Abhay Kadam

Background: An estimated 10% of tuberculosis (TB) survivors who recently completed treatment in India develop TB again. We sought to develop a parsimonious model for predicting TB recurrence that can help target post-treatment active case finding among the highest-risk TB survivors. Methods: The TB Aftermath trial enrolled TB survivors at treatment completion from 6 public TB clinics in Maharashtra, India, and assessed participants at 6-month intervals. Our prediction endpoint was recurrent TB diagnosed within 18 months of treatment completion. Candidate variables included risk factors for recurrence identified a priori and lung function assessments. We used LASSO (Least Absolute Shrinkage and Selection Operator) regression to shortlist predictors and estimated probability of recurrence using logistic regression. We conducted internal validation, assessed discrimination, and plotted calibration. Model selection was based on practical utility and predictive accuracy. For our selected model, we identified a cutoff for achieving 90% sensitivity. Results: Among 1033 participants, we identified 85 (8.2%) recurrences. Several 5-item models measurable at treatment completion had moderate discrimination. Our selected model included sex, household income, body mass index, peak expiratory flow from spirometry, and history of multiple TB episodes. The selected model had a cross-validated c-statistic of .69 (95% CI: .56–.77) and acceptable calibration (intercept: .03 [95% CI: −.03, .09]; slope: .66 [.08–1.24]). TB survivors with a predicted probability ≥3.7% accounted for 90% of recurrences. Conclusions: A 5-item tool, measurable at treatment completion, showed moderate predictive accuracy for recurrent TB. At scale, a simple 5-item prediction tool may increase efficiency of post-treatment active case finding.

Background: Approximately 7% of all reported tuberculosis (TB) cases each year are recurrent, occurring among people who have had TB in the recent or distant past. TB recurrence is particularly common in India, which has the largest TB burden worldwide. Although patients recently treated for TB are at high risk of developing TB again, evidence around effective active case finding (ACF) strategies in this population is scarce. We will conduct a hybrid type I effectiveness-implementation non-inferiority randomized trial to compare the effectiveness, cost-effectiveness, and feasibility of two ACF strategies among individuals who have completed TB treatment and their household contacts (HHCs). Methods: We will enroll 1076 adults (≥ 18 years) who have completed TB treatment at a public TB unit (TU) in Pune, India, along with their HHCs (averaging two per patient, n = 2152). Participants will undergo symptom-based ACF by existing healthcare workers (HCWs) at 6-month intervals and will be randomized to either home-based ACF (HACF) or telephonic ACF (TACF). Symptomatic participants will undergo microbiologic testing through the program. Asymptomatic HHCs will be referred for TB preventive treatment (TPT) per national guidelines. The primary outcome is rate per 100 person-years of people diagnosed with new or recurrent TB by study arm, within 12 months following treatment completion. The secondary outcome is proportion of HHCs < 6 years, by study arm, initiated on TPT after ruling out TB disease. Study staff will collect socio-demographic and clinical data to identify risk factors for TB recurrence and will measure post-TB lung impairment. In both arms, an 18-month “mop-up” visit will be conducted to ascertain outcomes. We will use the RE-AIM framework to characterize implementation processes and explore acceptability through in-depth interviews with index patients, HHCs and HCWs (n = 100). Cost-effectiveness will be assessed by calculating the incremental cost per TB case detected within 12 months and projected for disability-adjusted life years averted based on modeled estimates of morbidity, mortality, and time with infectious TB. Discussion: This novel trial will guide India’s scale-up of post-treatment ACF and provide an evidence base for designing strategies to detect recurrent and new TB in other high burden settings. Trial registration: NCT04333485, registered April 3, 2020. CTRI/2020/05/025059 [Clinical Trials Registry of India], registered May 6 2020.

Background: The COVID‐19 pandemic has placed healthcare professionals (HCP) in stressful circumstances with increased patient loads and a high risk of exposure. We sought to assess the mental health and quality of life (QoL) of Indian HCPs, the fourth highest‐burden country for COVID‐19.Method: Using snowball sampling, we conducted an online survey in May 2020 among HCPs. Data were collected on demographics, depression, and anxiety using validated tools, quality of life, and perceived stressors. Multivariable logistic regression and principal component analysis were performed to assess risk factors associated with mental health symptoms.Findings: Of 197 HCPs assessed, 157 (80%) were from Maharashtra, 130 (66%) from public hospitals, 47 (24%) nurses, 66 (34%) physicians, 101 (52%) females, and 81 (41%) ≤30 years. Eighty‐seven percent provided direct COVID‐19 care with 43% caring for >10 patients/day. A large proportion reported symptoms of depression (92, 47%), anxiety (98, 50%), and low QoL (89, 45%). Odds of combined depression and anxiety were 2.37 times higher among single HCPs compared to married (95% CI: 1.03–4.96). Work environment stressors were associated with 46% increased risk of combined depression and anxiety (95% CI: 1.15–1.85). Moderate to severe depression and anxiety were independently associated with increased risk of low QoL [OR: 3.19 (95% CI: 1.30–7.84), OR: 2.84 (95% CI: 1.29–6.29)].Conclusion: Our study demonstrated a high prevalence of symptoms of depression and anxiety and low QoL among Indian HCPs during the COVID‐19 pandemic. There is an urgent need to prevent and treat mental health symptoms among frontline HCPs.

Introduction: India’s national AIDS Control Organization implemented World Health Organization’s option B+ HIV prevention of mother‐to‐child transmission (PMTCT) guidelines in 2013. However, scalable strategies to improve uptake of new PMTCT guidelines to reduce new infection rates are needed. This study assessed impact of Mobile Health‐Facilitated Behavioral Intervention on the uptake of PMTCT services.Methods: A cluster‐randomized trial of a mobile health (mHealth)‐supported behavioural training intervention targeting outreach workers (ORWs) was conducted in four districts of Maharashtra, India. Clusters (one Integrated Counselling and Testing Center (ICTC, n = 119), all affiliated ORWs (n = 116) and their assigned HIV‐positive pregnant/postpartum clients (n = 1191)) were randomized to standard‐of‐care (SOC) ORW training vs. the COMmunity home Based INDia (COMBIND) intervention – specialized behavioural training plus a tablet‐based mHealth application to support ORW‐patient communication and patient engagement in HIV care. Impact on uptake of maternal antiretroviral therapy at delivery, exclusive breastfeeding at six months, infant nevirapine prophylaxis, and early infant diagnosis at six months was assessed using multi‐level random‐effects logistic regression models.Results: Of 1191 HIV‐positive pregnant/postpartum women, 884 were eligible for primary outcome assessment; 487 were randomized to COMBIND. Multivariable analyses identified no statistically significant differences in any primary outcome by study arm. COMBIND was associated with higher uptake of exclusive breastfeeding at two months (adjusted Odds Ratio (aOR), 2.10; 95% CI 1.06 to 4.15) and early infant diagnosis at six weeks (aOR, 2.19; 95% CI 1.05 to 3.98) than SOC.Conclusions: The COMBIND intervention was easily integrated into India’s existing PMTCT programme and improved early uptake of two PMTCT components that require self‐motivated health‐seeking behaviour, thus providing preliminary evidence to support COMBIND as a potentially scalable PMTCT strategy. Further study would identify modifications needed to optimize other PMTCT outcomes.

Background: A cluster-randomized trial recently demonstrated that an integrated behavioral and mobile technology intervention improved uptake of key components of a Prevention of Mother to Child Transmission (PMTCT) Option B+ program, among HIV- infected pregnant/breastfeeding women in India. To guide scale-up and optimize programmatic implementation, we conducted a mixed-methods evaluation of the feasibility and acceptability of this intervention. Methods: The COMmunity Home Based INDia (COMBIND) study, was conducted in four districts of Maharashtra, India and randomized 119 integrated counseling and testing centers (ICTC) and their outreach workers (ORWs) to the COMBIND intervention, an integrated mHealth application that allowed digital data capture, PMTCT educational videos, SMS alerts for missed visits and reminder for visits, combined with personal empowerment and motivational interviewing training for ORWs. This qualitative evaluation was done through 15 in-depth interviews (IDIs) with ORWs and 15 IDIs with HIV-infected pregnant/breastfeeding women from the intervention arm. Utilizing a concurrent nested mixed-method evaluation approach, we assess the feasibility and acceptability of the study intervention. Results: All 30 participants reported that the PMTCT videos were essential in providing easy to understand information on critical aspects of HIV and necessary care related to PMTCT practices. A majority of the ORWs reported that the personal empowerment training with motivational interviewing skills training increased their confidence, motivation and gave them the tools for effectively supporting their clients. The mHealth application improved their working style as it facilitated targeted PMTCT information support, systemized data capture, streamlined their health education delivery practice and provided a sense of work satisfaction. The SMS appointment alerts improved retention in HIV care for mother and baby to the smaller proportion that had access to their phones. Despite reported improvements in knowledge and communication, few ORWs reported that structural challenges such as limited drug stocks, lack of HIV kits or unavailability of trained staff at ICTC, may hamper the uptake of PMTCT services, thus resulting in limited significant impacts of COMBIND on PMTCT outcomes. Conclusion: This study found that COMBIND intervention is scalable, feasible, beneficial and very well accepted by ORWs and patients, however structural challenges in goods and services remain.

Antimicrobial resistance (AMR) is a growing threat to newborns in low- and middle-income countries (LMIC). We performed a prospective cohort study in 3 tertiary neonatal intensive care units (NICUs) in Pune, India, to describe the epidemiology of neonatal bloodstream infections (BSIs). All neonates admitted to the NICU were enrolled. The primary outcome was BSI, defined as positive blood culture. Early-onset BSI was defined as BSI on day of life (DOL) 0–2 and late-onset BSI on DOL 3 or later. From 1 May 2017 until 30 April 2018, 4073 neonates were enrolled. Among at-risk neonates, 55 (1.6%) developed early-onset BSI and 176 (5.5%) developed late-onset BSI. The majority of BSIs were caused by gram-negative bacteria (GNB; 58%); among GNB, 61 (45%) were resistant to carbapenems. Klebsiella spp. (n = 53, 23%) were the most common cause of BSI. Compared with neonates without BSI, all-cause mortality was higher among neonates with early-onset BSI (31% vs 10%, P < .001) and late-onset BSI (24% vs 7%, P < .001). Non–low-birth-weight neonates with late-onset BSI had the greatest excess in mortality (22% vs 3%, P < .001). In our cohort, neonatal BSIs were most commonly caused by GNB, with a high prevalence of AMR, and were associated with high mortality, even in term neonates. Effective interventions are urgently needed to reduce the burden of BSI and death due to AMR GNB in hospitalized neonates in LMIC.

Social media has played a crucial role in spreading awareness and knowledge about public health; however, it has also been misused for spreading fake news, hatred and creating racism during epidemics and civil unrest. We discuss how social media and societal response to COVID-19 negatively affected its control measures in India and what should be possible corrective measures.

The Prevention of Mother-to-Child Transmission of HIV (PMTCT) program in India is one of the largest in the world. It uses outreach workers (ORWs) to facilitate patient uptake of services, however, the challenges faced by the ORWs, and their views about the effectiveness of this program are unknown. The COMmunity-Home Based INDia (COMBIND) Prevention of Mother to Child Transmission of HIV study evaluated an integrated mobile health and behavioral intervention to enhance the capacity of ORWs in India. To understand the challenges faced by ORWs, and their perceptions of opportunities for program improvement, four group discussions were conducted among 60 ORW from four districts of Maharashtra, India, as part of the baseline assessment for COMBIND. Data were qualitatively analyzed using a thematic approach. Numerous personal-, social-, and structural-level challenges existed for ORW as they engaged with their patients. Personal-level challenges for ORWs included disclosure of their own HIV status and travelling costs for home visits. Personal-level challenges for patients included financial costs of travelling to ART centers, non-adherence to ART, loss of daily wages, non-affordability of infant formula, lack of awareness of the baby’s needs, financial dependence on family, four time points (6weeks, 6 months, 12 months and 18 months) for HIV tests, and need for nevirapine (NVP) prophylaxis. Social-level challenges included lack of motivation by patients and/or health care staff, social stigma, and rude behavior of health care staff and their unwillingness to provide maternity services to women in the PMTCT programme. Structural-level challenges included cultural norms around infant feeding, shortages of HIV testing kits, shortages of antiretroviral drugs and infant NVP prophylaxis, and lack of training/knowledge related to PMTCT infant feeding guidelines by hospital staff. The consensus among ORWs was that there was a critical need for tools and training to improve their capacity to effectively engage with patients, and deliver appropriate care, and for motivation through periodic feedback. Given the significant challenges in PMTCT programme implementation reported by ORW, novel strategies to address these challenges are urgently needed to improve patient engagement, and access to and retention in care.

Aims: Rising antimicrobial resistance (AMR) is a global health crisis. India has among the highest resistance rates and antibiotic consumption internationally. Extensive use of fixed‐dose combination (FDC) antibiotics and of unapproved formulations are claimed contributory factors but there has been no systematic examination of formulations or volumes sold. The aim of the present study was to investigate the regulatory approval status and sales volumes of systemic antibiotics marketed in India.Methods: This was an ecological study using regulatory records in India, the UK and the US to determine the approval status in each country of systemic antibiotic FDCs and single‐drug formulations (SDFs) sold in India. Pharmatrac® sales data were used to determine the formulations and volumes sold (2007–2012), branded‐product numbers and manufacturers.Results: Of 118 systemic antibiotic FDC formulations sold in India, 43 (36%) were approved but 75 (64%) had no record of regulatory approval; four (3%) formulations were approved in the UK and/or US. Almost half of formulations (58/118; 49%) comprised dual antimicrobials, most unapproved in India (43/58; 74%), and many were pharmacologically problematic. In contrast, 80/86 (93%) SDFs were approved in India and over two‐thirds in the UK and/or US. Total antibiotic sales increased by 26%, from 2056 million units (2007–08) to 2583 million units (2011–12). FDC sales rose by 38% vs. 20% for SDFs. By 2011–12, FDCs comprised one‐third of sales (872 million units). Over one‐third of FDCs sold (300.26 million units; 34.5%) were of unapproved formulations. Multinational companies manufactured unapproved formulations and accounted for 19% of all FDC and SDF sales annually.Conclusions: Sales in India of antibiotic FDCs, including unapproved formulations, are rising. In the context of increasing AMR rates nationally and globally, unapproved antibiotic FDCs undermine India's national AMR strategy and should be banned from sale.