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PubMed2003

Progress toward measles elimination in Germany.

While the former East Germany (FEG) achieved a reduction of measles incidence to <1 case per 100,000 population before reunification in 1990, the former West Germany (FWG) experienced significant measles morbidity. In 2001, according to statutory surveillance data, the incidence of measles was still higher in FWG than in FEG (8.7 vs. 0.7 cases/100,000 population). This article describes the development of the vaccination strategies in FEG and FWG, vaccination coverage, results of seroprevalence studies, measles surveillance in Germany, the epidemiology of a recent outbreak, and the role of laboratory diagnosis for measles control in Germany. Recent establishment of comprehensive nationwide surveillance and prevention programs to attain higher vaccine coverage have led to a decrease in measles incidence. However, further improvement of age-appropriate vaccine coverage and closure of immunity gaps in school-age children are necessary to eliminate measles in Germany.

Adolescent↗
PubMed2003

Impact of alternative approaches to accelerated measles control: experience in the African region, 1996-2002.

From 1996 to 2000, several African countries accelerated measles control by providing a second opportunity for measles vaccine through supplemental campaigns. Fifteen countries completed campaigns in children aged 9 months to 14 years. Seven countries completed campaigns in children aged 9-59 months. In almost all countries that conducted campaigns in children aged 9 months to 14 years, measles deaths were reduced to near zero. In six countries, near-zero measles mortality has been maintained for 4-6 years. Supplemental immunization in children <5 years old was only partially effective (range, 0-67%) in reducing mortality. Measles cases decreased by 50% when routine vaccination coverage increased from 50% to 80%. Initial measles campaigns in children aged 9 months to 14 years, follow-up campaigns in those aged 9-59 months every 3-5 years, and increased routine coverage to 80% will be needed to reduce and maintain measles deaths in African countries at near zero.

Adolescent↗
PubMed2004

Evolution of measles elimination strategies in the United States.

There have been 3 efforts to eliminate measles from the United States since the introduction of measles vaccine in 1963. To date, 10 major lessons have been learned from elimination efforts. First, elimination requires very high vaccination-coverage levels by age 2 years. Second, school immunization requirements ensure high coverage rates among schoolchildren. Third, a second dose of measles vaccine is needed to achieve satisfactory levels of immunity. Fourth, school immunization requirements can also ensure delivery of a second dose. Fifth, coverage assessment is crucial. Sixth, measles surveillance is critical for developing, evaluating, and refining elimination strategies. Seventh, surveillance requires laboratory backup to confirm a diagnosis. Eighth, tracking measles virus genotypes is critical to determining if an endemic strain is circulating. Ninth, once endemic transmission has been interrupted, internationally imported measles cases will continue and will cause small outbreaks. Tenth, collaborative efforts with other countries are essential to reduce imported measles cases.

Adolescent↗
PubMed2004

Measles outbreak epidemiology in the United States, 1993-2001.

To evaluate the extent of measles virus circulation and populations at risk in the United States, we reviewed measles outbreaks during 1993-2001. A total of 120 measles outbreaks, constituting 1804 outbreak-related cases, were reported during this period. The maximum outbreak size decreased from 233 cases in 1993-1995 to 119 cases in 1996-1998 and 15 cases in 1999-2001. The maximum outbreak duration decreased from 127 days in 1993-1995 to 65 days in 1999-2001. The majority of outbreaks resulted from documented spread from an internationally imported case (42%) or had a strain of measles virus not endemic in the United States (12%). Outbreaks in which adults were the predominant age group affected accounted for 35% of all outbreaks, compared with 29% of outbreaks predominantly affecting preschool children, 30% predominantly affecting school-aged children and adolescents, and 6% with no predominant age group. The extremely limited size and duration of measles outbreaks indicates very high population immunity to measles and suggests that measles is no longer endemic in the United States.

Adolescent↗
PubMed2006

Associations between measles vaccine immunity and single-nucleotide polymorphisms in cytokine and cytokine receptor genes.

BACKGROUND: Cytokines are key regulators of measles vaccine humoral and cellular immunity. Single-nucleotide polymorphisms (SNPs) that are associated with differences in cytokine levels should also influence measles vaccine-induced immunity. METHODS: We genotyped 118 measles-mumps-rubella-vaccinated subjects for SNPs from 6 cytokine genes (interleukin [IL]-2, IL-4, IL-10, IL-12A, IL-12B, and interferon [IFN]-gamma) and their receptors (IL-2RA, IL-2RB, IL-4RA, IL-10RA, IL-10RB, IL-12RB1, IL-12RB2, and IFN-gamma R). Associations of SNPs with measles-specific antibodies, lymphoproliferation, and secreted cytokines were determined using chi2 tests and analyses of covariance. RESULTS: We found significant associations (P<.05) between SNPs in the IL-2, IL-10, and IL-12RB genes and measles vaccine-induced immunity. The IVS1-100G (rs2069762) and the Ex2-34G (rs2069763) SNPs within the IL-2 gene were associated with high antibody and high lymphoproliferative responses, whereas SNPs within the IL-10 and IL-12R genes were associated with low antibody and lymphoproliferative responses to measles. SNPs within the IL-4RA and IL-12B genes varied significantly (P<.05) across immune response measures. Significant associations were also found between SNPs and secreted cytokine levels. CONCLUSIONS: Specific SNPs in the cytokine and cytokine receptor genes are significantly associated with variations in measures of the immune response to measles vaccination. These results need to be further validated in a larger cohort.

Cytokines↗
PubMed1994

Measles immunity in a population of healthcare workers.

OBJECTIVES: To evaluate measles seroprevalence among cohorts of new employees and to evaluate vaccine responses of susceptible adult healthcare workers. DESIGN: New employees were screened for measles susceptibility as part of employee evaluations. Anti-IgG measles antibody tests were completed on 2,473 workers. Demographic, measles history, and measles vaccination information was collected using a short questionnaire. Susceptible workers were vaccinated and screened for vaccine responses following vaccination. RESULTS: Ninety-three workers (4%) were seronegative, and 56 (2%) were equivocal. Individuals in the youngest cohort (born after 1956) were significantly more likely to be susceptible than those in the middle cohort (born 1951 to 1956) and those in the oldest cohort (born before 1951) (P < 0.01). The middle cohort included eight (5%) of the 149 seronegative or equivocal workers. Among the members of the youngest cohort, those from the United States were more likely to be susceptible (P < 0.01) than those from outside the United States. Of the 106 vaccinated susceptible workers whose follow-up serologies were determined, 90 (85%) developed positive IgG serologies, six had equivocal results, and 10 were seronegative. Eleven of the 16 non- or hyporesponders were revaccinated and re-evaluated; nine developed low positive IgG antimeasles levels, one exhibited an equivocal response, and one failed to respond. CONCLUSIONS: A small but important proportion of healthcare workers are susceptible to measles. Whenever feasible, measles immunity programs for healthcare workers should include workers born before 1957. Of workers born after 1956, those from outside the United States are more likely to be immune than workers from inside the United States. Using the currently available vaccine, revaccination of initial non- or hyporesponders appears to be effective.

Adolescent↗
PubMed2001

Evaluation of an early two-dose measles vaccination schedule.

Vaccination at 6 months of age followed by routine revaccination is recommended when exposure of infants to measles is likely. Dade County, Florida, began this early two-dose schedule during a large epidemic in 1986-1987 (i.e., 22% of cases occurred in infants aged 6-11 months). This schedule was continued routinely in high-risk areas. The effect of an early two-dose schedule on measles prevention in the county was examined by comparing measles vaccination coverage and epidemiology before (1985-1987) and after (1988-1996) the schedule became routine. To assess serologic response, seroprevalence of measles antibody among children aged 4-6 years in 1995 was examined. To evaluate vaccine effectiveness, a case-control study was conducted among preschool-aged children. Among those aged 2 years, vaccination coverage with > or =1 dose increased from 75% to 94% in 1996. The number of annual cases declined, and endemic measles transmission reportedly ended after 1993. Seroprevalence of plaque reduction neutralization antibody (titer > 1:120) among those receiving vaccination according to an early two-dose schedule and a single dose at age > or =12 months was 94% (95% confidence interval: 89, 98) and 98% (95% confidence interval: 95, 100). In these groups, vaccine effectiveness was comparably high. Early two-dose measles vaccination is associated with improved coverage and a comparably high level of humoral immunity and clinical protection as a single dose at age > or =12 months. This strategy can be useful in areas at high risk for measles among infants.

Antibodies, Viral↗
PubMed1993

Subacute measles encephalitis in the young immunocompromised host: report of two cases diagnosed by polymerase chain reaction and treated with ribavirin and review of the literature.

Two young patients with subacute measles encephalitis are described: a 20-year-old male hemophiliac infected with human immunodeficiency virus (HIV) and a 4-year-old girl with acute leukemia. Both patients were afebrile and had persistent focal seizures and slurred speech beginning 2 and 7 months, respectively, after the onset of uncomplicated acute measles. The diagnosis of subacute measles encephalitis was established by demonstration of paramyxovirus nucleocapsid on electron microscopy of brain tissue in one case and by detection of measles virus genome with the polymerase chain reaction in both. Treatment of the HIV-infected man with intravenous ribavirin was begun when the patient lost consciousness after several weeks of seizures; he died. The girl with leukemia was treated early after the onset of symptoms and recovered after a 15-week course. Review of 31 previously published cases revealed a typical clinical presentation. Cerebrospinal fluid (CSF) analysis, electroencephalography, measurement of measles antibody in serum and CSF, and computed tomography of the brain were not helpful in the diagnosis of subacute measles encephalitis. In contrast, histologic examination of brain tissue proved useful in establishing the diagnosis. On the basis of our experience and our literature review, we conclude that histologic and polymerase chain reaction studies of brain tissue are required for the early diagnosis of subacute measles encephalitis and that therapy with intravenous ribavirin is effective when administered early.

Adult↗
PubMed1994

Sex differences in the humoral antibody response to live measles vaccine in young adults.

BACKGROUND: Following vaccination of children using high-titre live measles vaccine, excess non-specific mortality was reported, particularly among females. Since vaccination with live measles virus results in a temporary depression of the immune response to other antigens, the female predominance in subsequent non-measles mortality may be due to sex differences in response to live measles vaccines. METHODS: In this study, the immunogenicity of standard titre live Schwarz strain measles vaccine was examined 2 and 4 weeks post-vaccination in 223 males and 66 female aged 18-20 years in Israel in 1991. RESULTS: Females had higher post-vaccination geometric mean titre (GMT) at all levels of pre-vaccination titres at both 2 and 4 weeks. Furthermore, after controlling for differences in pre-vaccination titres, overall the post-vaccination GMT for females was about 50% higher than for males (P < 0.001). CONCLUSIONS: These findings indicate that females exhibit a stronger humoral immune response to measles vaccine. Possible sex differences in immunosuppression following measles vaccination should be explored.

Adolescent↗
PubMed1997

Association of livebirths and the resurgence of measles.

BACKGROUND: The basis for the resurgence of measles in the US in 1989 and 1990 is not understood. This analysis was undertaken to test the hypothesis that an increase in the number of livebirths was associated with the resurgence of measles in the US. METHODS: We undertook an ecologic analysis of 20 cities/countries in the US with documented rates of immunization among 2-year-old children. RESULTS: Over the 6-year period 1985-1990, the numbers of livebirths and of susceptible preschool aged children increased by 18.5% and 17.7%, respectively. Livebirths, and the number and density of susceptible preschool-age children were significantly associated with the number and incidence of measles among preschool children (r = 0.83, P = 0.04). In a comparison between counties, numbers of livebirths were also significantly correlated with the mean number (r = 0.73, P = 0.0003) and incidence of measles cases (r = 0.51, P = 0.02). Mean immunization rates of 2-year-old children were also associated with the mean incidence of measles (r = -0.66, P = 0.0015, and r = -0.57, P = 0.009, respectively). In a logistic regression model, levels of immunization and susceptible density were independent predictors of measles epidemics among preschool children. CONCLUSIONS: These data suggest that the increase in livebirths, leading to an increase in the number and density of susceptible hosts, was associated with the resurgence of measles among preschool-age children.

Birth Rate↗
PubMed1994

A single 210-mumol oral dose of retinol does not enhance the immune response in children with measles.

This trial assessed the effect of vitamin A on reversing measles-induced unresponsiveness to recall antigens and on enhancing measles antibody production. These assessments were part of a randomized, double-masked clinical trial of the efficacy of 210 mumol of retinol as retinyl palmitate for reducing measles-associated morbidity. Two hundred children between 5 mo and 17 y of age with acute measles were enrolled at the Urban Health Centers in Ndola, Zambia; 110 subjects received a placebo and 90 received vitamin A. At enrollment and 2 wk later, blood samples were collected to determine measles hemagglutinin antibody titer and, at 1 and 2 wk post-enrollment, cutaneous delayed-type hypersensitivity tests (DTH) for seven antigens were applied. Both groups of subjects showed marked DTH unresponsiveness, but vitamin A-treated subjects had a significant prolongation of unresponsiveness to tuberculin [odds ratio (OR) 3.22 and 95% confidence interval (CI) 1.27-8.2], Candida (OR 5.43, CI 1.13-25.9) and Proteus (OR 5.17, CI 1.14-28.4), after adjustment for previous vaccination and age. DTH unresponsiveness was antigen specific, reflecting prior vaccination history, and was not associated with acute respiratory infection status. In addition, children in both treatment groups showed a significant increase in measles antibody titer from baseline to wk 2, but this increment was not significantly different between the groups (P = 0.25). These results indicate that a single oral dose of 210 mumol of retinol as retinyl palmitate in oil does not enhance the immune system during measles.

Administration, Oral↗
PubMed1985

Continuing measles transmission in students despite school-based outbreak control program.

FRom September 9, 1981 to January 5, 1982, a measles outbreak occurred in Warren County, Pennsylvania. The outbreak persisted for nine weeks following the implementation of a county-wide outbreak control program primarily consisting of identifying and vaccinating susceptible schoolchildren. Forty-six cases occurred among students more than two weeks after control program implementation. All 46 had a school record indicating adequate measles vaccination; 13 had been vaccinated at control program clinics by one jet-injector team (Team A). A seroprevalence survey demonstrated that persons vaccinated by Team a had a significantly higher rate of vaccination failure than children vaccinated by other teams (37.0% vs. 5.9%, p = 5.7 X 10(-7). A case-control study was undertaken to assess possible additional risk factors for developing measles. Individuals with measles were nine times more likely than control individuals to have records of measles immunization that could not be verified with providers or to have been vaccinated at 12 months of age. The most likely reasons that this outbreak was sustained among persons with adequate vaccination histories were: 1) impotent vaccines and/or improper vaccine administration techniques were used by one jet-injector team; 2) several persons with histories of adequate vaccination were really not adequately vaccinated; adn 3) a substantial number of persons had been vaccinated at 12 months of age. There is no evidence from this outbreak that transmission of measles can be sustained among the 2-10% of individuals expected to remain susceptible following a single appropriate measles vaccination.

Adolescent↗
PubMed1990

Measles, mumps and rubella immunization at nine months in a developing country.

The antibody responses and reactogenicity of a measles, mumps and rubella vaccine in 9-month-old and 15-month-old black children in South Africa were compared. The antibody response to the measles component was marginally better in the older group, but no differences were observed in the response to the mumps and rubella components. Reactogenicity was similar in the two age groups. Therefore it is possible that a trivalent measles, mumps and rubella vaccine can safely and effectively replace routine measles immunization at 9 months of age in this population. Whether routine immunization policy should incorporate such a vaccine depends on the extent of acceptance of measles vaccination. In urban populations of developing countries with high rates of measles immunization, routine vaccination at 9 months might interrupt circulating wild type rubella and provide sufficient herd immunity to protect susceptible women of childbearing age. It also should decrease significantly the complications associated with wild type mumps infection. The replacement of measles vaccine by a trivalent vaccine may be very cost-effective.

Black or African American↗
PubMed1999

Poor serologic responses five to seven years after immunization with high and standard titer measles vaccines.

BACKGROUND: Few data exist on the persistence of measles antibodies after vaccination of West African infants. Therefore we examined measles antibody titers 5 to 7 years after children in rural Senegal had received high titer Edmonston-Zagreb (EZ-HT), high titer Schwarz (SW-HT) or standard titer Schwarz (SW-STD) measles vaccines in infancy. METHODS: Children had received either high titer vaccines at 5 months of age or standard titer at 10 months of age. Finger prick blood samples were tested for measles antibody 5 to 7 years later by the hemagglutinin inhibition test. RESULTS: Persistence of antibody after high titer vaccines was poor with the result that 39 and 50% of the EZ-HT and the SW-HT groups had low titers of hemagglutinin inhibition measles antibodies (< or =125 mIU/ml). Nineteen percent of the children in the SW-STD group had low titers which is a lower prevalence than in the high titer groups [relative risk (95% confidence intervals), 0.05 (0.28 to 0.88) vs. EZ-HT; relative risk, 0.38 (0.22 to 0.66) vs. SW-HT]. Geometric mean (95% confidence interval) antibody titers in children with detectable values were 616 (435 to 871) in the EZ-HT, 1106 (616 to 1866) in the SW-HT and 1271 (871 to 1741) mIU/ml in the SW-STD groups, respectively. Multivariant regression analysis showed that mean titers were 2.00 (1.03 to 3.89) times higher for children with low prevaccination antibody titers (< or =125 mIU/ml) and 3.06 (1.90 to 4.94) times higher if blood was collected in the rainy season. INTERPRETATION: Given the rapid decline in antibody titers over a 5- to 6-year period in an area where measles vaccine coverage was high, it seems likely that multiple dose immunization schedules will be needed in the future to maintain protective antibody concentrations (>125 mIU/ml) in West Africa. The role of subclinical boosting by exposure to natural measles and the possible role of malaria, which increases immunoglobulin turnover, in influencing long term antibody persistence after vaccination deserve further investigation.

Antibodies, Viral↗
PubMed1996

Use of Texas birth certificate data to predict measles immunization status.

Inadequate immunization has been a major cause of epidemic measles, but risk factors for inadequate immunization are poorly characterized. By using measles data bases and computerized birth certificate files, we identified a retrospective cohort of 1,070 Texas-born children who were aged 15 months to 10 years when they had measles during the 1988 to 1991 epidemics. We used measles and birth certificate data, including prenatal care and demographic information, to determine immunization status and risk factors for inadequate measles immunization. Risk factors predicting lack of immunization in children with measles in stepwise logistic regression were black ethnicity, urban residence, poor prenatal care, preschool age, and an unknown father. Birth certificates contain information that can predict inadequate measles vaccination and should be evaluated prospectively.

Birth Certificates↗
PubMed2006

Detection of osteoprotegerin and TNF-alpha mRNA in ankylotic Stapes footplates in connection with measles virus positivity.

HYPOTHESIS: Otosclerosis is a bone remodeling disorder of the otic capsule causing conductive and sensorineural hearing loss. Persistent measles virus infection of the temporal bone with increased tumor necrosis factor (TNF)-alpha and decreased osteoprotegerin mRNA expression is supposed to be the main etiologic factor in otosclerosis. BACKGROUND: Determinants of measles virus infection and reactive inflammation were studied in otosclerosis. The presence of measles virus was shown in otosclerotic patients by reverse transcriptase-polymerase chain reaction (RT-PCR) amplification of the viral RNA. No report is available, however, about the role and interactions of bone-specific cytokines in otosclerosis. METHODS: : Nucleic acid was extracted from stapes footplates of clinically otosclerotic patients. Measles virus nucleoprotein RNA was amplified by seminested RT-PCR. TNF-alpha and osteoprotegerin mRNA coexpression was detected by RT-PCR in otosclerotic bone and was correlated to measles virus positivity. RESULTS: Among 154 clinically stapes fixation otosclerotic patients, 99 stapedes contained measles virus RNA. TNF-alpha mRNA was detectable in 88 virus-positive and in 6 virus-negative stapes footplates. Osteoprotegerin mRNA expression was significantly lower in the TNF-alpha-positive specimens (P < .0001) that was independent from virus positivity. CONCLUSION: Detection of TNF-alpha mRNA demonstrates activated osteoclast functions and inflammatory pathways in otosclerotic stapes footplates associated with measles virus presence. Increased expression of TNF-alpha and its action on RANK production inhibits the protective functions of osteoprotegerin on normal bone turnover in the otic capsule.

Adult↗
PubMed1987

Virological aspects of measles virus-induced encephalomyelitis in Lewis and BN rats.

Lewis and Brown Norway (BN) rats which are susceptible or resistant to autoimmune reactions against brain antigen, respectively, were inoculated intracerebrally with a neurotropic measles virus. Suckling rats died from a rapidly fatal acute encephalopathy (AE). With increasing age Lewis rats developed a subacute measles encephalomyelitis (SAME) whereas BN rats showed a clinically silent encephalitis (CSE). Infectious virus could occasionally be recovered from SAME animals using cocultivation techniques but not from BN rats with CSE. With monoclonal antibodies against measles virus, viral proteins were localized in brain tissue. Nucleocapsid and phosphoprotein were detected in infected brain cells of all animals with AE, SAME and CSE, whereas measles virus haemagglutinin, fusion and matrix proteins were either reduced or absent, suggesting a restricted synthesis of measles virus envelope proteins. These data suggest that the different diseases of the two rat strains are related to the immunogenetic background rather than to the replication of measles virus in the central nervous system. This animal model provides the opportunity to investigate further the events occurring during establishment of measles virus persistence in the brain, and the genetic control of associated immunological and immunopathological reactions.

Animals↗
PubMed2000

Molecular characterization of measles viruses isolated in Victoria, Australia, between 1973 and 1998.

Molecular epidemiology studies have made significant contributions to the control of measles virus infection through the identification of source and transmission pathways of the virus. These studies allow observation of changes in measles virus genotypes over time in a particular geographical location, clarification of epidemiological links during measles outbreaks, separation of indigenous strains from newly imported strains and distinction between vaccine- and wild-type virus-associated illness. A total of 35 wild-type measles viruses identified in Victoria, Australia, between 1973 and 1998 were characterized by nucleic acid sequence analysis of the nucleoprotein gene and, in some cases, the haemagglutinin gene. Relatedness between the viruses was studied and genotypes were assigned using a classification scheme recently proposed by the World Health Organization. Five recognized genotypes (C2, D1, D4, D5 and H) and one previously undescribed genotype, which we propose to be D7, were identified. Successive replacement of measles virus genetic lineages occurred in Victoria, with no evidence of temporal overlap, during this 25 year period. This pattern of circulation is likely to represent serial importation of wild-type measles virus strains from overseas foci of measles virus infections.

Adolescent↗