Silvia Damaso

Bio: Silvia Damaso is an academic researcher from GlaxoSmithKline. The author has contributed to research in topics: Vaccination & Rotavirus. The author has an hindex of 11, co-authored 19 publications receiving 3164 citations.

Safety and Efficacy of an Attenuated Vaccine against Severe Rotavirus Gastroenteritis

Abstract: Background The safety and efficacy of an attenuated G1P[8] human rotavirus (HRV) vaccine were tested in a randomized, double-blind, phase 3 trial. Methods We studied 63,225 healthy infants from 11 Latin American countries and Finland who received two oral doses of either the HRV vaccine (31,673 infants) or placebo (31,552 infants) at approximately two months and four months of age. Severe gastroenteritis episodes were identified by active surveillance. The severity of disease was graded with the use of the 20-point Vesikari scale. Vaccine efficacy was evaluated in a subgroup of 20,169 infants (10,159 vaccinees and 10,010 placebo recipients). Results The efficacy of the vaccine against severe rotavirus gastroenteritis and against rotavirus-associated hospitalization was 85 percent (P<0.001 for the comparison with placebo) and reached 100 percent against more severe rotavirus gastroenteritis. Hospitalization for diarrhea of any cause was reduced by 42 percent (95 percent confidence interval, 29 to 53 percen...

Evaluation of safety, immunogenicity and efficacy of an attenuated rotavirus vaccine, RIX4414: A randomized, placebo-controlled trial in Latin American infants.

Abstract: Background: A live attenuated monovalent rotavirus vaccine RIX4414 was developed with a human strain of G1P1A P[8] specificity to reduce the rotavirus burden in children. Methods: A double blind, randomized, placebo-controlled study evaluated the efficacy, immunogenicity, safety and reactogenicity of 2 oral doses of RIX4414 (10 4.7 , 10 5.2 or 10 5.8 focus-forming units) at 2 and 4 months coadministered with routine vaccinations and oral poliovirus vaccine given for study purposes at least 14 days apart. The 2155 infants (1618 vaccine/537 placebo) enrolled in Brazil, Mexico and Venezuela were followed until 1 year of age. Results: Antirotavirus IgA seroconversion rates 2 months after dose 2 ranged between 61% (10 4.7 ffu group) and 65% (10 5.8 ffu group), and most of the infants had seroprotective levels of antibodies to coadministered routine vaccinations. The reactogenicity profile of RIX4414 was similar to that of the placebo, and no vaccination-related serious adverse events were reported. Protective efficacy against severe and any rotavirus gastroenteritis from 15 days post-dose 2 was highest in the 10 5.8 ffu group [86%; 95% confidence interval (95% CI), 63-96% and 70% (95% CI 46-84%), P < 0.001, 2-sided Fisher's exact test]. The efficacy against hospitalization was 79% (95% CI 48-92%) for pooled vaccine groups. Multiple rotavirus serotypes [Gl (50%), G9 (40%), G2, G3 and G4] were identified from gastroenteritis stools (enzyme-linked immunosorbent assay and reverse transcription-polymerase chain reaction) during the study period. For severe gastroenteritis caused by G9 serotypes, the protection reached 77% (95% CI 18-96%) in the 10 5.8 ffu group, providing proof of concept that the monovalent G1P1A P[8] human rotavirus vaccine elicits cross-protection against the G9 strain. A reduction in any and severe rotavirus gastroenteritis was already observed at post-dose 1 (period: day of dose 1 to 14 days post-dose 2) in vaccinees compared with placebo recipients. Conclusions: Two doses of RIX4414 are highly efficacious, providing cross-protection (Gl and G9 strains, prevalent during this study) and early protection against any and severe rotavirus gastroenteritis and hospitalization to infants in Latin America.

Efficacy profile of a bivalent Staphylococcus aureus glycoconjugated vaccine in adults on hemodialysis: Phase III randomized study

Abstract: In a previous study in end-stage renal disease (ESRD) hemodialysis patients, a single dose of Staphylococcus aureus type 5 and 8 capsular polysaccharides (T5/T8) conjugated to nontoxic recombinant Pseudomonas aeruginosa exotoxin A investigational vaccine showed no efficacy against S aureus bacteremia 1 year post-vaccination, but a trend for efficacy was observed over the first 40 weeks post-vaccination Vaccine efficacy (VE) of 2 vaccine doses was therefore evaluated In a double-blind trial 3359 ESRD patients were randomized (1:1) to receive vaccine or placebo at week 0 and 35 VE in preventing S aureus bacteremia was assessed between 3-35 weeks and 3-60 weeks post-dose-1 Anti-T5 and anti-T8 antibodies were measured Serious adverse events (SAEs) were recorded for 42 days post-vaccination and deaths until study end No significant difference in the incidence of S aureus bacteremia was observed between vaccine and placebo groups between weeks 3-35 weeks post-dose 1 (VE -23%, 95%CI: -98;23, p = 039) or at 3-60 weeks post-dose-1 (VE -8%, 95%CI: -57;26, p = 070) Day 42 geometric mean antibody concentrations were 2724 μg/ml and 2420 μg/ml (T5 and T8, respectively) in vaccinees SAEs were reported by 24%/253% of vaccinees/placebo recipients These data do not show a protective effect of either 1 or 2 vaccine doses against S aureus bacteremia in ESRD patients The vaccine induced a robust immune response and had an acceptable safety profile Further investigation suggested possible suboptimal vaccine quality (manufacturing) and a need to expand the antigen composition of the vaccine This study is registered at wwwclinicaltrialsgov NCT00071214

Safety and Efficacy of an Attenuated Vaccine against Severe Rotavirus Gastroenteritis

Abstract: Background The safety and efficacy of an attenuated G1P[8] human rotavirus (HRV) vaccine were tested in a randomized, double-blind, phase 3 trial. Methods We studied 63,225 healthy infants from 11 Latin American countries and Finland who received two oral doses of either the HRV vaccine (31,673 infants) or placebo (31,552 infants) at approximately two months and four months of age. Severe gastroenteritis episodes were identified by active surveillance. The severity of disease was graded with the use of the 20-point Vesikari scale. Vaccine efficacy was evaluated in a subgroup of 20,169 infants (10,159 vaccinees and 10,010 placebo recipients). Results The efficacy of the vaccine against severe rotavirus gastroenteritis and against rotavirus-associated hospitalization was 85 percent (P<0.001 for the comparison with placebo) and reached 100 percent against more severe rotavirus gastroenteritis. Hospitalization for diarrhea of any cause was reduced by 42 percent (95 percent confidence interval, 29 to 53 percen...

Prevention of rotavirus gastroenteritis among infants and children. Recommendations of the Advisory Committee on Immunization Practices (ACIP).

Abstract: Rotavirus is the most common cause of severe gastroenteritis in infants and young children worldwide. Before initiation of the rotavirus vaccination program in the United States in 2006, approximately 80% of U.S. children had rotavirus gastroenteritis by age 5 years. Each year during the 1990s and early 2000s, rotavirus resulted in approximately 410,000 physician visits, 205,000272,000 emergency department visits, and 55,00070,000 hospitalizations among U.S. infants and children, with total annual direct and indirect costs of approximately $1 billion. In February 2006, a live, oral, human-bovine reassortant rotavirus vaccine (RotaTeq(R) [RV5]) was licensed as a 3-dose series for use among U.S. infants for the prevention of rotavirus gastroenteritis, and the Advisory Committee on Immunization Practices (ACIP) recommended routine use of RV5 among U.S. infants (CDC. Prevention of rotavirus gastroenteritis among infants and children: recommendations of the Advisory Committee on Immunization Practices [ACIP]. MMWR 2006;55[No. RR-12]). In April 2008, a live, oral, human attenuated rotavirus vaccine (Rotarix(R) [RV1]) was licensed as a 2-dose series for use among U.S. infants, and in June 2008, ACIP updated its rotavirus vaccine recommendations to include use of RV1. This report updates and replaces the 2006 ACIP statement for prevention of rotavirus gastroenteritis. ACIP recommends routine vaccination of U.S. infants with rotavirus vaccine. RV5 and RV1 differ in composition and schedule of administration. RV5 is to be administered orally in a 3-dose series, with doses administered at ages 2, 4, and 6 months. RV1 is to be administered orally in a 2-dose series, with doses administered at ages 2 and 4 months. ACIP does not express a preference for either RV5 or RV1. The recommendations in this report also address the maximum ages for doses, contraindications, precautions, and special situations for the administration of rotavirus vaccine.

2008 estimate of worldwide rotavirus-associated mortality in children younger than 5 years before the introduction of universal rotavirus vaccination programmes: a systematic review and meta-analysis

Abstract: Summary Background WHO recommends routine use of rotavirus vaccines in all countries, particularly in those with high mortality attributable to diarrhoeal diseases. To establish the burden of life-threatening rotavirus disease before the introduction of a rotavirus vaccine, we aimed to update the estimated number of deaths worldwide in children younger than 5 years due to diarrhoea attributable to rotavirus infection. Methods We used PubMed to identify studies of at least 100 children younger than 5 years who had been admitted to hospital with diarrhoea. Additionally, we required the studies to have a data collection midpoint of the year 2000 or later, to be done in full-year increments, and to assesses diarrhoea attributable to rotavirus with EIAs or polyacrylamide gel electrophoresis. We also included data from countries that participated in the WHO-coordinated Global Rotavirus Surveillance Network (consisting of participating member states during 2009) and that met study criteria. For countries that have introduced a rotavirus vaccine into their national immunisation programmes, we excluded data subsequent to the introduction. We classified studies into one of five groups on the basis of region and the level of child mortality in the country in which the study was done. For each group, to obtain estimates of rotavirus-associated mortality, we multiplied the random-effect mean rotavirus detection rate by the 2008 diarrhoea-related mortality figures for countries in that group. We derived the worldwide mortality estimate by summing our regional estimates. Findings Worldwide in 2008, diarrhoea attributable to rotavirus infection resulted in 453 000 deaths (95% CI 420 000–494 000) in children younger than 5 years—37% of deaths attributable to diarrhoea and 5% of all deaths in children younger than 5 years. Five countries accounted for more than half of all deaths attributable to rotavirus infection: Democratic Republic of the Congo, Ethiopia, India, Nigeria, and Pakistan; India alone accounted for 22% of deaths (98 621 deaths). Interpretation Introduction of effective and available rotavirus vaccines could substantially affect worldwide deaths attributable to diarrhoea. Our new estimates can be used to advocate for rotavirus vaccine introduction and to monitor the effect of vaccination on mortality once introduced. Funding None.

Vaccination greatly reduces disease, disability, death and inequity worldwide.

Abstract: In low-income countries, infectious diseases still account for a large proportion of deaths, highlighting health inequities largely caused by economic differences. Vaccination can cut health-care costs and reduce these inequities. Disease control, elimination or eradication can save billions of US dollars for communities and countries. Vaccines have lowered the incidence of hepatocellular carcinoma and will control cervical cancer. Travellers can be protected against "exotic" diseases by appropriate vaccination. Vaccines are considered indispensable against bioterrorism. They can combat resistance to antibiotics in some pathogens. Noncommunicable diseases, such as ischaemic heart disease, could also be reduced by influenza vaccination. Immunization programmes have improved the primary care infrastructure in developing countries, lowered mortality in childhood and empowered women to better plan their families, with consequent health, social and economic benefits. Vaccination helps economic growth everywhere, because of lower morbidity and mortality. The annual return on investment in vaccination has been calculated to be between 12% and 18%. Vaccination leads to increased life expectancy. Long healthy lives are now recognized as a prerequisite for wealth, and wealth promotes health. Vaccines are thus efficient tools to reduce disparities in wealth and inequities in health.