Taxane chemotherapy induces stromal injury that leads to breast cancer dormancy escape.

A major cause of cancer recurrence following chemotherapy is cancer dormancy escape. Taxane-based chemotherapy is standard of care in breast cancer treatment aimed at killing proliferating cancer cells. Here, we demonstrate that docetaxel injures stromal cells, which release protumor cytokines, IL-6 and granulocyte colony stimulating factor (G-CSF), that in turn invoke dormant cancer outgrowth both in vitro and in vivo. Single-cell transcriptomics shows a reprogramming of awakened cancer cells including several survival cues such as stemness, chemoresistance in a tumor stromal organoid (TSO) model, as well as an altered tumor microenvironment (TME) with augmented protumor immune signaling in a syngeneic mouse breast cancer model. IL-6 plays a role in cancer cell proliferation, whereas G-CSF mediates tumor immunosuppression. Pathways and differential expression analyses confirmed MEK as the key regulatory molecule in cancer cell outgrowth and survival. Antibody targeting of protumor cytokines (IL-6, G-CSF) or inhibition of cytokine signaling via MEK/ERK pathway using selumetinib prior to docetaxel treatment prevented cancer dormancy outgrowth suggesting a novel therapeutic strategy to prevent cancer recurrence.

Early Injury Landscape in Vein Harvest by Single-Cell and Spatial Transcriptomics.

BACKGROUND: Vein graft failure following cardiovascular bypass surgery results in significant patient morbidity and cost to the healthcare system. Vein graft injury can occur during autogenous vein harvest and preparation, as well as after implantation into the arterial system, leading to the development of intimal hyperplasia, vein graft stenosis, and, ultimately, bypass graft failure. Although previous studies have identified maladaptive pathways that occur shortly after implantation, the specific signaling pathways that occur during vein graft preparation are not well defined and may result in a cumulative impact on vein graft failure. We, therefore, aimed to elucidate the response of the vein conduit wall during harvest and following implantation, probing the key maladaptive pathways driving graft failure with the overarching goal of identifying therapeutic targets for biologic intervention to minimize these natural responses to surgical vein graft injury. METHODS: Employing a novel approach to investigating vascular pathologies, we harnessed both single-nuclei RNA-sequencing and spatial transcriptomics analyses to profile the genomic effects of vein grafts after harvest and distension, then compared these findings to vein grafts obtained 24 hours after carotid-carotid vein bypass implantation in a canine model (n=4). RESULTS: Spatial transcriptomic analysis of canine cephalic vein after initial conduit harvest and distention revealed significant enrichment of pathways (P<0.05) involved in the activation of endothelial cells (ECs), fibroblasts, and vascular smooth muscle cells, namely pathways responsible for cellular proliferation and migration and platelet activation across the intimal and medial layers, cytokine signaling within the adventitial layer, and ECM (extracellular matrix) remodeling throughout the vein wall. Subsequent single-nuclei RNA-sequencing analysis supported these findings and further unveiled distinct EC and fibroblast subpopulations with significant upregulation (P<0.05) of markers related to endothelial injury response and cellular activation of ECs, fibroblasts, and vascular smooth muscle cells. Similarly, in vein grafts obtained 24 hours after arterial bypass, there was an increase in myeloid cell, protomyofibroblast, injury response EC, and mesenchymal-transitioning EC subpopulations with a concomitant decrease in homeostatic ECs and fibroblasts. Among these markers were genes previously implicated in vein graft injury, including VCAN, FBN1, and VEGFC, in addition to novel genes of interest, such as GLIS3 and EPHA3. These genes were further noted to be driving the expression of genes implicated in vascular remodeling and graft failure, such as IL-6, TGFBR1, SMAD4, and ADAMTS9. By integrating the spatial transcriptomics and single-nuclei RNA-sequencing data sets, we highlighted the spatial architecture of the vein graft following distension, wherein activated and mesenchymal-transitioning ECs, myeloid cells, and fibroblasts were notably enriched in the intima and media of distended veins. Finally, intercellular communication network analysis unveiled the critical roles of activated ECs, mesenchymal-transitioning ECs, protomyofibroblasts, and vascular smooth muscle cells in upregulating signaling pathways associated with cellular proliferation (MDK [midkine], PDGF [platelet-derived growth factor], VEGF [vascular endothelial growth factor]), transdifferentiation (Notch), migration (ephrin, semaphorin), ECM remodeling (collagen, laminin, fibronectin), and inflammation (thrombospondin), following distension. CONCLUSIONS: Vein conduit harvest and distension elicit a prompt genomic response facilitated by distinct cellular subpopulations heterogeneously distributed throughout the vein wall. This response was found to be further exacerbated following vein graft implantation, resulting in a cascade of maladaptive gene regulatory networks. Together, these results suggest that distension initiates the upregulation of pathological pathways that may ultimately contribute to bypass graft failure and presents potential early targets warranting investigation for targeted therapies. This work highlights the first applications of single-nuclei and spatial transcriptomic analyses to investigate venous pathologies, underscoring the utility of these methodologies and providing a foundation for future investigations.

Development & validation of scales to assess stigma related to COVID-19 in India.

Background & objectives: COVID-19 pandemic has triggered social stigma towards individuals affected and their families. This study describes the process undertaken for the development and validation of scales to assess stigmatizing attitudes and experiences among COVID-19 and non-COVID-19 participants from the community. Methods: COVID-19 Stigma Scale and Community COVID-19 Stigma Scale constituting 13 and six items, respectively, were developed based on review of literature and news reports, expert committee evaluation and participants' interviews through telephone for a multicentric study in India. For content validity, 61 (30 COVID-19-recovered and 31 non-COVID-19 participants from the community) were recruited. Test-retest reliability of the scales was assessed among 99 participants (41 COVID-19 recovered and 58 non-COVID-19). Participants were administered the scale at two-time points after a gap of 7-12 days. Cronbach's alpha, overall percentage agreement and kappa statistics were used to assess internal consistency and test-retest reliability. Results: Items in the scales were relevant and comprehensible. Both the scales had Cronbach's α above 0.6 indicating moderate-to-good internal consistency. Test-retest reliability assessed using kappa statistics indicated that for the COVID-19 Stigma Scale, seven items had a moderate agreement (0.4-0.6). For the Community COVID-19 Stigma Scale, four items had a moderate agreement. Interpretation & conclusions: Validity and reliability of the two stigma scales indicated that the scales were comprehensible and had moderate internal consistency. These scales could be used to assess COVID-19 stigma and help in the development of appropriate stigma reduction interventions for COVID-19 infected, and mitigation of stigmatizing attitudes in the community.

Leukemia vaccine overcomes limitations of checkpoint blockade by evoking clonal T cell responses in a murine acute myeloid leukemia model.

We have developed a personalized vaccine whereby patient derived leukemia cells are fused to autologous dendritic cells, evoking a polyclonal T cell response against shared and neo-antigens. We postulated that the dendritic cell (DC)/AML fusion vaccine would demonstrate synergy with checkpoint blockade by expanding tumor antigen specific lymphocytes that would provide a critical substrate for checkpoint blockade mediated activation. Using an immunocompetent murine leukemia model, we examined the immunologic response and therapeutic efficacy of vaccination in conjunction with checkpoint blockade with respect to leukemia engraftment, disease burden, survival and the induction of tumor specific immunity. Mice treated with checkpoint blockade alone had rapid leukemia progression and demonstrated only a modest extension of survival. Vaccination with DC/AML fusions resulted in the expansion of tumor specific lymphocytes and disease eradication in a subset of animals, while the combination of vaccination and checkpoint blockade induced a fully protective tumor specific immune response in all treated animals. Vaccination followed by checkpoint blockade resulted in upregulation of genes regulating activation and proliferation in memory and effector T cells. Long term survivors exhibited increased T cell clonal diversity and were resistant to subsequent tumor challenge. The combined DC/AML fusion vaccine and checkpoint blockade treatment offers unique synergy inducing the durable activation of leukemia specific immunity, protection from lethal tumor challenge and the selective expansion of tumor reactive clones.

Psychosocial impact of COVID-19 pandemic on healthcare workers in India & their perceptions on the way forward - A qualitative study.

Background & objectives: The healthcare system across the world has been overburdened due to the COVID-19 pandemic impacting healthcare workers (HCWs) in different ways. The present study provides an insight into the psychosocial challenges faced by the HCWs related to their work, family and personal well-being and the associated stigmas. Additionally, the coping mechanisms adopted by them and their perceptions on the interventions to address these challenges were also explored. Methods: A qualitative study was conducted between September and December 2020 through in-depth telephonic interviews using an interview guide among 111 HCWs who were involved in COVID-19 management across 10 States in India. Results: HCWs report major changes in work-life environment that included excessive workload with erratic timings accentuated with the extended duration of inconvenient personal protection equipment usage, periods of quarantine and long durations of separation from family. Family-related issues were manifold; the main challenge being separated from family, the challenge of caregiving, especially for females with infants and children, and fears around infecting family. Stigma from the community and peers fuelled by the fear of infection was manifested through avoidance and rejection. Coping strategies included peer, family support and the positive experiences manifested as appreciation and recognition for their contribution during the pandemic. Interpretation & conclusions: The study demonstrates the psychological burden of HCWs engaged with COVID-19 care services. The study findings point to need-based psychosocial interventions at the organizational, societal and individual levels. This includes a conducive working environment involving periodic evaluation of the HCW problems, rotation of workforce by engaging more staff, debunking of false information, community and HCW involvement in COVID sensitization to allay fears and prevent stigma associated with COVID-19 infection/transmission and finally need-based psychological support for them and their families.

Acceptability of the Medication Event Reminder Monitor for Promoting Adherence to Multidrug-Resistant Tuberculosis Therapy in Two Indian Cities: Qualitative Study of Patients and Health Care Providers.

BACKGROUND: Patients with multidrug-resistant tuberculosis (MDR-TB) face challenges adhering to medications, given that treatment is prolonged and has a high rate of adverse effects. The Medication Event Reminder Monitor (MERM) is a digital pillbox that provides pill-taking reminders and facilitates the remote monitoring of medication adherence. OBJECTIVE: This study aims to assess the MERM's acceptability to patients and health care providers (HCPs) during pilot implementation in India's public sector MDR-TB program. METHODS: From October 2017 to September 2018, we conducted qualitative interviews with patients who were undergoing MDR-TB therapy and were being monitored with the MERM and HCPs in the government program in Chennai and Mumbai. Interview transcripts were independently coded by 2 researchers and analyzed to identify the emergent themes. We organized findings by using the Unified Theory of Acceptance and Use of Technology (UTAUT), which outlines 4 constructs that predict technology acceptance-performance expectancy, effort expectancy, social influence, and facilitating conditions. RESULTS: We interviewed 65 patients with MDR-TB and 10 HCPs. In patient interviews, greater acceptance of the MERM was related to perceptions that the audible and visual reminders improved medication adherence and that remote monitoring reduced the frequency of clinic visits (performance expectancy), that the device's organization and labeling of medications made it easier to take them correctly (effort expectancy), that the device facilitated positive family involvement in the patient's care (social influences), and that remote monitoring made patients feel more cared for by the health system (facilitating conditions). Lower patient acceptance was related to problems with the durability of the MERM's cardboard construction and difficulties with portability and storage because of its large size (effort expectancy), concerns regarding stigma and the disclosure of patients' MDR-TB diagnoses (social influences), and the incorrect understanding of the MERM because of suboptimal counseling (facilitating conditions). In their interviews, HCPs reported that MERM implementation resulted in fewer in-person interactions with patients and thus allowed HCPs to dedicate more time to other tasks, which improved job satisfaction. CONCLUSIONS: Several features of the MERM support its acceptability among patients with MDR-TB and HCPs, and some barriers to patient use could be addressed by improving the design of the device. However, some barriers, such as disease-related stigma, are more difficult to modify and may limit use of the MERM among some patients with MDR-TB. Further research is needed to assess the accuracy of MERM for measuring adherence, its effectiveness for improving treatment outcomes, and patients' sustained use of the device in larger scale implementation.

Mycobacterium tuberculosis strain lineage in mixed tribal population across India and Andaman Nicobar Island.

In India, the tribal population constitutes almost 8.6% of the nation's total population. Despite their large presence, there are only a few reports available on Mycobacterium tuberculosis (M. tb) strain prevalence in Indian tribal communities considering the mobile nature of this population and also the influence of the mainstream populations they coexist within many areas for their livelihood. This study attempts to provide critical information pertaining to the TB strain diversity, its public health implications, and distribution among the tribal population in eleven Indian states and Andaman & Nicobar (A&N) Island. The study employed a population-based molecular approach. Clinical isolates were received from 66 villages (10 states and Island) and these villages were selected by implying situation analysis. A total of 78 M. tb clinical isolates were received from 10 different states and A&N Island. Among these, 16 different strains were observed by spoligotyping technique. The major M. tb strains spoligotype belong to the Beijing, CAS1_DELHI, and EAI5 family of M. tb strains followed by EAI1_SOM, EAI6_BGD1, LAM3, LAM6, LAM9, T1, T2, U strains. Drug-susceptibility testing (DST) results showed almost 15.4% of clinical isolates found to be resistant to isoniazid (INH) or rifampicin (RMP) + INH. Predominant multidrug-resistant (MDR-TB) isolates seem to be Beijing strain. Beijing, CAS1_DELHI, EAI3_IND, and EAI5 were the principal strains infecting mixed tribal populations across India. Despite the small sample size, this study has demonstrated higher diversity among the TB strains with significant MDR-TB findings. Prevalence of Beijing MDR-TB strains in Central, Southern, Eastern India and A&N Island indicates the transmission of the TB strains.

Evaluation of the Accuracy of 99DOTS, a Novel Cellphone-based Strategy for Monitoring Adherence to Tuberculosis Medications: Comparison of DigitalAdherence Data With Urine Isoniazid Testing.

99DOTS is a cellphone-based strategy for monitoring tuberculosis medication adherence. In a sample of 597 Indian patients with tuberculosis, we compared 99DOTS' adherence assessments against results of urine isoniazid tests collected during unannounced home visits. 99DOTS had suboptimal accuracy for measuring adherence, partly due to poor patient engagement with 99DOTS.

Subtherapeutic Rifampicin Concentration Is Associated With Unfavorable Tuberculosis Treatment Outcomes.

BACKGROUND: The relationships between first-line drug concentrations and clinically important outcomes among patients with tuberculosis (TB) remain poorly understood. METHODS: We enrolled a prospective cohort of patients with new pulmonary TB receiving thrice-weekly treatment in India. The maximum plasma concentration of each drug was determined at months 1 and 5 using blood samples drawn 2 hours postdose. Subtherapeutic cutoffs were: rifampicin <8 µg/mL, isoniazid <3 µg/mL, and pyrazinamide <20 µg/mL. Factors associated with lower log-transformed drug concentrations, unfavorable outcomes (composite of treatment failure, all-cause mortality, and recurrence), and individual outcomes were examined using Poisson regression models. RESULTS: Among 404 participants, rifampicin, isoniazid, and pyrazinamide concentrations were subtherapeutic in 85%, 29%, and 13%, respectively, at month 1 (with similar results for rifampicin and isoniazid at month 5). Rifampicin concentrations were lower with human immunodeficiency virus coinfection (median, 1.6 vs 4.6 µg/mL; P = .015). Unfavorable outcome was observed in 19%; a 1-µg/mL decrease in rifampicin concentration was independently associated with unfavorable outcome (adjusted incidence rate ratio [aIRR], 1.21 [95% confidence interval {CI}, 1.01-1.47]) and treatment failure (aIRR, 1.16 [95% CI, 1.05-1.28]). A 1-µg/mL decrease in pyrazinamide concentration was associated with recurrence (aIRR, 1.05 [95% CI, 1.01-1.11]). CONCLUSIONS: Rifampicin concentrations were subtherapeutic in most Indian patients taking a thrice-weekly TB regimen, and low rifampicin and pyrazinamide concentrations were associated with poor outcomes. Higher or more frequent dosing is needed to improve TB treatment outcomes in India.

Infections among Contacts of Patients with Nipah Virus, India.

We conducted a serosurvey of 155 healthcare workers and 124 household and community members who had close contact with 18 patients who had laboratory-confirmed Nipah virus infections in Kerala, India. We detected 3 subclinical infections; 2 persons had IgM and IgG and 1 only IgM against Nipah virus.

Pretreatment loss to follow-up of tuberculosis patients in Chennai, India: a cohort study with implications for health systems strengthening.

BACKGROUND: Pretreatment loss to follow-up (PTLFU) is a barrier to tuberculosis (TB) control in India's Revised National TB Control Programme (RNTCP). PTLFU studies have not been conducted in India's mega-cities, where patient mobility may complicate linkage to care. METHODS: We collected data from patient registries for May 2015 from 22 RNTCP designated microscopy centers (DMCs) in Chennai and audited addresses and phone numbers for patients evaluated for suspected TB to understand how missing contact information may contribute to PTLFU. From November 2015 to June 2016, we audited one month of records from each of these 22 DMCs and tracked newly diagnosed smear-positive patients using RNTCP records, phone calls, and home visits. We defined PTLFU cases as including: (1) patients who did not start TB therapy within 14 days and (2) patients who started TB therapy but were lost to follow-up or died before official RNTCP registration. We used multivariate logistic regression to identify factors associated with PTLFU. RESULTS: In the audit of May 2015 DMC registries, out of 3696 patients evaluated for TB, 1273 (34.4%) had addresses and phone numbers that were illegible or missing. Out of 344 smear-positive patients tracked from November 2015 to June 2016, 40 (11.6%) did not start TB therapy within 14 days and 36 (10.5%) started therapy but were lost to follow-up or died before official RNTCP registration, for an overall PTLFU rate of 22.1% (95%CI: 17.8%-26.4%). Of all PTLFU patients, 55 (72.4%) were lost to follow-up and 21 (27.6%) died before starting treatment or before RNTCP registration. In the regression analysis, age > 50 years (OR 2.9, 95%CI 1.4-6.5), history of prior TB (OR 3.9, 95%CI 2.2-7.1), evaluation at a high patient volume DMC (OR 3.2, 95% CI 1.7-6.3), and absence of legible patient contact information (OR 4.5, 95%CI 1.3-15.1) were significantly associated with PTLFU. CONCLUSIONS: In an Indian mega-city, we found a high PTLFU rate, especially in patients with a prior TB history, who are at greater risk for having drug-resistance. Enhancing quality of care and health system transparency is critical for improving linkage of newly diagnosed patients to TB care in urban India.

A randomized clinical efficacy trial of a psychosocial intervention to strengthen self-acceptance and reduce HIV risk for MSM in India: study protocol.

BACKGROUND: Men who have sex with men (MSM) in India are a key group at risk for HIV acquisition and transmission. They are also an extremely marginalized and stigmatized population, facing immense psychosocial stressors including, but not limited to, stigma, homophobia, discrimination, criminalization, low self-esteem, low self-acceptance, distress, and, as a result, high rates of mental health problems. Although these multi-level psychosocial problems may put MSM at high risk for HIV acquisition and transmission, currently HIV prevention interventions in India do not address them. This paper describes the design of a psychosocial intervention to reduce HIV risk for MSM in India. METHODS: Funded by the National Institute of Mental Health, this study is a two-arm randomized clinical efficacy trial of a self-acceptance based psychosocial HIV prevention intervention, informed by the minority stress model and syndemic theory, that was developed with extensive community-based formative work and input from the Indian MSM community and key informants who are knowledgeable about the experiences faced by MSM in India. Participants are MSM in Chennai and Mumbai who endorsed recent sexual behaviors placing them at high risk for HIV/sexually transmitted infection (STI) acquisition and transmission. Enrolled participants are equally randomized to either 1) the experimental condition, which consists of four group and six individual counseling sessions and includes standard of care HIV/STI testing and counseling, or 2) the standard of care condition, which includes HIV/STI testing and counseling alone. The primary outcomes are changes in the frequency of condomless anal sex acts and STI incidence (syphilis seropositivity and urethral, rectal, and pharyngeal gonorrhea and chlamydia infection. Major study assessment visits occur at baseline, 4-, 8-, and 12-months. DISCUSSION: HIV prevention interventions that address the psychosocial stressors faced by MSM in India are needed; this study will examine the efficacy of such an intervention. If the intervention is successful, it may be able to reduce the national HIV/AIDS burden in India while empowering a marginalized and highly stigmatized group. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02556294 , registered 22 September 2015.

A Pilot Randomized Controlled Trial of an Integrated In-person and Mobile Phone Delivered Counseling and Text Messaging Intervention to Reduce HIV Transmission Risk among Male Sex Workers in Chennai, India.

Men who have sex with men (MSM) are at increased risk for HIV infection in India, particularly those who engage in transactional sex with other men (i.e., male sex workers; MSW). Despite the need, HIV prevention efforts for Indian MSW are lacking. As in other settings, MSW in India increasingly rely on the use of mobile phones for sex work solicitation. Integrating mobile phone technology into an HIV prevention intervention for Indian MSW may mitigate some of the challenges associated with face-to face approaches, such as implementation, lack of anonymity, and time consumption, while at the same time proving to be both feasible and useful. This is a pilot randomized controlled trial to examine participant acceptability, feasibility of study procedures, and preliminary efficacy for reducing sexual risk for HIV. MSW (N = 100) were equally randomized to: (1) a behavioral HIV prevention intervention integrating in-person and mobile phone delivered HIV risk reduction counseling, and daily, personalized text or voice messages as motivating "cognitive restructuring" cues for reducing condomless anal sex (CAS); or (2) a standard of care (SOC) comparison condition. Both groups received HIV counseling and testing at baseline and 6-months, and completed ACASI-based, behavioral and psychosocial assessments at baseline, 3, and 6 months. Mixed-effects regression procedures specifying a Poisson distribution and log link with a random intercept and slope for month of follow-up was estimated to assess the intervention effect on the primary outcomes: (1) CAS acts with male clients who paid them for sex, and (2) CAS acts with male non-paying sexual partners-both outcomes assessed over the past month. The intervention was both feasible (98% retention at 6-months) and acceptable (>96% of all intervention sessions attended); all intervention participants rated the intervention as "acceptable" or "very acceptable." A reduction in the reported number of CAS acts with male clients who paid them for sex in the past month was seen in both study conditions. MSW in the intervention condition reported a faster rate of decline in the number of CAS acts with male clients in the past month from the baseline to both the 3-month (B = -1.20; 95% CI -1.68, -0.73; p < 0.0001) and 6-month (B = -2.44; 95% CI -3.35, -1.53; p < 0.00001) assessment visits compared to the SOC condition. Post-hoc contrasts indicated that, at 3 months, participants in the intervention condition reported 1.43 (SD = 0.29) CAS acts with male clients in the past month compared to 4.85 (SD = 0.87) in the control condition (p = 0.0003). Furthermore, at 6 months, the intervention condition participants reported 0.24 (SD = 0.09) CAS acts with male clients in the past month compared to 2.79 (SD = 0.79) in the control condition (p < 0.0001). Findings are encouraging and provide evidence of feasibility and acceptability, and demonstrate initial efficacy (for reducing sexual risk for HIV) of a behavioral HIV prevention intervention for Indian MSW that combines daily, personalized text or voice messages with mobile phone-delivered sexual risk reduction counseling and skills building. Future testing of the intervention in a fully powered randomized controlled efficacy trial is warranted.

Transactional sex and the challenges to safer sexual behaviors: a study among male sex workers in Chennai, India.

Male sex workers (MSW) are a significant but invisible population in India who are at risk for HIV/sexually transmitted infections (STIs). Few studies from India have documented HIV risk factors and motivations for sex work in this population. Between 2013 and 2014, a community-based convenience sample of 100 MSW in Chennai (south India) completed a baseline risk assessment as part of a behavioral intervention. Participants were ≥18 years, and reported current sex work. We report medians and proportions, and Wilcoxon-Mann-Whitney and chi-square tests are used to examine differences between sex work and sexual behavior measures by income source. Participants were engaged in sex work for 5.0 years (IQR = 2.3-10.0), and earned 3000 (IQR = 2000-8000) Rupees (<50 USD) per month from sex work. Sixty-four percent reported ever testing for HIV and 20.2% for any STI. The most common reasons for starting sex work were money (83.0%) and pleasure (56.0%). Compared to participants with an additional source of income, those whose only source of income was sex work reported more male clients in the past month (10.0 vs. 6.0, p = .017), as well as more condomless anal sex acts with male clients (8.0 vs. 5.0, p = .008). Nearly 70.0% were offered more money not to use a condom during sex with a client, and 74.2% reported accepting more money not to use a condom. Three-quarters reported having experienced difficulty using condoms with clients. MSW in India engage in high levels of sexual risk for HIV/STIs. Money appears to be a driving factor for engaging in sex work and condomless sex with clients. HIV prevention interventions with MSW should focus on facilitating skills that will support their ability to negotiate sexual safety in the context of monetary disincentives.

Development and Open Pilot Trial of an HIV-Prevention Intervention Integrating Mobile-Phone Technology for Male Sex Workers in Chennai, India.

In India men who have sex with men and engage in sex work (i.e., male sex workers; MSW) have a high risk of transmitting HIV. Globally, sex workers have become more spatially mobile due to advances in mobile-phone technology. In 2012 in-depth qualitative feedback was garnered from 40 interviews with MSW and four focus groups with 35 key informants (KIs) who had expert knowledge of the local MSW community to inform the design of an HIV-prevention intervention among MSW in Chennai, India. All MSW were recruited during outreach by employees of a Chennai-based organization for MSM (men who have sex with men). The data were analyzed using a descriptive qualitative approach. MSW and KIs discussed the need for intervention content that went beyond basic HIV psychoeducation. They emphasized the importance of addressing psychological distress, alcohol-related risk, and sexual communication skills. Concerns were raised about confidentiality, privacy, and scheduling. Participants endorsed a combination of in-person and mobile-phone-delivered sessions as well as the integration of mobile-phone messaging. These findings served as the basis for the development of a theoretically driven, manual-based intervention incorporating mobile phones. An open pilot assessed the feasibility and acceptability of the intervention with eight MSW. Assessments and HIV testing were administered at baseline, 3, and 6 months post-baseline. Exit interviews were conducted at the conclusion of the intervention. Retention for session attendance and assessment follow-up was 100 %. There was a high level of acceptability for the format, structure, and content. These data show initial promise, feasibility, and acceptability of the intervention.

The Tuberculosis Cascade of Care in India's Public Sector: A Systematic Review and Meta-analysis.

BACKGROUND: India has 23% of the global burden of active tuberculosis (TB) patients and 27% of the world's "missing" patients, which includes those who may not have received effective TB care and could potentially spread TB to others. The "cascade of care" is a useful model for visualizing deficiencies in case detection and retention in care, in order to prioritize interventions. METHODS AND FINDINGS: The care cascade constructed in this paper focuses on the Revised National TB Control Programme (RNTCP), which treats about half of India's TB patients. We define the TB cascade as including the following patient populations: total prevalent active TB patients in India, TB patients who reach and undergo evaluation at RNTCP diagnostic facilities, patients successfully diagnosed with TB, patients who start treatment, patients retained to treatment completion, and patients who achieve 1-y recurrence-free survival. We estimate each step of the cascade for 2013 using data from two World Health Organization (WHO) reports (2014-2015), one WHO dataset (2015), and three RNTCP reports (2014-2016). In addition, we conduct three targeted systematic reviews of the scientific literature to identify 39 unique articles published from 2000-2015 that provide additional data on five indicators that help estimate different steps of the TB cascade. We construct separate care cascades for the overall population of patients with active TB and for patients with specific forms of TB-including new smear-positive, new smear-negative, retreatment smear-positive, and multidrug-resistant (MDR) TB. The WHO estimated that there were 2,700,000 (95%CI: 1,800,000-3,800,000) prevalent TB patients in India in 2013. Of these patients, we estimate that 1,938,027 (72%) TB patients were evaluated at RNTCP facilities; 1,629,906 (60%) were successfully diagnosed; 1,417,838 (53%) got registered for treatment; 1,221,764 (45%) completed treatment; and 1,049,237 (95%CI: 1,008,775-1,083,243), or 39%, of 2,700,000 TB patients achieved the optimal outcome of 1-y recurrence-free survival. The separate cascades for different forms of TB highlight different patterns of patient attrition. Pretreatment loss to follow-up of diagnosed patients and post-treatment TB recurrence were major points of attrition in the new smear-positive TB cascade. In the new smear-negative and MDR TB cascades, a substantial proportion of patients who were evaluated at RNTCP diagnostic facilities were not successfully diagnosed. Retreatment smear-positive and MDR TB patients had poorer treatment outcomes than the general TB population. Limitations of our analysis include the lack of available data on the cascade of care in the private sector and substantial uncertainty regarding the 1-y period prevalence of TB in India. CONCLUSIONS: Increasing case detection is critical to improving outcomes in India's TB cascade of care, especially for smear-negative and MDR TB patients. For new smear-positive patients, pretreatment loss to follow-up and post-treatment TB recurrence are considerable points of attrition that may contribute to ongoing TB transmission. Future multisite studies providing more accurate information on key steps in the public sector TB cascade and extension of this analysis to private sector patients may help to better target interventions and resources for TB control in India.

Garnering an in-depth understanding of men who have sex with men in Chennai, India: a qualitative analysis of sexual minority status and psychological distress.

Men who have sex with men (MSM) in India are a hidden and largely understudied population, and have an HIV prevalence 17 times higher than that of the general Indian population. Experiences of social marginalization and negative psychosocial conditions occur concurrent to HIV risk among Indian MSM. To better understand the contextual variables driving HIV risk and inform intervention development, five focus groups (n = 46) and nine key informant interviews were conducted with 55 MSM in Chennai in 2010. NVivo software was used to code the transcripts, and data were analyzed using qualitative descriptive analysis methodology. Participants described sources of psychological distress and low self-worth related to gender non-conformity and sexual minority status. These included stigma from society, pressure to marry, lack of familial acceptance, childhood sexual abuse, and the imperative to keep sexual minority status a secret. Participants' personal evaluations revealed that self-acceptance may be an important resilience factor that can shield these psychosocial and HIV risk factors. In promoting health-seeking behavioral changes for Indian MSM at an individual level, our findings point to the potential strength of strategies that focus on self-acceptance of one's sexual minority identity to foster better psychosocial and overall health.

Pulmonary tuberculosis among tribals in India: A systematic review & meta-analysis.

BACKGROUND & OBJECTIVES: There has been limited investigation on the prevalence of tuberculosis (TB) in tribal communities in India, a vulnerable section of Indian society. The lack of a population-based estimate prompted us to conduct a meta-analysis of existing studies to provide a single, population-based estimate of the TB prevalence for tribals. METHODS: Literature search was conducted in PubMed using the keywords - "tuberculosis", "tribals", "India", "prevalence", and "survey". References cited in the articles retrieved were also reviewed, and those found relevant were selected. TB prevalence rates estimated by the studies were used for our calculation of a pooled-estimate. RESULTS: The pooled estimate, based on the random effects model, was 703 per 100,000 population with a 95 % CI of 386-1011. The associated heterogeneity measures in terms of Cochran's Q was significant ( p=0 0.08 <0.1) and I [2] was moderate at 48 per cent. INTERPRETATION & CONCLUSIONS: The meta-analysis demonstrated a large variability in pulmonary TB prevalence estimates among the different studies with poor representation of the various tribal groups. The moderate level of heterogeneity found across the studies suggests that the pooled-estimate needs to be treated with caution. Our findings also highlight the need to assess the pulmonary TB burden in India.

Prevalence of chest symptoms amongst brick kiln migrant workers and care seeking behaviour: a study from South India.

BACKGROUND: Early detection and treatment of tuberculosis (TB) have been key principles of TB control. However, this can be a challenge with 'hard to reach' populations such as migrants. Brick kiln workers are one such group of migrants who are exposed to smoke, heat and dust from brick kilns which are one of the major causes of respiratory illnesses. METHODOLOGY: A cross-sectional community based study was carried out in Thiruvallur, Tamil Nadu, South India, from August 2011 to June 2012. A total of 4002 individuals from 55 brick kiln chambers were interviewed to determine the prevalence of chest symptoms and care seeking behaviour patterns. RESULTS: Three hundred and seventy-seven (9.4%) chest symptomatics were identified. The most significant variables associated with chest symptoms were illiteracy, alcohol abuse and heavy smoking. Of the chest symptomatics identified, 50.4% took action to get relief from their symptoms. The duration of over 6-month stay in the chamber was significantly associated with taking action (OR, 5.5, 95% CI: 2.3, 13.3). CONCLUSIONS: The TB control programme needs to further explore how to extend its services to such 'hard to reach' groups. Active case finding to ensure early diagnosis and treatment initiation amongst such groups needs consideration.