Macrophage migration inhibitory factor -173 G>C single nucleotide polymorphism and its association with active pulmonary tuberculosis

Purpose The establishment of candidate genes associated with susceptibility to TB is a challenge especially due to divergent frequencies among different populations. The objective of this study was to evaluate the association between macrophage migration inhibitory factor (MIF) -173 G>C single nucleotide polymorphism (SNP) and susceptibility to pulmonary TB in a population of southern Brazil. Methods Case-control study. Patients > 18 years old, diagnosed with pulmonary TB were included. The control group consisted of blood donors and household contacts, not relatives, healthy and > 18 years old. MIF -173 G>C SNPs were genotyped using real-time PCR using a TaqMan SNP Genotyping assay. Results 174 patients and 166 controls were included. There were no statistically significant differences between cases and controls regarding genotype prevalence (p>0.05). Comparing patients with normal genotype (GG) with those with at least one C allele, there was also no statistically significant difference (p = 0.135). Also, there was no statistically significant difference comparing the homozygous for the mutation (CC) with the other patients (GG and CG) (p = 0.864). Conclusions We did not find association between MIF -173 G>C polymorphism and susceptibility to pulmonary TB

Variant predictions in congenital adrenal hyperplasia caused by mutations in CYP21A2

CYP21A2 deficiency represents 95% of congenital adrenal hyperplasia (CAH) cases, a group of genetic disorders that affect steroid biosynthesis. The genetic and functional analysis provide critical tools to elucidate complex CAH cases. One of the most accessible tools to infer the pathogenicity of new variants is in silico prediction. Here, we analyzed the performance of in silico prediction tools to categorize missense single nucleotide variants (SNVs) of CYP21A2. SNVs of CYP21A2 characterized in vitro by functional assays were selected to assess the performance of online single and meta predictors. SNVs were tested separately or in combination with the related phenotype (severe or mild CAH form). In total, 103 SNVs of CYP21A2 (90 pathogenic and 13 neutral) were used to test the performance of 13 single-predictors and four meta-predictors. All SNVs associated with the severe phenotypes were well categorized by all tools, with an accuracy of between 0.69 (PredictSNP2) and 0.97 (CADD), and Matthews’ correlation coefficient (MCC) between 0.49 (PoredicSNP2) and 0.90 (CADD). However, SNVs related to the mild phenotype had more variation, with the accuracy between 0.47 (S3Ds&GO and MAPP) and 0.88 (CADD), and MCC between 0.18 (MAPP) and 0.71 (CADD). From our analysis, we identified four predictors of CYP21A2 variant pathogenicity with good performance, CADD, ConSurf, DANN, and PolyPhen2. These results can be used for future analysis to infer the impact of uncharacterized SNVs in CYP21A2

Alterações metabólicas associadas à terapia anti-retroviral em pacientes HIV-positivos

OBJECTIVE: To evaluate metabolic changes associated with highly active antiretroviral therapy (HAART) in HIV-positive patients, and to identify risk factors associated. METHODS: Retrospective study that included 110 HIV-positive patients who where on HAART in the city of Porto Alegre (Southern Brazil) between January 2003 and March 2004. Data on demographic variables, cigarette smoking, diabetes mellitus, cholesterol and triglyceride levels, stage of HIV infection, antiretroviral therapy and HCV coinfection were collected. General linear models procedure for repeated measures was used to test the interaction between HAART and HCV coinfection or protease inhibitor treatment. RESULTS: Total cholesterol, triglycerides, and glucose levels significantly increased after receiving HAART (pOBJETIVO: Evaluar las alteraciones metabólicas asociadas a la terapia anti-retroviral potente en pacientes HIV-positivos e identificar factores de riesgo asociados. MÉTODOS: Estudio retrospectivo con 110 pacientes HIV-positivos que estaban en terapia anti-retroviral potente (HAART) en la ciudad de Porto Alegre (Sur de Brasil), entre enero de 2003 y marzo de 2004. Los datos colectados incluyen variables demográficas, tabaquismo, diabetes mellitas, niveles de colesterol y triglicéridos, fase de la infección viral, terapia anti-retroviral y co-infección con hepatitis C. El análisis multivariado para medidas repetidas (General Linear Model procedure for Repeated Measures) fue utilizada para analizar la interacción entre el efecto de uso de HAART y el uso de inhibidores de proteasa o co-infección por hepatitis C. RESULTADOS: Fueron observados aumentos significativos en los niveles de colesterol total, triglicéridos y glucosa posterior al tratamiento con HAART (pOBJETIVO: Avaliar as alterações metabólicas associadas à terapia anti-retroviral potente em pacientes HIV-positivos e identificar fatores de risco associados. MÉTODOS: Estudo retrospectivo com 110 pacientes HIV-positivos que estavam sob terapia anti-retroviral potente (HAART) na cidade de Porto Alegre (RS), entre janeiro de 2003 e março de 2004. Os dados coletados incluem variáveis demográficas, tabagismo, diabetes mellitus, níveis de colesterol e triglicerídeos, estágio da infecção viral, terapia anti-retroviral e co-infecção com hepatite C. A análise multivariada para medidas repetidas (General Linear Model procedure for Repeated Measures) foi utilizada para testar a interação entre o efeito do uso de HAART e o uso de inibidores de protease ou co-infecção por hepatite C. RESULTADOS: Foram observados aumentos significativos nos níveis de colesterol total, triglicerídeos e glicose após o tratamento com HAART (

Detecção de DNA de Papilomavírus Humano (HPV) em mulheres grávidas utilizando a urina

Este trabalho foi realizado com o objetivo de investigar a incidência de DNA de Papilomavírus Humano(HPV) em urina de gestantes atendidas no Hospital Divina Providencia, do município de FredericoWestphalen da Região do Médio Uruguai. As amostras coletadas foram encaminhadas ao Laboratório deBiologia Molecular da ULBRA onde foram submetidas aos processos de extração de DNA e amplificaçãopor PCR (Polimerase Chain Reaction) utilizando primers específicos do genoma viral. Os fragmentosde DNA foram visualizados em eletroforese em gel de agarose (1,5%). Das 70 gestantes que participaramdo estudo, 9 apresentaram contaminação viral, sendo 12,9% da população estudada positiva paraHPV.Palavras-chave: Papilomavírus humano (HPV), gestantes, urina

DETECÇÃO DE DNA DE MYCOBACTERIUM TUBERCULOSIS EM LÂMINAS DE BACILOSCOPIA

A tuberculose é uma grave doença infectocontagiosa que infecta uma boa parcela da população mundial, fazendo comque medidas emergenciais de combate e controle da doença sejam tomadas. O presente estudo teve como objetivo detectar oDNA de Mycobacterium tuberculosis de amostra clínica fixada em lâmina de baciloscopia. Foram analisadas 113 amostrasde DNA extraído diretamente do material fixado na lâmina utilizando fenol/clorofórmio. Os resultados foram comparadoscom os obtidos na baciloscopia. A sensibilidade encontrada foi 100% e a especificidade foi 97%. Estes resultados indicama possibilidade do uso desta metodologia como um auxílio no diagnóstico ou ainda um método de obtenção de DNA paraestudos moleculares acerca deste agente

El primer caso de leishmaniasis visceral canina en la región sur de Santa Catarina, foco emergente de leishmaniasis visceral en Brasil : informe regional o reflejo de la realidad de un país?

Visceral leishmaniasis is among the most neglected diseases in the world and especially affects poor populations of some developing or underdeveloped countries, with human disease being a factor in the occurrence of thousands of deaths every year. Visceral leishmaniasis affect domestic dogs, main reservoirs of the Leishmania parasite in urban environments. Thus, the aim of this study was to analyze the prevalence of canine visceral leishmaniasis in two nonendemic municipalities located in southern Santa Catarina, as well as to identify the main risk factors for infection in dogs. A cross-sectional study was carried out with dogs living in two Zoonoses Control Centers located in the cities of Tubarão and Criciúma. Blood samples were collected and analyzed by real-time PCR for detection of Leishmania infection. Clinical examination and evaluation of the characteristics of the canine population were also carried out. A total of 107 dogs were evaluated, of which 19% were positive for Leishmania, and 85% of the positive cases were asymptomatic. In conclusion, we highlight the detection of cases of canine visceral leishmaniasis in two cities that had not yet reported cases. The high rate of positive asymptomatic animals suggests the maintenance of the parasite in the environment.A leishmaniose visceral está entre as doenças mais negligenciadas no mundo e atinge principalmente populações pobres de alguns países em desenvolvimento ou subdesenvolvidos, sendo a doença humana um fator na ocorrência de milhares de mortes a cada ano. A leishmaniose visceral afeta cães domésticos, principais reservatórios do parasita Leishmania em ambientes urbanos. Assim, o objetivo do presente trabalho foi analisar a prevalência de leishmaniose visceral canina em dois municípios não endêmicos localizados no sul de Santa Catarina, bem como, identificar os principais fatores de risco para infecção em cães. Foi realizado um estudo transversal com cães habitantes de dois Centros de Controle de Zoonoses localizados nas cidades de Tubarão e Criciúma. Amostras sanguíneas foram coletadas e analisadas por PCR em tempo real para detecção de infecção por Leishmania. Também foi realizado exame clínico e avaliação das características da população canina. Um total de 107 cães foram avaliados, destes, 19% foram positivos para Leishmania, sendo 85% dos casos positivos, assintomáticos. Em conclusão, destacamos a detecção de casos de leishmaniose visceral canina em duas cidades que ainda não haviam relatado casos. O alto índice de animais assintomáticos positivos sugere a manutenção do parasito no meio ambiente.La leishmaniasis visceral es una de las enfermedades más desatendidas del mundo y afecta especialmente a las poblaciones pobres de algunos países en desarrollo o subdesarrollados, siendo las enfermedades humanas un factor en la ocurrencia de miles de muertes cada año. La leishmaniasis visceral afecta a los perros domésticos, principales reservorios del parásito Leishmania en entornos urbanos. Así, el objetivo de este estudio fue analizar la prevalencia de leishmaniasis visceral canina en dos municipios no endémicos ubicados en el sur de Santa Catarina, así como identificar los principales factores de riesgo de infección en perros. Se realizó un estudio transversal con perros que viven en dos Centros de Control de Zoonosis ubicados en las ciudades de Tubarão y Criciúma. Se recolectaron y analizaron muestras de sangre mediante PCR en tiempo real para la detección de la infección por Leishmania. También se realizó examen clínico y evaluación de las características de la población canina. Se evaluaron un total de 107 perros, de los cuales el 19% fueron positivos para Leishmania y el 85% de los casos positivos fueron asintomáticos. En conclusión, destacamos la detección de casos de leishmaniasis visceral canina en dos ciudades que aún no habían reportado casos. La alta tasa de animales positivos asintomáticos sugiere el mantenimiento del parásito en el medio ambiente

Genomic-based surveillance reveals high ongoing transmission of multi-drug-resistant Mycobacterium tuberculosis in Southern Brazil

Funding Information: Funding: This study was funded, in part, by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - Brasil (Grant No. 001) and supported by Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul (Grant No. 17/1265–8 INCT-TB). JP is supported by Fundação para a Ciência e Tecnologia through Estímulo Individual ao Emprego Científico (CEECIND/00394/2017). Funding Information: The authors wish to thank TGen, C-Path and ReSeqTB for supporting WGS, and the Brazilian Network of Tuberculosis Research for enabling this partnership. The authors would also like to thank the Mycobacteria Laboratory at LACEN-RS/CEVS/SES-RS for performing and providing information on drug susceptibility testing. Funding: This study was funded, in part, by the Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior - Brasil (Grant No. 001) and supported by Funda??o de Amparo ? Pesquisa do Estado do Rio Grande do Sul (Grant No. 17/1265?8 INCT-TB). JP is supported by Funda??o para a Ci?ncia e Tecnologia through Est?mulo Individual ao Emprego Cient?fico (CEECIND/00394/2017). Competing interests: None declared. Ethical approval: This project was approved by the Research Ethics Committee of the Funda??o Estadual de Produ??o e Pesquisa em Sa?de (Protocol No. 1.587.621 CAAE: 18269313.0.0000.5320). Data availability: M. tuberculosis genome data were deposited in the NCBI BioProject database (IDs: PRJNA535343, PRJNA639713 and PRJNA692642). Individual accession numbers for genomes analysed in this study are given in the online supplementary material. Publisher Copyright: © 2021 Elsevier LtdGenomic-based surveillance on the occurrence of drug resistance and its transmission dynamics has emerged as a powerful tool for the control of tuberculosis (TB). A whole-genome sequencing approach, phenotypic testing and clinical-epidemiological investigation were used to undertake a retrospective population-based study on drug-resistant (DR)-TB in Rio Grande do Sul, the largest state in Southern Brazil. The analysis included 305 resistant Mycobacterium tuberculosis strains sampled statewide from 2011 to 2014, and covered 75.7% of all DR-TB cases identified in this period. Lineage 4 was found to be predominant (99.3%), with high sublineage-level diversity composed mainly of 4.3.4.2 [Latin American and Mediterranean (LAM)/RD174], 4.3.3 (LAM/RD115) and 4.1.2.1 (Haarlem/RD182) sublineages. Genomic diversity was also reflected in resistance of the variants to first-line drugs. A large number of distinct resistance-conferring mutations, including variants that have not been reported previously in any other setting worldwide, and 22 isoniazid-monoresistant strains with mutations described as disputed in the rpoB gene but causing rifampicin resistance generally missed by automated phenotypic tests as BACTEC MGIT. Using a cut-off of five single nucleotide polymorphisms, the estimated recent transmission rate was 55.1%, with 168 strains grouped into 28 genomic clusters. The most worrying fact concerns multi-drug-resistant (MDR) strains, of which 73.4% were clustered. Different resistance profiles and acquisition of novel mutations intraclusters revealed important amplification of resistance in the region. This study described the diversity of M. tuberculosis strains, the basis of drug resistance, and ongoing transmission dynamics across the largest state in Southern Brazil, stressing the urgent need for MDR-TB transmission control state-wide.publishersversionpublishe