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Jaya Prasad Tripathy1,2, Karuna D Sagili,1 Soundappan Kathirvel1,3, Archana Trivedi,1 Sharath Burugina Nagaraja,4 Om Prakash Bera1,5, Kiran Kumar Reddy,1 Srinath Satyanarayana1,2, Ashwani Khanna,6 Sarabjit S Chadha11Centre for Operational Research, International Union Against Tuberculosis and Lung Disease, New Delhi, India; 2Centre for Operational Research, International Union Against Tuberculosis and Lung Disease, Paris, France; 3Department of Community Medicine, Post Graduate Institute of Medical Education and Research, Chandigarh, India; 4Department of Community Medicine, Employees State Insurance Corporation Medical College, Post Graduate Institute of Medical Sciences and Research, Bangalore, India; 5Bloomberg Data for Health Initiative, Vital Strategies, Mumbai, India; 6Department of Health and Family Welfare, Government of Delhi, New Delhi, IndiaBackground: Weak public health systems have been identified as major bottlenecks in providing good quality diabetic care in low- and middle-income countries.Methodology: The present study assessed diabetic care services at public health facilities across six districts in three states of India using a mixed methods approach. The study described diabetes care services available at public health facilities and identified challenges and solutions needed to tackle them. The quantitative component included assessment of availability of services and resources, whilst the qualitative component was comprised of semistructured interviews with health care providers and persons with diabetes to understand the pathway of care.Results: A total of 30 health facilities were visited: five tertiary; eight secondary and 17 primary health facilities. Patient clinical records were not maintained at the facilities; the onus was on patients to keep their own clinical records. All had the facility for blood glucose measurement, but HbA1c estimation was available only at tertiary centers. None of the primary health centers in the three states provided HbA1c estimation, lipid examination, or foot care. Lifestyle modification support was available in only a few tertiary facilities. Antidiabetic drugs (biguanides and sulphonyl ureas) were available in most facilities, and given for 14 days. Insulin and statins were available only at secondary and tertiary care centers. Forty-two physicians were interviewed and poor follow-up, patient overload, and lack of specialized training were the major barriers that emerged from the interview responses. A total of 37 patients were interviewed. Patients had to visit tertiary facilities for drugs and routine follow-up, thereby congesting the facilities. There was no formal referral or follow-up mechanism to link patients to decentralized facilities.Conclusion: There is a wide gap between effective diabetes management practices and their implementation. There should be a greater role of secondary care facilities in follow-up investigations and screening for complications. A holistic diabetic care package with a robust recording and cohort monitoring system and adequate referral mechanism is needed.Keywords: diabetes mellitus, primary care, screening, noncommunicable disease, mixed methods

Objectives: How well patients adhere to their tuberculosis (TB) treatment influences their recovery and development of drug resistance, but influences on adherence are multiple and often competing. We synthesised qualitative studies from our setting in the Indian subcontinent to understand the dimensions and dynamics involved to help inform service provision., Design: Qualitative synthesis comprising inductive coding, thematic analysis and forming a conceptual framework., Data Sources: Medline (OVID), Embase (OVID), CINAHL (EBSCOHost), PsycINFO (EBSCOHost), Web of Science Core Collection, Cochrane Library and Epistemonikos were databases searched on 26 March 2020 for studies published since 1 January 2000., Eligibility Criteria for Selecting Studies: We included reports in English from the Indian subcontinent that used qualitative or mixed-methodology designs and reported findings around adherence to TB treatment. Full texts meeting eligibility were sampled based on 'thickness' (the richness of the qualitative data reported)., Data Extraction and Synthesis: Two reviewers used standardised methods to screen abstracts and code. Included studies were assessed for reliability and quality using a standard tool. Qualitative synthesis was performed by inductive coding, thematic analysis and developing conceptual framework., Results: Of 1729 abstracts screened from initial search, 59 were shortlisted for full-text review. Twenty-four studies that qualified as 'thick' were included in the synthesis. Studies were set in India (12), Pakistan (6), Nepal (3), Bangladesh (1) or in two or more of these countries (2). Of the 24 studies, all but one included people who were taking TB treatment (1 study included only healthcare providers), and 17 included healthcare workers, community members or both.We identified three themes: (1) personal influences on the people with TB include interconnections between their social role in the family unit, their own priorities in day-to-day living and their experience to date with the disease; (2) adherence is profoundly influenced by how individual healthcare providers interact with patients on treatment and address their needs; (3) adherence is influenced across communities by structural, social, economic and cultural factors related to treatment., Conclusion: Staff in TB programmes require an understanding of the various competing influences on individuals undergoing treatment. Programmes need to have more flexible and people-centred approaches to service provision in order to achieve adherence, and thus improve treatment outcomes., Prospero Registration Number: CRD42020171409., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To summarise latent tuberculosis infection (LTBI) management strategies among household contacts of bacteriologically confirmed pulmonary tuberculosis (TB) patients in high-TB burden countries., Methods: PubMed/MEDLINE (NCBI) and Scopus were searched (January 2006 to December 2021) for studies reporting primary data on LTBI management. Study selection, data management and data synthesis were protocol-driven (PROSPERO-CRD42021208715). Primary outcomes were the proportions of LTBI, initiating and completing tuberculosis preventive treatment (TPT). Reported factors influencing the LTBI care cascade were qualitatively synthesised., Results: From 3694 unique records retrieved, 58 studies from 23 countries were included. Most identified contacts were screened (median 99%, interquartile range [IQR] 82%-100%; 46 studies). Random-effects meta-analysis yielded pooled proportions for: LTBI 41% (95% confidence interval [CI] 33%-49%; 21,566 tested contacts); TPT initiation 91% (95% CI 79%-97%; 129,573 eligible contacts, 34 studies); TPT completion 65% (95% CI 54%-74%; 108,679 TPT-initiated contacts, 28 studies). Heterogeneity was significant (I 2  ≥ 95%-100%) and could not be explained in subgroup analyses. Median proportions (IQR) were: LTBI 44% (28%-59%); TPT initiation 86% (60%-100%); TPT completion 68% (44%-82%). Nine broad themes related to diagnostic testing, health system structure and functions, risk perception, documentation and adherence were considered likely to influence the LTBI care cascade., Conclusion: The proportions of household contacts screened, detected with LTBI and initiated on TPT, though variable was high, but the proportions completing TPT were lower indicating current strategies used for LTBI management in high TB burden countries are not sufficient., (© 2022 The Authors Tropical Medicine & International Health Published by John Wiley & Sons Ltd.)

Competing Interests: Competing interests: None declared.

Water quality surveillance can help to reduce waterborne diseases. Despite better access to safe drinking water in Sierra Leone, about a third of the population (3 million people) drink water from unimproved sources. In this cross-sectional study, we collected water samples from 15 standpipes and 5 wells and measured the physicochemical and bacteriological water quality, and the antimicrobial sensitivity of Escherichia coli (E. coli) in two communities in Freetown, Sierra Leone in the dry and wet seasons in 2021. All water sources were contaminated with E. coli, and all five wells and 25% of standpipes had at least an intermediate risk level of E. coli. There was no antimicrobial resistance detected in the E. coli tested. The nitrate level exceeded the WHO’s recommended standard (>10 parts per million) in 60% of the wells and in less than 20% of the standpipes. The proportion of samples from standpipes with high levels of total dissolved solids (>10 Nephelometric Turbidity Units) was much higher in the rainy season (73% vs. 7%). The level of water contamination is concerning. We suggest options to reduce E. coli contamination. Further research is required to identify where contamination of the water in standpipes is occurring.

Healthcare-associated infections (HAIs) result in millions of avoidable deaths or prolonged lengths of stay in hospitals and cause huge economic loss to health systems and communities. Primarily, HAIs spread through the hands of healthcare workers, so improving hand hygiene can reduce their spread. We evaluated hand hygiene practices and promotion across 13 public health hospitals (six secondary and seven tertiary hospitals) in the Western Area of Sierra Leone in a cross-sectional study using the WHO hand hygiene self-Assessment framework in May 2021. The mean score for all hospitals was 273 ± 46, indicating an intermediate level of hand hygiene. Nine hospitals achieved an intermediate level and four a basic level. More secondary hospitals 5 (83%) were at the intermediate level, compared to tertiary hospitals 4 (57%). Tertiary hospitals were poorly rated in the reminders in workplace and institutional safety climate domains but excelled in training and education. Lack of budgets to support hand hygiene implementation is a priority gap underlying this poor performance. These gaps hinder hand hygiene practice and promotion, contributing to the continued spread of HAIs. Enhancing the distribution of hand hygiene resources and encouraging an embedded culture of hand hygiene practice in hospitals will reduce HAIs.

India launched a national community-based active TB case finding (ACF) campaign in 2017 as part of the strategic plan of the National Tuberculosis Elimination Programme (NTEP). This review evaluated the outcomes for the components of the ACF campaign against the NTEP's minimum indicators and elicited the challenges faced in implementation. We supplemented data from completed pretested data proformas returned by ACF programme managers from nine states and two union territories (for 2017-2019) and five implementing partner agencies (2013-2020), with summary national data on the state-wise ACF outcomes for 2018-2020 published in annual reports by the NTEP. The data revealed variations in the strategies used to map and screen vulnerable populations and the diagnostic algorithms used across the states and union territories. National data were unavailable to assess whether the NTEP indicators for the minimum proportions identified with presumptive TB among those screened (5%), those with presumptive TB undergoing diagnostic tests (>95%), the minimum sputum smear positivity rate (2% to 3%), those with negative sputum smears tested with chest X-rays or CBNAAT (>95%) and those diagnosed through ACF initiated on anti-TB treatment (>95%) were fulfilled. Only 30% (10/33) of the states in 2018, 23% (7/31) in 2019 and 21% (7/34) in 2020 met the NTEP expectation that 5% of those tested through ACF would be diagnosed with TB (all forms). The number needed to screen to diagnose one person with TB (NNS) was not included among the NTEP's programme indicators. This rough indicator of the efficiency of ACF varied considerably across the states and union territories. The median NNS in 2018 was 2080 (interquartile range or IQR 517-4068). In 2019, the NNS was 2468 (IQR 1050-7924), and in 2020, the NNS was 906 (IQR 108-6550). The data consistently revealed that the states that tested a greater proportion of those screened during ACF and used chest X-rays or CBNAAT (or both) to diagnose TB had a higher diagnostic yield with a lower NNS. Many implementation challenges, related to health systems, healthcare provision and difficulties experienced by patients, were elicited. We suggest a series of strategic interventions addressing the implementation challenges and the six gaps identified in ACF outcomes and the expected indicators that could potentially improve the efficacy and effectiveness of community-based ACF in India.

Background: Antimicrobial resistance (AMR) is a growing global health problem. Staphylococcus aureus ( SA ) is a common bacterium associated with a variety of community and hospital infections. Methicillin-resistant Staphylococcus aureus (MRSA) accounts for most SA related morbidity and mortality. In this study, we determined the prevalence and factors associated with SA and MRSA in Myanmar., Methods: We collected the data retrospectively by reviewing an electronic register containing the results of bacterial culture and antibiotic susceptibility testing of biological specimens received from healthcare facilities during 2018-2019., Results: Of the 37,798 biological specimens with bacterial culture growth, 22% (8244) were Gram-positive. Among the Gram-positive bacteria, 42% (2801) were SA , of which 48% (1331) were judged as MRSA by phenotypic methods. The prevalence of MRSA was higher in the older age groups, in female patients, in urine specimens and specimens received from the intensive care unit and dermatology departments. One site (Site F) had the highest MRSA prevalence of the seven AMR sentinel sites. Most SA isolates were sensitive to vancomycin (90%) by phenotypic methods., Conclusions: The high prevalence of MRSA indicates a major public health threat. There is an urgent need to strengthen the AMR surveillance and hospital infection control program in Myanmar.

Globally, antibiotic resistance in bacteria isolated from neonatal sepsis is increasing. In this cross-sectional study conducted at a medical college teaching hospital in Nepal, we assessed the antibiotic resistance levels in bacteria cultured from neonates with sepsis and their in-hospital treatment outcomes. We extracted data of neonates with sepsis admitted for in-patient care from June 2018 to December 2019 by reviewing hospital records of the neonatal intensive care unit and microbiology department. A total of 308 neonates with sepsis were admitted of which, blood bacterial culture antibiotic sensitivity reports were available for 298 neonates. Twenty neonates (7%) had bacteriologic culture-confirmed neonatal sepsis. The most common bacterial species isolated were Staphylococcus aureus (8), followed by coagulase-negative Staphylococcus (5). Most of these bacteria were resistant to at least one first-line antibiotic used to manage neonatal sepsis. Overall, there were 7 (2%) deaths among the 308 neonates (none of them from the bacterial culture-positive group), and 53 (17%) neonates had left the hospital against medical advice (LAMA). Improving hospital procedures to isolate bacteria in neonates with sepsis, undertaking measures to prevent the spread of antibiotic-resistant bacteria, and addressing LAMA's reasons are urgently needed.

In India, under the National Tuberculosis Elimination Programme, the government provides free treatment for multidrug-resistant tuberculosis; however, many patients seek care elsewhere, which is costly. To determine those out-of-pocket expenses, we interviewed 40 presumptive patients and found that they spent more than their median annual income before registering for the government program.

Background: Nutrition support is one of the essential factors for envisioning Tuberculosis (TB) elimination in India by 2025. In this regard, Government of India introduced Nikshay Poshan Yojana (NPY) through Direct Benefit Transfer (DBT) as monthly financial assistance towards nutrition for TB patients in April, 2018. Assessment of early implementation challenges of the scheme is essential., Objective: (a) To determine the number (proportion) of TB patients who received the benefits (b) to explore the challenges encountered by the health care providers in delivering the NPY through DBT (c) to explore the ways the incentives were utilised by the patients., Material and Methods: It was a cross-sectional study conducted among patients registered for TB treatment at Ladosarai and Mehrauli DOTS centre between July-September, 2018.Health providers engaged in implementation of NPY at the study sites were also interviewed. The data were collected through structured questionnaires, double entered and analyzed in Epi Data., Results: Out of 119 patients registered, we interviewed 57 (47.9%) patients. Of which, 30 (52.6%) had received NPY for 2 months in the fourth and fifth month of treatment. The health providers reported increased workload, lack of training and complex reporting formats as main hurdles in implementation of the scheme. While, the patients cited non-availability of bank accounts and unlinked bank account with Aadhar card as difficulties to receive NPY through DBT., Conclusion: Nearly half of the interviewed TB patients received nutritional incentives of NPY through DBT for 2 months. Non-availability of bank accounts and unlinked bank accounts were some challenges faced by both health providers and patient. It is recommended to address these implementation on time in order to reap the benefit of scheme in improving nutritional status of TB patients. Further studies are needed to determine the effect of nutrition support on TB patients., (Copyright © 2020 Tuberculosis Association of India. Published by Elsevier B.V. All rights reserved.)

Context: India has adopted active case finding (ACF) as an additional strategy to find its missing tuberculosis (TB) cases since 2017. Treatment outcomes of patients identified through ACF may be similar or different from those detected through routine passive case finding (PCF); currently, there are limited studies on this in India., Aim: The aim of this study was to assess differences in treatment outcomes of patients detected through ACF and PCF under the national TB program., Study Design: A study was conducted in six TB units of Haridwar district where ACF campaigns were conducted in 2017-2018., Methods: Data from patients detected by ACF ( n = 72) and PCF ( n = 184) were extracted from program records., Results: Of 72 patients detected by ACF, only 54 (75%) were initiated on treatment. A high proportion of initial loss to follow-up (25% vs. 0%) and delay in treatment initiation (4 days vs. 0 days) was observed in ACF patients as compared to PCF. The proportion of unsuccessful treatment outcome was 33% ( n = 18) among ACF patients compared to 14% ( n = 25) among PCF patients (adjusted relative risk: 2.6, 95% confidence interval: 1.7-4.0)., Conclusion: High initial loss to follow-up, delay in treatment initiation, and poor treatment outcome among ACF patients are a major concern. The study results call for active follow-up after diagnosis and close monitoring during treatment for patients detected by ACF., Competing Interests: There are no conflicts of interest., (Copyright: © 2020 Journal of Global Infectious Diseases.)

Background: In 2007, a field observation from India reported 11% misclassification among 'new' patients registered under the revised national tuberculosis (TB) control programme. Ten years down the line, it is important to know what proportion of newly registered patients has a past history of TB treatment for at least one month (henceforth called 'misclassification'). Methods: A study was conducted among new smear-positive pulmonary TB patients registered between March 2016 and February 2017 in 18 randomly selected districts to determine the effectiveness of an active case-finding strategy in marginalised and vulnerable populations. We included all patients detected through active case-finding. An equal number of randomly selected patients registered through passive case-finding from marginalised and vulnerable populations in the same districts were included. Before enrolment, we enquired about any history of previous TB treatment through interviews. Results: Of 629 patients, we interviewed 521, of whom, 11% (n=56) had past history of TB treatment (public or private) for at least a month: 13% (34/268) among the active case-finding group and 9% (22/253) among the passive case-finding group (p=0.18). No factors were found to be significantly associated with misclassification. Conclusion: Around one in every ten patients registered as 'new' had previous history of TB treatment. Corrective measures need to be implemented, followed by monitoring of any change in the proportion of 'previously treated' patients among all registered patients treated under the programme at national level., Competing Interests: No competing interests were disclosed.

Background: Axshya SAMVAD is an active tuberculosis (TB) case finding (ACF) strategy under project Axshya (Axshya meaning 'free of TB' and SAMVAD meaning 'conversation') among marginalized and vulnerable populations in 285 districts of India., Objectives: To compare patient characteristics, health seeking, delays in diagnosis and treatment initiation among new sputum smear positive TB patients detected through ACF and passive case finding (PCF) under the national TB programme in marginalized and vulnerable populations between March 2016 and February 2017., Methods: This observational analytic study was conducted in 18 randomly sampled Axshya districts. We enrolled all TB patients detected through ACF and an equal number of randomly selected patients detected through PCF in the same settings. Data on patient characteristics, health seeking and delays were collected through record review and patient interviews (at their residence). Delays included patient level delay (from eligibility for sputum examination to first contact with any health care provider (HCP)), health system level diagnosis delay (from contact with first HCP to TB diagnosis) and treatment initiation delays (from diagnosis to treatment initiation). Total delay was the sum of patient level, health system level diagnosis delay and treatment initiation delays., Results: We included 234 ACF-diagnosed and 231 PCF-diagnosed patients. When compared to PCF, ACF patients were relatively older (≥65 years, 14% versus 8%, p = 0.041), had no formal education (57% versus 36%, p<0.001), had lower monthly income per capita (median 13.1 versus 15.7 USD, p = 0.014), were more likely from rural areas (92% versus 81%, p<0.002) and residing far away from the sputum microscopy centres (more than 15 km, 24% versus 18%, p = 0.126). Fewer patients had history of significant loss of weight (68% versus 78%, p = 0.011) and sputum grade of 3+ (15% versus 21%, p = 0.060). Compared to PCF, HCP visits among ACF patients was significantly lower (median one versus two HCPs, p<0.001). ACF patients had significantly lower health system level diagnosis delay (median five versus 19 days, p = 0.008) and the association remained significant after adjusting for potential confounders. Patient level and total delays were not significantly different., Conclusion: Axshya SAMVAD linked the most impoverished communities to TB care and resulted in reduction of health system level diagnosis delay., Competing Interests: The authors have declared that no competing interests exist.

Background : Community-based active case finding (ACF) for tuberculosis (TB) implemented among marginalised and vulnerable populations in 285 districts of India resulted in reduction of diagnosis delay and prevalence of catastrophic costs due to TB diagnosis. We were interested to know whether this translated into improved treatment outcomes. Globally, there is limited published literature from marginalised and vulnerable populations on the independent effect of community-based ACF on treatment outcomes when compared to passive case finding (PCF). Objectives : To determine the relative differences in unfavourable treatment outcomes (death, loss-to-follow-up, failure, not evaluated) of ACF and PCF-diagnosed people. Methods : Cohort study involving record reviews and interviews in 18 randomly selected districts. We enrolled all ACF-diagnosed people with new smear-positive pulmonary TB, registered under the national TB programme between March 2016 and February 2017, and an equal number of randomly selected PCF-diagnosed people in the same settings. We used log binomial models to adjust for confounders. Results : Of 572 enrolled, 275 belonged to the ACF and 297 to the PCF group. The proportion of unfavourable outcomes were 10.2% (95% CI: 7.1%, 14.3%) in the ACF and 12.5% (95% CI: 9.2%, 16.7%) in the PCF group (p = 0.468). The association between ACF and unfavourable outcomes remained non-significant after adjusting for confounders available from records [aRR: 0.83 (95% CI: 0.56, 1.21)]. Due to patient non-availability at their residence, interviews were conducted for 465 (81.3%). In the 465 cohort too, there was no association after adjusting for confounders from records and interviews [aRR: 1.05 (95% CI: 0.62, 1.77)]. Conclusion : We did not find significant differences in the treatment outcomes. Due to the wide CIs, studies with larger sample sizes are urgently required. Studies are required to understand how to translate the benefits of ACF to improved treatment outcomes.

Setting: Four Tuberculosis (TB) Units in the Union Territory of Puducherry in India. Objectives: To identify factors associated with unfavourable outcomes among retreatment TB cases in Puducherry. Design: The study had a mixed-methods design in which routinely reported TB data from retreatment TB cases registered during 2014 and 2015 were used for the quantitative part; the qualitative phase comprised interviews and focus group discussions with health care providers. Results: Among the 392 retreatment cases, 297 (75.8%) had favourable outcomes. Outcome for previous treatment such as loss to follow-up (LTFU) (adjusted relative risk [aRR] 1.6, 95%CI 1.1-2.4, P = 0.001), treatment failure (aRR 1.7, 95%CI 1.04-2.8, P = 0.03) and pre-treatment weight <40 kg (aRR 1.8, 95%CI 1.3-2.5, P = 0.001) had increased risk for unfavourable outcomes. Health care providers reported that alcoholism, lack of family support, job-related issues and lack of access to trained staff for injections were some of the reasons for unfavourable outcomes. Providing incentives, nutritional supplements and early retrieval of the LTFU cases were some of the suggestions to reduce unfavourable outcomes. Conclusion: Outcome of previous treatment and low pre-treatment weight of the patient affected retreatment outcomes. Health professionals and workers highlighted social and health system-related factors. Commitment at all levels on the part of health care providers and addressing their concerns can improve retreatment outcomes., Competing Interests: Conflicts of interest: none declared.

Setting: Sikkim, India, has the highest proportion of tuberculosis (TB) patients on first-line anti-tuberculosis regimens with the outcome 'failure' or 'shifted to regimen for multidrug-resistant TB (MDR-TB)'. Objective: To assess the factors associated with non-response to treatment, i.e., 'failure' or 'shifted to MDR-TB regimen'. Methods: We conducted a retrospective cohort study using Revised National Tuberculosis Control Programme data of all TB patients registered in 2015 for first-line TB treatment. In addition, we interviewed 42 patients who had not responded to treatment to ascertain their current status. Results: Of 1508 patients enrolled for treatment, about 9% were classified as non-response to treatment. Patient factors associated with non-response were urban setting (adjusted odds ratio [aOR] 2.39, 95%CI 1.22-4.67), ethnicity (being an Indian tribal, aOR 1.73, 95%CI 1.17-2.57, Indian [other] aOR 1.83, 95%CI 1.29-2.60 compared to patients of Nepali origin) and those on retreatment (aOR 2.40, 95%CI 1.99-2.91). Of the patients interviewed, 28 (67%) had received treatment for drug-resistant TB. Conclusion: In Sikkim, one in 11 patients had not responded to first-line anti-tuberculosis treatment. Host-pathogen genetics and socio-behavioural studies may be required to understand the reasons for the differences in non-response, particularly among ethnic groups., Competing Interests: Conflicts of interest: none declared.

Background: Early and accurate diagnosis of tuberculosis is a priority for TB programs globally to initiate treatment early and improve treatment outcomes. Currently, Ziehl-Neelsen (ZN) stain-based microscopy, GeneXpert and Light Emitting Diode-Fluorescence Microscopy (LED-FM) are used for diagnosing pulmonary drug sensitive tuberculosis. Published evidence synthesising the cost-effectiveness of these diagnostic tools is scarce., Methodology: PubMed, EMBASE and Cost-effectiveness analysis registry were searched for studies that reported on the cost-effectiveness of GeneXpert and LED-FM, compared to ZN microscopy for diagnosing pulmonary TB. Risk of bias was assessed independently by four authors using the Consensus Health Economic Criteria (CHEC) extended checklist. The data variables included the study settings, population, type of intervention, type of comparator, year of study, duration of study, type of study design, costs for the test and the comparator and effectiveness indicators. Incremental cost-effectiveness ratio (ICER) was used for assessing the relative cost-effectiveness in this review., Results: Of the 496 studies identified by the search, thirteen studies were included after removing duplicates and studies that did not fulfil inclusion criteria. Four studies compared LED-FM with ZN and nine studies compared GeneXpert with ZN. Three studies used patient cohorts and eight were modelling studies with hypothetical cohorts used to evaluate cost-effectiveness. All these studies were conducted from a health system perspective, with four studies utilising cost utility analysis. There were considerable variations in costing parameters and effectiveness indicators that precluded meta-analysis. The key findings from the included studies suggest that LED-FM and GeneXpert may be cost effective for pulmonary TB diagnosis from a health system perspective., Conclusion: Our review identifies a consistent trend of the cost effectiveness of LED-FM and GeneXpert for pulmonary TB diagnosis in different countries with diverse context of socio-economic condition, HIV burden and geographical distribution. However, all the studies used different parameters to estimate the impact of these tools and this underscores the need for improving the methodological issues related to the conduct and reporting of cost-effectiveness studies., Competing Interests: The authors have declared that no competing interests exist.

Setting and objectives: Tobacco use compromises tuberculosis (TB) treatment outcomes. Tobacco cessation is beneficial to TB patients at the individual level and from the perspective of a larger spectrum of non-communicable diseases associated with tobacco use. We assessed feasibility, effectiveness and provider perceptions on integrating brief tobacco cessation advice into routine TB care by DOTS providers from 27 TB treatment centres run by three non-governmental organisations (NGOs) in urban India. Design: A mixed-methods study (triangulation design) involving analysis of programme data and semi-structured interviews (quantitative) and thematic analysis of focus group discussions of TB treatment providers (qualitative) regarding brief advice and cessation support provided to self-reported tobacco users from August 2015 to July 2017. Results: All 27 centres initiated tobacco cessation. Of 2132 registered TB patients, 377 (18%) were tobacco users, 333 (88%) of whom used smokeless tobacco. There was a progressive drop in documentation of tobacco status at each visit, reaching respectively 36% and 30% at the end of treatment for new and retreatment TB patients. Seven-day point prevalence abstinence at 6 months was 32% among new and 15% among retreatment cases. Enablers for integration included NGO collaboration, supervision and capacity building. Challenges included providers spending 15-45 min per patient (10 min recommended), multiple addictions, documentation load, self-reporting and social normalisation of tobacco. Conclusions: Integration of tobacco cessation into routine TB care in an urban NGO setting was feasible, although without continued support, rigour in documentation declined. This should be scaled up with special attention paid to tackling smokeless tobacco and related operational challenges., Competing Interests: Conflicts of interest: none declared.

Background: Tuberculosis (TB) patients face substantial delays prior to treatment initiation, and out of pocket (OOP) expenditures often surpass the economic productivity of the household. We evaluated the pre-diagnostic cost and health seeking behaviour of new adult pulmonary TB patients registered at Primary Health Centres (PHCs) in Vellore district, Tamil Nadu, India., Methods: This descriptive study, part of a randomised controlled trial conducted in three rural Tuberculosis Units from Dec 2012 to Dec 2015, collected data on number of health facilities, dates of visits prior to the initiation of anti-tuberculosis treatment, and direct OOP medical costs associated with TB diagnosis. Logistic regression analysis examined the factors associated with delays in treatment initiation and OOP expenditures., Results: Of 880 TB patients interviewed, 34.7% presented to public health facilities and 65% patients sought private health facilities as their first point of care. The average monthly individual income was $77.79 (SD 57.14). About 69% incurred some pre-treatment costs at an average of $39.74. Overall, patients experienced a median of 6 days (3-11 IQR) of time to treatment initiation and 21 days (10-30 IQR) of health systems delay. Age ≤ 40 years (aOR: 1.73; CI: 1.22-2.44), diabetes (aOR: 1.63; CI: 1.08-2.44) and first visit to a private health facility (aOR: 17.2; CI: 11.1-26.4) were associated with higher direct OOP medical costs, while age ≤ 40 years (aOR: 0.64; CI: 0.48-0.85) and first visit to private health facility (aOR: 1.79, CI: 1.34-2.39) were associated with health systems delay., Conclusion: The majority of rural TB patients registering at PHCs visited private health facilities first and incurred substantial direct OOP medical costs and delays prior to diagnosis and anti-tuberculosis treatment initiation. This study highlights the need for PHCs to be made as the preferred choice for first point of contact, to combat TB more efficiently.

Background: The Global Fund encourages operational research (OR) in all its grants; however very few reports describe this aspect. In India, Project Axshya was supported by a Global Fund grant to improve the reach and visibility of the government Tuberculosis (TB) services among marginalised and vulnerable communities. OR was incorporated to build research capacity of professionals working with the national TB programme and to generate evidence to inform policies and practices., Objectives: To describe how Project Axshya facilitated building OR capacity within the country, helped in addressing several TB control priority research questions, documented project activities and their outcomes, and influenced policy and practice., Methods: From September 2010 to September 2016, three key OR-related activities were implemented. First, practical output-oriented modular training courses were conducted (n = 3) to build research capacity of personnel involved in the TB programme, co-facilitated by The Union, in collaboration with the national TB programme, WHO country office and CDC, Atlanta. Second, two large-scale Knowledge, Attitude and Practice (KAP) surveys were conducted at baseline and mid-project to assess the changes pertaining to TB knowledge, attitudes and practices among the general population, TB patients and health care providers over the project period. Third, studies were conducted to describe the project's core activities and outcomes., Results: In the training courses, 44 participant teams were supported to develop research protocols on topics of national priority, resulting in 28 peer-reviewed scientific publications. The KAP surveys and description of project activities resulted in 14 peer-reviewed publications. Of the published papers at least 12 have influenced change in policy or practice., Conclusions: OR within a Global Fund supported TB project has resulted in building OR capacity, facilitating research in areas of national priority and influencing policy and practice. We believe this experience will provide guidance for undertaking OR in Global Fund projects.

Background: There is limited evidence on whether active case finding (ACF) among marginalised and vulnerable populations mitigates the financial burden during tuberculosis (TB) diagnosis., Objectives: To determine the effect of ACF among marginalised and vulnerable populations on prevalence and inequity of catastrophic costs due to TB diagnosis among TB-affected households when compared with passive case finding (PCF)., Methods: In 18 randomly sampled ACF districts in India, during March 2016 to February 2017, we enrolled all new sputum-smear-positive TB patients detected through ACF and an equal number of randomly selected patients detected through PCF. Direct (medical and non-medical) and indirect costs due to TB diagnosis were collected through patient interviews at their residence. We defined costs due to TB diagnosis as 'catastrophic' if the total costs (direct and indirect) due to TB diagnosis exceeded 20% of annual pre-TB household income. We used concentration curves and indices to assess the extent of inequity., Results: When compared with patients detected through PCF (n = 231), ACF patients (n = 234) incurred lower median total costs (US$ 4.6 and 20.4, p < 0.001). The prevalence of catastrophic costs in ACF and PCF was 10.3 and 11.5% respectively. Adjusted analysis showed that patients detected through ACF had a 32% lower prevalence of catastrophic costs relative to PCF [adjusted prevalence ratio (95% CI): 0.68 (0.69, 0.97)]. The concentration indices (95% CI) for total costs in both ACF [-0.15 (-0.32, 0.11)] and PCF [-0.06 (-0.20, 0.08)] were not significantly different from the line of equality and each other. The concentration indices (95% CI) for catastrophic costs in both ACF [-0.60 (-0.81, -0.39)] and PCF [-0.58 (-0.78, -0.38)] were not significantly different from each other: however, both the curves had a significant distribution among the poorest quintiles., Conclusion: ACF among marginalised and vulnerable populations reduced total costs and prevalence of catastrophic costs due to TB diagnosis, but could not address inequity.

Setting: The introduction of accredited social health activists (ASHAs, community workers) in the community is encouraged by the Government of India as being of universal benefit for maternal and infant health. Objectives: In two informal settlements in Chandigarh, India, one with ASHAs and the other without, we assessed 1) whether ASHAs influenced certain selected maternal and infant health indicators, and 2) perceptions among women who did not contact the ASHAs. Design: This was a mixed-methods study conducted from April 2013 to March 2016 using quantitative (retrospective programme data) and qualitative (free-listing) components. Results: The increase in institutional deliveries from 2013 to 2015 was marginal, and was similar in both areas (86-99% in the settlement with ASHAs and 88-97% in the settlement without). Bacille Calmette-Guérin and pentavalent vaccination coverage were close to 100% in both areas during the 3 years of the study. Antenatal registration in the first trimester increased from 49% to 52% in the settlement with ASHAs and from 53% to 71% in the settlement without. Between 18% and 35% of women did not complete at least three antenatal visits. 'Not knowing ASHAs' and 'not feeling a need for ASHAs' were the main reasons for not using their services. Conclusion: While success has been achieved for institutional deliveries and immunisation coverage even without the ASHAs, their presence plays an important role in improving antenatal indicators.

We followed 188 euthyroidic persons undergoing treatment for multidrug resistant tuberculosis (MDR-TB) in the state of Karnataka, India to determine the incidence of hypothyroidism during anti-tuberculosis treatment. Overall, among MDR-TB patients with valid thyroid stimulating hormone (TSH) values, about 23% developed hypothyroidism (TSH value ≥10 mIU/ml) during anti-tuberculosis treatment; the majority (74%) occurring after 3 months of treatment. Among 133 patients who received a regimen that contained ethionamide, 42 (32%) developed hypothyroidism. Among 17 patients that received a regimen that contained para-aminosalicylate sodium, 6 (35%) developed hypothyroidism. Among 9 HIV positive patients on anti-retroviral treatment, 4 (44%) developed hypothyroidism. These results differ from previously reported 4% incidence of hypothyroidism amongst patients who passively reported thyroidal symptoms during treatment, suggesting routine serologic monitoring of TSH throughout the course of treatment for MDR-TB is warranted., Competing Interests: No conflicts declared.

Background: One-fifth of the patients on multidrug-resistant tuberculosis treatment at the Drug-Resistant-TB (DR-TB) Site in Gujarat are lost-to-follow-up(LFU)., Objective: To understand patients' and providers' perspectives on reasons for LFU and their suggestions to improve retention-in-care., Design: Qualitative study conducted between December 2013-March 2014, including in-depth interviews with LFU patients and DOT-providers, and a focus group discussion with DR-TB site supervisors. A thematic-network analysis approach was utilised., Results: Three sub-themes emerged: (i) Struggle with prolonged treatment; (ii) Strive against stigma and toward support; (iii) Divergent perceptions and practices. Daily injections, pill burden, DOT, migratory work, social problems, prior TB treatment, and adverse drugs effects were reported as major barriers to treatment adherence and retention-in-care by patients and providers. Some providers felt that despite their best efforts, LFU patients remain. Patient movements between private practitioners and traditional healers further influenced LFU., Conclusion: The study points to a need for repeated patient counselling and education, improved co-ordination between various tiers of providers engaged in DR-TB care, collaboration between the public, private and traditional practitioners, and promotion of social and economic support to help patients adhere to MDR-TB treatment and avoid LFU.

Background: Stigmatising and discriminating attitudes may discourage tuberculosis (TB) patients from actively seeking medical care, hide their disease status, and discontinue treatment. It is expected that appropriate knowledge regarding TB should remove stigmatising and discriminating attitudes. In this study we assessed the prevalence of stigmatising and discriminating attitudes towards TB patients among general population and their association with knowledge regarding TB., Method: A cross-sectional knowledge, attitude and practice survey was conducted in 30 districts of India in January-March 2011. A total of 4562 respondents from general population were interviewed using semi-structured questionnaires which contained items to measure stigma, discrimination and knowledge on TB., Result: Of the 4562 interviewed, 3823 were eligible for the current analysis. Of these, 73% (95% CI 71.4-74.2) had stigmatising and 98% (95% CI 97.4-98.3) had discriminating attitude towards TB patients. Only 17% (95% CI 15.6-18.0) of the respondents had appropriate knowledge regarding TB with even lower levels observed amongst females, rural areas and respondents from low income groups. Surprisingly stigmatising (adjusted OR 1.31 (0.78-2.18) and discriminating (adjusted OR 0.79 (0.43-1.44) attitudes were independent of knowledge regarding TB., Conclusion: Stigmatising and discriminating attitudes towards TB patients remain high among the general population in India. Since these attitudes were independent of the knowledge regarding TB, it is possible that the current disseminated knowledge regarding TB which is mainly from a medical perspective may not be adequately addressing the factors that lead to stigma and discrimination towards TB patients. Therefore, there is an urgent need to review the messages and strategies currently used for disseminating knowledge regarding TB among general population and revise them appropriately. The disseminated knowledge should include medical, psycho-social and economic aspects of TB that not only informs people about medical aspects of TB disease, but also removes stigma and discrimination.

Background: There are considerable numbers of patients coinfected with human immunodeficiency virus (HIV) and visceral leishmaniasis (VL) in the VL-endemic areas of Bihar, India. These patients are at higher risk of relapse and death, but there are still no evidence-based guidelines on how to treat them. In this study, we report on treatment outcomes of coinfected patients up to 18 months following treatment with a combination regimen., Methods: This retrospective analysis included all patients with confirmed HIV-VL coinfection receiving combination treatment for VL at a Médecins Sans Frontières treatment center between July 2012 and September 2014. Patients were treated with 30 mg/kg body weight intravenous liposomal amphotericin B (AmBisome) divided as 6 equal dose infusions combined with 14 days of 100 mg/day oral miltefosine (Impavido). All patients were encouraged to start or continue on antiretroviral therapy (ART)., Results: 102 patients (76% males, 57% with known HIV infection, 54% with a prior episode of VL) were followed-up for a median of 11 months (interquartile range: 4-18). Cumulative incidence of all-cause mortality and VL relapse at 6, 12, and 18 months was 11.7%, 14.5%, 16.6% and 2.5%, 6.0%,13.9%, respectively. Cumulative incidence of poor outcome at 6, 12, and 18 months was 13.9%, 18.4%, and 27.2%, respectively. Not initiating ART and concurrent tuberculosis were independent risk factors for mortality, whereas no factors were associated with relapse., Conclusions: In this Bihar-based study, combination therapy appeared to be well tolerated, safe, and effective and may be considered as an option for treatment of VL in HIV coinfected patients., (© The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.)

Background: Multidrug-resistant Tuberculosis (MDR-TB) is a rising global threat to public health and concerted efforts for its treatment are diluted if the outcomes are not successful, loss to follow up (LFU) being one of them. It is therefore necessary to know the proportion and the associated reasons for LFU and devise effective patient-centered strategies to improve retention in care., Methods: A retrospective cohort study was conducted at the MDR-TB treatment site (DR-TB Site)in Central Gujarat among all patients registered from February 2010 to June 2013.LFU patients were defined as those whose treatment was interrupted for two or more consecutive months for any reason. Descriptive statistics, survival analysis and multivariate modeling were used to determine the proportion of patients LFU and to assess associations between LFU and selected demographic and clinical factors., Results: A total of 796 patients were enrolled during the study period; 71.9% were male and the median age was 35 years [Interquartile range (IQR) 27-45].The overall proportion of LFU patients was 153/796 (19.2%).The majority of LFU patients (133/153 i.e.87%) were lost within the first 6 months of treatment. Ambulatory treatment initiation (adjusted Hazards ratio aHR=2.63, CI:1.01-6.86), different providers in IP and CP ( aHR=1.27, CI:1.18-1.38)and culture conversion after more than 4 months of treatment(aHR=1.34, CI: 1.21-1.49)were found to be significantly associated with LFU in multivariate models., Conclusions: A high proportion of LFU among patients on MDR-TB treatment was found in a programmatic setting in India. Clinical but equally important programmatic factors were associated with LFU, accounting for one-fifth of all the outcomes of MDR-TB treatment. Proper training for DOT providers and aggressive counseling and health system strengthening with patient friendly follow up services may help reduce LFU.

Objectives: To determine, in areas supported by BRAC, Bangladesh i) the pre-diagnosis and pre-treatment attrition among presumptive and confirmed Multi-Drug Resistant Tuberculosis (MDR-TB) patients and ii) factors associated with attrition., Methods: This was a retrospective cohort study involving record review. Presumptive MDR-TB patients from peripheral microscopy centres serving 60% of the total population of Bangladesh were included in the study. Attrition and turnaround time for MDR-TB diagnosis by Xpert MTB/RIF and treatment initiation were calculated between July 2012 and June 2014., Results: Of 836 presumptive MDR-TB patients referred from 398 peripheral microscopy centres, 161 MDR-TB patients were diagnosed. The number of diagnosed MDR-TB patients was less than country estimates of MDR-TB patients (2000 cases) during the study period. Among those referred, pre-diagnosis and pre-treatment attrition was 17% and 21% respectively. Median turnaround time for MDR-TB testing, result receipt and treatment initiation was four, zero and five days respectively. Farmers (RR=2.3, p=0.01) and daily wage laborers (RR=2.1, p=0.04) had twice the risk of having pre-diagnosis attrition. Poor record-keeping and unreliable upkeep of presumptive MDR-TB patient databases were identified as challenges at the peripheral microscopy centres., Conclusion: There was a low proportion of pre-diagnosis and pre-treatment attrition in patients with presumptive and confirmed MDR-TB under programmatic conditions. However, the recording and reporting system did not detect all presumptive MDR-TB patients, highlighting the need to improve the system in order to prevent morbidity, mortality and transmission of MDR-TB in the community.

Given the well-known linkage between diabetes mellitus (DM) and tuberculosis (TB), the World Health Organization recommends bidirectional screening. Here we report the first screening effort of its kind from a chest clinic in the Ampara district of Sri Lanka. Of 112 TB patients registered between January 2013 and October 2014, eight had pre-existing DM. Of those remaining, 83 (80%) underwent fasting plasma glucose testing, of whom two (2%) and 17 (20%) were found to have diabetes and impaired fasting glucose, respectively. All of these were enrolled in care. Screening TB patients for DM was found to be feasible at the district level. Further studies at the provincial/country level are required before making any decision to scale up bidirectional screening.

Background: With support from the Stop TB Partnership's TB REACH Wave 2 Grant, diagnostic microscopy services for tuberculosis (TB) were upgraded from conventional Ziehl-Neelsen (ZN) based sputum microscopy to light emitting diode technology-based fluorescence microscopy (LED FM) in 200 high-workload microscopy centres in India as a pilot intervention., Objective: To evaluate the cost-effectiveness of LED-FM over conventional ZN microscopy to inform further scale-up., Methods: A decision-tree model was constructed to assess the cost utility of LED FM over ZN microscopy. The results were summarised using incremental cost-effectiveness ratio (ICER); one-way and probabilistic sensitivity analyses were also conducted to address uncertainty within the model. Data were analysed from 200 medical colleges in 2011 and 2012, before and after the introduction of LED microscopes. A full costing analysis was carried out from the perspective of a national TB programme., Results: The ICER was calculated at US$14.64 per disability-adjusted life-year, with an 82% probability of being cost-effective at a willingness-to-pay threshold equivalent to Indian gross domestic product per capita., Conclusions: LED FM is a cost-effective intervention for detecting TB cases in India at high-workload medical college settings.

Background: Despite being a recognized standard of tuberculosis (TB) care internationally, mandatory TB case notification brings forth challenges from the private sector. Only three TB cases were notified in 2013 by private practitioners compared to 2000 TB cases notified yearly from the public sector in Alappuzha district. The study objective was to explore the knowledge, opinion and barriers regarding TB Notification among private practitioners offering TB services in Alappuzha, Kerala state, India., Methods & Findings: This was a mixed-methods study with quantitative (survey) and qualitative components conducted between December 2013 and July 2014. The survey, using a structured questionnaire, among 169 private practitioners revealed that 88% were aware of mandatory notification. All patient-related details requested in the notification form (except government-issued identification number) were perceived to be important and easy to provide by more than 80% of practitioners. While more than 95% felt that notification should be mandatory, punitive action in case of failure to notify was considered unnecessary by almost two third. General practitioners (98%) were more likely to be aware of notification than specialists (84 %). (P<0.01). Qualitative purposive personal interviews (n=34) were carried out among private practitioners and public health providers. On thematic framework analysis of the responses, barriers to TB notification were grouped into three themes: 'private provider misconceptions about notification', 'patient confidentiality, and stigma and discrimination 'and 'lack of cohesion and coordination between public and private sector'. Private practitioners did not consider it necessary to notify TB cases treated with daily regimen., Conclusion: Communication strategies like training, timely dissemination of information of policy changes and one-to-one dialogue with private practitioners to dispel misconceptions may enhance TB notification. Trust building strategies like providing feedback about referred cases from private sector, health personnel visit or a liaison private doctor may ensure compliance to public health activities.

Settings: Kerala State, India has reported the greatest dual burden of Tuberculosis (TB) and Diabetes Mellitus (DM). Malappuram district in Kerala has monitored and recorded DM status and its control from 2010 under Revised National Tuberculosis Control Program (RNTCP)., Objectives: To assess, under programme conditions, comprehensiveness of recording DM status among TB cases and the TB treatment outcomes among DM patients (disaggregated by glycemic control) and compare with-non DM patients., Design: This retrospective record review included 3,116TB patients from April 2010 to September 2011.DM was defined as per international guidelines and TB treatment outcomes were categorized as favourable(cured and treatment completed) and unfavourable(death, default, failure and transfer out). Relative Risk (RR) and 95% confidence intervals(CI) were calculated to assess the risk of unfavourable outcomes., Results: DM status was recorded in 90% of TB cases and 667 (24%) had DM. 17% of DM patients and 23% of patients with unknown DM status had unfavourable outcomes but this difference was not statistically significant. Unadjusted RR for poor glycemic control or unknown control status for unfavourable outcome were (2.00; 95% CI 0.97-4.13) and (2.14; 95% CI 1.11-4.13)., Conclusion: This study could not confirm an adverse association between DM or its control during treatment and the course of response to TB treatment.DM screening in TB cases and recording of DM care needs to be improved to enable more conclusive evidence.

Setting: The Revised National Tuberculosis Control Programme in an urban setting of Bangalore City, India., Objectives: To compare treatment outcomes and smear conversion rates among new smear-positive tuberculosis (TB) patients undergoing treatment administered by community directly observed treatment (DOT) providers with those undergoing treatment administered by institutional DOT providers in Bangalore City in 2010-2011., Method: Cohort study of routine data recorded from treatment cards of TB patients undergoing treatment under the public health services from 1 October 2010 to 30 September 2011., Result: Treatment records of 1864 new smear-positive TB patients registered during this period were evaluated. Among those evaluated, 604 (32%) had been administered treatment by community DOT providers and the remainder by institutional DOT providers. The treatment success rate in those undergoing community DOT was 93% (n = 564) and that of those undergoing institutional DOT was 75% (n = 951; RR 1.23, 95%CI 1.19-1.28). The sputum smear conversion rate of patients who underwent community DOT was 92% and that of those who underwent institutional DOT was 71% at the end of 2 months., Conclusion: We conclude that community DOT for treatment supervision of TB patients is more effective than institutional DOT and that it should be reinforced.

Background: Previous studies investigating the role of cytokines in the pathogenesis of leprosy have either been on only small numbers of patients or have not combined clinical and histological data. The INFIR Cohort study is a prospective study of 303 new multibacillary leprosy patients to identify risk factors for reaction and nerve damage. This study characterised the cellular infiltrate in skin and nerve biopsies using light microscopic and immunohistochemical techniques to identify any association of cytokine markers, nerve and cell markers with leprosy reactions., Methodology/principal Findings: TNF-α, TGF-β and iNOS protein in skin and nerve biopsies were detected using monoclonal antibody detection immunohistochemistry techniques in 299 skin biopsies and 68 nerve biopsies taken from patients at recruitment. The tissues were stained with hematoxylin and eosin, modified Fite Faraco, CD68 macrophage cell marker and S100., Conclusions/significance: Histological analysis of the biopsies showed that 43% had borderline tuberculoid (BT) leprosy, 27% borderline lepromatous leprosy, 9% lepromatous leprosy, 13% indeterminate leprosy types and 7% had no inflammation. Forty-six percent had histological evidence of a Type 1 Reaction (T1R) and 10% of Erythema Nodosum Leprosum. TNF-α was detected in 78% of skin biopsies (181/232), iNOS in 78% and TGF-β in 94%. All three molecules were detected at higher levels in patients with BT leprosy. TNF-α was localised within macrophages and epithelioid cells in the granuloma, in the epidermis and in dermal nerves in a few cases. TNF-α, iNOS and TGF-β were all significantly associated with T1R (p<0.001). Sixty-eight nerve biopsies were analysed. CD68, TNF-α and iNOS staining were detectable in 88%, 38% and 28% of the biopsies respectively. The three cytokines TNF-α, iNOS and TGF-β detected by immunohistochemistry showed a significant association with the presence of skin reaction. This study is the first to demonstrate an association of iNOS and TGF-β with T1R.

Background: Leprosy is an infectious disease in which the susceptibility to the pathogen Mycobacterium leprae and the clinical manifestations are attributed to host immune cell response. Receptor mediated events and signalling in the immune cells are mediated by protein phosphorylation. The main signalling pathways and protein kinases known to be involved in the regulation of immune cells are cAMP dependent kinases, calcium/calmodulin dependent kinases, protein kinase C and mitogen activated protein kinases. The cumulative consequence of alterations in signalling pathways can be evaluated by intrinsic cellular protein phosphorylation by gamma-P32 ATP. The present study was designed to assess the protein phosphorylation in the immune cells of leprosy patients as compared with normal individuals., Methodology: Lymphocyte protein phosphorylation was conducted in 15 leprosy patients and 9 normal individuals. Protein phosphorylation of lymphocytes was carried out in the presence/absence of protein kinase modulators. The phosphorylation patterns were documented and analysed consequent to SDS-PAGE, staining, destaining, drying and autoradiography., Results: The major phosphorylated proteins in lymphocytes were of molecular weights 20-22, 24-29, 30-35, 43, 46-50 and 66-68 kDa. In general, the major phosphorylated proteins were similar in the controls and in the patients. The phosphorylatability of these proteins varied with different modulators. Variations in the phosphorylation pattern were observed in 25% of the leprosy patients where there was a decrease of the 66 kDa protein and a decrease of 20-22 kDa protein phosphorylation., Conclusion: The observed alterations in the protein phosphorylation pattern could be due to alteration in kinases and/or their substrates or due to the effect of M. leprae on immune cells.