Immunogenicity and safety of two monovalent rotavirus vaccines, ROTAVAC® and ROTAVAC 5D® in Zambian infants.

BACKGROUND AND AIMS: ROTAVAC® (frozen formulation stored at -20 °C) and ROTAVAC 5D® (liquid formulation stable at 2-8 °C) are rotavirus vaccines derived from the 116E human neonatal rotavirus strain, developed and licensed in India. This study evaluated and compared the safety and immunogenicity of these vaccines in an infant population in Zambia. METHODS: We conducted a phase 2b, open-label, randomized, controlled trial wherein 450 infants 6 to 8 weeks of age were randomized equally to receive three doses of ROTAVAC or ROTAVAC 5D, or two doses of ROTARIX®. Study vaccines were administered concomitantly with routine immunizations. Blood samples were collected pre-vaccination and 28 days after the last dose. Serum anti-rotavirus IgA antibodies were measured by ELISA, with WC3 and 89-12 rotavirus strains as viral lysates in the assays. The primary analysis was to assess non-inferiority of ROTAVAC 5D to ROTAVAC in terms of the geometric mean concentration (GMC) of serum IgA (WC3) antibodies. Seroresponse and seropositivity were also determined. Safety was evaluated as occurrence of immediate, solicited, unsolicited, and serious adverse events after each dose. RESULTS: The study evaluated 388 infants in the per-protocol population. All three vaccines were well tolerated and immunogenic. The post-vaccination GMCs were 14.0 U/mL (95% CI: 10.4, 18.8) and 18.1 U/mL (95% CI: 13.7, 24.0) for the ROTAVAC and ROTAVAC 5D groups, respectively, yielding a ratio of 1.3 (95% CI: 0.9, 1.9), thus meeting the pre-set non-inferiority criteria. Solicited and unsolicited adverse events were similar across all study arms. No death or intussusception case was reported during study period. CONCLUSIONS: Among Zambian infants, both ROTAVAC and ROTAVAC 5D were well tolerated and the immunogenicity of ROTAVAC 5D was non-inferior to that of ROTAVAC. These results are consistent with those observed in licensure trials in India and support use of these vaccines across wider geographical areas.

Environmental predictors of diarrhoeal infection for rural and urban communities in south India in children and adults.

Diarrhoeal diseases are major causes of morbidity and mortality in developing countries. This longitudinal study aimed to identify controllable environmental drivers of intestinal infections amidst a highly contaminated drinking water supply in urban slums and villages of Vellore, Tamil Nadu in southern India. Three hundred households with children (<5 years) residing in two semi-urban slums and three villages were visited weekly for 12-18 months to monitor gastrointestinal morbidity. Households were surveyed at baseline to obtain information on environmental and behavioural factors relevant to diarrhoea. There were 258 diarrhoeal episodes during the follow-up period, resulting in an overall incidence rate of 0·12 episodes/person-year. Incidence and longitudinal prevalence rates of diarrhoea were twofold higher in the slums compared to rural communities (P < 0·0002). Regardless of study site, diarrhoeal incidence was highest in infants (<1 year) at 1·07 episodes/person-year, and decreased gradually with increasing age. Increasing diarrhoeal rates were associated with presence of children (<5 years), domesticated animals and low socioeconomic status. In rural communities, open-field defecation was associated with diarrhoea in young children. This study demonstrates the contribution of site-specific environmental and behavioural factors in influencing endemic rates of urban and rural diarrhoea in a region with highly contaminated drinking water.

A multicenter prospective hospital-based surveillance to estimate the burden of rotavirus gastroenteritis in children less than five years of age in India.

BACKGROUND: Rotavirus is the leading cause of severe, dehydrating diarrhea in children aged <5 years globally, with an estimated 25 million outpatient visits and 2 million hospitalizations attributable to rotavirus infections each year. The aim of this hospital-based surveillance was to summarize the local epidemiological and virological features of rotavirus and to estimate the disease burden in the population under surveillance in India. METHODS: During the 16 months surveillance period from April 2011 through July 2012, a total of 4711 children under the age of 5 years were admitted with acute diarrhea at 12 medical centers attached to medical schools throughout India. Stool samples were randomly collected from 2051 (43.5%) subjects and were analyzed for rotavirus positivity using commercial enzyme immunoassay kit (Premier Rotaclone Qualitative Elisa) at the respective study centers. Rotavirus positive samples were genotyped for VP7 and VP4 by reverse-transcription polymerase chain reaction (RT-PCR) at a central laboratory. RESULTS: During the study period, maximum number of rotavirus related hospitalizations were reported from December 2011 through February 2012. Out of the 2051 stool samples tested for rotavirus, overall 541 (26.4%) samples were positive for rotavirus VP6 antigen in stool. The highest positivity was observed in the month of December, 2011 (52.5%) and lowest in the month of May, 2011 (10.3%). We found that majority of the rotavirus positive cases (69.7%) were in children <24 months of age. The most common genotypes reported were G1 (38%), G2 (18%), G9 (18%), G12 (9%) and mixed strains (17%). CONCLUSIONS: The results of this study confirm the significant burden of acute rotavirus gastroenteritis as a cause of hospitalizations in under five children in India.

Detection and characterisation of rotaviruses from children less than 5 years hospitalised with acute gastroenteritis in Nagercoil.

Group A rotavirus continues to be the major cause of severe gastroenteritis in young children in developing countries. In this study, we report the prevalence and genotype of rotaviruses identified from children <5 years of age hospitalised with acute gastroenteritis from Nagercoil, Tamil Nadu from 2007-2010. From the 139 children included in the study, 71 samples (51%) were positive by ELISA and 65 samples were positive by PCR-based methods. G1P[8] (44.6%) was the most commonly identified genotype. In addition, we report detection of rotavirus in two of three CSF samples from children with seizures.

Detection and species identification of Campylobacter in stool samples of children and animals from Vellore, south India.

Campylobacter spp. are an important cause of bacterial gastroenteritis frequently isolated from animal, poultry and environmental samples. In this study, we investigated the zoonotic potential of Campylobacter spp. by comparing prevalence rates and species in 394 children with diarrhoea and 652 animals in Vellore using PCR-based tools. Eighteen children (4.5%) had campylobacteriosis, a majority of whom had co-pathogens (15/18) and most were infected with Campylobacter jejuni (16/18). A few C. coli and mixed infections with both species were also seen. Among the animal samples, 16/25 chicken samples (64%) were positive and all were found to be C. jejuni.