Strategies to detect and manage latent tuberculosis infection among household contacts of pulmonary TB patients in high TB burden countries - a systematic review and meta-analysis.

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 (I2 ≥ 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.

Pretreatment Out-of-Pocket Expenses for Presumptive Multidrug-Resistant Tuberculosis Patients, India, 2016-2017.

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.

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.

Combination Treatment for Visceral Leishmaniasis Patients Coinfected with Human Immunodeficiency Virus in India.

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.

Patient adherence to tuberculosis treatment in the Indian subcontinent: systematic review and meta-synthesis of qualitative research.

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.

Evaluation of Drinking Water Quality and Bacterial Antibiotic Sensitivity in Wells and Standpipes at Household Water Points in Freetown, Sierra Leone.

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.

How Well Are Hand Hygiene Practices and Promotion Implemented in Sierra Leone? A Cross-Sectional Study in 13 Public Hospitals.

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.

High Prevalence of Methicillin-Resistant Staphylococcus aureus among Healthcare Facilities and Its Related Factors in Myanmar (2018-2019).

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.

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.

Antimicrobial Resistance among Neonates with Bacterial Sepsis and Their Clinical Outcomes in a Tertiary Hospital in Kathmandu Valley, Nepal.

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.

"99DOTS"techno-supervision for tuberculosis treatment - A boon or a bane? Exploring challenges in its implementation at a tertiary centre in Delhi, India.

BACKGROUND: In India, daily regimen with fixed-dose combination along with 99DOTS adherence tool and one-stop service at Anti-Retroviral Treatment (ART) centres for HIV infected Tuberculosis (TB) patients was launched in 2017. No systematic evaluation of its implementation has been done so far in a tertiary care setting in urban India. METHODS: A mixed-methods study was conducted at National Institute of Tuberculosis and Respiratory Diseases, Delhi in 2018-19. Missed doses, average adherence and treatment outcomes were compared across 99DOTS dashboard and TB treatment card. In-depth interviews of patients and health care providers were conducted to explore the implementation challenges and benefits. RESULTS: Median of missed doses recorded during intensive and continuation phase were 56 and 68 respectively in 99DOTS as compared to 0 in the TB Treatment card (p<0.0001). Average adherence was observed to be 27% in 99DOTS versus 99% in the TB treatment card (p<0.0001). Technical issues like software malfunction, logistic difficulties such as missing custom envelops and patient's inability to give call were reported. Role clarity among ART and TB program staff was ambiguous, which contributed to poor information flow between them. Patient benefits such as reduced stigma, less travel costs and reduced work absenteeism were reported. CONCLUSION: Success of 99DOTS program under programmatic condition needs webtool stability, uninterrupted logistic supplies (envelops), training of staff and better coordination between TB and HIV program personnel. Despite the challenges in its implementation, the benefit of this tool in terms of greater convenience and reduced stigma for patients is encouraging.

Are Treatment Outcomes of Patients with Tuberculosis Detected by Active Case Finding Different From Those Detected by Passive Case Finding?

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.

Does Drug-Resistant Extrapulmonary Tuberculosis Hinder TB Elimination Plans? A Case from Delhi, India.

Extrapulmonary drug-resistant tuberculosis (DR-EPTB) poses a formidable diagnostic and therapeutic challenge.Besides associated with high morbidity, it is a major financial burden for the patient and the health system. In spite of this, it has often been neglected as it does not "pose" a visible public health threat. We study clinical profiles, treatment outcomes, and factors associated with unfavourable outcomes among DR-EPTB patients under programmatic settings in New Delhi, India, and evaluate how this could impact TB elimination. A retrospective analysis of all DR-EPTB patients registered at three nodal DR-TB centres in Delhi in 2016 was carried out. Of the 1261 DR-TB patients registered, 203 (16%) were DR-EPTB, with lymph nodes (118, 58%) being the most common site, followed by bone (69, 34%). Nearly 29% (n = 58) experienced adverse drug reactions with severe vomiting (26, 13 %), joint pain (21, 10%) and behavioral disorder (15, 7%). History of previous TB treatment was observed in a majority of the cases (87.7%). Nearly one-third of DR-EPTB cases (33%) had unfavourable treatment outcomes, with loss-to-follow-up (n = 40, 58%) or death (n = 14, 20%) being the most common unfavourable outcomes. In the adjusted analysis, weight band 31-50 kilograms (aRR = 1.8, 1.2-3.4) and h/o previous TB (aRR = 2.1, 1.1-4.8) were mainly associated with unfavourable outcomes. TB elimination efforts need to focus on all forms of TB, including DR-EPTB, leaving no one behind, in order to realise the dream of ending TB.

Nikshay Poshan Yojana (NPY) for tuberculosis patients: Early implementation challenges in Delhi, India.

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.

Byssinosis and tuberculosis amongst "home-based" powerloom workers in Madhya Pradesh State, India.

BACKGROUND: Byssinosis is an occupational lung disease observed among workers exposed to cotton, flax, and hemp dust. The severity and extent of Byssinosis are well recognised in the high-income countries and control measures have been implemented to prevent the disease. In India, there are conflicting evidence on burden estimation of the disease, followed by inadequate prevention and control of Byssinosis. DESIGN/METHODS: We did a cross-sectional study to assess the prevalence of Byssinosis in "home-based" power-loom workers in Mominpura, an administrative ward of Burhanpur Municipality with 2800 population in the state of Madhya Pradesh, India. 290 adults working from "home-based" power loom units were randomly selected, profiled and screened for Byssinosis like symptoms with the help of a semi-structured questionnaire and simple hand-held peak expiratory flow monitor. For epidemiological purposes the symptoms were classified based on Schilling's classification. Chest x-rays were done for selected subjects. Sputum smear microscopy for detecting TB was done for those who had Byssinosis like symptoms. RESULTS: Prevalence of Byssinosis among "home based" powerloom workers was found to be 98% [n = 283, 95 CI (95.65-98.96)]. Peak expiratory flow rate (PEFR) was reduced in 44% (n = 124), of which 81 (29%) had more than 50% PEFR reduction, and of these, 69 (29%) were in early stage of Byssinosis (Grade 0.5). 11% of study participants who had Byssinosis like symptoms, also had TB. CONCLUSIONS: Byssinosis is highly prevalent in "home-based" power loom units in Madhya Pradesh. Adequate advocacy on awareness and prevention; prompt diagnosis and linkages to treatment services in "home-based" power loom units are urgently required to address Byssinosis at an early disease stage.

Diabetes care in public health facilities in India: a situational analysis using a mixed methods approach.

BACKGROUND: 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.

Active versus passive case finding for tuberculosis in marginalised and vulnerable populations in India: comparison of treatment outcomes.

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.

Are we missing 'previously treated' smear-positive pulmonary tuberculosis under programme settings in India? A cross-sectional study.

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.

Patient characteristics, health seeking and delays among new sputum smear positive TB patients identified through active case finding when compared to passive case finding in India.

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.

Developing a model to predict unfavourable treatment outcomes in patients with tuberculosis and human immunodeficiency virus co-infection in Delhi, India.

BACKGROUND: Tuberculosis (TB) patients with human immunodeficiency virus (HIV) co-infection have worse TB treatment outcomes compared to patients with TB alone. The distribution of unfavourable treatment outcomes differs by socio-demographic and clinical characteristics, allowing for early identification of patients at risk. OBJECTIVE: To develop a statistical model that can provide individual probabilities of unfavourable outcomes based on demographic and clinical characteristics of TB-HIV co-infected patients. METHODOLOGY: We used data from all TB patients with known HIV-positive test results (aged ≥15 years) registered for first-line anti-TB treatment (ATT) in 2015 under the Revised National TB Control Programme (RNTCP) in Delhi, India. We included variables on demographics and pre-treatment clinical characteristics routinely recorded and reported to RNTCP and the National AIDS Control Organization. Binomial logistic regression was used to develop a statistical model to estimate probabilities of unfavourable TB treatment outcomes (i.e., death, loss to follow-up, treatment failure, transfer out of program, and a switch to drug-resistant regimen). RESULTS: Of 55,260 TB patients registered for ATT in 2015 in Delhi, 928 (2%) had known HIV-positive test results. Of these, 816 (88%) had drug-sensitive TB and were ≥15 years. Among 816 TB-HIV patients included, 157 (19%) had unfavourable TB treatment outcomes. We developed a model for predicting unfavourable outcomes using age, sex, disease classification (pulmonary versus extra-pulmonary), TB treatment category (new or previously treated case), sputum smear grade, known HIV status at TB diagnosis, antiretroviral treatment at TB diagnosis, and CD4 cell count at ATT initiation. The chi-square p-value for model calibration assessed using the Hosmer-Lemeshow test was 0.15. The model discrimination, measured as the area under the receiver operator characteristic (ROC) curve, was 0.78. CONCLUSION: The model had good internal validity, but should be validated with an independent cohort of TB-HIV co-infected patients to assess its performance before clinical or programmatic use.