BackgroundTuberculosis (TB) research is a key component of the End TB Strategy. To track research output, we conducted a bibliometric analysis of TB research from the past decade.MethodsThe Web of Science database was searched for publications from January 2007 to December 2016 with “tuberculosis” in the title. References were analysed using the R bibliometrix package. A year-stratified 5% random subset was drawn to extract funding sources and identify research areas.FindingsThe annual growth rate of publications was 7.3%, and was highest (13.1%) among Brazil, Russia, India, China and South Africa (BRICS). The USA was the most productive country, with 18.4% of references, followed by India (9.7%), China (7.3%), England (6.5%), and South Africa (3.9%). In the subset analysis, the most common research area was ‘fundamental research’ (33.8%). Frequently acknowledged funders were US and EU-based, with China and India emerging as top funders. Collaborations appeared more frequently between high-income countries and low/medium income countries (LMICs), with fewer collaborations among LMICs.ConclusionThe past decade has seen a continued increase in TB publications. While USA continues to dominate research output and funding, BRICS countries have emerged as major research producers and funders. Collaborations among BRICS would enhance future TB research productivity.

BACKGROUND: Increasing evidence suggests that post-TB lung disease (PTLD) causes significant morbidity and mortality. The aim of these clinical standards is to provide guidance on the assessment and management of PTLD and the implementation of pulmonary rehabilitation (PR).METHODS: A panel of global experts in the field of TB care and PR was identified; 62 participated in a Delphi process. A 5-point Likert scale was used to score the initial ideas for standards and after several rounds of revision the document was approved (with 100% agreement).RESULTS: Five clinical standards were defined: Standard 1, to assess patients at the end of TB treatment for PTLD (with adaptation for children and specific settings/situations); Standard 2, to identify patients with PTLD for PR; Standard 3, tailoring the PR programme to patient needs and the local setting; Standard 4, to evaluate the effectiveness of PR; and Standard 5, to conduct education and counselling. Standard 6 addresses public health aspects of PTLD and outcomes due to PR.CONCLUSION: This is the first consensus-based set of Clinical Standards for PTLD. Our aim is to improve patient care and quality of life by guiding clinicians, programme managers and public health officers in planning and implementing adequate measures to assess and manage PTLD.

BackgroundImproving patients’ tuberculosis (TB) knowledge is a salient component of TB control strategies. Patient knowledge of TB may encourage infection prevention behaviors and improve treatment adherence. The purpose of this study is to examine how TB knowledge and infection prevention behaviors change over the course of treatment.MethodsA matched patient-health worker dataset (n = 6,031) of publicly treated TB patients with NGO-provided treatment support health workers was compiled in nine Indian cities from March 2013 to September 2014. At the beginning and end of TB treatment, patients were asked about their knowledge of TB symptoms, transmission, and treatment and infection prevention behaviors.ResultsPatients beginning TB treatment (n = 3,424) demonstrated moderate knowledge of TB; 52.5% (50.8%, 54.2%) knew that cough was a symptom of TB and 67.2% (65.6%, 68.7%) knew that TB was communicable. Overall patient knowledge was significantly associated with literacy, education, and income, and was higher at the end of treatment than at the beginning (3.7%, CI: 3.02%, 4.47%). Infection prevention behaviors like covering a cough (63.4%, CI: 61.2%, 65.0%) and sleeping separately (19.3%, CI: 18.0%, 20.7%) were less prevalent. The age difference between patient and health worker as well as a shared language significantly predicted patient knowledge and adherence to infection prevention behaviors.ConclusionsSocial proximity between health worker and patients predicted greater knowledge and adherence to infection prevention behaviors but the latter rate remains undesirably low.

In general, chest radiographs (CXR) have high sensitivity and moderate specificity for active pulmonary tuberculosis (ptB) screening when interpreted by human readers. However, they are challenging to scale due to hardware costs and the dearth of professionals available to interpret cXR in low-resource, high ptB burden settings. Recently, several computer-aided detection (cAD) programs have been developed to facilitate automated cXR interpretation. We conducted a retrospective case-control study to assess the diagnostic accuracy of a cAD software (qXR, Qure.ai, Mumbai, india) using microbiologically-confirmed PTB as the reference standard. To assess overall accuracy of qXR, receiver operating characteristic (Roc) analysis was used to determine the area under the curve (AUc), along with 95% confidence intervals (CI). Kappa coefficients, and associated 95% CI, were used to investigate inter-rater reliability of the radiologists for detection of specific chest abnormalities. In total, 317 cases and 612 controls were included in the analysis. The AUC for qXR for the detection of microbiologicallyconfirmed PTB was 0.81 (95% CI: 0.78, 0.84). Using the threshold that maximized sensitivity and specificity of qXR simultaneously, the software achieved a sensitivity and specificity of 71% (95% CI: 66%, 76%) and 80% (95% CI: 77%, 83%), respectively. The sensitivity and specificity of radiologists for the detection of microbiologically-confirmed PTB was 56% (95% CI: 50%, 62%) and 80% (95% CI: 77%, 83%), respectively. For detection of key PTB-related abnormalities 'pleural effusion' and 'cavity', qXR achieved an AUC of 0.94 (95% CI: 0.92, 0.96) and 0.84 (95% CI: 0.82, 0.87), respectively. For the other abnormalities, the AUC ranged from 0.75 (95% CI: 0.70, 0.80) to 0.94 (95% CI: 0.91, 0.96). The controls had a high prevalence of other lung diseases which can cause radiological manifestations similar to PTB (e.g., 26% had pneumonia, 15% had lung malignancy, etc.). In a tertiary hospital in india, qXR demonstrated moderate sensitivity and specificity for the detection of PTB. There is likely a larger role for cAD software as a triage test for ptB at the primary care level in settings where access to radiologists in limited. Larger prospective studies that can better assess heterogeneity in important subgroups are needed.

Viral load (VL) is the preferred treatment-monitoring approach for HIV-positive patients. However, more rapid, near-patient, and low-complexity assays are needed to scale up VL testing. The Xpert HIV-1 VL assay (Cepheid, Sunnyvale, CA) is a new, automated molecular test, and it can leverage the GeneXpert systems that are being used widely for tuberculosis diagnosis. We systematically reviewed the evidence on the performance of this new tool in comparison to established reference standards. A total of 12 articles (13 studies) in which HIV patient VLs were compared between Xpert HIV VL assay and a reference standard VL assay were identified. Study quality was generally high, but substantial variability was observed in the number and type of agreement measures reported. Correlation coefficients between Xpert and reference assays were high, with a pooled Pearson correlation (n = 8) of 0.94 (95% confidence interval [CI], 0.89, 0.97) and Spearman correlation (n = 3) of 0.96 (95% CI, 0.86, 0.99). Bland-Altman metrics (n = 11) all were within 0.35 log copies/ml of perfect agreement. Overall, Xpert HIV-1 VL performed well compared to current reference tests. The minimal training and infrastructure requirements for the Xpert HIV-1 VL assay make it attractive for use in resource-constrained settings, where point-of-care VL testing is most needed.

BackgroundIndia has a high prevalence of tuberculosis (TB) as well as diabetes mellitus (DM). DM is a chronic disease caused by deficiency of insulin production by the pancreas. The risk of TB amongst DM patients is three times higher than those without. The estimated national prevalence of DM is 7.3%. Despite the growing burden of DM, there are limited studies describing the prevalence of TB-DM in India.ObjectiveOur study estimated the prevalence of DM amongst adult hospitalized TB patients at Kasturba Hospital, Manipal and determined factors associated with the likelihood of DM-TB co-prevalence.MethodsWe conducted a retrospective cohort study at Kasturba Hospital, Manipal Academy of Higher Education. All hospitalized adult patients diagnosed with pulmonary TB (PTB) and extrapulmonary TB (EPTB) between June 1st 2015 and June 30th 2016 were eligible for inclusion. Pediatric and pregnant TB patients were excluded from our study. Data were extracted from medical charts. Descriptive and multivariate analyses were performed in R. Multivariate analysis adjusted for age, gender, type of TB, history of TB, and nutrition (body mass index (BMI)) status.ResultsA total of 728 patients met the eligibility criteria, 517 (71%) were male, 210 (29%) female, 406 (56%) had PTB and 322 (44%) had EPTB. Amongst those with a nutritional status, 36 (30%) patients were underweight (BMI <18.4 kg/m2), 73 (40%) had a normal BMI (18.5kg/m2–24.9 kg/m2), 15 (8%) were overweight (BMI 25.0 kg/m2–29.9 kg/m2) and 9 (5%) were obese (BMI >30.0 kg/m2). A total of 720 (98.9%) of TB patients had at least one blood sugar test result. The overall prevalence of DM (n = 184) amongst TB patients was 25.3% (95% CI 22.2%, 28.6%). When stratified, it was 35.0% (30.4%, 39.9%) and 13.0% (9.7%, 17.3%) amongst PTB and EPTB patients respectively. TB patients aged 41–60 years had 3.51 times higher odds (aOR 3.51 (2.08, 6.07)) of having DM than patients 40 years or younger. Patients aged 60 years or older had 2.49 times higher odds (aOR 2.49 (1.28, 4.85)) of having DM than younger patients (<40 years). Females had lower odds (aOR 0.80 (0.46, 1.37)) of developing DM than male TB patients and patients with a history of TB had lower odds (aOR 0.73 (0.39, 1.32)) than newly diagnosed TB patients. Additionally, EPTB patients had significantly lower odds (aOR 0.26 (0.15, 0.43)) compared to PTB patients. Underweight patients also had significantly lower odds (aOR 0.25 (0.14, 0.42)) of having DM than normal weight patients.ConclusionOur study found a higher prevalence of TB-DM than the national average. TB-DM co-prevalence was significantly associated with age, type of TB and undernutrition. As India’s DM prevalence is expected to rise, TB-DM will become an increasingly important part of the TB epidemic requiring specialized study and care.

Research. The funding sources were not involved in this project or the manuscript. We are grateful to Cepheid India for their engagement and support, and for addressing the supply chain issues identified during the project.

BackgroundAntimicrobial resistance is a global health emergency, and one of the contributing factors is overuse and misuse of antibiotics. India is one of the world’s largest consumers of antibiotics, and inappropriate use is potentially widespread. This study aimed to use standardised patients (SPs) to measure over-the-counter antibiotic dispensing in one region.MethodsThree adults from the local community in Udupi, India, were recruited and trained as SPs. Three conditions, in both adults and children, were considered: diarrhoea, upper respiratory tract infection and acute fever. Adult SPs were used as proxies for the paediatric cases.ResultsA total of 1522 SP interactions were successfully completed from 279 pharmacies. The proportion of SP interactions resulting in the provision of an antibiotic was 4.34% (95% CI 3.04% to 6.08%) for adult SPs and 2.89% (95% CI 1.8% to 4.4%) for child SPs. In the model, referral to another provider was associated with an OR 0.38 (95% CI 0.18 to 0.79), the number of questions asked was associated with an OR 1.54 (95% CI 1.30 to 1.84) and an SP–pharmacist interaction lasting longer than 3 min was associated with an OR 3.03 (95% CI 1.11 to 8.27) as compared with an interaction lasting less than 1 min.ConclusionOver-the-counter antibiotic dispensing rate was low in Udupi district and substantially lower than previously published SP studies in other regions of India. Dispensing was lowest when pharmacies referred to a doctor, and higher when pharmacies asked more questions or spent more time with clients.