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Anion penetration into the semiconducting vertically aligned TiO2 nanotubes and conductive vertically aligned carbon nanotubes is examined using soft landing of well-characterized polyoxometalate anions.

The aim of this study was to independently evaluate the diagnostic accuracy of three artificial intelligence (AI)-based computer aided detection (CAD) systems for detecting pulmonary tuberculosis (TB) on global migrants screening chest x-ray (CXR) cases.Retrospective clinical data and CXR images were collected from the International Organization for Migration (IOM) pre-migration health assessment TB screening global database for US-bound migrants. A total of 2,812 participants were included in the dataset, of which 1,769 (62.9%) had accompanying microbiological test results. All CXRs were interpreted by three CAD systems (CAD4TB v6, Lunit INSIGHT v4.9.0, and qXR v2) offline and re-interpreted by two expert radiologists in a blinded fashion. The performance was evaluated using receiver operating characteristics curve (ROC), estimates of sensitivity and specificity at different CAD thresholds against both microbiological and radiological reference standards (MRS and RadRS, respectively).The area under the curve against MRS was highest for Lunit (0.85; 95% CI 0.83−0.87), followed by qXR (0.75; 95% CI 0.72−0.77) and then CAD4TB (0.71; 95% CI 0.68−0.73). At a set specificity of 70%, Lunit had the highest sensitivity (54.5%; 95% CI 51.7–57.3); at a set sensitivity of 90%, specificity was also highest for Lunit (81.4%; 95% CI 77.9–84.6). The CAD systems performed comparable to sensitivity (98.3%), and except CAD4TB, to specificity (13.7 %) of expert radiologist. Similar trends were observed when using RadRS.In conclusion, the study demonstrated that the three CAD systems had broadly similar diagnostic accuracy with regard to TB screening, and comparable accuracy to expert radiologist. Compared with different reference standards, Lunit performed better than both qXR and CAD4TB against MRS, and better than qXR against RadRS. Overall, these findings suggest that CAD systems could be a useful tool for TB screening programs in remote, high TB prevalent places where access to expert radiologists may be limited.

The World Health Organization Supranational TB Reference Laboratory Network (SRLN) has served as the backbone for TB drug-resistance surveillance and diagnosis since 1994 and remains a key WHO programme for antimicrobial resistance (AMR) surveillance at the global level. SRLN is a great technical resource for proficiency testing to ensure accuracy of drug-susceptibility testing, scale-up, capacity development in countries and provides unique support to the reliable detection of drug resistance. Technical assistance from individual SRLs has been supported by a variety of mechanisms but funding for the SRLN has become increasingly challenging.

Tests that can replace sputum smear microscopy have been identified as a top priority diagnostic need for tuberculosis by the World Health Organization. High-quality evidence on diagnostic accuracy for tests that may meet this need is an essential requirement to inform decisions about policy and scale-up. However, test accuracy studies are often of low and inconsistent quality and poorly reported, leading to uncertainty about true test performance. Here we provide guidance for the design of diagnostic test accuracy studies of sputum smear-replacement tests. Such studies should have a cross-sectional or cohort design, enrolling either a consecutive series or a random sample of patients who require evaluation for tuberculosis. Adults with respiratory symptoms are the target population. The reference standard should at a minimum be a single, automated, liquid culture, but additional cultures, follow-up, clinical case definition, and specific measures to understand discordant results should also be included. Inclusion of smear microscopy and Xpert MTB/RIF (or MTB/RIF Ultra) as comparators is critical to allow broader comparability and generalizability of results, because disease spectrum can vary between studies and affects relative test performance. Given the complex nature of sputum (the primary specimen type used for pulmonary TB), careful design and reporting of the specimen flow is essential. Test characteristics other than accuracy (such as feasibility, implementation considerations, and data on impact on patient, population and health systems outcomes) are also important aspects.

Existing high-priority target product profiles (TPPs) of the World Health Organization (WHO) establish important needs for tuberculosis (TB) diagnostic development. Building on this earlier work, this guidance series aims to provide study guidance for performing accuracy studies of novel diagnostic products that may meet the 4 high-priority WHO TPPs and thus enable adequate evidence generation to inform a WHO evidence review process. Diagnostic accuracy studies represent a fundamental step in the validation of all tests. Unfortunately, such studies often have limitations in design, execution, and reporting, leading to low certainty of the evidence about true test performance, which can delay or impede policy and scale-up decisions. This introductory paper outlines the following: (1) the purpose of this series of papers on study guidance; (2) WHO evidence needs and process for the development of policy guidelines for new TB diagnostic tests; and (3) study design considerations, ie, general diagnostic study considerations, intended use of test and role in the clinical pathway, choice of population and setting, index-test specific issues, suitable reference standard and comparators, study flow and specimen issues, and finally key issues beyond accuracy that should be considered. The other 4 papers in this series will provide more detailed guidance for each of the 4 WHO high-priority TPPs. By increasing the clarity around the clinical evaluation needs for tests that have the potential to meet the TPP specifications, we hope to support harmonized evidence generation and enable the WHO review process towards meeting the WHO End TB Strategy targets for reducing the incidence and mortality associated with TB.

Purpose of review Tuberculosis (TB) incidence has declined ∼1.5% annually since 2000, but continued to affect 10.4 million individuals in 2015, with 1/3 remaining undiagnosed or underreported. The diagnosis of TB among those co-infected with HIV is challenging as TB remains the leading cause of death in such individuals. Accurate and rapid diagnosis of active TB will avert mortality in both adults and children, reduce transmission, and assist in timeous decisions for antiretroviral therapy initiation. This review describes advances in diagnosing TB, especially among HIV co-infected individuals, highlights national program's uptake, and impact on patient care. Recent findings The TB diagnostic landscape has been transformed over the last 5 years. Molecular diagnostics such as Xpert MTB/RIF, which simultaneously detects Mycobacterium tuberculosis (MTB) resistance to rifampicin, has revolutionized TB control programs. WHO endorsed the use of Xpert MTB/RIF in 2010 for use in HIV/TB co-infected patients, and later in 2013 for use as the initial diagnostic test for all adults and children with signs and symptoms of pulmonary TB. Line probe assays (LPAs) are recommended for the detection of rifampicin and isoniazid resistance in sputum smear-positive specimens and mycobacterial cultures. A second-line line probe assay has been recommended for the diagnosis of extensively drug-resistant (XDR)-TB Assays such as the urine lateral flow (LF)-lipoarabinomannan (LAM), can be used at the point of care (POC) and have a niche role to supplement the diagnosis of TB in seriously ill HIV-infected, hospitalized patients with low CD4 cell counts of less than 100 cells/μl. Polyvalent platforms such as the m2000 (Abbott Molecular) and GeneXpert (Cepheid) offer potential for integration of HIV and TB testing services. While the Research and Development (R&D) pipeline appears to be rich at first glance, there are actually few leads for true POC tests that would allow for earlier TB diagnosis or rapid, comprehensive drug susceptibility testing, especially when considering the very high attrition rates observed between biomarker discovery and product market entry. Summary In this review, we describe diagnostic strategies specifically for HIV and TB co-infected individuals. Molecular diagnostics in particular within the past 5 years have revolutionized and 'disrupted' this field. They lend themselves to integration of services with platforms capable of polyvalent testing. Impact on patient care is, however, still debatable. What has been highlighted is the need for health system strengthening and for true POC testing that can be used in active case finding.

Drug-resistant tuberculosis poses a persistent public health threat. The ReSeqTB platform is a collaborative, curated knowledgebase, designed to standardize and aggregate global Mycobacterium tuberculosis complex (MTBC) variant data from whole genome sequencing (WGS) with phenotypic drug susceptibility testing (DST) and clinical data. We developed a unified analysis variant pipeline (UVP) ( https://github.com/CPTR-ReSeqTB/UVP ) to identify variants and assign lineage from MTBC sequence data. Stringent thresholds and quality control measures were incorporated in this open source tool. The pipeline was validated using a well-characterized dataset of 90 diverse MTBC isolates with conventional DST and DNA Sanger sequencing data. The UVP exhibited 98.9% agreement with the variants identified using Sanger sequencing and was 100% concordant with conventional methods of assigning lineage. We analyzed 4636 publicly available MTBC isolates in the ReSeqTB platform representing all seven major MTBC lineages. The variants detected have an above 94% accuracy of predicting drug based on the accompanying DST results in the platform. The aggregation of variants over time in the platform will establish confidence-graded mutations statistically associated with phenotypic drug resistance. These tools serve as critical reference standards for future molecular diagnostic assay developers, researchers, public health agencies and clinicians working towards the control of drug-resistant tuberculosis.

Approximately 3.6 million cases of active tuberculosis (TB) go potentially undiagnosed annually, partly due to limited access to confirmatory diagnostic tests, such as molecular assays or mycobacterial culture, in community and primary healthcare settings. This article provides guidance for TB triage test evaluations. A TB triage test is designed for use in people with TB symptoms and/or significant risk factors for TB. Triage tests are simple and low-cost tests aiming to improve ease of access and implementation (compared with confirmatory tests) and decrease the proportion of patients requiring more expensive confirmatory testing. Evaluation of triage tests should occur in settings of intended use, such as community and primary healthcare centers. Important considerations for triage test evaluation include study design, population, sample type, test throughput, use of thresholds, reference standard (ideally culture), and specimen flow. The impact of a triage test will depend heavily on issues beyond accuracy, primarily centered on implementation.

Xpert MTB/XDR is a new rapid molecular test for drug resistant tuberculosishttps://bit.ly/3l2t4op

10 Pages, 1 Figure, 3 Tables. Supplementary information: http://dx.doi.org/10.1038/s41598-018-33731-1, Drug-resistant tuberculosis poses a persistent public health threat. The ReSeqTB platform is a collaborative, curated knowledgebase, designed to standardize and aggregate global Mycobacterium tuberculosis complex (MTBC) variant data from whole genome sequencing (WGS) with phenotypic drug susceptibility testing (DST) and clinical data. We developed a unified analysis variant pipeline (UVP) ( https://github.com/CPTR-ReSeqTB/UVP ) to identify variants and assign lineage from MTBC sequence data. Stringent thresholds and quality control measures were incorporated in this open source tool. The pipeline was validated using a well-characterized dataset of 90 diverse MTBC isolates with conventional DST and DNA Sanger sequencing data. The UVP exhibited 98.9% agreement with the variants identified using Sanger sequencing and was 100% concordant with conventional methods of assigning lineage. We analyzed 4636 publicly available MTBC isolates in the ReSeqTB platform representing all seven major MTBC lineages. The variants detected have an above 94% accuracy of predicting drug based on the accompanying DST results in the platform. The aggregation of variants over time in the platform will establish confidence-graded mutations statistically associated with phenotypic drug resistance. These tools serve as critical reference standards for future molecular diagnostic assay developers, researchers, public health agencies and clinicians working towards the control of drug-resistant tuberculosis., This study was supported by the Bill & Melinda Gates Foundation under grant agreement OPP1115887 to C-Path for developing the ReSeqTB drug resistance data sharing platform and under grant agreement FIND OPP1115209 to address how to score mutations in the ReSeqTB data sharing platform initiative. The South African MRC and the EDCTP support K. Dheda. I. Comas is supported by the Ministerio de Economía y Competitividad (Spanish Government) research grant SAF2016-77346-R and the European Research Council (ERC) (638553-TB-ACCELERATE). L. Chindelevitch acknowledges support by NSERC, Genome Canada, and the Sloan Foundation. Use of trade names is for identification only and does not constitute endorsement by the US Department of Health and Human Services, the US Public Health Service, or the Centers for Disease Control and Prevention. The findings and conclusions in this report are those of the authors and do not necessarily represent the views of the funding agency.

Novel accurate tests are needed that identify individuals infected with Mycobacterium tuberculosis who have incipient disease and are likely to develop clinical tuberculosis (TB) in the near future to allow for targeted preventive treatment beyond the current risk groups. Recently, a target product profile was developed that outlines the minimal and optimal characteristics for such an incipient TB test. We describe an evaluation framework for generating evidence to inform the development of policy guidance for the use of such a new test by the World Health Organization. Two research objectives are addressed. 1) The predictive ability of an incipient TB test should be assessed in clinical evaluation studies that include the intended target population and follow-up of sufficient duration to observe whether individuals do or do not progress to clinical TB disease. 2) Studies are needed to evaluate the test under routine programmatic conditions and measure its impact on patient- or health-system-important outcomes. For both research objectives, study designs, methods and analysis are described, with the intent to inform the clinical development plans of test manufacturers, researchers and funders.

BACKGROUND: Novel diagnostics have been widely applied across human immunodeficiency virus (HIV) and tuberculosis prevention and treatment programs. To achieve the greatest impact HIV and tuberculosis diagnostic programs must carefully plan and implement within the context of a specific healthcare system and the laboratory capacity. METHODS: A workshop was convened in Cape Town in September 2014. Participants included experts from laboratory and clinical practices officials from ministries of health and representatives from industry. RESULTS: The article summarizes best practices challenges and lessons learned from implementation experiences across sub-Saharan Africa for (1) building laboratory programs within the context of a healthcare system; (2) utilizing experience of clinicians and healthcare partners in planning and implementing the right diagnostic; and (3) evaluating the effects of new diagnostics on the healthcare system and on patient health outcomes. CONCLUSIONS: The successful implementation of HIV and tuberculosis diagnostics in resource-limited settings relies on careful consideration of each specific context. Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.

The WHO TB Compendium facilitates the delivery of high-quality care to all persons affected by TB http://ow.ly/VzsM30iO8sO

Background In many countries, regular monitoring of the emergence of resistance to anti-tuberculosis drugs is hampered by the limitations of phenotypic testing for drug susceptibility. We therefore evaluated the use of genetic sequencing for surveillance of drug resistance in tuberculosis. Methods Population-level surveys were done in hospitals and clinics in seven countries (Azerbaijan, Bangladesh, Belarus, Pakistan, Philippines, South Africa, and Ukraine) to evaluate the use of genetic sequencing to estimate the resistance of Mycobacterium tuberculosis isolates to rifampicin, isoniazid, ofloxacin, moxifloxacin, pyrazinamide, kanamycin, amikacin, and capreomycin. For each drug, we assessed the accuracy of genetic sequencing by a comparison of the adjusted prevalence of resistance, measured by genetic sequencing, with the true prevalence of resistance, determined by phenotypic testing. Findings Isolates were taken from 7094 patients with tuberculosis who were enrolled in the study between November, 2009, and May, 2014. In all tuberculosis cases, the overall pooled sensitivity values for predicting resistance by genetic sequencing were 91% (95% CI 87-94) for rpoB (rifampicin resistance), 86% (74-93) for katG, inhA, andfabG promoter combined (isoniazid resistance), 54% (39-68) for pucA (pyrazinamide resistance), 85% (77-91) for gyrA and gyrB combined (ofloxacin resistance), and 88% (81-92) for gyrA and gyrB combined (moxifloxacin resistance). For nearly all drugs and in most settings, there was a large overlap in the estimated prevalence of drug resistance by genetic sequencing and the estimated prevalence by phenotypic testing. Interpretation Genetic sequencing can be a valuable tool for surveillance of drug resistance, providing new opportunities to monitor drug resistance in tuberculosis in resource-poor countries. Before its widespread adoption for surveillance purposes, there is a need to standardise DNA extraction methods, recording and reporting nomenclature, and data interpretation. Copyright (C) 2018 World Health Organization; licensee Elsevier. This is an Open Access article published under the CC BY 3.0 IGO license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. In any use of this article, there should be no suggestion that WHO endorses any specific organisation, products or services. The use of the WHO logo is not permitted. This notice should be preserved along with the article's original URL.

In industrialised countries, sufficient resources for establishing and maintaining fully equipped biosafety level 3 (BSL-3) laboratories according to international standards are generally available. BSL-3 laboratories are designed to provide several layers of containment to protect the laboratory worker as well as the outside environment and community from risk of exposure in case of local contamination. However, such facilities are scarce in high-burden settings, primarily due to the high financial burden and complexity of the initial construction and/or regular maintenance. Measures to prevent unintended exposure to Mycobacterium tuberculosis during laboratory manipulation of specimens and cultures is the first, and by far the most important, aspect of containment. This paper focuses on the need for risk containment at source. Assuming that in many settings the establishment of BSL-3 laboratories with all the required features is not achievable, this paper also discusses the minimum requirements necessary to mitigate risks associated with particular laboratory procedures. The term 'TB containment laboratory' is used throughout this paper to describe the minimum requirements for a laboratory suitable for high-risk procedures. The TB containment laboratory has many, but not all, of the features of a BSL-3 laboratory.

Drug-resistant tuberculosis (DR-TB) poses a major threat to control of tuberculosis worldwide. Diagnosis and treatment of DR-TB are considerably more difficult than for drug-susceptible tuberculosis (TB) and require higher level infrastructure and proficiency from laboratory specialists and clinicians. The World Health Organization (WHO) End TB Strategy calls for early diagnosis and initiation of appropriate treatment of all persons of all ages with any form of drug-susceptible TB or DR-TB. This requires ensuring access to WHO-recommended rapid diagnostics and universal drug susceptibility testing (DST) for all persons with signs and symptoms of TB. There are a number of laboratory tools available for diagnosis of DR-TB, including phenotypic culture-based DST as well as molecular methods. Optimal and complementary use of the available diagnostic tools at the different levels of the tiered network of TB laboratories, as well as correct interpretation of the diagnostic results provided by them is critical for accurate and timely diagnosis of DR-TB thus enabling effective treatment and care of patients.

In developing minimum biosafety precautions for laboratories that conduct diagnostic testing for tuberculosis (TB), a risk assessment-based approach was used to define minimum precautions for individual procedures and processes. A consensusbuilding approach involving three expert committees was necessary because risk assessment is a subjective process with judgments based sometimes on incomplete information. This article describes the process behind the development of recommendations for minimum biosafety precautions for TB laboratories in high-burden and low-resource settings. The recommendations of the expert committees are being used by the World Health Organization (WHO) to produce a safety manual for TB laboratories that is tentatively scheduled for publication in mid-2012. The intended audience for these recommendations is directors and managers of laboratories and programs that conduct testing for TB in resource-limited and high-burden settings. However, the process used here and the recommendations developed are suitable for consideration by all laboratories that conduct testing for TB.

Summary Background Pyrazinamide and fluoroquinolones are essential antituberculosis drugs in new rifampicin-sparing regimens. However, little information about the extent of resistance to these drugs at the population level is available. Methods In a molecular epidemiology analysis, we used population-based surveys from Azerbaijan, Bangladesh, Belarus, Pakistan, and South Africa to investigate resistance to pyrazinamide and fluoroquinolones among patients with tuberculosis. Resistance to pyrazinamide was assessed by gene sequencing with the detection of resistance-conferring mutations in the pncA gene, and susceptibility testing to fluoroquinolones was conducted using the MGIT system. Findings Pyrazinamide resistance was assessed in 4972 patients. Levels of resistance varied substantially in the surveyed settings (3·0–42·1%). In all settings, pyrazinamide resistance was significantly associated with rifampicin resistance. Among 5015 patients who underwent susceptibility testing to fluoroquinolones, proportions of resistance ranged from 1·0–16·6% for ofloxacin, to 0·5–12·4% for levofloxacin, and 0·9–14·6% for moxifloxacin when tested at 0·5 μg/mL. High levels of ofloxacin resistance were detected in Pakistan. Resistance to moxifloxacin and gatifloxacin when tested at 2 μg/mL was low in all countries. Interpretation Although pyrazinamide resistance was significantly associated with rifampicin resistance, this drug may still be effective in 19–63% of patients with rifampicin-resistant tuberculosis. Even though the high level of resistance to ofloxacin found in Pakistan is worrisome because it might be the expression of extensive and unregulated use of fluoroquinolones in some parts of Asia, the negligible levels of resistance to fourth-generation fluoroquinolones documented in all survey sites is an encouraging finding. Rational use of this class of antibiotics should therefore be ensured to preserve its effectiveness. Funding Bill & Melinda Gates Foundation, United States Agency for International Development, Global Alliance for Tuberculosis Drug Development.

Purpose To correlate the clinical presentation and treatment outcome of Nocardia keratitis with the time to diagnosis, different species and with the drug sensitivity pattern. Method Patients with Nocardia corneal ulcers were studied at a tertiary eye care center. Speciation of Nocardia isolates was done by sequencing the 16s rRNA gene. Clinical response to treatment was assessed by chart review. Results Twenty one (65.3%) patients presented within 15 days of the onset of symptoms with typical clinical features of Nocardia keratitis, ie, a ring-like distribution of superficial infiltrates in a wreath pattern. Eight patients (25%) who presented after 15 days and within 30 days had an ulcer resembling fungal keratitis. N. Cyriacigeorgica (n = 11; 34.37%), N. asteroides (n = 9; 28%), N. farcinica (n = 7; 22%,) and N. Otitidiscaviarum (n = 5; 16%). All the species had 100% sensitivity to amikacin, sulphamethoxazole, imipenem and co-trimoxazole. Time to diagnosis of the infection was significantly associated with the different types of clinical presentation; those presenting early having the typical clinical picture (P = 0.004). Patients (73%) presenting within 15 days showed a highest recovery rate. (P = 0.045). The recovery time of the patients when compared with species showed those who were infected with N. cyriageorgica had a healing time of less than 15 days. Clinically, healing was faster when treated with 2% amikacin. Visual outcome improved in fourteen patients (44%) and sixteen (50%) patients remained the same (P = 0.0001). Conclusion Characteristic clinical picture of Nocardia is dependant on early presentation. It could be mistaken for fungal keratitis. Microbiological confirmation is important. Drug of choice for Nocardia keratitis is amikacin.

On May 19, 2014, the 67th World Health Assembly (WHA) adopted WHO’s “Global strategy and targets for tuberculosis prevention, care and control after 2015”. This post-2015 global tuberculosis strategy, labelled the End TB Strategy, was shaped during the past 2 years. A wide range of stakeholders—from ministries of health and national tuberculosis programmes to technical and scientifi c institutions, fi nancial and development partners, civil society and health activists, non-governmental organisations, and the private sector—contributed to its development. The strategy has a vision of making the world free of tuberculosis, with zero deaths, disease, and suff ering due to the disease (see appendix p 1 for summary of the End TB Strategy). In 2013, 9 million people fell ill with tuberculosis and 1·5 million died; about a quarter of them were HIV positive. Poor and deprived groups also bore the brunt of the enormous socioeconomic burden imposed by the disease and deaths. Concerned by this persistent human suff ering due to tuberculosis, but encouraged by the progress achieved during the past two decades and recognising the need to mount a multisectoral response to eff ectively address the problem, the health ministers at the WHA approved WHO’s proposal to push the limit of ambition to “end the global tuberculosis epidemic” by 2035, marked by well defi ned milestones and targets set along the way. Ending the tuberculosis epidemic implies bringing the levels of tuberculosis in the whole world down to converge with those already attained by many rich countries: fewer than ten new tuberculosis cases occurring per 100 000 population per year amounting to 90% reduction in tuberculosis incidence and tuberculosis deaths reduced by 95%. The rich countries achieved remarkable reductions in the tuberculosis burden not only by delivering adequate tuberculosis services, but also by pursuing universal access to health care and social protection while rapidly improving nutrition and economic conditions. Ending the tuberculosis epidemic in high-incidence countries needs a similar approach that guarantees access to high-quality tuberculosis care and prevention to all while simul taneously addressing the social determinants of tuberculosis. To this eff ect, elimination of catastrophic costs that tuberculosis-aff ected families face is an important milestone to be achieved under the End TB Strategy well within the next decade. Importantly, though, achievement of universal access to currently available methods of tuberculosis care and prevention will not be enough to end the epidemic within two decades. Global investments and eff orts are also essential to develop improved methods to diagnose, treat, and prevent tuberculosis. Equal emphasis on achievement of universal access to tuberculosis care and prevention, addressing of weaknesses in health systems and social determinants of tuberculosis, and pursuing of research and innovation for improved approaches and strategies constitute the core of the End TB Strategy. The achievements of the past two decades provide the basis for further progress. The DOTS (directly observed treatment, short-course) strategy of 1995 expanded access to high-quality tuberculosis care. The Stop TB Strategy of 2006 widened its scope to address management of all forms of tuberculosis including HIV-associated and drug-resistant tuberculosis, through engagement of communities, involvement of all care providers, strengthening of health systems, and fostering of research. Subsequently, the tuberculosis-related Millennium Development Goal to “halt and begin to reverse the incidence of tuberculosis” was achieved; 37 million lives were saved between 2000 and 2013; and a new rapid molecular test to simultaneously diagnose tuberculosis and rifampicin resistance was developed and two novel drugs were introduced. These achievements notwithstanding, the enormity of the task ahead cannot be overemphasised. Overall, the current 2% annual reduction in the global tuberculosis incidence is too slow to achieve an end to the epidemic in the foreseeable future. Tuberculosis remains a top infectious killer of men and women. A third of estimated incident tuberculosis cases go un-notifi ed or undiagnosed and close to half a million multidrug-resistant cases emerge each year. HIV-associated tuberculosis aff ects more than a million people a year. An estimated 2 billion people with latent tuberculosis infection form a reservoir that sustains the global epidemic. Analyses of constraints to global tuberculosis control bring four major persisting barriers to the fore. First, weak health systems including the unregulated non-state sector prevent reaching the currently available methods of diagnosis and treatment to all sections of the populations and a lack of universal health coverage and social protection inhibit provision of comprehensive tuberculosis care and prevention without further impoverishment to those who need it most. Second, determinants such as poverty, under nutrition, migration, and ageing populations enhance vulnerability and maintain the cycle of infection and disease. The risk of tuberculosis is further enhanced by non-communicable health problems such as diabetes, harmful use of alcohol, and tobacco smoking. Third, the lack of optimum methods—a point-of-care test for rapid diagnosis of disease and latent infection; better and safer drug regimens to shorten treatment; and a vaccine to prevent Lancet 2015; 385: 1799–801

In 2003, a steer carcass was condemned at a Central Queensland abattoir because of metastatic tumors. In addition, a granulomatous lesion was found in the mediastinal lymph node. Histological examination showed this to be a pyogranuloma, typically associated with Rhodococcus or the Nocardia/ Streptomyces group. However, in this case, the only etiological agent was an acid-fast bacillus, which would normally be associated with a more fibrous lesion. A number of nucleic acid–based techniques were used, and the isolate was identified as Mycobacterium asiaticum. This organism is a rarely encountered opportunistic pathogen of humans, associated with subtropical climates. This is the first report of this organism causing infection in cattle. The similarities between this case and cases of human disease are discussed.

Tuberculosis and particularly multidrug resistant TB remains a major public health concern in the WHO European Region. In order to reduce the burden of the disease, early, accurate and rapid diagnoses play a crucial role. Sputum smear microscopy that has long been used as the main TB diagnostic method detects TB only with low sensitivity and phenotypic culture-based methods require several weeks and high biosafety laboratory infrastructures. The use of the WHO endorsed rapid molecular method for simultaneous detection of TB and rifampicin resistance detection has promising advantages to overcome these challenges and lead to major advances for early and accurate diagnosis of TB. With better understanding appearing discordances between phenotypic and genotypic methods, as well as the development and implementation of regionally adapted diagnostic algorithms, the precision of result acquisition and interpretation can advance even further.

Could therapeutic drug monitoring for fluoroquinolones have a role in the programmatic management of MDR-TB? http://ow.ly/wGdP309R7Z4

A knowledge, attitude, behaviour, and practice survey was conducted among labour migrants in Tajikistan to elucidate key factors influencing access to tuberculosis diagnosis and care both in their labour destination country and at home. 509 labour migrants were interviewed in Khaton and Rasht Valley regions in Tajikistan using a standardised questionnaire. In addition, in-depth interviews were conducted among ten tuberculosis patients who had recently worked abroad. The study showed that migrants have increased vulnerability to tuberculosis due to the working and living conditions in the destination country and that access to health services is limited due to their legal status or the high cost of health services abroad. The average knowledge of migrants regarding tuberculosis is low and misconceptions are frequent. In Tajikistan, although tuberculosis drugs are usually provided free of charge, tuberculosis diagnosis and ancillary treatment are charged, thus creating a significant financial burden for patients and their families. Improving the access of labour migrants to affordable early diagnosis and treatment in both host countries and Tajikistan is a priority.

Molecular techniques are now widely applied in Australia and elsewhere for the direct detection of Mycobacterium tuberculosis DNA in clinical specimens and culturally enhanced material. All nucleic acid testing methods have the potential to give false negative results due to mutations that may arise at primer or probe binding sites. We describe one such strain of M. tuberculosis that was encountered in 1995 and that has not been encountered in Australia since.