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1.
New Zealand has experienced a prolonged epidemic of meningococcal B disease since 1991. The epidemic has waned significantly since its most recent peak in 2001. A strain-specific vaccine, MeNZB, was introduced to control the epidemic in 2004, achieving 81% coverage of people under the age of 20. The vaccine was rolled out in a staged manner allowing the comparison of disease rates in vaccinated and unvaccinated individuals in each year.Vaccine effectiveness in people aged under 20 years is estimated using a Poisson regression model in the years 2001-2008, including adjustments for year, season, age, ethnicity, region and socioeconomic status. Further analyses investigate the dose response relationship, waning of the vaccine effect after one year, and cross-protection against other strains of meningococcal disease.The primary analysis estimates MeNZB vaccine effectiveness to be 77% (95% CI 62-85) after 3 doses and a mean follow-up time of 3.2 years. There is evidence for a protective effect after 2 doses 47% (95% CI 16-67), and no evidence for a waning of effectiveness after one year. Simultaneous modelling of invasive pneumococcal disease and epidemic strain meningococcal B suggests a degree of residual confounding that reduces the effectiveness estimate to 68%. There is evidence for some cross-protection of MeNZB against non-epidemic strains.The MeNZB vaccine was effective against the New Zealand epidemic strain of meningococcal B disease. Between July 2004 and December 2008 an estimated 210 epidemic strain cases (95% CI 100-380), six deaths and 15-30 cases of severe sequelae were avoided in New Zealand due to the introduction of the MeNZB vaccine. 相似文献
2.
This study evaluated the first use of a combination of the lyophilized components of the conjugated group C vaccine Menjugate reconstituted with the liquid group B outer membrane vesicle (OMV) vaccine MeNZB. At 6-week intervals, healthy residential students received three doses of MeNZB alone or concomitantly with one dose of Menjugate (MeNZB+MenC). Short-lasting injection-site reactions of mild or moderate intensity were frequent in both groups. There were no vaccine-related serious adverse events. After three doses, the percentage of subjects with serum bactericidal assay (SBA) titres > or = 1:8 against the serogroup B strain NZ98/254 was 82% for MeNZB+MenC and 78% for MeNZB. All subjects in the MeNZB+MenC group achieved SBA titres > or = 1:8 against serogroup strain C11 and 67% in the MeNZB group. All SBA and ELISA responses of the combined vaccine were at least as good as for MeNZB alone. After vaccination, the pharyngeal carriage rate of any meningococcus in the vaccinated group had declined from 40% to 21%. 相似文献
3.
O'Hallahan J Lennon D Oster P Lane R Reid S Mulholland K Stewart J Penney L Percival T Martin D 《Vaccine》2005,23(17-18):2197-2201
New Zealand has been affected by an epidemic of group B meningococcal disease dominated by a strain defined as, B:4:P1.7b,4. Over 5550 cases and 222 deaths have been reported since 1991 in a population of 4 million people.Meningococcal disease cases notified on EpiServ database operated by Institute of Environmental Science and Research Limited through to 30 September 2004. Through the collaborative efforts of a government agency, vaccine company, university and laboratory institute, clinical trials of the Chiron produced outer membrane vesicle (OMV) strain-specific MeNZB vaccine were run in rapid succession. The delivery of MeNZB will be New Zealand's largest immunisation programme with three doses given at 6-week intervals to over 1 million people aged 6 weeks-19 year olds inclusive. Planning, co-ordinating and delivering the immunisation programme is a challenging project for the New Zealand Health Sector. 相似文献
4.
The effectiveness of a new group B strain-specific meningococcal vaccine referred to as "MeNZB," developed by Chiron Vaccines (Siena, Italy) in collaboration with the Norwegian Institute of Public Health, was assessed in a prospective observational study following a nationwide vaccination program in New Zealand. The vaccination program began in July 2004, and the study uses data from January 2001 to June 2006. A generalized estimating equation model was used to estimate vaccine effectiveness that included potential confounding variables, such as disease progression over time, age, ethnicity, socioeconomic status, seasonality, and geographic region. The model provides strong statistical evidence for a vaccine effect (p < 0.0001), with estimated disease rates 3.7 times higher in the unvaccinated group than in the vaccinated group (95% confidence interval: 2.1, 6.8) and a vaccine effectiveness of 73% (95% confidence interval: 52, 85). An estimated 54 epidemic strain meningococcal cases were prevented in the 2 years since the vaccination program began (95% confidence interval assuming a fixed population size: 22, 115). In a sensitivity analysis, these estimates proved to be robust to modeling assumptions, including population estimates, estimates of the numbers vaccinated, effects of partial vaccination, and temporal autocorrelation. 相似文献
5.
MenBvac is an OMV vaccine against systemic serogroup B Neisseria meningitidis disease. MenBvac was developed for control of a B:15:P1.7,16 subtype epidemic in Norway and administered to 180,000 subjects in 28 clinical studies. MeNZB, a daughter vaccine of MenBvac, was developed for a clonal B:4:P1.7b,4 epidemic in New Zealand and administered to 1 million people <20 years. The vaccines were similar regarding reactogenicity profile. Serious adverse events (SAEs) in general and particularly neurologic SAEs were very rare. Despite frequently reported local reactions and fever in those under 5 years, these OMV-based vaccines containing 25 microg antigen can be considered safe for use in all age groups. 相似文献
6.
Fernández S Arreaza L Santiago I Malvar A Berrón S Vazquez JA Hervada X Gestal JJ 《Epidemiology and infection》1999,123(3):349-357
In Galicia, Spain, a dramatic increase in the incidence of meningococcal disease was seen in the 1995-6. The annual incidence rose to 11 per 10(5) inhabitants, and 80% of identified strains were C:2b:P1.2,5. This led to the implementation of an intensive A+C vaccination campaign for the population aged 18 months to 19 years. During this campaign the prevalence of carriage in areas with high and low incidence was studied. Nasopharyngeal swabs were taken from 9796 subjects immediately before the administration of meningococcal vaccine, plated onto Thayer-Martin plates, incubated and sent for analysis to the Reference Laboratory for Neisseria in Spain. The prevalence of the C:2b: P1.2,5 strains was 0.6% (95% CI 0.29-0.88) in the high incidence area, and 0.41% (95 % CI 0.00-1.04) in the low incidence area, and that of serogroup C (all strains) 1.36% (95% CI 0.80-1.80) and 0.89% (95% CI 0.09-1.69) respectively. The prevalence of N. meningitidis (all strains) was almost the same in both areas (8%). Carriers of the epidemic strain were not found in the 2-4 year age group, that most affected by the disease. Our data showed a wide distribution but a low carriage rate of the epidemic strain C:2b:P1.2,5 in the high and low disease incidence areas studied; the difference in the carriage rates between the two areas was not statistically significant. 相似文献
7.
Ameratunga S Macmillan A Stewart J Scott D Mulholland K Crengle S;Meningococcal Management Team 《Vaccine》2005,23(17-18):2231-2234
A nationwide strategy to control a group B meningococcal disease epidemic in New Zealand using an epidemic strain-specific vaccine (MeNZB ) commenced in 2004. In the absence of randomised controlled trials investigating the efficacy of this particular vaccine, a complement of observational methods are planned to evaluate the post-licensure effectiveness of this vaccine strategy. The two main approaches involve a Poisson regression model investigating the overall impact of the MeNZB programme on disease rates over time capitalising on detailed population-based disease surveillance data and the staged roll-out of the vaccine campaign, and a case-control study that aims to estimate vaccine effectiveness in pre-school children. The studies are designed to minimise the potential biases inherent in all observational methods and provide critical data on the effectiveness of a major public health intervention. 相似文献
8.
Thornton V Lennon D Rasanathan K O'Hallahan J Oster P Stewart J Tilman S Aaberge I Feiring B Nokleby H Rosenqvist E White K Reid S Mulholland K Wakefield MJ Martin D 《Vaccine》2006,24(9):1395-1400
As the first step towards control of a strain specific epidemic of meningococcal disease in New Zealand (NZ), this study, an observer-blind, randomised controlled trial in 75 healthy adults, evaluated safety and immunogenicity of two different dosages of a meningococcal group B vaccine administered in a three dose regime. The "tailor-made" outer membrane vesicle (OMV) vaccine (candidate vaccine) developed using a New Zealand meningococcal group B strain (B:4:P1.7b,4) was well tolerated with no vaccine related serious adverse events. Similar local and systemic reactions were observed in those receiving the New Zealand candidate vaccine and the control parent Norwegian vaccine (MenBvac). A four-fold rise in serum bactericidal antibodies (SBAb) against the vaccine strain 4-6 weeks after the third vaccination was achieved in 100% of New Zealand candidate vaccine 2,519 microg participants and in 87% of 50 microg participants. The safety and immunogenicity profile observed in this study of healthy adults enabled studies in children to be initiated using 25 microg dosage. 相似文献
9.
To control the devastating group B meningococcal epidemic in New Zealand a strain-specific OMV vaccine (MeNZB) was extensively tested before vaccination of >1,000,000 people under 20 years. After the three-dose course 75% of 6-8-month-old infants and 16-24-month-old toddlers showed four-fold increases in bactericidal antibodies. In 6-10-week-old infants a fourth dose was needed to obtain similar results. After primary vaccination, the antibody titre decline was most pronounced among the youngest but both young infants and toddlers showed a clear booster response to a fourth dose. MeNZB was safe and well tolerated. The comprehensive post-licensure safety surveillance revealed no safety concerns. 相似文献
10.
Giacomo Frosi Alessia Biolchi Morena Lo Sapio Fabio Rigat Stefanie Gilchrist Jay Lucidarme Jamie Findlow Ray Borrow Mariagrazia Pizza Marzia Monica Giuliani Duccio Medini 《Vaccine》2013
Background
4CMenB (Bexsero), a vaccine developed against invasive meningococcal disease caused by capsular group B strains (MenB), was recently licensed for use by the European Medicines Agency. Assessment of 4CMenB strain coverage in specific epidemiologic settings is of primary importance to predict vaccination impact on the burden of disease. The Meningococcal Antigen Typing System (MATS) was developed to predict 4CMenB strain coverage, using serum bactericidal antibody assay with human complement (hSBA) data from a diverse panel of strains not representative of any specific epidemiology.Objective
To experimentally validate the accuracy of MATS-based predictions against strains representative of a specific epidemiologic setting.Methods and results
We used a stratified sampling method to identify a representative sample from all MenB disease isolates collected from England and Wales in 2007–2008, tested the strains in the hSBA assay with pooled sera from infant and adolescent vaccinees, and compared these results with MATS. MATS predictions and hSBA results were significantly associated (P = 0.022). MATS predicted coverage of 70% (95% CI, 55–85%) was largely confirmed by 88% killing in the hSBA (95% CI, 72–95%). MATS had 78% accuracy and 96% positive predictive value against hSBA.Conclusion
MATS is a conservative predictor of strain coverage by the 4CMenB vaccine in infants and adolescents. 相似文献11.
Background
Nine randomized controlled clinical trials, including approximately 26,000 children aged 6 months to 17 years, have evaluated the efficacy of live attenuated influenza vaccine (LAIV) against culture-confirmed influenza illness compared with placebo or trivalent inactivated influenza vaccine (TIV). The objective of the current analysis was to integrate available LAIV efficacy data in children aged 2-17 years, the group for whom LAIV is approved for use.Methods
A meta-analysis was conducted using all available randomized controlled trials and a fixed-effects model. Cases caused by drifted influenza B were analyzed as originally classified and with all antigenic variants classified as dissimilar.Results
Five placebo-controlled trials (4 were 2-season trials) and 3 single-season TIV-controlled trials were analyzed. Compared with placebo, year 1 efficacy of 2 doses of LAIV was 83% (95% CI: 78, 87) against antigenically similar strains; efficacy was 87% (95% CI: 78, 93), 86% (95% CI: 79, 91), and 76% (95% CI: 63, 84) for A/H1N1, A/H3N2, and B, respectively. Classifying B variants as dissimilar, efficacy against all similar strains was 87% (95% CI: 83, 91) and 93% (95% CI: 83, 97) against similar B strains. Year 2 efficacy was 87% (95% CI: 82, 91) against similar strains. Compared with TIV, LAIV recipients experienced 44% (95% CI: 28, 56) and 48% (95% CI: 38, 57) fewer cases of influenza illness caused by similar strains and all strains, respectively. LAIV efficacy estimates for children from Europe, the United States, and Middle East were robust and were similar to or higher than those for the overall population.Conclusions
In children aged 2-17 years, LAIV demonstrated high efficacy after 2 doses in year 1 and revaccination in year 2, and greater efficacy compared with TIV. This meta-analysis provides precise estimates of LAIV efficacy among the approved pediatric age group. 相似文献12.
《Vaccine》2020,38(46):7393-7400
BackgroundA randomized, double-blind, placebo-controlled multicenter trial was conducted in healthy Chinese infants to assess the efficacy, immunogenicity and safety of a novel trivalent live human-lamb reassortant rotavirus vaccine (LLR3) against rotavirus gastroenteritis (RVGE).MethodsHealthy children aged 6–13 weeks were enrolled and randomized (1:1) to either 3 oral doses of LLR3 or placebo according to a 0, 1, 2 month schedule. The objectives were to evaluate vaccine efficacy (VE) against RVGE of any-severity, severe RVGE (sRVGE) and inpatient caused by rotavirus serotypes contained in the vaccine and not contained in the vaccine after the third dose. Immunogenicity was also assayed in a subgroup. All adverse events (AEs) were collected from 30 min after each dose for immediate reaction, even to the entire study period, including the serious AEs (SAEs) and intussusception.ResultsVE against RVGE of any-severity, sRVGE and inpatient caused by any serotype was 56.6% (95% CI: 50.7, 61.8), 70.3% (95% CI: 60.6, 77.6) and 74.0% (95% CI: 57.5, 84.1) respectively. VE against RVGE of any-severity, sRVGE caused by serotypes not contained in vaccine were 54.2% (95% CI: 47.5, 60.1) and 70.4% (95% CI: 60.4, 77.9). The rate of seroconversion and four-fold increase of rotavirus serotype G2-, G3-, and G4-specific IgA is 60.8%, 58.0%, and 60.6% in vaccine group, which was higher than 21.35%, 22.7%, and 23.1% in placebo group (p < 0.0001 for G2, G3, G4), as well as the Geometric Mean Titer (GMT). Through the entire trial, 65.91% and 67.79% of participants reported at least one AE, and 0.02% and 0.02% reported SAEs in the vaccine and placebo groups, respectively. Two intussusception cases were reported both in vaccine and placebo group.ConclusionsIn Chinese infants, LLR3 provided a substantial protection against RVGE of any-severity, sRVGE and inpatient caused by any serotype, and showed well immunogenicity and safety. 相似文献
13.
Streptococcus pneumoniae is a major cause of bacterial pneumonia and other respiratory tract infections (RTI) in children. The heptavalent conjugated pneumococcal vaccine (PCV7) is offering a promising strategy against pneumococcal disease in children younger than 2 years. In this prospective epidemiological study in Germany, children between 2 and 6 months of age received in a 3:1 ratio a routine childhood vaccine combination with or without PCV7 according to a four-dose schedule. Five thousand nine hundred and eighty-four children were evaluable 1 year after the booster dose. Due to German guidelines children with underlying medical conditions were preferentially included into the PCV7 group and hence 66% of the children in the PCV7 group had at least one medical risk factor and 40% were preterm born compared to 18% and 6% in the control group. Overall PCV7 reduced respiratory tract infections by 10.5% (95% CI: 2.9-17.3%) and clinically diagnosed pneumonia by 6.3% (95% CI: -15.9 to 23.7%) in this unbalanced situation. In a propensity score matched pair analysis controlling for risk factors, effectiveness of PCV7 against pneumonia was 24.8% (95% CI: 0.9-43.1%). In children with at least one medical risk factor vaccine effectiveness against pneumonia was 38.4% (95% CI: 10.7-55.9%) compared to 10.9% (95% CI: -20.2 to 33.9%) without a risk factor. In preterm and term born children, PCV7 was well tolerated when simultaneously administered with widely used hexavalent routine vaccine combinations. The results demonstrate that PCV7 is safe and effective against RTI in preterm children and in children with comorbidities stressing the benefit of pneumococcal conjugate vaccine in these children at high risk for pneumococcal disease. 相似文献
14.
15.
Soriano-Gabarró M Toé L Tiendrebeogo SR Nelson CB Dabal M Djingarey MH Plikaytis B Rosenstein N;WHO Trivalent Vaccine Impact Assessment Study Group 《Vaccine》2007,25(Z1):A92-A96
Following a large Neisseria meningitidis W135 (NmW135) epidemic in Burkina Faso (BF) during 2002, a newly licensed trivalent A/C/W135 meningococcal polysaccharide vaccine was introduced in 2003. We conducted a case-control study to assess the vaccine effectiveness (VE) against meningococcal disease. Thirty-two N. meningitidis A (NmA) and 3 NmW135 meningitis cases were enrolled and matched by age-neighborhood to 103 controls. After adjusting for confounding risk factors, VE against NmA or NmW135 was 83.6% (95% CI 31.8-97.0, p=0.01) for persons with verified vaccination. VE against probable/definite NmA alone was 94.0% (95% CI 58.7-99.0, p=0.0003). Low number of NmW135 cases did not allow estimation of VE against NmW135 alone. The vaccine was highly effective against the epidemic. Since 2003, the trivalent vaccine continues to be effectively used in Africa for the control of meningococcal disease epidemics. 相似文献
16.
Containing pandemic influenza with antiviral agents 总被引:17,自引:0,他引:17
For the first wave of pandemic influenza or a bioterrorist influenza attack, antiviral agents would be one of the few options to contain the epidemic in the United States until adequate supplies of vaccine were available. The authors use stochastic epidemic simulations to investigate the effectiveness of targeted antiviral prophylaxis to contain influenza. In this strategy, close contacts of suspected index influenza cases take antiviral agents prophylactically. The authors compare targeted antiviral prophylaxis with vaccination strategies. They model an influenza pandemic or bioterrorist attack for an agent similar to influenza A virus (H2N2) that caused the Asian influenza pandemic of 1957-1958. In the absence of intervention, the model predicts an influenza illness attack rate of 33% of the population (95% confidence interval (CI): 30, 37) and an influenza death rate of 0.58 deaths/1,000 persons (95% Cl: 0.4, 0.8). With the use of targeted antiviral prophylaxis, if 80% of the exposed persons maintained prophylaxis for up to 8 weeks, the epidemic would be contained, and the model predicts a reduction to an illness attack rate of 2% (95% Cl: 0.2, 16) and a death rate of 0.04 deaths/1,000 persons (95% CI: 0.0003, 0.25). Such antiviral prophylaxis is nearly as effective as vaccinating 80% of the population. Vaccinating 80% of the children aged less than 19 years is almost as effective as vaccinating 80% of the population. Targeted antiviral prophylaxis has potential as an effective measure for containing influenza until adequate quantities of vaccine are available. 相似文献
17.
Kawamura N Tokoeda Y Oshima M Okahata H Tsutsumi H Van Doorn LJ Muto H Smolenov I Suryakiran PV Han HH 《Vaccine》2011,29(37):6335-6341
A phase III, randomized, double-blind study evaluated the efficacy, reactogenicity, safety and immunogenicity of a human rotavirus vaccine, RIX4414 in Japanese infants aged 6-14 weeks when administered as two doses (0, 1-month schedule). Efficacy against any and severe rotavirus gastroenteritis leading to medical intervention caused by circulating wild-type rotavirus from two weeks post-Dose 2 until two years of age was 79.3% (95% CI: 60.5-89.8%) and 91.6% (95% CI: 62.4-99.1%), respectively. Solicited, unsolicited symptoms and serious adverse events were reported at a similar frequency in both groups. Serum anti-rotavirus antibody seroconversion rate one-month post-Dose 2 was 85.3% (95% CI: 68.9-95%) in RIXX4414 group. RIX4414 was efficacious, well-tolerated and immunogenic in Japanese infants and introduction of vaccination could help in reducing the disease burden. 相似文献
18.
Background
Trivalent seasonal influenza vaccines contain 2 A strains and 1 B strain. B strains of 2 antigenically distinct lineages, Yamagata and Victoria, have been co-circulating annually, and the B strain included in vaccines often has not been a lineage match to the major circulating strain. Thus, a vaccine containing B strains from both lineages could broaden protection against influenza. Quadrivalent live attenuated influenza vaccine (Q/LAIV) is an investigational 4-strain formulation of LAIV that contains 2 A strains, A/H1N1 and A/H3N2, and 2 B strains, 1 from each lineage.Methods
A randomized, double-blind, active-controlled study of Q/LAIV was conducted in 1800 adults aged 18-49 years to compare the immunogenicity and safety of Q/LAIV to trivalent LAIV (T/LAIV). Subjects were randomized 4:1:1 to receive an intranasal dose of Q/LAIV (n = 1200) or 1 of 2 matching T/LAIV vaccines, each containing 1 of the B strains included in Q/LAIV (n = 600 total). The primary endpoint was the comparison of the post-vaccination strain-specific geometric mean titers (GMT) of hemagglutination inhibition antibody in Q/LAIV recipients to those in T/LAIV recipients, with immunologic noninferiority of Q/LAIV to be demonstrated if the upper bound of the 2-sided 95% confidence interval (CI) for the ratio of the GMTs [T/LAIV divided by Q/LAIV] was ≤1.5 for all strains.Results and Conclusion
Q/LAIV met the criteria for noninferiority: the ratios of the GMTs for the A/H1N1, A/H3N2, B/Yamagata, and B/Victoria strains were 1.09 (95% CI, 1.01-1.18), 1.05 (95% CI, 0.96-1.14), 1.10 (95% CI, 0.97-1.25), and 0.92 (95% CI, 0.82-1.03), respectively. Solicited symptoms and adverse events were similar in the Q/LAIV and T/LAIV arms. Q/LAIV may confer increased protection against influenza by targeting B strains from both lineages. 相似文献19.
Johannes Elias Leo M. Schouls Ingrid van de Pol Wendy C. Keijzers Diana R. Martin Anne Glennie Philipp Oster Matthias Frosch Ulrich Vogel Arie van der Ende 《Emerging infectious diseases》2010,16(3):464-472
Emergence of serogroup B meningococci of clonal complex sequence type (ST) 41/44 can cause high levels of disease, as exemplified by a recent epidemic in New Zealand. Multiplication of annual incidence rates (3.1 cases/100,000 population) of meningococcal disease in a defined German region, the city of Aachen and 3 neighboring countries (Greater Aachen) prompted us to investigate and determine the source and nature of this outbreak. Using molecular typing and geographic mapping, we analyzed 1,143 strains belonging to ST41/44 complex, isolated from persons with invasive meningococcal disease over 6 years (2001–2006) from 2 German federal states (total population 26 million) and the Netherlands. A spatially slowly moving clone with multiple-locus variable-number tandem repeat analysis type 19, ST42, and antigenic profile B:P1.7–2,4:F1–5 was responsible for the outbreak. Bactericidal activity in serum samples from the New Zealand MeNZB vaccination campaign confirmed vaccine preventability. Because this globally distributed epidemic strain spreads slowly, vaccination efforts could possibly eliminate meningococcal disease in this area. 相似文献
20.
Rivera L Peña LM Stainier I Gillard P Cheuvart B Smolenov I Ortega-Barria E Han HH 《Vaccine》2011,29(51):9508-9513
Transmission of excreted vaccine-derived infectious virus from vaccinated to unvaccinated individuals is possible within close contacts. This randomized (1:1), double-blind study evaluated the potential for transmission of human rotavirus vaccine strain, HRV (Rotarix™) from vaccine recipients to unvaccinated close contacts (twins). 100 pairs of healthy twins aged 6-14 weeks at the time of Dose 1 of HRV vaccine/placebo were enrolled and one randomly selected twin from each pair received two vaccine doses and the other received placebo doses (at 2 and 4 months of age). Presence of vaccine strain in the stool samples of placebo recipients was an indicator of transmission. Serial stool samples were tested for rotavirus using ELISA at pre-determined time points; rotavirus positive stool samples were tested with RT-PCR and reverse hybridization assay to identify G1P[8] vaccine strain. If G1P[8] vaccine strain was detected, the complete genome was sequenced to assess the similarity between viral isolates. Immunogenicity and safety of HRV vaccine in transmission cases was assessed. 15 transmission cases were reported in 80 evaluable twins who received placebo and the transmission rate was 18.8% (95% CI: 10.9-29.0%). None of the transmission cases was associated with gastroenteritis symptoms. Anti-rotavirus IgA seroconversion was 62.5% (95% CI: 51.0-73.1%) (HRV) and 21.3% (95% CI: 12.9-31.8%) (placebo) 7-weeks post-Dose 2; seroconversion in transmission cases was 26.7% (95% CI: 7.8-55.1%). Genetic variations or amino acid substitutions in transmission cases were similar to that seen in corresponding vaccine recipients. Transmission of HRV vaccine strain to unvaccinated twins living in close contact occurred, however, they were not associated with increased of gastroenteritis. Whether transmission leads to indirect protection among unvaccinated individuals remains unknown at this stage. 相似文献