Dose Response and Efficacy of a Live, Attenuated Human Rotavirus Vaccine in Mexican Infants Effect of human rotavirus vaccine on severe diarrhea in African infants. Postmarketing Surveillance of Intussusception Following Mass Introduction of the Attenuated Human Rotavirus Vaccine in Mexico Safety, immunogenicity, and protective efficacy of two doses of RIX4414 live attenuated human rotavirus vaccine in healthy infants. Safety and efficacy of an attenuated vaccine against severe rotavirus gastroenteritis. Evaluation of Safety, Immunogenicity and Efficacy of an Attenuated Rotavirus Vaccine, RIX4414: A Randomized, Placebo-Controlled Trial in Latin American Infants Efficacy of a pentavalent rotavirus vaccine in reducing rotavirus-associated health care utilization across three regions (11 countries). Efficacy of the rhesus rotavirus-based quadrivalent vaccine in infants and young children in Venezuela. Safety and efficacy of high-dose rhesus-human reassortant rotavirus vaccines--report of the National Multicenter Trial. United States Rotavirus Vaccine Efficacy Group. Effectiveness of vaccination with the pentavalent rotavirus vaccine in Nicaragua as determined using the screening method Human Rotavirus Vaccine Is Highly Efficacious When Coadministered With Routine Expanded Program of Immunization Vaccines Including Oral Poliovirus Vaccine in Latin America Efficacy of the oral pentavalent rotavirus vaccine in Mali. Safety and efficacy of a pentavalent human-bovine (WC3) reassortant rotavirus vaccine. Analyses of health outcomes from the 5 sites participating in the Africa and Asia clinical efficacy trials of the oral pentavalent rotavirus vaccine. Efficacy and safety of an oral live attenuated human rotavirus vaccine against rotavirus gastroenteritis during the first 2 years of life in Latin American infants: a randomised, double-blind, placebo-controlled phase III study Community diarrhea incidence before and after rotavirus vaccine introduction in Nicaragua. Randomised placebo-controlled trial of rhesus-human reassortant rotavirus vaccine for prevention of severe rotavirus gastroenteritis Efficacy of pentavalent rotavirus vaccine against severe rotavirus gastroenteritis in infants in developing countries in sub-Saharan Africa: a randomised, double-blind, placebo-controlled trial Impact and Effectiveness of RotaTeq® Vaccine Based on 3 Years of Surveillance Following Introduction of a Rotavirus Immunization Program in Finland Burden and aetiology of diarrhoeal disease in infants and young children in developing countries (the Global Enteric Multicenter Study, GEMS): a prospective, case-control study
OBJECTIVE . Immunization against rotavirus has been proposed as the most cost-effective intervention to reduce the disease burden associated with this infection worldwide . The objective of this study was to determine the dose response , immunogenicity , and efficacy of 2 doses of an oral , attenuated monovalent G1[P8 ] human rotavirus vaccine in children from the same setting in Mexico , where the natural protection against rotavirus infection was studied . METHODS . From June 2001 through May 2003 , 405 healthy infants were r and omly assigned to 1 of 3 vaccine groups ( virus concentrations 104.7 , 105.2 , and 105.8 infectious units ) and to a  placebo group and were monitored to the age of 2 years . The vaccine/placebo was administered concurrently with diphtheria-tetanus toxoid-pertussis/hepatitis B/Haemophilus influenzae type b vaccine at 2 and 4 months of age . After the administration of the first vaccine/placebo dose , weekly home visits to collect information regarding infant health were conducted . Stool sample s were collected during each gastroenteritis episode and tested for rotavirus antigen and serotype . RESULTS . The vaccine was well tolerated and induced a greater rate of seroconversion than observed in infants who received placebo . For the pooled vaccine groups , efficacy after 2 oral doses was 80 % and 95 % against any and severe rotavirus gastroenteritis , respectively . Efficacy was 100 % against severe rotavirus gastroenteritis and 70 % against severe gastroenteritis of any cause with the vaccine at the highest virus concentration ( 105.8 infectious units ) . The predominant infecting rotavirus serotype in this cohort was wild-type G1 ( 85 % ) . Adverse events , including fever , irritability , loss of appetite , cough , diarrhea , and vomiting , were similar among vaccinees and placebo recipients . CONCLUSION . This new oral , live , attenuated human rotavirus vaccine was safe , immunogenic , and highly efficacious in preventing any and , more importantly , severe rotavirus gastroenteritis in healthy infants . This vaccine produced comparable protection to natural infection 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 . ) 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 OBJECTIVE To determine the safety , immunogenicity and efficacy of two doses of rotavirus vaccine in healthy Brazilian infants . METHODS A r and omized , multicenter , double-blind , placebo-controlled trial was conducted in Brazil , Mexico and Venezuela . Infants received two oral doses of vaccine or placebo at 2 and 4 months of age , concurrently with routine immunizations , except for oral poliomyelitis vaccine ( OPV ) . This paper reports results from Belém , Brazil , where the number of subjects per group and the viral vaccine titers were : 194 ( 10(4.7 ) focus forming units - FFU ) , 196 ( 10(5.2 ) FFU ) , 194 ( 10(5.8 ) FFU ) and 194 ( placebo ) . Anti-rotavirus ( anti-RV ) antibody response was assessed in 307 subjects .  Clinical severity of gastroenteritis episodes was measured using a 20-point scoring system with a score of > or= 11 defined as severe GE . RESULTS The rates of solicited general symptoms were similar in vaccine and placebo recipients . At 2 months after the second dose , a serum IgA response to RV occurred in 54.7 to 74.4 % of vaccinees . No interference was seen in the immunogenicity of routine vaccines . Vaccine efficacy against any rotavirus gastroenteritis ( RVGE ) was 63.5 % ( 95%CI 20.8 - 84.4 ) for the highest concentration ( 10(5.8 ) FFU ) . Efficacy was 81.5 % ( 95%CI 44.5 - 95.4 ) against severe RVGE . At its highest concentration ( 10(5.8 ) FFU ) , RIX4414 provided 79.8 % ( 95%CI 26.4 - 96.3 ) protection against severe RVGE by G9 strain . CONCLUSIONS RIX4414 was highly immunogenic with a low reactogenicity profile and did not interfere with seroresponse to diphtheria , tetanus , pertussis , hepatitis B and Hib antigens . Two doses of RIX4414 provided significant protection against severe GE caused by RV 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 : A live attenuated monovalent rotavirus vaccine RIX4414 was developed with a human strain of G1P1A P[8 ] specificity to reduce the rotavirus burden in children . Methods : A double blind , r and omized , placebo-controlled study evaluated the efficacy , immunogenicity , safety and reactogenicity of 2 oral doses of RIX4414 ( 104.7 , 105.2 or 105.8 focus-forming units ) at 2 and 4 months coadministered with routine vaccinations and oral poliovirus vaccine given for study purpose s at least 14 days apart . The 2155 infants ( 1618 vaccine/537 placebo ) enrolled in Brazil , Mexico and Venezuela were followed until 1 year of age . Results : Antirotavirus IgA seroconversion rates 2 months after dose 2 ranged between 61 % ( 10 4.7 ffu group ) and 65 % ( 105.8 ffu group ) , and most of the infants had seroprotective levels of antibodies to coadministered routine vaccinations . The reactogenicity profile of RIX4414 was similar to that of the placebo , and no vaccination-related serious adverse events were reported . Protective efficacy against severe and any rotavirus gastroenteritis from 15 days post-dose 2 was highest in the 105.8 ffu group [ 86 % ; 95 % confidence interval ( 95 % CI ) , 63–96 % and 70 % ( 95 % CI 46–84 % ) , P < 0.001 , 2-sided Fisher 's exact test ] . The efficacy against hospitalization was 79 % ( 95 % CI 48–92 % ) for pooled vaccine groups . Multiple rotavirus serotypes [ G1 ( 50 % ) , G9 ( 40 % ) , G2 , G3 and G4 ] were identified from gastroenteritis stools ( enzyme-linked immunosorbent assay and reverse transcription-polymerase chain reaction ) during the study period . For severe gastroenteritis caused by G9 serotypes , the protection reached 77 % ( 95 % CI 18–96 % ) in the 105.8 ffu group , providing proof of concept that the monovalent G1P1A P[8 ] human rotavirus vaccine elicits cross-protection against the G9 strain . A reduction in any and severe rotavirus gastroenteritis was already observed at post-dose 1 ( period : day of dose 1 to 14 days post-dose 2 ) in vaccinees compared with placebo recipients . Conclusions : Two doses of RIX4414 are highly efficacious , providing cross-protection ( G1 and G9 strains , prevalent during this study ) and early protection against any and severe rotavirus gastroenteritis and hospitalization to infants in Latin America OBJECTIVE To evaluate the effect of a human-bovine reassortant pentavalent rotavirus vaccine ( PRV ) on health care encounters in nearly 70 000 subjects r and omized in three regions - Europe , the United States , and Latin America/the Caribbean - in the Rotavirus Efficacy and Safety Trial ( REST ) . METHODS Healthy 6- to 12-week-old infants received 3 doses of PRV or placebo at 4- to 10-week intervals . The exact binomial method for ratios of Poisson counts was used to evaluate the effect of PRV on the rate of rotavirus-related hospitalizations and emergency department ( ED ) visits involving rotavirus G-types 1 - 4 occurring > or = 14 days after the third dose of vaccine for up to 2 years . RESULTS In fully vaccinated infants , reductions in rotavirus-associated hospitalizations and ED visits were 94.7 % ( 95 % CI : 90.9 , 96.9 ) in Europe , 94.9 % ( 95 % CI : 84.0 , 98.9 ) in the United States , and 90.0 % ( 95 % CI : 29.4 , 99.8 ) in the Latin American/Caribbean regions . CONCLUSIONS PRV reduced hospitalizations and ED visits within each region in REST . Results were consistent across regions and across the overall study cohort BACKGROUND Rotaviruses are the principal known etiologic agents of severe diarrhea among infants and young children worldwide . Although a rhesus rotavirus-based quadrivalent vaccine is highly effective in preventing severe diarrhea in developed countries , in developing countries its efficacy has been less impressive . We thus conducted a catchment study in Venezuela to assess the efficacy of the vaccine against dehydrating diarrhea . METHODS In this r and omized , double-blind , placebo-controlled trial , 2207 infants received three oral doses of the quadrivalent rotavirus vaccine ( 4x10(5 ) plaque-forming units per dose ) or placebo at about two , three , and four months of age . During approximately 19 to 20 months of passive surveillance , episodes of gastroenteritis were evaluated at the hospital . RESULTS The vaccine was safe , although 15 percent of the vaccinated infants had febrile episodes ( rectal temperature , > or = 38.1 degrees C ) during the six days after the first dose , as compared with 7 percent of the controls ( P<0.001 ) . However , the vaccine gave 88 percent protection against severe diarrhea caused by rotavirus and 75 percent protection against dehydration , and produced a 70 percent reduction in hospital admissions . Overall , the efficacy of the vaccine against a first episode of rotavirus diarrhea was 48 percent . Horizontal transmission of vaccine virus was demonstrated in 15 percent of the vaccine recipients and 13 percent of the placebo recipients with rotavirus-positive diarrhea . CONCLUSIONS In this study in a developing country , the quadrivalent rhesus rotavirus-based vaccine induced a high level of protection against severe diarrheal illness caused by rotavirus OBJECTIVE Rotavirus is a leading cause of morbidity and mortality from dehydrating gastroenteritis in infants and young children worldwide . Virtually every child is infected by age 4 years , justifying universal childhood immunization when a safe and effective vaccine is available . We report the results of a multicenter , placebo-controlled field trial in the United States of monovalent serotype 1 and tetravalent ( TV ) rhesus-human reassortant rotavirus vaccines ( RRVs ) . DESIGN In this r and omized , double-blind trial , 1278 healthy infants ages 5 to 25 weeks received three oral doses of RRV serotype 1 , RRV-TV , or a placebo at approximately 2 , 4 , and 6 months of age . Vaccines contained 4 x 10(5 ) plaque-forming units of virus . Gastroenteritis episodes were monitored , and severity was grade d throughout one rotavirus season . Two stool specimens per episode were tested for rotavirus . RESULTS The incidence of reactions did not differ among treatment groups during the 5-day , postvaccination safety surveillance period for any of the three doses . Both vaccines significantly reduced the incidence of rotavirus gastroenteritis . Vaccination was most protective against serious rotavirus illness ; RRV-TV prevented 49 % of rotavirus episodes , 80 % of very severe episodes , and 100 % of dehydrating rotavirus illness . Reduction of rotavirus disease by RRV-TV result ed in significantly fewer total episodes of gastroenteritis of all causes and an 82 % reduction in all cases of dehydrating diarrhea . CONCLUSION RRV-TV is highly protective against very severe , dehydrating rotavirus gastroenteritis The screening method is a surveillance tool to evaluate vaccine effectiveness ( VE ) using coverage data on cases and available administrative estimates of vaccine coverage in the population . The aim of this analysis was to evaluate the utility and limitations of using the screening methodology to estimate VE , particularly in a developing world country with a high coverage rate , and to compare it with the VE estimates from 2 case-control studies . Using data from 2008 , the screening method employed in this study estimated that VE for 3 doses of RV5 among children < 12 mo of age to prevent wild-type severe disease , result ing in hospitalization or emergency department visits , was 92 % ( 95 % confidence interval [ CI ] : 78–100 % ) . Additional sensitivity analysis demonstrated that the point estimates of VE against severe disease ranged from 72 % ( 95 % CI : 62–83 % ) to 92 % ( 95 % CI : 78–100 % ) ; this range of VE estimates , although wide , is relatively consistent with results reported from 2 case-control studies in Nicaragua for the same time period . When the infrastructure is in place to collect reasonably robust case data , the use of the screening method to estimate VE is possible in the developing world setting . Cases of severe wild-type rotavirus gastroenteritis were obtained through an observational , hospital-based , prospect i ve , surveillance program to assess rotavirus acute gastroenteritis . The proportion of cases vaccinated was estimated using the child ’s vaccination card or health record . The proportion of the population vaccinated was estimated using administrative population -based vaccination coverage estimates provided by the Nicaraguan Ministry of Health 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 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 BACKGROUND Rotavirus is a leading cause of childhood gastroenteritis and death worldwide . METHODS We studied healthy infants approximately 6 to 12 weeks old who were r and omly assigned to receive three oral doses of  live pentavalent human-bovine ( WC3 strain ) reassortant rotavirus vaccine containing human serotypes G1 , G2 , G3 , G4 , and P[8 ] or placebo at 4-to-10-week intervals in a blinded fashion . Active surveillance was used to identify subjects with serious adverse and other events . RESULTS The 34,035 infants in the vaccine group and 34,003 in the placebo group were monitored for serious adverse events . Intussusception occurred in 12 vaccine recipients and 15 placebo recipients within one year after the first dose including six vaccine recipients and five placebo recipients within 42 days after any dose ( relative risk , 1.6 ; 95 percent confidence interval , 0.4 to 6.4 ) . The vaccine reduced hospitalizations and emergency department visits related to G1-G4 rotavirus gastroenteritis occurring 14 or more days after the third dose by 94.5 percent ( 95 percent confidence interval , 91.2 to 96.6 percent ) . In a nested sub study , efficacy against any G1-G4 rotavirus gastroenteritis through the first full rotavirus season after vaccination was 74.0 percent ( 95 percent confidence interval , 66.8 to 79.9 percent ) ; efficacy against severe gastroenteritis was 98.0 percent ( 95 percent confidence interval , 88.3 to 100 percent ) . The vaccine reduced clinic visits for G1-G4 rotavirus gastroenteritis by 86.0 percent ( 95 percent confidence interval , 73.9 to 92.5 percent ) . CONCLUSIONS This vaccine was efficacious in preventing rotavirus gastroenteritis , decreasing severe disease and health care contacts . The risk of intussusception was similar in vaccine and placebo recipients . ( Clinical Trials.gov number , NCT00090233 . BACKGROUND Efficacy of the pentavalent rotavirus vaccine ( PRV ) , RotaTeq ( ® ) , against  severe rotavirus gastroenteritis ( RVGE )  was evaluated in two double-blind , placebo-controlled , multicenter Phase III clinical trials conducted in GAVI-eligible countries in Africa ( Ghana , Kenya , and Mali ) and in Asia ( Bangladesh and Vietnam ) from March 2007 through March 2009 . The findings from each continent have been analyzed and presented separately , according to a single identical protocol . Ad hoc analyses combining data from the five sites were performed to further assess the impact of PRV . METHODS 6674 infants ( 4705 infants from Africa and 1969 infants from Asia ) , r and omized 1:1 to receive 3 doses of PRV/placebo at approximately 6- , 10- , and 14-weeks of age according to each country 's EPI schedule , were included in the per protocol efficacy analysis . Breastfeeding and concomitant administration of EPI vaccines , including OPV , were allowed . Episodes of gastroenteritis ( GE ) in infants who presented to study facilities were captured and scored using the 20-point Vesikari scale . Stool sample s were analyzed by rotavirus-specific EIA to detect presence of rotavirus antigen and RT-PCR to determine the G/P genotypes . We assessed efficacy to prevent all-cause GE and RVGE at a variety of cut-off points ( score≥11 , severe ; score≥15 , very severe ) . RESULTS Vaccine efficacy ( VE ) against RVGE , regardless of serotype , through the entire follow-up period for any severity , severe ( score≥11 ) , and very severe ( score≥15 ) was 33.9 % , 95 % CI ( 22.7 , 43.5 ) , 42.5 % , 95 % CI ( 27.4 , 54.6 ) , and 51.2 % , 95 % CI ( 26.3 , 68.2 ) , respectively . Through the first year of life , VE against severe RVGE was 58.9 % , 95 % CI ( 40.0 , 72.3 ) and against all-cause severe GE was 23.0 % , 95 % CI ( 5.4 , 37.3 ) . VE against severe RVGE caused by non-vaccine G serotypes , G8 and G9 , through the entire follow-up period was 87.5 % , 95 % CI ( 6.8 , 99.7 ) and 48.0 % , 95 % CI ( -5.5 , 75.6 ) , respectively . All G8 strains were associated with P2A[6 ] ( a P-type not contained in PRV ) , while the majority of the G9 strains were associated with P1A[8 ] ( a P-type contained in PRV ) . CONCLUSIONS Combining data from the 5 sites strengthens the precision of VE estimates and reveals rising VE with increased RVGE severity . Extrapolating data from VE against severe GE and RVGE suggest that 39 % of severe GE episodes during the first year of life were due to rotavirus , highlighting substantial , potentially preventable , public health burden of RVGE . PRV provides protection against non-vaccine serotypes ( G8P2A[6 ] ) BACKGROUND Peak incidence of rotavirus gastroenteritis is seen in infants between 6 and 24 months of age . We therefore aim ed to assess the 2-year efficacy and safety of an oral live attenuated human rotavirus vaccine for prevention of severe gastroenteritis in infants . METHODS 15 183 healthy infants aged 6 - 13 weeks from ten Latin American countries r and omly assigned in a 1 to 1 ratio to receive two oral doses of RIX4414 or placebo at about 2 and 4 months of age in a double-blind , placebo-controlled phase III study were followed up until about 2 years of age . Primary endpoint was vaccine efficacy from 2 weeks after dose two until 1 year of age . Treatment allocation was concealed from investigators and parents of participating infants . Efficacy follow-up for gastroenteritis episodes was undertaken from 2 weeks after dose two until about 2 years of age . Analysis was according to protocol . This study is registered with Clinical Trials.gov , number NCT00140673 ( eTrack444563 - 023 ) . FINDINGS 897 infants were excluded from the according-to- protocol analysis . Fewer cases ( p<0.0001 ) of severe rotavirus gastroenteritis were recorded for the combined 2-year period in the RIX4414 group ( 32 [ 0.4 % ] of 7205 ; 95 % CI 0.3 - 0.6 ) than in the placebo group ( 161 [ 2.3 % ] of 7081 ; 1.9 - 2.6 ) , result ing in a vaccine efficacy of 80.5 % ( 71.3 - 87.1 ) to 82.1 % ( 64.6 - 91.9 ) against wild-type G1 , 77.5 % ( 64.7 - 86.2 ) against pooled non-G1 strains , and 80.5 % ( 67.9 - 88.8 ) against pooled non-G1 P[8 ] strains . Vaccine efficacy for hospital admission for rotavirus gastroenteritis was 83.0 % ( 73.1 - 89.7 ) and for admission for diarrhoea of any cause was 39.3 % ( 29.1 - 48.1 ) . No cases of intussusception were reported during the second year of follow-up . INTERPRETATION Two doses of RIX4414 were effective against severe rotavirus gastroenteritis during the first 2 years of life in a Latin American setting . Inclusion of RIX4414 in routine paediatric immunisations should reduce the burden of rotavirus gastroenteritis worldwide We estimated the incidence of  watery diarrhea in the community before and after introduction of the pentavalent rotavirus vaccine in León , Nicaragua . A r and om sample of households was selected before and after rotavirus vaccine introduction . All children < 5 years of age in selected households were eligible for inclusion . Children were followed every 2 weeks for watery diarrhea episodes . The incidence rate was estimated as numbers of episodes per 100 child-years of exposure time . A mixed effects Poisson regression model was fit to compare incidence rates in the pre-vaccine and vaccine periods . The pre-vaccine cohort ( N = 726 ) experienced 36 episodes per 100 child-years , and the vaccine cohort ( N = 826 ) experienced 25 episodes per 100 child-years . The adjusted incidence rate ratio was 0.60 ( 95 % confidence interval [ CI ] 0.40 , 0.91 ) during the vaccine period versus the pre-vaccine period , indicating a lower incidence of watery diarrhea in the community during the vaccine period BACKGROUND Rotavirus is the most common cause of acute childhood gastroenteritis . Vaccination with live oral heterologous rotavirus vaccines may prevent rotavirus gastroenteritis . We assessed the efficacy of rhesus-human reassortant rotavirus tetravalent vaccine ( RRV-TV ) against severe rotavirus gastroenteritis in Finnish children in a r and omised placebo-controlled double-blind trial . METHODS Placebo or RRV-TV ( titre 4x10(5 ) plaque-forming units ) was given to infants at ages 2 , 3 , and 5 months . The children were followed up for one or two rotavirus epidemic seasons . The main outcome measure was protection against severe rotavirus gastroenteritis ( score > or = 11 on a 20-point severity scale ) . 2398 children were enrolled and received at least one dose of RRV-TV ( n=1191 ) or placebo ( n=1207 ) . The primary efficacy analysis was based on children who received three doses of RRV-TV ( n=1128 ) or placebo ( n=1145 ) . FINDINGS 256 episodes of rotavirus gastroenteritis occurred at any time during the study ; 65 were among 1191 RRV-TV recipients , and 191 among 1207 placebo recipients ( vaccine efficacy 66 % [ 95 % CI 55 - 74 ] ; intention-to-treat analysis ) . 226 episodes were included in the primary efficacy analysis of fully vaccinated children ( 54 among 1128 RRV-TV recipients , 172 among 1145 placebo recipients ; vaccine efficacy 68 % [ 57 - 76 ] ) . 100 episodes were severe , eight in RRV-TV recipients and 92 in placebo recipients ( vaccine efficacy 91 % [ 82 - 96 ] ) . INTERPRETATION RRV-TV vaccine was highly effective against severe rotavirus gastroenteritis in young children . Incorporation of this vaccine into routine immunisation schedules of infants could reduce severe rotavirus gastroenteritis by 90 % and severe gastroenteritis of all causes in young children by 60 % BACKGROUND Rotavirus gastroenteritis causes many deaths in infants in sub-Saharan Africa . Because rotavirus vaccines have proven effective in developed countries but had not been tested in developing countries , we assessed efficacy of a pentavalent rotavirus vaccine against severe disease in Ghana , Kenya , and Mali between April , 2007 , and March , 2009 . METHODS In our multicentre , double-blind , placebo-controlled trial , undertaken in rural areas of Ghana and Kenya and an urban area of Mali , we r and omly assigned infants aged 4 - 12 weeks without symptoms of gastrointestinal disorders in a 1:1 ratio to receive three oral doses of pentavalent rotavirus vaccine 2 mL or placebo at around 6 weeks , 10 weeks , and 14 weeks of age . Infants with HIV infection were not excluded . R and omisation was done by computer-generated r and omisation sequence in blocks of six . We obtained data for gastrointestinal symptoms from parents on presentation to health-care facilities and clinical data were obtained prospect ively by clinicians . The primary endpoint was severe rotavirus gastroenteritis ( Vesikari score > or=11 ) , detected by enzyme immunoassay , 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 5468 infants were r and omly assigned to receive pentavalent rotavirus vaccine ( n=2733 ) or placebo ( n=2735 ) . 2357 infants assigned to vaccine and 2348 assigned to placebo were included in the per- protocol analysis . 79 cases of severe rotavirus gastroenteritis were reported in 2610.6 person-years in the vaccine group , compared with 129 cases in 2585.9 person-years in the placebo group , result ing in a vaccine efficacy against severe rotavirus gastroenteritis of 39.3 % ( 95 % CI 19.1 - 54.7 , p=0.0003 for efficacy > 0 % ) . Median follow-up in both groups was 527 days starting 14 days after the third dose of vaccine or placebo was given . 42 ( 1.5 % ) of 2723 infants assigned to receive vaccine and 45 ( 1.7 % ) of 2724 infants assigned to receive placebo had a serious adverse event within 14 days of any dose . The most frequent serious adverse event was gastroenteritis ( vaccine 17 [ 0.6 % ] ; placebo 17 [ 0.6 % ] ) . INTERPRETATION Pentavalent rotavirus vaccine is effective against severe rotavirus gastroenteritis in the first 2 years of life in African countries with high mortality in infants younger than 5 years . We support WHO 's recommendation for adoption of rotavirus vaccine into national exp and ed programmes on immunisation in Africa . FUNDING PATH ( GAVI Alliance grant ) and Merck Background : Finl and introduced universal rotavirus ( RV ) vaccination in September 2009 , with exclusive use of the pentavalent human-bovine reassortant RV vaccine RotaTeq ® and following a vaccination schedule at 2 , 3 and 5 months of age . This study monitored the impact of RV vaccination on hospitalizations due to RV acute gastroenteritis ( RVGE ) . The results following the first 3 RV seasons after implementation of universal RV vaccination are presented . Methods : Prospect i ve hospital-based surveillance identified children with acute gastroenteritis admitted to 2 University Hospitals ( Tampere and Oulu , Finl and ) , from December 2009 to August 2012 . The surveillance covered a population of approximately 173,000 children from the 2 hospitals ’ catchment areas . Stool sample s were taken and analyzed central ly for RV by enzyme-linked immunosorbent assay , with genotyping by reverse transcription polymerase chain reaction . International Classification of Diseases discharge codes were collected retrospectively pre- and postvaccination . Results : During the 3-year prospect i ve surveillance , 127 RVGE episodes were identified . Of these , 117 were in unvaccinated children and 6 were in fully vaccinated children ( RotaTeq , n = 3 ; Rotarix , n = 3 ) . The vaccine effectiveness against hospitalized RVGE for fully vaccinated children was 92.1 % [ 95 % confidence interval ( CI ) : 50.0–98.7 ] among children eligible for the National Immunization Program . When analyzing retrospectively the Tampere and Oulu hospital data bases for all children aged < 16 years , hospitalizations for RVGE had decreased by 78 % in the postvaccination period ( 2009–2012 ) compared with the prevaccination data ( 2001–2006 ) . Conclusions : Severe RVGE requiring hospitalization was virtually eliminated in vaccine-eligible children in the 3 years following implementation of universal RotaTeq vaccination in Finl and BACKGROUND Diarrhoeal diseases cause illness and death among children younger than 5 years in low-income countries . We design ed the Global Enteric Multicenter Study ( GEMS ) to identify the aetiology and population -based burden of paediatric diarrhoeal disease in sub-Saharan Africa and south Asia . METHODS The GEMS is a 3-year , prospect i ve , age-stratified , matched case-control study of moderate-to-severe diarrhoea in children aged 0 - 59 months residing in censused population s at four sites in Africa and three in Asia . We recruited children with moderate-to-severe diarrhoea seeking care at health centres along with one to three r and omly selected matched community control children without diarrhoea . From patients with moderate-to-severe diarrhoea and controls , we obtained clinical and epidemiological data , anthropometric measurements , and a faecal sample to identify enteropathogens at enrolment ; one follow-up home visit was made about 60 days later to ascertain vital status , clinical outcome , and interval growth . FINDINGS We enrolled 9439 children with moderate-to-severe diarrhoea and 13,129 control children without diarrhoea . By analysing adjusted population attributable fractions , most attributable cases of moderate-to-severe diarrhoea were due to four pathogens : rotavirus , Cryptosporidium , enterotoxigenic Escherichia coli producing heat-stable toxin ( ST-ETEC ; with or without co-expression of heat-labile enterotoxin ) , and Shigella . Other pathogens were important in selected sites ( eg , Aeromonas , Vibrio cholerae O1 , Campylobacter jejuni ) . Odds of dying during follow-up were 8·5-fold higher in patients with moderate-to-severe diarrhoea than in controls ( odd ratio 8·5 , 95 % CI 5·8 - 12·5 , p<0·0001 ) ; most deaths ( 167 [ 87·9 % ] ) occurred during the first 2 years of life . Pathogens associated with increased risk of case death were ST-ETEC ( hazard ratio [ HR ] 1·9 ; 0·99 - 3·5 ) and typical enteropathogenic E coli ( HR 2·6 ; 1·6 - 4·1 ) in infants aged 0 - 11 months , and Cryptosporidium ( HR 2·3 ; 1·3 - 4·3 ) in toddlers aged 12 - 23 months . INTERPRETATION Interventions targeting five pathogens ( rotavirus , Shigella , ST-ETEC , Cryptosporidium , typical enteropathogenic E coli ) can substantially reduce the burden of moderate-to-severe diarrhoea . New methods and accelerated implementation of existing interventions ( rotavirus vaccine and zinc ) are needed to prevent disease and improve outcomes . FUNDING The Bill & Melinda Gates Foundation
Background RotaTeq ™ ( RV5 ; Merck & Co. Inc. , USA ) and Rotarix ™ ( RV1 , GlaxoSmithKline , Belgium ) vaccines , developed to prevent rotavirus diarrhea in children under five years old , were both introduced into national immunization programs in 2006 .
As many countries in Latin America and the Caribbean have included either RV5 or RV1 in their routine childhood vaccination programs , we conducted a systematic review and meta- analysis to analyze efficacy , safety and effectiveness data from the region .