Measles outbreaks in the Bern canton

Currently, overall vaccination coverage against measles among infants ranges between 77% and 89% in Switzerland. Experience in other countries has shown that this level of vaccination is not sufficient to prevent measles outbreaks, especially among schoolchildren. During 1992 surveillance for measles outbreaks in closed populations was conducted in the Canton of Berne. Outbreaks were investigated for vaccine efficacy. Two measles outbreaks in schoolchildren were observed during the study period. In 2 Bernese suburban schools 6 measles cases in children (median age 12.5 years) occurred over a period of 37 days. One of the cases had been vaccinated. Vaccination rate in the healthy control children was 89.7%. Estimated vaccine efficacy was 97.7% (95% confidence interval [CI]: 68%, 99%). The second outbreak occurred in a rural region and comprised 21 measles cases (median age 7.5 years) within 43 days. 10 (47.6%) of the cases attended the same school. None of the cases had been vaccinated. Of the healthy control children 82.6% had received measles vaccine. Estimated vaccine efficacy was 100% (CI: 87%, 100%). These two measles outbreaks were due to failure to vaccinate rather than low vaccine efficacy. Surveillance for measles cases is currently not sufficient for the detection of measles outbreaks in our population. Laboratory confirmation of measles, especially in vaccinated persons, has become more important in a time of relatively low measles incidence.     

Novel methods for molecular dynamics simulations

HYPOTHESIS: Monovalent measles vaccine can be administered to children 6 to 11 months of age during an outbreak. Efficacy and effectiveness of this control measure still have to be assessed. METHODS: During and outbreak of measles, monovalent measles vaccine was administered as part of outbreak control to children aged 6 to 11 months. Active surveillance was used to detect cases of measles occurring during the following month. Children who did not develop measles were tested for measles antibody before their revaccination at 15 months of age. RESULTS: Of 81 children 6 to 11 months of age, 56 were vaccinated and two received immunoglobulins; the latter were excluded from the analysis. Measles occurred in 15 of the 79 children during and after the vaccination campaign, for an overall attack rate of 19%. The attack rate among unvaccinated children was 39% (9 of 23), compared with 11% (6 of 56) among those vaccinated (relative risk = 3.6, 95% confidence interval [CI] = 1.5 to 9.1). All of those who sustained measles in the vaccinated group developed the disease within 10 days after vaccination. The overall vaccine effectiveness was 73% (95% CI = 32% to 89%) when children were classified as vaccinated as soon as they were given measles vaccine. It rose to 96% (95% CI = 72% to 99%) when children were considered vaccinated 1 week postimmunization. Nineteen infants who were vaccinated and who did not develop measles during the outbreak were tested for measles antibody status at 15 months of age before revaccination. All had plaque reduction neutralizing antibody titers greater than 120. CONCLUSION: This study confirms that measles vaccination of infants aged 6 to 11 months is an effective intervention measure during measles outbreaks.     

Epidemiological investigations on measles in unvaccinated and vaccinated children (author's transl)

A national study, with participation of 82 paediatricians, was carried out on 9472 children over medium observation periods of between 3.13 and 5.46 years with evaluation of the history of measles, incidence of complications and details of vaccination procedure performed. The protection rate of primary vaccination with live vaccine was 0.89, with split vaccine (3 times) 0.67 and after a combination of split vaccine (3 times) with live vaccine (9 to 12 months later) 0.94. Complications due to measles in unvaccinated children were found in 5.9% of cases. Measles complications after failure of vaccination were found in 2.9% and 2.8% of children vaccinated with live or split vaccine, respectively. No such complications were observed in children vaccinated with a combination of split and live vaccines.     

Five year follow-up of morbidity and mortality among recipients of high-titre measles vaccines in Senegal

At 3-5 years of age, female recipients of Edmonston-Zagreb high-titre (EZ-HT) and Schwarz high-titre (SW-HT) measles vaccine had lower survival rates than female recipients of Schwarz standard measles vaccine (SW-STD) in Guinea-Bissau, Senegal and Haiti. In Senegal, the children who received high-titre vaccines have now been followed to the age of 5-7 years to determine whether the difference in mortality persisted, and whether differences in vaccine efficacy were apparent. At this age there was no difference in mortality between female recipients of high-titre and standard titre measles vaccines. There was no indication that high-titre EZ-HT vaccine at 5 months (EZ-HT,5m) provided suboptimal protection, as vaccine efficacy after exposure was 97% and 95%, respectively, for EZ-HT,5m and SW-STD,10m vaccines, whereas SW-HT,5m vaccine had an efficacy of 81%. The difference in mortality between recipients of high-titre vaccines and SW-STD observed in several studies during the first few years after vaccination may be explained by non-specific beneficial effects of the standard measles vaccine rather than a harmful effect of the high-titre vaccines.     

The effect of an accelerated immunisation schedule on pertussis in England and Wales

Notifications of pertussis in England and Wales have fallen dramatically from 65 810 during the epidemic year of 1982 to 3963 cases during the epidemic year of 1994, as vaccine coverage has risen. The incidence of pertussis has declined in all ages, including babies under 3 months of age who would have been at risk of disease from older siblings vaccinated under the accelerated schedule introduced in 1990 if immunity induced as result of this schedule had been short lived. To document the efficacy of the current whole cell vaccine under the accelerated schedule an enhanced surveillance scheme based on laboratory confirmed cases of pertussis was set up in 1994. Three deaths occurred in infants with confirmed pertussis, all of whom were under 8 weeks of age and unvaccinated. The overall vaccine efficacy for those over 6 months and under 5 years of age was 94%. This estimate may be inflated, as a number of biases could lead to the underascertainment of cases in vaccinated children, but it is similar to previous estimates obtained for children of the same age vaccinated under the 3, 5, and 10 month schedule. Vaccine efficacy was 89% for children aged over 5 and under 15 years. The enhanced surveillance scheme will enable us to monitor the duration of protection under the accelerated schedule and evaluate the continuing impact of pertussis infection.     

Podiatric casts used for surgery and trauma. Part II: Boot cast

Between April 18 and May 20, 1975, 16 cases of measles occurred in pupils in an elementary school in Baltimore County, Md., and 1 case occurred in a sibling at a junior high school. Measles was serologically confirmed in 16 of these pupils. Attack rates were determined by grade and by vaccine status. The measles attack rate was 2.1 percent for the 377 children who had been given measles vaccine at 1 year of age or later. The rates were 27.8 percent (13 times higher) for those vaccinated at less than 10 months of age and 20.0 percent (10 times higher) for those with no definite history of vaccine. The higher attack rates for children who were vaccinated only before 10 months of age supports the 1972 recommendation of the Public Health Service Advisory Committee on Immunization Practices that children vaccinated before this age need to be revaccinated with live measles virus vaccine to assure full protection. The finding that 2 of 10 children with a history of measles became ill during the outbreak suggests that such histories are not a totally reliable indicator of immunity. Containment of the outbreak was attributed to the high level of immunity in the community and prompt initiation of control measures.     

The influence of the HLA-DRB1*13 allele on measles vaccine response

BACKGROUND: Measles remains a public health threat in the United States with over 50,000 cases being reported from 1989 through 1991 with continued smaller outbreaks. Measles vaccine failure is in part to blame for these large-scale outbreaks. The human leukocyte antigen (HLA) genes are important determinants of immune response to measles virus and vaccine. To examine the influence that HLA polymorphisms may have on measles vaccine antibody response, we compared the distribution of HLA-DRB1 alleles between measles vaccine nonresponders and hyper-responders. METHODS: We determined the seroprevalence of measles antibody in 881 school children immunized with measles-mumps-rubella-II at age 15 months using a whole virus IgG EIA. We performed class II HLA-DR typing by PCR with sequence specific primers (PCR-SSP) on 81 nonresponders (IgG seronegative) and 65 hyper-responders (from the upper 10th percentile of IgG levels of all subjects). We then compared the distribution of alleles between nonresponders and hyper-responders. RESULTS: The distribution of HLA-DRB1 alleles among nonresponders compared to hyper-responders was significantly different (p = 0.014). Nonresponders were significantly less likely to carry the HLA-DRB1*13 alleles than were hyper-responders (7.4% vs 16.2%;p = 0.02). Nonresponders also had an excess of HLA-DRB1*07 alleles (15.4% vs 6.2%; p = 0.015). CONCLUSIONS: The absence of HLA-DRB1*13 alleles is associated with measles vaccine nonresponse. The absence of this allele has also been associated with susceptibility to other infectious diseases. The role of this gene in the immunogenetic response to infectious diseases requires further study.     

A measles epidemic controlled by immunisation

AIM: In 1997, an immunisation campaign, using measles-mumps-rubella vaccine, was planned for children aged 2-10 years to prevent a measles epidemic predicted by mathematical modelling. The epidemic started before the campaign and is described here. METHOD: Measles hospitalisation, notification and laboratory data were combined. RESULTS: The epidemic started in April 1997 and was largely over by January 1998. No deaths were identified and only one hospitalisation was coded as measles encephalitis, compared to seven deaths and ten cases of measles encephalitis in the 1991 epidemic. For the 12 months from 1 March 1997 there were 2,169 (60 per 100,000) measles cases identified, 314 (9 per 100,000) of whom were hospitalised. Two-thirds of hospitalised cases were notified. The age-standardised measles incidence rates were 33, 34, and 174 per 100,000 for Europeans, Maori and Pacific people, respectively. The respective age-standardised hospitalisation rates were 4, 9 and 32 per 100,000. Measles incidence was highest for under one-year-olds (904 per 100,000) and low for 11-16 year-olds (27 per 100,000)--the cohort previously offered a second vaccine dose. Most cases were aged 10 years and under, and this group were the main drivers of virus transmission. CONCLUSIONS: The immunisation campaign prevented 90-95% of predicted cases. The campaign was appropriately targeted at children aged 10 years and under.     

A comparison of alternate immunization regimes for measles in vaccinated populations

Infants today lose maternal measles antibody sooner than in the past. This is related to demographic changes in maternal immunization. Data for rates of decay of maternal antibody and seroconversion after measles vaccination for infants born to naturally immune (Group 1) or vaccinated (Group 2) mothers have been used to evaluate two vaccination schedules: Regime 1, measles-mumps-rubella (MMR) at 1 year of age and Regime 2, monovalent measles at 6 months followed by MMR at 15 months of age. Regime 2 costs less because MMR can be administered at 15 months with the last pentavalent booster. Months of protection/1000 children aged 0-15 months (child-months of protection) were estimated for infant populations ranging from 0 to 100% Group 1 for Regimes 1 and 2. Regime 1 provides more child-months of protection only for 100% Group 1 populations. For the study population Regime 2 provided at least 17% more child-months of protection than Regime 1. Regime 2 provides increased medical and financial benefits in proportion to the number of Group 2 infants in the population and thus is ever more advantageous for today's increasingly vaccinated populations.     

Nutritional status and delayed mortality following early exposure to measles

Community studies in Guinea-Bissau have found that exposure to measles prior to 6 months of age is associated with delayed mortality later in childhood. In an attempt to understand the underlying mechanism, we examined the role of pre-exposure nutritional status and the impact of exposure to measles on growth and subsequent mortality in these outbreaks. Though exposed children were lighter than controls, there was no association between pre-exposure weight-for-age and subsequent mortality adjusting for age. Although exposure was strongly associated with excess mortality, it did not have a negative impact on growth. Adjustment for state of nutrition did not alter the mortality ratio (MR) between 6 and 59 months of age for exposed children and controls; exposed children examined anthropometrically between 6-17 months had a MR of 3.70 compared with controls. This trend was the same for anthropometric measurements obtained at 18-59 months of age. Among the controls, there was a significant association between weight-for-age and subsequent mortality to the age of 5 years. However, for exposed children there was no association; the relation between weight-for-age and subsequent mortality was significantly different for exposed children compared with controls (tests for interaction between exposure and anthropometric measurements at 6-17 months: P = 0.05). Growth faltering as a consequence of early exposure to measles does not explain the marked excess mortality among these children. Further studies of the process underlying delayed mortality after early exposure to measles are warranted.     

Age-related seroprevalence of measles, mumps and rubella antibodies in 1996

In 1996 the effects on the immunity profile of a Swiss population exposed to MMR vaccination, which has been recommended since 1985, were evaluated with an age-stratified seroprevalence study for measles, mumps and rubella (MMR). At the age of 1.5-2.5 years, seroprevalence attained 76% for measles and rubella, which is respectively 17% and 24% above the values observed in 1992. The seroprevalence for mumps attained only 55% at the same age, which could reflect the poor immunogenicity of this component of the MMR vaccine. The seroprevalence for measles IgG showed a slow but steady increase from vaccination age to adulthood, attaining nearly 100%. The concentrations of measles IgG were about 700 IU/l into adolescence and rose to a plateau at about 1500 IU/l during young adulthood. These observations are compatible with low endemic activity of measles in the last 20 years and a predominance of vaccine-induced immunity up to about 20 years of age. This corresponds to the time period when measles vaccines--single or as MMR--have been in use. In 1992, at the peak of epidemic activity, seroprevalence for mumps rose substantially faster than in 1996. In addition, the rapid increase in quantitative values during preschool age mirrors the ongoing wild virus circulation with minimal vaccine effect. In the vaccine cohort (2-12 years of age) the seroprevalence of rubella IgG reached 70-80%. That there is no rise in the curve during school age shows that the recommended catch-up vaccinations before or during school age have been neglected. The median concentrations of rubella IgG were about 65 IU/ml at vaccination, declined to 40-50 IU/ml during preschool age, and rose again during school age, suggesting wild virus circulation. These data show that the MMR vaccine cover in Swiss children is insufficient to interrupt virus circulation, and administration of a second dose of MMR for catch-up immunisation has been omitted. The poor efficacy of the mumps component of the MMR vaccine that has mainly been used in Switzerland is also evident. The average age at infection is therefore expected to rise, thus involving a risk of increasing age-dependent complications. Efforts to implement the MMR vaccination program in Switzerland should be improved.     

Modelling the incidence of measles in Canada: an assessment of the options for vaccination policy

A range of vaccination policy options for improving the control of measles in Canada is investigated using a mathematical model to simulate transmission of the disease. Results suggest that a catch up campaign giving a second dose of vaccine to children aged up to 18 years would have an immediate impact on transmission, which could be maintained by the introduction of a routine second dose at either 18 months or 5 years of age. Introducing a routine second dose of vaccine without a catch up campaign would allow continued endemic transmission of measles among older children for at least 10-15 years.     

A non-specific, beneficial effect of measles vaccination. Analysis of mortality studies from developing countries

The study examined whether the reduction in mortality after standard titre measles immunization in developing countries can be explained by the prevention of acute measles and its long-term consequences. All studies comparing mortality of unimmunised children and children immunised with standard titre measles vaccine in developing countries were included; ten cohort and two case-control studies from Bangladesh, Benin, Burundi, Guinea-Bissau, Haiti, Senegal, and Zaire. We examined the protective efficacy of standard titre measles immunization against all cause mortality. Furthermore, by restricting the analysis to children who had not developed measles, we examined how much of the difference in mortality between immunised and unimmunised children could be explained by prevention of measles disease. In the ten cohort studies, protective efficacy against death after measles immunization was found to be in the range of 30-86%. Efficacy was highest in the studies with short follow-up and where children were immunised in infancy (range: 44-100%). Vaccine efficacy against death was much greater than the proportion of deaths attributed to acute measles disease. In four studies from Guinea-Bissau, Senegal and Burundi, vaccine efficacy against death remained almost unchanged when measles cases were excluded from the analysis. Hence, the reduction in mortality among immunized children cannot be explained by the prevention of acute and long-term consequences of measles. In contrast to the effect of measles vaccine, studies from Guinea-Bissau, Senegal and Benin suggest that diphtheria-tetanus-pertussis and polio vaccinations are not associated with reduction in mortality. These observations suggest that standard titre measles vaccine may confer a beneficial effect which is unrelated to the specific protection against measles disease.     

Seroconversion of a trivalent measles, mumps, and rubella vaccine in children aged 9 and 15 months

The serological response to MMR vaccine was evaluated in 109 9-month-old infants having no history of measles vaccination, and in 98 15-month-old children who had received monocomponent measles immunisation at 9 months. The combined vaccine contained Schwarz, Urabe Am9, and Wistar RA 27/3 live attenuated virus strains. Preimmunisation antibody levels were extremely low for the 9-month-old children, indicating that maternally-transmitted antibodies do not persist at this age. In the case of mumps, preimmunisation antibody levels were significantly higher in the 15-month-old than in the 9-month-old group. A difference between groups in terms of postimmunisation antibody titres was observed only for rubella, with titres being significantly higher in the older group. Seroconversion rates were high in both groups and no serious events attributable to vaccination were observed. The MMR vaccine can thus be administered to children as young as 9 months of age. Evidence for the efficacy of a two-dose schedule, i.e. at 9 and 15 months, is presented.     

A study of maternally derived measles antibody in infants born to naturally infected and vaccinated women

Maternal, cord and infant measles antibody levels were measured and compared in a group of 411 vaccinated mothers and 240 unvaccinated mothers, and their babies, between 1983 and 1991. Maternal and cord sera were tested by haemagglutination inhibition and/or enzyme-linked immunosorbent assay, and plaque reduction neutralization tests were also used to test infant sera. Geometric mean titres were significantly higher in the unvaccinated than in the vaccinated mothers (P < 0.001). Infants born to mothers with a history of measles had higher antibody levels at birth than infants of vaccinated mothers and, although the difference narrowed over time, continued to have higher levels up to 30 weeks of age. Between 5 and 7 months of age significantly more of the children of vaccinated mothers had plaque reduction neutralization antibody levels below that which would interfere with vaccination. As the boosting effect of circulating natural measles disappears, earlier measles vaccination may need to be considered, perhaps as part of a two-dose policy.     

Persistence of maternal antibody in infants beyond 12 months: mechanism of measles vaccine failure

A serologic study was made in 34 children immunized against measles at the age of 12 months. Using a sensitive virus neutralization test, it was found that many of the children had pre-existing maternal antibody to measles virus. Children with high pre-existing antibody titers failed to seroconvert. Children with lower pre-existing antibody titers seroconverted, but the resulting antibody titer was significantly lower than in children without pre-existing antibody titer. The results of this study demonstrate a probably mechanism for measles vaccine failure in 12-month-old children and support the recommendation of the Public Health Service Advisory Committee on Immunization Practices to postpone measles vaccination to 15 months of age.     

Measles control in the United States: problems of the past and challenges for the future

Elimination of indigenous measles from the United States has been a public priority since 1978. To assess the progress made toward this goal, we review the epidemiology of measles from 1963 to the present. From the 1970s through early into the recent measles epidemic, the majority of measles cases were in highly vaccinated, school-age children. This was due primarily to a 1 to 5% primary measles-mumps-rubella vaccine failure rate and nonrandom mixing patterns among school-age populations. To eliminate susceptible individuals in the school-age populations, a second dose of measles vaccine is now recommended between 5 and 6 years or 11 and 12 years by both the Advisory Committee on Immunization Practices and the American Academy of Pediatrics. Later in the epidemic, measles cases surged among unimmunized preschool children, especially among the poor in inner-city areas. Immunization rates have been documented to be low among preschool populations because of missed opportunities to administer vaccines at all health visits and barriers to access to immunizations. To raise immunization rates, the age for the first measles-mumps-rubella immunization was lowered to 12 to 15 months of age, federal immunization funding has increased, and new standards for immunization delivery have been developed and promulgated.     

The United States--The Netherlands Round Table Conference on immunization. Summary report

A group of public health scientists from the United States and The Netherlands met at a Bicentennial Round Table Conference December 1-2, 1982, to discuss the latest developments in immunization against infectious diseases, focusing on pertussis, poliomyelitis, measles, and rubella. The major differences in immunization practices in the two countries are: (a) In The Netherlands, inactivated polio vaccine is used exclusively; in the United States, the oral polio vaccine is used. Polio-myelitis has virtually disappeared from both countries. (b) In The Netherlands, the pertussis component of DTP (diphtheria, tetanus, pertussis) is not given to children over the age of 1 year, whereas in the United States, it is given to children up to their seventh birthday. (c) Rubella vaccine is given only to girls at ages 11-12 years in The Netherlands, but to all children at ages 12-15 months in the United States. (d) Mumps vaccine is not administered to children in The Netherlands, but in the United States it is given routinely to children at 12-15 months (in combination with measles and rubella vaccine). The participants concluded that both the United States and The Netherlands have effective immunization programs that have significantly reduced the impact of these diseases.     

Vesicoureteral reflux in children: incidence and severity in siblings

PURPOSE: We attempted to determine the incidence of vesicoureteral reflux in asymptomatic siblings of children with reflux at different ages and assess the incidence of renal damage in asymptomatic siblings with reflux. MATERIALS AND METHODS: We reviewed radionuclide cystograms of 482 consecutively referred siblings of children with vesicoureteral reflux, including 295 girls and 187 boys 2 weeks to 12.8 years old (mean age 2.8 years). Ultrasonograms and renal cortical scintigrams of children with reflux were evaluated. All siblings were considered asymptomatic by the referring physicians. RESULTS: The overall incidence of vesicoureteral reflux was 36.5%, and the incidence in girls and boys was 39.3 and 32.1%, respectively. Children 24 months old or younger had the highest incidence (45.7%) and the highest risk of bilateral reflux. From ages 25 to 72 months the incidence of reflux was 33.1% and in siblings older than 72 months it was 7%. Reflux of urine to the level of the renal pelvis was detected in 28.6% of all referred siblings. Renal damage was observed on sonography or scintigraphy in 4.7% of the siblings with reflux. CONCLUSIONS: The high incidence of vesicoureteral reflux through age 72 months indicates that it is important to screen siblings of children with reflux at an early age to prevent renal damage, which can occur in the absence of symptomatic urinary tract infection.     

A statewide survey of immunization rates in Minnesota school age children: implications for targeted assessment and prevention strategies

BACKGROUND: A retrospective statewide immunization survey of the 69115 Minnesota children who entered kindergarten in 1992 was conducted. METHODS: Information was collected from school immunization records on date of birth, dates of vaccination for each dose of vaccine, address of residence and race/ethnicity (when available). Immunization rates were assessed retrospectively for each month of a child's life from 2 to 48 months of age. Age-appropriate immunization was defined as receipt of all scheduled vaccines within 30 days of the recommended age. RESULTS: Immunization levels varied by vaccine, age of the child and race/ethnicity. For example at 19 months of age, 73% of students had received measles, mumps, rubella vaccine; however, only 39% had received their fourth dose of diphtheria, tetanus and pertussis vaccine. White, non-Hispanic students consistently had higher vaccination rates than children of other racial/ ethnic groups. For example 45% of white, non-Hispanic students were age-appropriately vaccinated at 16 months of age compared with 25% of Blacks, 30% of American Indians, 30% of white Hispanics and 28% of Asian-Pacific Islanders (Mantel-Haenzel chi square, P < 0.001 for each comparison). Furthermore coverage rates frequently varied significantly by neighborhood, thereby identifying pockets of underimmunization within communities. CONCLUSION: Our data demonstrate that vaccination rates can vary substantially by age, race/ ethnicity and neighborhood. Detailed immunization assessment is necessary so that effective targeted interventions can be developed.