Early Microbiologic Markers of Pulmonary Tuberculosis Treatment Outcomes.

Rationale: Earlier biomarkers of pulmonary tuberculosis (PTB) treatment outcomes are critical to monitor shortened anti-TB treatment (ATT). Objectives: To identify early microbiologic markers of unfavorable TB treatment outcomes. Methods: We performed a subanalysis of 2 prospective TB cohort studies conducted from 2013 to 2019 in India. We included participants aged ⩾18 years who initiated 6-month ATT for clinically or microbiologically diagnosed drug-sensitive PTB and completed at least one follow-up visit. Sputum specimens were subjected to a baseline Xpert Mycobacterium tuberculosis/rifampin (MTB/RIF) assay, acid-fast bacilli (AFB) microscopy and liquid and solid cultures, and serial AFB microscopy and liquid and solid cultures at weeks 2, 4, and 8. Poisson regression was used to assess the impact of available microbiologic markers (test positivity, smear grade, time to detection, and time to conversion) on a composite outcome of failure, recurrence, or death by 18 months after the end of treatment. Models were adjusted for age, sex, nutritional status, diabetes, smoking, alcohol consumption, and regimen type. Results: Among 1,098 eligible cases, there were 251 (22%) adverse TB treatment outcomes: 127 (51%) treatment failures, 73 (29%) recurrences, and 51 (20%) deaths. The primary outcome was independently associated with the Xpert MTB/RIF assay (medium-positive adjusted incidence rate ratio [aIRR], 1.91; 95% confidence interval [CI], 1.07-3.40; high-positive aIRR, 2.51; 95% CI, 1.41-4.46), positive AFB smear (aIRR, 1.48; 95% CI, 1.06-2.06), and positive liquid culture (aIRR, 1.98; 95% CI, 1.21-3.23) at baseline; Week 2 positive liquid culture (aIRR, 1.47; 95% CI, 1.04-2.09); and Week 8 positive AFB smear (aIRR, 1.63; 95% CI, 1.06-2.50) and positive liquid culture (aIRR, 1.54; 95% CI, 1.07-2.22). There was no evidence of Mycobacterium tuberculosis growth in the Mycobacterium Growth Indicator Tube at Week 4 conferring a higher risk of adverse outcomes (aIRR, 1.25; 95% CI, 0.89-1.75). Conclusions: Our analysis identifies Week 2 respiratory mycobacterial culture as the earliest microbiologic marker of unfavorable PTB treatment outcomes.

Clove stalk aspiration: An unusual cause of chronic cough.

Foreign body aspiration in adults is one of the uncommon causes of chronic cough and may be missed if the patient already has a known cause of chronic cough, but the same is not responding to therapy. A 72-year-old male patient, a known case of allergic rhinitis, presented with a history of cough for 6 months. There was unsatisfactory response to treatment with antibiotics, inhalational corticosteroids, oral corticosteroids, bronchodilators, and antireflux treatment. High-resolution computed tomography was normal. However, fiber optic bronchoscopy revealed a foreign body in the right lower lobe, which was removed and was identified as clove stalk. This led to rapid relief of symptoms. Clove stalk aspiration is an unusual foreign body causing chronic cough, which has not yet been reported.

An unusual complication secondary to kanamycin use in a patient of multidrug-resistant pulmonary tuberculosis.

Gitelman syndrome (GS) is a rare genetic renal disease characterized by hypomagnesemia, hypokalemia, hypocalciuria, and metabolic alkalosis. It usually presents in late childhood or early adulthood. A 30-year-old female diagnosed case of multidrug-resistant (MDR-TB) pulmonary tuberculosis 2 months ago presented to our outpatient department with intermittent painful spasms in all four limb muscles. Her treatment regimen consisted of kanamycin, levofloxacin, cycloserine, and ethionamide. On further evaluation, her investigations revealed hypokalemia, hypocalcemia, hypomagnesemia, metabolic alkalosis with normal serum creatinine level. She was initially treated with intravenous calcium and potassium. However, the electrolyte abnormalities and metabolic alkalosis persisted. All her lab parameters became normal after discontinuing kanamycin and electrolyte replacement for 4 weeks. She was discharged and advised to continue her antituberculosis treatment. There was no recurrence of symptoms on further follow up.

Glue ablation of Rasmussen's aneurysm in a case of epituberculosis.

A woman in her 40s presented with massive haemoptysis and breathlessness for 1 day. She had been diagnosed with pulmonary tuberculosis based on sputum CBNAAT (Cartridge Based Nucleic Acid Amplification Test) and was on antitubercular treatment for previous 2 weeks. Her chest X-ray showed right middle lobe lateral segment dense consolidation with bilateral nodular infiltrates. CT pulmonary angiography (CTPA) revealed a well-defined homogenously enhancing vascular lesion of size 10×11×13 mm in the right hilar region communicating with the descending branch of right pulmonary artery, suggesting a Rasmussen's aneurysm. It was in close proximity to the segmental bronchus that was almost completely occluded, suggesting epituberculosis. Transvenous pulmonary artery glue embolisation successfully achieved complete ablation of the aneurysm with preserved arterial flow. She has later completed 6 months of antitubercular treatment and is cured with no recurrence of haemoptysis. Her lung infiltrates have resolved with some lung scarring.

A Systematic Evaluation of Risk Predictors for COVID-19 Sequelae.

Background Multisystem involvement in coronavirus disease 2019 (COVID-19) is known since the beginning of the pandemic, and post-COVID-19 sequelae have often been reported. The term 'long Covid' encompasses these signs and symptoms. The aim of our study was to study different after-effects which patients endured within 12 months after recovery from acute COVID-19 and to study the various risk predictors. Methods This was a longitudinal observational study of a cohort of 146 patients who recovered from COVID-19 illness. Patients were enrolled during the first four weeks of the onset of their illness, and a monthly follow-up assessment was done for six months that included a detailed history of persistent or new symptoms, new illnesses diagnosed, and complete biochemical, pulmonary, cardiac, neurological and psychiatric evaluation, both objective and subjective. A final follow-up was also done at the end of one year of enrolment. Based on the patient's self-reported history and our multi-system assessment, recorded sequelae were classified according to the involved organ system. These were correlated with possible risk predictors and statistically significant associations were established. Results One hundred and twenty subjects out of 146 total subjects qualified for final analysis. Pulmonary sequelae (48/120; 40%) were the most followed by psychiatric (30/120; 25%), neurological (26/120; 21.7%), and opportunistic infections (7/120; 5.8%). A total of 39/120 (32.1%) cases complained of prolonged dyspnoea. Six out of 120 i.e. 5% of study participants had new-onset diabetes. Twenty-six out of 120 (21.7%) had radiological signs of pulmonary fibrosis. Patients with co-morbidities, older age, higher body mass index, and patients with severe disease were found to be at higher risk of developing these sequelae. Poor nutrition, female gender, and hospitalization were predictors of psychiatric sequelae. Diabetes and liberal steroid use during COVID-19 management were predictors of opportunistic fungal infections. Conclusion This study evaluated post-COVID-19 sequalae in-depth both objectively and subjectively. Some specific predictors for specific sequelae were confirmed on statistical correlation. Long-term follow-up of high-risk persons is therefore recommended after the cure of COVID-19.

TB patients: Is sputum disinfection important?

BACKGROUND: Patients with pulmonary tuberculosis (TB) may produce large amount of infectious sputum which needs to be handled carefully both in health care and household settings. As mycobacteria may survive for long duration in sputum; proper collection, disinfection and disposal is necessary to avoid potential disease transmission. We aimed to assess the efficacy of bedside disinfectant treatment of sputum produced by TB patients using easily available disinfectants that can be used both in TB wards and household settings, to sterilize the infected sputum and compared it with sputum without disinfectant treatment. METHODS: It was a prospective case control study. Sputum of total 95 patients with sputum smear positive pulmonary tuberculosis was collected in sputum containers with lids. Patients on anti-tubercular treatment for more than 2 weeks were excluded. Each patient was given 3 sterile sputum containers to expectorate, Container A containing 5% Phenol solution, Container B containing 4.8% Chloroxylenol and Container C without any disinfectant, acting as a control. Thick sputum was liquified with Mucolytic agent N-acetyl cysteine (NAC). Aliquots of the sputum were sent for culture in Lowenstein-Jensen medium on day 0 (to confirm alive mycobacteria) and on day 1 i.e., after 24 hours (to evaluate effective sterilization). Drug resistance testing was done on all grown mycobacteria. RESULTS: If the samples on day 0 did not grow mycobacteria (indicating non-viable mycobacteria) or day 1 sample grew contaminants in any of the three containers, they were excluded from the analysis (15/95). In remaining 80 patients, bacilli were alive on day 0 and remained alive even after 24 hours (day 1) in control samples (without disinfectants). The sputum was effectively disinfected resulting in no growth after 24 hours (day 1) in 71/80 (88.75%) containing 5% Phenol and 72/80 (90%) with 4.8% Chloroxylenol. The efficacy of disinfection was 71/73 (97.2%) and 72/73 (98.6%) for drug sensitive mycobacteria respectively. The mycobacteria however remained alive with these disinfectants in all 7 samples of drug-resistant mycobacteria with an efficacy of 0%. CONCLUSION: We recommend use of simple disinfectants like 5% Phenol or 4.8% Chloroxylenol for safe disposal of sputum of pulmonary tuberculosis patients. It is necessary as sputum collected without disinfection remained infectious after 24 hours. Resistance of all drug resistant mycobacteria to disinfectants was a novel chance finding. This needs further confirmatory studies.

Massive generalised lymphadenopathy: a rare presentation of tuberculosis with a favourable outcome.

We present a case of massive generalised necrotic lymphadenopathy due to tuberculosis (TB) without any solid organ involvement. An immunocompetent man in his early 30s presented 1 year ago with weight loss, cough and a solitary cervical node. Contrast-enhanced CT scan thorax showed massive enlargement of almost all groups of mediastinal nodes with large areas of necrosis. Ultrasound examination revealed multiple necrotic abdominal nodes. Core biopsy of the supraclavicular node confirmed TB by histopathology and molecular testing. His Mantoux test was negative suggesting tuberculin anergy. Biopsy of deep nodes was avoided. He responded well to standard antitubercular treatment in weight-corrected doses along with systemic steroids which were prescribed to prevent further breakdown/rupture of nodes. After the extended TB treatment for 12 months, he is asymptomatic and has gained weight, with complete resolution of cervical node and near complete resolution of all deep nodes.

Sex Differences in TB Clinical Presentation, Drug Exposure, and Treatment Outcomes in India.

BACKGROUND: The role of sex differences in clinical presentation, TB drug pharmacokinetic variables, and treatment outcomes is unclear. RESEARCH QUESTION: What is the effect of sex on TB disease severity, drug exposure, and treatment outcome? STUDY DESIGN AND METHODS: This study was a prospective cohort study conducted in India. It assessed TB disease severity; risk of unfavorable treatment outcomes (failure, recurrence, and death) according to sex; and risk factors for unfavorable outcomes stratified according to sex. Effects of sex on the pharmacokinetic variables (maximum concentration and area under the curve) of rifampicin, isoniazid, and pyrazinamide were estimated by using noncompartmental analyses. RESULTS: Of 1,541 people with microbiologically confirmed TB, 567 (37%) were women. Women had a lower risk of high mycobacterial burden (smear grade ≥ 2 and/or time to detection < 7 days) with an adjusted OR of 0.70 (95% CI, 0.56-0.87). Among the 744 participants who were followed up prospectively, 261 (35%) were women. Women had a lower risk of unfavorable treatment outcomes (adjusted incidence risk ratio, 0.60; 95% CI, 0.43-0.85), mostly because recurrence was lower (adjusted incidence risk ratio, 0.45; 95% CI, 0.23-0.86). Isoniazid (but not rifampicin and pyrazinamide) maximum concentration and area under the curve were significantly higher among women (P < .01) than men. Among women, unfavorable outcomes were more likely among those with cavitary disease, but among men, increased risk of unfavorable outcomes was associated with alcohol use, higher BMI, and lower glycated hemoglobin level. INTERPRETATION: Women present with lower mycobacterial burden, achieve higher TB drug exposure, and are less likely to have unfavorable treatment outcomes than men. Strategies to improve TB treatment success should take into account sex differences in risk factors for unfavorable outcomes.

Management of COVID-19: A comprehensive and practical approach.

Since the beginning of Corona Virus Disease (COVID) pandemic, there has been lack of clarity about the management protocols in spite of frequently updated national and international guidelines. Irrational use of unproven therapies has not been helpful in improving treatment outcomes. Early use of high-dose steroids or late use of antiviral medicines might have caused more harm than the benefit. There is also lot of fear about post-COVID fibrosis leading to extended use of steroids and antifibrotics. We reviewed the available COVID guidelines and treatment protocols in the light of scientific evidence generated over last 2 years by a systematic literature search using various databases (PubMed, Google Scholar, MEDLINE, UpToDate, Embase, and Web of Science). This article presents a comprehensive approach to the diagnosis, appropriate investigations, their interpretations, and use of specific therapies according to the stage of disease.

Letter to Editor in Response to Case Report Titled "A Novel Treatment for Malignant Cough Syncope" Published in JAPI 2020;68:83-85.

We read with interest the article titled "A Novel Treatment for Malignant Cough Syncope" published in JAPI 2020;68:83-85.

Tuberculosis notification: An inquiry among private practitioners in Pimpri-Chinchwad municipal corporation area of Maharashtra, India.

BACKGROUND: The Government of India implemented mandatory TB notification policy since 2012. After that India's TB notifications from the private sector steadily increased; however, less is known about private practitioners' (PP's) experiences with TB notification. The present study aims to fulfil this gap. METHODS: We conducted a cross-sectional study during November 2019 to March 2020 in Pimpri-Chinchwad Municipal Corporation (PCMC) area of Maharashtra State. We used a mixed methods approach which involved a survey of 200 PPs and in-depth interviews (IDIs) with 7 PPs and 8 National TB Elimination Program (NTEP) staff. The data were presented in the form of frequencies and percentages and thematic analysis was performed on the qualitative data. RESULTS: The study revealed that most PPs (194 of 200; 97%) were aware of TB notification and 75% reported that they notify TB cases to the NTEP. Of those who notify, majority (129 of 145; 89%) reported that they use paper-based notification being the convenient method due to in-person visit and help by the NTEP staff. Only a third of PPs were aware of electronic notification methods. The main reasons behind low utilization of web based and mobile application were unfamiliarity and technical issues such as poor network connectivity. A third of PPs were aware about monetary incentives for notification and only 17% reported actual receipt of incentive at some point. CONCLUSIONS: Our study identifies several areas where the NTEP can undertake interventions to strengthen the implementation of mandatory TB notification policy. Low awareness about electronic notification methods and preference for paper-based notification in this Study area suggest that more efforts are necessary for successful transitioning from paper-based to electronic notification system.

Diabetes Mellitus and Tuberculosis Treatment Outcomes in Pune, India.

BACKGROUND: Diabetes mellitus (DM) increases the risk of tuberculosis (TB) disease. Knowledge of the impact of DM on TB treatment outcomes is primarily based on retrospective studies. METHODS: We conducted a prospective cohort study of new pulmonary TB patients with and without DM (TB-DM and TB only) in India. The association of DM with a composite unfavorable TB treatment outcome (failure, recurrence, mortality) over 18 months was determined, and the effect of DM on all-cause mortality and early mortality (death during TB treatment) was assessed. RESULTS: Of 799 participants, 574 (72%) had TB only and 225 (28%) had TB-DM. The proportion of patients with DM who experienced the composite outcome was 20%, as compared with 21% for TB-only participants (adjusted hazard ratio [aHR], 1.13; 95% CI, 0.75-1.70). Mortality was higher in participants with DM (10% vs 7%), and early mortality was substantially higher among patients with DM (aHR, 4.36; 95% CI, 1.62-11.76). CONCLUSIONS: DM was associated with early mortality in this prospective cohort study, but overall unfavorable outcomes were similar to participants without DM. Interventions to reduce mortality during TB treatment among people with TB-DM are needed.

Lipid mediators of inflammation and Resolution in individuals with tuberculosis and tuberculosis-Diabetes.

Individuals with concurrent tuberculosis (TB) and Type 2 diabetes (DM) have a higher risk of adverse outcomes. To better understand potential immunological differences, we utilized a comprehensive panel to characterize pro-inflammatory and pro-resolving (i.e., mediators involved in the resolution of inflammation) lipid mediators in individuals with TB and TB-DM. A nested cross-sectional study of 40 individuals (20 newly diagnosed DM and 20 without DM) was conducted within a cohort of individuals with active drug-susceptible treatment-naïve pulmonary TB. Lipid mediators were quantified in serum samples through lipid mediator profiling. We conducted correlation-based analysis of these mediators. Overall, the arachidonic acid-derived leukotriene and prostaglandin families were the most abundant pro-inflammatory lipid mediators, while lipoxins and maresins families were the most abundant pro-resolving lipid mediators in individuals with TB and TB-DM. Individuals with TB-DM had increased correlations and connectivity with both pro-inflammatory and pro-resolving lipid mediators compared to those with TB alone. We identified the most abundant lipid mediator metabolomes in circulation among individuals with TB and TB-DM; in addition, our data shows a substantial number of significant correlations between both pro-inflammatory and pro-resolving lipid mediators in individuals with TB-DM, delineating a molecular balance that potentially defines this comorbidity.

Use of Smartphone-Based Video Directly Observed Therapy (vDOT) in Tuberculosis Care: Single-Arm, Prospective Feasibility Study.

BACKGROUND: India accounts for nearly one-quarter of the global tuberculosis (TB) burden. Directly observed treatment (DOT) through in-person observation is recommended in India, although implementation has been heterogeneous due largely to resource limitations. Video DOT (vDOT) is a novel, smartphone-based approach that allows for remote treatment monitoring through patient-recorded videos. Prior studies in high-income, low disease burden settings, such as the United States, have shown vDOT to be feasible, although little is known about the role it may play in resource-limited, high-burden settings. OBJECTIVE: The goal of the research was to assess the feasibility and acceptability of vDOT for adherence monitoring within a resource-limited, high TB burden setting of India. METHODS: We conducted a prospective, single-arm, pilot implementation of vDOT in Pune, India. Outcome measures included adherence (proportion of prescribed doses observed by video) and verifiable fraction (proportion of prescribed doses observed by video or verbally confirmed with the patient following an incomplete/unverifiable video submission). vDOT acceptability among patients was assessed using a posttreatment survey. RESULTS: A total of 25 patients enrolled. The median number of weeks on vDOT was 13 (interquartile range [IQR] 11-16). Median adherence was 74% (IQR 62%-84%), and median verifiable fraction was 86% (IQR 74%-98%). More than 90% of patients reported recording and uploading videos without difficulty. CONCLUSIONS: We have demonstrated that vDOT may be a feasible and acceptable approach to TB treatment monitoring in India. Our work expands the evidence base around vDOT by being one of the first efforts to evaluate vDOT within a resource-limited, high TB burden setting. To our knowledge, this is the first reported use of vDOT in India.

Effect of Diabetes Mellitus on the Pharmacokinetics and Pharmacodynamics of Tuberculosis Treatment.

Diabetes mellitus (DM) and tuberculosis (TB) are two common diseases with increasing geographic overlap and clinical interactions. The effect of DM and hemoglobin A1c (HbA1c) values on the pharmacokinetics (PK) and pharmacodynamics (PD) of anti-TB drugs remains poorly characterized. Newly diagnosed TB patients with and without DM starting fixed-dose, thrice-weekly treatment underwent sampling for PK assessments (predose and 0.5, 2, and 6 h postdose) during the intensive and continuation phases of treatment. The effect of DM and HbA1c values on the maximum concentration (Cmax) of rifampin, isoniazid, and pyrazinamide and the association between drug concentrations and microbiologic and clinical outcomes were assessed. Of 243 patients, 101 had DM. Univariate analysis showed significant reductions in the Cmax of pyrazinamide and isoniazid (but not rifampin) with DM or increasing HbA1c values. After adjusting for age, sex, and weight, DM was associated only with reduced pyrazinamide concentrations (adjusted geometric mean ratio = 0.74, P = 0.03). In adjusted Cox models, female gender (adjusted hazards ratio [aHR] = 1.75, P = 0.001), a lower smear grade with the Xpert assay (aHR = 1.40, P < 0.001), and the pyrazinamide Cmax (aHR = 0.99, P = 0.006) were independent predictors of sputum culture conversion to negative. Higher isoniazid or rifampin concentrations were associated with a faster time to culture conversion in patients with DM only. A pyrazinamide Cmax above the therapeutic target was associated with higher unfavorable outcomes (treatment failure, relapse, death) (odds ratio = 1.92, P = 0.04). DM and higher HbA1c values increased the risk of not achieving therapeutic targets for pyrazinamide (but not rifampin or isoniazid). Higher pyrazinamide concentrations, though, were associated with worse microbiologic and clinical outcomes. DM status also appeared to influence PK-PD relationships for isoniazid and rifampin.

The microbial colonization profile of respiratory devices and the significance of the role of disinfection: a blinded study.

INTRODUCTION: Approximately 10-40% of all the nosocomial infections are pulmonary, which lead to grave complications. Elderly, debilitated, or critically ill patients are at a high risk. The respiratory care equipments which include ventilators, humidifiers, nebulizers may have been identified as the potential vehicles which cause major nosocomial infections if they are colonized by fungi or bacteria. AIM: To determine the rate of colonization by bacteria and fungi of the oxygen humidifier chambers of the portable cylinders and central lines at our hospital. The Hudson's chambers of nebulizers were also studied for the same. METHODS: Swab samples were obtained from the equipments by using sterile cotton swabs on a tuesday, as these chambers were usually cleaned on every Saturday. Spot samples were taken from the ICUs, wards, the casualty and OPDs on a single day. Air samples were also obtained on the same day to determine whether the fungal spore load in the inhaled room air was normal or high. We performed a disinfection with 70% ethanol after cleaning these devices. RESULTS: 53/70 (75.71%) samples showed fungal growth; out of which, 23/33 (69.70%) were from the ICU, 24/30(80%) were from the wards and 6/7 (85.71%) were from the OPDs. 23/30 (76.66%) swabs from the central line humidifiers, 18/23(78.26%) swabs from the O2 cylinder humidifiers and 8/17 (47.5%) swabs from the nebulizers grew bacteria. Of the total 61(87.14%) bacterial isolates, 42(68.85%) were gram negative bacteria and 19(31.14%) were gram positive cocci. Out of the 42 gram negative bacteria, 17 were multi-drug resistant like ESBL producers ie. Pseudomonas spp. (6) Acinetobacter spp.(4), Klebseilla pneumoniae (4), E.coli (2) and Stenotrophomonas maltophila (1). Our findings (before disinfection) showed that the colonization rate for fungi was 75% and that for bacteria, it was 87%. After the 70% ethanol disinfection and strict compliance with the hand hygiene, the colonization rates reduced significantly. The fungal colonization rate was reduced and only 15% fungi grew after the disinfection, while only 12% bacterial colonization rate was found. CONCLUSION: This study indicates a potential in-hospital source of allergens and infections. The oxygen and nebulizer chambers need to be cleaned more frequently with disinfectants, to control the possible nosocomial infections.

A deadly combination of AIDS, TB and cardiac tumour.

Immunocompromised status in AIDS makes differential diagnosis of any symptom very difficult for a clinician. Sharp clinical judgement and plenty of investigations may be needed to reach the diagnosis, as in this case. We hereby present a case of AIDS and active tuberculosis (TB) under treatment. The patient developed acute onset multifocal neurological symptoms following an episode of fever and diarrhoea. The MRI scan revealed numerous large cerebral infarcts. On investigations to evaluate brain infarcts, we made a diagnosis of left atrial cardiac tumour. Association of cardiac tumours with AIDS has only been rarely reported. It is uncertain if these can be opportunistic tumours in AIDS. The patient successfully came out of this deadly combination of diseases, viz AIDS, TB and large brain infarcts due to atrial tumour; with almost complete recovery.