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Correlations among measles virus-specific antibody, lymphoproliferation and Th1/Th2 cytokine responses following measles-mumps-rubella-II (MMR-II) vaccination.

Immunity to measles is conferred by the interplay of humoral and cellular immune responses, the latter being critical in maintaining long-term recall response. Therefore, it is important to evaluate measles-specific humoral and cellular immunity in populations several years after vaccination and understand the correlations among these measures of immunity. We examined measles-specific antibodies, lymphoproliferation and the Th1/Th2 signature cytokines, interferon (IFN)-gamma and interleukin (IL)-4, in a population-based cohort of healthy children from Olmsted County, Minnesota after two doses of measles-mumps-rubella-II (MMR-II) vaccine. We detected positive measures of measles-specific cellular and humoral immunity in the majority of our study population. However, a small proportion of subjects demonstrated an immune response skewed towards the Th2 type, characterized by the presence of either IL-4 and/or measles-specific antibodies and a lack of IFN-gamma production. Further, we observed a significant positive correlation between lymphoproliferation and secretion of IFN-gamma (r = 0.20, P = 0.0002) and IL-4 (r = 0.15, P = 0.005). Measles antibody levels were correlated with lymphoproliferation (r = 0.12, P = 0.03), but lacked correlation to either cytokine type. In conclusion, we demonstrated the presence of both long-term cellular and humoral responses after MMR-II vaccination in a significant proportion of study subjects. Further, a positive correlation between lymphoproliferation and IL-4 and IFN-gamma suggests that immunity to measles may be maintained by both Th1 and Th2 cells. We speculate that the Th2 biased response observed in a subset of our subjects may be insufficient to provide long-term immunity against measles. Further examination of the determinants of Th1 versus Th2 skewing of the immune response and long-term follow-up is needed.

Adolescent↗

[The impact of immunization against measles on epidemiology of measles in Poland].

The measles vaccination has been introduced in Poland in 1975, and the second vaccine dose of measles vaccine in 1991. Mass immunization against measles exerted a significant impact on measles incidence, morbidity rate and mortality. The progressive increase of immunization coverage caused significant decrease of measles incidence rate among children at age below 10 years as well as among not vaccinated children up to 12 months of age. The lengthening of the interepidemic period and significant increase of morbidity rate among older children (over 10 years) and young adults were observed during the period after introduction of mass vaccination against measles. Since 1992 not a single case of death caused by measles was notified. Data on measles incidence and vaccination coverage during the period of observation will be used for development of the mathematical models for measles transmission and choice of optimal immunization strategy in Poland.

Adolescent↗

Measles and measles vaccine in Japan.

Before the introduction of measles vaccine in 1971, measles was a common and well-recognized disease in Japanese children. Seroepidemiological studies conducted before the general use of the vaccine disclosed that measles epidemics differed from community to community; in rural areas, epidemics appeared at intervals of several years with the accumulation of susceptibles, and in urban areas, measles was endemic affecting younger children. The measles vaccines developed in Japan showed excellent safety and efficacy in the clinical trials for general use. Since 1978 measles vaccines have been routinely given to children aged 12 months or older, and incidence of measles decreased dramatically. However, the vaccine acceptance rate has been only as high as 85% to 90% and small-scale outbreaks of measles have been observed periodically among unimmunized children: Measles is far from being eradicated in Japan. This is primarily due to the insufficient vaccine acceptance rate, and more efforts towards mobilization of parents to have their children vaccinated are now in progress.

Adolescent↗

Effect of monovalent measles and trivalent measles-mumps-rubella vaccines at various ages and concurrent administration with hepatitis B vaccine.

To determine the most suitable vaccination schedule in developing countries, a study was conducted to reevaluate the immunogenicity of monovalent measles vaccine and trivalent measles-mumps-rubella vaccine at different ages. The success rate of measles vaccination was 84% at 9 months, 88% at 12 months and 100% at 15 months of age. Vaccination with measles vaccines at 9 and 15 months of age was also 96% immunogenic. Most vaccinees (16 of 17) not responding to the first measles vaccine before 1 year of age developed measles antibody with another shot of vaccine after 15 months of age. Trivalent measles-mumps-rubella vaccine worked well in children ages 14 to 18 months. Administering trivalent vaccine and hepatitis B vaccine concurrently at 1 year of age, rubella and mumps antibodies developed in more than 95% of vaccinees, while measles antibody was detected in 88%. Responses to hepatitis B vaccine in this situation were good; 89% of vaccinees developed antibody against hepatitis B surface antigen (greater than or equal to 10 mIU/ml) and the geometric mean titer was 362.49 mIU/ml. In summary vaccination twice at 9 and 15 months is effective and is a useful regimen in developing countries where measles is still endemic. Trivalent vaccine and hepatitis B vaccine will not interfere with each other when given together at 1 year of age.

Age Factors↗

Perceptions, beliefs and practices of mothers in sub-urban and rural areas towards measles and measles vaccination in Northern Nigeria.

Measles is of particular concern in Nigeria because of the high fatality rate, and high morbidity rate, particularly in young children. Measles and its complications are a common reason for hospitalization, indicating very low immunization coverage. This study was carried out to elucidate the contributing factors from attitudes, beliefs and practices of mothers towards measles and its vaccination. A cross-sectional survey was conducted in Konduga Local Government Area. One per cent of the 500 mothers interviewed believed that measles is prevented by immunization, 16% that it is contagious or due to an infectious agent, 26% that it is caused by evil spirits, witchcraft and heat, and 25% had never heard of measles immunization. Twenty-seven per cent said they did not believe immunization was effective and 4% were not allowed to go for immunization by their husbands. Of those mothers whose children had developed measles, only 31% had been treated in formal health facilities. These results indicate an unfavourable attitude and practice by mothers in relation to measles and measles vaccination. There is the need for an intensive health education campaign to improve this state of affairs and to reduce the morbidity and mortality from measles.

Child, Preschool↗

Diagnosis of measles by clinical case definition in dengue-endemic areas: implications for measles surveillance and control.

In many countries, measles surveillance relies heavily on the use of a standard clinical case definition; however, the clinical signs and symptoms of measles are similar to those of dengue. For example, during 1985, in Puerto Rico, 22 (23%) of 94 cases of illnesses with rashes that met the measles clinical case definition were serologically confirmed as measles, but 32 (34%) others were serologically confirmed as dengue. Retrospective analysis at the San Juan Laboratories of the Centers for Disease Control showed also that at least 28% of all laboratory-confirmed cases of dengue in Puerto Rico in 1985 met the measles clinical case definition. If the true measles vaccine efficacy (VE) is assumed to be 90%, the occurrence of laboratory-confirmed dengue cases that meet the measles clinical case definition results in a reduction of the apparent measles VE to only 64% (a 29% relative reduction from the true VE). The results of the study demonstrate the importance of a laboratory-based surveillance system in measles control or elimination efforts in dengue-endemic areas.

Adolescent↗

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.

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 standard. 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.

Age Factors↗

Vaccine-induced measles virus antibodies after two doses of combined measles, mumps and rubella vaccine: a 12-year follow-up in two cohorts.

In Finland, a two-dose vaccination programme against measles, mumps and rubella (MMR) was begun in 1982. The programme with high coverage (97-98%) has eliminated these three diseases from Finland. The aim of the present study was to follow up the kinetics of measles virus antibodies in MMR vaccinated cohorts. We have followed the kinetics of measles virus antibody levels induced by vaccination in the same individuals immunized with their first MMR vaccine in 1982. After 12 years 80% of the original children remained available for sampling. Antibodies to measles virus were measured by haemagglutination inhibition (HI) and plaque reduction neutralization (NT) techniques. The primary dose induced 99.4% seroconversion for measles with a geometric mean HI antibody titre (GMT) of 1/269 (+/- 219), equivalent to 4304 mIU (milli-International Units) ml-1 in group A. The 12-year follow-up specimens showed a measles seropositivity rate of 100% as assayed with the HI and NT tests with a mean HI antibody titre of 1/39 (+/- 54), equivalent to 624 mIU ml-1. The vaccination-induced measles virus antibodies decline in the absence of natural booster infections. It is important to follow how long the protection achieved by the present vaccine programme will last after elimination of indigenous measles.

Antibodies, Viral↗

A mathematical model to measure the impact of the Measles Control Campaign on the potential for measles transmission in Australia.

BACKGROUND: The aims of this study were to determine the impact of the Australian Measles Control Campaign (MCC) on the transmission dynamics of measles by calculating the reproductive number (R) before and after the MCC, and to predict measles control in Australia in the future. METHODS: A national serosurvey was conducted before and after the MCC. Sera were tested for anti-measles IgG using enzyme immunoassay (EIA). A mathematical model, using serosurvey results and vaccine coverage estimates, was used to calculate the change in R after the MCC. RESULTS: The values of R calculated before and after the MCC were 0.90 and 0.57. At vaccine coverage levels indicated by the Australian Childhood Immunisation Register (ACIR), the value of R will exceed 1 (the epidemic threshold) in 2007-2008 nationally, and sooner in some regions of Australia. Coverage of at least 84% with two doses of MMR is required to sustain measles control. CONCLUSIONS: The Australian MCC had a significant impact on the transmission dynamics of measles. However, current vaccine coverage levels may result in indigenous measles transmission by 2007. Sustained efforts are required to improve coverage with two doses of MMR and to ensure elimination of indigenous measles transmission.

Adolescent↗

[Measles seroprevalence in the schoolchildren of Valencia. The Measles Study Group].

BACKGROUND: People born between 1978 and 1982 were the most affected by measles in the outbreaks occurring in the Valencian Community (Spain) in 1993. This age group has not been systematically immunized against measles and has not suffered the last large measles epidemics. HYPOTHESIS: global seroprevalence against measles in this age group is inadequate to prevent new outbreaks. METHODS: Prospective seroepidemiologic study in a sample of school-attending children, born between 1978 and 1982. Randomized sampling of all classrooms 5th to 8th grade high school of a Health Area; stratification depending on the population of the village (< 5,000, 5,001-20,000, > 20,000 inhabitants). Antecedents of measles immunization and the disease were collected. Measles IgG antibodies were measured by enzyme immunoassay, antibody titers 1:80 or higher were considered protective. RESULTS: Sample of 410 subjects, belonging to 17 classes. Measles antibody prevalence was 80.2% (95% CI: 76.6-83.8%), and was higher in less populated villages (p < 0.03). Immunization status was known in 253 subjects (61.7%). Protective titers were present in 86.1% of the vaccinated and in 68.1% of the non vaccinated (p < 0.001). CONCLUSIONS: There is a large percentage of subjects born between 1978 and 1982 unprotected against measles. Elimination of the disease will not be able unless an extraordinary vaccination campaign to include these subjects is taken.

Adolescent↗

Development of a measles specific IgM ELISA for use with serum and oral fluid samples using recombinant measles nucleoprotein produced in Saccharomyces cerevisiae.

In order to develop sensitive assays for detecting measles antibodies in oral fluid specimens, we have produced recombinant measles virus nucleoprotein (rMVN) in a yeast expression system and prepared monoclonal antibodies to the protein. Measles nucleoprotein gene from the Schwarz vaccine strain was cloned into a yeast expression vector, pFX7 under the control of the hybrid GAL10-PYK1 promoter. High levels of rMVN (20 mg/litre of yeast culture) were generated. Electron microscopy showed that the purified rMVN assembled into typical herring-bone structures. Monoclonal antibodies produced to the rMVN also reacted with native measles virus N in immunofluorescence tests. The purified rMVN and a monoclonal antibody to the rMVN conjugated to horseradish peroxidase were used to develop a measles specific IgM capture EIA (MACEIA) in both serum and oral fluid specimens. Evaluations of the MACEIA were performed by testing a) serum samples (n=80) and b) paired oral fluid/serum samples from measles cases (n=50, representing 16 cases) and oral fluids from controls with non-measles rash (n=59, representing 48 cases). The samples were also tested for measles IgM, using a reference radioimmunoassay (MACRIA). The sensitivity and specificity of the MACEIA compared with MACRIA for a) the serum samples were 100 and 96.6% respectively and b) for paired serum/oral fluids samples 100 and 100%, respectively.

Animals↗

UK measles outbreak in non-immune anthroposophic communities: the implications for the elimination of measles from Europe.

We describe the epidemiology of the first nationwide outbreak of measles infection in the UK since the implementation of a mass vaccination campaign. Notifications of infectious diseases, interview and postal questionnaire identified 293 clinical cases, 138 of which were confirmed by salivary IgM, measles virus isolation and PCR. Twelve were epidemiologically linked to confirmed cases. The outbreak began in London, after contact with measles infection probably imported from Italy. Measles genotyping determined by sequence analysis confirmed spread to other unimmunized anthroposophic communities in the north, south west and south coast of England. Only two cases had been vaccinated against measles infection, and 90% of cases were aged under 15 years. Measles virus can selectively target non-immune groups in countries with high vaccine uptake and broader herd immunity. Without harmonization of vaccination policies and uniform high coverage across Europe, the importation and spread of measles virus amongst non-immune groups may prevent the elimination of measles.

Adolescent↗

Lack of evidence of measles virus shedding in people with inapparent measles virus infections.

Serological evidence of measles virus infection has been detected among people exposed to measles who do not exhibit classical clinical symptoms. Throat swabs, lymphocytes, and serum and urine samples were collected from contacts of individuals with confirmed measles 12-16 days after exposure, during measles outbreaks occurring in 1998. Follow-up serum samples were drawn 2 weeks later. Samples were tested for measles IgM antibody by enzyme immunoassays and plaque reduction neutralization testing. Virus isolation and reverse transcriptase-polymerase chain reaction testing was attempted for all samples. None of the 133 contacts developed classical measles disease; 11 (8%) had serological evidence of infection. Duration of exposure of >or=3 h was the only significant risk factor for developing serological response (24% vs. 4% among contacts exposed for 1-2 h; relative risk, 6.0; 95% confidence interval, 1.9-19.2). None of the 133 contacts had virological evidence of infection by culture or polymerase chain reaction. We found no evidence that persons with inapparent measles virus infections shed measles virus.

Adolescent↗

The burden of acute respiratory infection due to measles in developing countries and the potential impact of measles vaccine.

Measles is a major cause of acute lower respiratory infection (ALRI) in developing countries. Hospital and community-based studies of ALRI have found that measles accounts for 6%-21% of the morbidity and 8%-93% of the mortality due to ALRI. Although live attenuated measles vaccine is one of the most effective vaccines in use today, measles has not been controlled in many parts of the world, primarily because the levels of vaccine coverage required to interrupt measles transmission have not been achieved. In addition, in some areas, a large percentage of cases of measles occur in infants who are younger than the age recommended for vaccination. Recent studies suggest that the Edmonston-Zagreb measles vaccine may be more immunogenic than other vaccine strains in young infants. A substantial proportion of ALRI could be prevented by increasing measles vaccine coverage and by the use of particular vaccine strains in younger children.

Acute Disease↗