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.

BackgroundAxshya 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.ObjectivesTo 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.MethodsThis 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.ResultsWe 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.ConclusionAxshya SAMVAD linked the most impoverished communities to TB care and resulted in reduction of health system level diagnosis delay.

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Bacteriophages are being considered as a promising natural resource for the development of alternative strategies against mycobacterial diseases, especially in the context of the wide-spread occurrence of drug resistance among the clinical isolates of Mycobacterium tuberculosis. However, there is not much information documented on mycobacteriophages from India. Here, we report the isolation of 17 mycobacteriophages using Mycobacterium smegmatis as the bacterial host, where 9 phages also lyse M. tuberculosis H37Rv. We present detailed analysis of one of these mycobacteriophages - PDRPv. Transmission electron microscopy and polymerase chain reaction analysis (of a conserved region within the TMP gene) show PDRPv to belong to the Siphoviridae family and B1 subcluster, respectively. The genome (69 110 bp) of PDRPv is circularly permuted double-stranded DNA with ∼66% GC content and has 106 open reading frames (ORFs). On the basis of sequence similarity and conserved domains, we have assigned function to 28 ORFs and have broadly categorized them into 6 groups that are related to replication and genome maintenance, DNA packaging, virion release, structural proteins, lysogeny-related genes and endolysins. The present study reports the occurrence of novel antimycobacterial phages in India and highlights their potential to contribute to our understanding of these phages and their gene products as potential antimicrobial agents.

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.

The cell wall of Mycobacterium tuberculosis (Mtb) consists of peptidoglycan, arabinogalactan and mycolic acids. The cytoplasmic steps in the peptidoglycan biosynthetic pathway, catalyzed by the Mur (A-F) enzymes, involve the synthesis of UDP-n-acetylmuramyl pentapeptide, a key precursor molecule required for the formation of the peptidoglycan monomeric building blocks. Mur enzymes are indispensable for cell integrity and their lack of counterparts in eukaryotes suggests them to be promising Mtb drug targets. However, the caveat is that most of the current assays utilize a single Mur enzyme, thereby identifying inhibitors against only one of the enzymes. Here, we report development of a one-pot assay that reconstructs the entire Mtb Mur pathway in vitro and has the advantage of eliminating the requirement for nucleotide intermediates in the pathway as substrates. The MurA-MurF enzymes were purified and a one-pot assay was developed through optimization of successive coupled enzyme assays using UDP-n-acetylglucosamine as the initial sugar substrate. The assay is biochemically characterized and optimized for high-throughput screening of molecules that could disrupt multiple targets within the pathway. Furthermore, we have validated the assay by performing it to identify D-Cycloserine and furan-based benzene-derived compounds with known Mur ligase inhibition as inhibitors of Mtb MurE and MurF.