Immunogenicity, reactogenicity and safety of a human rotavirus vaccine (RIX4414) in Korean infants: A randomized, double-blind, placebo-controlled, phase IV study Day-to-Day Reactogenicity and the Healthy Vaccinee Effect of Measles-Mumps-Rubella Vaccination FREQUENCY OF TRUE ADVERSE REACTIONS TO MEASLES-MUMPS-RUBELLA VACCINE: A Double-blind Placebo-controlled Trial in Twins Infant vaccinations and risk of childhood acute lymphoblastic leukaemia in the USA Effect of human rotavirus vaccine on severe diarrhea in African infants. Successful co-administration of a human rotavirus and oral poliovirus vaccines in Bangladeshi infants in a 2-dose schedule at 12 and 16 weeks of age. Postmarketing Surveillance of Intussusception Following Mass Introduction of the Attenuated Human Rotavirus Vaccine in Mexico Safety and efficacy of an attenuated vaccine against severe rotavirus gastroenteritis. Efficacy of a Pentavalent Human-bovine Reassortant Rotavirus Vaccine Against Rotavirus Gastroenteritis Among American Indian Children Postmarketing evaluation of the safety and effectiveness of varicella vaccine. Efficacy, Immunogenicity, and Safety of a Pentavalent Human-Bovine (WC3) Reassortant Rotavirus Vaccine at the End of Shelf Life Safety and reactogenicity of primary vaccination with the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine in Vietnamese infants: a randomised, controlled trial Evaluation of RIX4414, a live, attenuated rotavirus vaccine, in a randomized, double-blind, placebo-controlled phase 2 trial involving 2464 Singaporean infants. Risk of childhood leukemia associated with vaccination, infection, and medication use in childhood: the Cross-Canada Childhood Leukemia Study. An evaluation of the adverse reaction potential of three measles-mumps-rubella combination vaccines. Comparative Evaluation of Safety and Immunogenicity of Two Dosages of an Oral Live Attenuated Human Rotavirus Vaccine Risk of Serious Neurologic Disease After Immunization of Young Children in Britain and Ireland Immunogenicity, reactogenicity and safety of the human rotavirus vaccine RIX4414 oral suspension (liquid formulation) in Finnish infants. The efficacy in Navajo infants of a conjugate vaccine consisting of Haemophilus influenzae type b polysaccharide and Neisseria meningitidis outer-membrane protein complex. Experience of pentavalent human-bovine reassortant rotavirus vaccine among healthy infants in Taiwan. Rotavirus vaccine RIX4414 efficacy sustained during the third year of life: a randomized clinical trial in an Asian population. Safety and Immunogenicity of a Meningococcal Quadrivalent Conjugate Vaccine in Five- to Eight-Year-Old Saudi Arabian Children Previously Vaccinated with Two Doses of a Meningococcal Quadrivalent Polysaccharide Vaccine Safety and Efficacy of the Pentavalent Human-Bovine (WC3) Reassortant Rotavirus Vaccine in Healthy Premature Infants GRADE guidelines: 3. Rating the quality of evidence. Safety, Reactogenicity and Immunogenicity of the Human Rotavirus Vaccine in Preterm European Infants: A Randomized Phase IIIb Study Human Rotavirus Vaccine Is Highly Efficacious When Coadministered With Routine Expanded Program of Immunization Vaccines Including Oral Poliovirus Vaccine in Latin America Infections and vaccinations as risk factors for childhood Type I (insulin-dependent) diabetes mellitus: a multicentre case-control investigation Concomitant Use of an Oral Live Pentavalent Human-Bovine Reassortant Rotavirus Vaccine With Licensed Parenteral Pediatric Vaccines in the United States A postmarketing evaluation of the safety of Ann Arbor strain live attenuated influenza vaccine in children 5 through 17 years of age. Efficacy of the oral pentavalent rotavirus vaccine in Mali. Methodology and lessons-learned from the efficacy clinical trial of the pentavalent rotavirus vaccine in Bangladesh. Safety of measles, mumps and rubella vaccination in juvenile idiopathic arthritis Efficacy of pentavalent rotavirus vaccine against severe rotavirus gastroenteritis in infants in developing countries in Asia: a randomised, double-blind, placebo-controlled trial Safety, Reactogenicity, and Immunogenicity of Human Rotavirus Vaccine RIX4414 in Human Immunodeficiency Virus-positive Infants in South Africa Efficacy of RIX4414 Live Attenuated Human Rotavirus Vaccine in Finnish Infants The immunogenicity of three Haemophilus influenzae type B conjugate vaccines after a primary vaccination series in Philippine infants. The safety of inactivated influenza vaccine in adults and children with asthma. Safety and efficacy of human rotavirus vaccine during the first 2 years of life in Asian infants: randomised, double-blind, controlled study. Comparison of 2 different regimens for reactogenicity, safety, and immunogenicity of the live attenuated oral rotavirus vaccine RIX4414 coadministered with oral polio vaccine in South African infants.
Rotavirus ( RV ) infection is the primary cause for childhood gastroenteritis worldwide . In Korea , RV infection is most common among children less than 5 y of age . This post-licensure study was conducted to further evaluate the RV vaccine ( RIX4414 ) to provide additional local clinical data to the Korean Food and Drug Association . Healthy infants aged 6–12 weeks were enrolled to receive two doses of either RIX4414 or placebo as per 0 , 1–2 mo schedule . Blood sample s were collected before dose-1 and one month post-dose-2 of RIX4414/placebo to assess serum anti-RV IgA antibody concentrations using ELISA . Gastroenteritis stool sample s were tested for the presence of RV using ELISA . RV positive sample s were subjected to further analysis for G and P typing . Among 684 infants enrolled and vaccinated , 432 infants ( RIX4414 = 318 ; placebo = 114 ) were included in the according-to- protocol cohort for immunogenicity . The anti-RV IgA antibody seroconversion rates in the RIX4414 group following one month post-dose-2 were 88.1 % ( 95 % CI : 84.0–91.4 ) and the corresponding geometric mean concentration in the RIX4414 group was 208.5 U/ml ( 95 % CI : 174.2–249.5 ) . Occurrence of solicited and unsolicited adverse events were similar in both , RIX4414 and placebo groups . None of the gastroenteritis stool sample s tested positive for RV and no fatal SAEs were reported in either groups . The two-dose regimen of RIX4414 was observed to be immunogenic with a similar safety profile as compared with the placebo group , when administered to healthy Korean infants Objective . Revaccination policies adopted in many countries to control measles have raised various safety issues including those concerning the second vaccine dose . We performed a prospect i ve , double-blind , crossover trial among twins receiving a measles-mumps-rubella ( MMR ) vaccine .  Study Design . The study comprised 1162 monozygous and heterozygous twins , each of whom r and omly received placebo and then vaccine , or vice versa , 3 weeks apart , at 14 to 83 months of age . Most of the oldest children had previously been vaccinated against measles , and one half of the remainder of children had had the disease . Symptoms and signs were recorded daily on structured forms . Statistical methods included a complex analysis of the vaccine attributability of the symptoms and conditional logistic regression . Results . Vaccination-attributable events occurred in 6 % overall . At 14 to 18 months of age , reactions developed between days 6 and 14 , peaking at day 10 . The clearest vaccine-attributable effect was fever exceeding 101.3 ° F ( 38.5 ° C ; odds ratio : 3.28 ; 95 % confidence interval : 2.23–4.82 ; P < .001 ) , but the same trend was found for rash , arthralgia , conjunctivitis , staying in bed , drowsiness , and irritability . At 6 years of age , systemic reactions occurred 5 to 15 times less frequently , only arthralgia being associated with vaccination . Zygocity , gender , history of allergy , or infections did not modify reactions . Instead , respiratory symptoms developed within days postinjection to a level of 15 % to 20 % without subsequent decline and with no difference between vaccinees and placebo recipients . Conclusion . Vaccination was avoided during infections , but many small children became mildly ill within a week or so with no relation to vaccination ( the healthy vaccinee effect ) . MMR vaccine was virtually nonreactogenic when given at 6 years of age . vaccine , measles , mumps , rubella , reactogenicity , adverse events , zygocity , healthy vaccinee effect The vast majority of adverse reactions following immunisation of children with live measles-mumps-rubella ( MMR ) vaccine  were shown in a double-blind , placebo-controlled , cross-over study in 581 twin pairs to be only temporally but not causally related to the vaccination . The true frequency of side-effects caused by MMR vaccine , estimated from the discordance rates of individual signs and symptoms between MMR vaccinees and their placebo-injected twins , was between 0.5 and 4.0 % . Moreover , respiratory symptoms , nausea , and vomiting were observed more frequently in the placebo-injected group than in the MMR vaccinated group Summary Previous studies have suggested that infant vaccinations may reduce the risk of subsequent childhood leukaemia .  Vaccination histories were compared in 439 children ( ages 0–14 ) diagnosed with acute lymphoblastic leukaemia ( ALL ) in nine Midwestern and Mid-Atlantic states ( USA ) between 1 January 1989 and 30 June 1993 and 439 controls selected by r and om-digit dialing and individually matched to cases on age , race and telephone exchange . Among matched pairs , similar proportions of cases and controls had received at least one dose of oral poliovirus ( 98 % ) , diphtheria – tetanus – pertussis ( 97 % ) , and measles – mumps – rubella ( 90 % ) vaccines . Only 47 % of cases and 53 % of controls had received any  Haemophilus influenzae type b ( Hib ) vaccine  ( relative risk ( RR ) = 0.73 ; 95 % confidence interval ( CI ) 0.50–1.06 ) . Although similar proportions of cases ( 12 % ) and controls ( 11 % ) received the polysaccharide Hib vaccine ( RR = 1.13 ; 95 % CI 0.64–1.98 ) , more controls ( 41 % ) than cases ( 35 % ) received the conjugate Hib vaccine ( RR = 0.57 ; 95 % CI 0.36–0.89 ) . Although we found no relationship between most infant vaccinations and subsequent risk of childhood ALL , our findings suggest that infants receiving the conjugate Hib vaccine may be at reduced risk of subsequent childhood acute lymphoblastic leukemia . Further studies are needed to confirm this association and , if confirmed , to eluci date the underlying mechanism BACKGROUND Rotavirus is the most common cause of severe gastroenteritis among young children worldwide . Data are needed to assess the efficacy of the rotavirus vaccine in African children . METHODS We conducted a r and omized , placebo-controlled , multicenter trial in South Africa ( 3166 infants ; 64.1 % of the total ) and Malawi ( 1773 infants ; 35.9 % of the total ) to evaluate the efficacy of a live , oral rotavirus vaccine in preventing severe rotavirus gastroenteritis . Healthy infants were r and omly assigned in a 1:1:1 ratio to receive two doses of vaccine ( in addition to one dose of placebo ) or three doses of vaccine - the pooled vaccine group - or three doses of placebo at 6 , 10 , and 14 weeks of age . Episodes of gastroenteritis caused by wild-type rotavirus during the first year of life were assessed through active follow-up surveillance and were grade d with the use of the Vesikari scale . RESULTS A total of 4939 infants were enrolled and r and omly assigned to one of the three groups ; 1647 infants received two doses of the vaccine , 1651 infants received three doses of the vaccine , and 1641 received placebo . Of the 4417 infants included in the per- protocol efficacy analysis , severe rotavirus gastroenteritis occurred in 4.9 % of the infants in the placebo group and in 1.9 % of those in the pooled vaccine group ( vaccine efficacy , 61.2 % ; 95 % confidence interval , 44.0 to 73.2 ) . Vaccine efficacy was lower in Malawi than in South Africa ( 49.4 % vs. 76.9 % ) ; however , the number of episodes of severe rotavirus gastroenteritis that were prevented was greater in Malawi than in South Africa ( 6.7 vs. 4.2 cases prevented per 100 infants vaccinated per year ) . Efficacy against all-cause severe gastroenteritis was 30.2 % . At least one serious adverse event was reported in 9.7 % of the infants in the pooled vaccine group and in 11.5 % of the infants in the placebo group . CONCLUSIONS Human rotavirus vaccine significantly reduced the incidence of severe rotavirus gastroenteritis among African infants during the first year of life . ( Clinical Trials.gov number , NCT00241644 . ) Co-administration of oral live-attenuated human rotavirus vaccine RIX4414 ( Rotarix ) and oral polio vaccine ( OPV ) was assessed . Healthy infants were r and omised to receive 2-doses of either : RIX4414 or placebo co-administered with OPV ( 12 and 16 weeks of age ) ; or RIX4414 or placebo given 15 days after OPV . After vaccination , 56.5 - 66.7 % of RIX4414 and 18.6 % of placebo recipients had seroconverted for rotavirus IgA. No significant differences between RIX4414 groups with or without OPV co-administration were observed . No statistically significant differences were observed between groups for polio seroprotection rates . RIX4414 vaccine was immunogenic when co-administered with OPV and did not interfere with OPV seroprotection rates Background : Mexico initiated mass vaccination with the attenuated human rotavirus vaccine ( Rotarix ) in 2006 . This postlicensure study aim ed to assess any potential temporal association between vaccination and intussusception in Mexican infants . Methods : Prospect i ve , active surveillance for intussusception among infants aged less than 1 year was conducted in 221 hospitals across Mexico from the Mexican Institute of Social Security between January 2008 and October 2010 . The temporal association between vaccination and intussusception was assessed by self-controlled case-series analysis . Results : Of the 753 episodes of intussusception reported in 750 infants , 701 were in vaccinated infants ( 34.5 % post – dose 1 , 65.5 % post – dose 2 ) . The relative incidence of intussusception within 31 days of vaccination was 1.75 ( 95.5 % confidence interval [ CI ] : 1.24–2.48 ; P = 0.001 ) post – dose 1 and 1.06 ( 95.5 % CI : 0.75–1.48 ; P = 0.75 ) post – dose 2 . The relative incidence of intussusception within 7 days of vaccination was 6.49 post – dose 1 ( 95.5 % CI : 4.17–10.09 ; P < 0.001 ) and 1.29 post – dose 2 ( 95.5 % CI : 0.80–2.11 ; P = 0.29 ) . Clustering of intussusception within 7 days of vaccination was observed post – dose 1 . An attributable risk of 3 to 4 additional cases of intussusception per 100,000 vaccinated infants was estimated . Conclusion : This is the largest surveillance study for intussusception after rotavirus vaccination to date . A temporal increase in the risk for intussusception was seen within 7 days of administration of the first vaccine dose . It is still uncertain whether rotavirus vaccination has any impact on the overall incidence of intussusception . This finding has to be put in perspective with the well-documented substantial benefits of rotavirus vaccination BACKGROUND The safety and efficacy of an attenuated G1P[8 ] human rotavirus ( HRV ) vaccine were tested in a r and omized , double-blind , phase 3 trial . METHODS We studied 63,225 healthy infants from 11 Latin American countries and Finl and 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 grade d 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 percent ; P<0.001 ) . During the 31-day window after each dose , six vaccine recipients and seven placebo recipients had definite intussusception ( difference in risk , -0.32 per 10,000 infants ; 95 percent confidence interval , -2.91 to 2.18 ; P=0.78 ) . CONCLUSIONS Two oral doses of the live attenuated G1P[8 ] HRV vaccine were highly efficacious in protecting infants against severe rotavirus gastroenteritis , significantly reduced the rate of severe gastroenteritis from any cause , and were not associated with an increased risk of intussusception . ( Clinical Trials.gov numbers , NCT00139347 and NCT00263666 . Background : Before the widespread use of rotavirus vaccines , rotavirus was a leading cause of gastroenteritis among children . Navajo and White Mountain Apache children suffer a disproportionate burden of severe rotavirus disease compared with the general US population . Methods : We enrolled Navajo and White Mountain Apache infants in a multicenter , double-blind , placebo-controlled trial of pentavalent human-bovine reassortant rotavirus vaccine ( PRV ) . Subjects received 3 doses of vaccine or placebo at 4 to 10 week intervals , with the first dose given between 6 and 12 weeks of age . Gastroenteritis episodes were identified by active surveillance . Disease severity was determined by a st and ardized scoring system . Results : There were 509 and 494 r and omized children who received vaccine and placebo , respectively . Among placebo recipients , the incidence of rotavirus gastroenteritis was 34.2 episodes/100 child-years ( 95 % confidence interval [ 95 % CI ] : 25.8–38.9 ) versus 8.1 episodes/100 child-years ( 95 % CI : 5.4–12.5 ) in the vaccine group . The percentage of rotavirus episodes caused by serotypes G1 , G2 , and G3 was 72.3 % , 23.4 % , and 2.1 % , respectively . There were no severe rotavirus episodes among vaccinees and 4 among placebo recipients . PRV was 77.1 % ( 95 % CI : 59.7–87.6 ) , 89.5 % ( 95 % CI : 65.9–97.9 ) , and 82.9 % ( 95 % CI : 61.1–93.6 ) effective against G1–G4 rotavirus disease , severe and moderate rotavirus disease combined , and outpatient visits for rotavirus disease , respectively . The risk of adverse events was similar for the vaccine and placebo groups . Conclusions : PRV was highly effective in preventing rotavirus disease and related health care utilization in these American Indian infants . Vaccine efficacy and immunogenicity were similar to the overall study population enrolled in the multicenter trial BACKGROUND The Oka strain of live attenuated varicella virus was licensed for use in healthy children in the United States in March , 1995 . We report a postmarketing evaluation of the short term safety of this vaccine within Kaiser Permanente . METHODS After licensure varicella vaccination was introduced into the preventive care program of the Northern California Kaiser Permanente Medical Care Program . Potential adverse events after vaccination with varicella vaccine were identified from automated clinical data bases of hospitalizations , emergency room visits and clinic visits . Deaths were identified from automated clinical data bases at Kaiser as well as from the State death records for California . To evaluate safety , rates of diagnosis-specific events in the risk periods were compared with the rates of such diagnosis-specific events in two self control and one historical control period . RESULTS During the study period of April 1 , 1995 , to December 31 , 1996 , a total of 89753 adults and children received varicella vaccine .  A total of 3200 relative risks were calculated , and of these 5 hospital diagnostic categories , 9 emergency visit diagnostic categories and 30 outpatient diagnostic categories demonstrated at least 1 relative risk with a P value of < 0.05 in 1 or more age groups and in comparisons with 1 control period or more . The p value for these tests was not adjusted for multiple comparisons . Of these categories 14 demonstrated an increased risk either in more than 1 age group or against more than 1 comparison group . These categories included elective procedures , febrile seizure , febrile illness , well child , acute gastroenteritis , varicella , congenital anomaly , " rule out sepsis , " trauma , viral syndrome , apnea , back pain , congenital valvular heart disease and vision evaluation for glasses . Of these the outcomes of elective procedure , congenital anomaly , congenital valvular heart disease , well child and vision evaluation for glasses were judged not to have a biologically plausible association with vaccination . A second diagnostic grouping included febrile illness , viral illness , febrile seizure and " rule out sepsis . " In an analysis of these events which adjusted for the concomitant administration of M-M-R(II ) vaccine , none of the associations was statistically associated with receipt of varicella vaccine . The diagnostic category of " rule out sepsis " still had a relative risk of 1.95 with P = 0.02 . None of the children in the " rule out sepsis " category had positive bacteriologic cultures from any other normally sterile site . Because of the large number of gastroenteritis cases , we review ed a r and om sample of 100 exposed and 100 unexposed cases . From this review no consistent time association or clustering of any of these events was seen in the exposed follow-up time interval . Only gastroenteritis and negative evaluations for sepsis were thought to be possibly associated with receipt of varicella vaccine . Although there was a statistically significant increased risk over the entire 30 day-period , there was no clustering of these events within the 30-day window . CONCLUSION In this study population of 89753 children and adults , the varicella vaccine ( Oka strain , Merck ) appeared to have a favorable safety profile . In addition rates of varicella-like rash and of breakthrough cases were both low and consistent with the rates observed in prelicensure studies BACKGROUND . Rotavirus is the leading cause of dehydrating acute gastroenteritis in infants worldwide . Previous studies of a live pentavalent human-bovine reassortant rotavirus vaccine have shown it to be efficacious across a range of potencies . OBJECTIVE . Our goal was to evaluate the efficacy , immunogenicity , and safety of pentavalent rotavirus vaccine at the end of shelf life in healthy infants . PATIENTS AND METHODS . During 2002–2004 , 1312 healthy infants ∼6 to 12 weeks old from the United States ( 47 % ) and Finl and ( 53 % ) were r and omly assigned to receive 3 oral doses of vaccine ( vaccine at ∼1.1 × 107 infectious U per dose ) or placebo ∼4 to 10 weeks apart . Infants were to be followed for acute gastroenteritis through 1 rotavirus season after vaccination and for adverse events postvaccination . RESULTS . Three doses of pentavalent rotavirus vaccine at the end of shelf life demonstrated efficacy against rotavirus gastroenteritis caused by human G-serotypes included in the vaccine ( G1–G4 ) . Efficacy against severe rotavirus gastroenteritis was 100 % , and efficacy against any rotavirus gastroenteritis regardless of severity was 72.5 % . A threefold rise in G1 serum neutralizing was observed in 57 % and in anti-rotavirus immunoglobulin A in 96 % of pentavalent rotavirus vaccine recipients . No statistically significant increase in vomiting , diarrhea , or irritability was observed among pentavalent rotavirus vaccine recipients compared with placebo recipients within the 7-day period from each dose . A statistically significant increase in fevers ( ≥100.5 ° F , rectal equivalent ) was observed among pentavalent rotavirus vaccine recipients compared with placebo recipients after dose 1 . CONCLUSIONS . This pentavalent human-bovine rotavirus vaccine was generally well tolerated , efficacious , and immunogenic at the end of shelf life Background Pneumococcal infections are major causes of child mortality and morbidity worldwide and antibiotic resistance of Streptococcus pneumoniae is a major concern , especially in Asian countries . The present study was design ed to evaluate the reactogenicity and safety of the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine ( PHiD-CV ) when co-administered with the licensed diphtheria , tetanus , acellular pertussis , hepatitis B virus , inactivated poliovirus and H. influenzae type b vaccine ( DTPa-HBV-IPV/Hib ) in a 3-dose primary vaccination course in Vietnamese infants . Methods This phase III , open , r and omised study was conducted in one centre in Ho Chi Minh City between February and July 2011 . Healthy infants ( N=300 ) were r and omised ( 2:1 ) to receive either  PHiD-CV co-administered with DTPa-HBV-IPV/Hib ( PHiD-CV group ) or DTPa-HBV-IPV/Hib alone ( Control group ) at 2 , 3 , and 4 months of age . Results Within 31 days post-vaccination , 8.2 % of overall doses in the PHiD-CV group and 3.0 % of overall doses in the Control group were followed by at least one solicited and /or unsolicited , local and /or general adverse event of grade 3 intensity . Pain at injection site was the most common grade 3 solicited symptom , which was reported following 6.5 % and 1.0 % of overall doses in the PHiD-CV and Control groups , respectively . Within 4 days post-vaccination , the most common solicited local and general symptoms reported with any intensity were pain ( 48.9 % and 31.0 % of doses in the PHiD-CV and Control groups ) and irritability ( 58.0 % and 40.4 % of doses in the PHiD-CV and Control groups ) . Within 31 days post-vaccination , the incidence of unsolicited symptoms was comparable in both groups ( following 12.3 % and 14.8 % of doses in the PHiD-CV and Control groups , respectively ) . Throughout the study , 13 serious adverse events ( SAEs ) were reported in 9 infants in the PHiD-CV group and 11 SAEs in 6 infants in the Control group . None of them were fatal or considered causally related to vaccination . Conclusions PHiD-CV had a clinical ly acceptable safety profile when co-administered with DTPa-HBV-IPV/Hib in Vietnamese infants . The reactogenicity of PHiD-CV was comparable to that observed in other South-East Asian population s . Trial registration Clinical Trials.gov : BACKGROUND At present , no rotavirus vaccine is commercially available for use worldwide . Hence , a live , attenuated monovalent vaccine was developed with human strain RIX4414 ( G1P1A P[8 ] specificity ) . Vaccination trials involving infants are ongoing in developed and developing countries . METHODS This study was a r and omized , double-blind , placebo-controlled trial conducted at pediatric hospitals and polyclinics in Singapore for the evaluation of the immunogenicity , reactogenicity , and efficacy of 2 oral doses of RIX4414 . In total , 2464 healthy infants ( who were 11 - 17 weeks old when the first dose was administered , which is in accordance with the local immunization schedule ) were enrolled to receive RIX4414 at 3 concentrations of virus ( 10(4.7 ) , 10(5.2 ) , or 10(6.1 ) focus-forming units ) or placebo at 1-month intervals , concomitantly with routinely administered infant vaccines . RESULTS The RIX4414 vaccine was highly immunogenic , and virtually all vaccine recipients ( 98%-100 % ) experienced " vaccine take " ( i.e. , a combined immunogenicity end point based on seroconversion and /or shedding of RIX4414 in postvaccination stool sample s ) after receipt of 2 doses at all 3 dosage levels . Depending on the virus concentration , the anti-rotavirus IgA seroconversion rate varied from 76 % ( 95 % confidence interval [ CI ] , 68%-83 % ) to 91 % ( 95 % CI , 85%-95 % ) . Two doses of RIX4414 were well tolerated , with no increase in high fever , severe diarrhea , or vomiting after either dose or with increased viral concentration , compared with placebo . There was no observed interference with routine vaccinations of infants when RIX4414 was coadministered . The calculated efficacy of RIX4414 against rotavirus gastroenteritis was 82 % ( P = .046 ) ; however , this result was considered to be of limited conclusive value because of the low number of rotavirus gastroenteritis episodes identified during the follow-up period . CONCLUSIONS The live , attenuated rotavirus vaccine ( RIX4414 ) was well tolerated and highly immunogenic in Singaporean infants . The immunogenicity of routinely administered infant vaccines was not impaired by concomitant administration of RIX4414 vaccine Current hypotheses consonant with the peak in leukemia incidence in early childhood point to an infectious etiology . The authors examined the effect of postnatal exposures predicted to affect early immune functioning , including childhood vaccinations , illness , medication use , and breastfeeding patterns . Children 0 - 15 years of age diagnosed with leukemia from 1990 to 1994 and resident within principal cities across Canada were eligible for inclusion . Through pediatric oncology centers and population -based cancer registries , 399 cases were ascertained at the time of diagnosis . For each participating case , an age- , gender- , and area-matched control was r and omly selected from government health insurance rolls . Risk factor information was obtained through personal interviews with each child 's parents or guardians . Conditional logistic regression was used to calculate odds ratios , with adjustment for potential confounders . Use of immunosuppressant medication by the index child led to a deficit of risk ( odds ratio = 0.37 , 95 % confidence interval : 0.16 , 0.84 ) , while vitamin intake was positively associated with leukemia ( odds ratio = 1.66 , 95 % confidence interval : 1.18 , 2.33 ) . Breastfeeding for more than 6 months was also protective ( p < 0.05 ) . Results persisted for cases diagnosed with acute lymphoblastic leukemia and for children diagnosed at 1 - 5 years of age . These findings suggest a role for early immunologic challenge in the expression of childhood leukemia OBJECTIVE To compare the incidence of adverse events following the administration of three commercially available measles-mumps-rubella ( MMR ) combination vaccines . METHODS A r and omized double-blind clinical trial was performed in 1996 that involved a total of 10 142 students 6 - 12 years of age in the state of Rio Gr and e do Sul , in Brazil . An MMR vaccine containing the Edmonston-Zagreb , Leningrad-Zagreb , and RA 27/3 strains ( " vaccine A " ) was administered to 2 226 students ( 21.9 % of the total ) ; an MMR vaccine with the Moraten , Jeryl Lynn , and Wistar 27/3 strains ( " vaccine B " ) was administered to 2 216 children ( 21.8 % ) ; and an MMR vaccine containing the Schwartz , Urabe AM-9 , and Wistar 27/3 strains ( " vaccine C " ) was given to 2 179 students ( 21.5 % ) . A control group of 3 521 students ( 34.7 % ) was not vaccinated . Both the vaccinated subjects and the control subjects were followed daily for 30 days to detect any clinical manifestations . RESULTS Adverse events were more frequent in the vaccinated children than in the control group ( P < 0.01 ) . In terms of causing parotitis , vaccine A had a relative risk ( RR ) of 5.72 ( 95 % confidence interval ( CI ) = 3.11 - 10.54 ) when compared with vaccine B , and an RR of 2.33 ( 95 % CI = 1.52 - 3.58 ) when compared with vaccine C. Vaccine A was also associated with an increased risk of lymphadenopathy when compared with vaccine B ( RR = 3.11 ; 95 % CI = 1.78 - 5.45 ) and with vaccine C ( RR = 2.22 ; 95 % CI = 1.35 - 3.66 ) . Vaccine C was associated with an increased risk of parotitis when compared with vaccine B ( RR = 2.46 ; 95 % CI = 1.26 - 4.80 ) . Three cases of aseptic meningitis were detected among the children in the study group , but only one case of vaccine-related aseptic meningitis was identified , among the children receiving vaccine A. CONCLUSIONS The three MMR vaccines that we studied are associated with different risks of adverse events . We found vaccine A to cause more reactions than the two other vaccines , especially vaccine B. In addition , vaccine A presented both a temporal and a cause- and -effect association with one case of aseptic meningitis . We hope that this study will contribute information that can be used in choosing MMR vaccines with safe and effective strains , especially for mass vaccination strategies Background : Rotavirus is a major cause of gastroenteritis in children worldwide and is estimated to be responsible for more than 500,000 physician visits , 50,000 hospitalizations and 20 deaths in the United States each year . Objective : To compare the safety and immunogenicity of 2 dosages of a live attenuated oral monovalent G1 human rotavirus ( HRV ) vaccine in healthy infants . Design / Methods : In this r and omized , double blind trial conducted in the United States and Canada , 529 healthy infants 5–15 weeks of age received HRV vaccine containing either 105.2 or 106.4 focus-forming units or placebo . Two doses were administered orally at a 2-month interval concomitantly with routine childhood vaccines . Symptoms of fever , irritability/fussiness , diarrhea , vomiting , loss of appetite and cough/runny nose were solicited for 15 days postvaccination , nonserious adverse events for 43 days postvaccination and serious adverse events throughout the study . Vaccine take was defined as appearance of serum antirotavirus IgA in postimmunization sera at a titer of ≥20 units/mL or vaccine virus shedding in any stool sample collected between the first dose and 2 months after the second dose . Results : No serious adverse events considered related to vaccine were reported . The incidence of solicited symptoms was similar among treatment groups during the 15-day postvaccination surveillance periods . No significant difference in vaccine take after 2 doses ( 88.0 % in high dose group and 81.5 % in low dose group ) was seen between vaccine groups ( P = 0.153 ) . Conclusions : Two doses of either dosage level of HRV vaccine administered concurrently with routine childhood vaccines to healthy infants 5–15 weeks of age  were well-tolerated and were highly immunogenic OBJECTIVE . We sought to investigate the risk of serious neurologic disease after  immunization in early childhood . METHODS . The results of a 3-year prospect i ve study of children ( 2–35 months old ) in Britain and Irel and with encephalitis and /or severe illness with convulsions and fever were linked to each child 's vaccine history . Cases were reported via the British Paediatric Surveillance Unit 's network . The self-controlled case-series method was used to investigate associations between immunization and acute potential adverse events . The risk periods investigated were 0 to 3 and 0 to 7 days post – diphtheria , tetanus , whole cell pertussis , Haemophilus influenzae type b or meningococcal C conjugate vaccine and 6 to 11 and 15 to 35 days post – measles , mumps , rubella vaccine . RESULTS . A total of 157 disease episodes from 155 children met the analytical case definition . There were 11 cases of herpes simplex encephalitis and 23 cases of primary human herpesvirus 6 and /or 7 infection . There was no evidence of a raised relative incidence of serious neurologic disease in any of the specified risk periods with the exception of a raised relative incidence of 5.68 in the 6–11 days after measles , mumps , rubella vaccine . Based on this relative incidence , between 3 and 6 of the 6 cases in this period were estimated to be attributable to the vaccine with a best estimate of 5 . The 6 cases all had fever with convulsions lasting > 30 minutes ; in all but 1 , there was complete recovery by discharge from hospital . Of the 5 patients who recovered , 1 had a concurrent primary human herpesvirus 6 infection and one a primary human herpesvirus 7 . CONCLUSIONS . Six to 11 days after measles , mumps , rubella vaccine there is an increased risk of fever and convulsions lasting > 30 minutes . All 6 of the episodes temporally related to immunization met the criteria for complex febrile convulsions . The estimated attributable risk of serious neurological disease was similar to that previously found for measles vaccine The lyophilized formulation of a human rotavirus vaccine , Rotarix ™ ( RIX4414 ) is highly immunogenic . In order to comply with the World Health Organization 's ( WHO ) recommendation , a liquid formulation of the vaccine that does not require reconstitution was developed . The immunogenicity , reactogenicity and safety of the liquid formulation were compared with lyophilized formulation in two Finnish studies . In Study A infants aged 6 - 12 weeks received two doses of the lyophilized or liquid formulation of the vaccine or placebo following a 0,1 month schedule . In Study B , infants aged 10 - 17 weeks received two doses of either liquid or lyophilized formulation of the vaccine . In both studies , anti-rotavirus IgA antibodies were assessed pre-vaccination and one month post-Dose 2 . In Study A , the anti-rotavirus seroconversion rate was 90 % ( 95 % CI : 81.2 - 95.6 % ) and 83.7 % ( 95 % CI : 74.2 - 90.8 % ) in the groups that received the liquid and the lyophilized formulation of RIX4414 , respectively ; the respective anti-rotavirus IgA seroconversion rates in Study B were 88.6 % ( 95 % CI : 86.1 - 90.8 % ) and 90.5 % ( 95 % CI : 86.2 - 93.8 % ) . Reactogenicity and safety profiles of the two vaccine formulations were similar . Liquid formulation of the rotavirus vaccine allows greater flexibility in supply and reduces logistical costs BACKGROUND AND METHODS Several conjugate vaccines against Haemophilus influenzae type b have been developed in the search for one that induces protection even in young infants . We evaluated the safety and efficacy of a conjugate vaccine that links the H. influenzae type b capsular polysaccharide to the outer-membrane protein complex ( OMPC ) of Neisseria meningitidis serogroup B. We conducted a double-blind , placebo , controlled trial in Navajo infants , who are at high risk for systemic infections caused by H. influenzae type b. The infants were r and omly assigned to receive the first dose of vaccine or placebo at 42 to 90 days of age and the second at 70 to 146 days of age . RESULTS Of the infants in the trial , 2588 were assigned to receive the vaccine and 2602 to receive placebo .  The mean follow-up was 269 days in the vaccine group and 267 days in the placebo group . Before the age of 18 months , there was 1 systemic H. influenzae type b infection in the vaccine group , as compared with 22 in the placebo group ( P less than 0.001 ; point estimate of efficacy , 95 percent ; 95 percent confidence interval , 72 to 99 percent ) . Of the 22 H. influenzae type b infections in the placebo group , 13 were meningitis . Among the children who received both doses , there was 1 H. influenzae type b infection in the vaccine group ( n = 2056 ) and 14 in the placebo group ( n = 2105 ) ( P less than 0.001 ; point estimate of efficacy , 93 percent ; 95 percent confidence interval , 53 to 98 percent ) . The single infection in the vaccine group occurred at 15 1/2 months of age in an infant with osteomyelitis . Between the first and second doses there were no H. influenzae type b infections in the vaccine group and eight in the placebo group ( P less than 0.005 ; point estimate of efficacy , 100 percent ; 95 percent confidence interval , 41 to 100 percent ) . CONCLUSIONS The H. influenzae type b OMPC vaccine , administered at 2 and 4 months of age , is safe and induces a high rate of protection against invasive disease caused by H. influenzae type b in infants under the age of 18 months . Protection begins after the first dose BACKGROUND / PURPOSE Rotavirus infection is the most common etiology of acute gastroenteritis in young children worldwide . The first rotavirus vaccine was licensed by the United States Food and Drug Administration in 1998 but was suspended soon after in 1999 because of the possibility of induced intussusception . This study evaluated the safety and immunogenicity of a newly developed pentavalent rotavirus vaccine in Taiwanese children . METHODS This was a phase III global trial design ed to evaluate the safety and immunogenicity of an oral , live pentavalent rotavirus vaccine ( RotaTeq ) .  Taiwan was the only site in Asia enrolled in this trial . Normal healthy infants aged 6 - 12 weeks were enrolled , and each of the subjects received either three oral doses of the vaccine or placebo solution . The safety of the vaccine , particularly the risk of intussusception , and immunogenicity were studied . RESULTS A total of 189 infants were enrolled . No increased risk of intussusception or other adverse reactions were noted following the vaccination . RotaTeq was immunogenic among subjects enrolled in Taiwan . At least a three-fold rise in serum antirotavirus IgA antibody was found among 93 % of the vaccine group . The immunogenicity of RotaTeq in Taiwan was comparable to that in other areas . CONCLUSION The pentavalent human-bovine vaccine , RotaTeq , was safe , generally well-tolerated , and immunogenic among Taiwanese infants RIX4414 ( Rotarix ™ ) , has shown high efficacy during the first 2-years of life . A 2-year r and omized , double-blind , placebo-controlled trial in Singapore , Hong Kong , and Taiwan was extended for another year . Infants ( 6 - 17 weeks ) received 2-doses ( 1 - 2 months apart ) of RIX4414 ( n=5359 ) or placebo ( n=5349 ) . During the third-year follow-up , 4359 ( RIX4414 ) and 4328 ( placebo ) infants were monitored . 64 ( 1.2 % ) and 2 ( 0.04 % ) infants in the placebo and RIX4414 groups , respectively , reported severe rotavirus-gastroenteritis ( RVGE ) , result ing in a vaccine efficacy of 96.9 % ( 95 % CI [ 88.3 - 99.6 ] ) . Efficacy was 100 % ( 67.5 - 100 ) in the third-year . RIX4414 was efficacious against G1 ( 100.0 % [ 84.8 - 100 ] ) and pooled non-G1 RV types ( 94.9 % [ 80.2 - 99.4 ] ) . This study shows that the vaccine is highly efficacious , regardless of circulating RV-types , up to the first 3 years of life in affluent Asian urban population ABSTRACT Saudi Arabian children respond poorly to 2 doses of meningococcal quadrivalent polysaccharide vaccine ( MPSV4 ) when given before 2 years of age . This study examined whether such children were able to respond to 1 dose of quadrivalent meningococcal diphtheria toxoid conjugate vaccine ( MCV4 ) when they were older . Saudi Arabian children 5 to 8 years of age who had previously been vaccinated with 2 doses of MPSV4 when they were under 2 years of age ( termed the prior-MPSV4 group ) were enrolled in a controlled , open-label , multicenter study . In the prior-MPSV4 group , children ( n = 153 ) received 1 dose of MCV4 , as did a group of age-matched meningococcal vaccine-naïve children ( n = 85 ) . Blood sample s collected prevaccination and 28 days postvaccination were measured for serogroup-specific serum bactericidal antibody ( SBA ) levels in the presence of baby rabbit complement ( rSBA ) and for IgG antibody levels . Vaccine tolerability and safety were also evaluated . For all of the measured serogroups ( A , C , Y , and W-135 ) , the meningococcal vaccine-naïve participants achieved higher postvaccination rSBA geometric mean titers ( GMTs ) than did those in the prior-MPSV4 group . This was statistically significant for serogroup C ( 512 versus 167 ) . Percentages of participants with postvaccination titers of ≥8 and with ≥4-fold increases in prevaccination to postvaccination titers appeared to be quite similar in the 2 groups . No worrisome safety signals were detected . MCV4 induced robust immune responses and was well tolerated in Saudi Arabian children who previously received 2 doses of MPSV4 as well as in those who were previously meningococcal vaccine naïve Background : Premature infants seem to be at greater risk of hospitalization from rotavirus gastroenteritis than term infants . Safety and efficacy of the pentavalent human-bovine ( WC3 ) reassortant rotavirus vaccine were assessed in premature infants enrolled in the large-scale , blinded , placebo-controlled rotavirus efficacy and safety trial ( REST ) . Methods : Healthy infants 6–12 weeks of chronologic age at study entry were r and omized to receive 3 oral doses of pentavalent rotavirus vaccine or placebo at 4- to 10-week intervals . Infants born at ≤36 weeks of gestational age were eligible if thriving at the time of enrollment . Safety and efficacy were retrospectively assessed in these premature infants comparing vaccine with placebo recipients . Cases of rotavirus gastroenteritis were defined as forceful vomiting and /or ≥3 watery or looser-than-normal stools within a 24-hour period , accompanied by detection of rotavirus antigen in the stool . Results : A total of 2070 infants between 25 and 36 gestational weeks received at least 1 dose of vaccine or placebo ; 1005 vaccine recipients and 1061 placebo recipients were evaluable for safety . Serious adverse events occurred in 55 vaccine recipients ( 5.5 % ) and 62 placebo recipients ( 5.8 % ) . In a nested sub study of 308 premature infants evaluable for detailed safety ( 154 in each group ) , the frequencies of fever , diarrhea , vomiting , and irritability were comparable between vaccine and placebo recipients . Overall , 3 doses of the pentavalent vaccine reduced the rate of hospitalizations and emergency department visits in premature infants due to rotavirus gastroenteritis by 100 % ( 95 % CI : 82.2–100 ) compared with placebo . The vaccine also prevented 73.0 % ( 95 % CI : −2.2–95.2 ) of rotavirus gastroenteritis cases of any severity . Conclusions : In this post hoc analysis of healthy premature infants , the pentavalent rotavirus vaccine was generally well-tolerated and substantially reduced rotavirus-attributable hospitalizations and emergency department visits compared with placebo . Overall , vaccine safety and efficacy seemed to be generally comparable to the results in the REST study population as a whole . These results support vaccinating healthy premature infants on the same schedule as term infants This article introduces the approach of GRADE to rating  quality of evidence .  GRADE specifies four categories-high , moderate , low , and very low-that are applied to a body of evidence , not to individual studies . In the context of a systematic review , quality reflects our confidence that the estimates of the effect are correct . In the context of recommendations , quality reflects our confidence that the effect estimates are adequate to support a particular recommendation . R and omized trials begin as high- quality evidence , observational studies as low quality . " Quality " as used in GRADE means more than risk of bias and so may also be compromised by imprecision , inconsistency , indirectness of study results , and publication bias . In addition , several factors can increase our confidence in an estimate of effect . GRADE provides a systematic approach for considering and reporting each of these factors . GRADE separates the process of assessing quality of evidence from the process of making recommendations . Judgments about the strength of a recommendation depend on more than just the quality of evidence Background : Rotavirus disease is more severe in preterm infants than in full-term infants . This study assessed the safety , reactogenicity and immunogenicity of a human rotavirus vaccine , RIX4414 , in European preterm infants . Methods : A total of 1009 preterm infants were r and omized ( 2:1 , vaccine : placebo ) and stratified into 2 groups : 20 % of early ( 27–30 weeks , group 1 ) and 80 % of late ( 31–36 weeks , group 2 ) gestational age preterm infants in each group . Two doses of RIX4414/placebo were administered to these preterm infants according to the recommended chronologic age for full-term infants with an interval of 30–83 days between doses . Serious adverse events were recorded throughout the study period . Solicited and unsolicited adverse events were recorded for 15 and 31 days post-each dose . Antirotavirus IgA concentrations ( enzyme-linked immunosorbent assay cutoff = 20 U/mL ) and geometric mean concentration were determined pre-dose 1 and 30–83 days post-dose 2 in a subset of 300 infants . This study is registered with Clinical Trials.gov , number NCT00420745 ( eTrack106481 ) . Results : Serious adverse events were reported at a similar frequency in both groups ( P = 0.266 ) . Fifty-seven infants reported at least 1 serious adverse event ( 5.1 % [ 3.5–7.0 ] in the RIX4414 group and 6.8 % [ 4.3–10.0 ] in the placebo group ) . During the 15-day postvaccination follow-up period , diarrhea , vomiting and fever occurred at a similar frequency in both groups ; fever could have been due to concomitant vaccines . Five cases ( RIX4414 = 3 , Placebo = 2 ) of rotavirus gastroenteritis were reported . The onset of rotavirus gastroenteritis in the RIX4414 group was 1–5 days after vaccination ( vaccine strain identified in all cases ) and in the placebo group it was 3–4 days after receiving placebo ( wild-type rotavirus identified from both cases ) . Antirotavirus IgA seroconversion rates at 30–83 days post-dose 2 were 85.7 % ( 79.0–90.9 ) in the RIX4414 group and 16.0 % ( 8.8–25.9 ) in the placebo group . Geometric mean concentrations were 202.2 U/mL ( 153.1–267.1 ) in the RIX4414 group and < 20 U/mL in the placebo group . Seroconversion rate in groups 1 and 2 in RIX4414 recipients were 75.9 % ( 95 % confidence interval [ CI ] : 56.5–89.7 % ) and 88.1 % ( 95 % CI : 80.9–93.4 % ) , respectively ; the geometric mean concentrations in the respective groups were 110.2 U/mL ( 95 % CI : 56.1–216.5 ) and 234.8 U/mL ( 95 % CI : 173.4–318.0 ; exploratory analysis ) . Conclusions : Two doses of RIX4414 were immunogenic and well-tolerated in European preterm infants Background : The efficacy of a rotavirus vaccine against severe rotavirus gastroenteritis when coadministered with routine Exp and ed Program on Immunization ( EPI ) vaccines including oral polio vaccine ( OPV ) was evaluated in this study . Methods : Double-blind , r and omized ( 2:1 ) , placebo-controlled study conducted across 6 Latin American countries . Healthy infants ( N = 6568 ) 6 to 12 weeks of age received 2 doses of RIX4414 vaccine or placebo following a 0 , 1- to 2-month schedule . Routine vaccines including OPV were coadministered according to local EPI schedule . Vaccine efficacy ( VE ) against severe rotavirus gastroenteritis caused by circulating wild-type rotavirus from 2 weeks post-Dose 2 until 1 year of age was calculated with 95 % confidence interval [ CI ] . Safety was assessed during the entire study period . Immunogenicity of RIX4414 and OPV was also assessed . Results : During the efficacy follow-up period ( mean duration = 7.4 months ) , 7 and 19 cases of severe rotavirus gastroenteritis were reported in the vaccine and placebo groups , respectively , with a VE of 81.6 % ( 95 % CI : 54.4–93.5 ) . VE against severe rotavirus gastroenteritis caused by G1 type was 100 % ( 95 % CI : < 0–100 ) and 80.6 % ( 95 % CI : 51.4–93.2 ) against the pooled non-G1 rotavirus types , respectively . There was no difference ( P = 0.514 ) in the incidence of serious adverse events reported in the 2 groups . Antirotavirus IgA seropositivity rate at 1 to 2 months post-Dose 2 was 61.4 % ( 95 % CI : 53.7–68.6 ) in the RIX4414 group ; similar seroprotection rates ( ≥96.0 % ) against the 3 antipoliovirus types was observed 1 month post-Dose 3 of OPV in both groups . Conclusion : RIX4414 was highly efficacious against severe rotavirus gastroenteritis caused by the circulating wild-type rotavirus ( G1 and non-G1 ) when coadministered with routine EPI vaccines including OPV Aims /hypothesis . To determine if  vaccinations  and infections are associated with the subsequent risk of Type I ( insulin-dependent ) diabetes mellitus in childhood.¶ Method . Seven centres in Europe with access to population -based registers of children with Type I diabetes diagnosed under 15 years of age participated in a case-control study of environmental risk factors . Control children were chosen at r and om in each centre either from population registers or from schools and policlinics . Data on maternal and neonatal infections , common childhood infections and vaccinations  were obtained for 900 cases and 2302 control children from hospital and clinic records and from parental responses to a question naire or interview.¶  Results . Infections early in the child 's life noted in the hospital record were found to be associated with an increased risk of diabetes , although the odds ratio of 1.61 ( 95 % confidence limits 1.11 , 2.33 ) was significant only after adjustment for confounding variables . None of the common childhood infectious diseases was found to be associated with diabetes and neither was there evidence that any common childhood vaccination modified the risk of diabetes . Pre-school day-care attendance , a proxy measure for total infectious disease exposure in early childhood , was found , however , to be inversely associated with diabetes , with a pooled odds ratio of 0.59 ( 95 % confidence limits 0.46 , 0.76 ) after adjustment for confounding variables.¶ Conclusion /interpretation . It seems likely that the explanation for these contrasting findings of an increased risk associated with perinatal infections coupled with a protective effect of pre-school day care lies in the age-dependent modifying influence of infections on the developing immune system . [ Diabetologia ( 2000 ) 43 : 47–53 Background : A live pentavalent rotavirus vaccine ( PRV ) containing 5 human-bovine ( WC3 ) reassortants expressing human serotypes G1 , G2 , G3 , G4 and P1A[8 ] was evaluated in a blinded , placebo-controlled study . Possible interactions between PRV and concomitantly administered licensed pediatric vaccines were investigated in a United States-based nested sub study ( Concomitant Use Study ) of the Rotavirus Efficacy and Safety Trial . Methods : From 2002 to 2003 , healthy infants approximately 6 to 12 weeks of age at entry were r and omized to receive either 3 oral doses of PRV or placebo at 4- to 10-week intervals . Subjects were also to receive combined Haemophilus influenzae type b and hepatitis B vaccine ( 2 doses ) , diphtheria and tetanus toxoids and acellular pertussis vaccine ( 3 doses ) , inactivated poliovirus vaccine ( 2 doses ) and pneumococcal conjugate vaccine ( 3 doses ) on the same day ; oral poliovirus vaccine was not administered . Immunogenicity was assessed by measuring antibody responses to PRV and antigens contained in the licensed vaccines . Cases of rotavirus gastroenteritis were defined by forceful vomiting and /or ≥3 watery or looser-than-normal stools within a 24-hour period , and detection of rotavirus antigen in the stool . Safety was assessed by reporting of adverse events using diary cards . Results : The Concomitant Use Study enrolled 662 subjects in the PRV group and 696 subjects in the placebo group . For the 17 antigens in the concomitantly administered vaccines , antibody responses were similar in PRV and placebo recipients , except for moderately diminished antibody responses to the pertactin component of pertussis vaccine . Efficacy of PRV against rotavirus gastroenteritis of any severity was 89.5 % ( 95 % CI = 26.5–99.8 % ) . PRV was generally well tolerated when given concomitantly with the prespecified vaccines . Conclusions : In this study , antibody responses to the concomitantly administered vaccines were generally similar in PRV and placebo recipients . PRV was efficacious and well tolerated when given concomitantly with pediatric vaccines licensed in the United States BACKGROUND Live attenuated influenza vaccine ( LAIV ) was licensed in 2003 in the United States for use in individuals aged 5 - 49 years . METHODS A prospect i ve observational postmarketing study was conducted to evaluate the safety of LAIV .  Rates of medically attended events ( MAEs ) and serious adverse events ( SAEs ) in eligible children aged 5 - 17 years receiving LAIV as part of routine care from October 2003 to March 2008 were compared with rates in nonr and omized self , matched unvaccinated , and matched trivalent inactivated influenza vaccine (TIV)-vaccinated controls . All MAEs and SAEs through 42 days postvaccination and all hospitalizations and deaths through 6 months postvaccination were analyzed . Statistical significance was assigned without multiplicity adjustment . RESULTS 43,702 LAIV recipients were matched with similar numbers of TIV-vaccinated and unvaccinated children . Of approximately 9500 MAE incidence rate comparisons , 204 were statistically significantly higher and 168 were statistically significantly lower in LAIV recipients versus controls . No pattern of MAE rate differences suggested a safety signal with LAIV .  Asthma/wheezing MAEs were not statistically increased in LAIV recipients . No anaphylaxis events occurred within 3 days postvaccination . Rates of SAEs were similar between LAIV and control groups . Two SAEs were considered possibly related to LAIV :  Bell 's palsy and nonspecific paroxysmal spell . CONCLUSIONS Results of this postlicensure evaluation of LAIV safety in US children aged 5 - 17 years are consistent with preapproval clinical studies and Vaccine Adverse Event Reporting System reports , both of which demonstrated no significant increase in asthma/wheezing events or other adverse outcomes among eligible children who received LAIV The oral , pentavalent rotavirus vaccine ( PRV ) , RotaTeq was assessed for prevention of severe rotavirus gastroenteritis ( RVGE ) in young children in two multi-site , r and omized , placebo-controlled field trials ; one in Asia ( Vietnam and Bangladesh ) and the other in sub-Saharan Africa ( Ghana , Kenya and Mali ) . The efficacy results for the Mali site of the multi-country trial are presented here . We r and omly assigned infants in a 1:1 ratio to receive 3 doses of  PRV/placebo  at approximately 6 , 10 , and 14 weeks of age . Gastroenteritis episodes were captured passively at the local health centers and by home visits . The primary study outcome was severe RVGE , as defined by a score of ≥ 11 using the Vesikari Clinical Scoring System occurring ≥ 14 days after the third dose until the end of the study . Other efficacy analyses included efficacy against severe RVGE through the first year and during the second years of life , as well as efficacy after receiving at least one dose of vaccine . In total , 1960 infants were enrolled in the trial at the Mali site and sera were collected on a subset of infants ( approximately 150 ) for immunogenicity testing . In the first year of follow-up , largely due to cultural practice s to visit traditional healers as the first point of care , the point estimate of efficacy was unreliable : the per protocol vaccine efficacy against severe RVGE was 1 % ( 95 % confidence interval [ CI ] : -431.7 , 81.6 ) ; the intention-to-treat vaccine efficacy was 42.9 % ( 95 % CI : -125.7 , 87.7 ) . During the second year of follow-up , after the surveillance system was modified to adapt to local customs and health care seeking practice s , the point estimate of per- protocol vaccine efficacy was 19.2 % ( 95 % CI : -23.1,47.3 % ) . 82.5 % of Malian infants ( 95 % CI : 70.1,91.3 % ) who received PRV mounted a seroresponse ( ≥ 3-fold rise from baseline ( prevaccination ) to post-dose 3 vaccination ) of anti-rotavirus immunoglobulin A antibody , with a post third-dose geometric mean titer ( GMT ) of 31.3 units/mL. By contrast , only 20.0 % of placebo recipients ( 95 % CI : 10.0 , 33.7 % ) developed a seroresponse and the post-third dose GMT was 3.2 units/mL. None of the serious clinical adverse events observed were considered to be vaccine-related An efficacy clinical trial with pentavalent rotavirus vaccine ( PRV ) , RotaTeq ( ® ) , was conducted at Matlab field site of ICDDR , B , Bangladesh from March 2007 to March 2009 . The methodology , including operation logistics , and lessons-learned are described in this report . Vaccination was organized at 41 fixed-site clinics twice/month . A total of 1136 infants were r and omized 1:1 to receive 3 doses of PRV/placebo at approximately 6- , 10- , and 14-weeks of age with routine vaccines of the Exp and ed Programme on Immunization ( EPI ) schedule . Twelve field-workers routinely visited study participants for safety and efficacy follow-up . The study was conducted following good clinical practice s and maintaining cold-chain requirements . There were no temperature deviations of clinical vaccine supplies . Data entry was done using the source documents to a central data base developed by the sponsor which was linked to web . Among enrolled infants , 1128 ( 99.3 % ) received 3 doses of PRV/placebo and efficacy follow-up was conducted for a median of 554 days . For the evaluation of immunogenicity , blood sample s were collected from 150 participants predose 1 and from 147 ( 98 % ) of the same participants post dose 3 . Stool sample s were collected from 778 ( 99.9 % ) acute gastroenteritis episodes among children who reported to diarrhoea treatment centres . Thirty-nine serious adverse events , including 6 deaths , occurred among study participants . The efficacy of PRV against severe rotavirus gastroenteritis was 42.7 % through the entire follow-up period ; serum anti-rotavirus IgA response was 78.1 % . Inclement weather , difficult transportation , and movement of study participants were some of the challenges identified . This is the first vaccine trial in rural Bangladesh with online data entry . The study was well accepted in the community and was completed successfully Objective : To assess the effect of measles , mumps and rubella ( MMR ) vaccination on disease activity in children with juvenile idiopathic arthritis ( JIA ) . Methods : A retrospective observational multicentre cohort study was performed in 314 patients with JIA , born between 1989 and 1996 .  Disease activity and medication use were compared during the period of 6 months before vaccination versus 6 months after vaccination .  Disease activity was measured by joint counts , the Physician ’s global assessment scale and erythrocyte sedimentation rate . Next , we compared disease activity in patients vaccinated between 8 and 9 years of age with the activity in patients who had not been vaccinated at this time ( who received MMR between the ages of 9 and 10 years ) . Results : No increase in disease activity or medication use was seen in the 6 months after MMR vaccination ( n = 207 ) , including in patients using methotrexate ( n = 49 ) . No overt measles infections were noted . When disease activity in vaccinated patients ( n = 108 ) was compared with activity in those not yet vaccinated ( n = 86 ) , there were no significant differences . Conclusions : The MMR booster vaccination does not seem to aggravate disease activity in JIA . This indicates that the most patients with JIA can be vaccinated safely with the MMR vaccine . A prospect i ve study is recommended BACKGROUND Rotavirus vaccine has proved effective for prevention of severe rotavirus gastroenteritis in infants in developed countries , but no efficacy studies have been done in developing countries in Asia . We assessed the clinical efficacy of live oral pentavalent rotavirus vaccine for prevention of severe rotavirus gastroenteritis in infants in Bangladesh and Vietnam . METHODS In this multicentre , double-blind , placebo-controlled trial , undertaken in rural Matlab , Bangladesh , and urban and periurban Nha Trang , Vietnam , infants aged 4 - 12 weeks without symptoms of gastrointestinal disorders were r and omly assigned ( 1:1 ) to receive three oral doses of pentavalent rotavirus vaccine 2 mL or placebo at around 6 weeks , 10 weeks , and 14 weeks of age , in conjunction with routine infant vaccines including oral poliovirus vaccine . R and omisation was done by computer-generated r and omisation sequence in blocks of six . Episodes of gastroenteritis in infants who presented to study medical facilities were reported by clinical staff and from parent re collection . The primary endpoint was severe rotavirus gastroenteritis ( Vesikari score > or=11 ) arising 14 days or more after the third dose of placebo or vaccine to end of study ( March 31 , 2009 ; around 21 months of age ) . Analysis was per protocol ; infants who received scheduled doses of vaccine or placebo without intervening laboratory-confirmed naturally occurring rotavirus disease earlier than 14 days after the third dose and had complete clinical and laboratory results were included in the analysis . This study is registered with Clinical Trials.gov , number NCT00362648 . FINDINGS 2036 infants were r and omly assigned to receive pentavalent rotavirus vaccine ( n=1018 ) or placebo ( n=1018 ) . 991 infants assigned to pentavalent rotavirus vaccine and 978 assigned to placebo were included in the per- protocol analysis . Median follow up from 14 days after the third dose of placebo or vaccine until final disposition was 498 days ( IQR 480 - 575 ) . 38 cases of severe rotavirus gastroenteritis ( Vesikari score > or=11 ) were reported during more than 1197 person-years of follow up in the vaccine group , compared with 71 cases in more than 1156 person years in the placebo group , result ing in a vaccine efficacy of 48.3 % ( 95 % CI 22.3 - 66.1 ) against severe disease ( p=0.0005 for efficacy > 0 % ) during nearly 2 years of follow-up . 25 ( 2.5 % ) of 1017 infants assigned to receive vaccine and 20 ( 2.0 % ) of 1018 assigned to receive placebo had a serious adverse event within 14 days of any dose . The most frequent serious adverse event was pneumonia ( vaccine 12 [ 1.2 % ] ; placebo 15 [ 1.5 % ] ) . INTERPRETATION In infants in developing countries in Asia , pentavalent rotavirus vaccine is safe and efficacious against severe rotavirus gastroenteritis , and our results support exp and ed WHO recommendations to promote its global use . FUNDING PATH ( GAVI Alliance grant ) and Merck Background : Rotavirus and human immunodeficiency virus ( HIV ) infections are a cause of great public health concern in developing countries . The current study evaluated the safety , reactogenicity , and immunogenicity of RIX4414 vaccine in asymptomatic or mildly symptomatic ( clinical stages I and II according to WHO classification ) HIV-infected South African infants . Methods : A total of 100 HIV-positive infants aged 6 to 10 weeks enrolled in this double-blind , 1:1 r and omized , placebo-controlled study were allocated into 2 groups to receive 3 doses of RIX4414 vaccine/placebo according to a 0- , 1- , and 2-month schedule . Routine vaccines were concomitantly administered . Solicited and unsolicited symptoms were recorded for 15 and 31 days after each dose , respectively . Serious adverse events were recorded throughout the study period . Serum antirotavirus IgA concentrations ( enzyme-linked immunosorbent assay , cut-off ≥20 U/mL ) and the immunodeficiency status were determined at screening and 2 months post-Dose 3 . Stool sample s were analyzed for rotavirus using enzyme-linked immunosorbent assay at predetermined points and during diarrhea episodes . Results : All symptoms ( solicited and unsolicited ) occurred at a similar frequency in both groups . Six fatal serious adverse events in RIX4414 and 9 in placebo groups were reported . At 2 months post-Dose 3 , the seroconversion rates were 57.1 % ( 95 % CI : 34–78.2 ) in RIX4414 and 18.2 % ( 95 % CI : 5.2–40.3 ) in the placebo group . The mean absolute CD4 + cell count , CD4 + percentage , and HIV-1 viral load were comparable in both groups at screening and 2 months post-Dose 3 . Rotavirus shedding peaked at Day 7 after Dose 1 of RIX4414 with prolonged shedding was observed in 1 infant only . Conclusions : Three doses of RIX4414 vaccine was tolerated well by the South African HIV-positive infants . A satisfactory immune response was mounted without aggravating their immunologic or HIV condition Background : Rotavirus gastroenteritis , a major cause of mortality and morbidity worldwide , is a vaccine-preventable disease . New safe and effective c and i date rotavirus vaccines are needed to replace the withdrawn rhesus rotavirus-based oral vaccine . Methods : We evaluated a monovalent human rotavirus vaccine , serotype G1 , strain RIX4414 , for efficacy , immunogenicity and safety in a r and omized , double blind , placebo-controlled trial in Finl and . We r and omly allocated 405 healthy infants to receive 2 doses of vaccine or placebo  ( ratio 2:1 ) at ∼2 and 4 months of age . The infants were followed during 2 rotavirus epidemic seasons ( 2000 - 2002 ) for acute gastroenteritis . Rotaviruses in diarrheal stool sample s were primarily detected by enzyme-linked immunosorbent assay and confirmed and G-typed by reverse transciption-polymerase chain reaction . Results : The vaccine was well-tolerated . No vaccine-related serious adverse events were observed during the study period . Rotavirus IgA ( enzyme-linked immunosorbent assay ) seroconversion rate was 80 % after 2 doses . Thirty-eight cases of rotavirus gastroenteritis were detected during the entire follow-up period ; 35 of these were of the G1 type . RIX4414 vaccine significantly decreased the occurrence of any rotavirus compared with placebo . Efficacy during the first rotavirus epidemic season was 73 % [ 95 % confidence interval ( 95 % CI ) , 27 - 91 % ] and 90 % ( 95 % CI 10 - 100 % ) against any and severe rotavirus gastroenteritis , respectively , and during the entire follow-up period 72 % ( 95 % CI 42 - 87 % ) against any and 85 % ( 95 % CI 42 - 97 % ) against severe rotavirus gastroenteritis ( P < 0.05 for all comparisons ) . Conclusions : RIX4414 strain of G1 human rotavirus vaccine was well-tolerated , immunogenic and efficacious in infants against rotavirus gastroenteritis during a 2-year period . To further increase vaccine “ take ” and efficacy , a higher dose of this vaccine may be considered for future efficacy trials Serum antibody responses to three Haemophilus influenzae type b ( Hib ) capsular polysaccharide-protein conjugate vaccine ( PRP-OMP , PRP-T , and HbOC ) were evaluated in 174 Philippine infants after a primary vaccination series . Children were r and omized to receive one of the  Hib vaccines ( Hib groups ) or into a  control group . Vaccination was carried out at six , 10 and 14 weeks of age based on the local Exp and ed Program of Immunization schedule . Sera were collected at six weeks of age for the Hib groups and one month after the third dose for all subjects . Anti-Hib concentrations were determined by the Farr-type radioimmunoassay . There were no significant differences ( P = 0.3626 ) in the prevaccination anti-Hib geometric mean concentration ( GMC ) among the three Hib groups . Differences in the GMC after the primary series of three doses were significant ( P < 0.0001 ) ; GMC was highest for PRP-T ( 6.62 micrograms/ml ) , followed by HbOC ( 1.9 micrograms/ml ) , then PRP-OMP ( 1.06 micrograms/ml ) , and lowest for the control group ( 0.11 microgram/ml ) . We conclude that all three Hib conjugate vaccines ( PRP-T , HbOC , and PRP-OMP ) were immunogenic after three primary doses among Philippine infants BACKGROUND Influenza causes substantial morbidity in adults and children with asthma , and vaccination can prevent influenza and its complications . However , there is concern that vaccination may cause exacerbations of asthma . METHODS To investigate the safety of the inactivated trivalent split-virus influenza vaccine in adults and children with asthma , we conducted a multicenter , r and omized , double-blind , placebo-controlled , cross-over trial in 2032 patients with asthma ( age range , 3 to 64 years ) . The order of injection of vaccine and placebo was assigned r and omly , with a mean of 22 days between the injections . Each day during the two weeks after each injection , the patients recorded peak expiratory flow rates , symptoms thought to be related to the injection , use of asthma medications , unscheduled health care visits for asthma , and asthma-related absences from school or work . The primary outcome measure was an exacerbation of asthma in the two weeks after the injections . RESULTS The frequency of exacerbations of asthma was similar in the two weeks after the influenza vaccination and after placebo injection ( 28.8 percent and 27.7 percent , respectively ; absolute difference , 1.1 percent ; 95 percent confidence interval , -1.4 percent to 3.6 percent ) . The exacerbation rates were similar in subgroups defined according to age , severity of asthma , and other factors . Among symptoms thought to be associated with the injection , only body aches were more frequent after the vaccine injection than after placebo injection ( 25.1 percent vs. 20.8 percent , P<0.001 ) . CONCLUSIONS The inactivated influenza vaccine is safe to administer to adults and children with asthma , including those with severe asthma . Given the morbidity of influenza , all those with asthma should receive the vaccine annually This study evaluates the safety and efficacy against severe rotavirus gastroenteritis of the oral live attenuated human rotavirus vaccine RIX4414 ( Rotarix )  during the first 2 years of life in Asian infants from high-income countries . Healthy infants were enrolled to receive 2 doses of RIX4414 ( N=5,359 ) or placebo ( N=5,349 ) . From 2 weeks post-dose 2 to 2 years of age , vaccine efficacy was 96.1 % ( 95%CI:85.1 % ; 99.5 % ) against severe rotavirus gastroenteritis , 100 % ( 95%CI:80.8 % ; 100 % ) against wild-type G1P[8 ] and 93.6 % ( 95%CI:74.7 % ; 99.3 % ) against circulating non-G1 rotavirus types . No intussusception cases were reported within 31 days post-vaccination . RIX4414 shows a good safety profile and offers high protection during the first 2 years of life with potentially significant public health impact in this population BACKGROUND A phase II , r and omized , double-blind , placebo-controlled study was conducted in South Africa during 2003 - 2004 to evaluate the safety , reactogenicity , and immunogenicity of 2 regimens of the live attenuated oral human rotavirus vaccine RIX4414 when coadministered with the Exp and ed Program on Immunization childhood vaccines , including oral polio vaccine . METHODS Healthy infants were r and omized ( 2:2:1 ) to receive either 2 doses of RIX4414 ( n = 190 ; at 10 and 14 weeks , with placebo at 6 weeks ) , 3 doses of RIX4414 ( n = 189 ; at 6 , 10 , and 14 weeks ) , or 3 doses of placebo ( n = 96 ) , all with concomitant routine vaccinations . The antirotavirus IgA seroconversion rate was assessed using enzyme-linked immunosorbent assay at 2 months after the last dose of RIX4414 or placebo . Antipolio types 1 , 2 , and 3 antibodies were measured using a virus neutralization assay . Solicited symptoms were recorded for 15 days after each dose . RESULTS The antirotavirus IgA seroconversion rates were similar in the RIX4414 2- and 3-dose groups ( 44.3 % and 44.4 % , respectively ; P = .544 , by 1-sided Fisher exact test ) and antirotavirus IgA geometric mean concentrations were also comparable . Seroprotection rates for antipolio types 1 , 2 , and 3 antibodies were high ( 93%-100 % ) and were not significantly different among groups . Solicited symptoms reported within 15 days after vaccination were similar in all groups . CONCLUSIONS The immune seroconversion response to the RIX4414 vaccine with 3 doses was not superior to the 2-dose regimen . There was no interference by either regimen with antibody response to oral polio vaccine , and RIX4414 was well tolerated when given with routine vaccinations
BACKGROUND : Concerns about vaccine safety have led some parents to decline recommended vaccination of their children , leading to the resurgence of diseases .
Reassurance of vaccine safety remains critical for population health .
This study systematic ally review ed the literature on the safety of routine vaccines recommended for children in the United States .