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BackgroundThe persistence of antibodies against measles, mumps, and rubella induced by the measles-mumps-rubella (MMR) vaccine and the kinetics of antibody decline after the second MMR vaccine dose were studied in the same cohort for 20 years MethodsMeasles, mumps, and rubella antibodies were measured by enzyme immunoassay in 20-year follow-up serum samples (n=183) of twice-vaccinated individuals, and measles antibodies were also measured in oral fluids (n=177). Antibody decay was determined in a group (n=58) with subsequent samples collected 1, 8, and 15 years after the second MMR dose ResultsIn total, 95%, 74%, and 100% of 183 vaccinees were still seropositive for measles, mumps, and rubella, respectively, and 85% of 177 vaccinees had measurable measles antibodies in their oral fluids. The antibody levels declined significantly after the second dose, but subsequently the rate of decline was slower ConclusionsA high rate of seropositivity was found 20 years after the first MMR dose, particularly for rubella and measles. Our results show that MMR vaccine–induced antibodies wane significantly after the second dose. According to epidemiological data, the protection induced by MMR vaccination in Finland seems to persist at least until early adulthood. However, the situation requires constant vigilance

Maternal First-Trimester Enterovirus Infection and Future Risk of Type 1 Diabetes in the Exposed Fetus Hanna R. Viskari 1 , Merja Roivainen 2 , Antti Reunanen 2 , Janne Pitkäniemi 2 , Karita Sadeharju 1 , Pentti Koskela 3 , Tapani Hovi 2 , Pauli Leinikki 2 , Pekka Vilja 1 , Jaakko Tuomilehto 2 4 and Heikki Hyöty 1 5 1 Juvenile Diabetes Foundation International Center for the Prevention of type 1 diabetes in Finland and the Department of Virology, University of Tampere, Medical School, Tampere, Finland 2 National Public Health Institute, Helsinki, Finland 3 National Public Health Institute, Oulu, Finland 4 Department of Public Health, University of Helsinki, Helsinki, Finland 5 Department of Clinical Microbiology, Centre for Laboratory Medicine, Tampere University Hospital, Tampere, Finland Abstract Previous studies have suggested that enterovirus infections during pregnancy may increase the risk of type 1 diabetes in the offspring. Our aim was to evaluate the role of first trimester enterovirus infections in a larger cohort of pregnant women. Two series of pregnant women were analyzed as follows: 948 women (series 1) and 680 women (series 2) whose child developed clinical diabetes before the ages of 15 or 7 years, respectively. An equal number of control women with a nondiabetic child was selected. Acute enterovirus infections were diagnosed by measuring IgM class antibodies against coxsackievirus B5 (series 1) and a mixture of coxsackievirus B3, coxsackievirus A16, and echovirus 11 antigens (series 2). In series 2, all sera were also analyzed for IgG class antibodies against an enterovirus peptide antigen. In addition, 152 randomly selected case-control pairs and all IgM-positive mothers’ sera were tested for enterovirus RNA (series 2). In series 1, 3.1% of case women had IgM antibodies against coxsackievirus B5 antigen compared with 4.1% of control women (NS). In series 2, 7.1% of case and 5.3% of control women had IgM against the mixture of enterovirus antigens (NS). IgG class enterovirus antibodies did not differ between the groups. Enterovirus RNA was found only in one case woman (0.3%) of the subgroup of samples and in 5.7% of 70 IgM-positive women. The results suggest that enterovirus infection during the first trimester of pregnancy is not associated with increased risk for type 1 diabetes in the child. Footnotes Address correspondence and reprint requests to Dr. Hanna Viskari, University of Tampere, Medical School/FM3, 5th floor, Department of Virology, Lenkkeilijänkatu 10, 33520 Tampere, Finland. E-mail: hanna.viskari{at}uta.fi . Received for publication 21 February 2002 and accepted in revised form 17 May 2002. CAV, coxsackievirus A; CBV, coxsackievirus B; EIA, enzyme immunoassay; EIU, enzyme immunoassay unit; RIA, radioimmunoassay. DIABETES

The possible viral etiology of mumps-like illnesses in patients vaccinated for measles, mumps, and rubella (MMR) was studied by use of serum samples prospectively collected, during 1983–1998, from 601 acutely ill Finnish children and adolescents with mumps-like symptoms. Mumps virus was excluded by testing serum samples for mumps antibodies, and the serum samples were further tested for antibodies to adenovirus, enterovirus, Epstein-Barr virus, parainfluenza virus types 1–3, and parvovirus B19. The serum samples of 114 children <4 years old were also tested for antibodies to human herpesvirus 6 (HHV-6). A viral etiology was verified in 84 cases (14%), most commonly Epstein-Barr virus (7%), followed by parainfluenza virus types 1, 2, or 3 (4%) and adenovirus (3%). HHV-6 infection was found in 5 children <4 years old (4%). This study confirms that mumps-like symptoms in MMR-vaccinated children and adolescents are often not caused by mumps virus infection. Careful laboratory-based diagnostic testing of MMR-vaccinated children and adolescents who develop clinical symptoms compatible with those of mumps is important in the treatment of individual patients, in the comprehension of the true epidemiology of these illnesses, and in the evaluation of the impact of MMR vaccination programs

Peltola et al found no evidence for inflammatory bowel disease or autism caused by the measles, mumps, and rubella (MMR) vaccine. Illness that occurred among patients was mild, and may have resulted by concomitant infection.

A national two-dose vaccination program with a combined measles, mumps and rubella (MMR-II) vaccine was introduced in Finland, in 1982, immunizing children at the ages of 14–18 months and 6 years. Antibody levels were determined from serial samples from a group of originally 350 children during 15 years. The latest samples were taken 15.5 years after the first vaccination and 70% of the children could still be reached. The aim of this study was to determine the kinetics of rubella antibodies induced by the MMR-II vaccine in these individuals. Rubella antibodies were analyzed from three different cohorts: Group I seronegative children ( n=166) vaccinated at 14–18 months and 6 years, Group II seronegative children ( n=139) and Group III seropositive children ( n=16) vaccinated at 6 and 11–13 years. Samples collected 0–9 years after vaccination were analyzed by hemolysis-in-gel (HIG) and later samples by enzyme immunoassay (EIA) techniques. The primary vaccination induced 100% seropositivity in vaccinees with a mean zone diameter of 10 (±1.3), 10.2 (±1.1) and 11.5 (±0.9) mm, in Groups I, II and III, respectively. The seropositivity rate was still high at 15 years, 99%, 100% and 100% with the geometric mean titer 23, 46 and 105 IU/ml, respectively. At 15 years, antibody levels <15 IU/ml which is the suggested protective level, were found in 31, 9 and 0% of children in Groups I, II and III, respectively. Because almost a third of the individuals in Group I now, at the age of 17 years, had low levels of rubella antibodies, it is possible that rubella infections may re-emerge during pregnancy. A careful surveillance including serological follow-up is therefore very important.

Exposure to Coxsackie B virus or other enteroviruses prenatally or in childhood increases the risk for later manifestation of insulin-dependent diabetes mellitus (IDDM). The occurrence of enterovirus infectionswas analyzed in 23 initially nondiabetic and islet cell antibody (ICA)-negative siblings of IDDM patients who converted to ICA positivity during a prospective follow-up study. Increases in enterovirus antibody levels, documented by heavy chain-capture RIA and EIA techniques, were significantly more frequent in sample intervals in which ICA first appeared (18/23, 78%) than in other sample intervals in these siblings(30/92, 33%;P < .001)or all sample intervals in 97 ICA-negative control siblings (117/403, 29%;P < .001). The children who converted to ICA positivity during an enterovirus infection more often had the high-risk HLA-DQB1 genotype than did children who were constantly ICA-negative (P < .01).The results suggest that enteroviruses may be important in the induction of a beta cell damaging process long before the clinical manifestation of IDDM.

The viral etiology of measles- or rubella-like illnesses after MMR (measles, mumps, and rubella) vaccination was studied prospectively in 993 acutely ill Finnish children with fever and rash in 1983–1995. Their sera were tested for adeno-, entero-, and parvovirus B19 antibodies. Sera of 300 children <4 years old were also tested for human herpesvirus 6 (HHV-6) antibodies. Measles and rubella had been excluded by previous antibody testing. Serologic diagnosis of adeno-, entero-, or parvovirus infection was based on EIA (IgM or IgG antibodies) and that of HHV-6 on indirect immunofluorescence. A viral etiology was verified in 368 cases, most commonly parvovirus (20%), followed by enterovirus (9%) and adenovirus (4%). Among young children, HHV-6 infection was found in 37 (12%). Thirty-eight children (4%) had double infections. This study confirms that measles- or rubella-like illnesses in MMR-vaccinated children are often caused by other viruses. Each suspected vaccine failure requires laboratory confirmation to maintain reliable surveillance and control and to establish the specific etiology of the disease.

Peltola and Leinikki discuss genetic research on the rubella virus. Research indicates that women might be vaccinated during pregnancy without doing harm to the unborn child.