Suspected reactivation of extrapulmonary tuberculosis focus after non-medical abuse of anabolic androgenic steroids: a case report.

Background Youth population has a common tendency to use androgenic steroids. The reasons for such abuse vary from performance enhancement to muscle building in order to enhance physical appearance. Such rampant abuse, aided by fitness centers and gym trainers, has a huge risk of side effects such as hepatic dysfunctions and increased risk of infections. Case presentation We report a case of 21-year-old man who started with anabolic steroids, namely testosterone enanthate, nandrolone decanoate and boldenone undecylenate injections, for the purpose of muscle building and strength training at his fitness center. He presented to his family physician after 2 months with upper neck swelling on right side 5 × 4 cm for 15-20 days. He was started on Augmentin 625 mg tablet three times a day for 7 days. On seventh day, swelling persisted, and fine needle aspiration cytology (FNAC) was performed, which was suggestive of granulomatous lesion likely to be tuberculosis. The patient was started with anti-tubercular therapy (ATT) under category A, but swelling did not improve and repeated FNAC was advised. The ATT was withheld and Augmentin tablet was restarted for another 3 days. A revised diagnosis of acute suppurative lymphadenitis was made, and an incision and drainage of the abscess was performed. The patient was started on Amikacin 500 intramuscular injection for 5 days along with faropenem and cefuroxime axetil tablets for 14 days. He initially started recovering but returned with pustular discharge from the incision mark. It was decided to reinitiate the ATT-intensive phase medication for another 2 months. The patient finally recovered with complete healing of the wound. The frequent change of treating physician and misuse of antimicrobials made the diagnosis tougher, contributing to delay in the optimum therapy. Conclusion This case highlights the abuse of multiple steroids together in the form of stacking by a young adult, which leads to a rare serious adverse effect such as suspected tubercular reactivation.

Risk factors for tuberculous empyema in pleural tuberculosis patients.

Tuberculous empyema (TE) is associated with high mortality and morbidity. In the retrospective cohort study, we aimed to find risk factors for TE among pleural tuberculosis (TB) patients. Between July 2011 and September 2015, all culture-confirmed pleural TB patients (474 cases) were enrolled in our study. Empyema was defined as grossly purulent pleural fluid. Demographic and epidemiological data were collected for further analysis. Multivariate logistic regression analysis was used to evaluate risk factors of TE in pleural TB, age-adjusted odds ratio (OR) and 95% confidence interval (CI) were calculated to show the risk. The mean age was 35.7 ± 18.1 years old, males comprised 79.1% of the participants (375 cases). Forty-seven patients (9.9%) were multidrug-resistant TB (MDR-TB), 29 (6.1%) had retreatment TB, 26 (5.5%) had diabetes mellitus. The percentage of empyema patients was 8.9% (42 cases). Multivariate analysis revealed that male (adjusted OR = 4.431, 95% CI: 1.411, 13.919), pleural adenosine deaminase (ADA, >88 U/L) (adjusted OR = 3.367, 95% CI: 1.533, 7.395) and white blood cell (WBC, >9.52 109/L) (adjusted OR = 5.763, 95% CI: 2.473, 13.431) were significant risk factors for empyema in pleural TB, while pulmonary TB (adjusted OR = 0.155, 95% CI: 0.072, 0.336) was the protective factor for the patients. TE remains a serious threat to public health in China. Male sex is a significant risk factor for TE while the presence of pulmonary TB is protective, and high levels of pleural ADA and WBC count could aid in early diagnosis of TE. This finding would help towards reducing the mortality and morbidity associated with TE.

The characteristics of spatial-temporal distribution and cluster of tuberculosis in Yunnan Province, China, 2005-2018.

BACKGROUND: Tuberculosis (TB) makes a big challenge to public health, especially in high TB burden counties of China and Greater Mekong Subregion (GMS). The aim of this study was to identify the spatial-temporal dynamic process and high-risk region of notified pulmonary tuberculosis (PTB), sputum smear-positive tuberculosis (SSP-TB) and sputum smear-negative tuberculosis (SSN-TB) cases in Yunnan, the south-western of China between years of 2005 to 2018. Meanwhile, to evaluate the similarity of prevalence pattern for TB among GMS. METHODS: Data for notified PTB were extracted from the China Information System for Disease Control and Prevention (CISDCP) correspond to population information in 129 counties of Yunnan between 2005 to 2018. Seasonally adjusted time series defined the trend cycle and seasonality of PTB prevalence. Kulldorff's space-time scan statistics was applied to identify temporal, spatial and spatial-temporal PTB prevalence clusters at county-level of Yunnan. Pearson correlation coefficient and hierarchical clustering were applied to define the similarity of TB prevalence among borders with GMS. RESULT: There were a total of 381,855 notified PTB cases in Yunnan, and the average prevalence was 59.1 per 100,000 population between 2005 to 2018. A declined long-term trend with seasonality of a peak in spring and a trough in winter for PTB was observed. Spatial-temporal scan statistics detected the significant clusters of PTB prevalence, the most likely cluster concentrated in the northeastern angle of Yunnan between 2011 to 2015 (RR = 2.6, P < 0.01), though the most recent cluster for PTB and spatial cluster for SSP-TB was in borders with GMS. There were six potential TB prevalence patterns among GMS. CONCLUSION: This study detected aggregated time interval and regions for PTB, SSP-TB, and SSN-TB at county-level of Yunnan province. Similarity prevalence pattern was found in borders and GMS. The localized prevention strategy should focus on cross-boundary transmission and SSN-TB control.

Dose-related adverse events in South African patients prescribed clofazimine for drug-resistant tuberculosis.

BACKGROUND: Optimal drug levels and minimal toxicity are critical factors in improving treatment outcomes for patients prescribed new and repurposed medicine for drug-resistant (DR) tuberculosis (TB). The optimal dose and dose-related safety of clofazimine (CFZ), a repurposed medicine for DR TB, in the South African (SA) population are unknown. OBJECTIVES: To report on dose-related adverse events in patients receiving CFZ plus a background regimen for DR TB. METHODS: In a retrospective review of patient folders from 2012 to 2014, adverse events documented for patients receiving high- (≥200 mg) and low-dose (100 mg) CFZ in a centralised DR TB hospital in KwaZulu-Natal Province, SA, were investigated for an association between dose-weight interactions and adverse events. RESULTS: Of 600 patients included, 78.7% (n=472) weighed ≥50 kg. Of these, 17.4% (n=82) received 100 mg CFZ and 82.6% (n=390) received >200 mg. Of 128 patients (21.3%) who weighed <50 kg, 68.0% (n=87) received 100 mg CFZ and 32.0% (n=41) received ≥200 mg. Of 463 patients (77.2%) who were HIV-positive, 94.0% were on antiretrovirals. There was no difference between the dose-weight cohorts in the background regimen given in addition to high- or low-dose CFZ. The frequency and types of adverse events observed were similar to the published literature. When analysed per dose-weight cohort, patients weighing <50 kg and receiving high-dose CFZ (≥200 mg) had a 2.6 times higher risk of any adverse event (adjusted odds ratio (aOR) 2.57; 95% confidence interval (CI) 1.02 - 6.05; p=0.05: reference category <50 kg and 100 mg). Patients weighing <50 kg and receiving high-dose CFZ had a 3.3 times higher risk of gastrointestinal adverse events than patients weighing <50 kg and receiving 100 mg CFZ (aOR 3.30; 95% CI 1.51 - 7.19; p=0.003). A high risk of chest pain was observed in patients receiving high- and low-dose CFZ, irrespective of weight. Patients weighing <50 kg receiving high-dose CFZ had a slightly higher risk of adverse events related to the skin (aOR 1.2; 95% CI 0.55 - 2.62; p=0.7) There were no documented reports of the CFZ dose being reduced or the drug being stopped due to adverse events in the sample population. CONCLUSIONS: There is an association between dose-weight interaction and adverse events. The odds of any adverse event occurring were higher when low-weight patients (<50 kg) received high-dose CFZ (≥200 mg). Gastrointestinal and skin-related adverse events were more common when high-dose CFZ was used in patients weighing <50 kg. Chest pain was reported in patients receiving high- and low-dose CFZ, irrespective of weight, and may be a symptom of cardiac toxicity. Plasma concentrations of CFZ may be affected by drug-drug interactions, so active drug safety monitoring including electrocardiograms is recommended routinely when CFZ is part of the regimen.

Mucosal delivery of tuberculosis vaccines: a review of current approaches and challenges.

Introduction: Tuberculosis (TB) remains a major health threat and it is now clear that the current vaccine, BCG, is unable to arrest the global TB epidemic. A new vaccine is needed to either replace or boost BCG so that a better level of protection could be achieved. The route of entry of Mycobacterium tuberculosis, the causative organism, is via inhalation making TB primarily a respiratory disease. There is therefore good reason to hypothesize that a mucosally delivered vaccine against TB could be more effective than one delivered via the systemic route.Areas covered: This review summarizes the progress that has been made in the area of TB mucosal vaccines in the last few years. It highlights some of the strengths and shortcomings of the published evidence and aims to discuss immunological and practical considerations in the development of mucosal vaccines.Expert opinion: There is a growing body of evidence that the mucosal approach to vaccination against TB is feasible and should be pursued. However, further key studies are necessary to both improve our understanding of the protective immune mechanisms operating in the mucosa and the technical aspects of aerosolized delivery, before such a vaccine could become a feasible, deployable strategy.

Does completion of sputum smear monitoring have an effect on treatment success and cure rate among adult tuberculosis patients in rural Eastern Uganda? A propensity score-matched analysis.

BACKGROUND: Tuberculosis is a global public health problem. Bacteriologically confirmed pulmonary tuberculosis (BC-PTB) patients require three sputum smear monitoring (SSM) tests to establish cure or treatment success, but few studies have assessed the relationship. We evaluated the effect of completing SSM on treatment success rate (TSR) among adult BC-PTB patients in rural eastern Uganda. METHODS: We conducted a propensity score-matched (PSM) analysis of a retrospective observational cohort data. Participants who completed SSM were matched to those who had not, through nearest neighbor 1:1 caliper matching. Balance of baseline characteristics between the groups was compared before and after PSM using standardized mean differences. Logistic regression analysis was performed in matched and unmatched samples, reported as odds ratio (OR) with 95% confidence intervals (CI). Robustness of the results to hidden bias was checked through sensitivity analysis. The primary outcome was TSR (treatment completion or cure), while the secondary was cure rate, measured as an individual outcome. RESULTS: Before PSM, 591 (72.3%) of the 817 participants had incomplete SSM, with statistically significant differences in baseline covariates between completers and non-completers. After PSM, there were 185 participants in either group, balanced on baseline covariates. Before PSM, SSM completion was not associated with TSR, with unadjusted (OR, 0.92; 95%CI, 0.32-2.63) and adjusted analysis (Adjusted OR, 1.32; 95%CI, 0.41-4.22). For cure rate, there was a statistically significant effect before (OR, 93.34; 95%CI, 29.53-295.99) and after adjusted analysis (Adjusted OR, 86.24; 95%CI, 27.05-274.94), although imprecise. In PSM analysis, SSM completion was associated with increased odds of cure (OR, 87.00; 95%CI, 12.12-624.59) but not TSR (OR, 1.67; 95%CI, 0.40-6.97). CONCLUSIONS: Completing SSM increases cure but has no effect on TSR among adult BC-PTB patients in eastern Uganda. Implementation of SSM should be encouraged to ensure improvement in cure rates among tuberculosis patients in rural areas.

Impact of the change in the antitubercular regimen from three to four drugs on cure and frequency of adverse reactions in tuberculosis patients from Brazil: A retrospective cohort study.

BACKGROUND: The Ministry of Health in Brazil included ethambutol in the intensive phase of sensible tuberculosis (TB) treatment in March 2010, due to the increasing drug resistance, and implemented the fixed dose combination in the TB treatment guidelines. METHODS: A retrospective cohort study was performed to determine the impact of change from three to four drugs schemes on the TB cure and frequency of adverse drug reactions (ADRs) in TB patients. To answer this question, we used data from 730 randomly selected patients who received anti-TB treatment between January 2007 and December 2014 in a reference center from Salvador, Brazil. FINDINGS: TB patients who received the RHEZ regimen (n = 365) developed ADRs more frequently than those treated with the RHZ (n = 365) (86 [23.6%] vs. 55 [15.1%]; p = 0.01). This difference in ADR incidence was even higher in patients above 30 years-old (64 [74.4%] vs. 36 [65.5%]; p = 0.01). The overall number of ADR episodes was greater in patients from the RHEZ group than in the group that received RHZ (170 [61.4%] vs. 107 [38.6%]; p = 0.03). Multivariable logistic regression analysis adjusted for age, alcohol use and diabetes demonstrated that patients receiving the RHEZ regimen had increased odds of developing ADRs than those undertaking the RHZ scheme (odds ratio [OR]: 1.61, 95% confidence interval [CI]: 1.10-2.35; p = 0.015). The overall cure rate was similar between the distinct treatment groups. CONCLUSION: The patients treated with the four-drug regimen exhibited increased risk of ADRs compared to those who received the three-drug regimen, and especially in patients older than 30 years of age.

Tuberculosis-Related Hospitalizations in a Low-Incidence Country: A Retrospective Analysis in Two Italian Infectious Diseases Wards.

In recent years, a decrease in the incidence of tuberculosis (TB) has been recorded worldwide. However, an increase in TB cases has been reported in foreign people living in low-incidence countries, with an increase in extrapulmonary TB (EPTB) in the western region of the world. In the present work, a retrospective study was conducted in two Italian infectious diseases wards to evaluate the clinical characteristics of TB admission in the time period 2013-2017. A significant increase in TB was shown in the study period: 166 (71% males) patients with TB were enrolled, with ~70% coming from outside Italy (30% from Africa, 25% from Europe, and 13% from Asia and South America). Compared to foreign people, Italians were significantly older (71.5 (interquartile range, IQR: 44.5-80.0) vs. 30 (IQR: 24-40) years; p < 0.0001) more immunocompromised (48% vs. 17%; p < 0.0001), and affected by comorbidities (44% vs. 14%; p < 0.0001). EPTB represented 37% of all forms of the disease, and it was more incident in subjects coming from Africa than in those coming from Europe (39.3% vs. 20%, respectively). In logistic regression analysis, being European was protective (odd ratio, OR (95% CI): 0.2 (0.1-0.6); p = 0.004) against the development of EPTB forms. In conclusion, an increase in the rate of TB diagnosis was documented in two Italian reference centers in the period 2013-2017, with 39% of EPTB diagnosed in patients from outside Europe.

Latent Tuberculosis Infection among Healthcare Students and Postgraduates in a Mediterranean Italian Area: What Correlation with Work Exposure?

BACKGROUND: Tuberculosis screening is part of the standard protocol for evaluating the risk of infection in healthcare workers. The aim of this study was to evaluate the prevalence of latent tuberculosis infection (LTBI) among students attending various healthcare profession degree courses and postgraduate medical courses at the School of Medicine of the University of Palermo, Italy, and assess the possible professional origin of infection. METHODS: In total, 2946 students (2082 undergraduates and 864 postgraduates) took part in a screening program for LTBI between January 2014 to April 2019 using the tuberculin skin test (TST). Students with a positive TST result underwent a Quantiferon-TB test (QFT). RESULTS: Among the 2082 undergraduates, 23 (1.1%) had a positive TST; the result was confirmed with QFT for 13 (0.62%) of them. Among the 864 postgraduate students, 24 (2.78%) had a positive TST and only 18 (2.08%) showed a positive QTF. Latent tuberculosis infections were significantly more frequent among postgraduates than undergraduates (2.08% > 0.62%, p < 0.0001). There was a higher number of subjects previously vaccinated for TB (18.87% > 0.24%, p < 0.0001), and of vaccinated subjects found positive for TST and QTF (66.67% > 7.69%, p = 0.001) in the postgraduate group. CONCLUSION: Latent TB is relatively low among medical school students in our geographic area. Nevertheless, this infectious disease must be regarded as a re-emerging biohazard for which preventive strategies are required to limit the risk of infection, especially among exposed workers.

Effectiveness of vitamin D supplementation on the outcome of pulmonary tuberculosis treatment in adults: a meta-analysis of randomized controlled trials.

BACKGROUND: Tuberculosis (TB) is one of the most debilitating diseases worldwide. Current studies have shown that vitamin D plays a significant role in host immune defense against Mycobacterium tuberculosis, but clinical trials reported inconsistent results. Therefore, we systematically reviewed the literature to investigate whether vitamin D supplementation could improve the effect of anti-TB therapy. METHODS: We systematically searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials from their inception to February 8th, 2019 for randomized controlled trials on vitamin D supplementation in patients with pulmonary TB receiving anti-TB therapy. The primary outcomes were time to sputum culture and smear conversion and proportion of participants with negative sputum culture. The secondary outcomes were clinical response to treatment and adverse events. A random-effects model was used to pool studies. Data were analyzed using RevMan 5.3 software. RESULTS: Five studies with a total of 1126 participants were included in our meta-analysis. Vitamin D supplementation did not shorten the time to sputum culture and smear conversion (hazard ratio [HR] 1.04, 95% confidence interval [CI] 0.89-1.23, P = 0.60; HR 1.15, 95% CI 0.93-1.41, P = 0.20, respectively) and did not lead to an increase in the proportion of participants with negative sputum culture (relative risk [RR] 1.04, 95% CI 0.97-1.11, P = 0.32). However, it reduced the time to sputum culture conversion in the sub-group of participants with TaqI tt genotype (HR 8.09, 95% CI 1.39-47.09, P = 0.02) and improved the multidrug-resistant (MDR) TB sputum culture conversion rate (RR 2.40, 95% CI 1.11-5.18, P = 0.03). There was no influence on secondary outcomes. CONCLUSIONS: Vitamin D supplementation had no beneficial effect on anti-TB treatment, but it reduced the time to sputum culture conversion in participants with tt genotype of the TaqI vitamin D receptor gene polymorphism and improved the MDR TB sputum culture conversion rate.

Tuberculosis treatment outcomes among people living with HIV diagnosed using Xpert MTB/RIF versus sputum-smear microscopy in Botswana: a stepped-wedge cluster randomised trial.

BACKGROUND: Xpert® MTB/RIF (Xpert) has high sensitivity for diagnosing tuberculosis (TB) compared to sputum-smear microscopy (smear) and can reduce time-to-diagnosis, time-to-treatment and potentially unfavorable patient-level treatment outcome. METHODS: People living with HIV (PLHIV) initiating antiretroviral therapy at 22 HIV clinics were enrolled and underwent systematic screening for TB (August 2012-November 2014). GeneXpert instruments were deployed following a stepped-wedge design at 13 centers from October 2012-June 2013. Treatment outcomes classified as an unfavorable outcome (died, treatment failure or loss-to-follow-up) or favorable outcome (cured and treatment completed). To determine outcome, smear was performed at month 5 or 6. Empiric treatment was defined as initiating treatment without/before receiving TB-positive results. Adjusting for intra-facility correlation, we compared patient-level treatment outcomes between patients screened using smear (smear arm)- and Xpert-based algorithms (Xpert arm). RESULTS: Among 6041 patients enrolled (smear arm, 1816; Xpert arm, 4225), 256 (199 per 2985 and 57 per 1582 person-years of follow-up in Xpert and smear arms, respectively; adjusted incidence rate ratio, 9.07; 95% confidence interval [CI]: 4.70-17.48; p < 0.001) received TB diagnosis and were treated. TB treatment outcomes were available for 203 patients (79.3%; Xpert, 157; smear, 46). Unfavorable outcomes were reported for 21.7% (10/46) in the smear and 13.4% (21/157) in Xpert arm (adjusted hazard ratio, 1.40; 95% CI: 0.75-2.26; p = 0.268). Compared to smear, in Xpert arm median days from sputum collection to TB treatment was 6 days (interquartile range [IQR] 2-17 versus 22 days [IQR] 3-51), p = 0.005; patients with available sputum test result had microbiologically confirmed TB in 59.0% (102/173) versus 41.9% (18/43), adjusted Odds Ratio [aOR], 2.00, 95% CI: 1.01-3.96, p = 0.048). In smear arm empiric treatment was 68.4% (39/57) versus 48.7% (97/199), aOR, 2.28, 95% CI: 1.24-4.20, p = 0.011), compared to Xpert arm. CONCLUSIONS: TB treatment outcomes were similar between the smear and Xpert arms. However, compared to the smear arm, more patients in the Xpert arm received a TB diagnosis, had a microbiologically confirmed TB, and had a shorter time-to-treatment, and had a lower empiric treatment. Further research is recommended to identify potential gaps in the Botswana health system and similar settings. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02538952. Retrospectively registered on 2 September 2015.

The clinical impact of drug-induced hepatotoxicity on anti-tuberculosis therapy: a case control study.

BACKGROUND: There are limited data available on whether drug-induced hepatotoxicity (DIH) affects the clinical outcomes of tuberculosis (TB) treatment. We explored the effects of DIH on the clinical course and outcomes of pulmonary TB. METHODS: In this retrospective cohort study, we included patients with culture-proven pulmonary TB treated in a tertiary hospital from 2013 to 2016. DIH was defined as proposed by the official American Thoracic Society statement. We compared the clinical outcomes of DIH and non-DIH patients. RESULTS: Between January 1, 2013 and December 31, 2016, a total of 168 TB patients were included, and 20 (11.9%) were diagnosed with DIH. These patients were significantly older, had a higher Charlson Comorbidity Index score, exhibited more chronic liver disease, included more chronic alcoholics, and had a lower body mass index than non-DIH patients. We found no significant differences between DIH and non-DIH patients in the 2-month sputum culture conversion rate, the time to sputum culture conversion, treatment outcomes, or total treatment duration. However, the ratio of treatment interruption time to total treatment duration and the proportion of hepatotonic users were significantly higher among DIH patients. CONCLUSION: DIH development during TB treatment does not significantly affect the clinical outcomes of pulmonary TB. However, treatment interruption caused by DIH may increase the risks of future relapse and acquired resistance. Further study is needed.

Rare case of a proximal descending thoracic aorta mycotic aneurysm following intravesical BCG injections for the treatment of bladder cancer.

A 79-year-old man presented with an enlarging thoracic aneurysm on the background of superficial bladder cancer treated with intravesical bacillus Calmette-Guérin (BCG) injections. Following the injections, he developed deranged liver function tests and hepatomegaly. Liver biopsy revealed granulomatous hepatitis compatible with disseminated mycobacterial infection (BCG-osis) and was treated with anti-tuberculosis agents for 12 months. A surveillance CT scan performed as a follow-up for his bladder cancer in 2018 revealed a saccular thoracic aneurysm at the ligamentum arteriosum, which was metabolically active on positron emission tomography (PET) scan. Given the timeframe from intravesical instillation of BCG and the metabolic activity on PET scan, the lesion was consistent with a mycotic aneurysm secondary to disseminated mycobacterial infection. Following multidisciplinary team discussion, a thoracic endovascular aneurysm repair was performed. The stent grafts were placed distal to the left subclavian artery with good angiographic results and no immediate postoperative complications. He was initiated on long-term antibiotics to cover potential bacterial pathogens including mycobacterium.

Impact of multidrug-resistant tuberculosis and its medications on adverse maternal and perinatal outcomes: protocol for a systematic review and meta-analysis.

INTRODUCTION: Multidrug-resistant tuberculosis (MDR-TB) is a common public health problem affecting pregnant women. However, the impact of MDR-TB and its medication on pregnancy and perinatal outcomes has been poorly understood and inconsistently reported. Therefore, using the available literature, we aim to determine whether MDR-TB and its medications during pregnancy impact maternal and perinatal outcomes. METHODS AND ANALYSIS: This systematic review and meta-analysis will adhere to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Systematic searches will be conducted in PubMed, Scopus and Web of Science on 10 February 2020 for studies that reported adverse maternal and perinatal outcomes due to MDR-TB and/or its medication. The search will be performed without language and time restrictions. Adverse birth outcomes include miscarriage or abortion, stillbirth, preterm birth, low birth weight, small and large for gestational age, and neonatal death. Two independent reviewers will screen search records, extract data and assess the quality of the studies. The Newcastle-Ottawa Quality Assessment Scale will be used to assess the methodological quality of the included studies. In addition to a narrative synthesis, a random-effects meta-analysis will be conducted when sufficient data are available. I2 statistics will be used to assess the heterogeneity between studies. ETHICS AND DISSEMINATION: As it will be a systematic review and meta-analysis based on previously published evidence, there will be no requirement for ethical approval. Findings will be published in a peer-reviewed journal and will be presented at various conferences.

The risk of active tuberculosis among individuals living in tuberculosis-affected households in the Republic of Korea, 2015.

BACKGROUND: In the Republic of Korea (ROK), compared to other high-income countries, tuberculosis (TB) prevalence is relatively high. Active TB and latent TB infection (LTBI) surveillance of individuals living in TB-affected households has been conducted for several years. Although active case finding is an important strategy in low-prevalence, high-income countries, its effectiveness in a high prevalence setting is unclear. This study evaluated the risk of TB in household contact by calculating the incidence of TB among household contacts and comparing it with the general population of the ROK. METHODS: A retrospective cohort study, including 36,133 household-contacts of 17,958 TB patients reported in 2015, was conducted. The data was extracted from the Korean National TB Surveillance System (web-based TB cases notification system, KNTSS). The Cox proportional hazard regression model was used to evaluate risk factors for incidence of TB. A P-value < .05 was considered statistically significant. RESULTS: In this study, 319 (0.9%) of 36,133 household-contacts were reported as having TB within 1 year, which is a higher rate than the rate for the general population in the ROK. The rate of TB reported for contacts that had completed LTBI treatment (0.6%) was lower than for the LTBI group without treatment (4.6%). In multivariate analysis, age older than 65 (p < .001), being a spouse of a TB patient (p = .007), and LTBI without treatment (p = .013) were each a risk factor for TB incidence among contacts. Younger age (p < .001), presence of a cough (p < .001), testing positive for acid-fast bacilli (AFB; p < .001), and cavity on radiograph (p < .001) of the index patient were also statistically significant risk factors. CONCLUSIONS: Individuals living in TB-affected households are at high risk of developing TB in the ROK and active case finding among them is a strategy effective in the early detection and prevention of TB.

Expression of USP18 and IL2RA Is Increased in Individuals Receiving Latent Tuberculosis Treatment with Isoniazid.

BACKGROUND: The treatment of latent tuberculosis infection (LTBI) in individuals at risk of reactivation is essential for tuberculosis control. However, blood biomarkers associated with LTBI treatment have not been identified. METHODS: Blood samples from tuberculin skin test (TST) reactive individuals were collected before and after one and six months of isoniazid (INH) therapy. Peripheral mononuclear cells (PBMC) were isolated, and an in-house interferon-γ release assay (IGRA) was performed. Expression of chemokine ligand 4 (CCL4), chemokine ligand 10 (CXCL10), chemokine ligand 11 (CXCL11), interferon alpha (IFNA), radical S-adenosyl methionine domain-containing 2 (RSAD2), ubiquitin-specific peptidase 18 (USP18), interferon-induced protein 44 (IFI44), interferon-induced protein 44 like (IFI44L), interferon-induced protein tetratricopeptide repeats 1(IFIT1), and interleukin 2 receptor subunit alpha (IL2RA) mRNA levels were assessed by qPCR before, during, and after INH treatment. RESULTS: We observed significantly lower relative abundances of USP18, IFI44L, IFNA, and IL2RA transcripts in PBMC from IGRA-positive individuals compared to levels in IGRA-negative individuals before INH therapy. Also, relative abundance of CXCL11 was significantly lower in IGRA-positive than in IGRA-negative individuals before and after one month of INH therapy. However, the relative abundance of CCL4, CXCL10, and CXCL11 mRNA was significantly decreased and that of IL2RA and USP18 significantly increased after INH therapy, regardless of the IGRA result. Our results show that USP18, IFI44L, IFIT1, and IL2RA relative abundances increased significantly, meanwhile the relative abundance of CCL4, CXCL11, and IFNA decreased significantly after six months of INH therapy in TST-positive individuals. CONCLUSIONS: Changes in the profiles of USP18, IL2RA, IFNA, CCL4, and CXCL11 expressions during INH treatment in TST-positive individuals, regardless of IGRA status, are potential tools for monitoring latent tuberculosis treatment.

Use of GeneXpert and the role of an expert panel in improving clinical diagnosis of smear-negative tuberculosis cases.

SETTING: A high proportion of notified tuberculosis cases in the Philippines are clinically diagnosed (63%) as opposed to bacteriologically confirmed. Better understanding of this phenomenon is required to improve tuberculosis control. OBJECTIVES: To determine the percentage of smear negative presumptive tuberculosis patients that would be diagnosed by GeneXpert; compare clinical characteristics of patients diagnosed as tuberculosis cases; and review the impact that the current single government physician and a reconstituted Tuberculosis Diagnostic committee (expert panel) may have on tuberculosis over-diagnosis. DESIGN: This a cross-sectional study of 152 patients 15-85 years old with two negative Direct Sputum Smear Microscopy results, with abnormal chest X-ray who underwent GeneXpert testing and review by an expert panel. RESULTS: Thirty-two percent (48/152) of the sample were Xpert positive and 93% (97/104) of GeneXpert negatives were clinically diagnosed by a single physician. Typical symptoms and X-ray findings were higher in bacteriologically confirmed tuberculosis. When compared to the GeneXpert results the Expert panel's sensitivity for active tuberculosis was high (97.5%, 39/40), specificity was low (40.2%, 35/87). CONCLUSION: Using the GeneXpert would increase the level of bacteriologically confirmed tuberculosis substantially among presumptive tuberculosis. An expert panel will greatly reduce over-diagnosis usually seen when a decision is made by a single physician.

Measuring and addressing the childhood tuberculosis reporting gaps in Pakistan: The first ever national inventory study among children.

INTRODUCTION: Tuberculosis in children may be difficult to diagnose and is often not reported to routine surveillance systems. Understanding and addressing the tuberculosis (TB) case detection and reporting gaps strengthens national routine TB surveillance systems. OBJECTIVE: The present study aimed to measure the percentage of childhood TB cases that are diagnosed but not reported to the national surveillance system in Pakistan. DESIGN: The study design was cross sectional. The study was nationwide in 12 selected districts across Pakistan, each representing a cluster. Health facilities that diagnose and treat childhood TB from all sectors were mapped and invited to participate. Lists of child TB cases were created for the study period (April-June 2016) from all study facilities and compared against the list of child TB cases notified to the national TB surveillance system for the same districts and the same period. RESULTS: All public and private health facilities were mapped across 12 sampled districts in Pakistan and those providing health services to child TB cases were included in the study. From all private health facilities, 7,125 children were found with presumptive TB during the study period. Of them, 5,258 were diagnosed with tuberculosis: 11% were bacteriologically-confirmed and 89% clinically-diagnosed; only 4% were notified to National TB Control Program. An additional 1,267 children with TB were also registered in the National TB Control Program. Underreporting was measured to be 78%. CONCLUSION: This is the first nationwide childhood TB inventory study globally and confirmed that childhood TB underreporting is very high in Pakistan. TB surveillance in the country must be strengthened to address this, with particular attention to guiding and supporting general practitioners and pediatricians to notify their TB cases.

Mycobacterium tuberculosis and Pseudoramibacter alactolyticus coinfection in brain after dental extraction: A case report.

INTRODUCTION: More than 1200 different types of microbes were found in the human mouth, only some of these microorganisms were associated with intracranial bacterial infection. However, there are limited data available about the Pseudoramibacter alactolyticus (P alactolyticus) or Mycobacterium tuberculosis (MTB) intracranial infections oral origin. PATIENT CONCERNS: Here, we reported a rarely case with P alactolyticus and MTB coinfection in central nervous after dental extraction. The 44-year-old man presented with progressive headache over the last 2 weeks and a sustained fever >39°C, with a dental extraction performed 2 days before the onset of headache. DIAGNOSIS: P alactolyticus and MTB were confirmed by real-time polymerase chain reaction targeting the16S ribosomal RNA gene. The presence of MTB was also demonstrated by positive acid-fast staining of the purulent discharge. INTERVENTIONS: The patient was treated by metronidazole and anti-TB treatment OUTCOMES:: The patient fully recovered without sequela. CONCLUSION: In conclusion there should be awareness of the possibility of P alactolyticus or MTB intracranial infections following tooth extraction.

Serum proteome profiles to differentiate Crohn disease from intestinal tuberculosis and primary intestinal lymphoma: A pilot study.

The differential diagnosis of Crohn disease (CD) from intestinal tuberculosis (ITB) and primary intestinal lymphoma (PIL) is challenging in patients who exhibit atypical clinical characteristics. The aim of the present study was to explore the serum proteome profiles of CD, PIL and ITB and to identify their differentiations.Treatment-naïve patients with CD (n = 10), PIL (n = 10) and ITB (n = 10) were enrolled in the present study. Differentially expressed proteins (DEPs) in patient serum samples were compared between groups using tandem mass tag labeled proteomic technology. A principal component analysis (PCA) plot and volcano maps were also visualized. Functional pathway analysis was performed using Reactome. The Area under the Curve (AUC) was calculated for each DEP.A total of 818 proteins were identified through proteomic quantification. Among them, 108 DEPs were identified to be differentiated between CD and ITB, 105 proteins between CD and PIL and 55 proteins between ITB and PIL. The proteome from the three groups was distinguishable in the PCA plot. The results revealed that 19, 12, and 10 proteins (AUC ≥ 0.95) were differentially expressed between CD and PIL, CD and ITB, and PIL and ITB, respectively. Among these DEPs, tumor necrosis factor ligand superfamily member 13 was higher in CD than in ITB and PIL. Peroxiredoxin-5, T-complex protein 1 subunit Gamma, CutA, and Fibulin-5 were increased in CD and PIL when compared with ITB. The levels of fibrinogen chains were also significantly higher in patients with PIL compared with CD.The current study demonstrated that serum proteome was distinguishable among patients with CD, PIL, and ITB. The identified proteins may assist in the clinical differentiation among them.