The Immunogenicity of Monovalent Oral Poliovirus Vaccine Type 1 (mOPV1) and Inactivated Poliovirus Vaccine (IPV) in the EPI Schedule of India.

BACKGROUND: In 2016, the Global Polio Eradication Initiative (GPEI) recommended the cessation of using type 2 oral poliovirus vaccine (OPV) and OPV, with countries having to switch from the trivalent to bivalent OPV (bOPV) with the addition of inactivated poliovirus vaccine (IPV) in their routine immunization schedule. The current GPEI strategy 2022-2026 includes a bOPV cessation plan and a switch to IPV alone or a combination of vaccine schedules in the future. The focus of our study was to evaluate the immunogenicity of monovalent OPV type 1 (mOPV1) with IPV and IPV-only schedules. METHODS: This was a three-arm, multi-center randomized-controlled trial conducted in 2016-2017 in India. Participants, at birth, were randomly assigned to the bOPV-IPV (Arm A) or mOPV1-IPV (Arm B) or IPV (Arm C) schedules. Serum specimens collected at birth and at 14, 18, and 22 weeks old were analyzed with a standard microneutralization assay for all the three poliovirus serotypes. RESULTS: The results of 598 participants were analyzed. The type 1 cumulative seroconversion rates four weeks after the completion of the schedule at 18 weeks were 99.5% (97.0-99.9), 100.0% (97.9-100.0), and 96.0% (92.0-98.1) in Arms A (4bOPV + IPV), B (4mOPV1 + IPV), and C (3IPV), respectively. Type 2 and type 3 seroconversions at 18 weeks were 80.0% (73.7-85.1), 76.9% (70.3-82.4); 93.2% (88.5-96.1), 100.0% (98.0-100.0); and 81.9% (75.6-86.8), 99.4% (96.9-99.9), respectively, in the three arms. CONCLUSIONS: This study shows the high efficacy of different polio vaccines for serotype 1 in all three schedules. The type 1 seroconversion rate of mOPV1 is non-inferior to bOPV. All the vaccines provide high type-specific immunogenicity. The program can adopt the use of different vaccines or schedules depending on the epidemiology from time to time.

Postnatal Growth at 64 Weeks Postmenstrual Age in Preterm Infants Delivered at ≤ 34 Weeks' Gestation: A Single Center Study.

OBJECTIVE: To study the postnatal growth at 64 weeks postmenstrual age (PMA) in preterm neonates born at ≤ 34 weeks gestational age. METHODS: A cross-sectional study was conducted between August, 2019 and November, 2021, wherein, we took anthropometric measurements of neonates (delivered at ≤ 34 weeks' gestation) at 64 (± 2) weeks PMA. The rapidity of postnatal growth was categorized according to change in the z-score of anthropometric measures, viz, weight-for-age, length-for-age and head circumference-for-age, between birth and 64 weeks PMA. For each of the growth parameters, growth rate was categorized according to the change in z-score (z-score at 64 weeks PMA minus z score at birth) as slow (< -0.67), acceptable (-0.67 to < 0.67), and rapid (≥ 0.67). RESULTS: Out of the 156 preterm neonates evaluated, weight gain was slow, acceptable and rapid in 95 (60.8%), 45 (28.9%), and 16 (10.3%), respectively. Length gain was slow, acceptable, and rapid in 87 (55.7%), 49 (31.4%), and 20 (12.9%) infants, respectively. Likewise, Head circumference gain was slow, acceptable and rapid in 103 (66.5%), 42 (26.5%), and 11 (7.0%) infants, respectively. The risk [aOR 995% CI)] for slow weight gain increased with early initiation of complementary feeding [8.0 (3.5 - 18.0)] and decreased with a longer duration of EBF [0.4 (0.6 - 0.2), P < 0.001]. The risk for rapid weight gain also decreased with the longer duration of EBF [0.27 (0.5 - 0.1), P < 0.001]. Gestational age < 32 weeks ,weight for gestation at birth, and re-hospitalization following discharge were the other key factors influencing the growth rate. CONCLUSION: Among babies born preterm (≤ 34 weeks), more than half had slow gain in weight, length and head circumference. EBF till 6 months corrected age was protective against slow and rapid weight gain.

A phase III randomized-controlled study of safety and immunogenicity of DTwP-HepB-IPV-Hib vaccine (HEXASIIL®) in infants.

A fully liquid hexavalent containing Diphtheria (D), Tetanus (T) toxoids, whole cell Pertussis (wP), Hepatitis B (Hep B), type 1, 2, 3 of inactivated poliovirus (IPV) and Haemophilus influenzae type b (Hib) conjugate vaccine (DTwP-HepB-IPV-Hib vaccine, HEXASIIL®) was tested for lot-to-lot consistency and non-inferiority against licensed DTwP-HepB-Hib + IPV in an open label, randomized Phase II/III study. In Phase III part, healthy infants received DTwP-HepB-IPV-Hib or DTwP-HepB-Hib + IPV vaccines at 6, 10 and 14 weeks of age. Blood samples were collected prior to the first dose and 28 days, post dose 3. Non inferiority versus DTwP-HepB-Hib + IPV was demonstrated with 95% CIs for the treatment difference for seroprotection/seroconversion rates. For DTwP-HepB-IPV-Hib lots, limits of 95% CI for post-vaccination geometric mean concentration ratios were within equivalence limits (0.5 and 2). Vaccine was well-tolerated and no safety concerns observed.Clinical Trial Registration - CTRI/2019/11/022052.

Alterations of adipokines, pancreatic hormones and incretins in acute and convalescent COVID-19 children.

BACKGROUND: The Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), accountable for Coronavirus disease 2019 (COVID-19), may cause hyperglycemia and additional systemic complexity in metabolic parameters. It is unsure even if the virus itself causes type 1 or type 2 diabetes mellitus (T1DM or T2DM). Furthermore, it is still unclear whether even recuperating COVID-19 individuals have an increased chance to develop new-onset diabetes. METHODS: We wanted to determine the impact of COVID-19 on the levels of adipokines, pancreatic hormones, incretins and cytokines in acute COVID-19, convalescent COVID-19 and control children through an observational study. We performed a multiplex immune assay analysis and compared the plasma levels of adipocytokines, pancreatic hormones, incretins and cytokines of children presenting with acute COVID-19 infection and convalescent COVID-19. RESULTS: Acute COVID-19 children had significantly elevated levels of adipsin, leptin, insulin, C-peptide, glucagon and ghrelin in comparison to convalescent COVID-19 and controls. Similarly, convalescent COVID-19 children had elevated levels of adipsin, leptin, insulin, C-peptide, glucagon, ghrelin and Glucagon-like peptide-1 (GLP-1) in comparison to control children. On the other hand, acute COVID-19 children had significantly decreased levels of adiponectin and Gastric Inhibitory Peptide (GIP) in comparison to convalescent COVID-19 and controls. Similarly, convalescent COVID-19 children had decreased levels of adiponectin and GIP in comparison to control children. Acute COVID-19 children had significantly elevated levels of cytokines, (Interferon (IFN)) IFNγ, Interleukins (IL)-2, TNFα, IL-1α, IL-1ß, IFNα, IFNß, IL-6, IL-12, IL-17A and Granulocyte-Colony Stimulating Factors (G-CSF) in comparison to convalescent COVID-19 and controls. Convalescent COVID-19 children had elevated levels of IFNγ, IL-2, TNFα, IL-1α, IL-1ß, IFNα, IFNß, IL-6, IL-12, IL-17A and G-CSF in comparison to control children. Additionally, Principal component Analysis (PCA) analysis distinguishes acute COVID-19 from convalescent COVID-19 and controls. The adipokines exhibited a significant correlation with the levels of pro-inflammatory cytokines. CONCLUSION: Children with acute COVID-19 show significant glycometabolic impairment and exaggerated cytokine responses, which is different from convalescent COVID-19 infection and controls.

Factor Affecting Duration of Exclusive Breast Feeding in Preterm Infants With Gestational Age ≤ 34 Weeks.

OBJECTIVES: To study the factors influencing the duration of exclusive breastfeeding (EBF) in preterm (≤34 weeks) infants. METHODS: This study was done in 113 preterm infants with gestational age ≤34 weeks who were attending the well-baby clinic at the corrected age (CA) of 6 month. The birth details were noted from hospital records and feeding details were collected through a personal interview. RESULTS: The mean (SD) duration of EBF was 3.61 (2.3) months, and 35.3% babies had received EBF till CA of 6 month. Operative delivery [aOR (95% CI): 3.8 (1.0, 13.4) P=0.037], delay in initiating tube feeding, [aOR; 1.5 (1.0, 2.1); P=0.017], and delay in establishment of oral feeds [aOR1 (1.0, 1.08) P=0.016] were associated with a shorter duration of EBF. CONCLUSION: The prevalence of EBF till 6 months CA in preterm ≤34 weeks was 35.3%. Earlier initiation and establishment of full oral feeds may help in improving the duration of EBF.

Indian Academy of Pediatrics Guidelines on Screen Time and Digital Wellness in Infants, Children and Adolescents.

JUSTIFICATION: Screen-based media have become an important part of human lifestyle. In view of their easy availability and increasing use in Indian children, and their excessive use being linked to physical, developmental and emotional problems, there is a need to develop guidelines related to ensure digital wellness and regulate screen time in infants, children, and adolescents. OBJECTIVES: To review the evidence related to effects of screen-based media and excessive screen time on children's health; and to formulate recommendations for limiting screen time and ensuring digital wellness in Indian infants, children and adolescents. PROCESS: An Expert Committee constituted by the Indian Academy of Pediatrics (IAP), consisting of various stakeholders in private and public sector, reviewed the literature and existing guidelines. A detailed review document was circulated to the members, and the National consultative meet was held online on 26th March 2021 for a day-long deliberation on framing the guidelines. The consensus review and recommendations formulated by the Group were circulated to the participants and the guidelines were finalized. CONCLUSIONS: Very early exposure to screen-based media and excessive screen time (>1-2h/d) seems to be widely prevalent in Indian children. The Group recommends that children below 2 years age should not be exposed to any type of screen, whereas exposure should be limited to a maximum of one hour of supervised screen time per day for children 24-59 months age, and less than two hours per day for children 5-10 years age. Screen time must not replace other activities such as outdoor physical activities, sleep, family and peer interaction, studies and skill development, which are necessary for overall health and development of the children and adolescents. Families should ensure a warm, nurturing, supportive, fun filled and secure environment at home, and monitor their children's screen use to ensure that the content being watched is educational, age-appropriate and non-violent. Families, schools and pediatricians should be educated regarding the importance of recording screen exposure and digital wellness as a part of routine child health assessment, and detect any signs of cyberbullying or media addiction; and tackle it timely with expert consultation if needed.

Safety and immunogenicity of a multidose vial formulation of 13-valent pneumococcal conjugate vaccine administered with routine pediatric vaccines in healthy infants in India: A phase 4, randomized, open-label study.

PURPOSE: This phase 4, randomized, open-label, multicenter study in healthy Indian infants and toddlers evaluated the safety, tolerability, and immunogenicity of the 13-valent pneumococcal conjugate vaccine (PCV13) formulated in a multidose vial (MDV) or single prefilled syringe (PFS). METHODS: Healthy Indian infants (6 weeks of age) were randomized 1:1 to receive either PCV13-MDV or PCV13-PFS concomitant with routine pediatric vaccines. Subjects received a single dose of either PCV13-MDV or PCV13-PFS as a 4-dose schedule (infant series: 1 dose at 6, 10, and 14 weeks of age; toddler dose: 12 months of age). Safety was assessed, including local reactions, systemic events, and adverse events (AEs). Immunogenicity 1 month after both the infant series and toddler dose was measured by concentrations of serotype-specific immunoglobulin G (IgG) antibodies and opsonophagocytic activity titers. RESULTS: Rates and severities of local reactions and systemic events up to 7 days after each dose of either PCV13-MDV or PCV13-PFS were generally similar, with the majority being of mild or moderate severity. PCV13-MDV had a safety profile comparable with PCV13-PFS; both groups experienced a similar frequency of AEs. PCV13-MDV elicited immune responses comparable with those induced by PCV13-PFS. Clear boosting of immune responses after the PCV13-MDV toddler dose was observed; ≥96% of subjects showed serotype-specific IgG concentrations at or above the defined thresholds 1 month after the PCV13-MDV toddler dose. CONCLUSIONS: PCV13-MDV was safe, well tolerated, and immunogenic in healthy Indian infants and toddlers when coadministered with routine pediatric vaccinations. Safety and immunogenicity of PCV13-MDV was comparable with PCV13-PFS. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov: NCT03548337.

Factors Associated with Catch-up Growth in Term, Asymmetrical Small-for-Gestational Age Infants in the First Year of Life.

INTRODUCTION: Catch-up growth (CUG) in small-for-gestational age (SGA) infants is essential for their overall development. Knowledge about the factors influencing CUG might be critical in their effective management. Hence this study was performed with the aim of identifying factors that may influence CUG in SGA infants. METHODS: Asymmetrical SGA infants born at term were included in the study as per defined criteria, and their demographic details were recorded. Anthropometric data, feeding practice details, and intercurrent illnesses data were collected on follow-up at 6 weeks, 6 months, and 12-15 months of age. Catch-up growth weight was defined as improvement of weight to the normal range of -2 to +2 weight-for-age Z score (WAZ). Analysis was carried out using SPSS Expand 17 software. Chi-square test was used to find association between variables. Logistic regression analysis was used to measure effect. A P value of less than 0.05 was taken as significant. RESULTS: Out of 324 SGA infants born at term, 119 completed 12-15-month follow-up, of which 69.7% had achieved CUG weight. Exclusive breastfeeding >4 months, continued breastfeeding until 12-15 months, and absence of diarrheal episodes were positively associated with CUG. Pregnancy-induced hypertension, gestational diabetes, and maternal overweight/obesity were negatively associated with CUG. Maternal education status, conception age, gravida status, mode of delivery, vitamin D and iron supplementation, and intercurrent respiratory infections were not associated with CUG. On multivariate analysis, continued breastfeeding and absence of diarrheal episodes were independent factors associated with CUG. CONCLUSION: Breastfeeding practice, especially continued breastfeeding, and the absence of diarrheal illness are the key determinants for achieving CUG weight in term SGA infants, particularly in settings where resources are limited.

Asymptomatic Hypernatremia in an Infant with Midline Defects.

Holoprosencephaly is a developmental abnormality caused due to incomplete cleavage of the rostral neural tube (basal forebrain) structures during early embryogenesis. This defect causes incomplete separation of the right and left cerebral hemispheres. Children manifest a wide spectrum of clinical manifestations, the extent of which depends upon the degree of hemispheric nonseparation. We describe an infant with midline cleft referred for preoperative evaluation in whom, asymptomatic electrolyte abnormalities and holoprosencephaly were identified. On further evaluation, the infant was diagnosed to have isolated central diabetes insipidus and she responded well to oral desmopressin therapy. Cleft lip and palate is one of the commonest congenital malformations and midline clefts are likely to be associated with significant pituitary abnormalities. Awareness about the syndromic associations with clefts and the associated anomalies are important for early diagnosis and intervention in these children.

Rural Childhood Obesity - An Emerging Health Concern.

BACKGROUND: Childhood obesity is growing globally as an epidemic. It is the most common metabolic disease identified in children. OBJECTIVE: To assess the nutritional status of school going children in Poonamallee, Tamil Nadu and to compare the nutritional status between urban and rural school children. METHODS: A retrospective review of the school health records over a period of 9 months was done with Institutional Ethics Committee (IEC) approval for a total of 1,803 children aged 5 to 18 years (916- rural, 887-urban). Revised IAP growth charts (2015) were used to classify their nutrition status. RESULTS: The overall prevalence of overweight/obesity and thinness/severe thinness in our study was 20% and 9.4%, respectively. In the rural schools, the prevalence of overweight/obesity and thinness was 16.2% and 12.2%, respectively, whereas in the urban schools, it was 24% and 6.4%, respectively. The rural school children had lower mean Z scores of weight for age, height for age, and BMI for age compared to urban children (P < 0.001). CONCLUSION: Among rural school children overweight/obesity is more prevalent than undernutrition. There is an urgent need for nutrition education for the school children and community.

Vitamin D Deficiency as a Factor Influencing Asthma Control in Children.

OBJECTIVE: To study the association between asthma control and serum 25OH Vitamin D levels in children with moderate persistent asthma on preventer therapy. METHODS: Children aged 6-18 years, with moderate persistent asthma, on preventer therapy for ≥2 months were included. Control was categorized as good, partial or poor as per GINA guidelines. Serum 25 (OH) Vitamin D levels were measured and their relationship with the level of control was studied. RESULTS: Out of 50 children enrolled, 22 had well-controlled asthma, and 21 had partially controlled asthma. Vitamin D was deficient in 30 children and insufficient in 18 children. Children with vitamin D deficiency had significantly less well-controlled asthma as compared to those with insufficient or sufficient levels of 25 (OH) vitamin D (13.3% vs 88.9% vs 100%). CONCLUSIONS: Vitamin D deficiency is associated with suboptimal asthma control.

Immunogenicity and safety of measles-mumps-rubella vaccine delivered by disposable-syringe jet injector in India: A randomized, parallel group, non-inferiority trial.

BACKGROUND: We conducted a randomized, non-inferiority, clinical study of MMR vaccine by a disposable-syringe jet injector (DSJI) in toddlers in India in comparison with the conventional administration. METHODS: MMR vaccine was administered subcutaneously by DSJI or needle-syringe (N-S) to toddlers (15-18 months) who had received a measles vaccine at 9 months. Seropositivity to measles, mumps, and rubella serum IgG antibodies was assessed 35 days after vaccination. Non-inferiority was concluded if the upper limit of the 95% CI for the difference in the percent of seropositive between groups was less than 10%. Solicited reactions were collected for 14 days after vaccination by using structured diaries. RESULTS: In each study group, 170 subjects received MMR vaccine. On day 35, seropositivity for measles was 97.5% [95% CI (93.8%, 99.3%)] in the DSJI group and 98.7% [95% CI (95.5%, 99.8%)] in the N-S group; for mumps, 98.8% [95% CI (95.6%, 99.8%)] and 98.7% [95% CI (95.5%, 99.8%)]; and for rubella, 98.8% [95% CI (95.6%, 99.8%)] and 100% [95% CI (97.7%, 100.0%)]; none of the differences were significant. The day 35 post-vaccination GMTs in DSJI and N-S groups were measles: 5.48 IU/ml [95% CI (3.71, 8.11)] and 5.94 IU/ml [95% CI (3.92, 9.01)], mumps: 3.83 ISR [95% CI (3.53, 4.14)] and 3.66 ISR [95% CI (3.39, 3.95)] and rubella: 95.27 IU/ml [95% CI (70.39, 128.95)] and 107.06 IU/ml [95% CI (79.02, 145.06)]; none of the differences were significant. The DSJI group reported 173 solicited local reactions and the N-S group reported 112; most were mild grade. Of the total of 156 solicited systemic adverse events, most were mild, and incidence between the two groups was similar. CONCLUSIONS: MMR vaccination via DSJI is as immunogenic as vaccination by N-S. Safety profile of DSJI method is similar to N-S except for injection site reactions which are more with DSJI and are well-tolerated. Registration US National Institutes of Health clinical trials identifier - NCT02253407. Clinical trial registry of India identifier - CTRI/2013/05/003702.

Analysis of Serum Th1/Th2 Cytokine Levels in Patients with Acute Mumps Infection.

BACKGROUND: The mumps virus is frequently the causative agent of parotitis. There has been no study on serum cytokine levels of acute mumps parotitis except for a few which document cytokine levels in cerebrospinal fluid of mumps meningitis. It is with this notion, our study aimed to find Th1/Th2 cytokine levels from patients with acute mumps parotitis. MATERIALS AND METHODS: Concentrations of mumps-specific IgM, mumps, measles, rubella-specific IgG antibody, and Th1/Th2 cytokines, namely interferon-γ (IFN-γ), interleukin-2 (IL-2), IL-4, and IL-10 were measured simultaneously in serum from 74 patients (42 pediatric and 32 adult cases), 40 healthy subjects (20 pediatric and 20 adults) and in the supernatant of peripheral blood mononuclear cells stimulated with mumps virus genotype C which served as the positive control. Statistical significance was analyzed between each group by means of Mann-Whitney U-test, Kruskal-Wallis test, and Spearman's rank correlation coefficient test. RESULTS: IgM positivity confirmed acute infection in all 74 patients and of these 67 were vaccinated cases; however, very few of them (10/67) were positive for mumps IgG. We found that IFN-γ, IL-2, and IL-10 showed a statistically significant increase in both pediatric and adult patients with acute mumps infection when compared to healthy controls and values were comparable to the positive control. CONCLUSION: The Th1 cells play important roles during the acute phase of mumps parotitis.

Immunogenicity of bivalent types 1 and 3 oral poliovirus vaccine: a randomised, double-blind, controlled trial.

BACKGROUND: Poliovirus types 1 and 3 co-circulate in poliomyelitis-endemic countries. We aimed to assess the immunogenicity of a novel bivalent types 1 and 3 oral poliovirus vaccine (bOPV). METHODS: We did a randomised, double-blind, controlled trial to assess the superiority of monovalent type 2 OPV (mOPV2), mOPV3, or bOPV over trivalent OPV (tOPV), and the non-inferiority of bivalent vaccine compared with mOPV1 and mOPV3. The study was done at three centres in India between Aug 6, 2008, and Dec 26, 2008. Random allocation was done by permuted blocks of ten. The primary outcome was seroconversion after one monovalent or bivalent vaccine dose compared with a dose of trivalent vaccine at birth. The secondary endpoints were seroconversion after two vaccine doses compared with after two trivalent vaccine doses and cumulative two-dose seroconversion. Parents or guardians and study investigators were masked to treatment allocation. Because of multiple comparisons, we defined p≤0·01 as statistically significant. This trial is registered with Current Controlled Trials, ISRCTN 64725429. RESULTS: 900 newborn babies were randomly assigned to one of five vaccine groups (about 180 patients per group); of these 70 (8%) discontinued, leaving 830 (92%) for analysis. After the first dose, seroconversion to poliovirus type 1 was 20% for both mOPV1 (33 of 168) and bOPV (32 of 159) compared with 15% for tOPV (25 of 168; p>0·01), to poliovirus type 2 was 21% (35 of 170) for mOPV2 compared with 25% (42 of 168) for tOPV (p>0·01), and to poliovirus type 3 was 12% (20 of 165) for mOPV3 and 7% (11 of 159) for bOPV compared with 4% (7 of 168) for tOPV (mOPV3 vs tOPV p=0·01; bOPV vs tOPV; p>0·01). Cumulative two-dose seroconversion to poliovirus type 1 was 90% (151 of 168) for mOPV1 and 86% (136 of 159) for bOPV compared with 63% (106 of 168) for tOPV (p<0·0001), to poliovirus type 2 was 90% (153 of 170) for mOPV2 compared with 91% (153 of 168) for tOPV (p>0·01), and to poliovirus type 3 was 84% (138 of 165) for mOPV3 and 74% (117 of 159) for bOPV compared with 52% (87 of 168) for tOPV (p<0·0001). The vaccines were well tolerated. 19 serious adverse events occurred, including one death; however, these events were not attributed to the trial interventions. INTERPRETATION: The findings show the superiority of bOPV compared with tOPV, and the non-inferiority of bOPV compared with mOPV1 and mOPV3. FUNDING: GAVI Alliance, World Health Organization, and Panacea Biotec.

Youngest patient with Sydenham's chorea: a case report.

Rheumatic fever is common in India and the incidence has not shown the declining trends seen in the developed countries. Two-thirds of children with rheumatic fever are school aged (5-15 years of age). However, rheumatic fever does occur in children < 5 years of age and it is believed that younger children are more likely to have carditis and arthritis and less likely to have chorea. A case of rheumatic chorea occurring in a 3 4/12-year-old boy is reported. The patient was treated with penicillin, prednisolone and sodium valproate and responded favourably.