High-Resolution Plasma Metabolomics Identifies Alterations in Fatty Acid, Energy, and Micronutrient Metabolism in Adults Across the Leprosy Spectrum.

BACKGROUND: High-resolution metabolomics (HRM) is an innovative tool to study challenging infectious diseases like leprosy, where the pathogen cannot be grown with standard methods. Here, we use HRM to better understand associations between disease manifestations, nutrition, and host metabolism. METHODS: From 2018 to 2019, adults with leprosy and controls were recruited in Minas Gerais, Brazil. Plasma metabolites were detected using an established HRM workflow and characterized by accurate mass, mass to charge ratio m/z and retention time. The mummichog informatics package compared metabolic pathways between cases and controls and between multibacillary (MB) and paucibacillary (PB) leprosy. Additionally, select individual metabolites were quantified and compared. RESULTS: Thirty-nine cases (62% MB and 38% PB) and 25 controls were enrolled. We found differences (P < .05) in several metabolic pathways, including fatty acid metabolism, carnitine shuttle, retinol, vitamin D3, and C-21 steroid metabolism, between cases and controls with lower retinol and associated metabolites in cases. Between MB and PB, leukotrienes, prostaglandins, tryptophan, and cortisol were all found to be lower in MB (P < .05). DISCUSSION: Metabolites associated with several nutrient-related metabolic pathways appeared differentially regulated in leprosy, especially MB versus PB. This pilot study demonstrates the metabolic interdependency of these pathways, which may play a role in the pathophysiology of disease.

The Burden of Helminth Coinfections and Micronutrient Deficiencies in Patients with and without Leprosy Reactions: A Pilot Study in Minas Gerais, Brazil.

Leprosy reactions are immune-mediated complications occurring in up to 50% of patients. The immune consequences of helminth infections and micronutrient deficiencies suggest a potential role in type 1 reactions (T1R) or type 2 reactions (T2R). We conducted a case-control study in Minas Gerais, Brazil, to evaluate whether comorbidities and other factors are associated with reactions in patients with multibacillary leprosy. Stool and serum were tested for helminth infections. Deficiencies of vitamin A, D, and iron were measured using serum retinol, 25-hydroxyvitamin D, and ferritin, respectively. Logistic regression models identified associations between reactions and helminth infections, micronutrient deficiencies, and other variables. Seventy-three patients were enrolled, 24 (33%) with T1R, 21 (29%) with T2R, 8 (15%) with mixed T1R/T2R, and 20 (27%) without reactions. Evidence of helminth infections were found in 11 participants (15%) and included IgG4 reactivity against Schistosoma mansoni, Strongyloides, and Ascaris antigens. Thirty-eight (52%) had vitamin D deficiency, eight (11%) had vitamin A insufficiency, 21 (29%) had anemia, and one (1.4%) had iron deficiency. Multivariable logistic regression showed no statistically significant associations between helminth coinfections and total reactions (adjusted odds ratios [aOR]: 1.36, 95% CI: 0.22, 8.33), T1R (aOR: 0.85, 95% CI: 0.17, 4.17), or T2R (aOR: 2.41, 95% CI: 0.29, 20.0). Vitamin D deficiency and vitamin A insufficiency were also not statistically associated with reactions. However, vitamin deficiencies and helminth infections were prevalent in these patients, suggesting a potential role for additional treatment interventions. Studying reactions prospectively may further clarify the role of comorbidities in the clinical presentation of leprosy.

Micronutrientes: un eslabón clave en la inmunopatogénesis de la lepra / Micronutrients: a key link in the immunopathogenesis of leprosy

The purpose of this work was to analyze the prevalence of fetal mortality (FM) in mothers in early adolescence (10-14 years), late adolescence (15-19 years) and in adults (20-34 years), during the period 2014-2016, in the North Department of Santander-Colombia. The factors taken into account were: gestation time, fetal weight, childbirth, basic causes, area of residence, and educational level of the mothers. Method: The study was retrospective, correlational, analytical-comparative. The database was from a secondary public access source of the National Administrative Department of Statistics (DANE-Colombia). The analysis was performed using the following tests: chi-square, Kruskal-Wallis H, Cramer's V coefficient, Goodman and Kruskal's gamma, Tukey's post-hoc procedures and the Bonferroni method based on Student's t-test. Results: The prevalence of FM for the years 2014-2016 was 10.0 per 1000 live births in mothers in early adolescence, 19.2 in mothers in late adolescence and 18.6 in adult mothers. It emerged that the prevalence of FM in pregnancies of under 22 weeks was higher in adult mothers, before delivery and during childbirth (chi-square = 32.023; p = 0.021), and there was a slight negative relationship between mother's age and weight of the fetus (gamma = -0.186; p = 0.014). The prevalence of FM was higher in adult mothers residing in the municipal district (chi-square = 80.18; p = 0.000), in mothers with primary, secondary and professional-level basic education (chi-square = 105.56; p = 0.000), and greater in adult mothers due to obstetric complications and birth trauma

La lepra es una enfermedad infecciosa crónica causada por Mycobacterium leprae, la cual tiene una notoria afinidad por la piel y los troncos nerviosos periféricos. Esta enfermedad se caracteriza por tener una clínica polimorfa que depende de la respuesta inmune del hospedero. La inmunopatogénesis de esta enfermedad aún representa un reto para los investigadores, y un eslabón faltante en su comprensión es el estudio de los micronutrientes, los cuales se ha demostrado que tienen la capacidad de modular la respuesta inmune innata y adaptativa. El objetivo de esta revisión es describir y relacionar algunos nutrientes, como las vitaminas A, D, E, C y B6, el folato, el zinc y el hierro, con la respuesta inmune en la lepra. Además, proponemos que algunos micronutrientes (vitaminas A, D y C y zinc) serían importantes para mitigar la aparición de reacciones lepróticas por medio de la modulación de la respuesta inmune en el hospedero infectado por M. leprae, y que micronutrientes como las vitaminas A, D, B6 y D, el folato, el hierro y el zinc serían importantes para reducir la incidencia de la lepra, dado que promoverían una mejor respuesta inmune en convivientes. Por lo tanto, el estudio del estado nutricional y el aporte suplementario con micronutrientes en convivientes y en afectados con lepra sería clave en la eliminación de esta enfermedad que ha deformado cuerpos y ha destruido sueños a lo largo de los siglos.

Dietary diversity and poverty as risk factors for leprosy in Indonesia: A case-control study.

BACKGROUND: Poverty has long been considered a risk factor for leprosy and is related to nutritional deficiencies. In this study, we aim to investigate the association between poverty-related diet and nutrition with leprosy. METHODOLOGY/PRINCIPAL FINDINGS: In rural leprosy-endemic areas in Indonesia, we conducted a household-based case-control study using two controls for each case patient (100 recently diagnosed leprosy patients and 200 controls), matched for age and gender. All participants were interviewed to collect information on their demographics, socioeconomic situation, health, and diet. Body mass index, dietary diversity score, as well as anemia and iron micronutrient profiles were also obtained. By means of univariate, block-wise multivariate, and integrated logistic regression analyses, we calculated odds ratios between the variables and the occurrence of leprosy. Unstable income (odds ratio [OR], 5.67; 95% confidence interval [CI], 2.54-12.64; p = 0.000), anemia (OR, 4.01; 95% CI, 2.10-7.64; p = 0.000), and higher household food insecurity (OR, 1.13; 95% CI, 1.06-1.21; p = 0.000) are significantly associated with an increased risk of having leprosy. Meanwhile, higher education (OR, 0.34; 95% CI, 0.15-0.77; p = 0.009) and land ownership (OR, 0.39; 95% CI, 0.18-0.86; p = 0.019) have significant protective associations against leprosy. Although lower dietary diversity, lack of food stock, food shortage, low serum iron, and high ferritin were found more commonly in those with leprosy, the occurrence of leprosy was not significantly associated with iron deficiency (OR, 1.06; 95% CI, 0.10-11.37; p = 0.963). CONCLUSIONS/SIGNIFICANCE: Food poverty is an important risk factor for leprosy susceptibility, yet the mechanisms underlying this association other than nutrient deficiencies still need to be identified. With a stable incidence rate of leprosy despite the implementation of chemoprophylaxis and multidrug therapy, improving dietary diversity through food-based approaches should be initiated and directed toward high-prevalence villages. The possible underlying factors that link poverty to leprosy other than nutrient deficiencies also need to be identified.

Estresse oxidativo e micronutrientes na hanseníase / Oxidative stress and micronutrients in leprosy

Objetivo Avaliar o estresse oxidativo, perfil antioxidante e de micronutrientes em pacientes portadores de hanseníase multibacilar e paucibacilar antes do tratamento poliquimioterápico. Métodos Analisaram-se 52 amostras de soro de pacientes portadores de hanseníase - 38 multibacilares e 14 paucibacilares -, usuários do ambulatório de dermatologia de um hospital público universitário, além de 30 amostras controles. Quantificaram-se marcador de peroxidação lipídica malondialdeído pelo método de substâncias reativas ao ácido tiobarbitúrico, antioxidante glutationa reduzida pelo método baseado na quantificação de tiol solúvel em ácido, antioxidante vitamina E por cromatografia líquida de alta eficiência, minerais selênio, zinco, cobre, magnésio por espectrometria de massa com fonte plasma acoplado, e sorologia do anticorpo glicolipídio fenólico I pelo método Enzyme-Linked Immunosorbent Assay. Foi utilizado teste não paramétrico de Mann-Whitney para comparar as variáveis quantificadas neste estudo entre os diferentes grupos, e correlação de Pearson para verificar associação dessas variáveis com o anticorpo. O critério de significância adotado foi de p<0,05. Resultados Houve diferença significativa para o malondialdeído (p<0,001) e vitamina E (p<0,001) no grupo controle comparado aos grupos com hanseníase, multibacilar e paucibacilar. No entanto, essas mesmas variáveis não diferiram entre os grupos multibacilar e paucibacilar (p=0,495 e p=0,920 respectivamente). A glutationa reduzida foi superior no grupo controle em relação ao grupo com hanseníase (p=0,012) e multibacilar (p=0,001), no entanto não diferiu do grupo paucibacilar (p=0,920). Quando comparada com os multibacilares e paucibacilares, a glutationa reduzida também não diferiu (p=0,063). Quanto aos minerais, todos se apresentaram dentro da normalidade, exceto o magnésio, cujos níveis foram deficientes em todos os pacientes do estudo. Não foi possível observar correlação do ...

Objective To determine the oxidative stress and the antioxidant and micronutrient profile of patients with multibacillary and paucibacillary leprosy before polychemotherapeutic treatment. Methods Thirty control samples and fifty-two serum samples from leprosy patients who attended the dermatology outpatient clinic of a public university hospital were analyzed; 38 of them had multibacillary and 14 paucibacillarty. Malondialdehyde, a marker of lipid peroxidation, was determined using the thiobarbituric acid reacting substances assay; the antioxidant reduced glutathione was determined using a method based on the quantification of acid-soluble thiol; the antioxidant vitamin E was determined using High-Performance Liquid Chromatography; the minerals selenium, zinc, copper and magnesium were determined using coupled-mass spectrometry, and the serum phenol I glycolipid antibody was determined using Enzyme-Linked Immunosorbent Assay. The nonparametric Mann-Whitney test was used to compare the variables quantified in the present study between the different groups, and Pearson's correlation analysis was used to verify the association between these variables and the antibody. The significance level was set at p<0.05. Results There was a significant difference in the content of malondialdehyde (p<0.001) and vitamin E (p<0.001) between the groups with multibacillary and paucibacillary leprosy (p=0.495 and p=0.920, respectively) and the control groups. Reduced glutathione levels were higher in the control group compared with those of the group with leprosy (p=0.012) and multibacillary leprosy (p=0.001), but did it not differ from that of the paucibacillary group (p=0.920). Reduced glutathione levels did not differ between the multibacillary and paucibacillary groups (p=0.063) either. All minerals were within normal limits, except for magnesium; magnesium deficiency was detected in all groups studied. No correlation was observed between the ...

Micronutrients influencing the immune response in leprosy.

Leprosy is a chronic infectious disease caused by Mycobacterium leprae, an intracellular bacillus of airborne transmission. The disease affects the skin and peripheral nerves and can cause neurological sequelae. The bacillus multiplies slowly in the host and the disease probably occurs due to malfunctioning in host immune response. This review addresses the role of some specific micronutrients in the immune response, such as Vitamins A, D, E, C, Zinc and Selenium, detailing their mechanisms of actions in infectious diseases, and in leprosy. The immune response to pathogens releases harmful substances, which lead to tissue damage. This review discusses how a decreased level of antioxidants may contribute to an increased oxidative stress and complications of infectious diseases and leprosy. As the nutrients have a regulatory effect in the innate and adaptative immune responses, a perfect balance in their concentrations is important to improve the immune response against the pathogens.

Micronutrients influencing the immune response in leprosy / Micronutrientes que influyen en la respuesta immune en la lepra

La lepra es una enfermedad infecciosa crónica causada por el Mycobacterium leprae, un bacilo intracelular de transmisión aérea. La enfermedad afecta la piel y los nervios periféricos y causa secuelas neurológicas. El bacilo se multiplica lentamente en el hospedador y posiblemente la enfermedad ocurre por el mal funcionamiento de la respuesta inmunitaria del hospedador. Esta revisión aborda el papel de algunos micronutrientes específicos en la respuesta inmunitaria, tales como las vitaminas A, D, E, C, el cinc y el selenio, detallando sus mecanismos de acción en las enfermedades infecciosas y en la lepra. La respuesta inmunitaria a los patógenos libera sustancias nocivas que producen lesión tisular. Esta revisión también aborda cómo una menor cantidad de antioxidantes puede contribuir a un aumento del estrés oxidativo y a complicaciones de las enfermedades infecciosas y la lepra. Puesto que los micronutrientes poseen un efecto regulador de la respuesta inmunitaria innata y adaptativa, es importante un equilibrio perfecto de sus concentraciones para mejorar la respuesta inmunitaria frente a los patógenos (AU)

Leprosy is a chronic infectious disease caused by Mycobacterium leprae, an intracellular bacillus of airborne transmission. The disease affects the skin and peripheral nerves and can cause neurological sequelae. The bacillusmultiplies slowly in the host and the disease probably occurs due to malfunctioning in host immune response. This review addresses the role of some specific micronutrients in the immune response, such as Vitamins A, D, E, C, Zinc and Selenium, detailing their mechanisms of actions in infectious diseases, and in leprosy. The immune response to pathogens releases harmful substances, which lead to tissue damage. This review discusses how a decreased level of antioxidants may contribute to an increased oxidative stress and complications of infectious diseases and leprosy. As the nutrients have a regulatory effect in the innate and adaptative immune responses, a perfect balance in their concentrations is important to improve the immune response against the pathogens (AU)