The burden of norovirus disease in children: a multi-country study in Chile, Brazil, Thailand and the Philippines.

BACKGROUND: Noroviruses (NoVs) cause acute gastroenteritis (AGE) worldwide, affecting children in particular. We aimed to estimate the burden of disease due to NoV among children aged <6 years in Brazil, Chile, Philippines and Thailand. METHODS: This was a prospective, hospital-based, observational study. Children were recruited over one year between 2014 and 2017. Four cohorts were analysed: community-acquired AGE outpatients and inpatients, nosocomial AGE inpatients, and asymptomatic outpatients. We collected demographic and clinical data, and a stool sample that was tested for NoV. Positive samples were tested for Rotavirus (RV) and NoV-genotyped. Disease severity was assessed by the Vesikari and modified Vesikari scores. Prevalence and incidence of NoV-AGE were estimated by cohort and country. RESULTS: 1637 participants yielded valid laboratory results. The proportion of NoV-positive cases was 23.8% (95% CI 20.8-27.2) in the outpatient cohort, 17.9% (15.0-21.3) in the hospital cohort, 21.4% (12.7-33.8) in the nosocomial cohort and 9.6% (6.9-13.2) in the asymptomatic cohort. Genotype GII.4 was predominant (58%). Less than 4% samples had RV coinfection. In general, NoV-positive subjects had more severe presentations than NoV-negative subjects. CONCLUSIONS: NoV caused AGE with substantial burden throughout the studied settings, with higher relative frequency in Brazil where RV vaccination coverage is high.

Functional antibodies elicited by an 11-valent diphtheria-tetanus toxoid-conjugated pneumococcal vaccine.

The aluminium-adjuvanted 11-valent pneumococcal conjugate vaccine containing polysaccharides 1, 4, 5, 7F, 9V, 19F, and 23F (coupled to tetanus protein) and polysaccharides 3, 6B, 14, and 18C (coupled to diphtheria toxoid) elicits high antibody concentrations in Filipino infants when given at ages 6, 10, and 14 weeks and 9 months simultaneously with the national vaccination program. We evaluated functional activity of these antibodies by using a viable cell opsonophagocytic assay (OPA). The OPA titers correlated (r=0.53-0.74) with the respective antibody concentrations. The geometric mean OPA titers after 3 vaccine doses were 276.9 (serotype 4), 12.3 (serotype 6B), 46.0 (serotype 14), 119.3 (serotype 19F), and 206.3 (serotype 23F). The functionality of antibodies increased after the fourth dose of vaccine (i.e., the concentration required for in vitro killing of pneumococci decreased). Both the quantity and quality of antibodies are important in the evaluation of immunogenicity of pneumococcal vaccines.

Greater antibody responses to an eleven valent mixed carrier diphtheria- or tetanus-conjugated pneumococcal vaccine in Filipino than in Finnish or Israeli infants.

BACKGROUND: Antibody responses to pneumococcal conjugate vaccines may vary when administered in different populations or epidemiologic settings. Understanding the causes and significance of this variation could help to determine the number of doses and timing required for protection against pneumococcal diseases in each country. METHODS: This report compares antibody responses to aluminum-adjuvanted and nonadjuvanted mixed carrier 11-valent diphtheria- or tetanus-conjugated pneumococcal vaccine (11-PncTD) formulations when given at 6, 10 and 14 weeks and 9 months of age to Filipino infants (n = 51) and at 2, 4, 6 and 12 months of age to Finnish (n = 127) and Israeli (n = 124) infants. The study populations differ in their natural exposure to pneumococcus and risk factors for pneumococcal carriage and disease. RESULTS: Filipino and Israeli infants had slightly but significantly higher prevaccination geometric mean concentration (GMC) of antibodies than did the Finnish infants. After three doses of aluminum-adjuvanted 11-PncTD vaccine, the Filipino infants had 1.8 to 6.7 and 1.5 to 5.0 times higher GMC than the Finnish and Israeli infants, respectively, against pneumococcal serotypes conjugated to tetanus protein. The GMC of serotypes conjugated to diphtheria toxoid was 1.3 to 3.0 and 0.7 to 2.0 times the GMC in Finnish and Israeli infants, respectively. The nonadjuvanted vaccine formulation induced generally lower GMCs. CONCLUSIONS: The antibody responses to the tetanus-conjugated polysaccharides were considerably higher in the Filipino than in the Finnish or Israeli infants. This may be a result of several factors including the priming effect of tetanus toxoid given to pregnant women, early pneumococcal nasopharyngeal acquisition and genetic differences among populations.