RESUMO
Metabolic complications of malaria are increasingly recognized as contributing to severe and fatal malaria. Disorders of carbohydrate metabolism, including hypoglycaemia and lactic acidosis, are amongst the most important markers of disease severity both in adults and children infected with Plasmodium falciparum. Amino acid and lipid metabolism are also altered by malaria. In adults, hypoglycaemia is associated with increased glucose turnover and quinine-induced hyperinsulinaemia, which causes increased peripheral uptake of glucose. Hypoglycaemia in children results from a combination of decreased production and/or increased peripheral uptake of glucose, due to increased anaerobic glycolysis. Patients with severe malaria should be monitored frequently for hypoglycaemia and treated rapidly with intravenous glucose if hypoglycaemia is detected. The most common aetiology of hyperlactataemia in severe malaria is probably increased anaerobic glucose metabolism, caused by generalized microvascular sequestration of parasitized erythrocytes that reduces blood flow to tissues. Several potential treatments for hyperlactataemia have been investigated, but their effect on mortality from severe malaria has not been determined.
Assuntos
Malária Falciparum/complicações , Malária Falciparum/metabolismo , Acidose Láctica/etiologia , Aminoácidos/metabolismo , Permeabilidade Capilar , Humanos , Hipoglicemia/etiologia , Lactatos/sangue , Metabolismo dos LipídeosRESUMO
BACKGROUND: Low plasma glutamine levels in critical illness, neonates and burns patients are associated with poor outcome and increased risk of intercurrent infection. AIM: To investigate the relationship between plasma glutamine/glutamate levels and severity/outcome of malaria. DESIGN: Two-hospital prospective study, with both febrile and healthy controls. METHODS: We measured plasma glutamine and glutamate concentrations in 239 Gabonese patients: 145 children with malaria (86 with severe, 36 with moderate and 23 with uncomplicated disease), 42 healthy children, 44 febrile controls and eight healthy adults, and related findings to conventional markers of disease severity such as plasma lactate. RESULTS: Median (IQR) plasma glutamine was lower in uncomplicated falciparum malaria and in moderate malaria than in healthy controls: 353 (287-474) and 379 (293-448) vs. 485 (428-531) micromol/l, respectively; p<0.01 for both malaria groups vs. controls. In contrast, plasma glutamine was within the normal range in those with severe malaria and in febrile control children: 431 (342-525) and 472 (338-547) micromol/l, respectively. Furthermore, plasma glutamine was significantly higher in the children who died with malaria than in survivors: 514 (374-813) (n=12) vs. 399 (316-475) micromol/l (n=133), respectively; p=0.001. There were no significant differences in plasma glutamate concentrations between any of the study groups. DISCUSSION: In severe malaria, there was a positive correlation between plasma glutamine and lactate levels (p=0.009, r=0.281). This correlation may reflect impaired gluconeogenesis. Glutamine supplementation is probably not justified in severe P. falciparum infection.
Assuntos
Ácido Glutâmico/sangue , Glutamina/sangue , Malária Falciparum/sangue , Biomarcadores/sangue , Estudos de Casos e Controles , Pré-Escolar , Feminino , Gabão , Humanos , Lactente , Masculino , Estudos ProspectivosRESUMO
Mannose-binding lectin (MBL2) variants that decrease the plasma level of the protein or encode dysfunctional proteins are frequently associated with the severity of a number of infections and autoimmune disorders. The high frequencies of these variants in most populations of the world are probably maintained by some selective advantage against widespread diseases. We found 14 new MBL2 allelic haplotypes, two of them with non-synonymous variants, by screening 136 children with uncomplicated malaria, 131 children with severe malaria and 39 older healthy schoolchildren. We also found a significant association of a novel variant with susceptibility to severe malaria (P=0.010). Increased MBL plasma levels and corresponding MBL2 genotypes were associated with lower concentration of several cytokines and chemokines in plasma of malaria patients. We suggest that malaria could have been one of the evolutionary driving forces shaping the MBL2 polymorphism in the African population.