia. O(2) exposure significantly decreased the specific internal surface area by 13%. There was a nonsignificant 5.8% and 19.6% increase in mean chord length and mean alveolar diameter, respectively, as well as an 8.6% decrease in lung volume to body weight ratio. Inhibition of only one arm of the arachidonic-acid cascade by MK was not sufficient to prevent these oxygen-induced changes.
Glucocorticoids are widely used in perinatology, since they decrease the incidence of respiratory distress syndrome and chronic lung disease. However, evidence is now increasing that their use in this age group may result in impaired alveolar lung growth and general development. The aim of this study was to determine whether a low dose of hydrocortisone (1 mg/kg/day for 11 days) was deleterious to lung growth in rat pups, as compared to an equivalent dose of dexamethasone. While both dexamethasone and hydrocortisone increased alveolar diameter with thinning of the interairspace walls, only dexamethasone reduced the overall internal surface area of the lung available for respiratory exchange. Changes were more marked with dexamethasone as compared to hydrocortisone, which did not appear to affect alveolar septation. In conclusion, a prolonged course of low-dose hydrocortisone may be deleterious for alveolar lung growth in rat pups, but the changes are less marked than those caused by dexamethasone.
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