The Fight against HIV-Associated Disseminated Histoplasmosis in the Americas: Unfolding the Different Stories of Four Centers.

Disseminated histoplasmosis is a major opportunistic infection of HIV-infected patients, killing thousands in Latin America each year. Yet, it remains a neglected disease that is often confused with tuberculosis, for lack of simple, affordable, and rapid diagnostic tools. There is great heterogeneity in the level of histoplasmosis awareness. The purpose of this report was to describe how the historical "awakening" to the threat of histoplasmosis came to be in four different centers that have actively described this disease: In Brazil, the Sao José hospital in Fortaleza; in Colombia, the Corporación para Investigaciones Biológicas in Medellin; in French Guiana, Cayenne Hospital; and in Guatemala, the Association de Salud Integral in Guatemala city. In Brazil and French Guiana, the search for leishmaniasis on the buffy coat or skin smears, respectively, led to the rapid realization that HIV patients were suffering from disseminated histoplasmosis. With time and progress in fungal culture, the magnitude of this problem turned it into a local priority. In Colombia and Guatemala, the story is different because for these mycology centers, it was no surprise to find histoplasmosis in HIV patients. In addition, collaborations with the CDC to evaluate antigen-detection tests resulted in researchers and clinicians developing the capacity to rapidly screen most patients and to demonstrate the very high burden of disease in these countries. While the lack of awareness is still a major problem, it is instructive to review the ways through which different centers became histoplasmosis-aware. Nevertheless, as new rapid diagnostic tools are becoming available, their implementation throughout Latin America should rapidly raise the level of awareness in order to reduce the burden of histoplasmosis deaths.

Lower levels of leptin are associated with severity parameters in visceral leishmaniasis patients.

Visceral leishmaniasis (VL) is the most severe clinical form of leishmaniasis, and if untreated may be fatal. It affects important organs of the immune system and is characterized by a specific immunosuppression, along with intense cellular activation and cytokine storm. Moreover, VL is now recognized as a systemic inflammatory response syndrome (SIRS), in which multiple cytokines and other pro-inflammatory molecules are released. The action of these inflammatory mediators may be considered risk factors for poor prognosis and death. Leptin, a hormone derived from adipose tissue, has been described with several immunoregulatory functions in vitro and in vivo Leishmania infection models, particularly for enhancing the macrophage microbicidal mechanisms. Considering that evaluation of immunologic parameters that may be associated with this clinical scenario may help to decrease VL lethality, we evaluated whether leptin is associated with VL pathogenesis. Thirty-one patients were recruited in the active phase of VL, of which 22 were followed up until one month after therapy (1mpt). Except for creatinine levels, all clinical parameters were altered in active VL patients, especially leucocyte counts and albumin and hemoglobin levels. Also, elevated levels of lipopolysaccharide (LPS), immunoglobulins (Ig)G1 and G3 anti-Leishmania and interleukins (IL)-6 and -10 were higher than in healthy individuals. In contrast, active VL patients presented diminished serum leptin levels and positive correlation with leukocytes counts and hemoglobin and albumin levels. After 1mpt, VL patients showed a significant increase in leptin levels, reaching values similar to healthy volunteers. As expected, only LPS levels remained elevated after 1mpt. These findings suggest that leptin levels are affected in Leishmania infection and the correlation with important parameters associated with the prognosis of VL points to the involvement of this molecule in VL immunopathogenesis. Additional studies are needed to evaluate the possibility of leptin as a prognostic marker of VL.

Visceral Leishmaniasis hospitalizations and seasonality in Fortaleza, Ceará, Northeast Brazil between 2003 ­ 2012 / Hospitalização por leishmaniose visceral e sazonalidade em Fortaleza, Ceará, Nordeste do Brasil entre 2003 e 2012

Introduction: The knowledge of the relationship between Visceral Leishmaniosis and climatic aspects is already well established in the literature of other countries, but lack data of this relationship in Brazil. Objective: This study aimed to describe the seasonal distribution of hospitalizations for Visceral Leishmaniosis (VL) in a referral hospital for infectious diseases located in an endemic area of the semiarid in the Northeast of Brazil. Methods: The number of monthly hospitalizations between 2003 and 2012 was recorded retrospectively and was correlated with climate variables. Results: During this period 1,302 patients were hospitalized. We observed an inverse relationship with the monthly amount of precipitation (r = - 0.725; p = 0.008), the number of days per month with precipitation (r = - 0.683; p = 0.0144) and relative humidity (r = - 0.746; p = 0.005) when compared with the monthly number of hospitalizations due to VL. Inversely, there was a direct relationship with the maximum monthly mean temperature and the number of hospitalizations due to VL (r = 0.643; p = 0.024). Conclusions: The rainy season, characterized by more rainfall and higher humidity, was correlated with fewer hospitalizations for VL. Conversely, in months with higher temperatures the number of hospitalizations for VL was higher.

Efficacy and safety of available treatments for visceral leishmaniasis in Brazil: A multicenter, randomized, open label trial.

BACKGROUND: There is insufficient evidence to support visceral leishmaniasis (VL) treatment recommendations in Brazil and an urgent need to improve current treatments. Drug combinations may be an option. METHODS: A multicenter, randomized, open label, controlled trial was conducted in five sites in Brazil to evaluate efficacy and safety of (i) amphotericin B deoxycholate (AmphoB) (1 mg/kg/day for 14 days), (ii) liposomal amphotericin B (LAMB) (3 mg/kg/day for 7 days) and (iii) a combination of LAMB (10 mg/kg single dose) plus meglumine antimoniate (MA) (20 mg Sb+5/kg/day for 10 days), compared to (iv) standard treatment with MA (20 mg Sb+5/kg/day for 20 days). Patients, aged 6 months to 50 years, with confirmed VL and without HIV infection were enrolled in the study. Primary efficacy endpoint was clinical cure at 6 months. A planned efficacy and safety interim analysis led to trial interruption. RESULTS: 378 patients were randomized to the four treatment arms: MA (n = 112), AmphoB (n = 45), LAMB (n = 109), or LAMB plus MA (n = 112). A high toxicity of AmphoB prompted an unplanned interim safety analysis and this treatment arm was dropped. Per intention-to-treat protocol final analyses of the remaining 332 patients show cure rates at 6 months of 77.5% for MA, 87.2% for LAMB, and 83.9% for LAMB plus MA, without statistically significant differences between the experimental arms and comparator (LAMB: 9.7%; CI95% -0.28 to 19.68, p = 0.06; LAMB plus MA: 6.4%; CI95% -3.93 to 16.73; p = 0.222). LAMB monotherapy was safer than MA regarding frequency of treatment-related adverse events (AE) (p = 0.045), proportion of patients presenting at least one severe AE (p = 0.029), and the proportion of AEs resulting in definitive treatment discontinuation (p = 0.003). CONCLUSIONS: Due to lower toxicity and acceptable efficacy, LAMB would be a more suitable first line treatment for VL than standard treatment. ClinicalTrials.gov identification number: NCT01310738. TRIAL REGISTRATION: ClinicalTrials.gov NCT01310738.

Urbanization of visceral leishmaniasis (kala-azar) in Fortaleza, Ceará, Brazil / Urbanización de la leishmaniasis visceral (kala-azar) en Fortaleza, Ceará, Brasil

OBJECTIVES: Visceral leishmaniasis (VL) is endemic in Brazil and appears to occur in epidemic form in the state of Ceará. Few epidemiologic studies have been done on VL in this state. The aim of this study is to establish the epidemiologic pattern of VL in Fortaleza City and to show how urbanization has occurred in recent years. METHODS: Data were obtained from the State Health Department of Fortaleza, Ceará, and included all cases of VL registered in Fortaleza from January 2001 to December 2006. RESULTS: There were a marked increase and an elevated incidence of cases of VL in urban areas. Children and young people were the most affected group. CONCLUSION: The epidemic occurrence of VL in the region must convince authorities to adopt more adequate policies of disease control.

OBJETIVOS: La leishmaniasis visceral (LV) es endémica en Brasil y suele ocurrir en forma epidémica en el estado de Ceará. Se han realizado pocos estudios epidemiológicos sobre LV en ese estado. El objetivo de este estudio es establecer el patrón epidemiológico de LV en la ciudad de Fortaleza y mostrar cómo ha ocurrido la urbanización de esta enfermedad en los últimos años. MÉTODOS: Los datos se obtuvieron del Departamento Estatal de Salud de Fortaleza, Ceará, y abarcaron todos los casos de LV registrados en esa ciudad entre enero de 2001 y diciembre de 2006. RESULTADOS: Se observó un marcado incremento y una elevada incidencia de LV en las áreas urbanas. Los niños y jóvenes fueron los grupos más afectados. CONCLUSIÓN: La ocurrencia de epidemias de LV en la región debe convencer a las autoridades para que adopten políticas más apropiadas para el control de esta enfermedad.

Urbanization of visceral leishmaniasis (kala-azar) in Fortaleza, Ceará, Brazil.

OBJECTIVES: Visceral leishmaniasis (VL) is endemic in Brazil and appears to occur in epidemic form in the state of Ceará. Few epidemiologic studies have been done on VL in this state. The aim of this study is to establish the epidemiologic pattern of VL in Fortaleza City and to show how urbanization has occurred in recent years. METHODS: Data were obtained from the State Health Department of Fortaleza, Ceará, and included all cases of VL registered in Fortaleza from January 2001 to December 2006. RESULTS: There were a marked increase and an elevated incidence of cases of VL in urban areas. Children and young people were the most affected group. CONCLUSION: The epidemic occurrence of VL in the region must convince authorities to adopt more adequate policies of disease control.

Leishmaniose cutânea no Ceará: aspectos históricos, clínicos e evolução terapêutica / Cutaneous leishmaniasis in Ceara: historical, clinical and therapeutic evolution

A leishmaniose cutânea é um importante problema de saúde no Brasil, existindo como doença autóctone em todos os estados brasileiros. No período de 1980 a 2005, foram registrados 613.644 casos no país. No Ceará, é uma doença endêmica em várias regiões e em muitos municípios faz centenas de vítimas todos os anos. Em épocas de epidemias, o número de registros tem chegado a mais de 4000 notificações por ano. Nos últimos 28 anos (1980-2008) foram diagnosticados 55.925 pessoas acometidas da doença, o que reflete uma média de 2000 vítimas de leishmaniose cutânea por ano. Sabe-se que os primeiros registros da doença no Ceará datam de 1925. Apesar de ter todo este impacto na saúde pública do estado, existem muitas lacunas no conhecimento deste infecção, quer seja do ponto de vista histórico; do ponto de vista clínico e relacionadas ao tratamento. Objetivo: Fazer um levantamento sobre os aspectos históricos e as descobertas mais relevantes relacionadas as leishmanioses; investigar quando e como foi introduzida no estado do Ceará, bem como seus descobridores; descrever de modo detalhado as manifestações clínicas da leishmaniose cutânea no Ceará; relatar a evolução histórica do tratamento, bem como apresentar uma alternativa de tratamento para a leishmaniose cutânea. Metodologia: Foram consultadas fontes primárias e fontes secundárias...

Melioidosis in the Americas.

Melioidosis is a potentially severe bacterial infection caused by Burkholderia pseudomallei. There has been growing awareness of the disease in the Americas, particularly since the Vietnam conflict when it was diagnosed in returning service personnel. Accidental laboratory exposure indicates the difficulty making a culture-based diagnosis when melioidosis has not been considered in the differential diagnosis. Melioidosis is most likely underdiagnosed in tropical Central and South America where conditions are more suited to persistence of B. pseudomallei in the environment. Recent melioidosis case clusters in northeastern Brazil highlight the threat posed to rural populations located far from specialist services. Increased clinical awareness of the disease and improvements in laboratory diagnostic methods are likely to bring wider recognition of melioidosis in the Americas.