Performance of adenosine deaminase in synovial fluid for the diagnosis of tuberculous arthritis: A systematic review and meta-analysis / Rendimiento de la adenosina desaminasa en el líquido sinovial para el diagnóstico de la artritis tuberculosa: una revisión sistemática y metaanálisis

Objectives: Adenosine deaminase (ADA) activity has shown good performance in diagnosing pleural, peritoneal, and meningeal tuberculosis. This meta-analysis aimed to evaluate the performance of measuring ADA activity in synovial fluid for the early diagnosis of joint tuberculosis. Methods: We searched published information in MEDLINE, Embase, Cochrane Library, Web of Science, and MedRxiv databases, as well as unpublished information in the American College of Rheumatology and European League Against Rheumatism for conference abstracts (2012–2021). We also scanned the reference lists of articles. Two reviewers independently applied the criteria for selection, assessed quality, and extracted data (PROSPERO number CRD42021284472). Results: Seven independent studies (N=305 subjects) that compared ADA activity in synovial fluid with a composite reference diagnostic method for tuberculosis were included. Overall, the risk of bias was judged low. Studies were classified as high quality (n=3; 148 subjects) and low quality (n=4; 157 subjects). Pooled sensitivity and specificity of ADA activity was 94% (95% confidence interval [CI], 0.89–98; I2=23%) and 88% (95% CI, 83–92; I2=83%), respectively. The random-effects model for pooled diagnostic Odds ratio was 67.1 (95%CI, 20.3–222.2; I2=30%). The receiver operating characteristic curve area was 0.96 (95% CI, 0.92–0.99). Meta-regression did not identify the quality of the study, country of publication, or the type of assay as a source of heterogeneity. Conclusions: Measuring ADA activity in synovial fluid demonstrates good performance for the early diagnosis of joint tuberculosis.(AU)

Objetivos: La actividad de la adenosina desaminasa (ADA) ha mostrado un buen desempeño en el diagnóstico de la tuberculosis pleural, peritoneal y meníngea. Este metaanálisis tuvo como objetivo evaluar el rendimiento de la medición de la actividad de la ADA en el líquido sinovial para el diagnóstico precoz de la tuberculosis articular. Métodos: Se realizaron búsquedas de resúmenes de congresos en la información publicada en las bases de datos MEDLINE, Embase, Cochrane Library, Web of Science y MedRxiv, así como en información no publicada en el American College of Rheumatology y la European League Against Rheumatism (2012-2021). También se escanearon las listas de referencias de los artículos. Dos revisores aplicaron de forma independiente los criterios de selección, evaluaron la calidad y extrajeron los datos (número PROSPERO CRD42021284472). Resultados: Se incluyeron siete estudios independientes (n=305 sujetos) que compararon la actividad de la ADA en el líquido sinovial con un método diagnóstico compuesto de referencia para la tuberculosis. En general, el riesgo de sesgo se consideró bajo. Los estudios se clasificaron como de alta calidad (n=3; 148 sujetos) y de baja calidad (n=4; 157 sujetos). La sensibilidad y la especificidad agrupadas de la actividad de la ADA fueron del 94% (intervalo de confianza [IC] del 95%: 0,89-98; I2=23%) y del 88% (IC95%: 83-92; I2=83%), respectivamente. El modelo de efectos aleatorios para el odds ratio diagnóstico agrupado fue de 67,1 (IC95%: 20,3-222,2; I2=30%). El área de la curva característica de operación del receptor fue de 0,96 (IC95%: 0,92-0,99). La metarregresión no identificó la calidad del estudio, el país de publicación o el tipo de ensayo como fuente de heterogeneidad.Conclusiones: La medición de la actividad de ADA en el líquido sinovial demuestra un buen rendimiento para el diagnóstico precoz de la tuberculosis articular.(AU)

Mortality and sequelae of tuberculous meningitis in a high-resource setting: A cohort study, 1990–2017 / Mortalidad y secuelas de la meningitis tuberculosa en Barcelona (España): Estudio de cohortes, 1990-2017

Introduction: Tuberculous meningitis (TBM), the most serious form of tuberculosis, results in high mortality and long-term disability in low-resource countries. We investigated temporal trends in mortality and sequelae in a high-resource low-incidence country. Methods: We performed a retrospective cohort study of all adult patients with TBM at two third-level teaching hospitals in Barcelona (Spain), between January 1990 and December 2017, assessing temporal trends in mortality and sequelae after 12 months over four consecutive 7-year time windows. Rates observed across the four periods were adjusted for covariates. Results: Of the 135 cases included, all but one started tuberculosis (TB) treatment and 120 (89.6%) received rifampicin, isoniazid, and pyrazinamide, with or without ethambutol. The probability of being alive at month 12 was 81.8%, with no differences among the four periods: in comparison with the 1990–1996 period, the adjusted hazard ratios and 95% confidence intervals (CI) were 2.55 (0.71–9.25), 0.70 (0.13–3.85), and 1.29 (0.28–5.91) for the 1997–2003, 2004–2010, and 2011–2017 periods respectively. Sequelae were present in 28.3% at month 12, with no differences across the four periods in the adjusted analysis: in comparison with the 1990–1996 period, the odds ratios and 95% CIs were 0.80 (0.09–7.22); 1.94 (0.21–17.96), and 2.42 (0.25–23.07) for the 1997–2003, 2004–2010, and 2011–2017 periods respectively. Conclusion: This study shows that TBM still causes high mortality and disability even in a high-resource low-incidence TB setting and without improvement over time.(AU)

Introducción: La meningitis tuberculosa (TBM), la forma más grave de tuberculosis, provoca una alta mortalidad y discapacidad a largo plazo en países con bajos recursos. Nuestro objetivo es investigar la tendencia temporal de la mortalidad y las secuelas en un país con recursos elevados y baja incidencia. Métodos: Hemos realizado un estudio de cohortes retrospectivo de los pacientes adultos con TBM en dos hospitales universitarios de tercer nivel en Barcelona (España), entre 1990 y 2017, evaluando las tendencias temporales de mortalidad y secuelas a los 12 meses, comparando cuatro periodos consecutivos de siete años. Las tasas observadas en los cuatro periodos se han ajustado por covariables. Resultados: De los 135 casos incluidos, todos menos uno inició tratamiento antituberculoso y 120 (89,6%) recibieron rifampicina, isoniazida y pirazinamida, con o sin etambutol. La probabilidad de estar vivo a los 12 meses fue de 81,8%, sin diferencias entre los cuatro periodos: en comparación con el periodo 1990-1996, los coeficientes de riesgo ajustados y los intervalos de confianza (IC) del 95% fueron 2,55 (0,71-9,25), 0,70 (0,13-3,85) y 1,29 (0,28-5,91) para los periodos 1997-2003, 2004-2010 y 2011-2017, respectivamente. Las secuelas estaban presentes en 28,3% en el mes 12, sin diferencias entre los cuatro periodos en el análisis ajustado: en comparación con el periodo 1990-1996, los coeficientes de probabilidad y los IC 95% fueron 0,80 (0,09-7,22); 1,94 (0,21-17,96) y 2,42 (0,25-23,07) para los periodos 1997-2003, 2004-2010 y 2011-2017, respectivamente. Conclusión: Este estudio muestra que la TBM todavía causa una alta mortalidad y discapacidad sin mejoría con el tiempo, incluso en un entorno con baja incidencia de tuberculosis y con elevados recursos.(AU)

Flow cytometry method for absolute counting and single-cell phenotyping of mycobacteria.

Detection and accurate quantitation of viable Mycobacterium tuberculosis is fundamental to understanding mycobacterial pathogenicity, tuberculosis (TB) disease progression and outcomes; TB transmission; drug action, efficacy and drug resistance. Despite this importance, methods for determining numbers of viable bacilli are limited in accuracy and precision owing to inherent characteristics of mycobacterial cell biology-including the tendency to clump, and "differential" culturability-and technical challenges consequent on handling an infectious pathogen under biosafe conditions. We developed an absolute counting method for mycobacteria in liquid cultures using a bench-top flow cytometer, and the low-cost fluorescent dyes Calcein-AM (CA) and SYBR-gold (SG). During exponential growth CA + cell counts are highly correlated with CFU counts and can be used as a real-time alternative to simplify the accurate standardisation of inocula for experiments. In contrast to CFU counting, this method can detect and enumerate cell aggregates in samples, which we show are a potential source of variance and bias when using established methods. We show that CFUs comprise a sub-population of intact, metabolically active mycobacterial cells in liquid cultures, with CFU-proportion varying by growth conditions. A pharmacodynamic application of the flow cytometry method, exploring kinetics of fluorescent probe defined subpopulations compared to CFU is demonstrated. Flow cytometry derived Mycobacterium bovis bacillus Calmette-Guérin (BCG) time-kill curves differ for rifampicin and kanamycin versus isoniazid and ethambutol, as do the relative dynamics of discrete morphologically-distinct subpopulations of bacilli revealed by this high-throughput single-cell technique.

Real-time next-generation sequencing on shell-vial culture to contribute to diagnosis of lymphatic tuberculosis: a case report.

Lymph node tuberculosis is a of limited clinical suspicion form of Mycobacterium tuberculosis infection. After 15 days incubation in a cellular culture and directly from the supernatant, 11 minutes of Oxford Nanopore MinION sequencing provided a preliminary result of an antibiotic-susceptible M. tuberculosis Indo-Oceanic lineage strain. Oxford Nanopore MinION sequencing is a promising tool for optimising the laboratory diagnosis of lymph node tuberculosis.

LIODetect®TB-ST: Evaluation of novel blood test for a rapid diagnosis of active pulmonary and extra-pulmonary tuberculosis in IGRA confirmed patients.

Because of the current limits of immunological tests in the diagnosis of tuberculosis there is a need to identify new and rapid tests that can be carried out on a large scale in endemic countries and useful in the identification of infected subjects, but also able to discriminate those with latent infection from subjects with active. We have taken into consideration and analysed the LIODetect®TB-ST Tuberculosis Rapid Test, a membrane test for the qualitative detection of specific IgG, IgA, and IgM antibodies against Mycobacterium tuberculosis, performed on serum, plasma, or whole blood.85 samples positive to QuantiFERON TB-GOLD PLUS test were processed using this test and the results obtained were concordant with clinical diagnosis.To our knowledge, the LIODetect®TB-ST Tuberculosis Rapid Test is the only test; that identifies active tuberculosis disease with high sensitivity and specificity and its use might be of help in the diagnosis of tuberculosis, especially in endemic countries.

A Two-Gene Signature for Tuberculosis Diagnosis in Persons With Advanced HIV.

Background: Transcriptomic signatures for tuberculosis (TB) have been proposed and represent a promising diagnostic tool. Data remain limited in persons with advanced HIV. Methods: We enrolled 30 patients with advanced HIV (CD4 <100 cells/mm3) in India; 16 with active TB and 14 without. Whole-blood RNA sequencing was performed; these data were merged with a publicly available dataset from Uganda (n = 33; 18 with TB and 15 without). Transcriptomic profiling and machine learning algorithms identified an optimal gene signature for TB classification. Receiver operating characteristic analysis was used to assess performance. Results: Among 565 differentially expressed genes identified for TB, 40 were shared across India and Uganda cohorts. Common upregulated pathways reflect Toll-like receptor cascades and neutrophil degranulation. The machine-learning decision-tree algorithm selected gene expression values from RAB20 and INSL3 as most informative for TB classification. The signature accurately classified TB in discovery cohorts (India AUC 0.95 and Uganda AUC 1.0; p < 0.001); accuracy was fair in external validation cohorts. Conclusions: Expression values of RAB20 and INSL3 genes in peripheral blood compose a biosignature that accurately classified TB status among patients with advanced HIV in two geographically distinct cohorts. The functional analysis suggests pathways previously reported in TB pathogenesis.

Tuberculosis in key populations in Tajikistan - a snapshot in 2017.

INTRODUCTION: WHO End TB Strategy aims at achieving targets of 90% mortality reduction and 80% reduction in tuberculosis (TB) incidence by 2030, recommending better addressing TB and multidrug-resistant TB (MDR-TB) issues in key populations. AIM: The study aimed at having a snapshot of the epidemiological characteristics of the key populations among the new TB patients, registered in Tajikistan during 2017. METHODOLOGY: A cross-sectional study was conducted, using official TB registration data for all new TB case notification in Tajikistan in 2017. RESULTS: The key population included 1,029 (19.8%) patients among all 5,182 new TB cases registered in 2017. The following selected sub-populations were identified: migrant workers - 728 (70.7%), diabetics - 162 (15.7%), HIV-positive - 138 (13.4%), heavy drinkers - 74 (7.2%), drug users - 50 (4.8%), ex-prisoners - 50 (4.8%), and homeless - 9 (0.9%). Among the key population, 307 (29.8%) patients were smear-positive, 145 (14.1%) were drug-sensitive and 116 (11.3%) had MonoDR/MDR-TB. Time to treatment initiation for smear-positive cases was ≤ 5 days for 303 (98.7%) patients. Being a key population was inversely related to gender (female) (OR = 0.25, 95% CI (0.21, 0.29)) and population type (rural) (OR = 0.64, 95% CI (0.55, 0.74)). CONCLUSION: Among the key population the identified overlaps of selected sub-populations would enable more efficiently reaching the certain groups. TB case detection at PHC levels needs to be targeted for improved rates for key population detection. In the key population sub-group of migrant workers' special migration destinations are recommended to be explored and find out possible associations with drug resistance.

Who is doing worse? Retrospective cross-sectional study of TB key population treatment outcomes in Kyrgyzstan (2015-2017).

INTRODUCTION: Tuberculosis (TB) is a global public health problem. The incidence of TB is especially high among TB key populations, such as the homeless, people who use drugs, prisoners, and migrants. The study aimed to assess the associations between affiliation to TB key populations and treatment outcome. METHODOLOGY: This retrospective cross-sectional study used data extracted from the National TB Registry of Kyrgyzstan for the region of Chuy (including the city of Bishkek) for 2015-2017. Descriptive statistics was used to summarize the data. Logistic regression was used to assess the associations. RESULTS: The study included 1,526 patients among whom more than half (52.5%) fell into the youngest group (18-35 years old). Migrants were the most highly represented group comprising 67.8% of all TB key populations. Men (63.0%) and patients with pulmonary TB (83.0%) prevailed in the cohort. The proportions of patients who had completed the treatment were high among all the key populations. Logistic regression was used to assess the association between affiliation to a certain TB key population and the TB treatment outcome. Patients who belonged to more than one TB key population were found to have the highest risk of unsuccessful TB treatment outcomes, both in the region of Chuy (OR = 9.9, 95% CI 2.0-48.1, p = 0.04) and the city of Bishkek (OR = 24.9, 95% CI 7.2-86.4, p < 0.001). CONCLUSION: The homeless, people who use drugs, ex-prisoners, and TB patients who belonged to more than one TB key population were found to have higher risks of unsuccessful TB treatment outcome in comparison to migrants.

New approach for tuberculosis contact tracing implemented in the two regions of Kyrgyz Republic during 2017-2018.

INTRODUCTION: Tuberculosis (TB) contact investigation as a proved approach for finding new TB cases, is not fully performed in Kyrgyzstan. In 2018, the country started aligning the National Guidelines for tracking contacts with the WHO recommendations by expanding the definition for TB index cases to all close contacts, regardless of their TB risk status. METHODOLOGY: This cross-sectional census aimed to determine the active case detection changes among TB contacts after implementation of a new TB tracing strategy using the National Surveillance data. We compared populations in Chui and Issyk-Kul regions of Kyrgyzstan who had contacts with TB index cases before (2017) and after (2018) strategic changes for the rates of indexes, contacts, screened contacts, and detected TB among screened contacts. RESULTS: New TB tracing strategy resulted in increased numbers of indexes (21%) and contacts (36%). Though the smaller number of contacts (1730 vs. 1590) have been screened in 2018, the proportion of TB diagnosed was substantially higher (95% CI: 0.024-0.005; p = 0.002) in 2018 vs. 2017. The mean numbers of TB contacts per-one-index-case also has increased dramatically by 117% (1.8 vs. 3.9) in Chui and by 43% (3.0 vs. 4.3) in Issyk-Kul regions (95% CI: 3.20-3.37; p < 0.001 and 95% CI: 2.97-3.09; p < 0.001, respectively) between 2018 and 2017. CONCLUSION: Extending new tracing approach to other regions of Kyrgyzstan will increase the number of identified contacts, leading to better TB control in the country and prevention of more severe TB development among the unidentified contacts.

Active TB case finding in a high burden setting; comparison of community and facility-based strategies in Lusaka, Zambia.

INTRODUCTION: We conducted an implementation science study to increase TB case detection through a combination of interventions at health facility and community levels. We determined the impact of the study in terms of additional cases detected and notification rate and compared the yield of bacteriologically confirmed TB of facility based and community based case finding. METHODOLOGY: Over a period of 18 months, similar case finding activities were conducted at George health facility in Lusaka Zambia and its catchment community, an informal peri-urban settlement. Activities included awareness and demand creation activities, TB screening with digital chest x-ray or symptom screening, sputum evaluation using geneXpert MTB/RIF, TB diagnosis and linkage to treatment. RESULTS: A total of 18,194 individuals were screened of which 9,846 (54.1%) were screened at the facility and 8,348 (45.9%) were screened in the community. The total number of TB cases diagnosed during the intervention period were 1,026, compared to 759 in the pre-intervention period; an additional 267 TB cases were diagnosed. Of the 563 bacteriologically confirmed TB cases diagnosed under the study, 515/563 (91.5%) and 48/563 (8.5%) were identified at the facility and in the community respectively (P<0.0001). The TB notification rate increased from 246 per 100,000 population pre-intervention to 395 per 100,000 population in the last year of the intervention. CONCLUSIONS: Facility active case finding was more effective in detecting TB cases than community active case finding. Strengthening health systems to appropriately identify and evaluate patients for TB needs to be optimised in high burden settings. At a minimum, provider initiated TB symptom screening with completion of the TB screening and diagnostic cascade should be provided at the health facility in high burden settings. Community screening needs to be systematic and targeted at high risk groups and communities with access barriers.

Lipoarabinomannan antigenic epitope differences in tuberculosis disease subtypes.

An accurate urine test for diverse populations with active tuberculosis could be transformative for preventing TB deaths. Urinary liporabinomannan (LAM) testing has been previously restricted to HIV co-infected TB patients. In this study we evaluate urinary LAM in HIV negative, pediatric and adult, pulmonary and extrapulmonary tuberculosis patients. We measured 430 microbiologically confirmed pretreatment tuberculosis patients and controls from Peru, Guinea Bissau, Venezuela, Uganda and the United States using three monoclonal antibodies, MoAb1, CS35, and A194, which recognize distinct LAM epitopes, a one-sided immunoassay, and blinded cohorts. We evaluated sources of assay variability and comorbidities (HIV and diabetes). All antibodies successfully discriminated TB positive from TB negative patients. ROAUC from the average of three antibodies' responses was 0.90; 95% CI 0.87-0.93, 90% sensitivity, 73.5% specificity (80 pg/mL). MoAb1, recognizing the 5-methylthio-D-xylofuranose(MTX)-mannose(Man) cap epitope, performed the best, was less influenced by glycosuria and identified culture positive pediatric (N = 19) and extrapulmonary (N = 24) patients with high accuracy (ROAUC 0.87, 95% CI 0.77-0.98, 0.90 sensitivity 0.80 specificity at 80 pg/mL; ROAUC = 0.96, 95% CI 0.92-0.99, 96% sensitivity, 80% specificity at 82 pg/mL, respectively). The MoAb1 antibody, recognizing the MTX-Man cap epitope, is a novel analyte for active TB detection in pediatric and extrapulmonary disease.

Epidemiology and clinical characteristics of tuberculosis in leon bernard tuberculosis unit in algeria.

Background: This study aimed at highlighting some demographic and clinical features of tuberculosis (TB) at Leon Bernard TB unit, Algeria. Methods: This was a retrospective and descriptive study based on TB data extracted from TB patient records during 2009-2019 at Leon Bernard TB unit. Results: Of the total 1375 TB patients, 602 (43.8%) had extrapulmonary TB (EPTB), 482 (35.1%) had new sputum smear-positive pulmonary TB (PTB), 42 (3.1%) had sputum smear-negative with culture-positive PTB, and 97 (7%) EPTB patients had concomitant pulmonary involvement. The male-to-female ratio was 1.07. A total of 116 (8.4%) TB relapses were reported with predominance among ETPB cases (54.3%). Lymphadenitis TB was the most common manifestation of EPTB with 301 cases (39.6%), followed by pleural TB with 237 cases (31.2%). The number of bacteriologically not confirmed EPTB was 22.6% more than half (53.3%) of whom were pleural TB. Among patients with new sputum smear-positive PTB, 71.2% were males, whereas the reverse was observed among patients with EPTB where 62.3% were female. Two-third of recorded cases were between 15 and 45 years old. Nearly all children had EPTB (64/69). The results revealed that most of the patients who passed away were affected by PTB (15/18), and the most frequent cmorbidities were diabetes (9/18) and high blood pressure (6/18). Conclusion: Specific attention needs to be given to an examination of the risk factors of PTB among male population and of EPTB among female population and children and to diagnosis of pleural TB and primary PTB.

Epidemiological Trends in the Form of Childhood Tuberculosis in a Referral Tuberculosis Hospital in Shandong, China.

BACKGROUND: In China, the prevalence of tuberculosis (TB) diseases and epidemiological trends in the TB forms among children are still unclear; a retrospective study was conducted aiming to assess it. METHODS: Between January 2007 and September 2020, 1577 consecutive childhood TB patients (aged ≤ 15 years) were included in the study. Data, including demographic information and underlying diseases, were collected from medical records. Then, patients were categorized and reported according to the anatomical site of TB disease. To analyze the epidemiological trends in the proportion of each form of TB disease, a linear-by-linear association was used, and a P value of <0.05 was considered to indicate that a significant change had occurred in the proportion of TB disease over the studied period. RESULTS: During the fourteen-year study period, a total of 1577 children patients were enrolled, including 954 boys (60.5%) and 623 girls (39.5%), with a mean age of 9.26 ± 5.18 years. Among the studied patients, 810 (51.4%) patients have pulmonary TB, 1137 (72.1%) have extrapulmonary TB, 372 (23.6%) have both conditions, and another 765 (48.5%) extrapulmonary cases presented in isolated form. Pleural TB (29.0%) and tuberculous lymphadenitis (23.7%) were the most frequent two forms of childhood TB. In addition, during the past decade, the proportions of pulmonary TB, pleural TB, and tuberculous lymphadenitis showed an increasing trend (all P < 0.05). However, no significant trends in the proportions of other forms of TB disease, such as extrapulmonary TB (P > 0.05), tuberculous meningitis (P > 0.05), endobronchial TB (P > 0.05), and disseminated TB (P > 0.05), were found. CONCLUSION: Our findings suggest that childhood TB is facing new challenges, and the policy should be adjusted timely to fit the real situation.

Caracterización de la tuberculosis en pacientes de la provincia Guantánamo, Cuba / Characterization of tuberculosis in patients from the Guantánamo province, Cuba

RESUMEN Introducción: La lucha contra la tuberculosis es una responsabilidad social y profesional que requiere de su caracterización, la que no se ha realizado en Guantánamo en la última década. Objetivo: Caracterizar la tuberculosis en pacientes de la provincia Guantánamo durante el periodo comprendido entre 2012 y 2019. Método: El universo se constituyó por el total de pacientes diagnosticados (n=136). Se estudiaron las siguientes variables: edad, sexo, localización de la enfermedad, resultados de la baciloscopía, categoría al egreso y grupos de riesgo de tuberculosis. La información se obtuvo mediante los registros de enfermedades de declaración obligatoria cada año, y las encuestas epidemiológicas de los controles de focos realizados, y se resumió en números absolutos y porcentajes. Resultados: En el 80,1 % de los casos la tuberculosis se localizó en los pulmones, y fue más común el diagnóstico de pacientes con baciloscopía positiva (63,2 %). El 76,7 % de los pacientes con baciloscopía positiva fueron masculinos. Los grupos de riesgos para tuberculosis más usuales fueron: fumadores (26,4 %), inmunodeprimidos (21,6 %) y el alcoholismo (19,1 %). Conclusiones: En la provincia Guantánamo prevalece la tuberculosis de localización pulmonar y los pacientes con bacteriología positiva. Los afectados sobre todo son hombres, tienen edad entre 45 a 54 años y son de reciente diagnóstico. La enfermedad incide más en aquellos con antecedente de ser fumadores, inmunodeprimidos y los alcohólicos.

ABSTRACT Introduction: The fight against tuberculosis is a social and professional responsibility, which requires its characterization, which has not been carried out in Guantánamo in the last decade. Objective: To characterize tuberculosis in patients in the Guantánamo province during the period between 2012 and 2019. Method: The universe was made up of the total number of diagnosed patients (n = 136). The following variables were studied: age, sex, location of the disease, smear results, category at discharge, and tuberculosis risk groups. The information was obtained through the notifiable disease registries for each year and the epidemiological surveys of the outbreak controls carried out, and was summarized in absolute numbers and percentages. Results: In 80.1% of cases, tuberculosis is in the lungs, and the diagnosis of patients with positive smear microscopy (63.2%) is more common. 76.7% of smear-positive patients are male. The most common risk groups for tuberculosis are: smokers (26.4%), immunosuppressed (21.6%) and alcoholism (19.1%). Conclusions: In Guantánamo province, pulmonary localization tuberculosis and patients with positive bacteriology prevail. Those affected are mainly men, they are between 45 and 54 years old and have recently been diagnosed. The disease affects more in those with a history of being smokers, immunosuppressed and alcoholics.

Association of POR and PPARα polymorphisms with risk of anti-tuberculosis drug-induced liver injury in Western Chinese Han population.

OBJECTIVES: Anti-tuberculosis drug-induced liver injury (ATDILI) is a common and sometimes severe adverse drug reaction (ADR). This study was conducted to investigate the relationship between polymorphisms of two genes, cytochrome P450 oxidoreductase (POR) and peroxisome proliferator-activated receptor α (PPARα), and the risk of ATDILI in Western Chinese Han population. METHODS: A total of 118 tuberculosis (TB) patients with ATDILI and 628 TB patients without ATDILI during anti-TB treatment were recruited from West China Hospital of Sichuan University. DNA was extracted from peripheral blood, and genotypes of the selected 12 single nucleotide polymorphisms (SNPs) (3 SNPs in the POR gene and 9 SNPs in the PPARα gene) were determined. Three genetic models (additive, dominant, and recessive), as well as a haplotype, were used to test the genetic risk of ATDILI. Extended subgroup analysis was conducted according to age, sex and different causality assessments. RESULTS: The mutant allele, genotype and genetic model of rs3898649 in the POR gene were found to be associated with increased risk of ATDILI, especially in the younger (<50 years old), female and pulmonary tuberculosis subgroup. The other two SNPs rs28737229 and rs4728533 in the POR gene showed only a potential association with susceptibility to ATDILI after Bonferroni correction (P < .05 but PBonferroni > .05). The other 9 SNPs loci (rs135549, rs9626730, rs4253712, rs4823613, rs4253730, rs6007662, rs4253728, rs2024929 and rs135561) in the PPARα gene showed no significant differences between ATDILI and non-ATDILI in either allele frequencies or genotype (all P >.05). CONCLUSIONS: The results demonstrated the strong correlation between POR gene SNP rs3898649 and ATDILI susceptibility, suggesting the importance of POR rs3898649 in the pathogenesis and development of ATDILI. Therefore, our results indicated that POR rs3898649 might be a valuable biomarker potentially involved in ATDILI.

An optimized genomic VCF workflow for precise identification of Mycobacterium tuberculosis cluster from cross-platform whole genome sequencing data.

Whole-genome sequencing (WGS) data allow for an inference of Mycobacterium tuberculosis (Mtb) clusters by using a pairwise genetic distance of ≤12 single nucleotide polymorphisms (SNPs) as a threshold. However, a problem of discrepancies in numbers of SNPs and genetic distance measurement is a great concern when combining WGS data from different next generation sequencing (NGS) platforms. We performed SNP variant calling on WGS data of 9 multidrug-resistant (MDR-TB), 3 extensively drug-resistant tuberculosis (XDR-TB) and a standard M. tuberculosis strain H37Rv from an Illumina/NextSeq500 and an Ion Torrent PGM. Variant calls were obtained using four different common variant calling tools, including Genome Analysis Toolkit (GATK) HaplotypeCaller (GATK-VCF workflow), GATK HaplotypeCaller and GenotypeGVCFs (GATK-GVCF workflow), SAMtools, and VarScan 2. Cross-platform pairwise SNP differences, minimum spanning networks and average nucleotide identity (ANI) were analysed to measure performance of the variant calling tools. Minimum pairwise SNP differences ranged from 2 to 14 SNPs when using GVCF workflow while maximum pairwise SNP differences ranged from 7 to 158 SNPs when using VarScan 2. ANI comparison between SNPs data from NextSeq500 and PGM of MDR-TB and XDR-TB showed maximum ANI of 99.7% and 99.0%, respectively, with GVCF workflow while the other SNP calling results showed lower ANI in a range of 98.6% to 95.1%. In this study, we suggest that the GVCF workflow showed the best performing variant caller to avoid cross-platform pairwise SNP differences.

Clinical and epidemiological features of tuberculosis in children and adolescents / Características clínicas e epidemiológicas da tuberculose em crianças e adolescentes / Características clínicas y epidemiológicas de la tuberculosis en niños y adolescentes

ABSTRACT Objective: To analyze the clinical and epidemiological features of tuberculosis in children and adolescents in an infectious diseases reference hospital. Method: A documental and retrospective study was carried out with 88 medical files in an infectious diseases reference hospital in the state of Ceará. Data were analyzed by univariate, bivariate and multivariate approaches. Results: It was found that, depending on the tuberculosis type, its manifestations may vary. The logistic regression model considered only pulmonary tuberculosis due to a number of observations and included female sex (95% CI: 1.4-16.3), weight loss (95% CI: 1.8-26.3), bacilloscopic screening (95% CI: 1.5-16.6) and sputum collected (95% CI: 1.4-19.4) as possible predictors. Conclusions: Children and adolescents present different manifestations of the disease depending on the tuberculosis type that affects them. Knowing the most common features of each condition could enhance early diagnosis and, consequently, result in adequate treatment and care.

RESUMO Objetivo: Analisar as características clínicas e epidemiológicas da tuberculose em crianças e adolescentes de um hospital de referência em doenças infecciosas. Método: Foi realizado um estudo documental e retrospectivo com 88 prontuários médicos em um hospital de referência em doenças infecciosas no estado do Ceará. Os dados foram analisados através das abordagens univariada, bivariada e multivariada. Resultados: Verificou-se que, dependendo do tipo de tuberculose, suas manifestações podem variar. O modelo de regressão logística considerou apenas a tuberculose pulmonar devido a um número de observações e incluiu sexo feminino (IC 95%: 1,4-16,3), perda de peso (IC 95%: 1,8-26,3) e baciloscopia (IC 95%: 1,5-16,6) com coleta de escarro (IC95%: 1,4-19,4) como possíveis preditores. Conclusão: Crianças e adolescentes apresentam diferentes manifestações da doença dependendo do tipo de tuberculose que os afeta. Conhecer as características mais comuns de cada condição pode melhorar o diagnóstico precoce e, consequentemente, levar a tratamentos e cuidados adequados.

RESUMEN Objetivo: Analizar las características clínicas y epidemiológicas de la tuberculosis en niños y adolescentes en un hospital de referencia de enfermedades infecciosas. Método: Se realizó un estudio documental y retrospectivo con 88 archivos médicos en un hospital de referencia de enfermedades infecciosas en el estado de Ceará. Se analizaron los datos por enfoques univariados, bivariados y multivariados. Resultados: Se encontró que, dependiendo del tipo de tuberculosis, sus manifestaciones pueden variar. El modelo de regresión logística consideró solo la tuberculosis pulmonar, debido a varias, observaciones e incluyó el género femenino (IC 95%: 1,4-16,3), la pérdida de peso (IC 95%: 1,8-26,3), la revisión baciloscopia (95 % CI: 1,5-16,6) y el esputo recolectado (95% CI: 1,4-19,4) como posibles predictores. Conclusiones: Los niños y adolescentes presentan diferentes manifestaciones de la enfermedad en función del tipo de tuberculosis que los afecta. Conocer las características más comunes de cada afección podría mejorar el diagnóstico temprano y, en consecuencia, resultar en un tratamiento y atención adecuados.

Clinical and epidemiological features of tuberculosis in children and adolescents.

OBJECTIVE: To analyze the clinical and epidemiological features of tuberculosis in children and adolescents in an infectious diseases reference hospital. METHOD: A documental and retrospective study was carried out with 88 medical files in an infectious diseases reference hospital in the state of Ceará. Data were analyzed by univariate, bivariate and multivariate approaches. RESULTS: It was found that, depending on the tuberculosis type, its manifestations may vary. The logistic regression model considered only pulmonary tuberculosis due to a number of observations and included female sex (95% CI: 1.4-16.3), weight loss (95% CI: 1.8-26.3), bacilloscopic screening (95% CI: 1.5-16.6) and sputum collected (95% CI: 1.4-19.4) as possible predictors. CONCLUSIONS: Children and adolescents present different manifestations of the disease depending on the tuberculosis type that affects them. Knowing the most common features of each condition could enhance early diagnosis and, consequently, result in adequate treatment and care.

Addressing the under-reporting of adverse drug reactions in public health programs controlling HIV/AIDS, Tuberculosis and Malaria: A prospective cohort study.

BACKGROUND: Adverse Drug Reactions (ADRs) are a major clinical and public health problem world-wide. The prompt reporting of suspected ADRs to regulatory authorities to activate drug safety surveillance and regulation appears to be the most pragmatic measure for addressing the problem. This paper evaluated a pharmacovigilance (PV) training model that was designed to improve the reporting of ADRs in public health programs treating the Human Immunodeficiency Virus (HIV), Tuberculosis (TB) and Malaria. METHODS: A Structured Pharmacovigilance and Training Initiative (SPHAR-TI) model based on the World Health Organization accredited Structured Operational Research and Training Initiative (SOR-IT) model was designed and implemented over a period of 12 months. A prospective cohort design was deployed to evaluate the outcomes of the model. The primary outcomes were knowledge gained and Individual Case Safety Reports (ICSR) (completed adverse drug reactions monitoring forms) submitted, while the secondary outcomes were facility based Pharmacovigilance Committees activated and health facility healthcare workers trained by the participants. RESULTS: Fifty-five (98%) participants were trained and followed up for 12 months. More than three quarter of the participants have never received training on pharmacovigilance prior to the course. Yet, a significant gain in knowledge was observed after the participants completed a comprehensive training for six days. In only seven months, 3000 ICSRs (with 100% completeness) were submitted, 2,937 facility based healthcare workers trained and 46 Pharmacovigilance Committees activated by the participants. Overall, a 273% increase in ICSRs submission to the National Agency for Food and Drug Administration and Control (NAFDAC) was observed. CONCLUSION: Participants gained knowledge, which tended to increase the reporting of ADRs. The SPHAR-TI model could be an option for strengthening the continuous reporting of ADRs in public health programs in resource limited settings.

Análisis de situación de tuberculosis en el Área Programática del Hospital General de Agudos Parmenio Piñero: Año 2017 / Analysis of tuberculosis situation at Programmatic Area of the Acute General Hospital Parmenio Piñero: 2017

El área programática del Hospital Parmenio Piñero (AP-HGAPP) se localiza en el sur de la ciudad, e incluye parte de las comunas 7, 8, 9, 10, 6 y 4. Según datos provenientes del Censo 20105, se registraron 324.179 personas viviendo en este territorio, con un porcentaje de población con Necesidades Básicas Insatisfechas de 10,4% (superior al valor promedio de CABA de 7%). Se presenta en este informe un análisis de situación de tuberculosis, tomando como eje el territorio y la población a cargo del hospital y sus centros de salud y acción comunitaria. (AU)