Risk Factors for Adverse Prognosis and Death in American Visceral Leishmaniasis: A Meta-analysis

Background: In the current context of high fatality rates associated with American visceral leishmaniasis (VL), the appropriate use of prognostic factors to identify patients at higher risk of unfavorable outcomes represents a potential tool for clinical practice. This systematic review brings together information reported in studies conducted in Latin America, on the potential predictors of adverse prognosis (continued evolution of the initial clinical conditions of the patient despite the implementation of treatment, independent of the occurrence of death) and death from VL. The limitations of the existing knowledge, the advances achieved and the approaches to be used in future research are presented. Methods/Principal Findings: The full texts of 14 studies conforming to the inclusion criteria were analyzed and their methodological quality examined by means of a tool developed in the light of current research tools. Information regarding prognostic variables was synthesized using meta-analysis. Variables were grouped according to the strength of evidence considering summary measures, patterns and heterogeneity of effect-sizes, and the results of multivariate analyses. The strongest predictors identified in this review were jaundice, thrombocytopenia, hemorrhage, HIV coinfection, diarrhea, age 40–50 years, severe neutropenia, dyspnoea and bacterial infections. Edema and low hemoglobin concentration were also associated with unfavorable outcomes. The main limitation identified was the absence of validation procedures for the few prognostic models developed so far. Conclusions/Significance: Integration of the results from different investigations conducted over the last 10 years enabled the identification of consistent prognostic variables that could be useful in recognizing and handling VL patients at higher risk of unfavorable outcomes. The development of externally validated prognostic models must be prioritized in future investigations. Author Summary: In contrast to other clinical presentations of leishmaniasis in Latin America, American visceral leishmaniasis (VL) can lead to death in 5-10% of patients under treatment. The fatality rates associated with this disease have remained stable at a high level over the years in Brazil and are neither recorded in under-treatment patients from endemic countries of the Old World nor from non-endemic countries where such cases are imported. Since VL-induced lethality can occur even after the implementation of recommended therapy, the understanding of individual, clinical and laboratory factors that predispose to an unfavorable outcome might represent an important feature for informing better practice in the clinical management of cases. The present systematic review with meta-analysis brings together information on various prognostic variables associated with the severity of VL. Potential predictors identified in the studies surveyed were grouped according to the strength of evidence available, and 13 were considered to be of significant relevance. The gaps in the existing knowledge and the need for the development of externally validated prognostic models were also discussed. The results presented herein could be useful in identifying patients at higher risk of unfavorable evolution or death from VL, and might provide an aid in decision-making regarding the clinical management of VL cases.