Modelling vaccination programmes against measles in Taiwan

Vaccination has proved a powerful defence against measles. We reappraise measles seroepidemiological data in Taiwan from 1974 to 2004 having robust age-stratified serological information on exposure and immunity to quantitatively characterize measles vaccination programmes. We dynamically model measles seroepidemiology to estimate age-dependent intensity of infection associated with the effects of different contact patterns on pre- and post-vaccination. The WAIFM (who acquires infection from whom) contact matrix is employed to describe the transmission between and within each age group. A deterministic SEIR (susceptible-exposed-infected-recovery) model is used to capture subpopulation dynamics. Our study shows that mass regional or nationwide vaccination programmes could greatly reduce the potential for a major measles epidemic and have strong direct effects on the potential impact of childhood vaccination. We parameterize a predictive model that should reduce the socio-economic costs of measles surveillance in Taiwan and thereby encourage its continuance, especially for preschool children.     

Measles immunity in the first year after birth and the optimum age for vaccination in Kenyan children: Collaborative study by the Ministry of Health of Kenya and the World Health Organization*

There is still controversy about the optimum age for measles vaccination in developing countries, where the incidence of measles infection is higher in the first few months of life than it is in developed countries. This study was undertaken to collect reliable data in order to determine the optimum age for mass vaccination programmes. Haemagglutination inhibition (HI) antibodies were titrated periodically from birth to one year of age in children who were given the vaccine at different ages, between 5 and 9 months. It was found that 90% of children no longer have their maternal antibodies at 7-8 months of age, precisely at the period that the incidence of measles begins to rise sharply. Almost all children showed HI seroconversion when vaccinated at 71/2 months (or later, but not before), even if a low level of maternal antibody still persisted when the vaccine was given. These data show that there is an advantage in carrying out measles vaccination at 71/2 months of age in countries with conditions similar to that of Kenya. The duration of post-vaccinal immunity beyond one year of age has not been studied, but it can reasonably be expected that immunity after one vaccination can last for at least 3-5 years, thus exceeding the period when African children are most exposed to malnutrition.     

Measles in developing countries. Part I. Epidemiological parameters and patterns

This paper presents a review of published data concerning the epidemiology of measles in developing countries. Simple mathematical models provide a framework for data analysis and interpretation. The analyses highlight differences and similarities in the patterns of transmission of the measles virus in developed and developing countries. Whilst the rate of loss of maternally derived immunity to measles is broadly similar, the average age at infection is much lower, and case fatality rates are much higher in developing countries. Data analysis also serves to illustrate inter-relationships between different kinds of epidemiological data. Thus, for example, in order to correctly interpret an age stratified serological profile from a developing country it is necessary to have information on the rate of decay of maternal antibodies and age specific case fatality rates. To determine the probable impact of a given vaccination programme, information on the birth rate in the community concerned is also required. A discussion is given of the epidemiological data required in order to effectively design a community based vaccination programme aimed at the eradication of measles.     

The concept of herd immunity and the design of community-based immunization programmes.

The paper focuses on the concepts of transmission success and herd immunity and their relevance to the design of community-based immunization programmes for the control of infectious diseases. Recent work in a number of areas is reviewed, including the influence of mass vaccination on the average age of infection and the incidence of morbidity due to infection and vaccination, the age window of susceptibility and the problems of vaccine programme design in developing countries, the interaction between vaccine efficacy and vaccine safety and the design of vaccination programmes for the control of sexually transmitted infections. Discussions centre on the interplay between an understanding of the transmission dynamics of an infection and the design of community-based control programmes.     

Changes of the immunological patterns against measles, mumps and rubella. A vaccination programme studied 3 to 7 years after the introduction of a two-dose schedule

A two-dose vaccination programme using a combined measles, mumps and rubella vaccine (MMR) and administration at the ages of 18 months and 12 years was introduced in 1982. The 12-year-old schoolchildren were tested yearly from 1985 to 1989 on serum samples obtained prior to and after vaccination. Each year between 420 and 756 children were tested. The method used for antibody testing was the haemolysis-in-gel (HIG) assay. For measles also the enzyme-linked immunosorbent assay (ELISA) and the neutralization titre (NT) were applied. Only minor variations of the prevaccination immunity to measles were seen during the period 3-7 years after introduction of the programme. The age groups studied had partly been vaccinated against measles earlier. Between 12 and 16% lacked prevaccination immunity. In contrast the immunity to mumps and rubella of the 12-year-old children decreased considerably during the study period. No general vaccination against these diseases had been performed. Thus the susceptibility to mumps increased from 14% in 1985 to 39% in 1989 and to rubella from 41 to 57%. The seroconversion rate of children seronegative for measles was high, i.e. 100% in 1985 and later varied between 96 and 97%. For mumps, the seroconversion rate was lower and varied between 72 and 88%. All sera converted to rubella. During the follow-up period there was a declining incidence of measles, mumps and rubella. The relationship between the vaccination and reduction of disease and natural immunity strongly suggests that the association is causal and that this vaccination policy reduced the transmission of infection.     

Assessment of measles immunity among infants in Maputo City,Mozambique

Background  

The optimum age for measles vaccination varies from country to country and thus a standardized vaccination schedule is controversial. While the increase in measles vaccination coverage has produced significant changes in the epidemiology of infection, vaccination schedules have not been adjusted. Instead, measures to cut wild-type virus transmission through mass vaccination campaigns have been instituted. This study estimates the presence of measles antibodies among six- and nine-month-old children and assesses the current vaccination seroconversion by using a non invasive method in Maputo City, Mozambique.     

The effect of human immunodeficiency virus-1 infection and stunting on measles immunoglobulin-G levels in children vaccinated against measles in Uganda.

BACKGROUND: Measles is an important public health problem in developing nations and there is concern that immune response to measles vaccination may be compromised by paediatric human immunodeficiency virus (HIV) infection. Therefore, this study investigated the relationship of immunoglobulin-G (Ig-G) antibody levels in children vaccinated against measles and HIV-1 infection. Further analysis was done to assess the influence of nutritional status on this relationship. METHODS: The authors measured HIV and measles antibodies in 243 vaccinated children aged 17-41 months from Kampala, Uganda. Children were from paediatric and HIV clinics. Potential confounders of this relationship included nutritional anthropometric measures, age at and time since vaccination, measles exposure, family crowding, vaccination clinic and gender. Univariable and multivariable analyses were used to study these associations. RESULTS: Fifty children (21%) were HIV infected. In univariable analysis, low measles antibody (<15 ELISA units/ml) was associated with HIV (P = 0.05; odds ratio (OR) = 1.86) and stunting (P = 0.06; OR = 1.68). Stunting, measured as height-for-age and defined as <-2 standard deviations of the reference population median, was a surrogate for chronic malnutrition. HIV was strongly associated with stunting (P = 0.0001; OR = 6.62). In multiple logistic regression, HIV was not associated with low measles antibodies; however, stunting (P = 0.04; OR = 1.81), and <3 children in the home (P = 0.01; OR = 1.96) were. Conversely, being male (P = 0.05; OR = 0.58), and measles in the home in the previous month (P = 0.04; OR = 0.33) were associated with high antibody levels. CONCLUSIONS: These findings suggest that HIV in Ugandan children immunized for measles may indirectly interfere with measles antibody levels by causing malnutrition, the latter being the direct cause. Programmes to improve childhood nutrition, especially for HIV-infected children, should accompany measles control programmes in developing nations for maximum benefit from measles vaccination. HIV infection per se should not change measles vaccination programmes.     

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.     

Estimating the force of measles virus infection from hospitalised cases in Lusaka, Zambia

Estimates of the force of infection (the rate at which susceptible individuals acquire infection) are essential for modelling the transmission dynamics of infectious diseases and can be a useful tool in evaluating mass vaccination strategies. Few estimates exist of the force of infection of measles virus in sub-Saharan Africa. A mathematical model was applied to age-specific recorded hospital admissions between September 1996 and September 1999 to estimate the force of measles virus infection in Lusaka, Zambia. The average force of infection was estimated to be 20% per year (95% confidence intervals (CI) 16.5, 23.5) which was insensitive to varying assumptions about vaccine coverage. The force of infection varied from year to year (P < 0.001) reflecting the cyclic pattern of measles incidence. The estimated probability of a case being hospitalised decreased with age, consistent with less severe disease in older children. Estimates of the force of infection using routinely available data were consistent with those based upon serological surveys in other sub-Saharan African countries.     

北京市流动人口麻疹暴发疫情特征及控制策略

北京市近10年来本市户籍人群麻疹发病控制在历史最低水平,但随着流动人口不断增多,流动人口麻疹发病日益突出,并常以暴发的形式出现。其发病对象以学龄前儿童和建筑民工为主,发病主要原因是未接种过麻疹疫苗。加强麻疹监测,提高流动儿童常规免疫覆盖率,开展特定人群强化免疫,增强流动人口保健意识,是预测和控制暴发、降低该人群发病的有效策略．     

School-based measles outbreaks: correlation of age at immunization with risk of disease.

During the Spring of 1978, students with a history of previous measles vaccination accounted for over three-forths of 203 cases of measles in a metropolitan county. Seventy cases occurred in two schools where 99% of the students were vaccinated. We analyzed countywide data to determine past patterns of measles vaccination, including outbreak control and vaccination update clinics. We also examined records of children from the two schools to assess the relationship between disease incidence and age at vaccination. When susceptibility was determined by trained health workers rather than by parents, fewer doses of measles vaccine were estimated to be needed. The majority of cases occurred among children 5 to 9 years old. Attack rates were higher for children vaccinated at 12 months of age or younger than for those vaccinated at 13 months of age or older. There were no significant differences in attack rates among children vaccinated at 13 months of age or older. These findings support recommendations for delaying routine measles vaccination until after 12 months of age and suggest that, during outbreaks, all children vaccinated prior to 13 months of age be revaccinated.     

The 1991 measles epidemic in Israel.

INTRODUCTION AND METHODS. Prior to the institution of universal childhood vaccination against measles in Israel in 1967, large outbreaks occurred in epidemic cycles at intervals of 2-4 years. The mean annual incidence in the pre-vaccination period, 1950-66, was 470/100,000 per year. With the institution of routine measles vaccination, incidence rates fell, and since 1970 measles incidence has averaged less than one-tenth the pre-vaccination incidence rate, although epidemics occurred in 1975, 1982, 1984-85, and 1991. In this report, based upon cases of measles reported to and investigated by the Ministry of Health, we present an analysis of the 1991 measles epidemic, the measures taken to contain it, and an overview of the prospects for measles control in Israel in the future. RESULTS AND CONCLUSIONS. The 1991 measles epidemic, 1036 reported cases (incidence: 20.0/100,000), began in the south of the country among underimmunized Beduin children and spread to the Jewish population in the south and then to the rest of the country. The highest incidence was in children aged 12-23 months, followed by children less than 12 months of age and children aged 2-4 years. In the main, cases occurred in persons never immunized in the past, but in 37% of cases vaccine failure seems to have occurred. Control measures included mass vaccination of children in the south and lowering the age for routine measles vaccination nationwide to 12 months. Despite very substantial gains towards measles control in Israel, elimination of the disease is not a realistic goal, mainly because the transmission potential of the disease is too high and vaccine coverage and efficacy are not high enough. Trends in measles incidence over the last four decades allow a cautious optimism that measles containment can be achieved.     

Evaluating the impact of the HIV pandemic on measles control and elimination

OBJECTIVE: To estimate the impact of the HIV pandemic on vaccine-acquired population immunity to measles virus because high levels of population immunity are required to eliminate transmission of measles virus in large geographical areas, and HIV infection can reduce the efficacy of measles vaccination. METHODS: A literature review was conducted to estimate key parameters relating to the potential impact of HIV infection on the epidemiology of measles in sub-Saharan Africa; parameters included the prevalence of HIV, child mortality, perinatal HIV transmission rates and protective immune responses to measles vaccination. These parameter estimates were incorporated into a simple model, applicable to regions that have a high prevalence of HIV, to estimate the potential impact of HIV infection on population immunity against measles. FINDINGS: The model suggests that the HIV pandemic should not introduce an insurmountable barrier to measles control and elimination, in part because higher rates of primary and secondary vaccine failure among HIV-infected children are counteracted by their high mortality rate. The HIV pandemic could result in a 2-3% increase in the proportion of the birth cohort susceptible to measles, and more frequent supplemental immunization activities (SIAs) may be necessary to control or eliminate measles. In the model the optimal interval between SIAs was most influenced by the coverage rate for routine measles vaccination. The absence of a second opportunity for vaccination resulted in the greatest increase in the number of susceptible children. CONCLUSION: These results help explain the initial success of measles elimination efforts in southern Africa, where measles control has been achieved in a setting of high HIV prevalence.     

Evaluation of measles vaccination programme conducted in two separate health centres.

Measles vaccination programmes at two vaccination centres in Ibadan, Nigeria were evaluated using the following factors as indicators: type of vaccination centre, age at vaccination, titre of vaccine, economic, health and social status of vaccinee. There was a significant association between type of vaccination centre, vaccine titre and rate of conversion. Seroconversion rates of 64 and 26% were obtained in the two vaccination centres. This was associated with the difference in the method of vaccine handling during vaccination in the centres. Higher prevalence of maternal antibody was found among children with longer breast feeding period. Results obtained suggest that the Expanded Programme on Immunization (EPI) against measles is not effective, especially in rural health centres, because of improper vaccine handling. Recommendations on how to improve measles vaccination in the EPI are highlighted.     

Inadequate immunity to measles in children vaccinated at an early age: effect of revaccination

This report describes a follow-up serological study of 79 Brazilian children who, because of their young age, had failed to develop protective levels of immunity after vaccination against measles. There was serological evidence that infection with wild virus had occurred at a rate of about 17% per annum. Approximately 1½ years after the initial vaccination, 46% of the uninfected children maintained very low levels of neutralizing antibody, but did not have a measurable haemagglutination-inhibition titre. Revaccination did not elicit an IgM response in most children, but stimulated anti-measles IgG production in all of them. In 36% of the children, the IgG titres fell again within three months to levels that may permit reinfection. If it is assumed that some of the persistent titres can be attributed to wild virus infection, the actual effect of revaccination would have been to immunize no more than 60% of the susceptible group. The results suggest that early administration of measles vaccine may produce a cohort of children with inadequate immunity who cannot be fully immunized by revaccination. The implications of these findings for measles immunization programmes are discussed.     

Immune response to measles vaccine in Peruvian children.

OBJECTIVE: To evaluate the immune response in Peruvian children following measles vaccination. METHODS: Fifty-five Peruvian children received Schwarz measles vaccine (about 10(3) plaque forming units) at about 9 months of age. Blood samples were taken before vaccination, then twice after vaccination: one sample at between 1 and 4 weeks after vaccination and the final sample 3 months post vaccination for evaluation of immune cell phenotype and lymphoproliferative responses to measles and non-measles antigens. Measles-specific antibodies were measured by plaque reduction neutralization. FINDINGS: The humoral response developed rapidly after vaccination; only 4 of the 55 children (7%) had plaque reduction neutralization titres <200 mlU/ml 3 months after vaccination. However, only 8 out of 35 children tested (23%) had lymphoproliferative responses to measles antigens 3-4 weeks after vaccination. Children with poor lymphoproliferative responses to measles antigens had readily detectable lymphoproliferative responses to other antigens. Flow cytometric analysis of peripheral blood mononuclear cells revealed diffuse immune system activation at the time of vaccination in most children. The capacity to mount a lymphoproliferative response to measles antigens was associated with expression of CD45RO on CD4+ T-cells. CONCLUSION: The 55 Peruvian children had excellent antibody responses after measles vaccination, but only 23% (8 out of 35) generated detectable lymphoproliferative responses to measles antigens (compared with 55-67% in children in the industrialized world). This difference may contribute to the less than uniform success of measles vaccination programmes in the developing world.     

Age-related changes in the rate of disease transmission: implications for the design of vaccination programmes.

Mathematical models are developed to aid in the investigation of the implications of heterogeneity in contact with infection within a community, on the design of mass vaccination programmes for the control of childhood viral and bacterial infections in developed countries. Analyses are focused on age-dependency in the rate at which individuals acquire infection, the question of ''who acquires infection from whom'', and the implications of genetic variability in susceptibility to infection. Throughout, theoretical predictions are based on parameter estimates obtained from epidemiological studies and are compared with observed temporal trends in disease incidence and age-stratified serological profiles. Analysis of case notification records and serological data suggest that the rate at which individuals acquire many common infections changes from medium to high and then to low levels in the infant, child and teenage plus adult age groups respectively. Such apparent age-dependency in attack rate acts to reduce slightly the predicted levels of herd immunity required for the eradication of infections such as measles, when compared with the predictions of models based on age-independent transmission. The action of maternally derived immunity in prohibiting vaccination in infants, and the broad span of age classes over which vaccination currently takes place in the U.K., however, argue that levels of herd immunity of between 90 and 94% would be required to eliminate measles. Problems surrounding the interpretation of apparent age-related trends in the acquisition of infection and their relevance to the design of vaccination programmes, are discussed in relation to the possible role of genetically based variation in susceptibility to infection and observations on epidemics in ''virgin'' populations. Heterogeneous mixing models provide predictions of changes in serology and disease incidence under the impact of mass vaccination which well mirror observed trends in England and Wales.     

Immunization coverage and natural infection rates of vaccine-preventable diseases among children by questionnaire survey in 2005 in Japan

We performed questionnaire survey in 2005, just before the introduction of the MR vaccine, concerning child vaccination and/or infection history for measles, mumps, rubella, varicella, influenza, diphtheria-pertussis-tetanus (DPT), BCG, and Japanese encephalitis. The vaccination rate against measles and rubella did not exceed 95% at any age levels. As a result, children who had contracted measles and/or rubella were observed at all age levels. The vaccination rate was 95% or higher only for BCG and DPT. The vaccination rates for influenza, mumps, and varicella, although vaccination against which diseases was being performed voluntarily, were low, and outbreaks of these diseases were expected to persist. The vaccination rates at a low level for these infectious diseases might be one of the most possible risk factors to the high prevalence of the diseases in nursery schools (daycare centers), kindergartens, and elementary schools all over Japan.     

The pre-vaccination epidemiology of measles, mumps and rubella in Europe: implications for modelling studies

Data on the pre-vaccination patterns of infection for measles, mumps and rubella are collated from a number of European countries in order to compare the epidemiology of the three viruses. Key epidemiological parameters, such as the age-specific force of infection and the basic reproduction number (R0) are estimated from case notification or serological data using standard techniques. A method is described to compare force of infection estimates derived from serological data. Analysis suggests that the pre-vaccination patterns of measles and mumps infection in the different countries were similar. In contrast, the epidemiology of rubella was highly variable between countries. This suggests that it may be acceptable to use parameter values estimated from other countries to model measles and mumps transmission, but that this approach to modelling rubella transmission requires more caution. Estimates of R0 depend on underlying mixing assumptions. Constraints were placed on R0 estimates by utilising knowledge of likely mixing patterns. The estimates for R0 were highest for measles, intermediate for mumps, and generally lowest for rubella. Analysis of within- and between-age-group transmission rates suggested that mumps transmission tends to be more concentrated within young children than the other two viruses. The implications for the design of immunization programmes are that mumps may be the easiest to control via infant immunization since it is predominantly transmitted between the very young and the variability in rubella epidemiology requires that careful consideration of the possible effects of vaccination options should be made using local data when planning rubella immunization programmes.     

Difficulties in achieving and maintaining the goal of measles elimination in Bulgaria

Measles is a disease with almost a hundred year history of existing registration in Bulgaria and has been subject to mass immunization since 1969. In 2017, after a three-year period with a low number of measles cases registered, an epidemic upsurge has been recorded affecting 3 of the total 28 regions in the country. The purpose of this study was to analyze the changes of measles morbidity in Bulgaria over the period of 1921–2017 and focus on the epidemiological characteristics of the last outbreak in the region of Plovdiv in 2017. For the whole period (1921–2017) the average measles morbidity amounts to 157.69%ооо, decreasing from 525.02%ооо in 1921 to 2.32%ооо in 2017, with 99.5% rate of reduction. In the period prior to vaccination the average morbidity was 247.14%ооо while in the vaccination period it was 70.08%ооо. The ARIMA model could be used as a short-term forecast to predict the morbidity rate. Against the background of the downward tendency in morbidity this study reports a small measles outbreak in Plovdiv, involving 141 cases, after three years of no local virus transmission in the country. An unvaccinated child who returned from abroad probably imported the disease. The measles cases were mainly Roma children and a large number of them were infants. The low intensity and prolong course of the outbreak was indicative of relatively high vaccination coverage of the population. To achieve measles elimination goals, efforts must be made to strengthen surveillance and increase the vaccination coverage, targeting children and especially Roma children.