A systematic review and meta-analysis of circulating serum and plasma microRNAs in TB diagnosis.

BACKGROUND: Tuberculosis (TB) ranks as the second leading cause of death globally among all infectious diseases. This problem is likely due to the lack of biomarkers to differentiate the heterogeneous spectrum of infection. Therefore, the first step in solving this problem is to identify biomarkers to distinguish the different disease states of an individual and treat them accordingly. Circulating microRNA (miRNA) biomarkers are promising candidates for various diseases. In fact, we are yet to conceptualize how miRNA expression influences and predicts TB disease outcomes. Thus, this systematic review and meta-analysis aimed to assess the diagnostic efficacy of circulating miRNAs in Latent TB (LTB) and Active Pulmonary TB (PTB). METHODS: Literature published between 2012 and 2021 was retrieved from PubMed, Web of Science, Cochrane, Scopus, Embase, and Google Scholar. Articles were screened based on inclusion and exclusion criteria, and their quality was assessed using the QUADAS-2 tool. Funnel plots and forest plots were generated to assess the likelihood of study bias and heterogeneity, respectively. RESULTS: After the screening process, seven articles were selected for qualitative analysis. The study groups, which consisted of Healthy Control (HC) vs. TB and LTB vs. TB, exhibited an overall sensitivity of 81.9% (95% CI: 74.2, 87.7) and specificity of 68.3% (95% CI: 57.8, 77.2), respectively. However, our meta-analysis results highlighted two potentially valuable miRNA candidates, miR-197 and miR-144, for discriminating TB from HC. The miRNA signature model (miR197-3p, miR-let-7e-5p, and miR-223-3p) has also been shown to diagnose DR-TB with a sensitivity of 100%, but with a compromised specificity of only 75%. CONCLUSION: miRNA biomarkers show a promising future for TB diagnostics. Further multicentre studies without biases are required to identify clinically valid biomarkers for different states of the TB disease spectrum. SYSTEMATIC REVIEW REGISTRATION: PROSPERO (CRD42022302729).

Cost of digital technologies and family-observed DOT for a shorter MDR-TB regimen: a modelling study in Ethiopia, India and Uganda.

BACKGROUND: In 2017, the WHO recommended the use of digital technologies, such as medication monitors and video observed treatment (VOT), for directly observed treatment (DOT) of drug-susceptible TB. The WHO's 2020 guidelines extended these recommendations to multidrug-resistant tuberculosis (MDR-TB), based on low evidence. The impact of COVID on health systems and patients underscored the need to use digital technologies in the management of MDR-TB. METHODS: A decision-tree model was developed to explore the costs of several potential DOT alternatives: VOT, 99DOTS (Directly-observed Treatment, Short-course) and family-observed DOT. Assuming a 9-month, all-oral regimen (as evaluated within the STREAM trial), we constructed base-case cost models for the standard-of-care DOTs in Ethiopia, India, and Uganda, as well as for the three alternative DOT approaches. The models were populated with STREAM Stage 2 clinical trial outcome and cost data, supplemented with market prices data for the digital DOT strategies. Sensitivity analyses were conducted on key parameters. RESULTS: Modelling suggested that the standard-of-care DOT approach is the most expensive DOT strategy from a societal perspective in all three countries evaluated (Ethiopia, India, Uganda), with considerable direct- and indirect-costs incurred by patients. The second most expensive DOT approach is VOT, with high health-system costs, largely caused by up-front technology expenditure. Each of VOT, 99DOTS and family-observed DOT would reduce by more than 90% patients' direct and indirect costs compared to standard of care DOT. Results were robust to the sensitivity analyses. CONCLUSIONS: While data on the costs and efficacy of alternative DOT approaches in the context of shorter MDR-TB treatment is limited, our modelling suggests alternative DOT approaches can significantly reduce patient costs in all three countries. Health system costs are higher for VOT and lower for 99DOTS and family-observed therapy when compared to standard of care DOT, as low smartphone penetration and internet availability requires the VOT health system to fund the cost of making them available to patients.

Time Elapsed from onset of symptoms to antituberculosis treatment in children with central nervous system tuberculosis in a tertiary hospital in South India: A mixed-methods pilot study.

A pilot study with a mixed-methods design was conducted to estimate the time for tuberculosis (TB) treatment initiation and associated factors among children with central nervous system-TB (CNS-TB). A total of 38 children were enrolled for the quantitative component, and 20 in-depth interviews were conducted. The median duration (interquartile range) from onset of symptoms to treatment initiation was 23 (11, 55) days. About 44% and 31% of the children presented with Stage II and Stage III of CNS-TB, respectively. The major reasons for delay were symptoms not taken seriously (50%) and too many referrals (21%). About 89% of the families went into catastrophic health expenditure due to the disease. The treatment delay may be due to both patient delay and health system delay. Tailoring approaches to target the pediatric population could further improve early detection and treatment initiation of CNS-TB.

Application of mobile phone technology as intervention for the management of tuberculosis patients diagnosed through community survey.

Background & objectives: The delay in communicating the results to tuberculosis (TB) patients leads to increased rates of initial loss to follow up of treatment. The gap in communication among healthcare providers requires application of new tools that will address the challenges. Mobile phone technologies could be a useful tool in this context for the delivery of information. The objective was thus to evaluate communication by mobile applications such as the WhatsApp Messenger to decrease initial loss to follow up after initial treatment for TB. Methods: Indian Council of Medical Research-National Institute for Research in Tuberculosis, Chennai, India undertook a community prevalence survey to find the burden of TB. During this survey, mobile phone-based technology (WhatsApp messenger) was employed as an intervention among the healthcare providers and researchers involved for communicating. This was further evaluated for its usefulness by examining the initial loss to follow up and patients initiated on treatment. Results: The study covered four blocks of Thiruvallur district of Tamil Nadu, South India, namely Kadambathur, Poondi, Thiruvalangadu and Periyapalayam. The survey population was around 20,000 from each block, and the average patients diagnosed by community TB prevalence survey were 30 patients from each block. Among the patients diagnosed through this survey, in the first block, only 55 per cent were initiated on treatment; subsequently, with the intervention, the initial loss to follow up was significantly reduced from 45 to zero per cent. Interpretation & conclusions: After integrating of WhatsApp messenger application for communication among healthcare providers and researchers, the initial loss to follow up among patients being treated for TB was significantly decreased.

An influence of dew point temperature on the occurrence of Mycobacterium tuberculosis disease in Chennai, India.

Climate factors such as dew point temperature, relative humidity and atmospheric temperature may be crucial for the spread of tuberculosis. This study was conducted for the first time to investigate the relationship of climatic factors with TB occurrence in an Indian setting. Daily tuberculosis notification data during 2008-2015 were generated from the National Treatment Elimination Program, and analogous daily climatic data were obtained from the Regional Meteorological Centre at Chennai city, Tamil Nadu, India. The decomposition method was adopted to split the series into deterministic and non-deterministic components, such as seasonal, non-seasonal, trend and cyclical, and non-deterministic climate factors. A generalized linear model was used to assess the relation independently. TB disease progression from latent stage infection to active was supported by higher dew point temperature and moderate temperature. It had a significant association with TB progression in the summer and monsoon seasons. The relative humidity may be favored in the winter and post-monsoon. The water tiny dew droplets may support the TB bacterium to recuperate in the environment.

Prevalence of bacteriologically confirmed pulmonary tuberculosis and associated risk factors: A community survey in Thirvallur District, south India.

BACKGROUND: Tuberculosis (TB) prevalence surveys add to the active case detection in the community level burden of TB both national and regional levels. The aim of this study was to assess the prevalence of bacteriologically confirmed pulmonary tuberculosis (PTB) in the community. METHODS: Household community-based tuberculosis disease survey was conducted targeting 69054 population from 43 villages of 5 blocks in Tiruvallure district adopting cluster sampling methodology of ≥15 years old adult rural population of South India during 2015-2018. All eligible individuals with suspected symptoms of PTB were screened with chest X-ray. Two sputum specimens (one spot and the other early morning sample) were collected for M.tb smear and culture examination. Conversely demographical, smoking and alcohol drinking habits information were also collected to explore the risk factor. Stepwise logistic regression was employed to associate risk factors for PTB. RESULTS: A total of 62494 were screened among 69054 eligible population, of whom 6340 were eligible for sputum specimen collection. Sputum for M.tb smear and culture examination were collected in 93% of participants. The derived prevalence of PTB was 307/100000 population (smear-positive 130; culture positive 277). As expected that PTB has decreased substantially compared to preceding surveys and it showed that older age, male, low BMI, diabetes, earlier history of TB and alcohol users were significantly associated (p < .0001) with an increased risk of developing PTB. CONCLUSION: Upshot of the active survey has established a reduction in the prevalence of PTB in the rural area which can be accredited to better programmatic implementation and success of the National TB Control Programme in this district. It also has highlighted the need for risk reduction interventions accelerate faster elimination of TB.

Economic Evaluation of Implementing a Rapid Point-of-Care Screening Test for the Identification of Hepatitis C Virus under National Viral Hepatitis Control Programme in Tamil Nadu, South India.

INTRODUCTION: Viral hepatitis is a crucial public health problem in India. Hepatitis C virus (HCV) elimination is a national priority and a key strategy has been adopted to strengthen the HCV diagnostics services to ensure early and accurate diagnosis. METHODS: To conduct an economic evaluation of implementing a rapid point-of-care screening test for the identification of HCV among the selected key population under the National Viral Hepatitis Control Programme in Tamil Nadu, South India. Economic evaluation of a point-of-care screening test for HCV diagnosis among the key population attending the primary health care centers. A combination of decision tree and Markov model was developed to estimate cost-effectiveness of point-of-care screening test for HCV diagnosis at the primary health care centers. Total costs, quality-adjusted life years (QALYs) of the intervention and comparator, and incremental cost-effectiveness ratio (ICER) were calculated. The model parameter uncertainties which would influence the cost-effectiveness outcome has been evaluated by one-way sensitivity analysis and probabilistic sensitivity analysis. RESULTS: When compared to the tertiary level diagnostic strategy for HCV, the point-of-care screening for selected key population at primary health care level results in a gain of 57 undiscounted QALYs and 38 discounted QALYs, four undiscounted life years and two discounted life years. The negative ICER of the new strategy indicates that it is less expensive and more effective compared with the current HCV diagnosis strategy. CONCLUSIONS: The proposed strategy for HCV diagnosis in the selected key population in Tamil Nadu is dominant and cost-saving compared to the current strategy.

Long-term Survival of Treated Tuberculosis Patients in Comparison to a General Population In South India: A Matched Cohort Study.

OBJECTIVES: This study aimed to measure the mortality rate, potential years of life lost, and excess general mortality among individuals treated for pulmonary tuberculosis (TB) in a TB endemic country. METHODS: A retrospective analysis was conducted on a population-based cohort study of 4022 TB patients and 12,243 gender-matched and age-matched controls from prevalence surveys conducted between 2000 and 2004 in the Thiruvallur district of Tamil Nadu, South India. RESULTS: The mortality rate among TB patients was 59/1000 person-years. The excess standardized mortality ratio was 2.3 (95% CI: 1.7-3.1). The rate of potential years of life lost was 6.15/1000 (95% CI: 5.97-6.33) in the TB cohort compared to the general population of 1.52/1000 (95% CI: 1.46-1.60). Individuals aged >50 years, those underweight (<40 kg), with treatment failures, or lost to follow-up had higher mortality rates when compared with the rest of the TB cohort. The risk of death was significantly higher in the TB cohort until the end of the fourth year when compared with later years. CONCLUSION: Mortality in the TB cohort was 2.3 times higher than in the age-matched general population. Most deaths occurred in the first year after completing treatment. Post-treatment follow-ups and interventions for reducing comorbid conditions are necessary to prevent deaths.

Burden of pulmonary tuberculosis in modern prison: A cross sectional prevalence survey from south India.

BACKGROUND: The risk of spread of Pulmonary Tuberculosis (PTB) disease depends on several factors. One important factor is the situational and environmental vulnerabilities of the prison setting. Study was conducted in central prison in Chennai, south state, India to estimate the prevalence of PTB disease in 2013. METHODS: All inmates aged 15 years and above were available during survey period screened for symptoms suggestive of PTB and X-ray taken chest PA view. Two sputum specimens were collected for smear and culture examination. All culture positive samples were used for drug sensitivity testing for first line anti-TB drugs. Information on demographic, life style characteristics, past history of PTB treatment were collected through pre-coded interview schedule. RESULTS: Of 1854 jail inmates were screened, prevalence of symptoms suggestive of PTB was 35% and it was dominated by males. Out of all screened 16 PTB cases are diagnosed and the estimated overall prevalence of PTB among prison inmates was 16/1854 (863/100,000 population). CONCLUSIONS: Prevalence PTB was 2.5 times higher as compared to prevalence of PTB in general population in the same areas, and 3.4 times higher as compared to national average.

Psycho-Socio-Economic Issues Challenging Multidrug Resistant Tuberculosis Patients: A Systematic Review.

BACKGROUND: Limited treatment options, long duration of treatment and associated toxicity adversely impact the physical and mental well-being of multidrug-resistant tuberculosis (MDR-TB) patients. Despite research advances in the microbiological and clinical aspects of MDR-TB, research on the psychosocial context of MDR-TB is limited and less understood. METHODOLOGY: We searched the databases of PubMed, MEDLINE, Embase and Google Scholar to retrieve all published articles. The final manuscripts included in the review were those with a primary focus on psychosocial issues of MDR-TB patients. These were assessed and the information was thematically extracted on the study objective, methodology used, key findings, and their implications. Intervention studies were evaluated using components of the methodological and quality rating scale. Due to the limited number of studies and the multiple methodologies employed in the observational studies, we summarized these studies using a narrative approach, rather than conducting a formal meta-analysis. We used 'thematic synthesis' method for extracting qualitative evidences and systematically organised to broader descriptive themes. RESULTS: A total of 282 published articles were retrieved, of which 15 articles were chosen for full text review based on the inclusion criteria. Six were qualitative studies; one was a mixed methods study; and eight were quantitative studies. The included studies were divided into the following issues affecting MDR-TB patients: a) psychological issues b) social issues and economic issues c) psychosocial interventions. It was found that all studies have documented range of psychosocial and economic challenges experienced by MDR-TB patients. Depression, stigma, discrimination, side effects of the drugs causing psychological distress, and the financial constraints due to MDR-TB were some of the common issues reported in the studies. There were few intervention studies which addressed these psychosocial issues most of which were small pilot studies. There is dearth of large scale randomized psychosocial intervention studies that can be scaled up to strengthen management of MDR-TB patients which is crucial for the TB control programme. CONCLUSION: This review has captured the psychosocial and economic issues challenging MDR patients. However there is urgent need for feasible, innovative psychosocial and economic intervention studies that help to equip MDR-TB patients cope with their illness, improve treatment adherence, treatment outcomes and the overall quality of life of MDR-TB patients.

Profile and response to anti-tuberculosis treatment among elderly tuberculosis patients treated under the TB Control programme in South India.

INTRODUCTION: The demographic transition in India has resulted in an increase in the elderly population. There is limited data on the profile of elderly tuberculosis (TB) patients and their treatment outcomes in India. OBJECTIVE: To compare the clinical profile, presentation and response to anti-TB treatment among elderly (≥ 60 yrs) and younger (15-59 yrs) TB patients treated under the Revised National TB Control programme. METHODOLOGY: Retrospective cohort analysis of TB patients treated from May 1999 to December 2004 in one Tuberculosis Unit of Tiruvallur district, South India. RESULTS: Records of 865 elderly and 4343 younger TB patients were examined: elderly were more likely to be male (84% vs. 71%), smokers (46% vs.37%), illiterate (63% vs. 45%), identified by active case finding through survey (19% vs. 11%), have pulmonary TB (96% vs. 91%) and initial smear negative disease (46% vs. 36%) compared to younger (for all p<0.001). Among a total of 352 elderly and 1933 younger new smear positive pulmonary TB, the elderly had higher loss to follow-up (15% vs. 11%; p = 0.03) and death rates (9% vs. 4%; p<0.001). Mycobacterium tuberculosis susceptibility to first line anti-TB drugs did not differ (elderly 87% vs. younger 84%) (p = 0.20). Side effects related to anti-TB drugs were reported by a higher proportion of elderly patients (63% vs. 54%) (p = 0.005). Previously treated patients had similar treatment outcomes in both the groups. CONCLUSION: Elderly TB patients are less likely to have smear positive disease. Newly diagnosed elderly TB patients are more likely to be lost to follow-up or die and report drug side effects. Suitable interventions need to be developed for effective management and better treatment outcomes of TB in the elderly.

Impact of Chikungunya on health related quality of life Chennai, South India.

BACKGROUND: Chikungunya Virus (CHIKV) infection affects large populations and leads to prolonged and debilitating pain affecting health related quality of life (HRQoL). We assess the impact of CHIKV on HRQoL of clinical CHIKV (C-CHIKV) patients in a suburban locality of Chennai City, South India. Further, we determined factors associated with clinical recovery among C-CHIKV patients. METHODS: We followed-up 403 of 425 adult C-CHIKV cases identified during an outbreak. On the basis of a reassessment of their current clinical status through self-reporting, we categorized them as 'clinically recovered' (n = 308) or 'not recovered' (n = 95). In the absence of base-line information on HRQoL, we included a comparison group of healthy normal's recruited by frequency matching for age and sex from the neighbourhood (n = 308). We conducted a comparative cross-sectional study of these three groups and estimated HRQoL scores using SF-36 questionnaire. We tested the differences in the median scores by Kruksall Wallistest. We identified factors associated with 'recovery' as compared to not-recovery by calculating Adjusted Odds Ratio (AOR) and 95% Confidence Intervals through multiple regression analysis. RESULTS: As compared to 'normals', we observed a 20 and five-fold reductions in HRQoL scores for C-CHIKV patients 'not recovered' and 'recovered' respectively. Differences in HRQoL scores for all the domains were statistically significant between three groups (p<0·001). Younger age, male, absence of rashes, affliction of less than five types of joints and two weeks of joint swelling were significantly associated with recovery. HRQoL scores improved with time among those 'clinically recovered'. CONCLUSION: This study provides evidence for sharp reductions in quality of life not only during active C-CHIKV associated illness but also for several months after clinical recovery compared to healthy normals. This has implications for developing intervention programmes in countries with high risk of CHIKV outbreaks.

A study of condom acceptability among men in an urban population in South India.

This study examines the acceptability of condoms to men from Chennai, South India. A sample of 150 male respondents who, in the main, had at least one risky sexual experience with a commercial sex worker or multiple partners was interviewed. The respondents included HIV-positive and HIV-negative individuals at sexually transmitted disease clinics, college students, and homosexuals. Awareness of condom usage was high, and 83% had used condoms at least once. The reasons for using condoms were protection from disease (43%), protection from AIDS (20%), and partner insistence (25%). Seventy-three percent of the respondents expressed dissatisfaction. Of those who used condoms for the first time, 72% were HIV negative, compared to 34% among those who did not use condoms. This indicates the need for developing the "condom habit," as using condoms at the first sexual experience is a strong predictor of future condom use.