Dravet syndrome with SCN1B gene mutation: A rare entity.

Early infantile epileptic encephalopathy has a grave outcome. Dravet syndrome (DS), characterized by early onset, refractory seizures, and intellectual deficit is one of the variants of the condition. SCN1B gene mutation is one of the lesser known variants of DS. Increased awareness of genetic analysis has increased the early diagnosis of DS for an early prognostication as well as genetic counselling of parents. We present the case of a 7-month old male child who started having recurrent febrile, and thereafter, afebrile seizures, following administration of a vaccination at 3 months. He developed global developmental delay, and is presently on multiple anticonvulsants. Genetic analysis was suggestive of SCN1B gene mutation associated with DS.

Complete genotyping of unusual species A rotavirus G12P[11] and G10P[14] isolates and evidence of frequent in vivo reassortment among the rotaviruses detected in children with diarrhea in Kolkata, India, during 2014.

Species A rotaviruses (RVA) are the most important cause of acute gastroenteritis in the young of humans and many animal species globally. G1P[8], G2P[4], G3P[8], G4P[8], G9P[6/8] and G12P[6/8] are the predominantly isolated genotypes throughout the world including India. Unusual genotypes from different host species such as G5, G6, G8, G10 and G11 have also been reported in humans with low frequency. In the present study, among >650 RVA positive stool samples collected from children with diarrhea in Kolkata, India, during 2014, two isolates each of the genotype G12P[11] and G10P[14] were obtained and their genomes completely sequenced. The full genotype constellations were G12-P[11]-I1-R1-C1-M2-A1-N1-T2-E1-H1 and G12-P[11]-I1-R1-C1-M1-A5-N1-T1-E1-H1 for G12P[11] viruses, suggesting several reassortments between Wa- and DS-1-like human RVA strains, including possible reassortment of a simian NSP1 gene. The G10P[14] viruses (G10-P[14]-I2-R2-C2-M2-A11-N2-T6-E2-H3) were found to contain multiple genes closely related to RVAs of artiodactyl origin, highlighting the role of inter-host species transmissions of RVAs. From the G/P constellation of all RVA isolates, it could be concluded that approximately one quarter had likely arisen from reassortment events in vivo among RVAs of 'usual' genotypes.

Genetic characterization of group-A rotaviruses among children in eastern India during 2014-2016: Phylodynamics of co-circulating genotypes.

BACKGROUND: Group-A human rotaviruses (GARV) are among the major cause of childhood diarrhea worldwide. In lieu of monitoring the circulatory GARV strains and underscoring the burden of GARV related hospitalization, a systematic surveillance was conducted in three hospitals of eastern India. In this hospital-based diarrheal disease surveillance (2014-2016), GARV was the most common cause of acute infantile gastroenteritis. The strains were genotyped and characterized to understand their prevalence and phylodynamics prior to the introduction of vaccine in eastern India. MATERIALS AND METHODS: A total of 3652 stool samples were screened from children (≤5 years) hospitalized with acute diarrhea during 2014-2016. Initial screening for VP6 antigen was done by ELISA. GARV positive samples were genotyped by multiplex semi-nested PCR and DNA sequencing and phylogenetic analyses were based on the capsid proteins VP4 and VP7. RESULTS: Of 3652 samples, 1817 (49.8%) were GARV positive. G1, G2, G3 and G9 in conjunction with P[4], P[6]and P[8]genotypes were seen to co-circulate in the population. A sharp deflection from G1 to G3 occurred since 2016; upsurge of G9 strains was seen in alternate years, whereas G2 strains had a low frequency. All the circulating genotypes depicted a low phylogenetic relatedness to the vaccine strains. Differences in antigenic epitopes of VP4 and VP7 proteins in local strains were seen when compared to the vaccine strains. A significant difference in the degree of dehydration, duration of mean hospital stay and frequency of vomiting/24 h between GARV positive and negative children was evident. CONCLUSION: The study provides a relevant set of base-line data on high burden of rotaviral gastroenteritis and the varied genotypic diversity among children prior to the introduction of GARV vaccine in this endemic region. Continuous monitoring during post-vaccination era will be required to assess the impact of vaccination in this region.

Immunogenicity and lot-to-lot consistency of a ready to use liquid bovine-human reassortant pentavalent rotavirus vaccine (ROTASIIL - Liquid) in Indian infants.

BACKGROUND: A lyophilized bovine-human rotavirus reassortant pentavalent vaccine (BRV-PV, Rotasiil®) was licensed in 2016. A liquid formulation of this vaccine (LBRV-PV, Rotasiil - Liquid) was subsequently developed and was tested for non-inferiority to Rotasiil® and for lot-to-lot consistency. METHODS: This Phase II/III, open label, randomized study was conducted at seven sites across India from November 2017 to June 2018. Participants were randomized into four arms; Lots A, B, and C of LBRV-PV and Rotasiil® in 1:1:1:1 ratio. Three doses of study vaccines were given at 6, 10, and 14 weeks of age. Blood samples were collected four weeks after the third dose to assess rotavirus IgA antibody levels. Non-inferiority of LBRV-PV to Rotasiil was proven if the lower limit two-sided 95% confidence interval (CI) of geometric mean concentration (GMC) ratio was at least 0.5. Lot-to-lot consistency was proven if 95% CI of the GMC ratios of three lots were between 0.5 and 2. Solicited reactions were collected by using diary cards. RESULTS: Of the 1500 randomized infants, 1436 infants completed the study. The IgA GMC ratio of LBRV-PV to Rotasiil® was 1.19 (95% CI 0.96, 1.48). The corresponding IgA seropositivity rates were 60.41% (57.41, 63.35) and 52.75% (47.48, 57.97). The IgA GMC ratios among the three LBRV-PV lots were: Lot A versus Lot B: 1.34 (1.03, 1.75); Lot A versus Lot C: 1.22 (0.93, 1.60); and Lot B versus Lot C: 0.91 (0.69, 1.19). The 95% CIs for the GMC ratios were between 0.69 and 1.75. The incidence of solicited reactions was comparable across the four arms. Only one serious adverse event of gastroenteritis event in the Rotasiil® group was causally related. CONCLUSION: The immunological non-inferiority of LBRV-PV against Rotasiil® as well as lot-to-lot consistency of LBRV-PV was demonstrated. LBRV-PV had safety profile similar to Rotasiil®. TRIAL REGISTRATION NUMBER: Clinical Trials.Gov [NCT03474055] and Clinical Trial Registry of India [CTRI/2017/10/010104].

A Phase III open-label, randomized, active controlled clinical study to assess safety, immunogenicity and lot-to-lot consistency of a bovine-human reassortant pentavalent rotavirus vaccine in Indian infants.

BACKGROUND: A heat-stable bovine-human rotavirus reassortant pentavalent vaccine (BRV-PV, ROTASIIL®) was developed in India. In this study, the vaccine was tested for safety, immunogenicity and clinical lot-to-lot consistency. METHODS: This was a Phase III, open label, randomized, equivalence design study. The primary objective was to demonstrate lot-to-lot consistency of BRV-PV. Subjects were randomized into four arms, three arms received Lots A, B, and C of BRV-PV and the control arm, received Rotarix®. Three doses of BRV-PV or two doses of Rotarix® and one dose of placebo were given at 6, 10, and 14 weeks of age. Blood samples were collected four weeks after the third dose to assess rotavirus IgA antibody levels. The three lots of BRV-PV were equivalent if the 95% Confidence Intervals (CIs) of the geometric mean concentration (GMC) ratios were between 0.5 and 2. Solicited reactions were collected by using diary cards. RESULTS: The study was conducted in 1500 randomized infants, of which 1341 infants completed the study. The IgA GMC ratios among the three lots were around 1 (Lot A versus Lot B: 1.07; Lot A versus Lot C: 1.06; and Lot B versus Lot C: 0.99). The 95% CIs for the GMC ratios were between 0.78 and 1.36. The IgA GMCs were: BRV-PV group 19.16 (95% CI 17.37-21.14) and Rotarix® group 10.92 (95% CI 9.36-12.74) (GMC ratio 1.75; 90% CI 1.51-2.04). Seropositivity rates were 46.98% (95% CI 43.86-50.11) and 31.12% (95% CI 26.17-36.41). The incidence of solicited reactions was comparable across the four arms. No serious adverse events were associated with the study vaccines, except two gastroenteritis events in the BRV-PV groups. CONCLUSION: Lot-to-lot consistency of BRV-PV was demonstrated in terms of GMC ratios of IgA antibodies. The vaccine safety and immunogenicity profiles were similar to those of Rotarix®. Clinical Trials.Gov [NCT02584816] and Clinical Trial Registry of India [CTRI/2015/07/006034].

Non-interference of Bovine-Human reassortant pentavalent rotavirus vaccine ROTASIIL® with the immunogenicity of infant vaccines in comparison with a licensed rotavirus vaccine.

BACKGROUND: A newly developed bovine-human reassortant pentavalent vaccine (BRV-PV, ROTASIIL®) was tested for its potential effect on the immunogenicity of concomitantly administered EPI vaccines in infants in a randomized controlled study in India. METHODS: In this Phase III, multicenter, open label, randomized, controlled study, three doses of BRV-PV or two doses of Rotarix® and one dose of placebo were given to healthy infants at 6, 10, and 14 weeks of age. Subjects also received three doses of DTwP-HepB-Hib (diphtheria, tetanus, whole-cell pertussis, hepatitis B, and haemophilus influenzae type b conjugate - pentavalent vaccine) and oral polio vaccine concomitantly at 6, 10, and 14 weeks of age and a single dose of inactivated polio vaccine at 14 weeks of age. Blood samples were collected four weeks after the final vaccination to assess immune responses to all the vaccines administered. For diphtheria, tetanus, hepatitis B, Hib, polio type 1, and polio type 3 antibodies, non-interference was to be supported if the lower limit of the two-sided 90% confidence interval (CI) for the seroprotection rate difference for the BRV-PV group minus the Rotarix® group was >10.0%. For pertussis antibodies, non-interference was to be supported if the lower limit of the two-sided 90% CI for the ratio of geometric mean concentrations (GMCs) was >0.5. RESULTS: A total of 1500 infants were randomized to either BRV-PV (1125 infants) or Rotarix® (375 infants), of which 1341 completed the study as per the protocol. More than 97% of subjects achieved seroprotective antibody titres against diphtheria, tetanus, hepatitis B, Hib, polio type 1, and polio type 3 in both groups. The difference in seroprotection rates between the BRV-PV group and the Rotarix® group for all these antibodies was less than 1%. The ratio of GMCs of anti-pertussis IgG concentrations for the BRV-PV group versus Rotarix® was 1.04 [90% CI: 0.90; 1.19]. CONCLUSION: BRV-PV does not interfere with the immunogenicity of concomitantly administered routine infants vaccines.

Factors Affecting Outcome in Children with Dengue in Kolkata.

This observational, descriptive study was conducted on 260 dengue patients diagnosed as per the revised 2009 WHO guidelines in a tertiary-care hospital of eastern India between June and November 2015. Children were evaluated for clinical symptoms, signs, and laboratory parameters. Clinical variables viz., rash, nausea/vomiting, bleeding, oliguria, capillary leak and liver enlargement; and laboratory variables viz., rising haemoglobin, haematocrit, thrombocytopenia, blood urea, serum Creatinine, ALT, hypo albuminemia and cholesterol were found to be significantly associated with outcome.

Attention deficit hyperactivity disorder.

OBJECTIVE: To identify ADHD children, to show the prevalence of the disorder in the age group of 5-12 years and to study their socio-demographic variables, associated medical and co-morbid psychological problems. METHODS: This is a cross-sectional case study of ADHD children presenting to a child guidance clinic in a busy pediatric hospital over a one year period. The diagnosis of ADHD was based on DSM IV criteria. RESULTS: Of the 238 children referred, 37 were diagnosed as ADHD. 64.9% of the referrals were from pediatricians. The prevalence of ADHD in pediatric clinic was 15.5%, the inattention subtype was predominant. The mean age of boys and girls with ADHD was 8.49 years and 6.82 years respectively. The male to female ratio was 6.4:1. Majority of patients were from middle socio-economic status belonging to Hindu families. 27.0% of children had developmental problems. Oppositional defiant disorder was the most prevalent while depression was the least prevalent co morbid problem. CONCLUSION: ADHD is prevalent in India and the bunch of these children are mostly presenting to the pediatrician. They need to be aware of the profile of this disorder for early detection and intervention.

Macrophage activation syndrome in Kawasaki disease.

BACKGROUND: Kawasaki disease is an acute febrile vasculitis of childhood. Macrophage activation syndrome is a rare life threatening complication. CASE CHARACTERISTICS: 4-year-old boy with Kawasaki Disease treated with intravenous immunoglobulins. OBSERVATION: He developed encephalopathy, hepatosplenomegaly and pancytopenia. Blood investigations and bone marrow aspiration suggested macrophage activation syndrome. OUTCOME: Good response to pulse methylprednisolone (30 mg/kg/d) for 5 days. MESSAGE: Macrophage activation syndrome may complicate Kawasaki disease.