Recurrence of pulmonary tuberculosis in India: Findings from the 2019-2021 nationwide community-based TB prevalence survey.

Recurrent Tuberculosis patients contribute to a significant proportion of TB burden in India. A nationwide survey was conducted during 2019-2021 across India among adults to estimate the prevalence of TB. A total of 322480 individuals were screened and 1402 were having TB. Of this, 381 (27.1%) had recurrent TB. The crude prevalence (95% CI) of recurrent TB was 118 (107-131) per 100,000 population. The median duration between episodes of TB was 24 months. The proportion of drug resistant TB was 11.3% and 3.6% in the recurrent group and new TB patients respectively. Higher prevalence of recurrent TB was observed in elderly, males, malnourished, known diabetics, smokers, and alcohol users. (p<0.001). To prevent TB recurrence, all treated tuberculosis patients must be followed at least for 24 months, with screening for Chest X-ray, liquid culture every 6 months, smoking cessation, alcohol cessation, nutritional interventions and good diabetic management.

Upfront Xpert MTB/RIF for diagnosis of pediatric TB-Does it work? Experience from India.

BACKGROUND: Diagnosis of TB in pediatric population poses several challenges. A novel initiative was implemented in several major cities of India aimed at providing upfront access to free-of-cost Xpert MTB/RIF to presumptive pediatric TB cases. This paper aims to describe the experience of implementing this large initiative and assess feasibility of the intervention in high TB burden settings. METHODS: Data were drawn from the pediatric TB project implemented in 10 major cities of India between April 2014 and March 2018. In each city, providers, both public and private, were engaged and linked with a high throughput Xpert MTB/RIF lab (established in that city) through rapid specimen transportation and electronic reporting system. Rates and proportions were estimated to describe the characteristics of this cohort. RESULTS: Of the total 94,415 presumptive pediatric TB cases tested in the project, 6,270 were diagnosed positive for MTB (6.6%) on Xpert MTB/RIF (vs 2% on smear microscopy). Among MTB positives, 545 cases were rifampicin resistant (8.7%). The median duration between collection of specimens and reporting of results was 0 days (same day) and >89% cases were initiated on treatment. Approximately 50% of the specimens tested were non-sputum. The number of providers/facilities engaged under the project increased >10-fold (from 124 in Q2'14 to 1416 in Q1'18). CONCLUSION: This project, which was one of the largest initiatives globally among pediatric population, demonstrated the feasibility of sustaining rapid and upfront access to free-of-cost Xpert MTB/RIF testing. The project underscores the efficiency of this rapid diagnostic assay in tackling several challenges in pediatric TB diagnosis, identifies opportunities for further interventions as well as brings to light scope for effective engagement with healthcare providers. The findings have facilitated a policy decision by National TB Programme mandating the use of Xpert MTB/RIF as a primary diagnostic tool for TB diagnosis in children, which is being scaled-up.

Mapping the tuberculosis scientific landscape among BRICS countries: a bibliometric and network analysis

BACKGROUND The five BRICS (Brazil, Russian, Indian, China, and South Africa) countries bear 49% of the world's tuberculosis (TB) burden and they are committed to ending tuberculosis. OBJECTIVES The aim of this paper is to map the scientific landscape related to TB research in BRICS countries. METHODS Were combined bibliometrics and social network analysis techniques to map the scientific publications related to TB produced by the BRICS. Was made a descriptive statistical data covering the full period of analysis (1993-2016) and the research networks were made for 2007-2016 (8,366 records). The bubble charts were generated by VantagePoint and the networks by the Gephi 0.9.1 software (Gephi Consortium 2010) from co-occurrence matrices produced in VantagePoint. The Fruchterman-Reingold algorithm provided the networks' layout. FINDINGS During the period 1993-2016, there were 38,315 peer-reviewed, among them, there were 11,018 (28.7%) articles related by one or more authors in a BRICS: India 38.7%; China 23.8%; South Africa 21.1%; Brazil 13.0%; and Russia 4.5% (The total was greater than 100% because our criterion was all papers with at least one author in a BRICS). Among the BRICS, there was greater interaction between India and South Africa and organisations in India and China had the highest productivity; however, South African organisations had more interaction with countries outside the BRICS. Publications by and about BRICS generally covered all research areas, especially those in India and China covered all research areas, although Brazil and South Africa prioritised infectious diseases, microbiology, and the respiratory system. MAIN CONCLUSIONS An overview of BRICS scientific publications and interactions highlighted the necessity to develop a BRICS TB research plan to increase efforts and funding to ensure that basic science research successfully translates into products and policies to help end the TB epidemic.

Impact of Advocacy, Communication, Social Mobilization and Active Case Finding on TB Notification in Jharkhand, India.

Community-level benefits of screening for active tuberculosis (TB) disease remain uncertain. Project Axshya (meaning free of TB) conducted advocacy, communication, social mobilization, and active case finding among vulnerable/marginalized populations of India. Among 15 districts of Jharkhand state, the project was initiated in 36 subdistrict level administrative units - tuberculosis units (TUs) in a staggered manner between April 2013 and September 2014, and continued till the end of 2015. Seven TUs did not implement the project. We assessed the relative change in the quarterly TB case finding indicators (n = 4) after inclusion of a TU within the project. By fitting four multilevel models (mixed-effects maximum likelihood regression using random intercept), we adjusted for secular (over previous five quarters) and seasonal trends, baseline differences within Axshya and non-Axshya TUs, and population size and clustering within districts and within TUs. After inclusion of a TU within the project, we found a significant increase [95% confidence interval (CI)] in TU-level presumptive TB sputum examination rate, new sputum-positive TB Case Notification Rate (CNR), sputum-positive TB CNR, and all forms TB CNR by 12 (5.5, 18.5), 1.1 (0.5, 1.7), 1.3 (0.6, 2.0), and 1.2 (0.1, 2.2) per 100,000 population per quarter, respectively. Overall, the project resulted in an increase (95% CI) in sputum examination and detection of new sputum-positive TB, sputum-positive TB and all forms of TB patients by 22,410 (10,203, 34,077), 2066 (923, 3210), 2380 (1162, 3616), and 2122 (203, 4059), respectively. This provides evidence for implementing project Axshya over and above the existing passive case finding.

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.

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.

Active case finding among marginalised and vulnerable populations reduces catastrophic costs due to tuberculosis diagnosis.

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.

Recurrence of tuberculosis among newly diagnosed sputum positive pulmonary tuberculosis patients treated under the Revised National Tuberculosis Control Programme, India: A multi-centric prospective study.

INTRODUCTION: There is lack of information on the proportion of new smear-positive pulmonary tuberculosis (PTB) patients treated with a 6-month thrice-weekly regimen under Revised National Tuberculosis Control Programme (RNTCP) who develop recurrent TB after successful treatment outcome. OBJECTIVE: To estimate TB recurrence among newly diagnosed PTB patients who have successfully completed treatment and to document endogenous reactivation or re-infection. Risk factors for unfavourable outcomes to treatment and TB recurrence were determined. METHODOLOGY: Adult (aged ≥ 18 yrs) new smear positive PTB patients initiated on treatment under RNTCP were enrolled from sites in Tamil Nadu, Karnataka, Delhi, Maharashtra, Madhya Pradesh and Kerala. Those declared "treatment success" at the end of treatment were followed up with 2 sputum examinations each at 3, 6 and 12 months after treatment completion. MIRU-VNTR genotyping was done to identify endogenous re-activation or exogenous re-infection at TB recurrence. TB recurrence was expressed as rate per 100 person-years (with 95% confidence interval [95%CI]). Regression models were used to identify the risk factors for unfavourable response to treatment and TB recurrence. RESULTS: Of the1577 new smear positive PTB patients enrolled, 1565 were analysed. The overall cure rate was 77% (1207/1565) and treatment success was 77% (1210 /1565). The cure rate varied from 65% to 86%. There were 158 of 1210 patients who had TB recurrence after treatment success. The pooled TB recurrence estimate was 10.9% [95%CI: 0.2-21.6] and TB recurrence rate per 100 person-years was 12.7 [95% CI: 0.4-25]. TB recurrence per 100 person-years varied from 5.4 to 30.5. Endogenous reactivation was observed in 56 (93%) of 60 patients for whom genotyping was done. Male gender was associated with TB recurrence. CONCLUSION: A substantial proportion of new smear positive PTB patients successfully treated with 6 -month thrice-weekly regimen have TB recurrence under program settings.

HIV Testing among Patients with Presumptive Tuberculosis: How Do We Implement in a Routine Programmatic Setting? Results of a Large Operational Research from India.

BACKGROUND: In March 2012, World Health Organization recommended that HIV testing should be offered to all patients with presumptive TB (previously called TB suspects). How this is best implemented and monitored in routine health care settings in India was not known. An operational research was conducted in Karnataka State (South India, population 64 million, accounts for 10% of India's HIV burden), to test processes and learn results and challenges of screening presumptive TB patients for HIV within routine health care settings. METHODS: In this cross-sectional study conducted between January-March 2012, all presumptive TB patients attending public sector sputum microscopy centres state-wide were offered HIV testing by the laboratory technician, and referred to the nearest public sector HIV counselling and testing services, usually within the same facility. The HIV status of the patients was recorded in the routine TB laboratory form and TB laboratory register. The laboratory register was compiled to obtain the number of presumptive TB patients whose HIV status was ascertained, and the number found HIV positive. Aggregate data on reasons for non-testing were compiled at district level. RESULTS: Overall, 115,308 patients with presumptive TB were examined for sputum smear microscopy at 645 microscopy centres state-wide. Of these, HIV status was ascertained for 62,847(55%) among whom 7,559(12%) were HIV-positive, and of these, 3,034(40%) were newly diagnosed. Reasons for non-testing were reported for 37,700(72%) of the 52,461 patients without HIV testing; non-availability of testing services at site of sputum collection was cited by health staff in 54% of respondents. Only 4% of patients opted out of HIV testing. CONCLUSION: Offering HIV testing routinely to presumptive TB patients detected large numbers of previously-undetected instances of HIV infection. Several operational challenges were noted which provide useful lessons for improving uptake of HIV testing in this important group.

Microbiology of infected acellular dermal matrix (AlloDerm) in patients requiring complex abdominal closure after emergency surgery.

BACKGROUND: Acellular dermal matrix (AlloDerm) has recently been introduced as an option for complex abdominal closure for patients with loss of abdominal wall domain secondary to intra-abdominal sepsis or necrotizing fasciitis. AlloDerm has been touted as a promoter of neovascularization and collagen deposition. Currently, the rate of AlloDerm infection in contaminated cases is unknown. Our objective was to determine if the organisms cultured during source control would infect AlloDerm. METHODS: The medical records of patients who required complex abdominal closure with AlloDerm in a tertiary-care hospital were reviewed from January to December, 2005. For each patient demographic, the reason for urgent surgery, American Society of Anesthesiologists (ASA) class, Acute Physiology and Chronic Health Evaluation (APACHE) II score, serum albumin concentration, culture results of purulent fluid obtained during surgery, and culture results of biopsies of infected-appearing AlloDerm (change of color, delayed granulation, odor) were collected. Data are presented as mean +/- standard error of the mean. RESULTS: Seventeen patients required the use of AlloDerm for tension-free closure of the abdominal wall after surgery for source control in necrotizing fasciitis (13%) or intra-abdominal sepsis (87%). The mean age was 61 +/- 2 years; 73% of the patients were Caucasian, the remainder being African American. The mean APACHE II score was 23.7 +/- 2.0, and the median ASA class was 3. The mean preoperative albumin concentration was 2.27 +/- 0.26 g/dL. Most (76%) of the patients had a wound vacuum-assisted closure system placed over the AlloDerm. Four patients (24%) were noted to have an infection of the AlloDerm graft at 24 +/- 10 days postoperatively. The cultures obtained at operation and from infected AlloDerm show similar organisms (Pseudomonas in two, Escherichia coli and methicillin-resistant Staphylococcus aureus in one each). Infected AlloDerm was coated with silver sulfadiazene and moistened dressings, and all four patients had complete resolution of the AlloDerm infection with an adequate bed of granulation tissue, allowing skin grafting. CONCLUSION: Patients with contaminated abdomens who require complex closure with AlloDerm are at risk of developing infection of their graft material with organisms similar to those present at the time of surgery. Once culture results are obtained, topical antimicrobials with activity against the cultured organisms may be employed as part of the AlloDerm dressings to prevent infection and promote healing.