Total serum N-glycans mark visceral leishmaniasis in human infections with Leishmania infantum.

Visceral leishmaniasis (VL) is a clinical form of leishmaniasis with high mortality rates when not treated. Diagnosis suffers from invasive techniques and sub-optimal sensitivities. The current (affordable) treatment with pentavalent antimony as advised by the WHO is possibly harmful to the patient. There is need for an improved diagnosis to prevent possibly unnecessary treatment. N-glycan analysis may aid in diagnosis. We evaluated the N-glycan profiles from active VL, asymptomatic infections (ASYMP) and controls from non-endemic (NC) and endemic (EC) areas. Active VL has a distinct N-glycome profile that associates with disease severity. Our study suggests that the observed glycan signatures could be a valuable additive to diagnosis and assist in identifying possible markers of disease and understanding the pathogenesis of VL. Further studies are warranted to assess a possible future role of blood glycome analysis in active VL diagnosis and should aim at disease specificity.

Association between calcium/magnesium ratio and insulin resistance in women with obesity and normal-weight women

ABSTRACT The aim of this study was to evaluate the association between the calcium/magnesium (Ca/Mg) ratio and insulin resistance in women with obesity and normal-weight women. This was a cross-sectional study with 128 women (62 women with obesity and 66 normal-weight women). We measured dietary minerals intake and analyzed magnesium and calcium biomarkers. Ca/Mg ratio in diet, plasma and urine were calculated. We have evaluated glycemic parameters. Women with obesity had low dietary magnesium, reduced plasma and erythrocyte magnesium concentrations, and elevated urinary magnesium excretion. Plasma calcium concentration was lower and urinary calcium excretion was higher in patients with obesity than in the normal-weight group. Dietary magnesium and calcium intake per kilogram of body weight per day was lower in obese women than in the control group. Ca/Mg ratio in plasma and urine were elevated in women with obesity. We found a significant correlation among magnesium biomarkers and calcium parameters. Ca/Mg ratio seems to be associated with insulin resistance in obese women.

RESUMEN El objetivo de este estudio fue evaluar la asociación entre la relación Ca/Mg y la resistencia a la insulina en mujeres con obesidad y en mujeres con peso normal. El diseño del estudio fue transversal y participaron 128 mujeres (62 mujeres con obesidad y 66 mujeres con peso normal). Se analizó la ingesta de minerales en la dieta y se realizaron análisis de biomarcadores de magnesio y calcio. Se calculó la relación Ca/Mg en dieta, plasma y orina y se evaluaron los parámetros glicémicos. Las mujeres con obesidad tenían niveles bajos de magnesio en la dieta, concentraciones reducidas de magnesio en plasma y eritrocitos, y excreción urinaria de magnesio elevada. La concentración plasmática de calcio fue menor en pacientes con obesidad, y la excreción urinaria de calcio fue mayor que en el grupo de mujeres con peso normal. La ingesta dietética de magnesio y calcio por kilogramo de peso corporal por día fue menor en las mujeres con obesidad, que en el grupo control. La relación Ca/Mg en plasma y orina estaba elevada en mujeres con obesidad. Se encontró una correlación significativa entre los biomarcadores de magnesio y los parámetros de calcio. La relación Ca / Mg parece estar asociada con la resistencia a la insulina en mujeres con obesidad.

Visceral leishmaniasis and vulnerability conditions in an endemic urban area of Northeastern Brazil.

BACKGROUND: Visceral leishmaniasis (VL) is considered an urban endemic that may be related to sociodemographic factors and urban infrastructure. The objective of this study was to analyze the conditions of vulnerability and the incidence of VL, and to identify the spatiotemporal pattern of the disease. METHODS: Data on reported cases of VL were collected from 2007 to 2016. Thematic maps on the spatiotemporal distribution were produced using values normalized by the area of the neighborhoods. The primary indicators of vulnerability were normalized for later construction of the synthetic indicators of vulnerability of social structure, household structure, and urban infrastructure, and from these, a vulnerability index was developed. The bivariate global Moran index was used to verify the existence of spatial autocorrelation between the incidence of VL and the conditions of vulnerability, while the bivariate local Moran index was used to identify the existence of spatial clusters. RESULTS: The 695 cases reported presented a diffuse distribution when the spatial pattern was evaluated. The incidence of the disease was correlated with worsened living conditions. Statistically significant clusters were revealed between the incidence of the disease and the vulnerability indicators of social structure, household structure, urban infrastructure and composite vulnerability index. CONCLUSION: Addressing the local vulnerability conditions is important to the understanding of the distribution of visceral leishmaniasis, identifying the most susceptible areas, and planning control strategies.

Human Competence to Transmit Leishmania infantum to Lutzomyia longipalpis and the Influence of Human Immunodeficiency Virus Infection.

Visceral leishmaniasis (VL) caused by Leishmania infantum is a lethal disease transmitted by sand flies. Although, considered a zoonosis with dogs held as the main reservoirs, humans are also sources of infection. Therefore, control policies currently focused on dog culling may need to consider that VL and human immunodeficiency virus (HIV)/VL patients may also be infectious, contributing to transmission. Reservoir competence of patients with VL without and with HIV infection and of persons asymptomatically infected with Leishmania was assessed by xenodiagnosis with the vector Lutzomyia longipalpis. Parasites in sand fly's guts were identified by using optical microscopy and by conventional polymerase chain reaction (PCR). Leishmania infantum blood parasite burden was determined by quantitative PCR. Among the 61 participants, 27 (44%) infected sand flies as seen by microscopy or PCR. When infectiousness was assessed by microscopy, xenodiagnosis was positive in five (25%) patients not infected with HIV, whereas nine (45%) of those harboring HIV were positive. Among the 19 asymptomatic patients four (21%) infected sand flies only demonstrated by PCR. One (50%) asymptomatic patient with HIV had a positive xenodiagnosis by microscopy. 9/372 (2.4%) and 37/398 (9.2%) sand flies were infected when feeding in patients without and with HIV, respectively. Infectiousness was poorly correlated with quantitative PCR. The study shows that asymptomatic humans are capable of transmitting L. infantum, that ill persons with HIV infection are more infectious to sand flies, and that humans are more important reservoirs than previously thought. This fact may be considered when designing control policies for zoonotic VL.

Occurrence of Lutzomyia longipalpis Lutz & Neiva 1912 and Cerdocyon thous Linnaeus 1977, in a visceral leishmaniasis endemic area in Brazil.

Cerdocyon thous presents a wide geographic distribution in Brazil and its role as a possible Leishmania infantum reservoir in a visceral leishmaniasis (VL) transmission cycle regardless of dogs (Canis familiaris) has been discussed. From this perspective, this work describes the occurrence and use of the habitat by Cerdocyon thous in a Lutzomyia longipalpis occurrence area Teresina (Piaui - Brazil), VL endemic region. Three specimens of C. thous were monitored with the use of radio telemetry and trails and footprints, seeking to find possible natural dens in order to collect the sanflies from the site. Luminous CDC and Damasceno traps were simultaneously installed at the visited sites, where two specimens of L. longipalpis and one L. termitophila were captured. The identification of the dens and trails, allows us to infer that the dens are not used only by the C. thous. Finding the VL vector in natural C. thous natural dens, reinforces the hypothesis of transmission of Le. infantum in the outskirts of the large urban centers, in a cycle that independs from dogs.

Clinical severity of visceral leishmaniasis is associated with changes in immunoglobulin g fc N-glycosylation.

UNLABELLED: Visceral 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. IMPORTANCE: Immunoglobulins (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.

The risk factors for and effects of visceral leishmaniasis in graft and renal transplant recipients.

BACKGROUND: The aim of this study was to identify the risk factors for visceral leishmaniasis (VL) in renal transplant recipients and to analyze the impacts of this disease on graft success and patient health. METHODS: This retrospective, case-control study examined 120 renal transplant patients in a VL endemic area. The treatment group included patients (n=20) who developed VL after transplantation, and the control group (n=100) was composed of renal transplant recipients without VL. This study evaluated socioeconomic, demographic, clinical, and laboratory variables. Bivariate analysis and multiple logistic regressions were performed to identify potential risk factors. RESULTS: The average time between transplantation and Leishmania infection in the treatment group was 29.4 months. Seventeen (85%) patients were cured and 3 (15%) died. In 95% of the cases, a myelogram was used for initial identification of Leishmania forms. The significant risk factors for VL in renal transplant recipients were cytomegalovirus infection after transplantation (odds ratio [OR], 5.29; 95% confidence interval [CI], 1.27-21.97) and living with cats (OR, 5.74; 95% CI, 1.15-28.76). Bacterial infection after transplantation (OR, 3.00; 95% CI, 0.96-9.37) and unpaved streets in the neighborhood (OR, 2.14; 95% CI, 0.71-6.43) tended to increase the risk of VL, whereas a negative Rh factor tended to protect against VL (OR, 0.26; 95% CI, 0.06-1.02). CONCLUSION: Cytomegalovirus infection after transplantation and living with cats increased the risk of VL in renal transplant recipients living in VL endemic areas.