Persistence Of Measles Research Articles

Evaluating effective measles vaccine coverage in the Malaysian population accounting for between-dose correlation and vaccine efficacy

BackgroundMalaysia introduced the two dose measles-mumps-rubella (MMR) vaccine in 2004 as part of its measles elimination strategy. However, despite high historical coverage of MCV1 and MCV2, Malaysia continues to report high measles incidence. This study suggests a novel indicator for investigating population immunity against measles in the Malaysian population.MethodsWe define effective vaccine coverage (EVC) of measles as the proportion of a population vaccinated with measles-containing vaccine (MCV) and effectively protected against measles infection. A quantitative evaluation of EVC throughout the life course of Malaysian birth cohorts was conducted accounting for both vaccine efficacy (VE) and between-dose correlation (BdC). Measles vaccination coverage was sourced from WHO-UNICEF estimates of Malaysia’s routine immunisation coverage and supplementary immunisation activities (SIAs). United Nations World population estimates and projections (UNWPP) provided birth cohort sizes stratified by age and year. A step wise joint Bernoulli distribution was used to proportionate the Malaysian population born between 1982, the first year of Malaysia’s measles vaccination programme, and 2021, into individuals who received zero dose, one dose and multiple doses of MCV. VE estimates by age and doses received are then adopted to derive EVC. A sensitivity analysis was conducted using 1000 random combinations of BdC and VE parameters.ResultsThis study suggests that no birth cohort in the Malaysian population has achieved > 95% population immunity (EVC) conferred through measles vaccination since the measles immunisation programme began in Malaysia.ConclusionThe persistence of measles in Malaysia is due to pockets of insufficient vaccination coverage against measles in the population. Monitoring BdC through immunisation surveillance systems may allow for the identification of susceptible subpopulations (primarily zero-dose MCV individuals) and increase the coverage of individuals who are vaccinated with multiple doses of MCV. This study provides a tool for assessment of national-level population immunity of measles conferred through vaccination and does not consider subnational heterogeneity or vaccine waning. This tool can be readily applied to other regions and vaccine-preventable diseases.

1148. Long-term Persistence of Measles and Rubella Virus Neutralizing Antibody Levels among Adults with Three Doses of Measles-Mumps-Rubella Vaccine

Abstract Background A third dose of measles-mumps-rubella vaccine (MMR) may be administered for various reasons, but there are limited data on long-term immunogenicity. We assessed persistence of measles and rubella neutralizing antibodies among adults after receipt of three MMR doses. Methods Adults who received two MMR doses in childhood and a third dose as young adults (aged 18-28 years) in 2009-2010 were recalled at around 5 (2014-2016) and 9-11 (2019-2021) years after receipt of the third MMR dose. Measles and rubella antibody levels were assessed by plaque-reduction and soluble immunocolorimetric neutralization assays, respectively. Participants with measles antibody concentrations < 120 mIU/ml or rubella antibody concentrations < 10 U/mL were considered potentially susceptible to infection. Generalized estimating equations models were used to estimate geometric mean concentrations (GMC) and 95% confidence intervals (CI) of antibody levels over time. Results Approximately 5 and 9-11 years after receipt of the third MMR dose, 408 (aged 22-33 years) and 304 (aged 26-37 years) adults were reassessed, respectively. For measles, GMC was 428 mIU/mL (95% CI, 392 – 468 mIU/mL) at 5 years after the third MMR dose, declining to 381 mIU/mL (95% CI, 339 – 428 mIU/mL) at 11 years after the third MMR dose (Fig 1). Measles antibody concentrations during both long-term follow-up periods declined to levels lower than before receipt of the third dose (Fig 2). At the last follow-up visit (2019-2021), 10% of participants were potentially susceptible to measles infection compared to 3% before receipt of the third MMR dose up to 11 years earlier. For rubella, GMCs were stable throughout the long-term follow-up period (63 U/mL to 65 U/mL) (Fig 3). Rubella antibody concentrations during the long-term follow-up periods remained higher than levels before receipt of the third MMR dose and were similar to levels at 1 year after receipt of the third MMR dose (Fig 2). None of the participants were susceptible to rubella at the last follow-up visit. The solid black line shows the trend in population GMC estimates from before vaccination (0 year) through 12 years after receipt of the third MMR dose. The gray lines show the measles virus antibody concentrations over time for each individual. The dotted horizontal line shows concentration <120 mIU/mL used as the cutoff for susceptibility. The vertical dotted lines represent the cutoff for susceptibility. The geometric mean concentrations (GMCs) were estimated using generalized estimating equations model. The solid black line shows the trend in population GMC estimates from before vaccination (0 year) through 12 years after receipt of the third MMR dose. The gray lines show the rubella virus antibody concentrations over time for each individual. The dotted horizontal line shows concentration <10 U/mL used as the cutoff for susceptibility. Conclusion Neutralizing antibody levels to measles and rubella remained high and persisted through 11 years after vaccination among adults who received three MMR doses. However, some adults may become susceptible to measles infection over time despite receipt of three MMR doses. Disclosures Stephen N. Crooke, PhD, Bionano Genomics: Stocks/Bonds|Caribou Biosciences: Stocks/Bonds|Pfizer: Stocks/Bonds|Vistagen Therapeutics: Stocks/Bonds Huong McLean, PhD, MPH, Seqirus: Grant/Research Support

Determinants of measles persistence in Beijing, China: A modelling study.

In Beijing, the capital of China, routine measles mass vaccination has been in place for decades with high coverage; and since the 2000s, catch-up vaccination programmes have been implemented for migrant workers coming to the city. However, measles epidemics in Beijing persisted. Here, we explored the contributing factors of persistent measles transmission in Beijing using an epidemic model in conjunction with a particle filter. Model inputs included data on birth, death, migration, and vaccination. We formulated a series of hypotheses covering the impact of migrant influx, early waning of maternal immunity, and increased mixing among infants; we compared the plausibility of the hypotheses based on model fit to age-grouped, weekly measles incidence data from January 2005 to December 2014, and out-of-fit prediction during 2015-2019. Our best models showed close agreement with the data, and the out-of-fit prediction generally captured the trend of measles incidence from 2015 to 2019. We found that large influx of migrants with considerably higher susceptibility likely contributed to the persistent measles transmission in Beijing. Our findings suggest that stronger catch-up vaccination programmes for migrants may help eliminate measles transmission in Beijing.

Descriptive Characterisation of Suspected Measles Cases in Sokoto State 2010 -2016: A Secondary Data Analysis

Background: Measles is a disease with worldwide distribution; however, control efforts have substantially altered the global distribution. The incidence has decreased considerably in regions where routine vaccination is strong; however, this is not the case in developing countries like Nigeria. This study aims to describe the distribution of measles cases in Sokoto state in time, place and person. Methods: Descriptive analyses of measles surveillance data between 2010 and 2016 was carried out to describe the epidemiology of measles in Sokoto State in Time, Place and Person. Microsoft Excel and IBM SPSS were used to analyse the data. We reported frequencies and proportions; cross-tabulations and chi-square tests were used to find associations between variables. Results: A total of 13974 suspected cases of measles were line-listed between January 2010 and June 2016. Overall, 11008 (78.8%) were below five years, and 7421 (53.1%) were males. A majority, 12896 (92%), of the suspected measles cases were reported in the first half of each year of evaluation. Gwadabawa Local Government Area (LGA) recorded the highest measles cases, 1881 (14%). Ten thousand and twenty-seven (71.8%) of suspected measles cases did not receive the measles vaccine. The overall Case Fatality Rate (CFR) was 0.9%. However, Bodinga LGA had the highest CFR of 4%. Only 605(4%) suspected measles cases were tested for Measles IgM. One hundred and twenty-five (0.9%) deaths were recorded. Factors significantly associated with deaths are measles vaccination status (p = 0.001) and admission status (p < 0.001). Conclusion: There is the persistence of measles over the period affecting primarily children below five years with a low CFR. However, a majority of the children did not receive their measles vaccine. Based on this finding, measles will remain a public health problem unless significant efforts are put into place to increase vaccination coverage.

Investigating persistent measles dynamics in Niger and associations with rainfall.

Measles is a major cause of child mortality in sub-Saharan Africa. Current immunization strategies achieve low coverage in areas where transmission drivers differ substantially from those in high-income countries. A better understanding of measles transmission in areas with measles persistence will increase vaccination coverage and reduce ongoing transmission. We analysed weekly reported measles cases at the district level in Niger from 1995 to 2004 to identify underlying transmission mechanisms. We identified dominant periodicities and the associated spatial clustering patterns. We also investigated associations between reported measles cases and environmental drivers associated with human activities, particularly rainfall. The annual and 2–3-year periodicities dominated the reporting data spectrum. The annual periodicity was strong with contiguous spatial clustering, consistent with the latitudinal gradient of population density, and stable over time. The 2–3-year periodicities were weaker, unstable over time and had spatially fragmented clustering. The rainy season was associated with a lower risk of measles case reporting. The annual periodicity likely reflects seasonal agricultural labour migration, whereas the 2–3-year periodicity potentially results from multiple mechanisms such as reintroductions and vaccine coverage heterogeneity. Our findings suggest that improving vaccine coverage in seasonally mobile populations could reduce strong measles seasonality in Niger and across similar settings.

A competing-risks model explains hierarchical spatial coupling of measles epidemics en route to national elimination.

Apart from its global health importance, measles is a paradigm for the low-dimensional mechanistic understanding of local nonlinear population interactions. A central question for spatio-temporal dynamics is the relative roles of hierarchical spread from large cities to small towns and metapopulation transmission among local small population clusters in measles persistence. Quantifying this balance is critical to planning the regional elimination and global eradication of measles. Yet, current gravity models do not allow a formal comparison of hierarchical versus metapopulation spread. We address this gap with a competing-risks framework, capturing the relative importance of competing sources of reintroductions of infection. We apply the method to the uniquely spatio-temporally detailed urban incidence dataset for measles in England and Wales, from 1944 to the infection's vaccine-induced nadir in the 1990s. We find that despite the regional influence of a few large cities (for example, London and Liverpool), metapopulation aggregation in neighbouring towns and cities played an important role in driving national dynamics in the prevaccination era. As vaccination levels increased in the 1970s and 1980s, the signature of spatially predictable spread diminished: increasingly, infection was introduced from unidentifiable random sources possibly outside regional metapopulations. The resulting erratic dynamics highlight the challenges of identifying shifting sources of infection and characterizing patterns of incidence in times of high vaccination coverage. More broadly, the underlying incidence and demographic data, accompanying this paper, will also provide an important resource for exploring nonlinear spatiotemporal population dynamics.

Low percentages of measles vaccination coverage with two doses of vaccine and low herd immunity levels explain measles incidence and persistence of measles in the European Union in 2017-2018.

Several factors may explain why measles persisted in the European Union in 2017-2018. The study assessed mean measles vaccination coverage and anti-measles herd immunity levels in the target measles vaccination population in countries of the European Union during the 2015-2017 period. The study found that the measles vaccination coverage with two doses of vaccine was < 95% in 28 (96.5%) countries, and that the prevalence of individuals with vaccine-induced measles protection in the target vaccination population was lower than the herd immunity threshold of 94.4% in 22 (75.9%) countries during 2015-2017. The study found a significant negative correlation between the incidence of measles in 2017-2018 in different countries of the European Union and measles vaccination coverage with two doses of measles vaccine, prevalence of individuals with vaccine-induced measles protection and herd immunity levels in the target measles vaccination population during 2015-2017. Measles vaccination coverage and herd immunity levels did not improve from 2010-2015 to 2015-2017 in the European Union. Low percentages of measles vaccination coverage with two doses of vaccine and low herd immunity levels could explain measles incidence in countries of the European Union in 2017-2018. New measles prevention strategies should be developed to increase measles vaccination coverage and herd immunity levels in the European Union.

Measles in Zhejiang, China, 2004-2017: Population Density and Proportion of Floating Populations Effects on Measles Epidemic.

The target of eliminating measles has not been achieved, and measles has resurged in Zhejiang, China, since 2013. In this study, we hypothesized that population density and the proportion of the floating population were the potential causes of measles persistence in Zhejiang. Measles cases in Zhejiang from 2004 through 2017 were analyzed using data from the National Notifiable Diseases Reporting System (NNDRS). Reported measles incidence and annual incidence by age were described. Spearman correlation coefficients were used to assess correlations between measles incidence and population density and the proportion of floating population. A total of 48,648 measles cases were reported during the 14-year period. Two large measles epidemics occurred in 2005 (14,317 cases, incidence of 29.38/100,000) and 2008 (12,782 cases, incidence of 25.26/100,000). A higher proportion of cases occurred in young adults aged 20 to 34 years and infants under 1 year of age. A positive correlation was observed between measles incidence and either population density or proportion of inter-provincial floating populations. In general, Zhejiang suffers from a high incidence of measles partly because of its high population density and the low vaccination rates among inter-provincial floating populations. To meet the target of measles elimination, convincing susceptible young adults and migrant children to get vaccinated remains a critical issue.

Monitoring the age-specificity of measles transmissions during 2009-2016 in Southern China.

BackgroundDespite several immunization efforts, China saw a resurgence of measles in 2012. Monitoring of transmissions of individuals from different age groups could offer information that would be valuable for planning adequate disease control strategies. We compared the age-specific effective reproductive numbers (R) of measles during 2009–2016 in Guangdong, China.MethodsWe estimated the age-specific R values for 7 age groups: 0–8 months, 9–18 months, 19 months to 6 years, 7–15 years, 16–25 years, 26–45 years, and ≥46 years adapting the contact matrix of China. The daily numbers of laboratory and clinically confirmed cases reported to the Center for Disease Control and Prevention of Guangdong were used.ResultsThe peak R values of the entire population were above unity from 2012 to 2016, indicating the persistence of measles in the population. In general, children aged 0–6 years and adults aged 26–45 years had larger values of R when comparing with other age groups after 2012. While the peaks of R values for children aged 0–6 years dropped steadily after 2013, the peaks of R values for adults aged 26–45 years kept at a high range every year.ConclusionsAlthough the provincial supplementary immunization activities (SIAs) conducted in 2009 and 2010 were able to reduce the transmissions from 2009 to 2011, larger values of R for children aged 0–6 years were observed after 2012, indicating that the benefits of the SIAs were short-lived. In addition, the transmissions from adults aged between 26 and 45 years increased over time. Disease control strategies should target children and adult groups that carry high potential for measles transmission.

Analysis of measles surveillance data, Sokoto State, Nigeria: 2010 - 2016

Introduction: measles is a disease that has a worldwide distribution; however, control efforts have substantially altered the global distribution. The incidence has decreased substantially in regions where vaccination has been instituted. In spite of the increase in Measles immunization coverage aimed at building population immunity against the disease, Measles outbreaks still occur, especially in the developing countries like Nigeria. The aim of this study was to describe the distribution of Measles cases in Sokoto State in time place and person. Methods: descriptive analyses of Measles Surveillance data between 2010 and 2016 was carried out to describe the epidemiology of Measles in Sokoto State in time, place and person. Microsoft excel and Epi info were used to analyze the data. Proportions, cross tabulations and chi square test were used to find associations between variables. Results: a total of 13974 suspected cases were line listed between January 2010 and June 2016, there were a total of 13974 suspected Measles cases. Overall, 11107 (80%) were below 5 years and 6553 (47%) were females. Majority, 12896 (92%) of the suspected Measles cases were reported in the first half of each year of evaluation. Gwadabawa Local Government Area (LGA) recorded the highest number of Measles cases 1881 (14%). Ten thousand and twenty-seven (72%) of suspected Measles cases did not receive Measles vaccine. The overall case fatality rate (CFR) was 0.9%, however, Bodinga LGA had the highest CFR of 4% and over the period of surveillance year 2015 had the highest CFR (1.8%). Only 605(4%) suspected Measles cases were tested for Measles IgM. One hundred and twenty-five (0.9%) deaths were recorded; factors significantly associated with deaths are number of doses of Measles received (p = 0.001) and admission status (p < 0.001). Conclusion: there is persistence of Measles over the period affecting primarily children below five years. This may be due to vaccinations being missed by children despite activities to strengthen coverage. We recommend that there should be more awareness programs and strengthening of Measles immunization in the State.

Why does measles persist in Europe?

Several reasons may explain why measles was not eliminated by 2015 and continues to persist in Europe, including low measles vaccination coverage, low anti-measles herd immunity levels, and the mobility of individuals with measles across Europe. The study assessed the mean measles vaccination coverage in the European Union and the WHO European region with one and two doses of measles vaccine from 1980 to 2015, and the prevalence of vaccine-induced protected individuals and anti-measles herd immunity levels in the WHO European region during 2000-2015. The study found that measles vaccination coverage with two doses of vaccine was <90% in the European Union and the WHO European region from 1995 to 2015. In the WHO European region, the two-dose measles vaccination coverage during the 2000-2015 period was <95% in 41 countries (79%), and the prevalence of vaccine-induced protected individuals in the target vaccination population was lower than the herd immunity threshold of 94.4% in 33 countries (63%). The additional vaccination coverage required to establish herd immunity in these countries ranged from 0.2% to 18%. Two of the factors explaining measles persistence in Europe in 2015 were the two-dose measles vaccination coverage <95% and the prevalence of individuals with vaccine-induced protection of <94.4% in most countries of the WHO European region during the 2000-2015 period. Screening and vaccination programs should be developed to detect and immunize susceptible individuals in areas and population groups without anti-measles herd immunity in all European countries.

Periodicity, synchronization and persistence in pre-vaccination measles.

We investigate the relationship between periodicity, synchronization and persistence of measles through simulations of geographical spread on the British Isles. We show that the establishment of areas of biennial periodicity depends on the interplay between human mobility and local population size and that locations undergoing biennial cycles tend to be, on average, synchronized in phase. We show however that occurrences of opposition of phase are actually quite common and correspond to stable dynamics. We also show that persistence is strictly related to circulation of the disease in the highly populated area of London and that this ensures survival of the disease even when human mobility drops to extremely low levels.

Persistence of measles neutralizing antibody related to vaccine and natural infection acquired before HIV infection.

Little is known about long-lasting measles protective immunity when exposure to wild-type or vaccine measles virus precedes HIV infection. The results obtained suggest that measles immunity wanes and the lowest measles geometric mean titres (GMT) were significantly associated with measles vaccine-induced immunity in individuals that later developed HIV infection (86% prevalence, GMT 164 mIU/ml) compared to naturally induced immunity in HIV-infected adults (100% prevalence, GMT 340 mIU/ml, P = 0·0082) or non-HIV infected adults (100%, GMT 724 mIU/ml, P = 0·0001), and vaccine-induced immunity in non-HIV-infected adults (100%, GMT 347 mIU/ml, P = 0·017). The study was conducted in an area without wild-type virus circulation since 2000. The absence of virus circulating may alter the paradigm of lifelong immunity to measles virus after vaccination. As the proportion of HIV-infected individuals possessing only vaccine-induced immunity continues to grow, checking the status of measles immunity in this group is strongly recommended.

Think globally, act locally: the role of local demographics and vaccination coverage in the dynamic response of measles infection to control.

The global reduction of the burden of morbidity and mortality owing to measles has been a major triumph of public health. However, the continued persistence of measles infection probably not only reflects local variation in progress towards vaccination target goals, but may also reflect local variation in dynamic processes of transmission, susceptible replenishment through births and stochastic local extinction. Dynamic models predict that vaccination should increase the mean age of infection and increase inter-annual variability in incidence. Through a comparative approach, we assess national-level patterns in the mean age of infection and measles persistence. We find that while the classic predictions do hold in general, the impact of vaccination on the age distribution of cases and stochastic fadeout are mediated by local birth rate. Thus, broad-scale vaccine coverage goals are unlikely to have the same impact on the interruption of measles transmission in all demographic settings. Indeed, these results suggest that the achievement of further measles reduction or elimination goals is likely to require programmatic and vaccine coverage goals that are tailored to local demographic conditions.

Differences in persistence of measles, mumps, rubella, diphtheria and tetanus antibodies between children with rheumatic disease and healthy controls: a retrospective cross-sectional study

ObjectivesTo compare the persistence of measles, mumps, rubella, diphtheria and tetanus antibodies between patients with juvenile idiopathic arthritis (JIA) and healthy controls.MethodsMeasles, mumps, rubella (MMR) and diphtheria–tetanus toxoid (DT)-specific immunoglobulin...

Persistence of Measles, Mumps, and Rubella Protective Antibodies 3 Years after Revaccination in HIV‐Infected Children Receiving Antiretroviral Therapy

Three years after measles, mumps, and rubella revaccination in 38 human immunodeficiency virus-infected children who had achieved immune recovery after antiretroviral therapy, the prevalence of protective antibody levels was 85% for measles, 61% for mumps, and 79% for rubella, compared with 88%, 84%, and 100%, respectively, 1 month after revaccination.

Resolving the impact of waiting time distributions on the persistence of measles

Measles epidemics in human populations exhibit what is perhaps the best empirically characterized, and certainly the most studied, stochastic persistence threshold in population biology. A critical community size (CCS) of around 250,000-500,000 separates populations where measles is predominantly persistent from smaller communities where there are frequent extinctions of measles between major epidemics. The fundamental mechanisms contributing to this pattern of persistence, which are long-lasting immunity to re-infection, recruitment of susceptibles, seasonality in transmission, age dependence of transmission and the spatial coupling between communities, have all been quantified and, to a greater or lesser level of success, captured by theoretical models. Despite these successes there has not been a consensus over whether simple models can successfully predict the value of the CCS, or indeed which mechanisms determine the persistence of measles over a broader range of population sizes. Specifically, the level of the CCS has been thought to be particularly sensitive to the detailed stochastic dynamics generated by the waiting time distribution (WTD) in the infectious and latent periods. We show that the relative patterns of persistence between models with different WTDs are highly sensitive to the criterion of comparison-in particular, the statistical measure of persistence that is employed. To this end, we introduce two new statistical measures of persistence-fade-outs post epidemic and fade-outs post invasion. Contrary to previous reports, we demonstrate that, no matter the choice of persistence measure, appropriately parametrized models of measles demonstrate similar predictions for the level of the CCS.

Persistence of Measles, Mumps, and Rubella Antibodies in an MMR‐Vaccinated Cohort: A 20‐Year Follow‐up

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

How successful is South Africa in decreasing communicable diseases?

The success of the public health sanitation movement included the use of vaccines, and antibiotics led many to assume that all infectious diseases would sooner or later succumb to medical technology and public health measures. Unfortunately this did not happen. Late in the 20th century and now early in the 21st century we see the onset of new communicable diseases such as HIV/AIDS and severe acute respiratory syndrome (SARS) and the resurgence of old communicable diseases such as tuberculosis (TB) and malaria. The persistence of measles as a major killer of over one million children per year represents a failure in effective use of both the vaccines and the health systems in developing countries. Nowhere else can we see these problems better than in our own backyard. South Afr J Epidemiol Infect 2008;23(4):10-12

Transients and attractors in epidemics.

Historical records of childhood disease incidence reveal complex dynamics. For measles, a simple model has indicated that epidemic patterns represent attractors of a nonlinear dynamic system and that transitions between different attractors are driven by slow changes in birth rates and vaccination levels. The same analysis can explain the main features of chickenpox dynamics, but fails for rubella and whooping cough. We show that an additional (perturbative) analysis of the model, together with knowledge of the population size in question, can account for all the observed incidence patterns by predicting how stochastically sustained transient dynamics should be manifested in these systems.