Dose Of Measles-containing Vaccine Research Articles

Effect of Age on the Risk of Fever and Seizures Following Immunization With Measles-Containing Vaccines in Children

IMPORTANCE The first dose of live attenuated measles-containing vaccines is associated with an increased risk of febrile seizures 7 to 10 days following immunization among 12- to 23-month-old children. The combination measles, mumps, rubella, and varicella vaccine is associated with a 2-fold increased risk of febrile seizures 7 to 10 days following immunization compared with the separately administered measles, mumps, and rubella and varicella vaccines. It is unknown whether the magnitude of these increased risks depends on age at immunization. OBJECTIVE To examine the potential modifying effect of age on the risk of fever and seizures following immunization with measles-containing vaccines. DESIGN, SETTING, AND PARTICIPANTS Retrospective cohort study at 8 Vaccine Safety Datalink sites of a total of 840,348 children 12 to 23 months of age who had received a measles-containing vaccine from 2001 through 2011. EXPOSURES Any measles-containing vaccines and measles-containing vaccines by type. MAIN OUTCOMES AND MEASURES Fever and seizure events occurring during a 42-day postimmunization observation period. RESULTS In the analysis of any measles-containing vaccines, the increased risk of seizures during the 7- to 10-day risk interval, using the remainder of the observation period as the control interval, was significantly greater among older children (relative risk, 6.5; 95% CI, 5.3-8.1; attributable risk, 9.5 excess cases per 10,000 doses; 95% CI, 7.6-11.5) than among younger children (relative risk, 3.4; 95% CI, 3.0-3.9; attributable risk = 4.0 excess cases per 10,000 doses; 95% CI, 3.4-4.6). The relative risk of postimmunization fever was significantly greater among older children than among younger children; however, its attributable risk was not. In the analysis of vaccine type, measles, mumps, rubella, and varicella vaccine was associated with a 1.4-fold increase in the risk of fever and 2-fold increase in the risk of seizures compared with measles, mumps, and rubella vaccine administered with or without varicella vaccine in both younger and older children. CONCLUSIONS AND RELEVANCE Measles-containing vaccines are associated with a lower increased risk of seizures when administered at 12 to 15 months of age. Findings of this study that focused on safety outcomes highlight the importance of timely immunization of children with the first dose of measles-containing vaccines.

Prevalence of measles antibodies among health care workers in Catalonia (Spain) in the elimination era.

BackgroundInterruption of measles transmission was achieved in Catalonia (Spain) in 2000. Six years later, a measles outbreak occurred between August 2006 and June 2007 with 381 cases, 11 of whom were health care workers (HCW).The objective was to estimate susceptibility to measles in HCW and related demographic and occupational characteristics.MethodsA measles seroprevalence study was carried out in 639 HCW from six public tertiary hospitals and five primary healthcare areas. Antibodies were tested using the Vircell Measles ELISA IgG Kit. Data were analyzed according to age, sex, type of HCW, type of centre and vaccination history.The odds ratios (OR) and their 95% CI were calculated to determine the variables associated with antibody prevalence. OR were adjusted using logistic regression.Positive predictive values (PPV) and the 95% confidence intervals (CI) of having two documented doses of a measles containing vaccine (MCV) for the presence of measles antibodies and of reporting a history of measles infection were calculated.ResultsThe prevalence of measles antibodies in HCW was 98% (95% CI 96.6-98.9), and was lower in HCW born in 1981 or later, after the introduction of systematic paediatric vaccination (94.4%; 95% CI 86.4-98.5) and higher in HCW born between 1965 and 1980 (99.0%; 95% CI 97.0-99.8). Significant differences were found for HCW born in 1965–1980 with respect to those born in 1981 and after (adjusted OR of 5.67; 95% CI: 1.24-25.91).A total of 187 HCW reported being vaccinated: the proportion of vaccinated HCW decreased with age. Of HCW who reported being vaccinated, vaccination was confirmed by the vaccination card in 49%. Vaccination with 2 doses was documented in only 50 HCW, of whom 48 had measles antibodies. 311 HCW reported a history of measles.The PPV of having received two documented doses of MCV was 96% (95% CI 86.3-99.5) and the PPV of reporting a history of measles was 98.7% (95% CI 96.7-99.6).ConclusionsScreening to detect HCW who lack presumptive evidence of immunity and vaccination with two doses of vaccine should be reinforced, especially in young workers, to minimize the risk of contracting measles and infecting the susceptible patients they care for.

Timeliness and completeness of vaccination and risk factors for low and late vaccine uptake in young children living in rural southern Tanzania

We studied coverage and timeliness of vaccination and risk factors for low and delayed vaccine uptake in children aged <2 years in rural Tanzania. We used data from a cluster survey conducted in 2004, which included 1403 children. Risk factors were analysed by log-binomial regression adjusted for the clustering. The analysis was restricted to BCG, first and third dose of Diphtheria-Tetanus-Pertussis vaccines (DTP-1 and DTP-3) and first dose of measles-containing vaccine (MCV-1). Coverage for BCG, DTP-1, DTP-3 and MCV-1 was 94%, 96%, 90% and 86%, respectively. Delayed vaccination (>1 month after the recommended age) occurred in 398/1205 (33%) children for BCG, 404/1189 (34%) for DTP-1, 683/990 (69%) for DTP-3 and 296/643 (46%) for MCV-1. Coverage was lower for all vaccines except DTP-1 in children living ≥5 km from a healthcare facility. Delayed uptake was associated with poverty. Low and delayed MCV-1 vaccination was associated with low maternal education. Delayed BCG vaccination was associated with ethnicity and rainy season. Despite reasonably high vaccination coverage, we observed substantial vaccination delays, particularly for DTP-3 and MCV-1. We found specific factors associated with low and/or delayed vaccine uptake. These findings can help to improve strategies to reach children who remain inadequately protected.

False-Positive Results for Immunoglobulin M Serologic Results: Explanations and Examples.

Scenario* A measles outbreak occurred last month among a cluster of unvaccinated children in a suburban area in your referral region. Two weeks ago, an adolescent who received two doses of measles-containing vaccine in childhood developed a febrile illness with rash. This patient tested positive for measles IgM in a commercial assay. Subsequent testing by the Centers for Disease Control and Prevention demonstrated seronegativity for measles IgM. (A low positive concentration of measles IgG was detected.) The initial IgM test result has been labeled as false positive. The family of the patient is upset about the disruption of life experienced due the false positive IgM result. The pediatrician who ordered the test has called to ask you how this result could have happened. What are potential explanations for this? The false-positive rate of any diagnostic test is a function of the specificity of the test and prevalence of the disease in the population represented by the patient. For serologic assays, the presence of antibodies that cross-react with microbial antigens used in the assay or interfering substances that interact with assay components can also lead to false-positive results. Technical performance issues such as over-reading of weakly reactive bands on immunoblots can also lead to false-positive serologic tests results for microbes for which these assays are used (eg, Borrelia burgdorferi )[ 1]. Thus, positive IgM assay results can require cautious interpretation—consideration of clinical course compatibility and epidemiological factors—and/or confirmation by other serological or molecular testing methods. The issue of reactivation of IgM production against herpes viruses is beyond the scope of this review.

Do income inequality and social capital associate with measles-containing vaccine coverage rate?

ObjectiveWe investigated the association between income inequality and social capital with measles-containing vaccine (MCV) coverage rates in Japan. MethodsMCV coverage data for all 1750 municipalities were collected from statistics publicized by the Ministry of Health, Labour and Welfare of Japan in 2010. Prefectural Gini coefficients in 2009 (an indicator of income inequality) and social capital indicators (including voting rates, volunteer rates at the prefectural level, and move-in ratios at the municipal level) were linked to MCV coverage using a multilevel analysis adjusting for covariates (population, age distribution, average income, average number of household members). ResultsCoverage of the first dose of MCV (MCV1), and second dose (MCV2), decreased by 3.98% (95% confidence interval [CI]: 0.26–7.71) and 4.28% (95% CI: 0.60–7.60) per each 0.1-unit increase in Gini coefficients within large municipalities (with a population 50,000 or more), respectively. Conversely, coverage of MCV2 increased by 0.26% (95% CI: 0.08–0.45) per 1% increase in voting rate within large municipalities. Volunteer rates were inversely associated with MCV2 coverage within large municipalities. Move-in ratios at the municipal level were inversely associated with MCV2 coverage within medium-sized municipalities (with a population between 10,000 and 50,000). ConclusionsWhile higher income inequality at a prefectural level was associated with lower MCV coverage rates, higher social capital was associated with higher coverage in large municipalities. To enhance MCV coverage in Japan, we recommend that income inequality be addressed and social capital boosted at the prefectural level.

Waning population immunity to measles in Taiwan

To evaluate the population immunity to measles in Taiwan where the coverage rate of the measles vaccine was >95% for more than a decade, anti-measles IgG was determined in 3552 Taiwanese volunteers in 2007. The overall seroprevalence was 74.7% (95% confidence interval [CI]: 73.3–76.1%). In subgroups aged 2–25 years, to whom at least 2 doses of measles-containing vaccine were given, there was a declining trend of seropositivity with age from 94.5% at 2 years to 50.6% at 21–25 years (p<0.0001). Age (odds ratio [OR]: 1.0464, 95% CI: 1.043–1.085) and male gender (OR: 1.466, 95% CI: 1.131–1.901) were independent factors predicting seronegative sera in this population. Seroprevalence was uniformly >95% in the older population (≥35 years) who had not been immunized against measles. The waning vaccine-induced immunity may have impact on the control of measles in the future, especially when the vaccinated population becomes older.

Independence of measles-specific humoral and cellular immune responses to vaccination

With a larger, independent cohort and more sophisticated measures, we sought to confirm our work that indicated independence of humoral and cellular immunity following measles vaccination. We recruited an age-stratified random cohort of 764 healthy subjects from all socioeconomic strata, all with medical-record documentation of 2 age-appropriate doses of measles-containing vaccine. We quantified measles-specific neutralizing antibody levels and assayed the interferon-γ (IFN-γ) enzyme-linked immunosorbent spot assay (ELISPOT) response to measles virus. We also measured secreted cytokines from the peripheral blood mononuclear cells (PBMCs) in response to measles virus by performing enzyme-linked immunosorbent assays as secondary measures of cellular immune status. The median antibody level and median IFN-γ ELISPOT response were 844 mIU/mL (interquartile range [IQR]: 418-1,752) and 36 (IQR: 13.00-69.00) spot-forming cells (per 2 × 10(5) PBMCs), respectively. We observed only a very weak and negative correlation (Spearman's r(s) or ρ of -0.090 [95% confidence interval: -0.162--0.018]). We observed a similar lack of quantitatively important correlations between the neutralizing antibody level and any of the secondary measures. Our data confirm the independence of humoral and cellular immune responses after the second dose of measles vaccination. As researchers pursue novel measles vaccine and measles vaccine delivery systems, they must not infer that humoral responses predict cellular responses.

Consistency of HLA associations between two independent measles vaccine cohorts: A replication study

Associations between HLA genotypes and measles vaccine humoral and cellular immune responses were examined to better understand immunogenetic drivers of vaccine response. Two independent study cohorts of healthy schoolchildren were examined: cohort one, 346 children between 12 and 18 years of age; and cohort two, 388 children between 11 and 19 years of age. All received two age-appropriate doses of measles-containing vaccine. The purpose of this study was to identify and replicate associations between HLA genes and immune responses following measles vaccination found in our first cohort. Associations of comparable magnitudes and with similar p-values were observed between B*3503 (1st cohort p=0.01; 2nd cohort p=0.07), DQA1*0201 (1st cohort p=0.03; 2nd cohort p=0.03), DQB1*0303 (1st cohort p=0.10; 2 cohort p=0.02), DQB1*0602 (1st cohort p=0.07; 2nd cohort p=0.10), and DRB1*0701 (1st cohort p=0.03; 2nd cohort p=0.07) alleles and measles-specific antibody levels. Suggestive, yet consistent, associations were observed between the B7 (1st cohort p=0.01; 2nd cohort p=0.08) supertype and higher measles antibody levels in both cohorts. Also, in both cohorts, the B*0801 and DRB1*0301 alleles, C*0802 and DPA1*0202 alleles, and DRB1*1303 alleles displayed consistent associations with variations in IFN-γ, IL-2 and IL-10 secretion, respectively. This study emphasizes the importance of replicating HLA associations with measles vaccine-induced humoral and cellular immune responses and increases confidence in the results. These data will inform strategies for functional studies and novel vaccine development, including epitope-based measles vaccines. This is the first HLA association replication study with measles vaccine-specific immune responses to date.

Controlling measles in NSW: how are we doing in the context of other countries in the Western Pacific?

[Extract] Global measles control over the past decade has been very successful. Estimated deaths have fallen by 74% from 535 300 in 2000 to 139 300 in 2010.¹ While the goal of eradicating global measles transmission has not yet been formally adopted, five of six World Health Organization (WHO) regions have set deadlines for elimination of endemic measles transmission* (the exception being the South East Asian Region).² This was achieved in the Americas in 2002 and has been maintained since then.³ However, after 8 years of decline, global case numbers have increased in the past 3 years due to substantial outbreaks in Africa and Europe.⁴ In Europe in 2011 there were more than 30 000 cases of measles notified with at least eight deaths.⁵Significant outbreaks occurred in France (15 000 cases), Italy, Spain, Romania and Germany. More than 80% of cases occurred in unvaccinated persons – the main reason for these outbreaks is failure to vaccinate. It is likely that countries with major outbreaks will need to consider 'catch-up' programs, as well as improved primary vaccination coverage with two doses of measles-containing vaccine. In Africa large outbreaks have recently been experienced in 60% of countries.⁶

The re-emergence of measles in developed countries: Time to develop the next-generation measles vaccines?

The re-emergence of measles in developed countries: Time to develop the next-generation measles vaccines?

Immunization Coverage and Its Determinants Among Children Born in 2008-2009 by Questionnaire Survey in Zhejiang, China

The study aimed to assess the determinants of immunization coverage in children born in 2008-2009, living in Zhejiang Province. The World Health Organization's cluster sampling technique was applied. Immunization coverage of 5 vaccines was assessed: BCG vaccine, diphtheria and tetanus toxoids and pertussis vaccine, poliomyelitis vaccine, hepatitis B vaccine, and measles-containing vaccine. Determinants for age-appropriate immunization coverage rates were explored using logistic regression models. Immunization coverage of 5 vaccines were all greater than 90%, but the age-appropriate immunization coverage rates for 3 months and for first dose of measles-containing vaccine was 41.3% and 64.5%, respectively. Siblings in household, mother's education level, household registration, socioeconomic level of resident areas, satisfaction with clinical immunization service, and convenient access to local immunization clinic were associated with age-appropriate coverage rates. Age-appropriate immunization coverage rates should be given more attention and should be considered as a benchmark to strive for in the future intervention.

Epidemiological analysis of measles and evaluation of measles surveillance system performance in Iraq, 2005–2010

The objectives of this study were to identify the risk factors for measles and low vaccination rates, to evaluate the performance of surveillance, and to calculate vaccine effectiveness and failure in Iraq for the years 2005 to 2010. Logistic regression was used on measles surveillance data from Iraq obtained during the period 1 January 2005 to 31 December 2010; adjusted odds ratios were calculated. The performance of surveillance was evaluated according to World Health Organization (WHO) guidelines. Of 18,746 suspected cases, a measles diagnosis was made for 81.4%. Children aged 1-5 years were the most affected (>48%). The odds of measles were significantly higher in the central and southern provinces than in the northern provinces. Those vaccinated with at least one dose of measles-containing vaccine had a 3.7-times lower risk of contracting measles than those who were not vaccinated. Lower odds of vaccination were noted for adults aged 18 years and older and those living in central and southern provinces, as well as those living outside the capital city of a province. Three WHO performance indicators were lower than the recommended cut-off levels. A vaccine failure rate of 66.1% and effectiveness of 90.03% were estimated. Measles continues to be an important cause of morbidity in Iraq. Improvements in vaccine coverage, proper vaccine handling, and prompt reporting of suspected cases are all necessary to eliminate measles from Iraq.

Measles in Geneva between 2003 and 2010: persistence of measles outbreaks despite high immunisation coverage

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Global Use of Rubella Vaccines, 1980–2009

In most developing countries, rubella vaccine has not been included in the Expanded Programme on Immunization because of lack of information on the burden of disease caused by rubella virus, increased cost associated with adding rubella vaccine, and the concern that if high vaccine coverage cannot be achieved and maintained, the risk of congenital rubella syndrome (CRS) may increase. Data for 2009 reported by countries to the World Health Organization (WHO) and United Nations Children's Fund through the annual Joint Reporting Form were used to indicate patterns in the worldwide use of rubella vaccines, describe the number of reported rubella and CRS cases by WHO Region, and explore factors associated with decisions by countries to introduce rubella vaccine in their national childhood immunization programs. The number of WHO Member States using rubella-containing vaccine (RCV) in their national childhood immunization schedule increased from 83 (43%) in 1996 to 130 (67%) in 2009. Although scheduled ages for rubella vaccination vary across countries and regions, most countries have a 2-dose schedule using a combined measles-mumps-rubella vaccine. Among 130 countries using RCV in 2009, median coverage with the first dose of measles-containing vaccine (MCV1) was 95% (interquartile range [IQR], 90%-98%), compared with a median MCV1 coverage of 76% (IQR, 64%-88%) in countries not using RCV. The median per capita gross national income among 130 countries using RCV was US $6300 (IQR, $3227-$20 916), compared with $635 (IQR, $337-$1027) for 63 countries not using RCV. In 2009, 121 344 rubella cases from 167 countries were reported to WHO. However, only 165 CRS cases were reported globally, of which 67 were in the Eastern Mediterranean Region. Further improvements in surveillance are needed to better document the burden of CRS, and new financing mechanisms will be required to catalyze the introduction of rubella vaccine in developing countries that currently meet the coverage criteria for introduction of rubella vaccine.

Human leukocyte antigen associations with humoral and cellular immunity following a second dose of measles-containing vaccine: Persistence, dampening, and extinction of associations found after a first dose

Previously we found human leukocyte antigen (HLA) associations with humoral immunity following a single dose of measles-containing vaccine. In this study, we sought to determine if HLA associations exist with humoral and cellular immunity following a second dose of measles-containing vaccine and if the associations we found with humoral immunity after the first dose persist following a second dose. We recruited a population-based sample of 346 schoolchildren, all who previously received two doses of a measles-containing vaccine. Molecular HLA classes I and II typing as well as humoral and cellular immune assays (measles-specific IgG antibody levels and lymphoproliferative response) were performed in these subjects. We found significant associations with class I HLA-B (p=0.05) as well as class II HLA-DPB1 (p=0.01) and -DPA1 (p=0.03) genes for measles vaccine-induced antibody levels after the second dose. Similarly, we found significant associations with class II HLA-DQB1 (p=0.05) and -DRB1 (p=0.01) genes for measles-specific lymphoproliferation after the second dose. While we found HLA associations after the second dose that we previously found after the first dose of measles containing vaccine, fewer alleles had statistically significant associations, suggesting that the second dose had a dampening or extinguishing effect on the HLA associations. It appears that the second dose overcomes HLA restriction through an as yet unknown mechanism. Future studies of HLA associations should consider both the effect of dose and the role that subsequent doses might play on genetic associations found with the response to a first dose.

Field Effectiveness of Live Attenuated Measles-Containing Vaccines: A Review of Published Literature

Information on measles vaccine effectiveness (VE) is critical to help inform policies for future global measles control goals. We reviewed results of VE studies published during 1960-2010. Seventy papers with 135 VE point estimates were identified. For a single dose of vaccine administered at 9-11 months of age and ≥12 months, the median VE was 77.0% (interquartile range [IQR], 62%-91%) and 92.0% (IQR, 86%-96%), respectively. When analysis was restricted to include only point estimates for which vaccination history was verified and cases were laboratory confirmed, the median VE was 84.0% (IQR, 72.0%-95.0%) and 92.5% (IQR, 84.8%-97.0%) when vaccine was received at 9-11 and ≥12 months, respectively. Published VE vary by World Health Organization region, with generally lower estimates in countries belonging to the African and SouthEast Asian Regions. For 2 doses of measles-containing vaccine, compared with no vaccination, the median VE was 94.1% (IQR, 88.3%-98.3%). The VE of the first dose of measles-containing vaccine administered at 9-11 months was lower than what would be expected from serologic evaluations but was higher than expected when administered at ≥12 months. The median VE increased in a subset of articles in which classification bias was reduced through verified vaccination history and laboratory confirmation. In general, 2 doses of measles-containing vaccine provided excellent protection against measles.

International Measles Incidence and Immunization Coverage

Measles is exquisitely sensitive to immunization programs. We investigated the decline in measles incidence after immunization with 1 or 2 doses of measles-containing vaccine (MCV), with or without supplementary immunization activities (SIAs). Using data from the World Health Organization, we modeled the impact of measles immunization using a negative binomial regression model. All countries offer measles immunization, and 192 of 193 countries offer a second dose of MCV (MCV2), using either a routine second dose, SIAs, or both. The incidence of measles fell from a median of 70.9 cases/100,000/year when coverage with a first dose of MCV (MCV1) was in the range of 0%-39% to a median of .9 cases/100,000/year when MCV1 coverage was 90%-100%, in both cases with no MCV2. Further reductions followed the introduction of MCV2 and SIAs. Modeling showed that each 1% increase in MCV1 coverage was followed by a 2.0% decrease in incidence in the same and following years (95% confidence interval [CI], 2.0%-1.9%, and 2.1%-1.9%, respectively). For a second dose, a rise of 1% in MCV2 coverage was followed by a decrease in measles incidence by .4% (95% CI, .3%-.5%) in the same year and .3% (95% CI, .2%-.5%) in the following year. SIAs were followed by decreases of measles incidence by 40.3% (95% CI, 46.3%-33.8%) in the same year and 45.2% (95% CI, 51.1%-48.7%) in the following year. A herd immunity effect was demonstrated with MCV1 coverage of >80%, and SIAs are an extraordinarily effective strategy for measles control.

Progress Toward Measles Elimination in the Russian Federation, 2003–2009

Successful implementation of the Russian Federation's national measles elimination program has been ensured by high vaccine coverage (>95%) of the target population (with 2 doses of measles-containing vaccine), case-based laboratory investigation of measles, and active surveillance of measles cases among patients with rashes and/or fever. As a result, the incidence of measles has decreased to <1 case per 1,000,000 population (2007-2009); no circulation of D6 genotype, which was endemic in the Russian Federation, has been observed since the second half of 2007; and the proportion of imported measles cases of different genotypes increased to 19.8% in 2007 from 1% in 2003. To confirm successful elimination of indigenous measles, a documentation system was initiated in the Russian Federation.

South-East Asia Regional Update on Measles Mortality Reduction and Elimination, 2003–2008

In 2005, the World Health Assembly endorsed a global goal of 90% reduction in measles mortality from 2000 to 2010. Substantial progress has been made toward achieving this goal in countries of the South-East Asia Region (SEAR). More than 120 million children received a second dose of measles-containing vaccine during supplemental immunization activities conducted from 2000 to 2008; routine first-dose measles-containing vaccine coverage increased from 63% in 2000 to 75% by 2008; and measles surveillance is supported in all countries by the Measles-Rubella Laboratory Network. Overall, the estimated number of measles deaths decreased by 46% from 2000 to 2008, and all countries with the exception of India have already achieved the 90% mortality reduction target. Sustained political and financial commitment from SEAR countries is needed to achieve regional measles mortality reduction and elimination.

Progress Toward Measles Elimination in the Eastern Mediterranean Region

Since 1997, when the goal of interrupting measles transmission by 2010 was adopted, substantial progress has been made toward the elimination of measles in the Eastern Mediterranean Region (EMR). For the 22 EMR member countries, routine coverage with the first dose of a measles-containing vaccine (MCV) increased from 70% in 1997 to 82% in 2009. All 22 countries conducted measles catch-up vaccination campaigns during 1994-2009, and most conducted follow-up campaigns as needed. Of the 22 EMR countries, 19 have established case-based surveillance for measles with laboratory confirmation. Reported measles cases decreased by 86% during 1998-2008, and estimated measles mortality decreased by 93% during 2000-2008, accounting for 17% of global measles mortality reduction during that period. Despite these successes, several significant challenges remain, and the EMR will not be able to achieve measles elimination by the end of 2010. Achieving and maintaining high population immunity with 2 doses of MCV, improving sensitive case-based surveillance, identifying and vaccinating high-risk subpopulation groups, and appropriately responding to outbreaks are key steps needed to achieve the goal.