Empirical Anti-tuberculosis Treatment Research Articles

PET-CT guided characterisation of progressive, preclinical tuberculous infection and its association with low-level circulating Mycobacterium tuberculosis DNA in household contacts in Leicester, UK: a prospective cohort study

Incipient tuberculosis, a progressive state of Mycobacterium tuberculosis infection with an increased risk of developing into tuberculosis disease, remains poorly characterised. Animal models suggest an association of progressive infection with bacteraemia. Circulating M tuberculosis DNA has previously been detected in pulmonary tuberculosis by use of Actiphage, a bacteriophage-based real-time PCR assay. We aimed to investigate whether serial [18F]fluorodeoxyglucose ([18F]FDG)-PET-CT could be used to characterise the state and progressive trajectory of incipient tuberculosis, and examine whether these PET-CT findings are associated with Actiphage-based detection of circulating M tuberculosis DNA. We did a prospective 12-month cohort study in healthy, asymptomatic adults (aged ≥16 years) who were household contacts of patients with pulmonary tuberculosis, and who had a clinical phenotype of latent tuberculosis infection, in Leicester, UK. Actiphage testing of participants' blood samples was done at baseline, and [18F]FDG PET-CT at baseline and after 3 months. Baseline PET-CT features were classified as positive, indeterminate, or negative, on the basis of the quantitation (maximum standardised uptake value [SUVmax]) and distribution of [18F]FDG uptake. Microbiological sampling was done at amenable sites of [18F]FDG uptake. Changes in [18F]FDG uptake after 3 months were quantitatively categorised as progressive, stable, or resolving. Participants received treatment if features of incipient tuberculosis, defined as microbiological detection of Mtuberculosis or progressive PET-CT change, were identified. 20 contacts were recruited between Aug 5 and Nov 5, 2020; 16 of these participants had a positive result on IFNγ release assay (QuantiFERON-TB Gold Plus [QFT]) indicating tuberculosis infection. Baseline PET-CT scans were positive in ten contacts (all QFT positive), indeterminate in six contacts (three QFT positive), and negative in four contacts (three QFT positive). Four of eight PET-CT-positive contacts sampled had M tuberculosis identified (three through culture, one through Xpert MTB/RIF Ultra test) from intrathoracic lymph nodes or bronchial wash and received full antituberculosis treatment. Two further unsampled PET-CT-positive contacts were also treated: one with [18F]FDG uptake in the lung (SUVmax 9·4) received empirical antituberculosis treatment and one who showed progressive [18F]FDG uptake received preventive treatment. The ten untreated contacts with [18F]FDG uptake at baseline (seven QFT positive) had stable or resolving changes at follow-up and remained free of tuberculosis disease after 12 months. A positive baseline Actiphage test was associated with the presence of features of incipient tuberculosis requiring treatment (p=0·018). Microbiological and inflammatory features of incipient tuberculosis can be visualised on PET-CT and are associated with M tuberculosis detection in the blood, supporting the development of pathogen-directed blood biomarkers of tuberculosis risk. MRC Confidence in Concept.

“Miliary lung parenchymal opacities” as presenting feature of metastatic papillary type of thyroid malignancy: It’s not tuberculosis always!

Pulmonary tuberculosis (TB) is the most common cause of mortality and morbidity in South East Asia due to infective causes and tops the list of all infectious etiologies in India. Radiological presentations in pulmonary TB are diverse with the most common in them, which are nodules, consolidation, cavitation, and lung parenchymal destruction with or without collapse and consolidation. In this case report, a 31-year-old female presented with constitutional symptoms with miliary opacities in chest X-ray without microbiological evidence for TB in smear microscopy or nucleic acid amplification tests. She was treated as a case of miliary TB with antituberculosis treatment (ATT) on two occasions in the past 2 years as an “X-ray-positive case” on the basis of symptoms and chest radiology findings. She was never shown any clinical and radiological response in the past 1½ years in spite of satisfactory ATT adherence and compliance. After retrospective analysis of this case at our center, we have documented worsening of radiological findings and chest high-resolution computed tomography conformed miliary nodules and not typical miliary mottling favoring TB. We have noted right thyroid enlargement with a nodule in contrast tomography of neck. Fine-needle aspiration cytology confirmed as papillary carcinoma of the thyroid. We have confirmed this case as miliary metastasis due to primary thyroid malignancy. Miliary metastasis should be considered in cases with atypical radiological and clinical presentations with negative microbiological workup. No empirical ATT should be offered in the era of highly sensitive nucleic acid amplification tests and the term “X-ray-positive with negative microbiological tests” should be phased out.

Catch them young: Knowledge gaps about drug resistant tuberculosis among Homoeopathy college interns: Apre and post-test study

Background: India is the highest Tuberculosis (TB) burden country in the world. It also has the second highest burden of Multidrug-resistant TB globally. Many precious lives are lost due to Drug-resistant TB (DR TB) every day. To achieve the goal of TB elimination in India, robust primary health care is mandatory. Ayurveda, Yoga and Naturopathy, Unani, Siddha, and Homeopathy (AYUSH) practitioners provide a quarter of primary health care in India. Since interns working at Homoeopathic Medical college will be the future primary care providers, their awareness about DR TB will help reach the target of End TB by 2025. Objective:The study objective was to assess the knowledge gained by Homoeopathy college interns in the diagnosis and treatment of DR TB following a single-day training session. Materials and methods: This cross-sectional study was carried out among 33 interns of Bharati Vidyapeeth (Deemed to be University) Homoeopathic Medical College, Pune. Aquestionnaire was given in the form of a pre-test before the training session. The training comprised the epidemiology of DR TB, its diagnosis,treatment, counseling, and need for referral. After completion of training, a post-test was given, and scores were calculated. A two-tailed paired sample t-test was used to assess gain in knowledge. The proportion of participants with correct responses for every question was determined and compared before and after training using the McNemar test. P<0.05 was considered statistically significant. Result: The mean pre-test score was 2.30 ± 1.24, while the mean post-test score was 4.24 ± 2.00 (p<0.001). There was less knowledge about the regime for DR TB, pre-treatment evaluation, gene Xpert method, and empirical Anti-tuberculosis Treatment. Conclusion: This study highlights that there are significant gaps in knowledge about DR TB among Homoeopathy college interns. It also showed that a short training session significantly improved their knowledge.

A rare case report of pulmonary nocardiosis mimicking as lung malignancy

Pulmonary nocardiosis is a rare infectious disorder mainly affecting immunocompromised patients. It may remain cryptic which gradually progresses in its course. Our patient was a 37 years old immunocompetent female who presented with radiological picture of left upper lobe opacification. She was treated with empirical anti tuberculosis treatment outside, no radiological improvement seen. After she reported here, she was evaluated with bronchoscopy with biopsy and bronchial wash culture showed Nocardia species. She was managed with trimethoprim-sulphamethoxazole and amikacin with regular follow up for 6 months. She had radiological resolution and clinical improvement after 4 months of treatment. Hence we made the diagnosis of this rare infection in immunocompetent individual and successfully treated her, which was mistreated as pulmonary tuberculosis elsewhere.

Cavitating lung disease is not always due to tuberculosis! Wegener’s granulomatosis with mycetoma with deep vein thrombosis lower limb: Case report with review of literature

Pulmonary tuberculosis is most common cause for bilateral pulmonary cavities with constitutional symptoms in India being endemic and more prevalent nature of disease, irrespective of microscopy or nucleic acid amplification test abnormalities. Pulmonary manifestations of systemic vasculitis have very diverse involvement ranging from nodule, consolidation, and cavitation. In this case report, 49-year female, presented with constitutional symptoms with lung parenchymal consolidations progressed to cavitation’s and started empirical anti-tuberculosis treatment without mycobacterial microscopic or genome documentation in sputum with clinical or radiological worsening. Bronchoscopy workup is inconclusive and tropical screen for bacterial, TB, and malignancy were negative and fungal yield aspergillus colonization. Vasculitis workup done in presence of clinical and radiological worsening documented PR3-ANCA positive with very highly raised titers. We have started on steroids, cyclophosphamide with antifungals and clinical response documented with near complete resolution of shadows in 24 weeks. She had developed DVT (deep vein thrombosis) lower limb during course of illness and documented excellent response to anticoagulation. DVT prophylaxis is must in all cases taking steroids with decreased daily activities to prevent fatal cardiovascular complications.

An Unusual Cause of Calcific Thoracic Metastases

An 18-year-old male presented with progressive breathlessness and cough of two months duration. He also complained of generalised body pains, low grade intermittent fever, anorexia and weight loss. He was started on empiric daily anti-tuberculosis treatment with rifampicin, isoniazid, pyrazianmide and ethambutol from elsewhere for right-sided pleural effusion one month ago. He presented to us as he did not experience improvement in his condition. There was no other significant medical history. Physical examination showed a 10cm x 8cm, non-tender hard bony mass with ill-defined margins over the upper third of left arm. There was no evidence of digital clubbing or peripheral lymphadenopathy. Respiratory system examination showed features of a right-sided pleural effusion.

Comparison of clinical and radiological characteristics in autoimmune GFAP astrocytopathy, MOGAD and AQP4-IgG+ NMOSD mimicking intracranial infection as the initial manifestation

ObjectiveSeveral autoimmune CNS inflammatory diseases, including autoimmune glial fibrillary acidic protein astrocytopathy (A-GFAP-A), myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) and aquaporin-4-immunoglobulin-G-positive neuromyelitis optica spectrum disorders (AQP4-IgG+NMOSD) often presented initially with similar symptoms mimicking intracranial infection, are not easy to be differentiated during early-onset lacking the detection of autoantibody. MethodsIn our single-center cohorts, those patients mimicking intracranial infection as initial symptoms, including 9 with A-GFAP-A, 17 with MOGAD and 11 with AQP4-IgG+NMOSD, were retrospectively included. The autoantibodies were detected by cell-based assays. The clinical, immunological and radiological characteristics were summarized. ResultsIn the cohort, tremor and positive Kernig's sign were predominated in A-GFAP-A (44.4% and 77.8%, respectively) over MOGAD (5.9%, p = 0.034; 29.4%, p = 0.038) and AQP4-IgG+NMOSD (0, p = 0.026; 18.2%, p = 0.022). Ten patients (A-GFAP-A, 4; MOGAD, 5; AQP4-IgG+NMOSD, 1) were initially misdiagnosed as tubercular or viral meningoencephalitis, however, resistant to empiric anti-tuberculosis or anti-viral treatment, and finally were in partial or complete remission with the immunotherapy when adjusted treatments. On cerebrospinal fluid (CSF) examination, white blood cell counts in CSF was higher in A-GFAP-A cohort (median, 90×106/L [IQR, 41-209]) compared to AQP4-IgG+ NMOSD (median, 6 × 106/L [IQR, 1-10], p = 0.018). Importantly, the higher increase in CSF protein (1319 mg/L [IQR, 1035-1519]), lactate dehydrogenase (LDH, 53.9 ± 37.2 U/L), lactic acid (3.50 ± 0.88 mmol/L), IgG (130.9 ± 60.4 mg/L), IgM (8.6 ± 6.1 mg/L) and IgA (23.0 ± 11.4 mg/L) levels in A-GFAP-A was found compared to MOGAD (CSF protein: 441 mg/L [IQR, 330–776], p = 0.004; LDH: 53.9 ± 37.2 U/L, p = 0.005; lactic acid: 2.15 ± 0.62 mmol/L, p = 0.001; IgG: 77.9 ± 71.3 mg/L, p = 0.018; IgM, 2.7 ± 2.9 mg/L, p = 0.015) and AQP4-IgG+ NMOSD (CSF protein: 386 mg/L [IQR, 369-453], p = 0.002; LDH: 23.7 ± 11.0 U/L, p = 0.048; lactic acid: 2.40 ± 0.66 mmol/L, p = 0.040; IgG, 53.2 ± 30.3 mg/L, p = 0.015; IgM, 2.1 ± 3.9 mg/L, p = 0.004; IgA, 5.2 ± 5.0 mg/L, p < 0.001). Of Note, smaller (< 2 cm), symmetrical lesions in ganglia and thalamus (5/8, 62.5%) were showed in over half of the A-GFAP-A patients (5/8, 62.5%), but never in MOGAD (0%, p = 0.001) and AQP4-IgG+NMOSD (0%, p = 0.026). In addition, diffuse meningeal enhancement was more common in A-GFAP-A (8, 88.9%) compared to MOGAD (5, 29.4%, p = 0.011) and AQP4-IgG+NMOSD (1/6, 16.7%, p = 0.011), respectively. Acute disseminated encephalomyelitis (ADEM) -like lesions occurred more frequently in MOGAD (6/16, 37.5%) but never in A-GFAP-A and AQP4-IgG+NMOSD (p = 0.02). ConclusionOur study demonstrates that several distinct features including the symptom of tremor, higher CSF immunological profiles, bilateral symmetrical lesions in ganglia, and diffuse meningeal enhancement are frequent in A-GFAP-A, whereas ADEM-like lesions seem to occur mainly in MOGAD. These signs provide crucial clinical implications in differential diagnosis for those mimicking intracranial infection as initial symptoms. Clinicians should consider the possibility of these autoimmune CNS inflammatory diseases masquerading as intracranial infection.

A case of Rosai-Dorfman’s disease as isolated mediastinal lymphadenopathy: a diagnostic challenge

BackgroundMediastinal lymphadenopathy is seen in a variety of diseases, like tuberculosis, sarcoidosis, and metastasis. The diagnosis can be confirmed by tissue sampling with endobronchial ultrasound and transbronchial needle aspirate. A middle-aged male presented to us with a history similar to tuberculosis, and was on empirical anti-tuberculosis treatment was evaluated again by EBUS-TBNA and proved to be Rosai-Dorfman’s disease. This case report emphasizes on confirming the cases of mediastinal lymphadenopathy with tissue sampling.ConclusionAll mediastinal lymphadenopathy should be evaluated in detail as the symptoms of the possible diseases, like tuberculosis, sarcoidosis, Kikuchi’s disease, Rosai-Dorfman’s disease, and malignancy can be similar. Hence, tissue sampling will confirm the diagnosis and help in appropriate management.

Unexplained fever, weight loss, and worsened dyspnea with pulmonary hypertension as the presenting symptoms of mixed connective tissue disease with interstitial lung disease: A case report with review of literature

Pulmonary manifestations of mixed connective tissue disease (MCTD) include as bronchiolitis, bronchiectasis, and interstitial lung disease with or without pulmonary hypertension. Tuberculosis (TB) is the most common diagnosis in India in the presence of constitutional symptoms such as cough, fever, and weight loss with lung parenchymal abnormality, irrespective of microscopic or nucleic acid amplification test abnormalities due to high tuberculosis prevalent tropical setting. In this case report, a 35 year old female presented with constitutional symptoms and lung parenchymal nodules, interstitial involvement with lung fibrosis and pulmonary hypertension. Mediastinal window documented necrotic mediastinal lymph nodes, without negative mycobacterial microscopic (smear examination) or genome documentation (Gene Xpert MTB/RIF). She had received empirical anti tuberculosis treatment for three months without clinical or radiological response, resulted in progression of disease with clinical and radiological worsening and referred to our unit for further workup. Bronchoscopy guided evaluation for tropical screen including bacterial, fungal and tuberculosis with malignancy was inconclusive. Vasculitis and CTD workup documented antinuclear antibody (ANA) test strongly positive with very highly raised titres, with positive antigen as U1 small nuclear ribonucleoprotein particle, SSA/RO, single strand DNA, and Scl 70. Treatment initiated with systemic steroids, tadalafil, mycophenolate and diuretics, and satisfactory clinical response documented as near complete resolution of pulmonary parenchymal abnormalities in 24 weeks and pulmonary hypertension in 12 weeks. Pulmonary manifestations of MCTD are common, underestimated in the presence of constitutional symptoms, and early pickup of entity in course of illness will have good outcome with excellent prognosis.

Tuberculous meningitis during infancy: 26 cases in South Turkey among 20years.

Due to the lack of a standard case definifion and the diffuculty in estabilishing a definitive diagnsos, TB in children needs increasing attention by physicians caring for pediatric patients. Tuberculous meningitis (TBM) is the most serious form of extrapulmonary tuberculosis that is associated with significant morbidity and mortality rate in the pediatric age group, especially in infants. This descriptive study was conducted in an University hospital, at the South of Turkey, from May 1999 to May 2019. The hospital records of 26 TBM infant that was diagnosed at our hospital were retrospectively evaluated. The epidemiological findings (age, gender, family history of TB, tuberculin skin test results, status of BCG scaring), stage of TBM at admission and clinical, laboratory and radiological features were collected. Of the 26 infants, 61.5% were male and mean age of the patients was 7,65±2,6 (range, 3-12 months). The history of close contact with an infected adult was encountered in 73.1% (19 infant) of the cases. Only 69.2% of the patients (18 case) had a BCG scar. The prodromal stage (period between the onset of symptoms to hospital admission) ranged from 4 days to 180 days (39±51.3). 2 cases were defined as stage I, 10 cases as stage II and 14 cases as stage III TBM. Only two patients were initially positive for PPD test. While no neurological findings were found in 2 patients (diagnosed as stage I), neurologic findings at the time of admission included increased intracranial pressure; alteration in consciousness (92.3%), seizures (88.4%), vomiting (61.5%) cranial nerve palsy (23%), irritability 19.2%, hemiplegia 15.3% and meningeal signs (7%, only 2 patients). The presence of hepatomegaly 26.9 % and/or splenomegaly 11.5 % and/or extrapulmonary lymphadenopathy 3.8 % in nearly half of the cases suggested that totally 42,2% of cases had disseminated of tuberculosis. On admission, 46.1% of the patients were noted to have hyponatremia. Microbiologic confirmation was established in eleven (42.3%) of the 26 infant. A positive CSF culture for Mtb and/or smear for AFB and/or PCR was obtained in only 5 (19.2%) patients, whereas 3 of the cases had accompaining gastric aspirate examination positivity. Pulmonary consolidation in 14 (53.8%) patients, miliary patern in 10 (41.6%) and pulmonary hilar lymphadenopathy in only 5 (20.8%) patients. 23 (88.4 %) had hydrocephalus, 15 (57.6 %) infarction, 10 (38.4 %) basilar meningitis and 9 (34.6%) tuberculomas. Empiric anti-tuberculosis treatment was instituted in all, at a median of 3 days (range 1-15 days) following admission. 8 (30.7%) died, 3 (11.5%) recovered completely, and 15 (57.6%) recovered with sequelae. 12 case (2 died) of the infants had required ventriculoperitoneal shunting. As early diagnosis and specific treatment appears to prevent serious complications and reduce mortality, a high index of suspicion among pediatricians is especially required in an infant with an atypical picture suggestive of tuberculosis infection.

Overlapping syndrome mimicking infectious meningoencephalitis in a patient with MOG and GFAP IgG

BackgroundCentral nervous system overlapping autoimmune syndromes are uncommon, especially with the coexistence of MOG-IgG and GFAP-IgG.Case presentationA 23-year-old woman presented with transient convulsions, a loss of consciousness, persistent fever, headache, and vomiting. Cerebrospinal fluid (CSF) analysis revealed elevated cellularity, and magnetic resonance imaging (MRI) showed diffuse leptomeningeal enhancement. She had fever and headache with antiviral and antibiotic treatment for 2 weeks, and she had empirical anti-tuberculosis treatment and oral prednisolone therapy. She was followed for 3 months after presentation with improved symptoms and normal CSF analysis. A 3-month follow-up MRI showed asymmetric lesions in the cerebellum, corona radiata, and white matter with enhancement. The anti-tuberculosis treatment was continued, and steroid therapy was discontinued. After she stopped taking prednisolone, an interrupted headache gradually appeared. MRI at 4 months after presentation revealed a partial reduction in lesions but enlarged areas in the left cerebellum and right parietal white matter and a new lesion in the region of the right ependyma with linear enhancement. Her CSF was positive for anti-myelin oligodendrocyte glycoprotein (MOG) and anti-glial fibrillary acidic protein (GFAP) antibodies using a transfected cell-based assay. She was diagnosed with overlapping syndrome of MOG‑IgG‑associated disease and GFAP astrocytopathy. She received steroid pulse therapy (methylprednisolone, 1 g for 5 days), followed by a gradual tapering of oral prednisolone and the addition of an immunosuppressant (tacrolimus, 3 mg per day). Six months after the initial presentation, she had no symptoms. An MRI showed that the lesions had diminished, and no enhancement was found.ConclusionsWe report a case that was positive for double antibodies, which was initially misdiagnosed as infectious meningoencephalitis. This case broadens the clinical and phenotypic presentation of the overlapping syndrome spectrum.

Meigs syndrome with pleural effusion as initial manifestation: A case report

BACKGROUNDMeigs syndrome is a rare neoplastic disease characterized by the triad of benign solid ovarian tumor, ascites, and pleural effusion. In postmenopausal women with pleural effusions, ascites, elevated CA-125 level, and pelvic masses, the probability of disseminated disease is high. Nevertheless, the final diagnosis is based on its histopathologic features following surgical removal of a mass lesion. Here we describe a case of Meigs syndrome with pleural effusion as the initial manifestation.CASE SUMMARYA 52-year-old woman presented with a 2-mo history of dry cough and oppression in the chest and was admitted to our hospital due to recurrent pleural effusion and gradual worsening of dyspnea that had occurred over the previous month. Two months before admission, the patient underwent repeated chest drainage and empirical anti-tuberculosis treatment. However, the pleural fluid accumulation persisted, and the patient began to experience dyspnea on exertion leading to admission. A computed tomography scan of the chest, abdominal ultrasound, and magnetic resonance imaging confirmed the presence of right-sided pleural effusion and ascites with a right ovarian mass. Serum tumor markers showed raised CA-125. With a suspicion of a malignant tumor, the patient underwent laparoscopic excision of the ovarian mass and the final pathology was consistent with an ovarian fibrothecoma. On the seventh day postoperation, the patient had resolution of the right-sided pleural effusion.CONCLUSIONDespite the relatively high risk of malignancy when an ovarian mass associated with hydrothorax is found in a patient with elevated serum levels of CA-125, clinicians should be aware about rare benign syndromes, like Meigs, for which surgery remains the preferred treatment.

S2302 Empiric Anti-Tuberculosis Treatment as a Way to Help Solve Diagnostic Challenges Between Intestinal Tuberculosis and Crohn’s Disease—A Case Presentation

S2302 Empiric Anti-Tuberculosis Treatment as a Way to Help Solve Diagnostic Challenges Between Intestinal Tuberculosis and Crohn’s Disease—A Case Presentation

Miliary tuberculosis presenting with acute respiratory distress syndrome in a patient with down syndrome

Introduction. Miliary tuberculosis (TB) is a rare and potentially fatal form of disseminated TB. It is caused by a widespread haematogenous dissemination of Mycobacterium tuberculosis from an active caseous focus to different organs. Sometimes it can have an acute presentation with a rapidonset clinical deterioration and death. Miliary TB complicated with an acute respiratory distress syndrome (ARDS) requiring mechanical ventilation (MV) is rare, even in countries with a high incidence of TB. Case report. A 35-yearold woman with Down syndrome (DS) was admitted to the Clinic for Pulmonology, Clinical Centre Kragujevac, due to an evaluation of cough and weight loss during last 2 months. Laboratory findings revealed anaemia, leukocytosis, elevated C-reactive protein (CRP) and hypoalbuminemia. A chest x-ray showed bilateral reticulonodular shadows, predominantly in the mid and lower right lung lobes. A purified protein derivative (PPD) skin test and induced sputum smear for acid-fast bacilli (AFB) were both negative. On the fifth day following admission, her health condition suddenly declined, and after developing a moderate ARDS, she was put on the mechanical ventilation. Due to a high clinical suspicion of miliary TB and the fact that her life was compromised, an empirical anti-tuberculosis therapy was initiated. Despite all therapeutic and supportive measures, the patient expired 3 days later. The diagnosis of miliary TB was established post-mortem. Conclusion. Miliary TB should be kept in mind in patients with DS due to immunosuppression associated with deficient cell-mediated immunity. The development of ARDS as a complication of miliary TB is difficult to identify due to a low causal association. High clinical suspicion and a chest radiograph with a typical appearance of miliary pattern justify the initiation of empirical anti-tuberculosis treatment in such patients, as an attempt to change poor prognosis.

Janus kinase 1/2 inhibition for the treatment of autoinflammation associated with heterozygous TNFAIP3 mutation

Janus kinase 1/2 inhibition for the treatment of autoinflammation associated with heterozygous TNFAIP3 mutation

Primary encapsulating peritoneal sclerosis in a tuberculosis-endemic region.

Primary encapsulating peritoneal sclerosis is an enigmatic entity that may be erroneously diagnosed as abdominal tuberculosis in tuberculosis-endemic regions. In patients with a history of recurrent intestinal obstruction, a high index of suspicion along with characteristic images of computed tomography scan can help in diagnosis. Unless there is strong supportive evidence preoperatively, empirical antituberculosis treatment should be avoided.

Chronic lung disease in adult recurrent tuberculosis survivors in Zimbabwe: a cohort study.

To examine the prevalence and magnitude of chronic lung disease (CLD) and its association with empiric anti-tuberculosis treatment (due to lack of bacteriologic confirmation) among recurrent tuberculosis (TB) survivors in a human immunodeficiency virus (HIV) prevalent setting. Prospective cohort study of retreatment TB survivors in Harare, Zimbabwe. At median follow-up of 2 years post-treatment initiation, we characterized mortality, respiratory impairment, and mental health. Among 175 retreatment TB survivors, 65% of whom were HIV-positive and 21% had been empirically treated, multiparameter CLD was noted at follow-up among 14% of patients (95%CI 9.0-19.7), with a six-fold increase in age-adjusted death in the first year following treatment completion. Empirically treated TB (relative risk [RR] 3.4, 95%CI 1.4-8.3) was associated with CLD, as was the number of previous anti-tuberculosis treatment courses in dose-dependent fashion (three vs. one, RR 6.2, 95%CI 1.7-22.1). Among retreatment TB survivors, 33% (95%CI 26.0-40.1) had persistent respiratory symptoms (Chronic Obstructive Pulmonary Disease Assessment Test score 10); 26% (95%CI 19.8-33.0) significant deficits in exercise capacity (median incremental shuttle walk test distance, 550 m; Q1-Q₃ 440-730 m); 83% (95%CI 75.7-89.7) residual radiographic abnormalities on chest X-ray; 12% (95%CI 6.6-16.1%) moderate-to-severe obstruction on spirometry; and 13% (95%CI 7.6-17.5%) major depression. Despite successful treatment, retreatment TB survivors retain a substantial risk of morbidity and mortality.

Microbiological diagnosis of tuberculous meningitis: Phenotype to genotype.

Tuberculous meningitis (TBM) is a commonly encountered central nervous system infection. Characteristic clinical, imaging and cerebrospinal fluid parameters help clinicians to make a prompt presumptive diagnosis that enables them to start empirical anti-tuberculosis treatment. There are several close mimic to TBM, such as partially treated pyogenic meningitis, fungal meningitis, sarcoidosis, meningeal metastases and meningeal lymphomatosis. Microbiological confirmation instils a sense of confidence amongst treating physicians. With conventional phenotypic methods (cerebrospinal fluid microscopy and culture), in more than 50 per cent patients, microbiological confirmation is not achieved. Moreover, these methods take a long time before providing conclusive results. Negative result does not rule out Mycobacterium tuberculosis infection of the brain. Genotypic methods, such as IS6110 polymerase chain reaction and automated Xpert M. tuberculosis/rifampicin (MTB/RIF) assay system improved the TBM diagnostics, as results are rapidly available. Xpert MTB/RIF assay, in addition, detects rifampicin resistance. Xpert MTB/RIF Ultra is advanced technology which has higher (60-70%) sensitivity and is being considered a game-changer in the diagnostics of TBM. A large number of TBM cases remain unconfirmed. The situation of TBM diagnostics will remain grim, if low-cost technologies are not widely available. Till then, physicians continue to rely on their clinical acumen to start empirical anti-tuberculosis treatment.

Evaluation of the culture-enhanced Xpert MTB/RIF assay for the diagnosis of smear-negative tuberculosis

ObjectivesTo evaluate a new tool for the early diagnosis of tuberculosis. MethodsA total of 374 smear-negative clinical specimens from patients with suspected tuberculosis were evaluated using a new procedure consisting of a preliminary step of culture in broth bottles followed by the detection of Mycobacterium tuberculosis complex (Mtb) and rifampicin resistance by the Xpert MTB/RIF assay (XMTB-RIF). ResultsA total of 30 Mtb strains were isolated, all susceptible to rifampicin. When broth cultures were subjected to XMTB-RIF analysis after 15 days of incubation, sensitivity, specificity, PPV, and NPV were each 100% when compared with liquid culture. ConclusionThe XMTB-RIF assay used in 15-day broth cultures may provide a final culture result for smear-negative specimens. This process, combined with clinical signs, may contribute to rapidly diagnosing tuberculosis and also to the early reevaluation of empirical antituberculosis treatment.

Hodgkin lymphoma, HIV, and Epstein-Barr virus in Malawi: Longitudinal results from the Kamuzu Central Hospital Lymphoma study.

Contemporary descriptions of classical Hodgkin lymphoma (cHL) are lacking from sub-Saharan Africa where human immunodeficiency virus (HIV) and Epstein-Barr virus (EBV) are prevalent. We describe a prospective cHL cohort in Malawi enrolled from 2013 to 2015. Patients received standardized treatment and evaluation, including HIV status and EBV testing of tumors and plasma. Among 31 patients with confirmed cHL, the median age was 19 years (range, 2-51 years) and 22 (71%) were male. Sixteen patients (52%) had stage III/IV, 25 (81%) B symptoms, and 16 (52%) performance status impairment. Twenty-three patients (74%) had symptoms >6 months, and 11 of 29 (38%) had received empiric antituberculosis treatment. Anemia was common with median hemoglobin 8.2 g/dL (range, 3.1-17.1 g/dL), which improved during treatment. No children and 5 of 15 adults (33%) were HIV+. All HIV+ patients were on antiretroviral therapy for a median 15 months (range, 2-137 months), with median CD4 count 138 cells/μL (range, 23-329 cells/μL) and four (80%) having undetectable HIV. EBV was present in 18 of 24 (75%) tumor specimens, including 14 of 20 (70%) HIV- and 4 of 4 (100%) HIV+. Baseline plasma EBV DNA was detected in 25 of 28 (89%) patients, with median viral load 4.7 (range, 2.0-6.7) log10 copies/mL, and subsequently declined in most patients. At 12 months, overall survival was 75% (95% confidence interval [CI], 55%-88%) and progression-free survival 65% (95% CI, 42%-81%). Baseline plasma EBV DNA and persistent viremia during treatment were associated with poorer outcomes. cHL in Malawi is characterized by delayed diagnosis and advanced disease. Most cases were EBV associated and one-third of adults were HIV+. Despite resource limitations, 12-month outcomes were good.