Development of the India COVID-19 vaccine tracker

COVID-19 was declared a pandemic by the World Health Organization (WHO) on March 11, 2020. Since then, efforts were initiated to develop safe and effective vaccines. Till date, 11 vaccines have been included in the WHO’s emergency use list. The emergence and spread of variant strains of SARS-CoV-2 has altered the disease transmission dynamics, thus creating a need for continuously monitoring the real-world effectiveness of various vaccines and assessing their overall impact on disease control. To achieve this goal, the Indian Council of Medical Research (ICMR) along with the Ministry of Health and Family Welfare, Government of India, took the lead to develop the India COVID-19 Vaccination Tracker by synergizing three different public health databases: National COVID-19 testing database, CoWIN vaccination database and the COVID-19 India portal. A Vaccine Data Analytics Committee (VDAC) was constituted to advise on various modalities of the proposed tracker. The VDAC reviewed the data related to COVID-19 testing, vaccination and patient outcomes available in the three databases and selected relevant data points for inclusion in the tracker, following which databases were integrated, using common identifiers, wherever feasible. Multiple data filters were applied to retrieve information of all individuals ?18 yr who died after the acquisition of COVID-19 infection with or without vaccination, irrespective of the time between vaccination and test positivity. Vaccine effectiveness (VE) against the reduction of mortality and hospitalizations was initially assessed. As compared to the hospitalization data, mortality reporting was found to be much better in terms of correctness and completeness. Therefore, hospitalization data were not considered for analysis and presentation in the vaccine tracker. The vaccine tracker thus depicts VE against mortality, calculated by a cohort approach using person-time analysis. Incidence of COVID-19 deaths among one- and two-dose vaccine recipients was compared with that among unvaccinated groups, to estimate the rate ratios (RRs). VE was estimated as 96.6 and 97.5 per cent, with one and two doses of the vaccines, respectively, during the period of reporting. The India COVID-19 Vaccination Tracker was officially launched on September 9, 2021. The high VE against mortality, as demonstrated by the tracker, has helped aid in allaying vaccine hesitancy, augmenting and maintaining the momentum of India’s COVID-19 vaccination drive

Pediatric Appropriate Evaluation Protocol for India (PAEP-India): Tool for Assessing Appropriateness of Pediatric Hospitalization

Objectives: To develop and assess Pediatric AppropriatenessEvaluation Protocol for India (PAEP-India) for inter-rater reliabilityand appropriateness of hospitalization.Design: Cross-sectional study.Setting: The available PAEP tools were reviewed and adaptedfor Indian context by ten experienced pediatricians followingsemi-Delphi process. Two PAEP-India tools; newborn (?28 days)and children (>28 days-18 years) were developed. These PAEP-India tools were applied to cases to assess appropriateness ofadmission and inter-rater reliability between assessors.Participants: Two sets of case records were used: (i) 274cases from five medical colleges in Delhi-NCR [?28 days (n=51);>28 days to 18 years (n=223)]; (ii) 622 infants who werehospitalized in 146 health facilities and were part of a cohort (n=30688) from two southern Indian states.Interventions: Each case-record was evaluated by twopediatricians in a blinded manner using the appropriate PAEP-India tools, and ‘admission criteria’ were categorized asappropriate, inappropriate or indeterminate.Main outcome measures: The proportion of appropriatehospitalizations and inter-rater reliability between assessors(using kappa statistic) were estimated for the cases.Results: 97.8% hospitalized cases from medical colleges werelabelled as appropriate by both reviewers with inter-rateragreement of 98.9% (k=0.66). In the southerm Indian set ofinfants, both reviewers labelled 80.5% admissions as appropriatewith inter-rater agreement of 96.1% (k= 0.89).Conclusions: PAEP-India (newborn and child) tools are simple,objective and applicable in diverse settings and highly reliable.These tools can potentially be used for deciding admissionappropriateness and hospital stay and may be evaluated later forusefulness for cost reimbursements for insurance proposes.

INCLEN Diagnostic Tool for Neuromotor Impairments (INDT-NMI) for Primary Care Physician: Development and Validation.

Objectives: To develop and validate a diagnostic tool for use by primary care physicians for diagnosing neuro-motor impairment among 2-9 year old children in primary care settings. Study design: Modified Delphi technique involving national (n=49) and international (n=6) experts was used for development of INDT-NMI. The tool was then validated through a cross sectional study. Setting: Neurology specialty clinics of three tertiary care pediatric centers in New Delhi, India. Participants: 454 children aged 2-9 years [mean (SD) age: 60.4 (23.7) mo], selected through systematic random sampling, underwent assessment for identification and classification of neuromotor impairments (NMI). Intervention: All study subjects were first administered INDTNMI (candidate test) by a trained physician followed by expert assessment for NMI and other neurodevelopment disorders (NDD) by team of two pediatric neurologists (Gold standard). Results: According to expert evaluation, 171 (37.8%) children had neuromotor impairments. There were four categories of subjects: NMI alone (n=66); NMI+other NDDs (n=105); Other NDDs without NMI (n=225) and ‘Normal’ group (n=58). Using expert evaluation as gold standard, overall sensitivity of the INDTNMI was 75.4% and specificity was 86.8%. INDT-NMI helped graduate physicians to correctly classify 86.6% (112/129) children with NMI into different types (cerebral palsy, neuromotor diseases and other NMI). Graduate physicians assigned 40 children (8.8%) as ‘indeterminate’, 38 (95%) of whom had either NDD and/or NMI and thus merited referral. Misclassification of NMI occurred in those with mild changes in muscle tone, dystonia, or ataxia and associated NDDs. Conclusion: Graduate primary care physicians with a structured short training can administer the new tool and diagnose NMI in 2-9 year old children with high validity. INDT-NMI requires further evaluation in actual primary care settings.

INCLEN Diagnostic Tool for Epilepsy (INDT-EPI) for Primary Care Physicians: Development and Validation.

Objective: To evaluate the diagnostic accuracy of a new diagnostic instrument for epilepsy – INCLEN Diagnostic Tool for Epilepsy (INDT-EPI) – with evaluation by expert pediatric neurologists. Study design: Evaluation of diagnostic test. Setting: Tertiary care pediatric referral centers in India. Methods: Children aged 2-9 years, enrolled by systematic random sampling at pediatric neurology out-patient clinics of three tertiary care centers were independently evaluated in a blinded manner by primary care physicians trained to administer the test, and by teams of two pediatric neurologists. Outcomes: A 13-item questionnaire administered by trained primary care physicians (candidate test) and comprehensive subject evaluation by pediatric neurologists (gold standard). Results: There were 240 children with epilepsy and 274 without epilepsy. The candidate test for epilepsy had sensitivity and specificity of 85.8% and 95.3%; positive and negative predictive values of 94.0% and 88.5%; and positive and negative likelihood ratios of 18.25 and 0.15, respectively. Conclusion: The INDT-EPI has high validity to identify children with epilepsy when used by primary care physicians.

INCLEN Diagnostic Tool for Attention Deficit Hyperactivity Disorder (INDT-ADHD): Development and Validation.

Objective: To develop and validate INCLEN Diagnostic Tool for Attention Deficit Hyperactivity Disorder (INDT-ADHD). Design: Diagnostic test evaluation by cross sectional design. Setting: Tertiary care pediatric centers. Participants: 156 children aged 65-117 months. Methods: After randomization, INDT-ADHD and Connor’s 3 Parent Rating Scale (C3PS) were administered, followed by an expert evaluation by DSM-IV-TR diagnostic criteria. Main outcome measures: Psychometric evaluation of diagnostic accuracy, validity (construct, criterion and convergent) and internal consistency. Results: INDT-ADHD had 18 items that quantified symptoms and impairment. Attention deficit hyperactivity disorder was identified in 57, 87 and 116 children by expert evaluation, INDT-ADHD and C3PS, respectively. Psychometric parameters of INDT-ADHD for differentiating attention deficit hyperactivity disorder and normal children were: sensitivity 87.7%, specificity 97.2%, positive predictive value 98.0% and negative predictive value 83.3%, whereas for differentiating from other neuro-developmental disorders were 87.7%, 42.9%, 58.1% and 79.4%, respectively. Internal consistency was 0.91. INDT-ADHD has a 4-factor structure explaining 60.4% of the variance. Convergent validity with Conner’s Parents Rating Scale was moderate (r =0.73, P= 0.001). Conclusions: INDT-ADHD is suitable for diagnosing attention deficit hyperactivity disorder in Indian children between the ages of 6 to 9 years.

INCLEN Diagnostic Tool for Autism Spectrum Disorder (INDT-ASD): Development and Validation.

Objective: To develop and validate INCLEN Diagnostic Tool for Autism Spectrum Disorder (INDT-ASD). Design: Diagnostic test evaluation by cross sectional design Setting: Four tertiary pediatric neurology centers in Delhi and Thiruvanthapuram, India. Methods: Children aged 2-9 years were enrolled in the study. INDT-ASD and Childhood Autism Rating Scale (CARS) were administered in a randomly decided sequence by trained psychologist, followed by an expert evaluation by DSM-IV TR diagnostic criteria (gold standard). Main outcome measures: Psychometric parameters of diagnostic accuracy, validity (construct, criterion and convergent) and internal consistency. Results: 154 children (110 boys, mean age 64.2 mo) were enrolled. The overall diagnostic accuracy (AUC=0.97, 95% CI 0.93, 0.99; P<0.001) and validity (sensitivity 98%, specificity 95%, positive predictive value 91%, negative predictive value 99%) of INDT-ASD for Autism spectrum disorder were high, taking expert diagnosis using DSM-IV-TR as gold standard. The concordance rate between the INDT-ASD and expert diagnosis for ‘ASD group’ was 82.52% [Cohen’s κ=0.89; 95% CI (0.82, 0.97); P=0.001]. The internal consistency of INDT-ASD was 0.96. The convergent validity with CARS (r = 0.73, P= 0.001) and divergent validity with Binet-Kamat Test of intelligence (r = -0.37; P=0.004) were significantly high. INDT-ASD has a 4-factor structure explaining 85.3% of the variance. Conclusion: INDT-ASD has high diagnostic accuracy, adequate content validity, good internal consistency high criterion validity and high to moderate convergent validity and 4-factor construct validity for diagnosis of Autistm spectrum disorder.

Alpha 1 Antitrypsin Deficiency in Children with Chronic Liver Disease in North India.

Objective: We attempted to determine the role of alpha-1- antitrypsin (AAT) deficient variants as an etiologic factor for chronic liver disease in North Indian children. Design: This study investigated 1700 children (682 retrospectively and 1018 prospectively) (840 CLD, 410 neonatal cholestasis and 450 without liver disease) for AAT deficiency. Setting: Tertiary referral center, All India Institute of Medical Sciences, New Delhi. Patients: Of 1250 liver disease patients, 98 (7.8%) were suspected to be AAT deficient on the basis of screening tests (low serum AAT levels and/or absent/faint alpha-1- globulin band on serum agarose electrophoresis and/or diastase resistant PAS positive granules on liver biopsy). Main outcome measures: AAT deficient Z or S allele in suspected patients. Results: Z or S allele was not observed on phenotyping (1700 subjects), or with PCR-RFLP, SSCP and sequencing done in 50 of 98 suspected AAT deficient patients. A novel mutation G-to-A at position 333 in exon V was found in two siblings having positive immunohistochemistry for AAT on liver biopsy, both of whom had significant liver disease with portal hypertension. Conclusion: In conclusion, AAT deficiency as an etiologic factor for chronic liver disease in childhood appeared to be uncommon in North India.

Infantile Hookworm Disease.

Hookworm infection is common but has rarely been reported in neonates or infants. Two cases of hookworm infestation in early infancy are described. The infants presented with malena, severe pallor, lethargy and failure to gain weight. Initial stool examination was non-contributory and diagnosis was made by upper gastrointestinal endoscopy

Deconstructing social resistance to pulse polio campaign in two north indian districts.

Objective: To gain an insight into the phenomenon of social resistance and rumors against pulse polio campaign. Design: Qualitative, community-based investigation, mapping perceptions of various stakeholders through in-depth interviews (IDIs), focus group discussions (FGDs), non-formal interactions and observations. Setting: Moradabad and JP Nagar districts of Uttar Pradesh. Subjects: IDIs (providers 33, mothers 33, community leaders 10); FGDs (providers 4, mothers 8) and non-formal interactions (156) with community leaders, parents, businessmen, journalists (Hindi and Urdu media), mobilizers, vaccinators and supervisors. Results: A distinct machination of social resistance and rumors against oral polio vaccine during supplementary immunization activities (SIA) was observed in some minority dominated areas. The pattern can be understood through a model that emerged through qualitative evidence. Inspite of all this, most parents in minority areas supported the SIAs. Only a few clusters from extremely marginalized sections continued to evade SIAs, with an endemic pattern. Through social osmosis, these rumors reached majority community as well and some parents were affected. However, in such cases, the resistance was sporadic and transient. Conclusion: While the program’s focus was on microbiological issues, the obstacles to polio eradication lie in the endemicity of social (and/or cultural) resistance in some pockets, leading to clustering of perpetually unimmunized children - inspite of good coverage of SIAs at macro level. This may sustain low levels of wild poliovirus transmission, and there can be exceptions to the robustness of the pulse approach. A micro level involvement of volunteers from marginalized pockets of minorities might be able to minimize or eliminate this resistance.

Non-alcoholic fatty liver disease and childhood obesity.

Obesity has emerged as a significant global health problem in the pediatric population. Pediatric liver disease is a serious complication of childhood obesity. Non-alcoholic steatohepatitis (NASH) is an entity in the spectrum of non-alcoholic fatty liver disease (NAFLD) ranges from fat in the liver--simple steatosis, NASH/ steatohepatitis--fat with in.ammation and/or fibrosis to advanced fibrosis and cirrhosis when fat may no longer be present. NASH is associated with obesity, diabetes, insulin resistance (IR), and hypertriglyceridemia. Children get NAFLD, and the incidence of this pediatric liver disease is rising as childhood obesity becomes increasingly prevalent. Although much remains to be learned about pediatric NAFLD, it is already evident that children with NASH risk progressive liver damage, including cirrhosis. Liver biopsy is required for definitive diagnosis, and other causes of fatty liver in childhood must be excluded. Gradual weight loss through increased regular exercise and a low-fat, low-refined carbohydrate diet appears to be effective. Drug treatments are being developed. The important message is that childhood obesity poses important health problems, including but not limited to potentially severe chronic liver disease. Early diagnosis of children who are only overweight is a worthy goal so that strategies to limit obesity can be instituted as early as possible. Identification of genetic risks is important, but management will invariably require changes in environmental factors. In addition to individual treatment, a multifaceted, societal initiative is required for solving the childhood obesity epidemic.

Cost of curative pediatric services in a public sector setting.

OBJECTIVE: To estimate the cost of ambulatory (out-patient) and in-patient pediatric health services for the year 1999 provided by All India Institute of Medical Sciences (AIIMS) at all the three levels-primary, secondary and tertiary level. METHODS: The costing module developed by Children's Vaccines Initiative (CVI) was used. This rapid assessment tool focuses on collection of data at macro level by using key informants like doctors, nursing staff, accountant, store keeper, engineer etc. Cost per beneficiary was estimated separately for in-patients and out-patients and was calculated by dividing the total cost of the services by the number of beneficiaries for the year 1999. For the out-patient, the beneficiaries were the total out-patient attendees and for the in-patient, it was the total pediatric admissions multiplied by mean duration of stay in days. RESULTS: The cost per out-patient visit was INR.20.2 (US0.44 dollars@1US dollars=INR.46) at primary level, higher than INR14.5 (US0.31 dollars) at the secondary level, while at tertiary level it was INR 33.8 (US 0.73 dollars). At the primary and secondary level, non-physician cost was more than the physician cost, and for tertiary level, physician cost was much higher than the other costs. There were no in-patient services at primary level. The cost of in-patient services at secondary level was estimated as INR 419.30 (US 9.1 dollars) per patient per day with a bed occupancy rate of 60%. Two-fifths of the cost was due to nursing and other supportive staff and one fifth due to the doctor costs and overhead costs. The unit cost of INR 928 (US 20.2 dollars) per patient per day incurred at AIIMS with a bed occupancy rate of 100% was almost twice that of secondary level. In contrast to the secondary level, almost half the total costs at tertiary level was due to the doctors costs. CONCLUSIONS: Effective use of resources at lower level of care especially ambulatory care at primary level and inpatient care at secondary level can result in much higher savings for the system and also, the society. These would need to be appropriately strengthened.