Статті в журналах: "Anti-TB Therapy"

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Ye, L., L. Wu, J. Tang, R. Mao, and Q. Cao. "P502 Different presentation of tuberculosis associated with anti-TNF therapy among patients with Inflammatory Bowel Disease in endemic area: observation from China." Journal of Crohn's and Colitis 16, Supplement_1 (January 1, 2022): i464. http://dx.doi.org/10.1093/ecco-jcc/jjab232.629.

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Abstract Background Anti-tumor necrosis factor (TNF) therapy increased the risk of tuberculosis(TB), and the characteristic clinical feature of western patients with inflammatory bowel disease (IBD) receiving anti-TNF therapy were predominantly extrapulmonary TB. We aimed to analyze the clinical features of patients with IBD who in TB-endemic area (China) that developed active tuberculosis after receiving anti-TNF therapy. Methods Patients from 9 hospital in 7 provinces developed active TB after the initial treatment with infliximab. Demographics, interval between the time at the first dose of anti-TNF therapy and active TB development, tests for latent TB infection (LTBI), concomitant medications, and the details of diagnosis were analyzed in our study. The diagnosis of active TB and LTBI were made based on comprehensive evaluation including TB skin test (TST), interferon gamma releasing assay (IGRA), X-ray test and computed tomography (CT). Results Totally 43 patients developed active TB during infliximab therapy. Among 43 patients, 6 patients had a past TB history and 11 patients were confirmed as LTBI before infliximab treatment. Six patients with LTBI received anti-TB prophylaxis as the same time as anti-TNF treatment. The mean time between initiation of infliximab therapy and active tuberculosis diagnosis in patients with LTBI was significantly shorter than patients without LTBI (216.9±83.2 days versus 410.9±220.3 days, p=0.042). Among 43 active TB patients, 29 patients (29/43, 67.4%) had isolated pulmonary tuberculosis and 11 patients (11/43, 25.6%) had pulmonary TB concomitantly with other organ involvement. Conclusion IBD patients with LTBI develop TB earlier than those without LTBI during anti-TNF treatment, and history of treatment and anti-TB prophylaxis didn’t fully prevent active TB. The most common disease site is lung in China, most of cases were diagnosed by imaging. Chinese physicians should be aware of the potential for TB development during anti-TNF therapy, especially pulmonary tuberculosis.

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Mandic, Dragana, Radmila Curcic, Gordana Radosavljevic, Nemanja Damjanov, Dusan Stefanovic, Igor Mitic, and Aleksandar Dimic. "Recommendations for tuberculosis screening before and during treatment with tumour necrosis factor inhibitors." Srpski arhiv za celokupno lekarstvo 137, no. 3-4 (2009): 211–16. http://dx.doi.org/10.2298/sarh0904211m.

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Patients with an autoimmune disease, such as rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, Crohn's disease, ulcerative colitis, uveitis or psoriasis, and treated with the anti-tumour necrosis factor (TNF) alpha inhibitors are at high risk of developing various infections including tuberculosis (TB). Serious infections are the result of the patients' immunocompromised status that is caused by the primary disease itself, as well as by previous immunosuppressive therapy. In order to decrease the risk of developing TB, prior to the introduction of the anti-TNF alpha therapy, all patients should undergo screening for TB. Experiences from the countries that have already implemented recommendations for TB screening show a significant decrease in TB occurrence in the anti-TNF alpha treated patients. The PPD skin test result is considered positive if induration is of size ?5 mm. The BCG vaccine applied at birth has no effect on interpretation of PPD test results in adults. The diagnosis of active TB is contraindicated for the introduction of the anti-TNF alpha therapy; first, such patients should receive the TB treatment; and 6 months after the completion of the TB treatment, the introduction of the anti-TNF alpha therapy may be considered. The patients with the diagnosis of the latent TB infection (LTBI) should not immediately start with the anti-TNF alpha therapy, but they should first receive the TB chemoprophylaxis; not earlier than a month upon the introduction of the TB chemoprophylaxis, the anti-TNF alpha therapy may be introduced. The first TB follow-up screening during the anti-TNF alpha therapy is recommended 6 months after the anti-TNF alpha therapy has been introduced and the next one should be scheduled after 12 months.

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Mazlun, Muhamad Harith, Siti Fatimah Sabran, Maryati Mohamed, Mohd Fadzelly Abu Bakar, and Zunoliza Abdullah. "Phenolic Compounds as Promising Drug Candidates in Tuberculosis Therapy." Molecules 24, no. 13 (July 4, 2019): 2449. http://dx.doi.org/10.3390/molecules24132449.

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Tuberculosis (TB), caused by Mycobacterium tuberculosis (MTB) remains one of the deadliest, infectious diseases worldwide. The detrimental effects caused by the existing anti-TB drugs to TB patients and the emergence of resistance strains of M. tuberculosis has driven efforts from natural products researchers around the globe in discovering novel anti-TB drugs that are more efficacious and with less side effects. There were eleven main review publications that focused on natural products with anti-TB potentials. However, none of them specifically emphasized antimycobacterial phenolic compounds. Thus, the current review’s main objective is to highlight and summarize phenolic compounds found active against mycobacteria from 2000 to 2017. Based on the past studies in the electronic databases, the present review also focuses on several test organisms used in TB researches and their different distinct properties, a few types of in vitro TB bioassay and comparison between their strengths and drawbacks, different methods of extraction, fractionation and isolation, ways of characterizing and identifying isolated compounds and the mechanism of actions of anti-TB phenolic compounds as reported in the literature.

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Ibrahim, Chandra Satria. "Anti-TB Drug for Tuberculosis Spondylitis." Neurologico Spinale Medico Chirurgico 1, no. 2 (August 7, 2018): 18. http://dx.doi.org/10.15562/nsmc.v1i2.96.

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Tuberculosis spondylitis, or spinal tuberculosis, is a disease that occurs throughout the world. Conservative therapy that is given to patients with spinal tuberculosis actually gives good results, but in certain cases, it requires surgery and rehabilitation therapy. The incidence of tuberculous spondylitis varies worldwide and is usually associated with the quality of available public health service facilities as well as the social factors in the country. Currently, tuberculosis spondylitis is a major source of morbidity and mortality in underdeveloped countries, especially in Asia, where malnutrition and population still remains a major issue. The goals of therapy in tuberculosis spondylitis are eradication of infection or at least to prevent neurological deterioration, and prevention or correction of a deformity or neurological deficit. Administration of anti-tuberculosis drugs is a major therapeutic principle in all cases including spinal tuberculosis. Early administration of anti-tuberculous drugs can significantly reduce morbidity and mortality.

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Noguera-Julian, Antoni, Joan Calzada-Hernández, Folke Brinkmann, Robindra Basu Roy, Olga Bilogortseva, Michael Buettcher, Isabel Carvalho та ін. "Tuberculosis Disease in Children and Adolescents on Therapy With Antitumor Necrosis Factor-ɑ Agents: A Collaborative, Multicenter Paediatric Tuberculosis Network European Trials Group (ptbnet) Study". Clinical Infectious Diseases 71, № 10 (4 грудня 2019): 2561–69. http://dx.doi.org/10.1093/cid/ciz1138.

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Abstract Background In adults, anti–tumor necrosis factor-α (TNF-α) therapy is associated with progression of latent tuberculosis (TB) infection (LTBI) to TB disease, but pediatric data are limited. Methods Retrospective multicenter study within the Paediatric Tuberculosis Network European Trials Group, capturing patients <18 years who developed TB disease during anti–TNF-α therapy. Results Sixty-six tertiary healthcare institutions providing care for children with TB participated. Nineteen cases were identified: Crohn’s disease (n = 8; 42%) and juvenile idiopathic arthritis (n = 6; 32%) were the commonest underlying conditions. Immune-based TB screening (tuberculin skin test and/or interferon-γ release assay) was performed in 15 patients before commencing anti–TNF-α therapy but only identified 1 LTBI case; 13 patients were already receiving immunosuppressants at the time of screening. The median interval between starting anti–TNF-α therapy and TB diagnosis was 13.1 (IQR, 7.1–20.3) months. All cases presented with severe disease, predominantly miliary TB (n = 14; 78%). One case was diagnosed postmortem. TB was microbiologically confirmed in 15 cases (79%). The median duration of anti-TB treatment was 50 (IQR, 46–66) weeks. Five of 15 (33%) cases who had completed TB treatment had long-term sequelae. Conclusions LTBI screening is frequently false-negative in this patient population, likely due to immunosuppressants impairing test performance. Therefore, patients with immune-mediated diseases should be screened for LTBI at the point of diagnosis, before commencing immunosuppressive medication. Children on anti–TNF-α therapy are prone to severe TB disease and significant long-term morbidity. Those observations underscore the need for robust LTBI screening programs in this high-risk patient population, even in low-TB-prevalence settings.

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Kumar, P., S. K. Vuyyuru, B. Kante, P. Sahu, S. Goyal, D. Madhu, S. Jain, et al. "P531 Stringent screening strategy significantly reduces reactivation rate of Tuberculosis in Patients with Inflammatory Bowel Disease on anti-TNF therapy in a TB endemic region." Journal of Crohn's and Colitis 16, Supplement_1 (January 1, 2022): i484. http://dx.doi.org/10.1093/ecco-jcc/jjab232.658.

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Abstract Background Anti-tumour necrosis factor (anti-TNF) therapy use in patients with inflammatory bowel disease (IBD) leads to increased risk of tuberculosis (TB) reactivation despite LTB screening, especially in TB endemic regions. We evaluated the effect of stringent screening strategy and latent tuberculosis (LTB) prophylaxis on TB reactivation. Methods We performed an ambispective comparison between patients who were started on anti-TNF therapy after January 2019 (Cohort A) and between Jan 2005-Dec 2018 (Cohort B). Cohort A patients were subjected to stringent screening criteria which included all: history of past TB/recent contact with active TB, CT (computed tomography) chest, IGRA (interferon-gamma release assay), TST (tuberculin skin test), and if any positive were given chemoprophylaxis. A cohort comparison was done to evaluate for risk reduction of TB following the stringent screening strategy. Results One hundred seventy-one patients (63-Ulcerative colitis/108-Crohn’s disease; mean age diagnosis-28.5±13.4 years; 60% males; median follow-up duration after anti-TNF:33months [interquartile range, 23–57 months]) were included. Among 112 in Cohort B 22(19.6%) had LTB and 19(17%) developed TB. In comparison, 26(44%) had LTB and only 1(1.7%) developed TB in Cohort A (p<0.01). On survival analysis, patients in Cohort B had a higher probability of TB reactivation compared to Cohort A at 5 years of follow up, HR-14.39 (95% CI,1.88- 109.81[p=0.010]) after adjusting for gender, age at anti-TNF therapy initiation, concomitant immunosuppression, the total number of anti-TNF doses and therapy escalation. *Log rank p value=0.006 Figure 1: Kaplan Meier curve analysis for probability of remaining free from tuberculosis between patients who were started on anti- TNF therapy till January 2019 (Cohort B) and those who were started on anti-TNF after January 2019 (Cohort A). *Log rank p value=0.02 Figure 2: Kaplan Meier curve analysis for probability of remaining free from tuberculosis between patients who had incomplete latent TB screening and those with complete TB screening. Conclusion The high risk of TB reactivation with anti-TNF therapy in TB endemic regions can be significantly mitigated with stringent LTB screening and chemoprophylaxis.

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Paz, M. E. Pinto, L. Bueno Lazo, D. Carrera Palao, D. F. Pinto Ruiz, M. R. Huaman, and A. M. Quispe. "Efficacy and safety of oncoplastic surgery plus drug therapy for chronic tuberculous granulomatous mastitis." International Journal of Tuberculosis and Lung Disease 24, no. 6 (June 1, 2020): 585–90. http://dx.doi.org/10.5588/ijtld.19.0478.

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BACKGROUND: Chronic tuberculous granulomatous mastitis (CTGM) is a rare form of tuberculosis (TB) treated primarily with anti-TB drugs. Oncoplastic surgery (OS) has been proposed as adjuvant therapy for CTGM.METHOD: We followed for 1 year every CTGM patients and assessed the efficacy (defined as non-recurrence and no need for corticosteroids) and safety attributable to the standard anti-TB drugs therapy with and without OS.RESULTS: We analysed 128 CTGM cases, including 78 (61%) treated with OS plus anti-TB drugs and 50 (39%) with anti-TB drugs only. We observed a significantly higher efficacy among those exposed vs. unexposed to OS (100% vs. 92%; prevalence ratio [PR] 1.09, 95% CI 1.00–1.18), with no difference in the number of complications (21% vs. 8%; PR 2.56, 95% CI 0.91–7.26). We also observed that the incidence of post-operative complications decreased by 50% when OS was postponed from after Month 1 to after completing Month 2 of anti-TB drugs treatment (19% to 8%; PR 0.46, 95% CI 0.13–1.62).CONCLUSION: OS appears to represent an efficacious and safe adjuvant therapy when combined with anti-TB drugs in the treatment of CTGM patients, but clinical trials are needed to prove this observation.

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Sugiyama, Yuya, Nobuhiro Ueno, Shion Tachibana, Yu Kobayashi, Yuki Murakami, Takahiro Sasaki, Aki Sakatani, et al. "The safety of vedolizumab in a patient with Crohn’s disease who developed anti-TNF-alpha agent associated latent tuberculosis infection reactivation: A case report." Medicine 102, no. 28 (July 14, 2023): e34331. http://dx.doi.org/10.1097/md.0000000000034331.

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Rationale: Latent tuberculosis (TB) infection screening before inducing anti-tumor necrosis factor (anti-TNF) alpha agents is important to prevent TB reactivation. However, latent TB infection reactivation may still occur, and the ideal therapeutic strategy for patients with inflammatory bowel disease (IBD) who develop active TB infection has not been established. Vedolizumab (VDZ) has a good safety profile, with low incidence rates of serious infections. However, its safety in patients with latent TB infection reactivation associated with anti-TNF-alpha agents remains unknown. Patient concerns: A 21-year-old Vietnamese male patient presented to our hospital with hemorrhagic stool. He had no personal or family history of IBD or TB. Diagnoses: Colonoscopy revealed multiple longitudinal ulcers and a cobblestone appearance in the terminal ileum, as well as multiple small erosions and aphtha throughout the colon. Computed tomography revealed a right lung nodular lesion. Serological interferon-gamma release assay and several culture tests were all negative. Thus, he was diagnosed with ileocolonic Crohn’s disease (CD) without TB. Interventions: The intravenous anti-TNF-alpha agent administration with an immunomodulator was initiated. Outcomes: Computed tomography revealed nodular lesion expansion at the right lung, and serological interferon-gamma release assay was positive. He was diagnosed with latent TB infection reactivation. Anti-TNF-alpha agent with an immunomodulator was immediately discontinued, and anti-TB therapy was initiated. His endoscopic findings were still active, and VDZ was selected for maintenance therapy because VDZ has a favorable safety profile with low incidence rates of serious infections. Consequently, mucosal healing was achieved without active TB relapse. Lessons: This case report presented a patient in whom VDZ was continued as maintenance therapy without inducing TB relapse in a patient with CD who developed latent TB infection reactivation associated with anti-TNF-alpha agents and summarized the safety profile of VDZ for patients with IBD with active or latent TB infection. VDZ may be a safe option for induction and maintenance therapy in patients with CD, even in cases with latent TB infection reactivation.

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Hidayat, Edi Yanuarto, Nasirun Zulqarnain, and Muchlis Achsan Udji Sofro. "Perbandingan Gambaran Foto Toraks Pasien TB-HIV Dua dan Enam Bulan Pengobatan Anti-Tuberkulosis + Anti-Retroviral." Jurnal Radiologi Indonesia 1, no. 2 (September 1, 2015): 91–98. http://dx.doi.org/10.33748/jradidn.v1i2.12.

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Background: Tuberculosis (TB) remains a global health issues and mostly located in developing countries. As cases of HIV/AIDS increase every year, it is estimated that TB cases also increase. TB is the leading cause of death in people with HIV and HIV infection, and became the biggest risk factor in the conversion of latent TB cases to become active TB. Radiographic manifestation of TB in AIDS patients depends on antiretroviral therapy (ART).Materials and Methods: This is an observational study which compares 2 and 6 months chest radiographs from TB-HIV patients with anti-TB drugs+ART in 24 adults patients with TB-HIV in the Internal Medicine Polyclinic and Ward at Dr. Kariadi Hospital and BKPM Semarang.Result: Most patients were male with 19 subjects (79.2%). The large stage group based on the proportion of AIDS cases is 20-29 years (45.84%). After 6 months of anti-TB drugs+ART there were radiographic improvement in consolidation, cavitation, lymphadenopathy and pleural e?usion. Wilcoxon Signed Ranks Test showed signifcant changes in consolidation and lymphadenopathy between 2 and 6 months of anti-TB drugs+ART, but no signifcant changes in cavity and pleural e?usion.Discussion: At 6 months chest radiographs examination, not all patients with anti-TB drugs+ART show radiographic improvement. Therefore, the decision to stop TB therapy in HIV patients in 6 months time seems inadequate.Conclusion: There are signifcant change between 2 and 6 months of anti-TB drugs+ART with radiographic improvement are consolidation and lymphadenopathy.

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Frolova, K. S., and S. E. Borisov. "RISK OF DEVELOPING ACTIVE TB IN IBD PATIENTS TREATED WITH ATNI-TNF." Koloproktologia, no. 1 (March 30, 2018): 49–56. http://dx.doi.org/10.33878/2073-7556-2018-0-1-49-56.

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AIM. To develop an investigation complex for IBD-patients with the anti-TNF therapy to decrease the risk of active TB. METHODS. In Moscow Research and Clinical Center for TB Control 454 patients with IBD were screened prior to initiation of anti-TNF treatment and 167 (36,8%) of them - during the anti-TNF therapy. Tuberculin skin test (TST) and chest radiography were used for screening and evaluation of pulmonary adverse effects (every 6 months and additionally in cases of any respiratory signs). RESULTS. Of 454 patients investigated during screening X-ray, chest radiography findings were detected in 29 (6,4%), which required additional investigation, among them in 14 patients, findings considered as residual TB lesions. In the other 15 patients, the radiographic findings caused by previous non-specific pulmonary infections. Positive TST implicates preventive antituberculosis therapy, which was provided 37 patients (before and under anti-TNF therapy). During provided to 167 patients the anti-TNF therapy, were developed pulmonary adverse effects: 10 incidences of active TB lung infection 3 case of sarcoidosis, 1 case of fibrosing alveolitis, and two case of non-CONCLUSION. The patients with IBD, treated by anti-TNF therapy, have a risk of development of a wide variety of infectious and non-infectious pulmonary complications, including TB. It is therefore highly important to carefully monitor the patients prior and during the anti-TNF therapy (every 6 months) for a timely detection of pulmonary conditions potentially associated with the treatment.

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Yoo, Jung-Wan, Kyung-Wook Jo, Bo-Hyung Kang, Mi Young Kim, Bin Yoo, Chang-Keun Lee, Yong-Gil Kim та ін. "Mycobacterial diseases developed during anti-tumour necrosis factor-α therapy". European Respiratory Journal 44, № 5 (7 серпня 2014): 1289–95. http://dx.doi.org/10.1183/09031936.00063514.

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Nontuberculous mycobacterial (NTM) disease and tuberculosis (TB) develop during anti-tumour necrosis factor (TNF)-α therapy. We compared clinical characteristics and outcomes between the two diseases.A total of 1165 patients were screened for TB and treated with TNF-α antagonists from July 2004 to July 2013 for the following conditions: inflammatory bowel disease (n = 422), rheumatoid arthritis (n = 320), and ankylosing spondylitis (n = 389).TB and NTM disease were diagnosed at baseline screening in four and three patients, respectively, and developed during anti-TNF-α therapy in 19 and six patients, respectively. The incidence rate of TB and NTM disease was 747.7 per 100 000 and 238.2 per 100 000 person-years, respectively. Patients with NTM disease were older, with a greater proportion of females. All cases of NTM disease involved the lung, with rheumatoid arthritis (83.3%) being the most frequent underlying disease. The most common radiological feature was consolidation in NTM disease, and honeycombing was present in two rheumatoid arthritis patients with NTM disease. The most common pathogen wasMycobacterium intracellulare(n = 3) followed byMycobacterium avium(n = 2). Both the NTM and TB group showed favourable outcomes.The clinical characteristics differed between NTM disease and TB that developed on anti-TNF-α agents, but clinical outcomes were favourable in both diseases.

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Maarman, Gerald` J. "Could melatonin be an adjunct therapy for post-TB lung disease?" Melatonin Research 4, no. 3 (September 30, 2021): 431–39. http://dx.doi.org/10.32794/mr112500103.

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Post-tuberculosis (post-TB) lung disease is a complex interplay between organism, host, and environmental factors, and it affects long-term respiratory health. It associates with underlying processes such as inflammation, fibrosis, and oxidative stress. Decades of research has demonstrated melatonin as a potent anti-inflammatory, anti-fibrotic, antioxidant, and vasodilatory agent. These effects have been observed in numerous experimental and clinical models of lung diseases. Moreover, melatonin has significant anti-microbial activity, which has also been observed in the context of TB bacterial growth. It is worth pointing out that these effects of melatonin are a reminder of the pathologic processes that underpin post-TB lung disease. Based on the intriguing evidence presented and discussed in this paper, melatonin could be considered a safe, affordable, and adjunct therapy against post-TB lung disease. Melatonin may provide health benefits in this context, mediated via its anti-inflammatory, anti-fibrotic, vasodilatory, antimicrobial and antioxidant properties.

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Tan, J., N. Hejazifar, E. Vantomme, and K. Tsoi. "A175 RECURRENT GASTROINTESTINAL BLEED – A LATE MANIFESTATION OF COLONIC TUBERCULOSIS TREATED CONSERVATIVELY." Journal of the Canadian Association of Gastroenterology 3, Supplement_1 (February 2020): 41–42. http://dx.doi.org/10.1093/jcag/gwz047.174.

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Abstract Background The incidence of active tuberculosis (TB) in Canada is 4.8 per 100000 persons. Globally, gastrointestinal (GI) TB is rare and accounts for 5% of all extra-pulmonary cases. Clinical manifestations of intestinal TB include weight loss (75%), abdominal pain (54%), and changes in bowel habits (50%). GI bleeding has been observed in 5–15% of confirmed cases of colorectal TB. The cecum is the most common site of involvement, with the most common gross finding on colonoscopy being ulcerations (88%), and the least common being polypoid lesions (10%). Intestinal TB is treated the same as pulmonary TB, with endoscopic healing observed in the majority of cases following 9 months of anti-TB therapy. Surgery is entertained in cases of non-resolving obstruction, perforation, or fistula formation. Aims Management of stable, recurrent, large volume GI bleeding in TB colitis is not well established. We report such a case that resolved solely by anti-TB regimen. Methods Case report Results A 56 year old man with chronic kidney disease presented with cachexia and 40 pound weight loss over 6 months after return from India. He underwent computerized tomography scan of his chest, abdomen and pelvis. Multiple, large, cavitary lesions in the right upper lung lobe were seen, and confirmed to be TB by bronchoalveolar lavage. Abdominal imaging identified moderate circumferential wall thickening at the cecum concerning for intestinal TB. These findings were also retrospectively noted on a review of an abdominal MRI 4 months prior. His course was complicated by episodes of large, alternating bright red blood per rectum and melena stools starting 5 days after initiation of anti-TB therapy. Colonoscopy revealed polypoid lesions in the cecum as well as blood throughout the colon, with no active source of bleeding. Surgery was considered for ongoing bleeding, however, because biopsies were negative for malignancy and positive on acid-fast stain, he continued conservative management with blood transfusions and anti-TB therapy. GI bleeding decreased significantly within the first 2 weeks, and resolved by day 25. He completed 1 year of anti-TB therapy, with no signs of colitis detected radiographically at the 6-month mark. Conclusions To our knowledge, this is the first report of GI bleeding as a very late manifestation of colonic TB, resolved with anti-TB therapy alone. Time from initial evidence of intestinal TB on imaging to the first bleed was 159 days, and time from initial symptoms was 6 months. As polypoid lesions are the least common gross finding on colonoscopy, a high degree of suspicion should be held in the right clinical setting. Surgical management should be considered only after conventional anti-TB therapy has failed. Funding Agencies None

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Oshima, M., A. Fukui, and Y. Takakura. "A CASE OF TUBERCULOUS TENOSYNOVITIS IN A PATIENT WITH SYSTEMIC LUPUS ERYTHEMATOSUS." Hand Surgery 09, no. 01 (July 2004): 109–13. http://dx.doi.org/10.1142/s0218810404002042.

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A 52-year-old woman with systemic lupus erythematosus (SLE) was infected with tuberculosis (TB) on her forearm and hand, after 16 years of steroid therapy. Debridements and anti-TB therapy were performed successfully. Recently, the risk of significant morbidity from TB has been on the rise; this appears to be a complication of steroid therapy used to treat AIDS and some collagen vascular diseases. It is thought that steroid therapy causes an increased risk of TB. In this paper, we report our experience of this SLE patient who developed tuberculous tenosynovitis. We suggest that TB infection must be considered in the differential diagnosis whenever a patient presents with a chronic wrist or hand inflammation that is non-responsive to steroid treatment. Once TB infection is suspected, both histopathological and bacteriological examinations should be performed. Emergent treatment includes surgical debridement and the institution of early anti-TB therapy immediately after completing histopathological examination.

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Kim, Minji Jennifer, Nicholas Jones, and Laura R. Steeples. "Miliary tuberculosis developing during adalimumab treatment for Behçet’s disease with uveitis." BMJ Case Reports 11, no. 1 (December 2018): e226772. http://dx.doi.org/10.1136/bcr-2018-226772.

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Tumour necrosis factor-alpha (TNF-α) is a key proinflammatory cytokine in non-infective uveitis (NIU). Adalimumab, an anti-TNF-α monoclonal antibody, is approved for the treatment of severe NIU by the European Medicines Agency. There is a recognised risk of serious infections, including tuberculosis (TB), during anti-TNF-α therapy in systemic immune-mediated diseases. We describe miliary pulmonary TB during adalimumab therapy for severe NIU. To our knowledge, this is the first detailed report of this complication in a patient with uveitis. We present the challenges of managing vision-threatening uveitis during life-threatening infection necessitating withdrawal of adalimumab and oral immunosuppression therapy. Uveitis activity was controlled during anti-TB therapy with oral corticosteroid therapy.

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Huang, Xiaojing, Xiao Zheng, and Chenyang Shen. "Antiviral Therapy with Entecavir following Antituberculosis Therapy Alleviates Liver Injury and Restores Innate Immunity in Tuberculosis Patients Coinfected with Hepatitis B Virus." Evidence-Based Complementary and Alternative Medicine 2021 (November 2, 2021): 1–8. http://dx.doi.org/10.1155/2021/2884151.

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Objective. Coinfection of tuberculosis (TB) and viral hepatitis may increase the risk of antituberculosis treatment-induced hepatotoxicity, which is regarded as a common cause of termination of the first-line antituberculosis drugs. The study aimed at investigating the protective effects of antiviral therapy on the liver and innate immunity in patients with TB-HBV coinfection. Methods. A total of 100 patients with TB-HBV coinfection were recruited and split into antituberculosis and antiviral groups, 50 per group, according to odd or even date of hospital admission from December 2019 to October 2020. The patients in the anti-TB group received antituberculosis therapy, and those in the antiviral group received antiviral therapy. The clinical effectiveness; HBV-DNA negative conversion rate; liver function assessment involving alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin (TBIL); immune function evaluation including CD4+, CD8+, CD4+/CD8+, and CD3+ T cells; inflammatory cytokines containing tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interferon-γ (IFN-γ); and intestinal microflora including bifidobacterium, lactobacillus, enterobacterium, enterococcus, and clostridium were main outcome measures after treatment. Results. It was found that the total response rate in the antiviral group was significantly higher than the anti-TB group after treatment (χ2 = 3.157, P = 0.017 ). There was a significant difference in HBV-DNA negative conversion rates between the antiviral group and anti-TB group (82% vs. 58%, χ2 = 6.384, P = 0.001 ). The ALT, AST, and TBIL in the two groups were all increased after treatment ( P < 0.05 ), but the antiviral group indicated a rise of the above indices compared to the anti-TB group ( P < 0.05 ). The two groups showed a rise on the concentration of CD3+, CD4+, and CD4+/CD8+ T cells and a decline on the CD8+ T cells after treatment ( P < 0.05 ), but these changes in the antiviral group were more evident to those in the anti-TB group ( P < 0.05 ). There was an increase on the IFN-γ level and decrease on the TNF-α and IL-6 levels in both groups after treatment ( P < 0.05 ), but the antiviral group revealed a higher level of IFN-γ with lower levels of TNF-α and IL-6 compared to the anti-TB group ( P < 0.05 ). After treatment, the number of bifidobacteria and lactobacilli was increased, and the number of enterobacteria, enterococci, and clostridium were decreased in the two groups ( P < 0.05 ), while these changes in the antiviral group were more remarkable compared to the anti-TB group ( P < 0.05 ). There was no significant difference in the incidence of adverse reactions between the two groups (χ2 = 0.267, P = 0.731 ). Conclusion. Antiviral therapy for tuberculosis-HBV coinfected patients could inhibit HBV replication, providing protection against liver damage, improving innate immunity, and balancing intestinal microflora.

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Prosvetov, Yu V., A. Yu Gusarova, S. S. Barinov, and A. V. Husarova. "CORRECTION OF SOME SIDE EFFECTS TO ANTI-TUBERCULOSIS THERAPY IN MODERN CONDITIONS." Modern medical technology, no. 2(53) (June 10, 2022): 19–25. http://dx.doi.org/10.34287/mmt.2(53).2022.4.

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Introduction. Tuberculosis has not been eradicated in any country in the world. Chemotherapy plays a leading role in this fight. In the last two decades, the level of chemoresistant tuberculosis has increased significantly, contributing to an increase in the total number of side effects, often severe and widespread. The aim of the study. Improving the effectiveness of treatment and quality of life of TB patients. This is based on scientific substantiation and development of methods for drug correction of toxic side effects of anti-TB therapy. Materials and methods. 818 cases of complications from the use of anti-TB therapy were analyzed among patients treated at Zaporizhzhia Regional Clinical TB Dispensary between 2012 and 2016. Side effects increased over these years, due to an increased attention to pharmacovigilance. Results. During the treatment of patients with pulmonary TB with preserved sensitivity to anti-TB therapy, side effects occurred in 48.8% of cases and in chemoresistant forms 51.2%. Patients with resistant forms of the process which were assigned to the 4th category of treatment predominated with complications of anti-TB therapy. Their percentage was 55.1%, which was 10.2% more than patients with preserved sensitivity. The structure of side effects was dominated by hepatotoxic reactions (36.0%) which were most often (28.0%) associated with the use of pyrazinamide and later returned to normal from the use of ademethionine. In total, the use of pyrazinamide resulted in 40.4% of cases of side effects. Conclusions. The course of ademethionine helps to normalize clinical and laboratory parameters, regression of symptoms of toxic liver disease and improves the quality of life of patients with chemoresistant tuberculosis with toxic side effects of anti-TB therapy, which significantly reduces the length of hospital stay and increases treatment efficiency with compliance.

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Zeller, Michelle P., Jan H. Beumer, Susan M. Christner, and Anargyros Xenocostas. "Pharmacokinetics of Dasatinib in a Patient with Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia During Treatment with Anti-Tuberculosis Therapy." Blood 118, no. 21 (November 18, 2011): 5006. http://dx.doi.org/10.1182/blood.v118.21.5006.5006.

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Abstract Abstract 5006 Objectives: Dasatinib is a second generation protein-tyrosine kinase inhibitor (TKI) indicated for first line treatment of chronic myeloid leukemia (CML) and second line treatment of Philadelphia chromosome-positive acute lymphoblastic leukemia (ALL) in patients who are imatinib resistant or intolerant. In this study, we present the case of a patient with Philadelphia chromosome- positive ALL, intolerant to imatinib, who developed reactivated tuberculosis (TB) while receiving dasatinib during maintenance chemotherapy. The purpose of our study was to determine the effects of concomitant anti-TB therapy on dasatinib exposure by measuring plasma dasatinib levels using three different oral doses of the drug in this patient. Methods: The patient was treated with isoniazid, rifampin, ethambutol, pyrazinamide and pyridoxine for 2 months, followed by isoniazid, rifampin and pyridoxine for an additional 4 months. Dasatinib therapy was continued at the initiation of TB therapy using 100 mg po od, and titrated by 50 mg increments to 200 mg po od. Dasatinib plasma levels were measured prior to initiating anti-TB treatment and at regular intervals during concomitant treatment using three different dasatinib doses. Results: Eight days after initiation of anti-tuberculosis therapy, the apparent clearance of dasatinib had increased from 1410 to 2174 L/h at 100 mg. However, at 150 mg and 200 mg doses, apparent clearance had decreased to levels lower than baseline. As expected, the direction of peak plasma concentration changes was inverse to the changes in apparent clearance: Cmax values were 30 at baseline, and 22, 46, 102 ng/mL for the 3 doses of dasatinib during anti-TB therapy, respectively. Conclusions: Our findings suggest dasatinib clearance is increased by approximately 50% shortly after initiating anti-tuberculosis treatment and increasing the dose of dasatinib during anti-TB therapy was able to restore dasatinib plasma levels to those observed before initiation of anti-TB therapy. (This work was supported by an unrestricted grant from Bristol Myers Squib) Disclosures: No relevant conflicts of interest to declare.

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Nasser, Abdullah Al Shekeili, Muhammad Tareq Khan Yaseer, and Ismail Mousa Tia Khalid. "Use of Corticosteroid as an Adjunct with Antitubercular Therapy in the Management of Miliary Tuberculosis Associated with Organizing PneumoniaA Case Report." Journal of Clinical Cases & Reports 2, no. 1 (January 31, 2019): 5–11. http://dx.doi.org/10.46619/joccr.2019.2-1029.

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In miliary TB, the role of steroid remains to be unclear. Till date, extremely limited studies have been conducted to evaluate corticosteroids’ role in miliary TB. We report a patient with miliary TB and co-existing organizing pneumonia (OP), a condition that was managed successfully by anti-TB chemotherapy in adjunct with the corticosteroid. To the best of our knowledge, this association has not been reported or extremely infrequently reported in the existing literature. The adjunctive use of corticosteroids does not appear to diminish the efficacy of ‘adequate’ anti-tuberculosis therapy. The use of corticosteroids has significant short- and long-term benefits in most forms of tuberculosis.

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Singh, Dhiraj Kumar, Sultan Tousif, Ashima Bhaskar, Annu Devi, Kriti Negi, Barnani Moitra, Anand Ranganathan, Ved Prakash Dwivedi, and Gobardhan Das. "Luteolin as a potential host-directed immunotherapy adjunct to isoniazid treatment of tuberculosis." PLOS Pathogens 17, no. 8 (August 20, 2021): e1009805. http://dx.doi.org/10.1371/journal.ppat.1009805.

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Tuberculosis (TB) remains a major health problem throughout the world with one third of the population latently infected and ~1.74 million deaths annually. Current therapy consists of multiple antibiotics and a lengthy treatment regimen, which is associated with risk for the generation of drug-resistant Mycobacterium tuberculosis variants. Therefore, alternate host directed strategies that can shorten treatment length and enhance anti-TB immunity during the treatment phase are urgently needed. Here, we show that Luteolin, a plant-derived hepatoprotective immunomodulator, when administered along with isoniazid as potential host directed therapy promotes anti-TB immunity, reduces the length of TB treatment and prevents disease relapse. Luteolin also enhances long-term anti-TB immunity by promoting central memory T cell responses. Furthermore, we found that Luteolin enhances the activities of natural killer and natural killer T cells, both of which exhibit antitubercular attributes. Therefore, the addition of Luteolin to conventional antibiotic therapy may provide a means to avoid the development of drug-resistance and to improve disease outcome.

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Mdivani, Nino, Haijing Li, Maka Akhalaia, Medea Gegia, Leila Goginashvili, Douglas S. Kernodle, George Khechinashvili, and Yi-Wei Tang. "Monitoring Therapeutic Efficacy by Real-Time Detection of Mycobacterium tuberculosis mRNA in Sputum." Clinical Chemistry 55, no. 9 (September 1, 2009): 1694–700. http://dx.doi.org/10.1373/clinchem.2009.124396.

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Abstract Background: Current laboratory methods for monitoring the response to therapy for tuberculosis (TB) rely on mycobacterial culture. Their clinical usefulness is therefore limited by the slow growth rate of Mycobacterium tuberculosis. Rapid methods to reliably quantify the response to anti-TB drugs are desirable. Methods: We developed 2 real-time PCR assays that use hydrolysis probes to target DNA of the IS6110 insertion element and mRNA for antigen 85B. The nucleic acids are extracted directly from concentrated sputum samples decontaminated with sodium hydroxide and N-acetyl-l-cysteine. We prospectively compared these assays with results obtained by sputum mycobacterial culture for patients receiving anti-TB therapy. Results: Sixty-five patients with newly diagnosed TB and receiving a standardized first-line anti-TB drug regimen were evaluated at week 2 and at months 1, 2, and 4 after therapy initiation. Both the DNA PCR assay (98.5% positive) and the mRNA reverse-transcription PCR (RT-PCR) assay (95.4% positive) were better than standard Ziehl–Neelsen staining techniques (83.1%) for detecting M. tuberculosis in culture-positive sputum samples. The overall agreement between culture and mRNA RT-PCR results for all 286 sputum samples was 87.1%, and compared with culture, the mRNA RT-PCR assay’s diagnostic sensitivity and specificity were 85.2% and 88.6%, respectively. For monitoring efficacy of therapy, mRNA RT-PCR results paralleled those of culture at the follow-up time points. Conclusions: The continued presence of viable M. tuberculosis according to culture and results obtained by RT-PCR analysis of antigen 85B mRNA correlated clinically with resistance to anti-TB drugs, whereas the DNA PCR assay showed a high false-positive rate. This mRNA RT-PCR assay may allow rapid monitoring of the response to anti-TB therapy.

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Ribeiro-Rodrigues, Rodrigo, Tatiana Resende Co, John L. Johnson, Fabiola Ribeiro, Moises Palaci, Ricardo T. Sá, Ethel L. Maciel, et al. "Sputum Cytokine Levels in Patients with Pulmonary Tuberculosis as Early Markers of Mycobacterial Clearance." Clinical and Vaccine Immunology 9, no. 4 (July 2002): 818–23. http://dx.doi.org/10.1128/cdli.9.4.818-823.2002.

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ABSTRACT Sputum and serum from patients with active pulmonary tuberculosis (TB), healthy purified protein derivative-positive adults, and patients with bacterial pneumonia were collected to simultaneously assess local immunity in the lungs and peripheral blood. To determine whether cytokine profiles in sputum from TB patients and control subjects were a reflection of its cellular composition, cytospin slides were prepared in parallel and assessed for the presence of relative proportions of epithelial cells, neutrophils, macrophages, and T cells. Gamma interferon (IFN-γ) in sputum from TB patients was markedly elevated over levels for both control groups. With anti-TB therapy, IFN-γ levels in sputum from TB patients decreased rapidly and by week 4 of treatment were comparable to those in sputum from controls. Further, IFN-γ levels in sputum closely followed mycobacterial clearance. Although detected at fourfold-lower levels, IFN-γ immunoreactivities in serum followed kinetics in sputum. TNF-α, interleukin 8 (IL-8) and IL-6 also were readily detected in sputum from TB patients at baseline and responded to anti-TB therapy. In contrast to IFN-γ, however, TNF-α and IL-8 levels also were elevated in sputum from pneumonia controls. These data indicate that sputum cytokines correlate with disease activity during active TB of the lung and may serve as potential early markers for sputum conversion and response to anti-TB therapy.

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Todoriko, L. D., О. V. Pidverbetska, І. О. Semianiv, І. V. Yeremenchuk, and М. М. Kuzhko. "Applications of infusion therapy in the difficult form of tuberculosis." Infusion & Chemotherapy, no. 3.1 (October 11, 2020): 77. http://dx.doi.org/10.32902/2663-0338-2020-3.1-64.

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Objective. Analysis of the prevalence of the difficult cases of tuberculosis (TB) and assessment of the effectiveness of the treatment when using infusion anti-TB drugs in standard regimens. Materials and methods. A retrospective analysis was carried out for 2017-2019 of the electronic database the register of patients and the inpatient case history KU “Chernivtsi Regional Clinical TB Dispensary”. Results and discussion. From 16 to 46 % of patients with TB infection have concomitant signs of diabetes mellitus. In 58.9 % of patients with sensitive TB, the absorption capacity of the small intestine significantly decreases with a predominant decrease in the intestinal permeability index from 3.1 to 6 (in 21.9 % of cases). At multiple-drug resistance TB decrease the absorptive function of intestines is observed in 76,1 % of cases with the prevalence of severe degree of disturbance (in 42,3 % of patients). The proportion of severe forms of sensitive TB is more than 42 % of cases, of which 69.6±1.6 % were diagnosed with destruction. The share of common forms of TB among all cases of drug-resistant TB (DRTB) treated in 4th categories is 47 %, of which with destructive forms – 78.5±3.6 %. The frequency of adverse reactions increases in severe forms of DRTB and amounts to 38 % of all analyzed cases. Conclusions. Early detection of patients with severe forms of TB, especially in the presence of concomitant pathology, and their allocation into a separate category of “severe patients with TB” using parenteral forms of anti-TB drugs, especially in the early stages of treatment (during the intensive phase, which is the most critical period), it facilitates to reduce the unfavorable prognosis of the course of the underlying disease.

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Alghamdi, Wael A., Sampson Antwi, Anthony Enimil, Hongmei Yang, Albert Dompreh, Lubbe Wiesner, Taimour Langaee, Charles A. Peloquin, and Awewura Kwara. "Population pharmacokinetics of efavirenz in HIV and TB/HIV coinfected children: the significance of genotype-guided dosing." Journal of Antimicrobial Chemotherapy 74, no. 9 (June 26, 2019): 2698–706. http://dx.doi.org/10.1093/jac/dkz238.

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Abstract Objectives The current WHO weight-based dosing recommendations for efavirenz result in a wide variability of drug exposure in children. Our objectives are to characterize the effects of rifampicin- and isoniazid-containing anti-TB therapy and CYP2B6 activity on efavirenz concentrations in children, using non-linear mixed-effects modelling. Methods This is a pharmacokinetic (PK) substudy of a prospective study that examined the interactions between anti-TB therapy and efavirenz in HIV-infected children with and without TB. PK samples were obtained 4 weeks after starting efavirenz (PK1) and repeated 4 weeks after completing TB therapy (PK2) in TB/HIV coinfected patients. Drug concentrations were measured using LC-MS/MS. Composite CYP2B6 516/983/15582 genotype was determined. Population PK modelling was performed in Monolix. Simulations were performed to obtain the predicted mid-dose concentrations (C12). Results One hundred and five HIV-infected Ghanaian children (46 with TB/HIV) were included. The median age and weight were 7 years and 19 kg. The efavirenz concentrations over time were adequately described using a one-compartment model. Weight, composite CYP2B6 genotype and PK visit had a significant influence on the PK parameters, while TB therapy had no significant effect. Simulations showed adequate C12 for intermediate composite CYP2B6 metabolizers only. Conclusions Our model showed that rifampicin- and isoniazid-containing anti-TB therapy does not influence efavirenz PK parameters. On the other hand, it describes the effect of efavirenz autoinduction after completing TB treatment. In addition, dosing efavirenz in children based only on weight results in a large variability in drug exposure. We propose dose adjustments for slow and extensive composite CYP2B6 metabolizers.

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Subhash, H. S., I. Ashwin, U. Mukundan, D. Danda, G. John, A. M. Cherian, and K. Thomas. "Drug Resistant Tuberculosis in Diabetes Mellitus: A Retrospective Study from South India." Tropical Doctor 33, no. 3 (July 2003): 154–56. http://dx.doi.org/10.1177/004947550303300311.

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This study was conducted in a tertiary care teaching hospital in south India to evaluate the association of drug resistant tuberculosis (TB) in diabetic subjects. There were: 361 subjects with positive mycobacterial culture and susceptibility tests results over a 3-year period; 267 (74%) acid-fast bacillus smear positive; and 94 (26%) smear negative cases. One hundred and seventy-seven (49%) had resistant isolates to any one first line anti TB drugs (resistant group) and 184 (51%) had isolates sensitive to all drugs (non-resistant group). In the resistant and non-resistant subjects the mean duration of TB symptoms was, respectively, 22 months and 4.5 months, past history of TB 126 (71%) and 48 (26%), past anti TB drug therapy 126 (71%) and 47 (25%), inadequate anti TB drug therapy 42 (24%) and 23 (13%), HIV positive six and 13 subjects. There were 72 diabetic subjects [35 and 37, respectively] with a duration of diabetes 5.8 ± 7.5 years and 3.7 ± 5.0 years in the resistant and non-resistant groups. Twenty-six per cent of the diabetic subjects (19/72) had multi-drug resistant TB. Drug resistance to first line anti-TB drugs was not found to be associated with diagnosis or duration of diabetes mellitus.

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P. R., Shreenivas, and S. Nagaraja Prasad. "Study of price variation among the different brands of anti-tubercular drugs available in India." International Journal of Basic & Clinical Pharmacology 6, no. 3 (February 24, 2017): 660. http://dx.doi.org/10.18203/2319-2003.ijbcp20170832.

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Background: India is one of the largest Tuberculosis (TB) burden countries in the world. Although Revised National Tuberculosis Control Programme provides free cost of therapy, sometimes patient get treated by private practioners. This can sometimes lead to irregular course of treatment due to decreased patient compliance. This in turn may lead to multi drug resistance among TB bacilli. One of the reasons for decreased patient compliance is cost of therapy. The present study was undertaken to evaluate the cost of therapy of various anti-TB drugs and their combinations available in India.Methods: The maximum and minimum cost in rupees (INR) of all anti-TB drugs manufactured by various pharmaceutical companies was noted. The cost of 10 tablets/capsules or their fixed dose combinations (FDCs) was calculated. The cost ratio and percentage price variation were calculated for each brand and compared.Results: Percentage variation in cost of oral anti-TB drugs marketed in India was highest in ethambutol 400mg (474.51), cycloserine 250mg (384.61), ethambutol 800mg (321.84) and rifampin 450mg (258.45). The lowest percentage cost variation was seen with pyrazinamide 225mg (10.04), ethambutol 1000mg (18.82) and rifampin 100mg (22.78). Among the FDCs lowest percentage cost variation seen with rifampin 150mg +isoniazid 75mg+pyrazinamide 400mg (0.16) and highest percentage cost variation is seen with rifampin 450mg+isoniazid 300mg+pyrazinamide 750mg+ethambutol 800mg (232.73).Conclusions: There is a significant variation in the cost of different brands of oral anti-TB drugs and their FDCs available in India. The National Pharmaceutical Pricing Authority (NPPA) should take more proactive steps for bringing down the prices of first line anti-TB drugs and the clinicians prescribing them should be aware of the price variation among the various brands of anti-TB drugs available in India.

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A, Vijayalakshmi, Thanmayi G, and Jayakumari S. "A PROSPECTIVE STUDY ON ABNORMAL LFT PATTERNS IN PATIENTS RECEIVING ANTITUBERCULOSIS THERAPY." Asian Journal of Pharmaceutical and Clinical Research 9, no. 5 (September 1, 2016): 136. http://dx.doi.org/10.22159/ajpcr.2016.v9i5.12756.

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ABSTRACTObjective: Identification of risk factors associated with anti-tuberculosis drug-induced hepatotoxicity (anti-TB-DIH) is important, especially in anendemic area for TB and liver disease. This study assessed the incidence and risk factors of anti-TB-DIH. Hence, the present study was designed toevaluate the abnormal liver function test (LFT) in antitubercular therapy.Methods: A total of 100 consecutive TB patients were prospectively followed up both clinically and biochemically before and during their course ofanti-TB therapy with daily doses of isoniazid, rifampin, ethambutol, and pyrazinamide, or streptomycin.Results: In the study, 18-30 years 17 (17%), 31-50 years 28 (28%), 51-70 years 37 (37%), and 71-80 years 18 (18%) aged patients were found where63 (63%) are males and 37 (37%) are females. Comparison between before treatment and 2 months treatment showed a significant increase in the levelof aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP), viz., 51.6±3.92, 42.7±3.21, and 129±3.2 (U/L),respectively, as compared to pre-treatment levels. Comparison between before treatment and 2 months treatment showed a significant increase inthe level of AST, ALT, and ALP, viz., 51.6±3.92, 42.7±3.21, and 129±3.2 (U/L), respectively, as compared to pre-treatment levels. Comparison betweenbefore treatment and after treatment (6 months) revealed a significant increase in the level of AST, ALT, ALP and gamma glutamyl transpeptidase(GGT) viz., 59.9±3.12, 51.6±3.66, 131.6±3.2, and 61±3.2 (U/L) respectively. The total bilirubin and direct bilirubin were found between 2.1±0.9 and0.6±0.3 mg/dL respectively, when compared with before treatment.Conclusion: Anti-TB-DIH is not uncommon, needs early recognition and treatment and is more in patients with pre-existing liver disease and lowerbody mass index.Keywords: Anti-tuberculosis, Liver function test, Hepatotoxicity.

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Das, Priya, Asesh Banerjee, and Dr Prithviraj Karak. "Molecular Interplay between Vitamin D and Immunity can Aid Antitubercular Treatment Vitamin D in Immunomodulation of TB." Defence Life Science Journal 7, no. 3 (September 13, 2022): 209–20. http://dx.doi.org/10.14429/dlsj.7.17566.

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Tuberculosis (TB) causes maximum mortality and morbidity worldwide. 25 per cent of the global population harbour Mycobacterium tuberculosis (Mtb) and therefore are at risk of developing active disease. Of late, the disseminated diseases of TB are on the increase. Nearly one-third of all TB infections can be classified as extrapulmonary-TB (EPTB). TB can spread to the bone, brain, intestine, peritoneum, genitourinary system, and female genital sites leading to problems of conception. Therefore undoubtedly, TB has turned out to be a tremendous public health problem globally. The emergence of drug-resistant bacteria calls for new anti-tuberculous drugs to enhance response to antimicrobial therapy for active TB. However, discoveries of very effective anti-TB new medicines have not materialised yet. Thus, nutritional anti-TB intervention is highly important. In the pre-antibiotic era, Vitamin D was used for the treatment of TB. Its active component 1,25-dihydroxy-vitamin D3 was shown to display anti-TB activity in vitro. Vitamin D deficient humans display greater susceptibility to TB. Vitamin D deficiency induces worse disease progression in TB cases as observed in many clinical trials. The efficacy of the addition of vitamin D supplements in TB treatment has also been estimated. Thus, by now, the role of vitamin D in TB prevention and treatment is well established. Knowledge of the molecular mechanism of vitamin D is crucially vital for new anti-TB drug design. This review article discusses the recent advancement regarding the molecular mechanism of vitamin D-related anti-TB action. Further elucidation of this area may help novel anti-TB drug development.

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Davarpanah, Mohammad Ali, and Seyed Mohammad Hoseini. "Incidence of Active Tuberculosis Among Human Immunodeficiency Virus (HIV)-Positive Patients and Evaluation of Their Responses to Usual Anti-Tuberculosis Medications in Shiraz, South West of Iran." Galen Medical Journal 4, no. 2 (March 21, 2015): 115–20. http://dx.doi.org/10.31661/gmj.v4i2.260.

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Background: Human Immunodeficiency Virus (HIV) makes infected cases prone to opportunistic infections like Tuberculosis (TB) due to impaired immunity of the body, especially Multi Drug Resistant (MDR) ones which are a major concern. With HIV outbreak starting late in the 20th century, the international health community is observing a huge rise in the incidence of this complex disease. Herein, we estimated the incidence of TB among HIV-positive individuals and their responses to anti-tuberculosis medications in Shiraz, Southwest of Iran. Materials and Methods: 840 HIV-positive patients were included in this cross-sectional study. During the first examination CD4+ count and PPD test was obtained, patients were checked for other symptoms too. Patients, if diagnosed with TB, received proper medication. If therapy failed, second-line therapy was prescribed for them. Type of resistance was studied and recorded. Patients continued their routine anti-viral therapy during the study. Results: Of 840 participants, 29 were diagnosed with Active TB (3.4%), 76% of them were diagnosed with PCR and culture and other with acid fast. Males were the majority of TB positives (82.8%). Most patients suffering from TB had CD4+ count lower than 200 (55.1%); 17.2% of the cases were MDR-TB. Conclusion: Low CD4+ count makes the patient vulnerable to TB. It is necessary to maintain patient’s immunity in order to treat and prevent tuberculosis; so, anti-viral therapies still play important roles in preventing TB in HIV-positive patients.[GMJ.2015;4(2):115-20]

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Rawal, Gautam, Sankalp Yadav, and Sujana Rajamma. "Myocardial tuberculosis: A rare case report." Discussion of Clinical Cases 9, no. 2 (March 6, 2023): 13. http://dx.doi.org/10.5430/dcc.v9n2p13.

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Tuberculosis (TB) is one of the most common causes of mortality and morbidity globally, with Indian subcontinent having quite a large number of TB cases. TB can involve any organ system in humans; however, the disease affecting the cardiovascular system is rare. On the other hand, myocardial tuberculosis is a serious entity and can, unfortunately, be fatal if the diagnosis is missed or delayed. Therefore, the possibility of TB involving the myocardium should always be considered in areas with a high prevalence of TB, like the Indian subcontinent. Anti-TB therapy (with corticosteroids in some cases), along with early detection and suspicion, is proven to be quite effective in management and cure in most cases. We describe a case of sputum AFB (acid-fast bacilli) positive pulmonary TB with dilated cardiomyopathy, and impaired/decreased left ventricular systolic function, which gradually improved after anti-tubercular decongestive therapy.

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Said, Bibie, Edwin Nuwagira, Alphonce Liyoyo, Rinah Arinaitwe, Catherine Gitige, Rhina Mushagara, Peter Buzaare, et al. "Early empiric anti-Mycobacterium tuberculosis therapy for sepsis in sub-Saharan Africa: a protocol of a randomised clinical trial." BMJ Open 12, no. 6 (June 2022): e061953. http://dx.doi.org/10.1136/bmjopen-2022-061953.

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IntroductionSub-Saharan Africa shoulders the highest burden of global sepsis and associated mortality. In high HIV and tuberculosis (TB) prevalent settings such as sub-Saharan Africa, TB is the leading cause of sepsis. However, anti-TB therapy is often delayed and may not achieve adequate blood concentrations in patients with sepsis. Accordingly, this multisite randomised clinical trial aims to determine whether immediate and/or increased dose anti-TB therapy improves 28-day mortality for participants with HIV and sepsis in Tanzania or Uganda.Methods and analysisThis is a phase 3, multisite, open-label, randomised controlled clinical 2×2 factorial superiority trial of (1) immediate initiation of anti-TB therapy and (2) sepsis-specific dose anti-TB therapy in addition to standard of care antibacterials for adults with HIV and sepsis admitted to hospital in Tanzania or Uganda. The primary endpoint is 28-day mortality. A sample size of 436 participants will provide 80% power for testing each of the main effects of timing and dose on 28-day mortality with a two-sided significance level of 5%. The expected main effect for absolute risk reduction is 13% and the expected OR for risk reduction is 1.58.Ethics and disseminationThis clinical trial will determine the optimal content, dosing and timing of antimicrobial therapy for sepsis in high HIV and TB prevalent settings. The study is funded by the National Institutes of Health in the US. Institutional review board approval was conferred by the University of Virginia, the Tanzania National Institute for Medical Research, and the Uganda National Council for Science and Technology. Study results will be published in peer-reviewed journals and in the popular press of Tanzania and Uganda. We will also present our findings to the Community Advisory Boards that we convened during study preparation.Trial registration numberClinicalTrials.gov (NCT04618198).

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Tao, Lina, Xiaoyu Qu, Yue Zhang, Yanqing Song, and Si-xi Zhang. "Prophylactic Therapy of Silymarin (Milk Thistle) on Antituberculosis Drug-Induced Liver Injury: A Meta-Analysis of Randomized Controlled Trials." Canadian Journal of Gastroenterology and Hepatology 2019 (January 10, 2019): 1–11. http://dx.doi.org/10.1155/2019/3192351.

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Background. Prophylactic therapy with silymarin to prevent the development of antituberculosis drug-induced liver injury (anti-TB DILI) has been under debate. We aimed to evaluate the effect of silymarin in the prevention of anti-TB DILI. Methods. We searched MEDLINE, PubMed, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) up to 30th November 2018. Randomized controlled trials (RCTs) that compared silymarin and placebo to prevent anti-TB DILI were included. All statistical analyses were conducted using STATA 12.0 software. Standardized mean difference (SMD) and risk ratio (RR) with 95% confidence intervals (CIs) were used to evaluate the effect of silymarin. The quality of included studies was assessed according to Cochrane handbook. Funnel plots and Egger’s tests were carried out to evaluate publication bias. Sensitivity analysis was conducted to assess the influence of each study. Results. A total of 1198 patients from five RCTs (585 with silymarin and 613 with placebo groups) were included. Overall, silymarin significantly reduced the occurrence of anti-TB DILI at week 4 [RR: 0.33, 95% CI (0.15, 0.75)]. In addition, silymarin exerted protective effect on liver function in patients undergoing anti-TB drugs [SMD = − 0.15, 95% CI (−0.24, −0.07), P < 0.001 (ALT); SMD =−0.14, 95% CI (−0.23, −0.06), P = 0.001(AST); SMD =−0.12, 95% CI (−0.20, −0.03), P = 0.008 (ALP)]. Silymarin led to similar AEs in placebo groups [OR: 1.09, 95% CI (0.86, 1.39), P = 0.47]. Conclusion. Prophylactic therapy of silymarin is contributed to a noticeably reduced risk of development of anti-TB DILI four weeks after the initiation. In addition, silymarin significantly improved the liver function in patients who are receiving anti-TB drugs.

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Raymond E Eworo, Augusta C Nsonwu-Anyanwu, Unyime A Fabian, Patience A Akpan, and Peace E Udo. "Nutritional background of low-income pulmonary tuberculosis patients on anti-tuberculosis therapy at Infectious Disease Hospital, Calabar, Nigeria: A case-control study." Open Access Research Journal of Science and Technology 5, no. 1 (July 30, 2022): 070–79. http://dx.doi.org/10.53022/oarjst.2022.5.1.0044.

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Background: Poverty and malnutrition are associated with the risk of developing tuberculosis (TB). Nutritional reintegration with anti-TB therapy may improve treatment success rate. Aim: To investigate the nutritional status of low-income pulmonary TB patients in relation to the different anti-TB treatment phases. Methods: Forty five pulmonary TB patients and 40 controls aged 19-54 years, receiving treatment at Infectious Disease Hospital, Calabar, Nigeria, between September 2018 and July 2019 were studied. Serum total protein, albumin, iron and vitamin A were determined by colorimetric and HPLC methods respectively. Height and weight were measured and BMI computed, and data analysed using Student’s t-test, ANOVA, and Pearson’s correlation at P<0.05. Results: Among TB patients, 66.7%, 35.5%, and 22.22% were albumin, iron, and vitamin A deficient respectively. Total protein and globulins levels were higher while BMI, albumin, iron, and vitamin A were lower in the TB patients compared to the control (P=0.001). Albumin and iron levels of TB patients on continuation phase of anti-TB treatment (CPAT) were higher than those of TB-HIV coinfection on the same phase of treatment, TB patients on intensive phase of anti-TB treatment (IPAT) and controls (p<0.05). Comparing TB patients on CPAT and IPAT, also CPAT-HIV and IPAT-HIV patients, BMI and biochemical indices studied were not significantly different (P>0.05) respectively. Albumin and iron were significantly lower in CPAT-HIV compared with CPAT patients. Albumin correlated positively and significantly with iron (r=0.405, p=0.006) in TB patients. Conclusion: Tuberculosis is associated with decreased BMI, albumin, iron and vitamin A, and higher total protein, and globulin, suggesting that malnutrition may be associated with TB risk, poor treatment compliance and outcomes.

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Khadka, Anjan. "BEDAQUILINE: A long but much fruitful wait since seventies." Medical Journal of Shree Birendra Hospital 13, no. 1 (July 19, 2015): 40–42. http://dx.doi.org/10.3126/mjsbh.v13i1.13000.

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Tuberculosis (TB) is a major health problem in developing countries one of the leading cause of deaths due to infectious disease in the world. Drug treatment had being successful with anti-tubercular drugs available, but Multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant TB (XDR-TB) are serious forms of TB which have emerged as real concern. Bedaquiline (TMC-207 or R207910), is a new anti TB agent been approved as a part of drug regimen therapy in pulmonary MDR-TB. Bedaquiline acts on energy metabolism of the bacteria. It acts as a bactericidal drug. There are two important black box warnings for this drug, firstly prolongation of QT interval and secondly increased risk of death with bedaquiline as compared to placebo treatment. Fast track approval for bedaquiline was based on two phase 2 trials. The FDA has approved bedaquiline on Dec 2012, for the treatment of MDR-TB in adults (>18 years) as part of combination therapy under the fast track designation, priority review and orphan-product designation based on two Phase II trials. Careful use of this drug along with monitoring of the potential adverse effects and drug interactions becomes very important, as this new anti-tubercular drug has being approved after forty years, since last anti tubercular drug was approved.doi: http://dx.doi.org/10.3126/mjsbh.v13i1.13000

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Esmael, Ahmed, Adane Mihret, Tamrat Abebe, Daniel Mussa, Sebsibe Neway, Joel Ernst, Jyothi Rengarajan, Liya Wassie, and Rawleigh Howe. "Persistent expression of activation markers on Mycobacterium tuberculosis-specific CD4 T cells in smear negative TB patients." PLOS ONE 17, no. 8 (August 30, 2022): e0271234. http://dx.doi.org/10.1371/journal.pone.0271234.

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Background T cell activation (HLA-DR, CD-38), proliferation (KI-67), and functional (IFN-γ, TNF-α) markers have recently been shown to be useful in predicting and monitoring anti-TB responses in smear positive TB, but previous research did not characterize the activation and proliferation profiles after therapy of smear negative TB. Methodology In this study, we used polychromatic flow cytometry to assess selected PPD-specific T cell markers using fresh PBMC of smear negative and positive pulmonary tuberculosis (PTB) patients, recruited from health facilities in Addis Ababa. Result Levels of activation (HLA-DR, CD38) and proliferation (Ki-67) among total unstimulated CD4 T cells decreased significantly after therapy, particularly at month 6. Similarly, levels of PPD-specific T cell activation markers (HLA-DR, CD-38) were significantly lower in smear positive PTB patients following treatment, whereas a consistent decline in these markers was less apparent among smear negative PTB patients at the sixth month. Conclusion After six months of standard anti-TB therapy, persistent levels of activation of HLA-DR and CD-38 from PPD specific CD4+T cells in this study could indicate that those markers have little value in monitoring and predicting anti-TB treatment response in smear negative pulmonary TB patients in Ethiopian context.

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Garfein, R. S., L. Liu, J. Cuevas-Mota, K. Collins, D. G. Catanzaro, F. Muñoz, K. Moser, et al. "Evaluation of recorded video-observed therapy for anti-tuberculosis treatment." International Journal of Tuberculosis and Lung Disease 24, no. 5 (May 1, 2020): 520–25. http://dx.doi.org/10.5588/ijtld.19.0456.

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BACKGROUND: Asynchronous video directly observed therapy (VDOT) may reduce tuberculosis (TB) program costs and the burden on patients. We compared VDOT performance across three cities in the United States, each of which have TB incidence rates above the national average.METHODS: Patients aged ≥18 years who are currently receiving directly observed anti-TB treatment were invited to use VDOT for monitoring treatment. Pre- and post-treatment interviews and medical records were used to assess site differences in treatment adherence and patient characteristics and perceptions.RESULTS: Participants were enrolled in New York City, NY (n = 48), San Diego, CA (n = 52) and San Francisco, CA, USA (n = 49). Overall, the mean age was 41 years (range 18–87); 59% were male; most were Asian (45%) or Hispanic/Latino (30%); and 77% were foreign-born. The median fraction of expected doses observed (FEDO) was 88% (IQR 76–96). At follow-up, 97% thought VDOT was “very or somewhat easy to use” and 95% would recommend VDOT to other TB patients. Age, race/ethnicity, annual income, and country of birth differed by city (P < 0.05), but FEDO and VDOT perceptions did not.CONCLUSIONS: TB programs in three large US cities observed a high FEDO using VDOT while minimizing staff time and travel. Similar findings across sites support VDOT adoption by other large, urban TB programs.

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Adeniji, Adetomiwa A., Kirsten E. Knoll, and Du Toit Loots. "Potential anti-TB investigational compounds and drugs with repurposing potential in TB therapy: a conspectus." Applied Microbiology and Biotechnology 104, no. 13 (May 5, 2020): 5633–62. http://dx.doi.org/10.1007/s00253-020-10606-y.

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Sutanto, Yusup Subagio, Magdalena Sutanto Sutanto, and Agnes Sri Harti. "Anti-Tuberculosis Drugs against the Resistance Level of Mycobacterium tuberculosis isolates." Jurnal Kesehatan Masyarakat 17, no. 1 (July 24, 2021): 14–23. http://dx.doi.org/10.15294/kemas.v17i1.24158.

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Prolonged MDR-TB therapy can have side effects, namely a correlation between cure rates and changes in bacterial profiles related to resistance to anti-tuberculosis drugs (ATD) which can affect the incidence rate of MTB and MDR-TB in a region. The research objective was to analyze the effectiveness of the type of ATD against the resistance level of Mycobacterium tuberculosis (MTB) isolates with the incidence of tuberculosis (TB) and MDR-TB. The research method used was a retrospective cohort based on tracing medical record data at the Surakarta City Center General Hospital 2016 until 2017 with total sampling. The independent variable of this study was the type of ATD, while the dependent variable was the resistance level of MTB isolates. The characteristics of the most patient respondent suspect TB were male with the level of resistance of MTB isolates to ATD relatively varied. The results of the analysis of different tests showed a p value of 0.000 so that the p value was 0.05, so there was an effect of the type of ATD (Strepttomycin, Isoniazid, Rifampicin and Ethambutol) on the resistance of TB isolates from patients with suspected TB. This is useful to determine the success of TB therapy in terms of mortality and the effectiveness of therapy in TB patients.

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Tang, Peijun, Xingnian Chen, Junchi Xu, Yunlong Hu, Zhijian Ye, Xiafang Wang, Yumei Xiao, et al. "Autologous Cytokine-Induced Killer Cell Immunotherapy Enhances Chemotherapy Efficacy against Multidrug-Resistant Tuberculosis." Journal of Immunology Research 2022 (March 17, 2022): 1–10. http://dx.doi.org/10.1155/2022/2943113.

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Objective. Multidrug-resistant tuberculosis (MDR-TB) causes persistent infection and challenges tuberculosis control worldwide. T cell-mediated immunity plays a critical role in controlling Mycobacterium tuberculosis (Mtb) infection, and therefore, enhancing Mtb-specific T cell immune responses represents a promising therapeutic strategy against TB. Cytokine-induced killer (CIK) immunotherapy is based on autologous infusion of in vitro expanded bulk T cells, which include both pathogen-specific and nonspecific T cells from patient peripheral blood mononuclear cells (PBMC) into TB patients. Preclinical mouse studies have shown that the adoptive T cell therapy inhibited Mtb infection. However, the efficacy of CIK immunotherapy in the treatment of MDR-TB infection has not been evaluated in clinical trials. Methods. We performed a retrospective study of MDR-TB patients who received CIK immunotherapy in combination with anti-TB chemotherapy and those who had standard chemotherapy. Results. Our results showed that CIK immunotherapy in combination with anti-TB chemotherapy treatment increased the conversion rate of sputum smear and Mtb culture, alleviated symptoms, improved lesion absorption, and increased recovery. The kinetics of serology and immunology index monitoring data showed good safety profiles for the CIK treatment. Conclusion. Our study has provided strong evidence that CIK immunotherapy in combination with anti-TB chemotherapy is beneficial for MDR-TB patients. A multicenter clinical trial is warranted to evaluate CIK as a new immune therapy for MDR-TB.

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Shevchenko, Olha S., Liliia D. Todoriko, Olha O. Pohorelova, Ihor O. Semianiv, Irina A. Ovcharenko, Rostislav S. Shevchenko, Stanislav I. Shevchenko, Inga V. Yeremenchuk, Olena V. Pidverbetska, and Yana I. Toderika. "FUNCTIONAL STATE OF THE LIVER IN PULMONARY TUBERCULOSIS IN THE DYNAMICS OF PATHOGENETIC TREATMENT WITH A COMPLEX OF AMINO ACIDS." Wiadomości Lekarskie 76, no. 2 (2023): 352–59. http://dx.doi.org/10.36740/wlek202302116.

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The aim: To investigate the in!uence of prescribing a complex of amino acids in pathogenetic therapy in patients with pulmonary tuberculosis on liver function. Materials and methods: The study included 50 patients with drug susceptible TB and 50 patients with drug-resistant TB (multidrug-resistant and extensively drug-resistant). Results: The study included 50 patients with drug susceptible tuberculosis (TB) and 50 patients with drug-resistant TB. When comparing biochemical pa-rameters characterizing liver function in patients with drug-susceptible TB after 1 month of anti-tuberculosis therapy, it was found that patients receiving additional therapy with a complex of amino acids had a lower level of bilirubin, p<0.05. After 60 doses, patients receiving additional therapy with amino acids had signi"cantly lower bilirubin levels alanine aminotransferase (ALT) and aspartate aminotransferase (AST), p <0.05. When comparing the biochemical parameters characterizing liver function in patients with drug-resistant tuberculosis after a month of anti-tuberculosis therapy, signi"cantly higher protein level was found in the groups of patients receiving additional therapy with amino acids, as well as signi"cantly lower ALT level, AST and creatinine p<0.05. Conclusions: The additional appointment of the complex of amino acids in the pathogenetic therapy of patients with pulmonary tuberculosis makes it possible to reduce the severity of hepatotoxic reactions manifested by the main parameters (AST, ALT, total bilirubin) and to increase the protein-synthetic function of the liver, which allows us to recommend their appointment to improve the tolerance of anti-tuberculosis therapy.

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Abdulaziz, S., S. Attar, W. Bajhammoh, E. A. Sindi, D. M. Ayish, and E. Bakhashwain. "POS1153 EFFECTIVENESS OF SCREENING IN PATIENTS WITH RHEUMATIC DISEASE ON BIOLOGICAL THERAPY AND RISK OF ACTIVE TUBERCULOSIS." Annals of the Rheumatic Diseases 80, Suppl 1 (May 19, 2021): 855.1–856. http://dx.doi.org/10.1136/annrheumdis-2021-eular.1617.

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Background:Treatment with biologic therapy has been associated with a high risk of reactivation of latent tuberculosis (TB). Preventive strategies for tuberculosis remain a crucial step before initiating biologics in rheumatic disease.Treatment with biological therapy has been associated with high risk of reactivation of latent tuberculosis (TB). Prevention strategies remain a crucial step before initiating biologics.Objectives:We aimed to assess the effectiveness of TB screening before the initiation of biologics and the risk of occurrence of active TB among patients with rheumatic diseases on biologic therapies.The study aimed to access the effectiveness of TB screening recommendations before the initiation of biological therapy and identify the incidence of active TB among these patients.Methods:We performed a hospital-based retrospective cohort study among rheumatic disease patients on biological therapy in two centers in Jeddah between January 2005 to December 2019. Medical files were retrospectively reviewed for demographics data, baseline screening for TB, use of prophylaxis, information on DMARDs and biological therapies, and outcomes results were collected.Results:A total of 365 patients were included over a period of 14 years. Two hundred ninety-two (80%) had Rheumatoid arthritis (RA),13% psoriatic arthritis (PSA), 9% spondyloarthritis (SPA), 2% SLE, and 4% others. The mean age was 47.54 (±14.2), 311 (85%) were females with a mean duration of disease 8.45 years (± 6.58). Hundred forty-nine (42.3%) were on steroids. Anti TNFs were prescribed in 213 (58.4%) patients, Non Anti-TNFs 124 (36.6%) patients, and Jak inhibitors 18 (5%) patients.TB screening was done to all patients except 3 patients (data missing) before commencing biologics. Forty-four (12.1%) patients had latent TB at baseline and all received chemoprophylaxis with isoniazid before starting biologics. Four patients with active TB were identified (one with Behcet’s disease and three with RA). One patient had a reactivation of latent TB and 3 patients developed de novo TB. Three out of four had an infection in the first 6 months of treatment (one on infliximab and two on rituximab) and one case after 1 year of stopping adalimumab. Two cases had pulmonary TB and two others with extrapulmonary TB (pericarditis and brain abscess each). All four patients with active TB were treated with standard anti TB medications. Three had complete resolution of their TB and one died.Conclusion:Baseline screening has been effectively carried out in our cohort as per recommendations. Physician should be vigilant not only for reactivation of latent TB but occurrence of de novo TB in patients on biological therapy.References:[1]Gardam, M. A. et al. Anti-tumour necrosis factor agents and tuberculosis risk: mechanisms of action and clinical management. Lancet. Infect. Dis.3, 148-155, doi:10.1016/s1473-3099(03)00545-0 (2003).[2]Winthrop, K. L., Yamashita, S., Beekmann, S. E. & Polgreen, P. M. Mycobacterial and other serious infections in patients receiving anti-tumor necrosis factor and other newly approved biologic therapies: case finding through the Emerging Infections Network. Clin. Infect. Dis.46, 1738-1740, doi:10.1086/587989 (2008).[3]Cantini, F., Niccoli, L. & Goletti, D. Tuberculosis risk in patients treated with non-anti-tumor necrosis factor-α (TNF-α) targeted biologics and recently licensed TNF-α inhibitors: data from clinical trials and national registries. J. Rheumatol. Suppl.91, 56-64, doi:10.3899/jrheum.140103 (2014).Acknowledgements:We would acknowledge Dr. Noran Alhashmi, Dr. Roaa Jodah, and Dr. Lamis Ramadan for their assistance in data collection.Disclosure of Interests:None declared.

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Kale, Monali Raghunath, Mirza Shiraz Baig, and Avinash Lamb. "A prospective observational pharmacovigilance study of adverse drug reaction monitoring in patients of tuberculosis receiving category I and II treatment regimens at tertiary care hospital." International Journal of Basic & Clinical Pharmacology 8, no. 5 (April 23, 2019): 875. http://dx.doi.org/10.18203/2319-2003.ijbcp20191568.

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Background: First line Anti-TB therapy with rifampicin, isoniazid, pyrazinamide, and ethambutol / streptomycin is very effective. However, major adverse reactions to antituberculous drugs can cause significant morbidity and mortality. One of the main reasons for non‑adherence to anti‑TB therapy (ATT) is ADRs, even under DOTS. Present study was carried out in tertiary care hospital. The objective of the study was to evaluate types and frequency of ADRs in intensive and continuation phase of category I and II Anti-TB medication.Methods: A prospective observational study conducted in Department of TB- Chest and Medicine, Govt. Medical College, Aurangabad, Maharashtra, India. All the TB patients reporting at DOTS Center of institute were enrolled and monitored for ADRs. The causality and severity of the reactions were determined using Naranjo algorithm and Hartwig questionnaire.Results: Total, n = 241 tuberculosis patients on DOTS therapy were enrolled for the study. Out of 241 patients, 17 were dropouts so 224 patients assessed for ADRs. 127 (56.69%) developed adverse drug reactions. The higher numbers of ADRs were observed in age group 31-40 yrs followed by 21-30 yrs, ADRs were more common in men. Pulmonary TB (73.66%) cases were more common than extra pulmonary TB. Majority of adverse drug reactions were Gastrointestinal (GI) problems (30.92%), followed by Liver dysfunction and Hepatotoxicity (20.39%) and skin problems (17.10%). The causality of ADRs, in majority cases were found to be Probable (56.57%). Around 19 patients require treatment interruption and most of the patients were managed with supportive medication without removing anti tubercular drug from regimen.Conclusions: ADRs are major limiting factor for completion of drug therapy under RNTCP and occurrence of drug resistance which requires attention of all health care professionals.

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Muhammad, N., S. Mehboob, and M. Abbas. "Pyrazinamide Induced Hyperuricemia in the Induction Phase of Anti-Tuberculosis Therapy." Pakistan Journal of Medical and Health Sciences 15, no. 5 (May 30, 2021): 1136–38. http://dx.doi.org/10.53350/pjmhs211551136.

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Background: Tuberculosis (TB) is a global public health concern; although there are several recognized anti-tuberculosis drugs (ATDs) that effectively combat Mycobacterium tuberculosis (MTB), the associated adverse effects lead to frequent discontinuation. Objective: To assess the metabolic disturbances resulting from Pyrazinamide, the altered serum uric acid (SUA) levels among TB patients in District Bunir. Study Design: Cross-sectional study Place and Duration of Study: Department of Medicine, Bilal Medical Trust Hospital, Bunir-KPK from 1st January to 30th September 2019. Methodology: One hundred and nine tuberculosis patients were included in the study. All these patients were on ATD with Pyrazinamide and were regularly followed up, and their SUA levels were determined at weeks 0, 4 and 8. Results: The serum uric acid levels were high in almost 85.3% in the intensive phase of anit-TB Therapy (ATT). Among female TB patients, the incidence rate of hyperuricemia was comparatively higher than males (88.1% vs. 81.0%), but there were no significant gender disparities. Conclusion: The anti-tuberculosis drug with pyrazinamide is associated with an increased risk of hyperuricemia. Therefore, the illness needs to be closely monitored during the intensive phase of therapy. Key words: Pyrazinamide, Tuberculosis, Hyperuricaemia

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Goovaerts, Odin, Marguerite Massinga-Loembé, Pascale Ondoa, Ann Ceulemans, William Worodria, Harriet Mayanja-Kizza, Robert Colebunders, and Luc Kestens. "Lack of elevated pre-ART elastase-ANCA levels in patients developing TB-IRIS." PLOS ONE 15, no. 12 (December 31, 2020): e0244800. http://dx.doi.org/10.1371/journal.pone.0244800.

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Background Tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) in HIV-TB co-infected patients receiving antiretroviral therapy (ART) has been linked to neutrophil activation. Anti-neutrophil cytoplasmic antibodies (ANCAs) are also associated with neutrophil activation. Since ANCAs are reportedly skewed in TB and HIV infections, we investigated plasma levels of 7 ANCAs in TB-IRIS patients. Methods We retrospectively compared 17 HIV-TB patients who developed TB-IRIS with controls of similar CD4 count, age and gender who did not (HIV+TB+ n = 17), HIV-infected patients without TB (HIV+TB-, n = 17) and 10 HIV-negative (HIV-TB-) controls. Frozen plasma was collected before ART, at 3 and 9 months of ART, and examined by ELISA for levels of 7 ANCAs directed against; Proteinase 3 (PR3), Myeloperoxidase (MPO), Permeability-increasing protein (BPI), Elastase, Cathepsin, Lysozyme, and Lactoferrin. Results Compared to HIV+TB+ controls, pre-ART anti-elastase levels were lower in TB-IRIS patients (p = 0.026) and HIV-TB- controls (p = 0.044), whereas other ANCAs did not show significant differences between groups at any time point. A significant decrease over time could be observed in TB-IRIS patients during ART for anti -PR3 (p = 0.027), -lysozyme (p = 0.011), and -lactoferrin (p = 0.019). Conversely, HIV+TB+ controls showed a significant decrease over time for anti -MPO (p = 0.002), -lyzosyme (p = 0.002) and -elastase (p < 0.001). Conclusion The lack of elevated anti-elastase levels in TB-IRIS patients as opposed to HIV+TB+ controls correspond to previous findings of lowered immune capacity in patients that will develop TB-IRIS. This may suggest a specific role for anti-elastase, elastase or even matrix-metalloproteinases in TB-IRIS. The precise dynamics of neutrophil activation in HIV-TB merits further investigation and could provide more insight in the early mechanisms leading up to TB-IRIS.

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Xi, Ying, Wei Zhang, Rui-Jun Qiao, and Jun Tang. "Risk factors for multidrug-resistant tuberculosis: A worldwide systematic review and meta-analysis." PLOS ONE 17, no. 6 (June 16, 2022): e0270003. http://dx.doi.org/10.1371/journal.pone.0270003.

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Background Since multidrug-resistant tuberculosis (MDR-TB) is a significant public health problem worldwide, identifying associated risk factors is critical for developing appropriate control strategies. Methods A systematic review and meta-analysis was conducted for identifying factors independently predicting MDR-TB. The random-effects model was used to determine pooled odds ratios (ORs) and respective 95% confidence intervals (CIs) for the related factors. Results Of the 2301 retrieved reports, 28 studies were analyzed, assessing 3152 MDR-TB and 52715 DS-TB cases. Totally 22 related factors were analyzed. The pooled ORs were 1.478 (95%CI 1.077–2.028) for positive sputum AFB smear, 1.716 (95%CI 1.149–2.564) for lung cavity, 6.078 (95%CI 2.903–12.725) for previous TB disease and 5.427 (95%CI 3.469–8.490) for a history of anti-TB therapy. All Z test p values were below 0.05, indicating these parameters were significantly associated with MDR-TB. Conclusions Positive sputum AFB smear, lung cavity, previously diagnosed TB and a history of anti-TB therapy are significant risk factors for MDR-TB, which are independent of the clinical setting worldwide. Increased attention should be paid to cases with such parameters to achieve more effective TB control and avoid MDR-TB through the development of a global policy.

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Lancella, Laura, Luciana Abate, Laura Cursi, Giulia Chiopris, Laura Nicoletti, Nicola Principi, Alberto Villani, and Susanna Esposito. "Abdominal Tuberculosis in Children: A Case Series of Five Patients." Microorganisms 11, no. 3 (March 12, 2023): 730. http://dx.doi.org/10.3390/microorganisms11030730.

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Tuberculosis remains (TB) to be one of the most common causes of child morbidity and mortality. Abdominal TB is not frequently diagnosed and, although its incidence is not definitively established, there are data that seem to indicate that it accounts for approximately 1–3% of all pediatric TB cases and for no more than 10% of those with extrapulmonary manifestations. It seems, however, that abdominal TB is significantly more common than usually thought as signs and symptoms are non-specific and may mimic other diseases. The delayed or wrong diagnosis of pediatric abdominal TB can have dramatic consequences as they can lead to untreated TB with miliary dissemination, unnecessary surgery, or dangerous drug therapies. This report describes five cases of abdominal TB diagnosed among 216 pediatric patients admitted for TB in Italy from 2011 to 2021. Our cases evidence that abdominal TB is a complex and potentially very severe disease that, when not appropriately diagnosed, may be associated with severe complications and prolonged anti-TB therapy. Discussion among specialists is crucial to achieve an early diagnosis and to promptly start the anti-TB treatment. Further studies are needed to clarify the appropriate duration of therapy as well as management of MDR abdominal TB cases.

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Lozovskaya, Marina E., Yulia A. Yarovaya, Elena B. Vasilieva, Ludmila V. Klochkova, Elena A. Malysheva, and Olga M. Noskova. "Combination of tuberculosis of the intra thoracic lymph nodes and acute lymphoblastic leukemia in a child." Pediatrician (St. Petersburg) 12, no. 6 (April 18, 2022): 89–96. http://dx.doi.org/10.17816/ped12689-96.

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According to scientific research, malignant neoplasms in children are biomedical risk factors for the development of tuberculosis (TB). On the contrary, the occurrence of oncological disease in a child against the background of an existing tuberculous process is extremely rare. The combination of malignant neoplasm and tuberculosis creates difficulties in differential diagnosis, treatment of diseases, prevention of exacerbations and relapses. This article presents a clinical observation the development of acute lymphoblastic leukemia (ALL) in a 6-year-old child against the background of TB of the intrathoracic lymph nodes during treatment. TB proceeded favorably despite multiple family contact in the child and resistance of Mycobacterium tuberculosis to anti-tuberculosis drugs in adult relatives of the patient. At the onset of ALL, bilateral pulmonary infiltrates and pleural effusion were observed, which were not associated with TB. Specific polychemotherapy for ALL and continued chemotherapy for TB led to the cure of two diseases. Supportive cytostatic and immunosuppressive therapy for ALL required periodic courses of anti-relapse anti-tuberculosis therapy for 5 years. After 10 years of observation, the child is healthy. Thus, the possibility of a rare in clinical practice combination of TB and ALL in children should be taken into account in the diagnosis and treatment of these diseases. During courses of immunosuppressive therapy for ALL, there is a risk of reactivation of TB. It is necessary to recommend long-term observation of such children by a phthisiatrician and an oncologist to prevent recurrence of both diseases.

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Dutta, Noton K., Natalie Bruiners, Matthew D. Zimmerman, Shumin Tan, Véronique Dartois, Maria L. Gennaro, and Petros C. Karakousis. "Adjunctive Host-Directed Therapy With Statins Improves Tuberculosis-Related Outcomes in Mice." Journal of Infectious Diseases 221, no. 7 (October 12, 2019): 1079–87. http://dx.doi.org/10.1093/infdis/jiz517.

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Abstract Background Tuberculosis (TB) treatment is lengthy and complicated and patients often develop chronic lung disease. Recent attention has focused on host-directed therapies aimed at optimizing immune responses to Mycobacterium tuberculosis (Mtb), as adjunctive treatment given with antitubercular drugs. In addition to their cholesterol-lowering properties, 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) have broad anti-inflammatory and immunomodulatory activities. Methods In the current study, we screened 8 commercially available statins for cytotoxic effect, anti-TB activity, synergy with first-line drugs in macrophages, pharmacokinetics and adjunctive bactericidal activity, and, in 2 different mouse models, as adjunctive therapy to first-line TB drugs. Results Pravastatin showed the least toxicity in THP-1 and Vero cells. At nontoxic doses, atorvastatin and mevastatin were unable to inhibit Mtb growth in THP-1 cells. Simvastatin, fluvastatin, and pravastatin showed the most favorable therapeutic index and enhanced the antitubercular activity of the first-line drugs isoniazid, rifampin, and pyrazinamide in THP-1 cells. Pravastatin modulated phagosomal maturation characteristics in macrophages, phenocopying macrophage activation, and exhibited potent adjunctive activity in the standard mouse model of TB chemotherapy and in a mouse model of human-like necrotic TB lung granulomas. Conclusions These data provide compelling evidence for clinical evaluation of pravastatin as adjunctive, host-directed therapy for TB.

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Kaushal, Deepak, Dhiraj K. Singh, and Smriti Mehra. "Immune Responses in Lung Granulomas during Mtb/HIV Co-Infection: Implications for Pathogenesis and Therapy." Pathogens 12, no. 9 (September 1, 2023): 1120. http://dx.doi.org/10.3390/pathogens12091120.

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HIV and TB are the cause of significant worldwide mortality and pose a grave danger to the global public health. TB is the leading cause of death in HIV-infected persons, with one in four deaths attributable to TB. While the majority of healthy individuals infected with M. tuberculosis (Mtb) are able to control the infection, co-infection with HIV increases the risk of TB infection progressing to TB disease by over 20-fold. While antiretroviral therapy (ART), the cornerstone of HIV care, decreases the incidence of TB in HIV-uninfected people, this remains 4- to 7-fold higher after ART in HIV-co-infected individuals in TB-endemic settings, regardless of the duration of therapy. Thus, the immune control of Mtb infection in Mtb/HIV-co-infected individuals is not fully restored by ART. We do not fully understand the reasons why Mtb/HIV-co-infected individuals maintain a high susceptibility to the reactivation of LTBI, despite an effective viral control by ART. A deep understanding of the molecular mechanisms that govern HIV-induced reactivation of TB is essential to develop improved treatments and vaccines for the Mtb/HIV-co-infected population. We discuss potential strategies for the mitigation of the observed chronic immune activation in combination with both anti-TB and anti-retroviral approaches.

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Novikov, Vasiliy E., Natalia E. Usacheva, and Tatyana V. Myakisheva. "Modern approaches to pharmacotherapy of tuberculosis infection in children." Research Results in Pharmacology 7, no. 4 (December 3, 2021): 47–53. http://dx.doi.org/10.3897/rrpharmacology.7.66627.

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Anti-TB drugs for children: Aetiotropic therapy is used for the treatment of tuberculosis (TB) in children, as well as in adult patients. Anti-tuberculosis drugs (anti-TB drugs) are divided into 3 lines, taking into account drug sensitivity in Mycobacterium tuberculosis (MBT). First-line anti-TB drugs (basic) are used to treat TB caused by drug-susceptible MBT. Second- and third-line (reserve) drugs are recommended for the treatment of MBT-induced multidrug-resistant (MDR) and extensively drug-resistant (XDR) TB, respectively. Stages and regimens to treat tuberculosis: Chemotherapy of tuberculosis in children is carried out in 2 stages (intensive treatment and continuation of treatment) and includes 5 regimens. Each regimen assumes a certain combination of anti-TB drugs, indicating the duration and frequency of their administration. The final chemotherapy regimen is chosen only according to the results of determining the drug sensitivity. To improve the TB epidemic among children, it is important to improve the regimens for the use of anti-TB drugs. The effectiveness of anti-tuberculosis pharmacotherapy is largely determined by the MBT sensitivity and the rational choice of the chemotherapy regimen. The wrong choice of a chemotherapy regimen or its violation threatens to reduce the effectiveness of pharmacotherapy and expand the spectrum of resistance of the pathogen. The development of fixed-dose combination anti-TB drugs and special dosage forms for children will improve the quality of chemotherapy and adherence to treatment. Pharmacoeconomic studies are needed to increase the effectiveness of drug pharmacotherapy for tuberculosis infection in children and to optimize the costs of its implementation.

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