Standard Antituberculous Therapy Research Articles

Spinal Tuberculosis in Pregnancy: A Case Series

Spinal Tuberculosis (Pott’s Spine) infection during pregnancy poses significant challenges in early diagnosis, as it often resembles typical back pain experienced during pregnancy. Delayed diagnosis has resulted in maternal and foetal complications, including paraplegia, premature labor, preterm delivery, and foetal growth restriction. Treatment approaches are tailored to individual clinical presentations and may involve conservative or surgical intervention. Surgical decompression should be considered when there is a neurological deficit that could complicate the delivery process. The standard Antituberculous Therapy (ATT) regimen for 12 months is an accepted treatment protocol according to the World Health Organisation (WHO) guidelines during the antenatal period. The present case series comprises four middle-aged pregnant women (two aged 19 years, one aged 21 years, and one aged 35 years, all primigravida) diagnosed with Pott’s spine at various trimesters, exhibiting a range of clinical presentations from mild back pain to acute neurological deficits. One patient in the late trimester with a neurological deficit required surgical decompression, while the remaining patients were successfully managed with appropriate ATT

The incidence of tuberculosis recurrence: Impacts of treatment duration of and adherence to standard anti-tuberculous therapy

BackgroundWe investigated the impacts of the standard treatment durations of and adherence to standard anti-tuberculous therapy (ATT) on recurrence after the successful completion of tuberculosis (TB) treatment. MethodsWe recruited patients with TB who had received treatment for six or nine months from the 2008–2017 databases of the Taiwanese National Health Insurance Research Database. Treatment duration and adherence to standard ATT were analyzed for their impacts on recurrence within two years. Complete adherence to standard ATT was defined as daily use of ethambutol, isoniazid, pyrazinamide, and rifampin for the first two months, and daily use of isoniazid and rifampin for the first six months. ResultsA total of 33,298 TB patients with new-onset TB were identified and classified into two groups by treatment duration: six months (n = 25,849, 77.63%) and nine months (n = 7449). Sex and age distributions varied between the groups. Treatment duration did not affect TB recurrence within two years (adjusted hazard ratio (AHR): 1.18, 95% confidence interval (C.I.) [0.96–1.44], p = 0.1156). Multivariable logistic regression showed that incomplete adherence to standard anti-tuberculous therapy (80–89% and 90–99% standard anti-TB therapy, AHR: 1.57, 95% C.I. [1.26–1.95], and 1.63, 95% C.I. [1.26–2.06], respectively, p < 0.0001) increased TB recurrence. In addition, male sex, older age, and comorbidity with diabetes mellitus or chronic obstructive pulmonary disease were independent risk factors for TB recurrence within two years. ConclusionsTB recurrence was 1.54% within two years under a DOT era. TB treatment durations of six or nine months did not affect TB recurrence within two years after completion of TB treatment, but incomplete adherence to standard anti-tuberculous therapy might increase the TB recurrence rate.

Presumed tuberculosis-related scleritis

AimsTo evaluate the clinical characteristics and therapeutic outcome of patients with recurrent scleritis of unknown demonstrable aetiology and positive QuantiFERON-TB Gold In-Tube test (QFT).MethodsRetrospective chart review of the demographic, clinical,...

Empirical anti-tuberculous therapy for the massive pericardial effusion of unknown etiology

Objective The aim of this study was to evaluate the efficacy and safety of empirical anti-tuberculous therapy (ATT) in patients with massive pericardial effusion (MPE) of unknown etiology in China. Methods In-hospital patients with MPE were assessed retrospectively. Based on thorough examination excluding neoplastic, autoimmune, and non-tuberculous infectious diseases, patients who had no evidence of tuberculosis (TB) were treated with empirical ATT (Group A) or not treated with empirical ATT (Group C), whereas those who had evidence of TB were treated with standard ATT (Group B). Clinical outcomes and mitigation of MPE were compared among the three groups to identify the effectiveness of ATT. The survival free of composite endpoint was estimated using the Kaplan-Meier method. Results A total of 185 eligible patients were recruited: 77 in Group A, 80 in Group B, and 28 in Group C. The average follow-up was 52.9 ± 30.7, 49.4 ± 29.7, and 51.8 ± 30.2 months for Groups A, B, and C, respectively. The incidence of composite endpoint was 23.3, 24.4, and 85.7% in Groups A, B, and C, respectively (p < .0001). However, the clinical recovery rate was greater in Group B compared with Group A (p = .027). No significant difference in the safety profile of ATT was noted between Groups A and B. MPE did not spontaneously decrease in 85.7% of patients in Group C. Conclusions Empirical ATT should be considered in MPE of unknown etiology in countries with a high burden of TB.

Remodeling the matrix: doxycycline modulates tuberculosis immunopathology.

Pulmonary cavitation is a hallmark of Mycobacterium tuberculosis (Mtb) infection that provides an immune-privileged niche for extracellular bacillary replication, which associates with increased transmission rates, drug resistance, and chronic lung dysfunction following antituberculous therapy (ATT). Inhibitors of matrix metalloproteinases (MMPs), which are induced by Mtb infection, have shown efficacy in preclinical models and improved microbiologic and immunopathologic outcomes. In this issue of the JCI, Hao Miow et al. performed a double-blind, randomized controlled trial exploring host-directed effects of the MMP inhibitor doxycycline versus placebo when added to standard ATT for pulmonary tuberculosis. Doxycycline treatment over two weeks durably modulated host blood transcription profiles, including the resolution of inflammatory gene programs. Reduced immunopathology markers in doxycycline-treated participants also included improved lung cavity volumes and lower MMP levels in blood and sputum. These findings provide mechanistic insight and momentum for using experimental medicine trials to develop host-directed therapies for tuberculosis.

Evaluation of intracranial vasculitis in tuberculous meningitis using magnetic resonance vessel wall imaging technique.

Tuberculous meningitis (TBM) is a global health problem with important complications such as acute infarcts secondary to vasculitis contributing to adverse outcomes. The objective of this study is to assess intracranial vasculitis in patients with TBM, either during their initial diagnosis or during follow-up while on standard antituberculous therapy. Ten patients with TBM underwent magnetic resonance (MR) based vessel wall imaging (VWI) to identify intracranial vasculitis (five patients during their initial presentation and the other five patients during their follow-up visit). Vasculitis was seen in 60% of the patients wherein 70% of their intracranial vessels were affected. Acute and chronic infarcts were seen in four and two patients respectively, one of whom had both acute and chronic infarcts. Leptomeningeal enhancement and basal cisternal tuberculomas were frequently seen in patients with vasculitis. Vasculitis was also seen many days after the commencement of the antituberculous therapy thus explaining late-onset infarcts in this disease. Intracranial vasculitis is common in the patient with TBM. MR-based VWI technique has the potential for infarct risk assessment and to help guide the treatment for its possible prevention.

'Beehive-like'appearance in thoracic tuberculous lymphadenopathy.

Sir, A 12-year-old girl presented with intermittent fever of moderate grade, since 15 days with normal examination findings. Mantoux test was positive. Radiograph of chest showed hilar lymphadenopathy (Figure 1: Panel a: Red arrow). Computerised tomography of the thorax and abdomen with oral and intravenous contrast showed enlarged lymph node mass in the mediastinum with hypointense spaces giving 'beehive like appearance' likely due to necrosis/caseation at the centre of lymph nodes. Lymph node groups involved included superior mediastinal (Figure 1: Red arrows in panels b and e) and inferior mediastinal (yellow arrow in panel c and d) but sparing groups on the left of the aorta. Lung fields were clear. No lymph node masses were present in the abdomen. Blood tests revealed lymphocytosis and elevated erythrocyte sedimentation rate (100 mm/h). She was treated with standard antituberculous therapy [isoniazid 300 mg once a day [OD], rifampicin 450 mg OD, ethambutol 800 mg OD and pyrazinamide 1 g OD] and on follow-up after 1 month was responding to treatment with absence of fever and good appetite. Tuberculous lymphadenopathy has been reported in several publications.[12] However, the 'beehive appearance' in this case is striking in appearance and is important to be recognized for distinguishing from other causes of mediastinal masses in children such as lymphoma, germ cell tumour and neuroblastoma.[3] It is especially important when there is no primary lung focus visible on the chest X-ray as in our case. And it is an important non-invasive sign for tuberculous lymphadenopathy for early and proper management.Figure 1: (a) X-ray chest: widened mediastinum due to enlarged lymph node mass. (b-d) Computerised tomography scan chest coronal view, e (axial view): beehive sign in tuberculosis-enlarged lymph node mass with cavities of various sizes surrounding tracheobronchial treeTeaching point: This is a useful sign to distinguish tuberculous adenopathy from other mediastinal masses. This will help minimise the need for invasive tests such as fine-needle aspiration cytology studies or biopsy to detect tuberculosis. Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.

Drug resistant TB spine in a two year old child: A case report

Spinal tuberculosis (TB) is a disease of high morbidity that is associated with deformity and neurological sequelae, especially in growing children. Children diagnosed with spinal TB need to be monitored closely for clinical improvements. Previous history of antituberculous therapy (ATT), poor adherence to previous ATT, contact with persons having known drug-resistant (DR) TB, or clinical worsening despite regular ATT are strong indicators for the diagnosis of DR TB of the spine. We report a case of spinal DRTB in a two year old child with no previous history of ATT and contact with a person on irregular treatment for drug sensitive TB that did not show regression of the spinal lesions despite standard ATT.

Tuberculous pleural effusion.

Tuberculous effusion is a common disease entity with a spectrum of presentations from a largely benign effusion, which resolves completely, to a complicated effusion with loculations, pleural thickening and even frank empyema, all of which may have a lasting effect on lung function. The pathogenesis is a combination of true pleural infection and an effusive hypersensitivity reaction, compartmentalized within the pleural space. Diagnostic thoracentesis with thorough pleural fluid analysis including biomarkers such as adenosine deaminase and gamma interferon achieves high accuracy in the correct clinical context. Definitive diagnosis may require invasive procedures to demonstrate histological evidence of caseating granulomas or microbiological evidence of the organism on smear or culture. Drug resistance is an emerging problem that requires vigilance and extra effort to acquire a complete drug sensitivity profile for each tuberculous effusion treated. Nucleic acid amplification tests such as Xpert MTB/RIF can be invaluable in this instance; however, the yield is low in pleural fluid. Treatment consists of standard anti-tuberculous therapy or a guideline-based individualized regimen in the case of drug resistance. There is low-quality evidence that suggests possible benefit from corticosteroids; however, they are not currently recommended due to concomitant increased risk of adverse effects. Small studies report some short- and long-term benefit from interventions such as therapeutic thoracentesis, intrapleural fibrinolytics and surgery but many questions remain to be answered.

Treatment of a broncho-esophageal fistula complicated by severe ARDS

Broncho-esophageal fistula formation is a rare complication of tuberculosis, most often seen in immunocompromised patients. In this paper, we report the case of a young non-immunocompromised refugee from Somalia diagnosed with open pulmonary tuberculosis complicated by extensive osseous involvement and a broncho-esophageal fistula with consecutive aspiration of gastric contents. The patient rapidly developed a severe acute respiratory distress syndrome (ARDS) requiring venovenous extracorporeal membrane oxygenation (ECMO) therapy for nearly 2 months. The fistula was initially treated by standard antituberculous combination therapy and implantation of an esophageal and a bronchial stent. Long-term antibiotic treatment was instituted for pneumonia and mediastinitis. 7 months later, discontinuity resection of the esophagus was performed and the bronchial fistula covered by an intercostal muscle flap. This case illustrates that tuberculosis should always be suspected in patients from high-incidence countries in case of lung involvement and that an interdisciplinary approach including long-term intensive care management can enable successful treatment of tuberculosis with severe, near-fatal complications.

The Role of Steroids in a Child with Spinal Pre-Extensively Drug-Resistant Tuberculosis

AbstractThere has been a rise in the number of reported cases of drug-resistant tuberculosis (TB) in children in the recent past. Beneficial effects of steroids in the treatment of spine TB on standard antituberculous therapy are known. However, the role of steroids in patients with spinal drug-resistant TB is not established. We report on a 10-year-old girl with pre-extensively drug resistant (XDR) spinal TB and the effect of steroids in drug resistant TB.

Pancreatic Tuberculosis.

Tuberculosis of the pancreas is extremely rare and in most of the cases mimics pancreatic carcinoma. There are a number of case reports on pancreatic tuberculosis with various different presentations, but only a few case series have been published, and most of our knowledge about this disease comes from individual case reports. Patients of pancreatic tuberculosis may remain asymptomatic initially and manifest as an abscess or a mass involving local lymph nodes and usually present with non-specific features. Pancreatic tuberculosis may present with a wide range of imaging findings. It is difficult to diagnose tuberculosis of pancreas on imaging studies as they may present with masses, cystic lesions or abscesses and mass lesions in most of the cases mimic pancreatic carcinoma. As it is a rare entity, it cannot be recommended but suggested that pancreatic tuberculosis should be considered in cases with a large space occupying lesions associated with necrotic peripancreatic lymph nodes and constitutional symptoms. Ultrasonography/computed tomography/endosonography-guided biopsy is the recommended diagnostic technique. Most patients achieve complete cure with standard antituberculous therapy. The aims of this study are to review clinical presentation, diagnostic studies, and management of pancreatic tuberculosis and to present our experience of 5 cases of pancreatic tuberculosis.

Role of endoscopy in recalcitrant intraventricular tuberculoma—innovative novel treatment adjunct

Introduction. Intraventricular tuberculomas are rare entities. To the best of our knowledge, only 14 cases have been reported in English literature. Medical management of cerebral tuberculomas is well accepted. Intraventricular tuberculomas may be recalcitrant for unclear reasons. An effective management protocol for this entity is unclear. To the best of our knowledge, the definitive indication, timing, and possible role of surgery in these lesions have not been discussed in literature. Materials and methods. A 27-year-old nursing professional who was undergoing treatment for miliary tuberculosis at another center presented to us in 2008 with right hemiparesis, deteriorating vision, and progressive decline in consciousness. In addition to antituberculous therapy (ATT), she underwent multiple CSF diversion procedures for the obstructive hydrocephalus secondary to a recalcitrant third ventricular tuberculoma. Finally, she underwent endoscopic decompression of the lesion with a very good clinical response at 1-year follow-up. Discussion. We discuss a patient with recalcitrant intraventricular tuberculoma managed using neuroendoscopy along with the standard antituberculous therapy. We also discuss in detail the technique we utilized for endoscopic management of this lesion. Conclusion. Being a rare entity, a consensus for management of these lesions is not possible, but we have demonstrated that neuroendoscopic management of these rare entities is an option giving the advantage of definitive diagnosis when required, hastening the resolution, and clearing the CSF pathway.

Concomitant Multidrug-resistant Pulmonary Tuberculosis and Susceptible Tuberculous Meningitis

Concomitant Multidrug-resistant Pulmonary Tuberculosis and Susceptible Tuberculous Meningitis

Tuberculous uveitis in China

To assess tuberculous uveitis in Chinese patients. The hospital-based observational case series study included patients who attended a third-referral hospital and presented with chronic and recurrent uveitis without primarily detected aetiology. The patients underwent the tuberculin skin test (TST) and/or interferon gamma release test (IGRA). Patients with positive test results received standard antituberculous therapy. Patients who responded to the therapy and did not show recurrence of uveitis in the follow-up period were diagnosed as tuberculous uveitis and formed the study group. The remaining patients were diagnosed as non-tuberculous uveitis and formed the control group. The clinical characteristics were compared between both groups. The study group with tuberculous uveitis included 46 patients and the non-tuberculous group 38 patients. Multifocal choroiditis [n = 9 (20%) versus n = 1(3%); p = 0.04] and retinal vasculitis [n = 25(54%) versus 8 = (21.1%); p = 0.002] were significantly more common in the study group. Of 25 patients with retinal vasculitis in the study group, 11 patients (44%) additionally showed choroiditis lesions, compared with only one (13%) of eight patients in the control group (p = 0.01). In multivariate regression analysis, multifocal choroiditis [odds ratio (OR): 32.1], choroidal granuloma (OR: 21.4) and retinal vasculitis (OR: 11.2) were independent predictors of tubercular uveitis. About 50% of a group of 84 patients with primarily unexplained chronic posterior uveitis had tuberculosis and showed multifocal choroiditis, choroidal granuloma and retinal vasculitis. These features had a high predictive value for the diagnosis of tuberculous uveitis. Tuberculosis is an important part in the differential diagnosis of unexplained uveitis.

Uncommon Site of Primary Tuberculosis: Sternum

Primary tuberculosis (TB) of the sternum is uncommon even in endemic countries. It can present as swelling, discharging sinus, erosion and spontaneous fracture of sternum, and with secondary infection (abscess). A proper history with physical examination, computed tomography, Ziehl-Neelsen staining of aspirate, and histopathology of biopsy are the keys to forming a suitable differential diagnosis. Its treatment consists of standard antituberculous therapy with or without antibiotics as done for other forms of extra-pulmonary TB. We report one case of primary tubercular osteomyelitis of the sternum causing its destruction without any underlying pulmonary lesion. The patient was successfully managed with debridement and with second-line anti-tubercular therapy (ATT).

High dose versus low dose steroids in children with tuberculous meningitis

Guidelines for the best steroid dose in children with tuberculous meningitis (TBM) have not been established. We enrolled 63 children with TBM and divided them into three steroid dose groups: Group 1 (prednisolone 2mg/kg/day over 4weeks), Group 2 (prednisolone 4mg/kg/day over 1week and 2mg/kg/day for the next 3weeks) and Group 3 (prednisolone 4mg/kg/day over 4weeks). All patients received standard antituberculous therapy. Optic atrophy, tuberculoma, hydrocephalus, mental retardation, spasticity, hearing impairment, vasculitis and mortality outcomes were compared. Optic atrophy was higher in Group 3 compared to Group 1 (odds ratio [OR]=2.8) and Group 2 (OR=2.8), although Group 3 had a high incidence of optic atrophy at diagnosis. Tuberculomas were more frequent in Group 1 (OR=2.4) and Group 3 (OR=3.0) as compared to Group 2. Infarcts were more common in Group 3 than in Group 1 (OR=1.9) and in Group 2 (OR=3.5). Hearing loss was higher in Group 2 as compared to Group 1 (OR=2.88) and Group 3 (OR=4.8). Evolving hydrocephalus was higher in Group 3 as compared to Group 2 (OR=2.8) and Group 1 (OR=3.1). Mental retardation was higher in children in Group 3 (OR=1.6) and in Group 2 (OR=1.9) as compared to Group 1. Spasticity was higher in Group 3 (OR=2.0) and in Group 2 (OR=1.4) as compared to Group 1. There was no difference in mortality between the groups. We conclude that prednisolone at a dose of 4mg/kg/day for 1week followed by 2mg/kg/day for 3weeks is associated with fewer tuberculomas and infarcts but a higher incidence of hearing loss. A prolonged period of high dose steroids increases the risk of optic atrophy and hydrocephalus. Prednisolone at a dose of 2mg/kg/day is associated with lower risk of mental retardation and spasticity.

Reply to Wakefield and Kumar

Sir, We would like to thank Wakefield and Kumar1 for their useful comments. It is true that the exact association between latent TB and uveitis is not known. In our series, all patients with presumed intraocular TB and active TB elsewhere received standard anti-tuberculous therapy (ATT). Patients with presumed intraocular TB and latent TB were generally offered ATT, but this was done after careful consideration of individual risk/benefit. Indeed, as we state in our article, two patients with latent TB and presumed intraocular TB received no ATT, because we estimated that the risks of treatment outweighed any potential benefit in them.2 ATT has well-recognized systemic and ocular adverse effects. On the other hand, it is known that ATT can eliminate latent TB and decrease a person's lifetime risk of developing active TB by 90%.3 Moreover, administering corticosteroid or immunosuppressive therapy for severe intraocular inflammation without the coverage of ATT may cause re-activation of systemic TB, resulting in severe disseminating TB or even panophthamlitis.4, 5 In a large series of patients with presumed intraocular TB and latent TB combination treatment with corticosteroids and ATT reduced the risk of developing recurrence of the uveitis by approximately two-thirds compared to treatment with corticosteroids alone.6 Based on the above and on the results of our study, we stated that a minimum of 6 months standard ATT is generally justified in patients with presumed intraocular TB and latent TB. However, we agree with Wakefield and Kumar1 that ATT should be considered with some caution in patients with latent TB who have high risk of complications. Decision to administer ATT should be made on an individual basis in these cases.

Intestinal Tuberculosis as First Manifestation of Human Immunodeficiency Virus (HIV) Infection. A Single History Snapshot

A 33-year-old man was admitted in 1999 because of abdominal pain, fever, and weight loss. After a presumptive diagnosis of acute complicated appendicitis, laparotomy was carried out. Since cecum and terminal ileum showed a `carcinomatous appearance´ ileocecal resection and right hemicolectomy were performed. Pathological assessment revealed the presence of acid-fast bacilli which were later identified as Mycobacterium tuberculosis. There was no evidence of neoplasia. As the patient had been intravenous drug user and had absolute lymphopenia, Human Immunodeficiency Virus serology was requested after surgery, with the result being positive. The patient was placed on standard antituberculous therapy and was discharged. However, he decided to stop quickly the treatment and was readmitted 3 month after discharge because of fever and cervical lymphadenitis. Culture of a neck lymph node sample grew Mycobacterium tuberculosis. This time, the patient took appropriately antituberculous drugs and also initiated antiretroviral treatment. Except for some diarrheic episodes, he has remained well throughout the follow-up period (from June, 1999 to December, 2013). It is well known that there is no such thing as an easy diagnosis of intestinal tuberculosis, even nowadays. We have just tried to remember it.

Tuberculous pyloric stenosis; successful medical therapy may obviate surgery

Gastroduodenal involvement occurs in only 0.3 to 2.3% of patients with tuberculosis (TB). Clinically, it may resemble peptic ulcer disease or malignancy. We present a 36 year old man with gastric outlet obstruction proven to be pyloric stricture due to primary pyloric tuberculosis. Diagnosis was established endoscopically and patient was successfully managed by standard anti-tuberculous therapy. Although rare, tuberculous involvement of the stomach should be considered in the differential diagnosis of gastric outlet obstruction especially in regions where tuberculosis is endemic. This case also emphasizes that medical management with anti-TB medications can be tried solely as the first line therapy for strictured pyloric stenosis. However, surgical intervention is required more often than none in cases where gastrointestinal obstruction is the main clinical problem.