Fatores de prognóstico na leishmaniose visceral: alterações clínicas e laboratoriais associadas à resposta imune, aos distúrbios da coagulação e à morte

Abstract

Background: Visceral leishmaniasis (VL), may present from asymptomatic or oligosymptomatic infection to a devastating and fatal disease and the syndrome frequently encompasses fever, weight loss, hepatosplenomegaly,and pancytopenia. The risk factors for death and the pathogenesis of the disturbances are poorly recognized. The aim of this work is to investigate the clinical aspects, the markers ofinflammation and disseminated intravascular coagulation (DIC) in VL patients and to develop a prognostic score system model for death. Patients and Methods:An open hospital based cohort of 883 was conductedfrom September 2005 to August 2008. A sub group of 314 infants was described in detail. Two case-cohort studies were designed to investigate the bleeding disorders and the immune response. Markers for disseminated intravascular coagulation were evaluated in 185 patients. Serum levels of pro-inflammatory cytokines and markers of unspecific inflammatory response were measured in 134 patients of the inflammation case-control study. Results:Most patients (92.5%) were successfully treated but 66 (7.5%) patients died. Mortality rate was 7.5%. Infants, oldest patients and HIV co-infected patients had the most severe disease with a higher mortality. Malnutrition was more frequent in adults and not associated to bleeding events or death but recent weight loss was related to death. The signs and symptoms associated to death were jaundice, vomiting, diarrhea, edema, lethargy, anorexia, cough, bacterial infections and bleeding events. Risk of death was higher in patients with thrombocytotopenia, leucopenia, anemia, low glomerular filtration rate e increased liver enzymes. High levels of D-dimer were seen in 183 (98.9%) patients and high levels of FPA were seen in 67(63.8%) patients. FDP latex agglutination was positive in 121(65.7%) cases. Levels of D-dimer and positivity of FDP latex agglutination were higher in patients with bleeding disorders. Elevated levels of ultra sensitive C-reactive protein (CRPhigh)were seen in 85 (68.6%) patients were and the erythrocyte sedimentation rate (ESR) was over 10 mm (µ=61,1mm) in 154 (90.6%). The CRPhigh was correlated to digestive bleeding and bacterialinfections. Cytokines levels were associated with jaundice, respiratory distress, vomiting, edema and diarrhea. Levels of IL-6, CXCL-8 and IFN-were higher among deceased patients. Patients withbleeding had higher levels of IL-1, IL-6, IL-8 and IFN-.Cytokines levels were not associated with bacterial infections without hemorrhages. A prognostic score system model for death prediction is presented. Conclusions:VL was especially severe in infants and adults. Most VL patients present coagulation activation. Bacterial infections are co-factors that exacerbate inflammation and bursts hemorrhages. High levels of the pro-inflammatory cytokines IL-8, IL-1, IL-10 and IFN-are correlated to anemia, neutropenia, respiratory distress, hepatitis, renal and intestinal injury, diarrhea and vomits. The prognostic model may be helpful in identifying patients at high risk of death.