Site Of Extrapulmonary Tuberculosis Research Articles

A physiologically-based pharmacokinetic model for tuberculosis drug disposition at extrapulmonary sites.

Tuberculosis (TB) is a leading cause of mortality attributed to an infectious agent. TB primarily targets the lungs, but in about 16% cases can affect other organs as well, giving rise to extrapulmonary TB (EPTB). However, an optimal regimen for EPTB treatment is not defined. Although the recommended treatment for most forms of EPTB is the same as pulmonary TB, the pharmacokinetics of EPTB therapy are not as well studied. To address this gap, we formulate a whole-body physiologically-based pharmacokinetic (PBPK) model for EPTB that for the first time includes the ability to simulate drug concentrations in the pleura and lymph node, the most commonly affected sites of EPTB. Using this model, we estimate the time-dependent concentrations, at potential EPTB infection sites, of the following four first-line anti-TB drugs: rifampicin, ethambutol, isoniazid, and pyrazinamide. We use reported plasma concentration kinetics data to estimate model parameters for each drug and validate our model using reported concentration data not used for model formulation or parameter estimation. Model predictions match the validation data, and reported pharmacokinetic parameters (maximum plasma concentration, time to reach maximum concentration) for the drugs. The model also predicts ethambutol, isoniazid, and pyrazinamide concentrations in the pleura that match reported experimental values from an independent study. For each drug, the predicted drug concentrations at EPTB sites are compared with their critical concentration. Simulations suggest that although rifampicin and isoniazid concentrations are greater than critical concentration values at most EPTB sites, the concentrations of ethambutol and pyrazinamide are lower than their critical concentrations at most EPTB sites.

Effect of Gender on Clinical Presentation of Tuberculosis (TB) and Age-Specific Risk of TB, and TB-Human Immunodeficiency Virus Coinfection.

Previous studies have shown gender differences in tuberculosis (TB) incidence; however, gender disparity has not been well documented across granular categorizations of anatomic sites affected by TB and in the presence of human immunodeficiency virus (HIV) coinfection, largely due to small sample size for less common TB clinical presentations and lack of detailed clinical data. The study population included TB cases aged ≥15 years (n = 41, 266) diagnosed in Harare, Zimbabwe. This cross-sectional study estimated male-to-female ratio (M/F ratio) for (1) age-specific TB incidence, (2) age-specific HIV prevalence among incident TB cases, and (3) 9 types of TB defined by affected anatomic site. Males were at a 53% higher risk of TB compared to females (risk ratio [RR] = 1.53; 95% confidence interval [CI], 1.12-2.09). Based on adjusted odds ratios (aORs) from multinomial logistic regression model, the odds of abdominal TB (aOR = 0.51; 95% CI, .39-.68), TB bones/joints/spine (aOR = 0.63; 95% CI, .45-.90), and "other" extrapulmonary TB sites (aOR = 0.69; 95% CI = .59-.81) versus pulmonary TB were lower among males compared to females. The risk of TB-HIV coinfection among males was 17% (RR = .83; 95% CI, .74-.93) and 8% (RR = 0.92; 95% CI, .88-.95) lower in the 15- to 24-year and 25- to 44-year age groups, respectively. This study revealed a nuanced role of gender across finer categorizations of TB, indicating the need for future research to delineate underlying mechanisms driving gender disparities in TB. The finding that women had a greater likelihood of severe forms of TB and TB-HIV coinfection compared to men has important implications for women's health in TB-HIV high-burden settings.

Clinical profile of extra pulmonary tuberculosis: A retrospective south Indian study

: Tuberculosis (TB) is one of the most important global health problems. The prevalence of TB is high among the developing world. India has the highest TB burden, accounting for 1.9 million cases of the 9.1 million cases of globally. Although tuberculosis is primarily the disease affecting the lungs, Called Pulmonary TB (PTB), it may also affect other sites such as lymph nodes, central nervous system, bones, and gastrointestinal tract which is known as Extra pulmonary tuberculosis (EPTB). Extra-pulmonary TB patient reporting has been increased from 17% to 21% over period of 10 years which demands the evaluation of clinical profiles of EPTB in order to diagnose and implement the precise treatment plan. : To Determine the clinical profile of extra pulmonary tuberculosis (EPTB) patients in South Indian population. : Three years’ retrospective data of TB patients from 2015 – 2017 registered in 4 TB units of central Chennai was collected. The Study included the confirmed cases of EPTB without co-infections. Parameters such as Socio-demographic variables, clinical features and treatment outcome was collected. Age and gender wise comparisons was done for all the parameters using descriptive statistics. Lymphnode TB was the most common type of EPTB and significant association between age, gender and site of EPTB was found in the study necessitating well planned strategies, program-specified protocols for the diagnosis and treatment of extra pulmonary tuberculosis cases.

Esophageal tuberculosis induced dysphagia: a case report

BackgroundPatients can present for a wide variety of etiologies for dysphagia, and it is important to consider less common causes once common etiologies have been ruled out. Extrapulmonary Mycobacterium tuberculosis (TB) presentations are rare to see in the western populations due to relative lack of TB exposure and overall less immunocompromised populations, but should be considered for at-risk patients. Gastrointestinal (GI) TB is rare, and the GI tract is considered only the sixth most frequent site of extrapulmonary TB (EPTB).Case presentationThis is a case report of a 35-year-old Ethiopian male presenting with dysphagia and retrosternal odynophagia who was found to have infiltration of mediastinal lymphadenopathy into the esophageal wall secondary to TB. This patient underwent an upper endoscopy, which revealed a linear 2 cm full thickness mucosal defect in the middle esophagus concerning for an infiltrative process with full thickness tear. Computed tomography (CT) of the chest demonstrated a subcarinal soft tissue mass that was inseparable from the esophagus. He was referred to thoracic surgery and underwent an exploratory mediastinal dissection. A mediastinoscopy scope was inserted and the mediastinal dissection was made until the subcarinal nodes were identified and removed. Biopsy results showed necrotizing and non-necrotizing granulomas, and acid-fast bacilli (AFB) culture from the surgically removed lymph node showed Mycobacterium TB complex growth. He had no known TB exposures and did not have any TB risk factors. He then followed up in infectious disease clinic and was managed with anti-tuberculosis treatment (ATT) with complete resolution of symptoms.ConclusionsOur patient was ultimately found to have esophageal TB secondary to mediastinal invasion into the esophageal wall from lymphadenopathy associated with TB. This is an extremely rare presentation in western populations due to diminished exposure rates and overall less immunocompromised populations compared to impoverished countries with increased TB exposure and human immunodeficiency virus (HIV) infection rates. Although TB is not as commonly seen in western populations, it should be considered on the differential for any atypical presentations of GI diseases for patients with clinical or geographic risk factors.

Clinical spectrum and outcome of extra-pulmonary tuberculosis in children.

Objective: To determine the types, clinical spectrum and outcome of Extra-Pulmonary Tuberculosis (EPTB) in children admitted at a tertiary care hospital. Study Design: Cross Sectional study. Setting: The Children's Hospital and The Institute of Child Health, Lahore. Period: May to December 2019. Material & Methods: A total of 63 patients diagnosed with EPTB aged 1 month to 16 years were included. All patients with lung involvement were excluded from the study. Anti-tuberculous therapy (ATT) was started in all patients and outcome was monitored during the hospital stay. Results: In a total of 63 patients, mean age was 9.03+3.1 years. There were 35 (55.5%) male and 28 (44.4%) female. The mean duration of symptoms at the time of presentation was 5.93+2.4 months. The common sites of EPTB were meninges noted in 17(26.9%), pleural in 13 (20.6%), abdominal in 12 (19.04%), lymph nodes in 11 (17.4%), disseminated in 6 (9.52%) and bone and joints in 4 (6.34%) patients. The most common systemic complaints were fever in 58 (92.06%), weight loss in 48 (76.1%) and anorexia in 45 (71.4%). After treatment, fifty-four patients improved and discharged while 9 (14.2%) patients died. Conclusion: The commonest sites of EPTB were meninges, pleural, abdomen and lymph nodes. Fever, weight loss and anorexia were the most frequent systemic complaints. Most of the patients recovered while the most common cause of mortality was tuberculous meningitis.

Trends in pattern of tuberculosis in Sharkia Governorate at Ministry of Health and Population Chest Hospitals from 2016 to 2019

BackgroundTuberculosis is a communicable disease that is one of the leading cause of death from a single infectious agent (ranking above human immunodeficiency virus/acquired immunodeficiency syndrome). The aim of this work was to study the trend of applying the tuberculosis control program at the ministry of health and population chest hospitals, Sharkia, Egypt.ResultsThis retrospective cross-sectional study was carried out using medical records from the tuberculosis registry at Ministry of Health and Population chest hospitals, Sharkia Governorate. The investigated variables included demographic characteristics, type of tuberculosis infection, and affected organs. All data were coded and statistically analyzed. A total 1404 cases of tuberculosis were notified between 2016 and 2019 with male predominance, where 67.1% were males and 32.9% were females. The highest number of tuberculosis patients was from the reproductive age groups. During the 4-year study period, the highest percentage of cases was new cases and the highest frequency of cases was during 2017 and the lowest frequency was during 2016. There was a decline in the total number of cases in 2018 and 2019 after sharp increase of total cases in 2017: pulmonary tuberculosis cases showed a sharp decline in 2017; however, there was an increase in extrapulmonary tuberculosis cases during 2017 then a slight decrease in 2018 and 2019. Of the pulmonary tuberculosis cases, 83.8% were smear-positive tuberculosis.ConclusionsPulmonary smear-positive and new cases were the most common among the recorded cases of tuberculosis. Productive age groups represented large percentage of the studied cases of tuberculosis. Lymph node and bones were the most common sites of extrapulmonary tuberculosis among reported cases in this study.

The evaluation of the cases with extrapulmonary tuberculosis

Objective: Tuberculosis (TB) that can involve all organs is a disease progressing with a wide range of clinical presentations. It is especially difficult to diagnose the cases of extrapulmonary tuberculosis (EPTB) due to the atypical course, and the cases of EPTB constitute approximately 35% of all TB cases in our country. In our study, it was aimed to examine the distribution rates, diagnostic methods, and treatment processes of EPTB in terms of the involved systems.
 Material-Method: Of 308 patients diagnosed with TB, 119 cases having EPTB were retrospectively analyzed in The Konya Training and Research Hospital of Health Sciences University between 1st January 2015 and 30th June 2019.
 Results: While 119 (38.6%) EPTB cases of 308 cases diagnosed with TB were included in the study. 63 (52.9%) and 56 (47%) patients were women and men, respectively. The average age was found as 44.42±18.8 years (min: 18- max: 91 years). The distribution of involvement sites of EPTB was as follows: lymphadenitis, 45.3%; pleural tuberculosis, 24.3%; peritonitis, 14.2%; bone-joint tuberculosis, 7.5%; meningitis, 2.5%; miliary tuberculosis, 1.6%; others, 4.2%. In terms of EPTB, 83 (69.7%) cases were diagnosed histopathologically, 28 (23.5%) and nine (7.5%) were found to have culture and acido-resistant bacilli (ARB) positivity, respectively. A total of 29 (24.3%) cases were diagnosed microbiologically, and the purified protein derivative (PPD) positivity was detected in 106 (89%) cases. While the success rate of the treatment was found to be 93.2%, the mortality rate was measured as 3.3%. 
 Conclusion: It should be kept in mind that TB is a common multisystem disease in our country and may present itself with a wide range of symptoms. In the presence of clinical suspicion, supportive tests should be performed; biopsy and culture samples should be obtained from the appropriate tissues; anti-TB treatment should be initiated at once if clinicians have sufficient evidence.

A Camouflaged Case of Disseminated Tuberculosis Presenting as Adrenal Crisis

Lymphohematogenous spread of mycobacterium tuberculosis to multiple organs presents a complex diagnostic challenge to any physician. A holistic and vigilant approach is required in the quest to diagnose disseminated tuberculosis causing adrenal failure. Although tuberculosis can affect various endocrine glands of the body yet adrenal remains the most common.[1] It is also the fifth most common site for extra-pulmonary tuberculosis.[2] The incidence of tuberculous Addison’s disease has lowered courtesy of anti-tubercular medications accounting for only 7-20% of cases.[1] Here we showcase a rare incidence where a 39 years old gentleman with no constitutional symptoms and no known co-morbidities presenting with neck pain went into adrenal crisis and eventually was found to be due to disseminated tuberculosis which affected his lungs, adrenal glands, cervical spine, and brain.

Molecular characteristics of drug-resistance Mycobacterium tuberculosis strains isolated from extra pulmonary tuberculosis sites

ObjectivesChina is the second high tuberculosis (TB) burden country in the world. This article was to determinate the molecular characteristic of drug resistance Mycobacterium tuberculosis (DRTB) strains from extra pulmonary tuberculosis (EPTB). MethodsThe medical records of patients with EPTB were reviewed and collected from 2006 to 2016. The drug sensitivity of all samples was studied. All multiple drug resistance (MDR) and extensive drug resistance (XDR) strains were included. The detection of the deletion of region of difference 105 (RD105) and mycobacterial interspersed repetitive-unit variable-number tandem-repeat (MIRU-VNTR) were used to discriminate the molecular type of EPTB strains. Results162 DRTB isolates were from patients with EPTB including 104 male and 58 female. Beijing genotype had a significant correlation with the patterns of DR (P<0.05), re-treatment patients (P<0.05) and gender (P<0.05). The history of treatment had a statistically significant correlation with patterns of DR (P<0.05) and gender (P<0.05). Patterns of DR had no correlation with gender (P>0.05). Of 162 strains Beijing family strains represented 91.4%. The cluster rate was 17.9% and clustering ratio was 11.1%. Beijing family genotype is predominant in the patients with EPTB. The cluster rate and clustering ratio was low. ConclusionsBeijing family genotype is predominant and highly epidemic in the patients with drug resistance extra pulmonary tuberculosis (DR-EPTB). The cluster rate and clustering ratio was low. Genotype of re-treatment male patient with DR-EPTB is more likely Beijing family genotype.

Prevalence of Extrapulmonary Tuberculosis in Newly Registered HIV Patients

Introduction: Human Immunodeficiency Virus infection and Tuberculosis are among the ten leading causes of death worldwide. In advanced AIDS, M. tuberculosis frequently causes disseminated Extra-Pulmonary Tuberculosis (EPTB). EPTB being paucibacillary infection poses a diagnostic challenge. The emergence of Cartridge Based Nucleic Acid Amplification Test (CBNAAT) has marked an important development in the field of rapid molecular diagnostics of tuberculosis. Aims and Objective: The purpose of this study was to determine the prevalence of EPTB in newly registered HIV patients visiting ART clinic and to find the prevalence of Rifampicin resistance using CBNAAT. Materials and Method: 213 newly registered HIV patients were included in the study recruited over 10 months time period and followed up for six months from recruitment. Case record of each patient with detailed history, clinical examination and necessary blood, radiological and specimen sampling done to investigate for tuberculosis was maintained. The data obtained were analyzed using SPSS 20.0 software. Result: The prevalence of EPTB in newly registered HIV patients was found to be 14.5%, with abdomen being the most common site for EPTB. Rifampicin resistance was seen in 3.2% cases. Conclusion: The result of this study showed that the prevalence of EPTB was higher compared to PTB in HIV patients. CBNAAT sensitivity for different samples were variable. This study showed maximum sensitivity of CBNAAT for lymph node aspirate (100%) and minimum for CSF (0%). Overall the sensitivity of CBNAAT was low, yet it is a very useful investigation for detection of EPTB with high positive predictive value.

Update on urogenital tuberculosis in Southern Tunisia: a review of a 26-year period.

Tuberculosis affects commonly the lungs, but any other organs can be affected as well. Urogenital tuberculosis is usually misdiagnosed. In this perspective, we aimed to give an update on the epidemiological, clinical and evolutionary features of urogenital tuberculosis in Southern Tunisia. We conducted a retrospective study including all patients with extrapulmonary tuberculosis notified during the period from 1992 to 2017 in Southern Tunisia. We specified the particularities of urogenital tuberculosis cases, and we compared them with other extrapulmonary tuberculosis cases. Overall, we analyzed 240 cases with urogenital tuberculosis, among 1702 patients with extrapulmonary tuberculosis (14.1%). There were 121 women (50.4%). The mean age was 49±17 years. Multifocal tuberculosis was noted in 29 cases (12.1%). There were 169 cases with urinary tract tuberculosis (70.4%). Chronological trends analysis showed that the median age at diagnosis increased significantly (Rho=0.41; p=0.039) and the number of urogenital tuberculosis declined during the study period, without a statistical significance (Rho = -0.07; p=0.721). Compared to other extrapulmonary tuberculosis sites, patients aged 60 years and above (OR=2.7; p<0.001) and coming from rural areas (OR=1.4; p=0.021) were more frequently diagnosed with urogenital tuberculosis. Treatment duration was significantly longer in patients with urogenital tuberculosis (10.13±3.79 vs 9.20±3.77 months; p<0.001). As for the disease evolution, relapse was significantly more frequent in patients with urogenital tuberculosis (OR=4.1; p=0.045). Although decreasing trends over time were noted, the prognosis of urogenital tuberculosis was more severe compared to other extrapulmonary tuberculosis sites.

Machine learning reveals that Mycobacterium tuberculosis genotypes and anatomic disease site impacts drug resistance and disease transmission among patients with proven extra-pulmonary tuberculosis

BackgroundThere is a general dearth of information on extrapulmonary tuberculosis (EPTB). Here, we investigated Mycobacterium tuberculosis (Mtb) drug resistance and transmission patterns in EPTB patients treated in the Tshwane metropolitan area, in South Africa.MethodsConsecutive Mtb culture-positive non-pulmonary samples from unique EPTB patients underwent mycobacterial genotyping and were assigned to phylogenetic lineages and transmission clusters based on spoligotypes. MTBDRplus assay was used to search mutations for isoniazid and rifampin resistance. Machine learning algorithms were used to identify clinically meaningful patterns in data. We computed odds ratio (OR), attributable risk (AR) and corresponding 95% confidence intervals (CI).ResultsOf the 70 isolates examined, the largest cluster comprised 25 (36%) Mtb strains that belonged to the East Asian lineage. East Asian lineage was significantly more likely to occur within chains of transmission when compared to the Euro-American and East-African Indian lineages: OR = 10.11 (95% CI: 1.56–116). Lymphadenitis, meningitis and cutaneous TB, were significantly more likely to be associated with drug resistance: OR = 12.69 (95% CI: 1.82–141.60) and AR = 0.25 (95% CI: 0.06–0.43) when compared with other EPTB sites, which suggests that poor rifampin penetration might be a contributing factor.ConclusionsThe majority of Mtb strains circulating in the Tshwane metropolis belongs to East Asian, Euro-American and East-African Indian lineages. Each of these are likely to be clustered, suggesting on-going EPTB transmission. Since 25% of the drug resistance was attributable to sanctuary EPTB sites notorious for poor rifampin penetration, we hypothesize that poor anti-tuberculosis drug dosing might have a role in the development of resistance.

Molecular characteristics of drug-resistance Mycobacterium tuberculosis strains isolated from extra pulmonary tuberculosis sites

ObjectivesChina is the second high tuberculosis (TB) burden country in the world. This article was to determinate the molecular characteristic of drug resistance Mycobacterium tuberculosis (DRTB) strains from extra pulmonary tuberculosis (EPTB). MethodsThe medical records of patients with EPTB were reviewed and collected from 2006 to 2016. The drug sensitivity of all samples was studied. All multiple drug resistance (MDR) and extensive drug resistance (XDR) strains were included. The detection of the deletion of region of difference 105 (RD105) and mycobacterial interspersed repetitive-unit variable-number tandem-repeat (MIRU-VNTR) were used to discriminate the molecular type of EPTB strains. Results162 DRTB isolates were from patients with EPTB including 104 male and 58 female. Beijing genotype had a significant correlation with the patterns of DR (P<0.05), re-treatment patients (P<0.05) and gender (P<0.05). The history of treatment had a statistically significant correlation with patterns of DR (P<0.05) and gender (P<0.05). Patterns of DR had no correlation with gender (P>0.05). Of 162 strains Beijing family strains represented 91.4%. The cluster rate was 17.9% and clustering ratio was 11.1%. Beijing family genotype is predominant in the patients with EPTB. The cluster rate and clustering ratio was low. ConclusionsBeijing family genotype is predominant and highly epidemic in the patients with drug resistance extra pulmonary tuberculosis (DR-EPTB). The cluster rate and clustering ratio was low. Genotype of re-treatment male patient with DR-EPTB is more likely Beijing family genotype.

The execution rate of procedures to diagnose extrapulmonary tuberculosis in Botswana

Background: Extra-pulmonary tuberculosis (EPTB) accounts for about 20% of TB cases worldwide. Its diagnosis is challenging. Aim: This study meant to assess the prevalence of EPTB types, procedures to diagnose EPTB and medical officers’ (MOs) views on procedures performed in the diagnosis of EPTB over a 2-year period in Botswana. Setting: The study was conducted in 13 urban and rural facilities of 29 health districts in Botswana. Methods: This was a cross-sectional study that reviewed patients’ TB data and administered a questionnaire to MOs. Results: About 2 in 10 TB ( n = 2996, 22.7%) cases were classified as EPTB. The most common site of EPTB was pleural ( n = 1066, 36.7%) followed by lymph node (LN) ( n = 546, 18.8%). A pleural tap was performed in 182 (17.0%) cases of pleural TB and a fine needle aspiration (FNA) in one-third ( n = 160, 29.6%) of LN TB cases. There were statistical differences in work experience amongst MOs’ responses regarding their self-reported confidence to undertake basic procedures to diagnose EPTB such as pleural tap ( p = 0.032) or FNA ( p &lt; 0.0001). Conclusion: This study reviewed and evaluated the proportion of EPTB and inquired about MO’s experience in managing EPTB. Despite MOs’ attendance at Botswana National Tuberculosis Programme (BNTP) TB case management (TBCM) training, the emphasis by the BNTP guidelines and availability of logistics, the execution rate of procedures to diagnose EPTB was still low in Botswana.

Prevalence of extrapulmonary tuberculosis among people living with HIV/AIDS in sub-Saharan Africa: a systemic review and meta-analysis.

BackgroundThe double burden of infectious diseases such as tuberculosis (TB) and HIV disproportionately affects Africa. Our objective was to summarize the prevalence of extrapulmonary TB (EPTB) among people living with HIV/AIDS (PLWHA) in sub-Saharan Africa (SSA).MethodsWe searched PubMed and Google Scholar for studies done on the prevalence of EPTB among PLWHA which published in English from 1990 to 2017. We also searched bibliographic indices and browsed through reference lists of articles and journals. We critically appraised the quality of articles and abstracted the data with Joanna Briggs Institute (JBI) checklists. We used Review Manager Software (version 5.3) and Compressive Meta-analysis Software (version 2.2) for analysis. Finally, we summarized the effect estimate by using random-effects model and explored potential sources of heterogeneity by subgroup and sensitivity analyses. We assessed publication bias by funnel plot and statistical test. Finally, we used PRISMA format for reporting.ResultsWe included, in this review, 31 studies that fulfilled our inclusion criteria, with a total population of 28,659. The prevalence estimate of EPTB among PLWHA ranged from 6.4% (95% CI: 3.8, 9.0) to 36.8% (95% CI: 28.6, 45); random-effects pooled prevalence of EPTB among PLWHA was found to be 20% (95% CI: 17, 22; heterogeneity: τ2=0; χ2=509.09, degrees of freedom [df]=30, P<0.00001; I2=94%). No evidence of publication bias was observed (P=0.44 for Egger’s regression analysis and P=0.11 for Begg’s rank correlation analysis).ConclusionWe can conclude from our analyses that the prevalence of EPTB among PLWHA was high. It is necessary to give emphasis for EPTB, especially when screening TB among PLWHA, widening the spectrum of screening to include all EPTB sites in the countries with high EPTB and/or HIV prevalence in the general population.

Primary tubercular submandibular abscess: a rare presentation in two years old girl

Extra pulmonary tuberculosis (TB) continues to be a serious problem in developing countries. The prevalence of extra pulmonary tuberculosis (EPTB) is higher in immunocompromised, especially human immunodeficiency virus (HIV) co-infected patients. The most common site of extra pulmonary tuberculosis is lymph node followed by pleura. Lymph nodes are pivotal component of immune system and hence they are affected in various conditions like infections, autoimmune disorder, malignancy However, tubercular affliction of submandibular lymph node is not common. Only a few cases of tubercular submandibular abscess in immune-competent children have been reported in literature. Here we report a case of two-year old girl with non-healing multiple submandibular lymph node abscess presenting as a primary tuberculosis that proved diagnostically challenging. She responded favourably to a five drug anti-tubercular regimen.

Thoracoscopic pleural biopsy improves yield of Xpert MTB/RIF for diagnosis of pleural tuberculosis.

Extrapulmonary tuberculosis (EPTB) accounts for ~15% of all TB patients, and TB pleural effusion is the second most common site of EPTB. The diagnosis of pleural TB is challenging due to the pauci-bacillary nature of the disease. Histopathology of thoracoscopically obtained pleural biopsy provides the highest diagnostic yield. The Xpert MTB/RIF assay (Xpert) is a PCR test that can identify both Mycobacterium tuberculosis (MTB) and rifampicin resistance. Currently, there is a lack of clarity regarding the value of Xpert on pleural tissue. We report our experience of using Xpert on thoracoscopic pleural biopsy samples. We retrospectively reviewed the records of patients who underwent thoracoscopy in our institution over a 1-year period. Relevant clinical details; indications; and results of tests on pleural tissue and fluid, including histopathology, mycobacterial cultures and Xpert, were extracted. Of the 156 patients who underwent thoracoscopy, 73 (47%) had TB, 66 (42%) malignancy and 17 (11%) other conditions. Histopathology was diagnostic in all the 73 TB patients (100%). The yields of the microbiological tests against histopathology on thoracoscopic biopsy sample and pleural fluid were: pleural tissue Xpert 45%, pleural tissue culture 39%, pleural fluid culture 17% and pleural fluid Xpert 14%. Pleural tissue provided higher yields than fluid in both Xpert and culture (P < 0.05). Pleural tissue Xpert provided a higher yield than culture and substantially improved yield compared with closed pleural biopsy as we previously reported. Thoracoscopic pleural biopsy results in increased sensitivity on Xpert testing.

Whole Genome Sequencing of Mycobacterium tuberculosis Isolates From Extrapulmonary Sites.

Tuberculosis (TB) remains one of the leading causes of morbidity and mortality worldwide. Extrapulmonary tuberculosis (EPTB) constitutes around 15-20% of TB cases in immunocompetent individuals. Extrapulmonary sites that are affected by TB include bones, lymph nodes, meningitis, pleura, and genitourinary tract. Whole genome sequencing has emerged as a powerful tool to map genetic diversity among Mycobacterium tuberculosis (MTB) isolates and identify the genomic signatures associated with drug resistance, pathogenesis, and disease transmission. Several pulmonary isolates of MTB have been sequenced over the years. However, availability of whole genome sequences of MTB isolates from extrapulmonary sites is limited. Some studies suggest that genetic variations in MTB might contribute to disease presentation in extrapulmonary sites. This can be addressed if whole genome sequence data from large number of extrapulmonary isolates becomes available. In this study, we have performed whole genome sequencing of five MTB clinical isolates derived from EPTB sites using next-generation sequencing platform. We identified 1434 nonsynonymous single nucleotide variations (SNVs), 143 insertions and 105 deletions. This includes 279 SNVs that were not reported before in publicly available datasets. We found several mutations that are known to confer resistance to drugs. All the five isolates belonged to East-African-Indian lineage (lineage 3). We identified 9 putative prophage DNA integrations and 14 predicted clustered regularly interspaced short palindromic repeats (CRISPR) in MTB genome. Our analysis indicates that more work is needed to map the genetic diversity of MTB. Whole genome sequencing in conjunction with comprehensive drug susceptibility testing can reveal clinically relevant mutations associated with drug resistance.

Utility of pleural fluid routine and microscopy examination plus adenosine deaminase levels in the diagnosis of tuberculous pleural effusion

Background: Tuberculous pleural effusion is the second most common site of extrapulmonary tuberculosis. Not all centers have access to advanced and invasive tests and affordability is also an issue. Hence, diagnosis is largely based on history, clinical examination, and pleural fluid analysis. Objectives: Our aim was to evaluate the utility of pleural fluid routine micro examination along with adenosine deaminase (ADA) levels in diagnosis of tuberculous pleural effusion. Materials and Methods: A retrospective analysis was done of the 100 adult patients with pleural effusion predefined criteria were adopted to label a case as tuberculous. Using MS Excel 2007 sensitivity, specificity, positive and negative likelihood ratio, accuracy, etc., were derived and various parameters in pleural fluid were also studied. Result: The sensitivity, specificity, positive, and negative predictive values, positive and negative likelihood ratios, accuracy, and discordance were 95.74%, 94.33%, 93.75%, 96.15%, 16.88%, 4.51%, 95%, and 5%, respectively. Conclusion: Pleural fluid routine micro examination along with ADA levels has an acceptable sensitivity, specificity, and accuracy for the diagnosis of tuberculous pleural effusion.

Sternoclavicular Joint Tuberculosis: A rare extra pulmonary manifestation

The sternoclavicular joint is a rare site for extra pulmonary tuberculosis. Diagnosis may be delayed because of its rarity and unusual clinical presentation. Early diagnosis and prompt treatment with standard antituberculous agents would hasten complete recovery. We report a patient with sternoclavicular joint tuberculosis in association with pleural effusion.