CD38+CD27-TNF-α + on Mtb-specific CD4+ T Cells Is a Robust Biomarker for Tuberculosis Diagnosis.

BACKGROUND: Early and accurate diagnosis followed by timely treatment are the key prerequisites to fight tuberculosis (TB) and reduce its global burden. Despite scientific advances, the rapid and correct diagnosis of both pulmonary and extrapulmonary tuberculosis remains a challenge because of traditional reliance on detection of the elusive bacilli. Mycobacterium tuberculosis (Mtb)-specific host immune activation and cytokine production have shown significant promise as alternative means of detecting and distinguishing active disease from latent infection. We queried the diagnostic ability of phenotypic markers on Mtb-specific cytokine-producing immune cell subsets for identifying active TB. METHODS: Subjects belonging to the following groups were recruited: pulmonary and extrapulmonary TB, latent TB, cured TB, sick controls, and healthy controls. Polychromatic flow cytometry was used to identify host immune biomarkers in an exploratory cohort comprising 56 subjects using peripheral blood mononuclear cells. Clinical performance of the identified biomarker was evaluated using whole blood in a blinded validation cohort comprising 165 individuals. RESULTS: Cytokine secreting frequencies of Mtb-specific cluster of differentiation 4-positive (CD4+) T cells with CD38+CD27- phenotype clearly distinguished infected individuals with active tuberculosis from those without disease. Tumor necrosis factor-α (TNF-α) secretion from CD38+CD27-CD4+ T cells upon stimulation with ESAT6/CFP10 peptides had the best diagnostic accuracy at a cutoff of 9.91% (exploratory: 96.67% specificity, 88.46% sensitivity; validation: 96.15% specificity, 90.16% sensitivity). Additionally, this subset differentiated treatment-naive patients with TB from individuals cured of TB following completion of anti-TB therapy. CONCLUSIONS: Mtb-specific CD38+CD27-TNF-α +CD4+ T-cell subset is a robust biomarker both for diagnosing TB and assessing cure.

Mandatory TB notification in Mysore city, India: Have we heard the private practitioner's plea?

BACKGROUND: The Government of India, made TB notification by private healthcare providers mandatory from May 2012 onwards. The National TB Programme developed a case based web based online reporting mechanism called NIKSHAY. However, the notification by private providers has been very low. We conducted the present study to determine the awareness, practice and anticipated enablers related to TB notification among private practitioners in Mysore city during 2014. METHODS: A cross-sectional study was conducted among private practitioners of Mysore city in south India. The private practitioners in the city were identified and 258 representative practitioners using probability proportional to size were interviewed using semi-structured questionnaire. RESULTS: Among the 258 study participants, only 155 (60%) respondents agreed to a detailed interview. Among those interviewed, 141 (91%) were aware that TB is a notifiable disease; however 127 (82%) of them were not aware of process of notification and NIKSHAY. Only one in six practitioners was registered in NIKSHAY, while one in three practitioners are notifying without registration. The practitioners expected certain enablers from the programme like free drugs, training to notify in NIKSHAY and timely feedback. 74 (47%) opined that notification should be backed by legal punitive measures. CONCLUSION: The programme should develop innovative strategies that provide enablers, address concerns of practitioners while having simple mechanisms for TB notification. The programme should strengthen its inherent capacity to monitor TB notification.

TB operational research in India - Gaps and pragmatic solutions.

Operational research (OR) plays a pivotal role in the management and improvement of national tuberculosis (TB) programs in India. This article underscores the indispensable value of OR in optimizing resource allocation, enhancing treatment protocols, improving diagnostics, ensuring patient adherence, monitoring program performance, and informing policy decisions. However, it is vital to address existing gaps in the operational research mechanisms of the National Tuberculosis Elimination Program (NTEP) in India to maximize its effectiveness. In conclusion, India's healthcare system can significantly benefit from the systematic implementation of operational research, especially in the context of TB control. To achieve this, India must continue to invest in research infrastructure, enhance research capacity among healthcare professionals, and promote collaboration among researchers, healthcare providers, and policymakers. By doing so, India can harness the power of operational research to lead the fight against TB and enhance the well-being of its citizens.

Tuberculosis screening for pediatric household contacts in India: Time to adapt newer strategies under the National TB Elimination Programme!

INTRODUCTION: The study aimed to evaluate the effectiveness of screening pediatric household contacts (under the age of 15 years) for tuberculosis (TB) in India through verbal screening, tuberculin skin testing, and chest radiography at intervals of 0, 3, 6, 9, and 12 months. The study also aimed to determine the proportion of contacts who tested positive for TB and to describe the challenges in implementing regular follow-up. Current National TB Elimination Programme (NTEP) guidelines only require verbal screening for contacts under 6 years old at TB treatment initiation. The study aimed to fill this knowledge gap and provide valuable insights for improving TB screening in pediatric household contacts in India. METHODS: The study was conducted in two districts of Karnataka, India from 2021 to 2022, and utilized a cohort study design to enroll contacts of index tuberculosis (TB) cases diagnosed under the National TB Elimination Programme (NTEP). Participants were followed up at regular intervals for one year to evaluate the effectiveness of TB screening in pediatric household contacts. RESULTS: In this study, 686 pediatric household contacts were enrolled and screened for tuberculosis (TB) using verbal symptom screening, tuberculin skin testing (TST), and chest radiography. Projected figures estimated that 0.8%, 42%, and 4% of contacts would test positive for symptomatic screening, TST, and chest radiography, respectively. TB cases were detected in 2.91% (1.84-4.38) of contacts, with females above 6 years of age having a 22% higher risk of contracting the infection than males above 6 to < 15 years. However, not all cases were subjected to TST and chest radiography. The primary reason for not investigating child contact for TB was their reported healthy or asymptomatic status. CONCLUSION: The implementation of regular screening intervals for tuberculin skin test (TST) and chest radiography, along with verbal screening, among pediatric household contacts under the age of 15 years seems to be beneficial for the National TB Elimination Programme (NTEP), despite the challenges faced during implementation. Innovative strategies should be explored by NTEP to ensure effective implementation.

Chasing END TB 2025: Arithmetic needed for logistics!

India adopted changes in NTEP (Erstwhile RNTCP, Revised National TB Program, renamed as National TB Elimination Program) in the recent years with an aim to End TB by 2025 way ahead of the global target of ending TB by 2030. It is taking a long time for the changes to trickle down to the grass root level to change the behavior of the ground level force to understand and adopt to the changes that are being ordered and several other changes that are being pushed to the field in tandem. This has made field workers to be on their toes to understand and implement all the changes. The logistics like referral forms, GeneXpert/CBNAAT cartridges, slides etc., required for the program need to be calculated and used as per the changes. Shortages in the procurement or indenting will result in hampering the smooth functioning of the program. Accordingly, we calculated the logistics required for the patients estimated to occur in an area depending on the previous year's patient load. The breakup of the patients was adopted from the available references given. Also, the 2019 data of the load of different type of patients in India and the world were also taken. Total logistics were calculated for two hundred patients. Based on the calculations, a generic formula was derived. When the total number of patients in the previous year/quarter/or any period is N, then below is the formula which can estimate the required logistics for the next similar period.

Active Case Finding for Tuberculosis in India: A Syntheses of Activities and Outcomes Reported by the National Tuberculosis Elimination Programme.

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.

Challenges Perceived by Health Care Providers for Implementation of Contact Screening and Isoniazid Chemoprophylaxis in Karnataka, India.

Background: In India, challenges in pediatric TB contact screening and chemoprophylaxis initiation are still underexplored. Elucidating these challenges will help in better implementation of the programme at the grass-roots level thereby helping in early detection of pediatric cases and timely initiation of preventive therapy. This study aimed at exploring the challenges faced by the health care provider in contact screening and chemoprophylaxis initiation implementation of the pediatric household contacts. Methods: A qualitative study was conducted in the districts of Bengaluru and Udupi and in-depth interviews of key participants were adopted to explore the challenges. Qualitative data analysis was done after developing transcripts by generating themes and codes. Results: The key challenges were identified as stigma towards the disease, migrant patients with changing address, difficulty in sample collection, anxiety among parents due to long duration of the prophylactic treatment and adherence to IPT is not well documented, inadequate transportation from rural areas, and the ongoing COVID-19 pandemic. Conclusions: It is important for the National TB programme to address these challenges efficiently and effectively. Innovative solutions, feasible engagements, and massive efforts are to be taken by the programme to improve contact screening and isoniazid chemoprophylaxis implementation.

Qualitative enquiry on irregular intake of antihypertensive medications to inform a model of care to improve blood pressure control.

Background: A large proportion of people with hypertension do not take medications regularly. There is little understanding of this complex behaviour in India.Methods: A descriptive qualitative study was conducted in two districts of Andhra Pradesh, India, to explore the reasons for irregular intake of anti-hypertensive drugs from patient's and health care provider's (HCP) perspectives. In-depth interviews and focus group discussions were carried out among HCPs and patients with irregular drug intake.Results: The major themes that emerged were: (i) patient's perception of immediate relief and poor awareness about the disease, (ii) patient's misconceptions about the drug and fear of life long medications, (iii) busy schedule and forgetfulness, (iv) health system factors such as lack of patient counselling, high cost of care and non-availability of medicines, and (v) lack of peer/family/social support and social stigma.Conclusion: Better patient education and counselling services and active engagement of family members and peers are needed to improve medication adherence. The NPCDCS program should implement mechanisms to assess and monitor adherence to medications in chronic diseases particularly for hypertension.Impact: Currently there is no strategy to ensure medication adherence in India. The results of the study will be utilized in developing a community model of care to improve the level of adherence and better control of blood pressure.KEYWORDS: hypertension; medication adherence; compliance; qualitative study.

Is Chemoprophylaxis for Child Contacts of Drug-Resistant TB Patients Beneficial? A Systematic Review.

BACKGROUND: Preventive therapy for child contacts of multidrug-resistant tuberculosis (MDR-TB) patients is poorly studied, and no consensus about the role and the rationale of chemoprophylaxis has been reached. OBJECTIVE: To conduct systematic review with an aim to determine the effectiveness of TB preventive therapy in reducing the incidence of TB disease in pediatric contacts of MDR-TB patients. METHODS: We conducted a literature search for randomized control trials, cohort studies, and case reports of chemoprophylaxis for pediatric contacts of MDR-TB patients in PubMed, EMBASE, Cochrane Databases of Systematic Reviews, metaRegister of Controlled Trials, and other clinical registries through March 2017, using appropriate search strategy. In addition we searched abstracts from international conferences and references of published articles and reviews. RESULTS: Of the 153 references assessed from various databases, seven studies were identified as relevant after adaption of eligibility criteria and assessed for systematic review. Of these, only two studies contributed data for the pooled meta-analysis. CONCLUSIONS: Though the available evidences suggest that the chemoprophylaxis for child contacts of MDR-TB patients is beneficial, data to support or reject preventive therapy is very limited. Further clinical research, in Tb endemic settings like India, needs to be performed to prove the beneficial effect of chemoprophylaxis for pediatric contacts of MDR-TB.

TB Notification from Private Health Sector in Delhi, India: Challenges Encountered by Programme Personnel and Private Health Care Providers.

OBJECTIVE: To identify the challenges encountered by private health care providers (PHCP) to notify tuberculosis cases through a programme developed web-based portal mechanism called "NIKSHAY." Study Design. It is a descriptive qualitative study conducted at two revised national tuberculosis control programme (RNTCP) districts of New Delhi. The study included in-depth interviews of PHCP registered with "NIKSHAY" and RNTCP programme personnel. Grounded theory was used to conceptualise the latent social patterns in implementation of tuberculosis case notification process and promptly identifying their challenges. RESULTS: The analysis resulted in identification of three broad themes: (a) system implementation by RNTCP: it emphasizes the TB notification process by the RNTCP programme personnel; (b) challenges faced by PHCP for TB notification with five different subthemes; and (c) perceived gaps and suggestions: to improvise the TB notification process for the private health sector. The challenges encountered by PHCP were mainly related to unsystematic planning and suboptimal implementation by programme personnel at the state and district level. The PHCP lacked clarity on the need for TB notification. CONCLUSION: Implementation of TB notification among private health care providers requires systematic planning by the programme personnel. The process should be user-friendly with additional benefits to the patients.

How do patients who fail first-line TB treatment but who are not placed on an MDR-TB regimen fare in South India?

SETTING: Seven districts in Andhra Pradesh, South India. OBJECTIVES: To a) determine treatment outcomes of patients who fail first line anti-TB treatment and are not placed on an multi-drug resistant TB (MDR-TB) regimen, and b) relate the treatment outcomes to culture and drug susceptibility patterns (C&DST). DESIGN: Retrospective cohort study using routine programme data and Mycobacterium TB Culture C&DST between July 2008 and December 2009. RESULTS: There were 202 individuals given a re-treatment regimen and included in the study. Overall treatment outcomes were: 68 (34%) with treatment success, 84 (42%) failed, 36 (18%) died, 13 (6.5%) defaulted and 1 transferred out. Treatment success for category I and II failures was low at 37%. In those with positive cultures, 81 had pan-sensitive strains with 31 (38%) showing treatment success, while 61 had drug-resistance strains with 9 (15%) showing treatment success. In 58 patients with negative cultures, 28 (48%) showed treatment success. CONCLUSION: Treatment outcomes of patients who fail a first-line anti-TB treatment and who are not placed on an MDR-TB regimen are unacceptably poor. The worst outcomes are seen among category II failures and those with negative cultures or drug-resistance. There are important programmatic implications which need to be addressed.