A mobile health-facilitated behavioural intervention for community health workers improves exclusive breastfeeding and early infant HIV diagnosis in India: a cluster randomized trial.

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.

Acceptability and feasibility of a behavioral and mobile health intervention (COMBIND) shown to increase uptake of prevention of mother to child transmission (PMTCT) care in India.

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.

Drug-resistant Enterobacteriaceae colonization is associated with healthcare utilization and antimicrobial use among inpatients in Pune, India.

BACKGROUND: Healthcare exposure may increase drug-resistant Enterobacteriaceae colonization risk. Nascent antimicrobial stewardship efforts in low- and middle-income countries require setting-specific data. We aimed to evaluate risk factors for inpatient drug resistant Enterobacteriaceae colonization in a resource-limited setting in India. METHODS: Patients age ≥ 6 months admitted with ≥24 h of fever to a tertiary hospital in Pune, India were enrolled in a prospective cohort. Perirectal swabs, collected on admission and hospitalization day 3 or 4, were cultured in vancomycin- and ceftriaxone-impregnated media to assess for ceftriaxone-resistant Enterobacteriaceae (CTRE) and carbapenem-resistant Enterobacteriaceae (CPRE). Multivariable analyses assessed risk factors for drug-resistant Enterobacteriaceae colonization among participants without admission colonization. RESULTS: Admission perirectal swabs were collected on 897 participants; 87 (10%) had CTRE and 14 (1.6%) had CPRE colonization. Admission CTRE colonization was associated with recent healthcare contact (p < 0.01). Follow-up samples were collected from 620 participants, 67 (11%) had CTRE and 21 (3.4%) had CPRE colonization. Among 561 participants without enrollment CTRE colonization, 49 (9%) participants were colonized with CTRE at follow-up. Detection of CTRE colonization among participants not colonized with CTRE at admission was independently associated with empiric third generation cephalosporin treatment (adjusted odds ratio [OR] 2.9, 95% CI 1.5-5.8). Follow-up transition to CPRE colonization detection was associated with ICU admission (OR 3.0, 95% CI 1.0-8.5). CONCLUSIONS: Patients who receive empiric third generation cephalosporins and are admitted to the ICU rapidly develop detectable CTRE and CPRE colonization. Improved antimicrobial stewardship and infection control measures are urgently needed upon hospital admission.

Challenges and opportunities for outreach workers in the Prevention of Mother to Child Transmission of HIV (PMTCT) program in India.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Vector-Borne Disease is a Common Cause of Hospitalized Febrile Illness in India.

Acute febrile illness (AFI) is a major cause of morbidity and mortality in India and other resource-limited settings, yet systematic etiologic characterization of AFI has been limited. We prospectively enrolled adults (N = 970) and children (age 6 months to 12 years, N = 755) admitted with fever from the community to Sassoon General Hospital in Pune, India, from July 2013 to December 2015. We systematically obtained a standardized clinical history, basic laboratory testing, and microbiologic diagnostics on enrolled participants. Results from additional testing ordered by treating clinicians were also recorded. A microbiological diagnosis was found in 549 (32%) participants; 211 (12%) met standardized case definitions for pneumonia and meningitis without an identified organism; 559 (32%) were assigned a clinical diagnosis in the absence of a confirmed diagnosis; and 406 (24%) had no diagnosis. Vector-borne diseases were the most common cause of AFI in adults including dengue (N = 188, 19%), malaria (N = 74, 8%), chikungunya (N = 15, 2%), and concurrent mosquito-borne infections (N = 23, 2%) occurring most frequently in the 3 months after the monsoon. In children, pneumonia was the most common cause of AFI (N = 214, 28%) and death. Bacteremia was found in 68 (4%) participants. Central nervous system infections occurred in 58 (6%) adults and 64 (8%) children. Etiology of AFI in India is diverse, highly seasonal, and difficult to differentiate on clinical grounds alone. Diagnostic strategies adapted for season and age may reduce diagnostic uncertainty and identify causative organisms in treatable, fatal causes of AFI.

Antibiotic Utilization and the Role of Suspected and Diagnosed Mosquito-borne Illness Among Adults and Children With Acute Febrile Illness in Pune, India.

Background: Antibiotic resistance mechanisms originating in low- and middle- income countries are among the most common worldwide. Reducing unnecessary antibiotic use in India, the world's largest antibiotic consumer, is crucial to control antimicrobial resistance globally. Limited data describing factors influencing Indian clinicians to start or stop antibiotics are available. Methods: Febrile adults and children admitted to a public tertiary care hospital in Pune, India, were enrolled. Antibiotic usage and clinical history were recorded. Immunoassays for mosquito-borne disease and bacterial cultures were performed by protocol and clinician-directed testing. Clinical factors were assessed for association with empiric antibiotic initiation and discontinuation by day 5 using multivariable logistic regression and propensity score-matched Cox proportional hazard models. Results: Among 1486 participants, 683 (82%) adults and 614 (94%) children received empiric antibiotics. Participants suspected of having mosquito-borne disease were less likely to receive empiric antibiotics (adjusted odds ratio [AOR], 0.5; 95% confidence interval [CI], .4-.8). Empiric antibiotics were discontinued in 450 (35%) participants by day 5. Dengue or malaria testing performed before day 4 was positive in 162 (12%) participants, and was associated with antibiotic discontinuation (AOR, 1.7; 95% CI, 1.2-2.4). In a propensity score-matched model accounting for admission suspicion of mosquito-borne disease, positive dengue or malaria tests increased hazard of antibiotic discontinuation (hazard ratio, 1.6; 95% CI, 1.2-2.0). Conclusions: Most patients with acute febrile illness in an Indian public hospital setting receive empiric antibiotics. Mosquito-borne disease identification is associated with reduced empiric antibiotic use and faster antibiotic discontinuation.

High Burden of Antimicrobial Resistance and Mortality Among Adults and Children With Community-Onset Bacterial Infections in India.

Background: In India, antimicrobial consumption is high, yet systematically collected data on the epidemiology, risk factors, and outcomes of antimicrobial-resistant infections are limited. Methods: A prospective study of adults and children hospitalized for acute febrile illness was conducted between August 2013 and December 2015. In-hospital outcomes were recorded, and logistic regression was performed to identify independent predictors of community-onset antimicrobial-resistant infections. Results: Among 1524 patients hospitalized with acute febrile illness, 133 isolates were found among 115 patients with community-onset infections; 66 isolates (50.0%) were multidrug resistant and, of 33 isolates tested for carbapenem susceptibility, 12 (36%) were resistant. Multidrug-resistant infections were associated with recent antecedent antibiotic use (adjusted odds ratio [aOR], 4.17; 95% confidence interval [CI], 1.19-19.7) and were independently associated with mortality (aOR, 6.06; 95% CI, 1.2-55.7). Conclusion: We found a high burden of community-onset antimicrobial-resistant infection among patients with acute febrile illness in India. Multidrug-resistant infection was associated with prior antibiotic use and an increased risk of mortality.

High prevalence of cryptococcal antigenaemia amongst asymptomatic advanced HIV patients in Pune, India.

BACKGROUND: The World Health Organization recommends routine cryptococcal antigen (CrAg) screening in advanced AIDS patients initiating antiretroviral treatment (ART). India has yet to adopt this strategy as the burden of cryptococcal antigenaemia is unknown. METHODS: A prospective study was conducted in a large public sector ART centre and the inpatient wards of Sassoon Hospital, Pune, India. All consenting patients> 18 years of age with CD4 count <100 cells/mm3 were screened for CrAg by latex agglutination assay. Those with positive CrAg underwent cerebrospinal fluid analysis, chest radiograph and abdominal ultrasound to rule out cryptococcal disease. The impact of CrAg positivity on all-cause mortality was assessed by logistic regression analysis. RESULTS: Amongst 208 AIDS patients with CD4 cells <100 cells/mm3 who underwent CrAg testing, median age was 40 (interquartile range [IQR], 35-49) years, 134 (64%) were male and median CD4 count was 64.5 cells/mm3 (IQR, 37-82). Overall, 16 (8%, 95% confidence interval [CI], 4-12) patients were positive for CrAg, of which 8 (50%) had CD4 cells <50 cells/mm3 and 3 (19%) CrAg-positive patients had incidental cryptococcal meningitis. At 6-month follow-up, the case fatality rate was higher amongst CrAg-positive patients (38%) compared with CrAg-negative patients (18%) (P = 0.06). After adjusting for age, sex, CD4 count and ART, there was a trend towards increased all-cause mortality (adjusted OR, 3.18, 95% CI, 0.60-16.88,P= 0.17). CONCLUSIONS: We found an 8% prevalence of cryptococcaemia amongst adult AIDS patients with CD4 cells <100 cells/mm3. Given the high fatality rates observed, routine screening for CrAg should be considered for all Indian persons with advanced HIV disease.

Quantitative IFN-γ and IL-2 Response Associated with Latent Tuberculosis Test Discordance in HIV-infected Pregnant Women.

RATIONALE: Pregnant women with latent tuberculosis infection (LTBI) are at high risk for development of TB, especially if infected with HIV. OBJECTIVES: To assess the performance of LTBI tests in pregnant and postpartum women infected with HIV, investigate the immunology behind discordance in pregnancy, and explore the implications for the development of postpartum TB. METHODS: We screened pregnant women in their second/third trimester and at delivery for LTBI using the tuberculin skin test (TST) and IFN-γ release assay (IGRA) (QuantiFERON Gold). A subset of antepartum women had longitudinal testing, with repeat testing at delivery and postpartum and additional cytokines measured from the IGRA supernatant. The kappa statistic and Wilcoxon rank sum test were used to determine agreement and comparison of cytokine concentrations, respectively. MEASUREMENTS AND MAIN RESULTS: Of 252 enrolled, 71 (28%) women had a positive IGRA but only 27 (10%) had a positive TST (P < 0.005). There was 75% agreement (kappa, 0.25). When stratified by pregnancy versus delivery, 20% had IGRA(+)/TST(-) discordance at each time point. A positive IGRA was associated with known TB contact (odds ratio, 3.6; confidence interval, 1.2-11.1; P = 0.02). Compared with IGRA(+)/TST(+), women with IGRA(+)/TST(-) discordance had significantly less IFN-γ (1.85 vs. 3.48 IU/ml; P = 0.02) and IL-2 (46.17 vs. 84.03 pg/ml; P = 0.01). Five developed postpartum TB, of which three had IGRA(+)/TST(-) discordance during pregnancy. CONCLUSIONS: Choice of LTBI test in pregnant women infected with HIV affects results. Pregnant women with IGRA(+)/TST(-) discordance had less IFN-γ and IL-2 than those with concordant-positive results and may represent an especially high-risk subset for the development of active TB postpartum.

Source Case Investigation for Children with TB Disease in Pune, India.

Setting. Contact tracing is broadly encouraged for tuberculosis (TB) control. In many high-burden countries, however, little effort is made to identify contacts of newly diagnosed TB patients. This failure puts children, many of whom live in poor crowded communities, at special risk. Objectives. To perform source-case investigations for 50 pediatric TB cases in Pune, India. Design. A descriptive cross-sectional observational study of pediatric TB cases < 5 years of age. Information was collected about the index case and household contacts. Results. In 15 (30%) of the 50 pediatric index cases, the household contained known TB contacts, 14 (86%) of whom were adults. Prior to their own diagnosis of TB, only one of the 15 pediatric index cases who met criteria for isoniazid preventive therapy received it. The index cases with known household TB contacts had a longer delay in initiating TB treatment than those without TB contacts (17.5 versus 2 days; P = 0.03). Use of contact tracing identified 14 additional household TB suspects, 8 (57%) of whom were children. Conclusions. This study identified missed opportunities for TB prevention, as contact tracing is poorly implemented in resource-limited countries, like India. Further strategies to improve the implementation of TB prevention, especially in young children, are urgently needed.

Pregnancy differentially impacts performance of latent tuberculosis diagnostics in a high-burden setting.

BACKGROUND: Targeted screening for latent TB infection (LTBI) in vulnerable populations is a recommended TB control strategy. Pregnant women are at high risk for developing TB and likely to access healthcare, making pregnancy an important screening opportunity in developing countries. The sensitivity of the widely-used tuberculin skin test (TST), however, may be reduced during pregnancy. METHODS: We performed a cross-sectional study comparing the TST with the QuantiFERON Gold In-tube (QGIT) in 401 HIV-negative women presenting antepartum (n = 154), at delivery (n = 148), or postpartum (n = 99) to a government hospital in Pune, India. A subset of 60 women enrolled during pregnancy was followed longitudinally and received both tests at all three stages of pregnancy. RESULTS: The QGIT returned significantly more positive results than the TST. Of the 401 women in the cross-sectional study, 150 (37%) had a positive QGIT, compared to 59 (14%) for the TST (p<0.005). Forty-nine (12%) did not have their TST read. Of 356 who had both results available, 46 (13%) were concordant positive, 91 (25%) were discordant (12 (3%) TST+/QGIT-; 79 (22%) TST-/QGIT+), and 206 (57%) concordant negative. Comparison by stage of pregnancy revealed that QGIT percent positivity remained stable between antepartum and delivery, unlike TST results (QGIT 31-32% vs TST 11-17%). Median IFN-γ concentration was lower at delivery than in antepartum or postpartum (1.66 vs 2.65 vs 8.99 IU/mL, p = 0.001). During postpartum, both tests had significantly increased positives (QGIT 31% vs 32% vs 52%, p = 0.01; TST 17% vs 11% vs 25%, p<0.005). The same trends were observed in the longitudinal subset. CONCLUSIONS: Timing and choice of LTBI test during pregnancy impact results. QGIT was more stable and more closely approximated the LTBI prevalence in India. But pregnancy stage clearly affects both tests, raising important questions about how the complex immune changes brought on by pregnancy may impact LTBI screening.

Correlates of premarital relationships among unmarried youth in Pune district, Maharashtra, India.

CONTEXT: Although premarital partnerships-whether or not they involve sex-are widely discouraged in India, some youth do form such partnerships. It is important to know more about the nature of and the factors associated with these relationships. METHODS: Data are drawn from a community-based study of 15-24-year-olds in urban slum and rural settings in Pune District, Maharashtra. Multivariate analyses were conducted to identify associations between youths' individual, peer and family factors and their experience of romantic relationships and physical intimacy, including intercourse. RESULTS: Among young men, 17-24% had had a romantic relationship, 20-26% had engaged in some form of physical intimacy and 16-18% had had sex; the proportions among young women were 5-8%, 4-6% and 1-2%, respectively. Exposure to alcohol, drugs or pornographic films and having more frequent interaction with peers were positively associated with romantic and sexual relationships for both young women and young men. Educational attainment was negatively associated with both types of relationships for young women, but only with sexual relationships for young men. Closeness to parents was negatively associated with relationships only for young women. Young women whose father beat their mother were more likely than other young women to form romantic partnerships, and those beaten by their family had an elevated risk of entering romantic and sexual partnerships. Youth who reported strict parental supervision were no less likely than others to enter relationships. CONCLUSIONS: Program interventions should ensure that youth are fully informed and equipped to make safe choices and negotiate wanted outcomes, while positively influencing their peer networks; encourage closer interaction between parents and children; and be tailored to the different circumstances and experiences of young women and men.

Romance and sex: pre-marital partnership formation among young women and men, Pune district, India.

Using qualitative and survey data in a rural and an urban slum setting in Pune district, India, this paper describes patterns of pre-marital romantic partnerships among young people aged 15-24, in spite of norms that discourage opposite-sex interaction before marriage. 25-40% of young men and 14-17% of young women reported opposite-sex friends. Most young people devised strategies to interact with others, largely from the same neighbourhood. There were wide gender differences with regard to making or receiving romantic proposals, having a romantic partner and experiencing hand-holding, kissing and sexual relations. For those who engaged in sexual relations, the time from the onset of the partnership to having sexual relations was short. Sex most often took place without protection or communication, and for a disturbing minority of young women only after persuasion or without consent. Among those who were unmarried, a large percentage had expected to marry their romantic partner, but for a third of young women and half of young men the relationship had been discontinued. Partnership formation often leads to physical intimacy, but intimacy should be wanted, informed and safe. Findings call for programmes that inform youth in non-threatening, non-judgmental and confidential ways, respect their sexual rights and equip them to make safe choices and negotiate wanted outcomes.