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India aims to eliminate rubella and congenital rubella syndrome (CRS) by 2023. We conducted serosurveys among pregnant women to monitor the trend of rubella immunity and estimate the CRS burden in India following a nationwide measles and rubella vaccination campaign. We surveyed pregnant women at 13 sentinel sites across India from Aug to Oct 2022 to estimate seroprevalence of rubella IgG antibodies. Using age-specific seroprevalence data from serosurveys conducted during 2017/2019 (prior to and during the vaccination campaign) and 2022 surveys (after the vaccination campaign), we developed force of infection (FOI) models and estimated incidence and burden of CRS. In 2022, rubella seroprevalence was 85.2% (95% CI: 84.0, 86.2). Among 10 sites which participated in both rounds of serosurveys, the seroprevalence was not different between the two periods (pooled prevalence during 2017/2019: 83.5%, 95% CI: 82.1, 84.8; prevalence during 2022: 85.1%, 95% CI: 83.8, 86.3). The estimated annual incidence of CRS during 2017/2019 in India was 218.3 (95% CI: 209.7, 226.5) per 100, 000 livebirths, resulting in 47,120 (95% CI: 45,260, 48,875) cases of CRS every year. After measles-rubella (MR) vaccination campaign, the estimated incidence of CRS declined to 5.3 (95% CI: 0, 21.2) per 100,000 livebirths, resulting in 1141 (95% CI: 0, 4,569) cases of CRS during the post MR-vaccination campaign period. The incidence of CRS in India has substantially decreased following the nationwide MR vaccination campaign. About 15% of women in childbearing age in India lack immunity to rubella and hence susceptible to rubella infection. Since there are no routine rubella vaccination opportunities for this age group under the national immunization program, it is imperative to maintain high rates of rubella vaccination among children to prevent rubella virus exposure among women of childbearing age susceptible for rubella. [ABSTRACT FROM AUTHOR]

Background: India has set a goal to eliminate measles and rubella/Congenital Rubella Syndrome (CRS) by 2023. Towards this goal, India conducted nationwide supplementary immunization activity (SIA) with measles-rubella containing vaccine (MRCV) targeting children aged between 9 months to <15 years and established a hospital-based sentinel surveillance for CRS. Reliable data about incidence of CRS is necessary to monitor progress towards the elimination goal. Methods: We conducted serosurveys in 2019–20 among pregnant women attending antenatal clinics of 6 hospitals, which were also sentinel sites for CRS surveillance, to estimate the prevalence of IgG antibodies against rubella. We systematically sampled 1800 women attending antenatal clinics and tested their sera for IgG antibodies against rubella. We used rubella seroprevalence data from the current survey and the survey conducted in 2017 among antenatal women from another 6 CRS surveillance sites to construct a catalytic models to estimate the incidence and burden of CRS. Result: The seroprevalence of rubella antibodies was 82.3% (95% CI: 80.4–84.0). Rubella seropositivity did not differ by age group and educational status. Based on the constant and age-dependent force of infection models, we estimated that the annual incidence of CRS in India was 225.58 per 100,000 live births (95% CI: 217.49–232.41) and 65.47 per 100,000 live births (95% CI: 41.60–104.16) respectively. This translated to an estimated 14,520 (95% CI: 9,225–23,100) and 50,028 (95% CI: 48,234–51,543) infants with CRS every year based on age-dependent and constant force of infection models respectively. Conclusions: Our findings indicated that about one fifth of women in the reproductive age group in India were susceptible for rubella. The estimates of CRS incidence will serve as a baseline to monitor the impact of MRCV SIAs, as well progress towards the elimination goal of rubella/CRS. Author summary: Rubella infection during the first trimester of pregnancy can affect fetus, resulting in spontaneous abortion, stillbirth or birth of a baby with a combination of birth defects known as congenital rubella syndrome (CRS). Vaccination with rubella containing vaccine (RCV) is recommended as one of the strategies for eliminating rubella/CRS. The Southeast Asia region has set a target to eliminate rubella/CRS by 2023. Towards this goal, India completed nationwide immunization campaigns using measles-rubella vaccine during 2017–19, targeting children aged 9 months to <15 years. A case-based surveillance for CRS was initiated in five sentinel hospitals (Phase-1) in 2016 and later expanded to additional 6 sites (Phase-2) in 2019, to estimate burden of CRS and monitor its trend. As an adjunct to CRS surveillance, periodic serologic surveys were also planned to monitor the rubella seroprevalence among the pregnant women. A serosurvey conducted in 2017 indicated that 83.4% pregnant women attending antenatal clinics of Phase-1 sentinel hospitals had IgG antibodies against rubella. The second serosurvey conducted during 2019–20 in 6 Phase-2 sites indicated a comparable seroprevalence of 82.3%. Using seroprevalence data from these two serosurveys, we estimated that the annual incidence of CRS in India was 225.58 per 100,000 live births with constant force of infection and 65.47 per 100,000 live births with age-dependent force of infection model. This incidence rates translated to an estimated 14,520 to 50,028 infants with CRS every year. The estimates of CRS incidence will serve as a baseline to monitor the progress towards the elimination goal of rubella/CRS in India. [ABSTRACT FROM AUTHOR]

Background: Patients with TB have additional nutritional requirements and thus additional costs to the household. Ni-kshay Poshan Yojana(NPY) is a Direct Benefit Transfer (DBT) scheme under the National Tuberculosis Elimination Programme(NTEP) in India which offers INR 500 monthly to all notified patients with TB for nutritional support during the period of anti-TB treatment. Five years after its implementation, we conducted the first nationwide evaluation of NPY. Methods: In our retrospective cohort study using programmatic data of patients notified with TB in nine randomly selected Indian states between 2018 and 2022, we estimated the proportion of patients who received at least one NPY instalment and the median time to receive the first instalment. We determined the factors associated (i) with non-receipt of NPY using a generalised linear model with Poisson family and log link and (ii) with time taken to receive first NPY benefit in 2022 using quantile regression at 50th percentile. Results: Overall, 3,712,551 patients were notified between 2018 and 2022. During this period, the proportion who received at least one NPY instalment had increased from 56.9% to 76.1%. Non-receipt was significantly higher among patients notified by private sector (aRR 2.10;2.08,2.12), reactive for HIV (aRR 1.69;1.64,1.74) and with missing/undetermined diabetic status (aRR 2.02;1.98,2.05). The median(IQR) time to receive the first instalment had reduced from 200(109,331) days in 2018 to 91(51,149) days in 2022. Patients from private sector(106.9;106.3,107.4days), those with HIV-reactive (103.7;101.8,105.7days), DRTB(104.6;102.6,106.7days) and missing/undetermined diabetic status (115.3;114,116.6days) experienced longer delays. Conclusions: The coverage of NPY among patients with TB had increased and the time to receipt of benefit had halved in the past five years. Three-fourths of the patients received at least one NPY instalment, more than half of whom had waited over three months to receive the first instalment. NTEP has to focus on timely transfer of benefits to enable patients to meet their additional nutritional demands, experience treatment success and avoid catastrophic expenditure. [ABSTRACT FROM AUTHOR]

Background: In 2022, India's national tuberculosis (TB) elimination program (NTEP) commissioned a national level evaluation of active case finding (ACF) for TB to guide evidence-based strategic planning. As part of this evaluation, based on secondary data analysis we observed that the quality of ACF was suboptimal in 2021. Hence, this study aimed to understand the enablers, barriers, and suggested solutions to improve ACF for TB in India from NTEP staff (provider) perspective. Methods: This was a descriptive qualitative study involving key informant interviews from six districts and eight states, conducted between February and August 2023. We purposively selected key state- district- and sub-district-level program managers and implementers who were experienced and vocal. The interviews were audio recorded and transcribed verbatim by research interns and investigators. Two investigators independently did manual descriptive thematic analysis, and a third investigator resolved inconsistencies. The themes and categories emerged by collating together the results of the coding process. Results: A total of 34 key informant interviews were conducted and of these, four were repeat interviews. Adequate budgets for ACF including incentives, performance review mechanism, engagement of all stakeholders, adopting a community friendly approach, use of rapid diagnostic tests and digitalization were the perceived enablers. In some states ACF was implemented in general population (not restricted to high-risk population) following directives at state level. There were limited mechanisms to ensure ACF quality indicators were met before disbursing incentives and cross-verification of the aggregate ACF care cascade numbers that were reported in Ni-kshay (electronic TB information management system under NTEP). In addition to the state and district level implementers having limited understanding of concepts around ACF (quality indicators, number needed to screen and yield), we also inferred the presence of a 'know-do' gap for many activities under ACF. The suggested solutions were around capacity building and quality improvement strategies. Conclusion: The existing national ACF guidance should be revised to emphasize capacity building, need to carry out ACF in high-risk (not general) population, quality control-linked incentives, and regular implementation monitoring of the activities. This should contribute towards better coverage and improved quality translating into better ACF outcomes. [ABSTRACT FROM AUTHOR]

Background: Ni-kshay Poshan Yojana (NPY) is a direct benefit transfer scheme of the Government of India introduced in 2018 to support the additional nutritional requirements of persons with TB (PwTB). Our recent nationwide evaluation of implementation and utilization of NPY using programmatic data of PwTB from nine randomly selected Indian states, reported a 70% coverage and high median delay in benefit credit. We undertook a qualitative study between January and July 2023, to understand the detailed implementation process of NPY and explore the enablers and barriers to effective implementation and utilization of the NPY scheme. Methods: We followed a grounded theory approach to inductively develop theoretical explanations for social phenomena through data generated from multiple sources. We conducted 36 in-depth interviews of national, district and field-level staff of the National Tuberculosis Elimination Programme (NTEP) and NPY beneficiaries from 30 districts across nine states of India, selected using theoretical sampling. An analytical framework developed through inductive coding of a set of six interviews, guided the coding of the subsequent interviews. Categories and themes emerged through constant comparison and the data collection continued until theoretical saturation. Results: Stakeholders perceived NPY as a beneficial initiative. Strong political commitment from the state administration, mainstreaming of NTEP work with the district public healthcare delivery system, availability of good geographic and internet connectivity and state-specific grievance redressal mechanisms and innovations were identified as enablers of implementation. However, the complex, multi-level benefit approval process, difficulties in accessing banking services, perceived inadequacy of benefits and overworked human resources in the NTEP were identified as barriers to implementation and utilization. Conclusion: The optimal utilization of NPY is enabled by strong political commitment and challenged by its lengthy implementation process and delayed disbursal of benefits. We recommend greater operational simplicity in NPY implementation, integrating NTEP activities with the public health system to reduce the burden on the program staff, and revising the benefit amount more equitably. [ABSTRACT FROM AUTHOR]

Introduction: Relapse of leprosy among patients released from treatment (RFT) is an indicator of the success of anti-leprosy treatment. Due to inadequate follow-up, relapse in leprosy patients after RFT is not systematically documented in India. Relapsed leprosy patients pose a risk in the transmission of leprosy bacilli. We determined the incidence of relapse and deformity among the patients RFT from the leprosy control programme in four districts in South India. Methods: We conducted two follow-up surveys in 2012 and 2014 among the leprosy patients RFT between 2005 and 2010. We assessed them for any symptoms or signs of relapse, persistence and deformity. We collected slit skin samples (SSS) for smear examination. We calculated overall incidence of relapse and deformity per 1000 person-years (PY) with 95% confidence intervals (CI) and cumulative risk of relapse. Results: Overall, we identified 69 relapse events, 58 and 11, during the first and second follow-up surveys, respectively. The incidence of relapse was 5.42 per 1000 PY, which declined over the years after RFT. The cumulative risk of relapse was 2.24%. The rate of deformity among the relapsed patients was 30.9%. The overall incidence of deformity was 1.65 per 1000 person years. The duration of M. leprae detection in smears ranged between 2.38 and 7.67 years. Conclusions: Low relapse and deformity rates in leprosy RFT patients are indicative of treatment effectiveness. However, a higher proportion of detection of deformity among relapsed cases is a cause for concern. Periodic follow-up of RFT patients for up to 3 years to detect relapses early and ensure appropriate treatment will minimize the development of deformity among relapsed patients. Author summary: India achieved leprosy elimination (<1 case/10000 population) in 2005. However, it remains a country with a high burden of leprosy (120,334 cases in 2017–18), with an annual detection of more than 10000 new cases, including children, indicating widespread active transmission. In addition to the untreated leprosy cases, even patients who relapse after release from leprosy treatment play a significant role in disease transmission. Early detection and management of leprosy relapse cases will minimize the disease transmission and might prevent leprosy-associated deformity. Leprosy management services are primarily provided by the government healthcare system in India and supported by several major non-governmental charitable organizations. The burden of leprosy relapse in India cannot be measured since there is no provision to follow-up the patients who complete multi-drug treatment (MDT) in the national leprosy program. We report the incidence of leprosy relapse among the patients who completed leprosy treatment from the national leprosy control program in four districts in South India. The report also highlights the effectiveness of MDT in program settings, the lower risk of developing deformity after treatment completion, and the need to incorporate an appropriately designed follow-up strategy. [ABSTRACT FROM AUTHOR]

Introduction: Rubella is an important infectious, vaccine-preventable etiology of congenital defects. The aim of the study was to develop a prediction nomogram to assess the probability of an infant being at risk for congenital rubella based on demographics and ophthalmological findings. Methods: This was a cross-sectional sentinel surveillance study conducted at 5 centers spanning pan-India and involved 1134 infants. The diagnosis of rubella was made using standard guidelines. For the construction of the prediction model, laboratory-confirmed cases were grouped as "at-risk" (AR) infants and the discarded cases into "not at risk" (NAR) infants. Univariate analysis (p value cut-off < 0.05) followed by multivariate binary logistic regression model development was performed. Results: The average (median) age of the suspected CRS infants was 3 (IQR 1–6) months, and the average (mean) age of their mothers was 25.8 ± 4.1 years. Out of the total infants, 81 (7.3%) died, 975 (88%) were alive, and 55 (5.0%) were lost to follow-up. The final model showed that the odds of cataract, retinopathy, glaucoma, microcornea, and age of the infant at presentation were 3.1 (2.2–4.3), 4.9(2.3–10.4), 2.7(1.1–5.9), 2.3(1.1–4.7), and 1.1 (1–1.1), respectively, for the AR infant as compared to NAR infant. AUC of final model was 0.68 (95% CI Delong, 0.64–0.72). Bootstrapping for calibration of the model showed satisfactory results. Nomogram, along with a web version, was developed. Conclusion: The developed nomogram would have a wide community-based utilization and will help in prioritizing attention to high-risk children, thereby avoiding loss to follow-up. [ABSTRACT FROM AUTHOR]

Background: Government of India is committed to eliminate measles and control rubella/congenital rubella syndrome (CRS) by 2020. In 2016, CRS surveillance was established in five sentinel sites. We analyzed surveillance data to describe the epidemiology of CRS in India. Methodology/Principal findings: We used case definitions adapted from the WHO-recommended standards for CRS surveillance. Suspected patients underwent complete clinical examination including cardiovascular system, ophthalmic examination and assessment for hearing impairment. Sera were tested for presence of IgM and IgG antibodies against rubella. Of the 645 suspected CRS patients enrolled during two years, 137 (21.2%) were classified as laboratory confirmed CRS and 8 (1.2%) as congenital rubella infection. The median age of laboratory confirmed CRS infants was 3 months. Common clinical features among laboratory confirmed CRS patients included structural heart defects in 108 (78.8%), one or more eye signs (cataract, glaucoma, pigmentary retinopathy) in 82 (59.9%) and hearing impairment in 51. (38.6%) Thirty-three (24.1%) laboratory confirmed CRS patients died over a period of 2 years. Surveillance met the quality indicators in terms of adequacy of investigation, adequacy of sample collection for serological diagnosis as well as virological confirmation. Conclusions/Significance: About one fifth suspected CRS patients were laboratory confirmed, indicating significance of rubella as a persistent public health problem in India. Continued surveillance will generate data to monitor the progress made by the rubella control program in the country. Author summary: Rubella infection during the first trimester of pregnancy can affect the fetus, resulting in spontaneous abortion, stillbirth or an infant born with a combination of birth defects known as congenital rubella syndrome (CRS). Government of India is committed to eliminate measles and control rubella/CRS and has completed nationwide immunization campaigns using measles-rubella vaccine targeting children aged 9 months to 14 years. A case-based surveillance for CRS is one of the strategies for achieving elimination. The Indian Council of Medical Research and the Ministry of Health and Family Welfare initiated surveillance for CRS in five sentinel sites to estimate the disease burden. During 2016–18, the surveillance sites enrolled 645 suspected CRS patients, 137 (21.2%) were classified as laboratory confirmed CRS and 8 (1.2%) as congenital rubella infection. Common clinical features among laboratory confirmed CRS patients included structural heart defects (78.8%), one or more eye signs (cataract, glaucoma, pigmentary retinopathy (59.9%)) and hearing impairment (38.6%). Thirty-three (24.1%) laboratory confirmed CRS patients died over a period of 2 years. The surveillance data indicated significance of rubella as persistent public health problem in India. [ABSTRACT FROM AUTHOR]

Systemic lupus erythematosus (SLE) and other autoimmune rheumatic diseases (AIRD) tend to co-aggregate in families, making positive familial history a risk factor. We aimed to estimate familial aggregation of AIRD in SLE patients and to compare between ones having a positive and negative family history of autoimmunity in our cohort. We included families of 157 consecutive SLE patients in a hospital-based, cross-sectional design for a three-generation pedigree study. Clinical and laboratory parameters of these patients were recorded. AIRD was seen in families of 39 SLE patients amounting to a familial prevalence of 24.8% [95% confidence interval (CI) 18.1, 31.6] with a relative risk (λ) of 4.3 for first-degree relatives (FDRs) and 1.1 for second-degree relatives (SDRs). SLE was the commonest AIRD seen in families of 19 patients with a familial prevalence of 12.1% (95% CI 7.0, 17.2) and λ of 78.2 for FDRs and 18.1 for SDRs. AIRD as a whole and SLE alone were seen more commonly with parental consanguinity (p < 0.05). Familial aggregation in SLE patients also showed a relatively higher percentage of affected males and lesser presentation with constitutional features (p < 0.05) than sporadic SLE patients. Rheumatoid arthritis (RA) was the second most common AIRD seen in 16/39 (41%) families with a RR of 3.1 in FDRs of SLE patients. In conclusion, Asian Indian SLE patients seem to have a high familial aggregation of AIRD, which is more pronounced in the background of parental consanguinity. SLE is the commonest AIRD seen amongst FDRs and SDRs of SLE patients, followed by RA, with FDRs being at highest risk. [ABSTRACT FROM AUTHOR]

Background: Hemangiopericytomas (HPCs) and solitary fibrous tumors (SFTs) are unique entities in the central nervous system (CNS) and even rarer in the spine with propensity to recurrence and metastasis. Both these tumors were detected to share the NAB2-STAT6 fusion gene with frequent morphologic overlap that necessitated the need for the combined term SFT/HPC in the CNS by the World Health Organization (WHO) in 2016.Aims: This study aims to describe the clinical outcome of intracranial and spinal SFT/HPCs based on detailed histomorphologic and immunohistochemical features.Materials and Methods: A retrospective analysis of these tumors was conducted over a period of 10 years from January 2006 to January 2017 at our institute. Based on the elaborative assessment of morphology and immunohistochemistry, these tumors were categorized into three grades as per WHO criteria.Results: A total of 13 cases were encountered involving mainly extra-axial and supratentorial regions. Among intracranial HPCs, anaplastic subtypes constituted significantly higher proportion (39%) when compared with peripheral HPCs. Peculiar morphological patterns like micropapillae and pseudoangiomatous arrangement of tumor cells were observed in high-grade tumors. A panel of immunomarkers were used to confirm the diagnosis and rule out other mimickers. Gross total resection was achieved in 54% (7/13) of the cases with local recurrence observed in 31% (4/13). Grade II tumors showed recurrence in 28% cases. No case showed distant metastasis.Conclusion: To conclude, not just clinical parameters but morphologic features such as unusual patterns, mitosis, and proliferative index also play a pivotal role in predicting the clinical behaviour of SFT/HPC. [ABSTRACT FROM AUTHOR]

Background: Pesticide suicides are considered the single most important means of suicide worldwide. Centralized pesticide storage facilities have the possible advantage of delaying access to pesticides thereby reducing suicides. We undertook this study to examine the feasibility and acceptability of a centralized pesticide storage facility as a preventive intervention strategy in reducing pesticide suicides. Methods: A community randomized controlled feasibility study using a mixed methods approach involving a household survey; focus group discussions (FGDs) and surveillance were undertaken. The study was carried out in a district in southern India. Eight villages that engaged in floriculture were identified. Using the lottery method two were randomized to be the intervention sites and two villages constituted the control site. Two centralized storage facilities were constructed with local involvement and lockable storage boxes were constructed. The household survey conducted at baseline and one and a half years later documented information on sociodemographic data, pesticide usage, storage and suicides. Results: At baseline 4446 individuals (1097 households) in the intervention and 3307 individuals (782 households) in the control sites were recruited while at follow up there were 4308 individuals (1063 households) in the intervention and 2673 individuals (632 households) in the control sites. There were differences in baseline characteristics and imbalances in the prevalence of suicides between intervention and control sites as this was a small feasibility study. The results from the FGDs revealed that most participants found the storage facility to be both useful and acceptable. In addition to protecting against wastage, they felt that it had also helped prevent pesticide suicides as the pesticides stored here were not as easily and readily accessible. The primary analyses were done on an Intention to Treat basis. Following the intervention, the differences between sites in changes in combined, completed and attempted suicide rates per 100,000 person-years were 295 (95% CI: 154.7, 434.8; p < 0.001) for pesticide suicide and 339 (95% CI: 165.3, 513.2, p < 0.001) for suicide of all methods. Conclusions: Suicide by pesticides poisoning is a major public health problem and needs innovative interventions to address it. This study, the first of its kind in the world, examined the feasibility of a central storage facility as a means of limiting access to pesticides and, has provided preliminary results on its usefulness. These results need to be interpreted with caution in view of the imbalances between sites. The facility was found to be acceptable, thereby underscoring the need for larger studies for a longer duration. [ABSTRACT FROM AUTHOR]

Background: This multi-center study from India details the profile and outcomes of patients admitted to the intensive care unit (ICU) with pandemic Influenza A (H1N1) 2009 virus [P(H1N1)2009v] infection. Materials and Methods: Over 4 months, adult patients diagnosed to have P(H1N1)2009v infection by real-time RT-PCR of respiratory specimens and requiring ICU admission were followed up until death or hospital discharge. Sequential organ failure assessment (SOFA) scores were calculated daily. Results: Of the 1902 patients screened, 464 (24.4%) tested positive for P(H1N1)2009v; 106 (22.8%) patients aged 35±11.9 (mean±SD) years required ICU admission 5.8±2.7 days after onset of illness. Common symptoms were fever (96.2%), cough (88.7%), and breathlessness (85.9%). The admission APACHE-II and SOFA scores were 14.4±6.5 and 5.5±3.1, respectively. Ninety-six (90.6%) patients required ventilation for 10.1±7.5 days. Of these, 34/96 (35.4%) were non-invasively ventilated; 16/34 were weaned successfully whilst 18/34 required intubation. Sixteen patients (15.1%) needed dialysis. The duration of hospitalization was 14.0±8.0 days. Hospital mortality was 49%. Mortality in pregnant/puerperal women was 52.6% (10/19). Patients requiring invasive ventilation at admission had a higher mortality than those managed with non-invasive ventilation and those not requiring ventilation (44/62 vs. 8/44, P<0.001). Need for dialysis was independently associated with mortality (P=0.019). Although admission APACHE-II and SOFA scores were significantly (P<0.02) higher in non-survivors compared with survivors on univariate analysis, individually, neither were predictive on multivariate analysis. Conclusions: In our setting, a high mortality was observed in patients admitted to ICU with severe P(H1N1)2009v infection. The need for invasive ventilation and dialysis were associated with a poor outcome. [ABSTRACT FROM AUTHOR]