Point-of-care breath test for biomarkers of active pulmonary tuberculosis

Rationale: Volatile organic compounds (VOCs) in breath provide biomarkers of tuberculosis (TB) because Mycobacterium tuberculosis manufactures VOC metabolites that are detectable in the breath of infected patients. Objectives: We evaluated breath VOC biomarkers in subjects with active pulmonary TB, using an internet-linked rapid point-of-care breath test. Methods: 279 subjects were studied at four centers in three countries, Philippines, UK, and India, and data was analyzed from 251 (130 active pulmonary TB, 121 controls). A point-of-care system collected and concentrated breath and air VOCs, and analyzed them with automated thermal desorption, gas chromatography, and surface acoustic wave detection. A breath test was completed in 6 min. Chromatograms were converted to a series of Kovats Index (KI) windows, and biomarkers of active pulmonary TB were identified by Monte Carlo analysis of KI window alveolar gradients (abundance in breath minus abundance in room air). Measurements and main results: Multiple Monte Carlo simulations identified eight KI windows as biomarkers with better than random performance. Four KI windows corresponded with KI values of VOCs previously identified as biomarkers of pulmonary TB and metabolic products of M. tuberculosis, principally derivatives of naphthalene, benzene and alkanes. A multivariate predictive algorithm identified active pulmonary TB with 80% accuracy (area under curve of receiver operating characteristic curve), sensitivity = 71.2%, and specificity = 72%. Accuracy increased to 84% in age-matched subgroups. In a population with 5% prevalence, the breath test would identify active pulmonary TB with 98% negative predictive value and 13% positive predictive value. Conclusions: A six-minute point-of-care breath test for volatile biomarkers accurately identified subjects with active pulmonary TB. © 2011 Elsevier Ltd. All rights reserved

The epidemiology, pathogenesis, transmission, diagnosis, and management of multidrug-resistant, extensively drug-resistant, and incurable tuberculosis.

Global tuberculosis incidence has declined marginally over the past decade, and tuberculosis remains out of control in several parts of the world including Africa and Asia. Although tuberculosis control has been effective in some regions of the world, these gains are threatened by the increasing burden of multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis. XDR tuberculosis has evolved in several tuberculosis-endemic countries to drug-incurable or programmatically incurable tuberculosis (totally drug-resistant tuberculosis). This poses several challenges similar to those encountered in the pre-chemotherapy era, including the inability to cure tuberculosis, high mortality, and the need for alternative methods to prevent disease transmission. This phenomenon mirrors the worldwide increase in antimicrobial resistance and the emergence of other MDR pathogens, such as malaria, HIV, and Gram-negative bacteria. MDR and XDR tuberculosis are associated with high morbidity and substantial mortality, are a threat to health-care workers, prohibitively expensive to treat, and are therefore a serious public health problem. In this Commission, we examine several aspects of drug-resistant tuberculosis. The traditional view that acquired resistance to antituberculous drugs is driven by poor compliance and programmatic failure is now being questioned, and several lines of evidence suggest that alternative mechanisms-including pharmacokinetic variability, induction of efflux pumps that transport the drug out of cells, and suboptimal drug penetration into tuberculosis lesions-are likely crucial to the pathogenesis of drug-resistant tuberculosis. These factors have implications for the design of new interventions, drug delivery and dosing mechanisms, and public health policy. We discuss epidemiology and transmission dynamics, including new insights into the fundamental biology of transmission, and we review the utility of newer diagnostic tools, including molecular tests and next-generation whole-genome sequencing, and their potential for clinical effectiveness. Relevant research priorities are highlighted, including optimal medical and surgical management, the role of newer and repurposed drugs (including bedaquiline, delamanid, and linezolid), pharmacokinetic and pharmacodynamic considerations, preventive strategies (such as prophylaxis in MDR and XDR contacts), palliative and patient-orientated care aspects, and medicolegal and ethical issues

Understanding the potential impact of different drug properties on SARS-CoV-2 transmission and disease burden : a modelling analysis

Q1Q1Background The unprecedented public health impact of the COVID-19 pandemic has motivated a rapid search for potential therapeutics, with some key successes. However, the potential impact of different treatments, and consequently research and procurement priorities, have not been clear. Methods and Findings develop a mathematical model of SARS-CoV-2 transmission, COVID-19 disease and clinical care to explore the potential public-health impact of a range of different potential therapeutics, under a range of different scenarios varying: i) healthcare capacity, ii) epidemic trajectories; and iii) drug efficacy in the absence of supportive care. In each case, the outcome of interest was the number of COVID-19 deaths averted in scenarios with the therapeutic compared to scenarios without. We find the impact of drugs like dexamethasone (which are delivered to the most critically-ill in hospital and whose therapeutic benefit is expected to depend on the availability of supportive care such as oxygen and mechanical ventilation) is likely to be limited in settings where healthcare capacity is lowest or where uncontrolled epidemics result in hospitals being overwhelmed. As such, it may avert 22% of deaths in highincome countries but only 8% in low-income countries (assuming R=1.35). Therapeutics for different patient populations (those not in hospital, early in the course of infection) and types of benefit (reducing disease severity or infectiousness, preventing hospitalisation) could have much greater benefits, particularly in resource-poor settings facing large epidemics. Conclusions There is a global asymmetry in who is likely to benefit from advances in the treatment of COVID-19 to date, which have been focussed on hospitalised-patients and predicated on an assumption of adequate access to supportive care. Therapeutics that can feasibly be delivered to those earlier in the course of infection that reduce the need for healthcare or reduce infectiousness could have significant impact, and research into their efficacy and means of delivery should be a priorityRevista Internacional - Indexad

Worldwide Effects of Coronavirus Disease Pandemic on Tuberculosis Services, January–April 2020

Coronavirus disease has disrupted tuberculosis services globally. Data from 33 centers in 16 countries on 5 continents showed that attendance at tuberculosis centers was lower during the first 4 months of the pandemic in 2020 than for the same period in 2019. Resources are needed to ensure tuberculosis care continuity during the pandemic

Tropical pulmonary eosinophilia - A review

Tropical pulmonary eosinophilia (TPE) is a syndrome of wheezing, fever and eosiniphilia seen predominantly in the Indian subcontinent and other tropical areas. Its etiological link with Wuchereria bancrofti and Brugia malayi has been well established. The pathogenesis is due to an exaggerated immune response to the filarial antigens which includes type I, type III and type IV reactions with eosinophils playing a pivotal role. Peripheral blood eosinophilia is usually striking with levels over 3000/΅l being common. High serum levels of IgE and filarial-specific IgE and IgG are also found. The pathology may vary from an acute eosinophilic alveolitis to histiocytic infiltration depending on the stage of the disease. While earlier studies had suggested that the disease runs a benign course, more recent work has shown that untreated TPE could result in a fair degree of respiratory morbidity. Pulmonary function tests may show a mixed restrictive and obstructive abnormality with a reduction in diffusion capacity. The bronchoalveolar lavage (BAL) eosinophil count has a negative correlation with the diffusion capacity. Treatment consists of diethylcarbamazine (DEC) for at least three weeks. Despite treatment with DEC, about 20 per cent of patients may relapse. Steroids have shown to have a beneficial effect but the exact dose and duration is yet to be confirmed by randomized controlled trials. A specific and easily available marker is required for TPE in order to distinguish it from other parasitic and non-parasitic causes of pulmonary eosinophilia

Tuberculosis Management by Private Practitioners in Mumbai, India: Has Anything Changed in Two Decades?

Setting: Mumbai, India. A study conducted in Mumbai two decades ago revealed the extent of inappropriate tuberculosis (TB) management practices of private practitioners. Over the years, India’s national TB programme has made significant progress in TB control. Efforts to engage private practitioners have also been made with several successful documented public-private mix initiatives in place. Objective: To study prescribing practices of private practitioners in the treatment of tuberculosis, two decades after a similar study conducted in the same geographical area revealed dismal results. Methods: Survey questionnaire administered to practicing general practitioners attending a continuing medical education programme. Results: The participating practitioners had never been approached or oriented by the local TB programme. Only 6 of the 106 respondents wrote a prescription with a correct drug regimen. 106 doctors prescribed 63 different drug regimens. There was tendency to over treat with more drugs for longer durations. Only 3 of the 106 respondents could write an appropriate prescription for treatment of multidrug-resistant TB. Conclusions: With a vast majority of private practitioners unable to provide a correct prescription for treating TB and not approached by the national TB programme, little seems to have changed over the years. Strategies to control TB throug

Improved pulmonary function following pirfenidone treatment in a patient with progressive interstitial lung disease associated with systemic sclerosis

Pirfenidone is an anti-fibrotic drug which has been approved for the management of patients with Idiopathic Pulmonary Fibrosis (IPF). However, its role in interstitial lung disease (ILD) due to other causes such as systemic sclerosis (SSc) is not clear. We present a case of a patient with SSc associated ILD who showed a subjective as well as objective improvement in lung function with pirfenidone