Phase III randomized clinical studies to evaluate the immunogenicity, lot-to-lot consistency, and safety of ROTAVAC® liquid formulations (ROTAVAC 5C & 5D) and non-inferiority comparisons with licensed ROTAVAC® (frozen formulation) in healthy infants.

The WHO pre-qualified rotavirus vaccine, ROTAVAC®, is derived naturally from the neonatal 116E rotavirus strain, and stored at -20°C. As refrigerator storage is preferable, immunogenicity and safety of liquid formulations kept at 2-8°C, having excipients to stabilize the rotavirus, with or without buffers, were compared with ROTAVAC® in different clinical studies. Study-1, the pivotal trial for this entire product development work, was a randomized, single-blind trial with two operationally seamless phases: (i) an exploratory phase involving 675 infants in which two formulations, ROTAVAC 5C (LnHRV-1.5 mL and LnHRV-2.0 mL) containing buffer and excipients to stabilize the virus against gastric acidity and temperature, were compared with ROTAVAC®. As the immune response of ROTAVAC 5C (LnHRV-2.0 mL) was non-inferior to ROTAVAC®, it was selected for (ii) confirmatory phase, involving 1,302 infants randomized 1:1:1:1 to receive three lots of LnHRV-2.0 mL, or ROTAVAC®. Primary objectives were the evaluation of non-inferiority and lot-to-lot consistency. The secondary objectives were to assess the safety and interference with the concomitant pentavalent vaccine. As it was separately established that buffers are not required for ROTAVAC®, in Study-2, the safety and immunogenicity of ROTAVAC 5D® (with excipients) were compared with ROTAVAC® and lot-to-lot consistency was assessed in another study. All lots elicited consistent immune responses, did not interfere with UIP vaccines, and had reactogenicity similar to ROTAVAC®. ROTAVAC 5C and ROTAVAC 5D® were immunogenic and well tolerated as ROTAVAC®. ROTAVAC 5D® had comparable immunogenicity and safety profiles with ROTAVAC® and can be stored at 2-8°C, leading to WHO pre-qualification.Clinical Trials Registration: Clinical Trials Registry of India (CTRI): CTRI/2015/02/005577CTRI/2016/11/007481 and CTRI/2019/03/017934.

Immunogenicity and safety of a liquid Pentavalent (DTwP-Hb-Hib) combination vaccine manufactured by Human Biologicals Institute in 6-8 weeks old healthy infants: A phase III, randomized, single blind, non-inferiority study.

BACKGROUND: A liquid Pentavalent (DTwP-Hb-Hib) combination vaccine, developed by Human Biologicals Institute, underwent a Phase III clinical study in India. In this randomized, single blind, non-inferiority study, the immunogenicity and safety of this Investigational vaccine was compared with Pentavac SD® vaccine in 6-8 weeks old healthy infants. METHODS: A total of 405 healthy infants aged 6-8 weeks old were randomized in 2:1 ratio to receive three doses of either the Investigational liquid Pentavalent (DTwP-Hb-Hib) combination vaccine or Pentavac SD® vaccine at four to six weeks interval. Immunogenicity was compared by estimation of antibody titers before the first dose and 4-6 weeks after the third dose of vaccination. Safety of each vaccine was assessed and compared by collection of data on solicited and unsolicited adverse events throughout the study period. RESULTS: Out of a total of 405 enrolled subjects, 387 subjects completed the study. The seroconversion rates, seroprotection rates and geometric mean titres of the Investigational liquid Pentavalent (DTwP-Hb-Hib) combination vaccine group were found to be comparable and non-inferior to the Pentavac SD® vaccine group at 4-6 weeks after the third dose of vaccination. Pain, erythema and swelling at the site of injection were found to be the most common local adverse events whereas fever, irritability and unusual crying were found to be the most common systemic adverse events in both the vaccine groups. No vaccine related serious adverse event was reported. In this study, both the Investigational vaccine as well as the Comparator vaccine were found to be immunogenic and well tolerated. CONCLUSION: After assessment of the results of the study it was concluded that the Investigational liquid Pentavalent (DTwP-Hb-Hib) combination vaccine developed by Human Biologicals Institute was immunogenic and safe when administered to infants aged 6-8 weeks and was non-inferior in immunogenicity and safety to Pentavac SD® vaccine. Clinical Trial Registry of India Identifier: CTRI/2016/01/006541.

Study of Parental Perceptions on Health & Social Needs of Children with Neuro-Developmental Disability and It's Impact on the Family.

INTRODUCTION: The term Neuro Developmental Disorder (NDD) is used for conditions caused by a dysfunction in any part of the brain or nervous system, resulting in physical and/or psychological symptoms as a child develops. Family of children with NDD face many problems. It is very important to find them and create awareness so that gaps in essential services and supports can be decreased. AIM: To explore parental perceptions on health & social needs of children with NDD, to understand the impact of disability on the families having children with disability, and to find out the parental perceptions on availability of services for children with NDD and its utilization by families. MATERIALS AND METHODS: The parents of 30 children with NDD were interviewed using a questionnaire and data elicited in these interviews were analysed. The questionnaire had preliminary information about parents and child with NDDs, socio-demographic profile of the family and the parental perceptions on health and social needs of their child having NDDs. RESULTS: There were total 30 patients 17 were males and 13 were females. Most of the patients suffered from Cerebral Palsy (13 cases) and were diagnosed by General Practitioner (22 cases) while Developmental Neurologist/paediatrician had diagnosed remaining cases of NDD (8 cases). Most common disability for which parents were worried was inability to walk (17 cases). Common difficulties countered in daily care by parents were feeding and bathing (10 cases). Only 2 children were given assistance with tuition & psychologist (cases of ADHD). Most of the parents knew about special schools but didn't know which place such facilities were available and none of the children were attending special schools. Twenty two parents said they have no plans for the future studies but wish that at least child learns to read & write. With help of spiritual power (doing prayers and pooja) 25 parents got courage to face the difficulties and discrimination. Two parents required antidepressants. Six Mothers had to quit their jobs so as to concentrate and give more time to their children. Experience with services provided was satisfactory in 17 cases, while 13 parents reported problem of arranging money, adjusting time for long travelling and regular follow-up. CONCLUSION: The findings can be utilized in developing supportive activities for families with disabled children. It addresses the need for new prospective of stigma reduction in our society. The study has found that the care givers of child with NDDs suffer from significant physical and mental stress, and their health should be taken into consideration. The study has found need of "care givers' support group". The professionals can help parents in establishing positive thinking towards care giving. There is need of provision of comprehensive and latest rehabilitation/ support resources & information.

Exploring the concurrent presence of hepatitis A virus genome in serum, stool, saliva, and urine samples of hepatitis A patients.

The use of saliva and urine as an alternative to serum samples for detection of anti-hepatitis A virus (HAV) IgM antibodies has been documented. However, these samples remain underreported or unexplored for shedding of HAV. To address this issue, paired serum, stool, saliva, and urine samples collected from hepatitis A patients were screened by reverse transcription polymerase chain reaction for detection of HAV RNA. HAV RNA was detected in 67.6% (44/65), 52.3% (34/65), 8.7% (5/57), and 12.3% (8/65) of the serum, stool, saliva, and urine samples, respectively. Phylogenetic analysis of nucleotide sequences obtained for partial RNA polymerase region grouped HAV strains from all of the clinical samples of the study in subgenotype IIIA. Low frequency of HAV nucleic acid in saliva and urine samples indicates limited utility of these samples in genomic studies on HAV but suggests its potential for transmission and infection of hepatitis A.

Epidemiological, clinical, and molecular features of norovirus infections in western India.

The study was conducted to investigate the molecular epidemiology of noroviruses (NoVs) from western India. A total of 830 fecal specimens were collected during July 2005-June 2007 from children, < or =7 years of age suffering from acute gastroenteritis in Pune, Nagpur, and Aurangabad cities. All the specimens were subjected to RT-PCR, sequencing and phylogenetic analysis for detection and characterization of Genogroup I (GI) and GII NoVs. NoV positivity varied between 6.3% and 12.6% in different cities with the predominance of GII (96.6%). NoV infections were very common in the patients < or =2 years of age. A majority (55%) of the patients suffered from severe disease, however, vomiting was not experienced in 35%. Coinfections with rotaviruses were found in 10% cases. Summer month seasonality supported NoV infections in western India. The phylogenetic analysis of partial RNA polymerase and VP1 (capsid) genes identified 2 GI (GI. 2 and GI.6) and 5 GII (GII.4, GII.6, GII.7, GII.8, and GII.14) genetic clusters with possible occurrence of "2007 new-variant" of GII.4. Six different combinations of RdRp and capsid genes (GII.b/GII.3, GII.b/GII.4, GII.d/GII.3, GII.b/GII.18, GII.1/GII.12 and GII.3/GII.13) were also identified. GII.4 (52%) prevailed in 2005-2006 while the predominance of probable recombinant NoV strains (58%) was noted in 2006-2007 with the contribution of GII.b/GII.3 at 79% level. GII.b/GII.18 type identified in 37% infections in 2005-2006 was completely replaced by GII.b/GII.3 type in 2006-2007. This is the first report that highlights the norovirus epidemiology and strain diversity demonstrating possible circulation of new variants in patients with acute gastroenteritis from western India.

Neem oil poisoning.

We report an unusual case of neem oil poisoning in a previously normal 5 year old child. The child presented with refractory seizures and was having metabolic acidosis. Late neurological sequelae in the form of auditory and visual disturbances, and ataxia were present.