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Early clinical manifestations associated with death from visceral leishmaniasis.

ABSTRACT: BACKGROUND:In Brazil, lethality from visceral leishmaniasis (VL) is high and few studies have addressed prognostic factors. This historical cohort study was designed to investigate the prognostic factors for death from VL in Belo Horizonte (Brazil). METHODOLOGY:The analysis was based on data of the Reportable Disease Information System-SINAN (Brazilian Ministry of Health) relating to the clinical manifestations of the disease. During the study period (2002-2009), the SINAN changed platform from a Windows to a Net-version that differed with respect to some of the parameters collected. Multivariate logistic regression models were performed to identify variables associated with death from VL, and these were included in prognostic score. PRINCIPAL FINDINGS:Model 1 (period 2002-2009; 111 deaths from VL and 777 cured patients) included the variables present in both SINAN versions, whereas Model 2 (period 2007-2009; 49 deaths from VL and 327 cured patients) included variables common to both SINAN versions plus the additional variables included in the Net version. In Model 1, the variables significantly associated with a greater risk of death from VL were weakness (OR 2.9; 95%CI 1.3-6.4), Leishmania-HIV co-infection (OR 2.4; 95%CI 1.2-4.8) and age ?60 years (OR 2.5; 95%CI 1.5-4.3). In Model 2, the variables were bleeding (OR 3.5; 95%CI 1.2-10.3), other associated infections (OR 3.2; 95%CI 1.3-7.8), jaundice (OR 10.1; 95%CI 3.7-27.2) and age ?60 years (OR 3.1; 95%CI 1.4-7.1). The prognosis score was developed using the variables associated with death from VL of the latest version of the SINAN (Model 2). The predictive performance of which was evaluated by sensitivity (71.4%), specificity (73.7%), positive and negative predictive values (28.9% and 94.5%) and area under the receiver operating characteristic curve (75.6%). CONCLUSIONS:Knowledge regarding the factors associated with death from VL may improve clinical management of patients and contribute to lower mortality.

SUBMITTER: de Araujo VE

PROVIDER: S-EPMC3274500 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Early clinical manifestations associated with death from visceral leishmaniasis.

de Araújo Valdelaine Etelvina Miranda VE Morais Maria Helena Franco MH Reis Ilka Afonso IA Rabello Ana A Carneiro Mariângela M

PLoS neglected tropical diseases 20120207 2

<h4>Background</h4>In Brazil, lethality from visceral leishmaniasis (VL) is high and few studies have addressed prognostic factors. This historical cohort study was designed to investigate the prognostic factors for death from VL in Belo Horizonte (Brazil).<h4>Methodology</h4>The analysis was based on data of the Reportable Disease Information System-SINAN (Brazilian Ministry of Health) relating to the clinical manifestations of the disease. During the study period (2002-2009), the SINAN changed ...[more]

PMID: 22347514

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Project description:UnlabelledVisceral leishmaniasis (VL) has a high fatality rate if not treated; nevertheless, the majority of human infections with the causative agent, Leishmania infantum chagasi, are asymptomatic. Although VL patients often present with increased levels of serum immunoglobulins, the contribution of antibodies to resistance or progression to disease remains unknown. Effector and regulatory functions of antibodies rely on their interactions with type I and II Fc receptors, and these interactions are tuned by the patterns of antibody Fc N-glycosylation. In view of these facts, we applied a robust method of IgG Fc N-glycopeptide profiling of serum samples from 187 patients with VL, 177 asymptomatic individuals, 116 endemic controls (individuals residing in areas where VL is endemic) and 43 nonendemic controls (individuals living in an area where VL is not endemic). We show that, in comparison to the overall IgG Fc N-glycan profiles of asymptomatic or uninfected healthy individuals, those of patients with VL are profoundly altered. These changes correlate with levels of serum cytokines and the inflammation marker C-reactive protein. We also fitted univariate and multivariate ordinal logistic regression models to demonstrate the ability of IgG Fc N-glycosylation features and immunity regulators present in serum to predict disease severity in VL patients. Importantly, we show that Fc N-glycosylation profiles change after treatment of VL. This study introduces important concepts contributing to the understanding of antibody responses in infections with Leishmania parasites and provides new insights into the pathology of human VL.ImportanceImmunoglobulins (Ig) have been shown to present pro- and anti-inflammatory functions according to the profile of carbohydrates attached to their Fc region. Glycosylation features of serum IgG have been examined in relation to several autoimmune and infectious diseases and provide a mechanistic basis for the protective or pathogenic role of antibodies. Leishmania infantum chagasi is the causative agent of visceral leishmaniasis (VL) in South America, and we show that VL patients produce IgG with patterns of Fc glycans similar to those found in other inflammatory conditions. Specific Fc N-glycosylation features and levels of serum cytokines and C-reactive protein are significantly associated with the development of severe clinical symptoms and, notably, Fc glycosylation changes after treatment. The modifications detected in the N-glycosylation features of IgG Fc from VL patients raise new perspectives on the effector or regulatory role of antibodies in immune responses elicited by infection with Leishmania parasites.

Project description:ObjectivesTo perform a temporal validation of a predictive model for death in children with visceral leishmaniasis (VL).MethodsA temporal validation of a children-exclusive predictive model of death due to VL (Sampaio et al. 2010 model), using a retrospective cohort, hereby called validation cohort. The validation cohort convenience sample was made of 156 patients less than 15 years old hospitalized between 2008 and 2018 with VL. Patients included in the Sampaio et al. 2010 study are here denominated derivation cohort, which was composed of 546 patients hospitalized in the same hospital setting in the period from 1996 to 2006. The calibration and discriminative capacity of the model to predict death by VL in the validation cohort were then assessed through the procedure of logistic recalibration that readjusted its coefficients. The calibration of the updated model was tested using Hosmer-Lemeshow test and Spiegelhalter test. A ROC curve was built and the value of the area under this curve represented the model's discrimination.ResultsThe validation cohort found a lethality of 6.4%. The Sampaio et al. 2010 model demonstrated inadequate calibration in the validation cohort (Spiegelhalter test: p=0.007). It also presented unsatisfactory discriminative capacity, evaluated by the area under the ROC curve = 0.618. After the coefficient readjustment, the model showed adequate calibration (Spiegelhalter test, p=0.988) and better discrimination, becoming satisfactory (AUROC = 0.762). The score developed by Sampaio et al. 2010 attributed 1 point to the variables dyspnea, associated infections, and neutrophil count <500/mm3; 2 points to jaundice and mucosal bleeding; and 3 points to platelet count <50,000/mm3. In the recalibrated model, each one of the variables had a scoring of 1 point for each.ConclusionThe temporally validated model, after coefficient readjustment, presented adequate calibration and discrimination to predict death in children hospitalized with VL.

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Early clinical manifestations associated with death from visceral leishmaniasis.

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Early clinical manifestations associated with death from visceral leishmaniasis.

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