Serological evaluation of a measles, mumps, and rubella vaccine. FREQUENCY OF TRUE ADVERSE REACTIONS TO MEASLES-MUMPS-RUBELLA VACCINE: A Double-blind Placebo-controlled Trial in Twins Trivalent combined measles-mumps-rubella vaccine. Findings in clinical-laboratory studies. Clinical and serologic evaluation of measles, mumps, and rubella (HPV-77:DE-5 and RA 27/3) virus vaccines, singly and in combination. Incomplete evidence: the inadequacy of databases in tracing published adverse drug reactions in clinical trials Illness after measles-mumps-rubella vaccination. Clinical evaluation of a new measles-mumps-rubella trivalent vaccine. Mumps vaccine L-Zagreb, prepared in chick fibroblasts. I. Production and field trials. A new combined trivalent live measles (AIK-C strain), mumps (Hoshino strain), and rubella (Takahashi strain) vaccine. Findings in clinical and laboratory studies. Evaluation of a trivalent measles, mumps, rubella vaccine in children. A randomised single blind trial of a combined mumps measles rubella vaccine to evaluate serological response and reactions in the UK population. Combined trivalent and bivalent measles, mumps and rubella virus vaccination Immunogenicity and efficacy of one dose measles-mumps-rubella (MMR) vaccine at twelve months of age as compared to monovalent measles vaccination at nine months followed by MMR revaccination at fifteen months of age.
Combined measles , mumps , and rubella vaccination is soon to become available in Britain in the routine immunisation programme . A controlled study was performed in 319 children , aged 13 months , to assess the antibody response and clinical reactions to a new combined measles , mumps , and rubella vaccine in comparison with a single component measles vaccine . In the children who received the combined vaccine , seroconversion was established in 93 % for measles , 99 % for rubella , and 100 % for mumps . In the children who received the single measles vaccine , seroconversion was established in 92 % for measles and in none for rubella and mumps . There was no increase in clinical reactions after the measles , mumps , and rubella vaccine compared with the measles vaccine . These results suggest that this combined vaccine would be effective and safe in a British population and give further support for the introduction of the combined measles , mumps , and rubella vaccine to Britain 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 Four lots of combined trivalent Moraten measles , Jeryl Lynn mumps , and HPV-77 duck rubella vaccine were administered to a total of 715 children , 7 months to 7 years of age , who were initially without antibody against any of the three viruses . Overall , 96 % of the children developed measles hemagglutination-inhibiting , 95 % developed mumps neutralizing , and 94 % developed rubella hemagglutination-inhibiting antibodies . The most important clinical reaction to the trivalent vaccine was mild fever in a portion of the children , such as is expected following administration of Moraten measles vaccine alone . Joint involvement was notably absent during the six-to-nine week follow-up . The combined measles-mumps-rubella vaccine provides a simple means for immunizing against all three of these diseases without impairment of antibody response and without significant increase in clinical reaction A double-blind , placebo-controlled comparison of single component and combination measles , mumps , and rubella ( HPV-77:DE-5 and RA 27/3 ) virus vaccines involving 502 young children was conducted . The rubella antibody response was similar with RA 27/3 rubella and measles-mumps-rubella ( RA 27/3 ) vaccines , but was diminished with the combination vaccine that incorporated HPV-77:DE-5 rubella . There was no evidence of enhanced clinical reactivity with either of the measles-mumps-rubella vaccines Background We would expect information on adverse drug reactions in r and omised clinical trials to be easily retrievable from specific search es of electronic data bases . However , complete retrieval of such information may not be straightforward , for two reasons . First , not all clinical drug trials provide data on the frequency of adverse effects . Secondly , not all electronic records of trials include terms in the abstract or indexing fields that enable us to select those with adverse effects data . We have determined how often automated search methods , using indexing terms and /or textwords in the title or abstract , would fail to retrieve trials with adverse effects data . Methods We used a sample set of 107 trials known to report frequencies of adverse drug effects , and measured the proportion that ( i ) were not assigned the appropriate adverse effects indexing terms in the electronic data bases , and ( ii ) did not contain identifiable adverse effects textwords in the title or abstract . Results Of the 81 trials with records on both MEDLINE and EMBASE , 25 were not indexed for adverse effects in either data base . Twenty-six trials were indexed in one data base but not the other . Only 66 of the 107 trials reporting adverse effects data mentioned this in the abstract or title of the paper . Simultaneous use of textword and indexing terms retrieved only 82/107 ( 77 % ) papers . Conclusions Specific search strategies based on adverse effects textwords and indexing terms will fail to identify nearly a quarter of trials that report on the rate of drug adverse effects OBJECTIVES To provide accurate information on the common sequelae of measles-mumps-rubella ( MMR ) vaccination and to compare post-vaccine symptoms in children vaccinated at 13 and 15 months . DESIGN Prospect i ve cluster r and omized controlled trial . SETTING Twenty-two family practice s in southwestern Ontario . PATIENTS All 376 infants who were due to receive MMR vaccine in the next year , 253 ( 67.3 % ) successfully completed the study . INTERVENTION MMR vaccine administered at 13 months by half of the family physicians and at 15 months by the remaining half . OUTCOME MEASURES Family physician 's physical findings in children 7 days and 30 days after vaccine ; reported illnesses by mothers in a daily diary in the month before and after vaccination and medical records of visits to family physicians and hospital admissions in the month before and after vaccination . RESULTS Compared with the incidence rates in the corresponding weeks before vaccination , the rates of lymphadenopathy ( 23.8 % ) and fever ( 16.8 % ) were higher 1 week afterward and the rate of rash ( 26.9 % ) was higher 7 to 14 days afterward . Fewer health problems were reported in the third and fourth weeks after vaccination than in the corresponding weeks beforeh and . Hospital admissions after vaccination were no more frequent than those before once cause and time of admission were taken into account . The two age groups did not differ in any of the outcomes . CONCLUSIONS Mothers should be informed about the possibility of increased physical findings in the weeks after MMR vaccination , especially lymphadenopathy , nasal discharge and rash . Since the occurrence of sequelae does not seem to differ significantly between 13-month-old recipients and 15-month-old recipients , it should not influence the decision of when to administer the vaccine In a series of clinical studies of a combined measles ( Schwarz strain ) , mumps ( Jeryl Lynn strain ) , and rubella ( Cendehill strain ) vaccine , 1,481 children received the vaccine or a placebo .  The vaccine did not cause any significant reactions . The frequencies of mild , transient fever or rash or both in triple-susceptible vaccinees were similar to those that follow use of Schwarz strain measles vaccine alone . Measles , mumps , and rubella seroconversion rates in triple-susceptible vaccinees ranged from 95 % to 100 % . Geometric mean antibody titers were as high as those that usually result from use of these same virus strains as monovalent vaccines Leningrad-L3 Mumps Vaccine virus has been further attenuated by adaptation and passage on SPF chick embryo fibroblast cell cultures . This new mumps strain has been design ated L-Zagreb and has been used to prepare mumps vaccines which meet the WHO requirements . Observations during both the field trial period prior to registration and during the later use of the vaccine showed that the few reactions observed were mild and that seroconversion was obtained in 88 - 98 % of vaccines . The morbidity of mumps in Croatia declined more than tenfold after the introduction of the new vaccine . During a mumps epidemic , vaccine efficiency was calculated to be 97 - 100 % Trivalent virus vaccine , containing measles AIK-C strain , mumps Hoshino strain , and rubella Takahashi strain , was administered to a total of 1369 healthy children , 8 months to 18 years of age . For comparative study , monovalent vaccines of AIK-C strain and Hoshino strain were administered to 147 and 122 initially seronegative children , respectively . The clinical and serological responses following vaccination were analyzed . Among the recipients of the trivalent vaccine , 893 were initially seronegative to all three viruses . Inoculation induced sufficient serological responses : 99.7 % for measles and rubella viruses and 96.3 % for mumps virus . The incidence of febrile reaction ( greater than or equal to 37.5 degrees C axillary temperature ) was low , 15.9 % , and a temperature of 39.0 degrees C or higher occurred in only 1.3 % of the subjects . The seroconversion rate , magnitude of antibody titers , and incidence of clinical reactions following the trivalent vaccination were similar to those occurring after the monovalent measles vaccination Vaccine . The vaccine was a combination of Schwarz strain live , attenuated measles virus , 2 Jeryl Lynn strain five , attenuated mumps virus ? and Cendehill strain live , and attenuated rubella virus ?  Three different production lots were used in this study . All lots contained at least 1,000 50 % tissue culture infective doses of measles and rubella viruses and 5,000 TCIDs0 of mumps virus . The trivalent vaccine was dispensed into single dose vials , lyophilized , and stored at 5~ until administered . Placebo . The placebo used in the study was identical to the vaccine in all respects except it did not contain virus . Serology . All serologic assays were performed in the Assay Laboratory of The Dow Chemical Company in Zionsville , Indiana . Antibodies to measles and rubella viruses were determined by the hemagglutination inhibition method in microtiter plates ? , 6 Four units of hemagglutination antigen were used ; the end point was taken as the highest serum dilution that completely Four hundred and twenty children were r and omly assigned to receive either mumps measles rubella ( MMR ) vaccine ( 207 ) or measles vaccine ( 213 ) in a single blind study , to investigate the reactogenicity and serology of the MMR vaccine . There was no significant difference between the number of children developing symptoms after MMR vaccination to those developing symptoms after measles vaccination . Both vaccines are associated with a rash , temperature and restlessness five to thirteen days after vaccination . The serological response to  measles vaccine  was similar in both groups with 92 - 6 % seroconverting with MMR , and 96 - 8 % with measles . Seroconvertion against mumps and rubella with the MMR vaccine was 88 % and 96 % respectively . This study confirms the safety and efficacy of the  MMR vaccine  in a UK population Summary Combined live measles-mumps-rubella and mumps-rubella vaccine were tested in a small scale trial on a series of infants and young children . Children of the same age given live rubella vaccine only were used as a control group . The antibody response to all vaccinal viruses was very good . The vaccines were very well tolerated . The combined vaccines seem to provide practical advantages in the routine immunization practice , by saving time and man-power , and eventually increasing the coverage of the target groups . ZusammenfassungEine kombinierte Masern-Mumps-Röteln-und Mumps-Röteln-Vakzine wurde an einer kleinen Zahl von Säuglingen und Kleinkindern getestet . Gleichaltrigen Kindern einer Kontrollgruppe wurde Röteln-Lebendvakzine gegeben . Dieser Impfstoff wurde gut toleriert . Die kombinierte Vakzine weist praktische Vorteile bei der Routineimmunisierung auf , weil sie den Arbeitsaufw and reduziert und möglicherweise eine breitere Zielgruppe erfassen kann BACKGROUND AND METHODS measles is a common cause of morbidity and mortality in developing countries . Although the measles-mumps-rubella vaccine ( MMR ) is currently in use in developed countries , monovalent measles vaccine ( MV ) is routinely recommended by World Health Organization ( WHO ) at 9 months of age in Turkey , as in many other developing countries . In this study , 442 Turkish children received MV  at 9 months of age and were revaccinated with MMR vaccine at 15 months of age . In the second group 495 children received MMR at 12 months of age with no earlier measles vaccination .  Antibodies were measured before the first vaccination and 6 weeks after the MMR . All children had been followed for occurrence of measles infection for 60 months . Two vaccination schedules were compared for immunogenicity and protection rates . CONCLUSIONS seroconversion and clinical protection rates were significantly higher in children who received only MMR at 12 months of age than in children revaccinated at 15 months of age . Seroconversion rate for measles was 69.9 % in children who received MMR at 12 months of age and 90.3 % in children revaccinated at 15 months of age ( P=0.0003 ) . While there was no measles case in children who were revaccinated , 12 ( 2.7 % ) children in the first group acquired measles during the follow-up period . Vaccination at 12 months of age appeared to be better than the current national st and ard . The late elimination of maternal antibodies and the inhibitory effect of a weak antibody response after the first dose of vaccine at 9 months may explain the better immunogenicity and efficacy of the MMR vaccine given at 12 months of age
Public debate over the safety of the trivalent measles , mumps and rubella ( MMR ) vaccine and the drop in vaccination rates in several countries persists despite its almost universal use and accepted effectiveness .
We carried out a systematic review to assess the evidence of unintended effects ( beneficial or harmful ) associated with MMR and the applicability of systematic review ing methods to the field of safety evaluation .