Effect of Measles Vaccination on Incidence of Measles in the Community

A study of the effect of measles vaccination on the incidence of the disease in eight separate areas of England and Wales was begun in 1966. It showed an inverse association between the proportion of children vaccinated and the incidence of measles in the area in the following year, but measles epidemics occurred in several of the areas in subsequent years, despite continuing vaccinations.Measles vaccination was introduced on a large scale in Britain in 1968. Analysis of the notification and vaccination statistics shows that the vaccination of about 10% of the child population (under 15 years) in 1968 sufficed to “replace” the measles epidemic which had been expected in the period October 1968 to September 1969 by a low incidence of the disease, typical of that in previous “interepidemic” years. Further, the effect of the vaccinations was to prevent the development of natural measles in susceptible unvaccinated children as well as in the vaccinated subjects. Thus the number of immune subjects in the community was increased by the vaccinations, but as a result there was a reduction in the number of subjects who acquired immunity from natural measles. These opposed results can therefore explain why vaccination may be effective in the community for only a year or two, though vaccination protects the individual for much longer.It is estimated that a continuing vaccination rate of 40 to 50% of the children born each year would be necessary to replace the regular biennial measles epidemics in Britain by a continuous endemic incidence, and might perhaps lead to the disappearance of the disease without a further major epidemic, but that a continuing vaccination rate of 80 to 90% of children born each year would then be necessary to prevent its reintroduction. The long-term control of measles by vaccination will thus probably prove more difficult than for any other infectious disease.     

Pulse vaccination strategy in the SIR epidemic model

Theoretical results show that the measles ‘pulse’ vaccination strategy can be distinguished from the conventional strategies in leading to disease eradication at relatively low values of vaccination. Using the SIR epidemic model we showed that under a planned pulse vaccination regime the system converges to a stable solution with the number of infectious individuals equal to zero. We showed that pulse vaccination leads to epidemics eradication if certain conditions regarding the magnitude of vaccination proportion and on the period of the pulses are adhered to. Our theoretical results are confirmed by numerical simulations. The introduction of seasonal variation into the basic SIR model leads to periodic and chaotic dynamics of epidemics. We showed that under seasonal variation, in spite of the complex dynamics of the system, pulse vaccination still leads to epidemic eradication. We derived the conditions for epidemic eradication under various constraints and showed their dependence on the parameters of the epidemic. We compared effectiveness and cost of constant, pulse and mixed vaccination policies.     

A link between the North Atlantic Oscillation and measles dynamics during the vaccination period in England and Wales

Ecologists have become aware of the role played by interannual climatic variability on the temporal dynamics of infectious diseases. In this report, I present evidence from data on measles cases in England and Wales showing that during the post-vaccination period, the interannual variability of winter weather (represented by the North Atlantic Oscillation, NAO) influences the annual dynamics of the disease. Using annual measles data from seven cities and simple logistic models, this study reveals how, after vaccination, NAO increases its effects on measles fluctuations. In addition, this study shows that vaccination may be represented as a simple vertical and lateral perturbation effect (Royama's classification), by reducing the maximum per capita growth rate and the equilibrium number of infected individuals . The results suggest that vaccination will not lead to outbreaks of measles from regular cyclic to irregular chaotic dynamics. In contrast, because of the reduction in per capita growth rates, the disease dynamics appear to be more stable than during the pre-vaccination period. The analysis of annual data on infectious diseases may be useful for detecting long-term effects of climate and complements the classical analyses and modeling based on monthly or seasonal time-step data.     

Results of virological and serological studies of three influenza A Hong-Kong epidemics in Leningrad.

An analysis of morbidity of the population in the course of 3 influenza A/Hong-Kong epidemics showed a pronounced decrease in influenza affection of adult population in the last epidemic in 1971--1972. Comparative studies of the diagnostic value of CFR and HIT demonstrated identical sensitivity of CFR as a method of influenza diagnostics in both the epidemic and interepidemic periods. HIT was suitable for the detection of influenza only in the epidemic period. In the interepidemic period, the percentage of influenza infection diagnosed by means of HIT ammounted to only 23--24 of all serologically confirmed cases of influenza. The highest percentage of virus isolation was observed when material from patients with serologically confirmed influenza was used. All strains of influenza A virus isolated in 1969 and 1970 were similar in their sensitivity to inhibitors of animal sera. During the last influenza epidemic, 2 of the 136 isolated strains were found to be resistant to gamma inhibitors and highly sensitive to the inhibitors showed their close relationship to gamma inhibitors. Antigenic analysis of the influenza A strains isolated during the 3 influenza epidemics revealed changes in the antigenic structure of the agents of the influenza epidemic in Leningrad in comparison with the standard strain A/Hong-Kong/I/68 (H3N2).     

Decline in measles mortality: nutrition,age at infection,or exposure?

The mortality from measles was studied in an urban area of Guinea-Bissau one year before and five years after the introduction of a vaccination programme. The years after the introduction of immunisation saw a decline in mortality among unvaccinated children with measles. This decline occurred despite a lower age at infection and an increasing prevalence of malnourished children. State of nutrition (weight for age) did not affect the outcome of measles infection. The incidence of isolated cases, however, increased in the period after the introduction of measles vaccination. As mortality was lower among these cases, diminished clustering explained some of the reduction in mortality. Comparison between the urban district and a rural area inhabited by the same ethnic group showed a lower age at infection, less clustering of cases, and lower case fatality ratios in the urban area.Endemic transmission of measles in urban districts leads to less clustering of cases, which may help explain the usually lower case fatality ratios in these areas. As measles vaccination increases herd immunity and diminishes clustering of cases, it may reduce mortality even among unvaccinated children who contract the disease.     

Economic effectiveness of using a live measles vaccine in an agricultural area of the Ukrainian SSR

Economic effectiveness of vaccination against measles in an agricultural region of the Ukrainian SSR has been studied. At the period preceding vaccination expenses for each measles patient in the country were three times as low as those in towns. At the period of vaccination a considerable decrease in expenses covering the payment of sick-leave certificates given to mothers taking care of their sick children, in losses connected with absenteeism, in expenses for gamma globulin prophylaxis and the hospital treatment and outpatient servicing of measles patients was observed due to the sharp drop of the total morbidity rate and the increased number of school children among measles patients. In urban and rural areas the equalization of expenses for each patient occurred. In spite of increased expenses for each measles patient, the considerable economy of sums spent for controlling measles was achieved: about 70,000 rubles per annum.     

Revaccination of children during school-based measles outbreaks: potential impact of a new policy recommendation.

OBJECTIVE: To evaluate the potential impact of revaccination on measles outbreak control during school-based epidemics. DESIGN: Retrospective cohort study. SETTING: Thirty-two public elementary and high schools in 14 communities on the west island of Montreal. PARTICIPANTS: All 19,439 children attending these schools during the 1989 measles epidemic in Quebec. INTERVENTION: After notification of a case children with provider-verified records of vaccination on or after their first birthday were identified; the remaining children were vaccinated or excluded from school. OUTCOME MEASURE: Clinical or confirmed measles cases not prevented by this intervention that could have been prevented had revaccination been included during the outbreak. RESULTS: Of the 88 measles cases (74 confirmed) proof of one adequate vaccination was present in 48 (55%). Intervention generally occurred within 5 school days after case notification. The nonpreventable cases involved 75 children who had measles onset before the intervention and 11 (7 vaccinated) who had onset within 8 days after the intervention. The two remaining cases occurred 20 and 25 days after the intervention among nonvaccinated students who refused to be vaccinated. Except for these two cases measles was eliminated at every school. Application of the new Canadian guidelines for measles outbreak control would have required the administration of at least 10,000 additional doses during the outbreak to students vaccinated before 1980; implementation of the new US guidelines would have required the administration of 16,629 additional doses to children previously vaccinated only once. Well-enforced provincial regulations ensuring vaccination of every student upon school entry might have prevented 38 (43%) of the cases. The US recommendation of two routine doses of vaccine before school entry might have prevented 86 (98%) of the cases. However, revaccination during the outbreak would not have prevented a single additional case. CONCLUSION: Revaccination of previously vaccinated students during a measles outbreak would have been costly and of little benefit.     

Implementation of a National Measles Elimination Program in Iran: Phylogenetic Analysis of Measles Virus Strains Isolated during 2010–2012 Outbreaks

Measles virus (MV) causes small and large outbreaks in Iran. Molecular assays allow identifying and the sources of measles imported from neighboring countries. We carried out a phylogenetic analysis of measles virus circulating in Iran over the period 2010–2012. Specimens from suspected cases of measles were collected from different regions of Iran. Virus isolation was performed on urine and throat swabs. Partial nucleoprotein gene segments of MV were amplified by RT-PCR. PCR products of 173 samples were sequenced and analyzed. The median age of confirmed cases was 2 years. Among all confirmed cases, 32% had unknown vaccination status, 20% had been vaccinated, and 48% had not been vaccinated. Genotypes B3 and D8 (for the first time), H1 and D4 were detected mainly in unvaccinated toddlers and young children. Genotype B3 became predominant in 2012 and was closely related to African strains. H1 strains were also found in small and large outbreaks during 2012 but were not identical to Iranian H1-2009 strains. A majority of the Iranian D4 strains during 2010–2012 outbreaks were linked to the D4 strain identified in the Pakistan in 2007. We identified a single case in 2010 belonging to D8 genotype with 99.7% identity to Indian isolates. Although the vaccination program is currently good enough to prevent nationwide epidemics and successfully decreased measles incidence in Iran, the fraction of protected individuals in the population was not high enough to prevent continuous introduction of cases from abroad. Due to increasing number of susceptible individuals in some areas, sustained transmission of the newly introduced viral genotype remains possible.     

Seasonal transmission dynamics of measles in China

Measles, a highly contagious infection caused by the measles virus, is a major public health problem in China. The reported measles cases decreased dramatically from 2004 to 2012 due to the mandatory measles vaccine program started in 2005 and the goal of eliminating measles by 2012. However, after reaching its lowest level in 2012, measles has resurged again since 2013. Since the monthly data of measles cases exhibit a seasonally fluctuating pattern, based on the measles model in Earn et al. (Science 287:667–670, 2000), we propose a susceptible, exposed, infectious, and recovered model with periodic transmission rate to investigate the seasonal measles epidemics and the effect of vaccination. We calculate the basic reproduction number \({\mathcal {R}}_{0}\), analyze the dynamical behavior of the model, and use the model to simulate the monthly data of measles cases reported in China. We also carry out some sensitivity analysis of \({\mathcal {R}}_{0}\) in the terms of various model parameters which shows that measles can be controlled and eventually eradicated by increasing the immunization rate, improving the effective vaccine management, and enhancing the awareness of people about measles.     

Implications of vaccination and waning immunity

For infectious diseases where immunization can offer lifelong protection, a variety of simple models can be used to explain the utility of vaccination as a control method. However, for many diseases, immunity wanes over time and is subsequently enhanced (boosted) by asymptomatic encounters with the infection. The study of this type of epidemiological process requires a model formulation that can capture both the within-host dynamics of the pathogen and immune system as well as the associated population-level transmission dynamics. Here, we parametrize such a model for measles and show how vaccination can have a range of unexpected consequences as it reduces the natural boosting of immunity as well as reducing the number of naive susceptibles. In particular, we show that moderate waning times (40–80 years) and high levels of vaccination (greater than 70%) can induce large-scale oscillations with substantial numbers of symptomatic cases being generated at the peak. In addition, we predict that, after a long disease-free period, the introduction of infection will lead to far larger epidemics than that predicted by standard models. These results have clear implications for the long-term success of any vaccination campaign and highlight the need for a sound understanding of the immunological mechanisms of immunity and vaccination.     

深圳市南山区西丽人民医院辖区2005-2009年麻疹疫情分析

为了掌握深圳市南山区西丽人民医院辖区内麻疹病毒流行现状,评价该院辖区麻疹疫苗接种效果,为今后制订麻疹预防控制策略提供依据。采用回顾性调查方法,将2005-2009年间的麻疹发病情况作了分析。2005、2007两年发病人数最多,发病率较高,随着麻疹疫苗强化免疫活动的开展,使疫情有了较大的下降趋势。结果表明,接种麻疹疫苗是最有效地预防麻疹疫情的手段。     

Evaluation of the eight-year period of compulsory measles vaccination in the Czech Socialist Republic (CSR)

The object of the study is the evaluation of a more than 8-year period of compulsory vaccination against measles in the CSR. So far, a total of 1,850,000 children have been vaccinated. A pronounced decrease has been achieved in morbidity while mortality and lethality reached zero values as early as in 1973. Changes occur in the epidemiological characteristic of measles manifested primarily by the shift of the age distribution of notified cases into older age groups, by continuous prolongation of interepidemic intervals and by gradual disappearances of typical seasonal incidence. Regular immunological surveys have become the most efficient tools in epidemiological surveillance of this infection and in monitoring the vaccination programme. The results of immunological surveys indeed led to the introduction in 1975 of so-called second vaccination compulsory for children starting the first year of school attendance. Up to the present, a total of 24,000 cases of measles have been recorded in children vaccinated earlier, i.e., 1.5% of the total of vaccinated children. It can be expected that measles as a mass disease will be eliminated from the territory of the CSR in the next few years.     

Impact of Birth Seasonality on Dynamics of Acute Immunizing Infections in Sub-Saharan Africa

We analyze the impact of birth seasonality (seasonal oscillations in the birth rate) on the dynamics of acute, immunizing childhood infectious diseases. Previous research has explored the effect of human birth seasonality on infectious disease dynamics using parameters appropriate for the developed world. We build on this work by including in our analysis an extended range of baseline birth rates and amplitudes, which correspond to developing world settings. Additionally, our analysis accounts for seasonal forcing both in births and contact rates. We focus in particular on the dynamics of measles. In the absence of seasonal transmission rates or stochastic forcing, for typical measles epidemiological parameters, birth seasonality induces either annual or biennial epidemics. Changes in the magnitude of the birth fluctuations (birth amplitude) can induce significant changes in the size of the epidemic peaks, but have little impact on timing of disease epidemics within the year. In contrast, changes to the birth seasonality phase (location of the peak in birth amplitude within the year) significantly influence the timing of the epidemics. In the presence of seasonality in contact rates, at relatively low birth rates (20 per 1000), birth amplitude has little impact on the dynamics but does have an impact on the magnitude and timing of the epidemics. However, as the mean birth rate increases, both birth amplitude and phase play an important role in driving the dynamics of the epidemic. There are stronger effects at higher birth rates.     

Several physiologic features of the body and their role in the process of vaccination against measles]

The work was carried out under conditions of mass measles immunization at the polyclincs of Moscow and Dushanbe. The role of the macroorganism at the time of vaccination on the measles vaccination process was investigated. A thorough study of the anamnesis, its allergic predisposition was conducted; blood and C-RB were examined, and the content of serum immunoglobulins was determined by Macini's method. The results obtained pointed to the insufficiently complete detection of children with an altered reactivity by a simple examination by the physician alone. It was revealed that children suffering from various forms of allergy having in the anamnesis hypotrophy rickets and frequent acute respiratory diseases and chronic foci of infections had decreased indice of nonsecific immunological reactivity even at the period of clinical well-being, and could be detected only by means of laboratory methods of study. To the administration of measles vaccine such children responded not only by the development of clinical reactions of different intensity, but also by a significant reduction of antibody formation. All the aforesaid indicates a necessity of further study of the mechanism of establishment of postvaccinal measles immunity with consideration to the individual reactivity of the child organism.     

Four years of measles elimination in the Czech Socialist Republic

In 1982, Czechoslovakia succeeded in eliminating measles infection throughout the country. The paper describes the strategy of the measles immunization program following its introduction in 1969, showing it to reflect the objective epidemiological situation as revealed by the regular immunological surveys carried out in a broad population sample. As it turned out, decisive for achieving and maintaining a permanent measles elimination in the country was the introduction of second vaccination into the regular immunization schedule. Since 1982, its timing of is from 6 to 10 months after primary immunization. Over the 4-year period between 1982 and 1985, confirmed measles occurred only sporadically in the CSR, 115 cases altogether, and of these as many as 67 were classified as imported or their immediate contacts (38 measles patients were tourists from abroad). Of these 115 measles cases, 52 had had vaccination prior to acquiring the disease, 46 were individuals who had never before been vaccinated and in the remaining 17 patients no vaccination data were available. The vaccine failures, at least in 18 cases, could have been explained by the primary immunization prior to reaching 15 months of age. According to the estimates, at least 670 thousand cases of measles, 470 deaths, 100 thousand complications and some 33 thousand hospitalizations had been averted between 1972 and 1985 on the territory of CSR as a result of the introduction of the measles immunization program in Czechoslovakia.     

Altered Reactivity to Measles Virus in Previously Vaccinated Children

In children vaccinated with killed measles vaccine, exposure to natural rubeola within two to four years can result in a clinical syndrome of altered measles reactivity.During a small epidemic of measles in Edmonton, Alberta, 51 children who had received their last killed measles vaccination 27 to 45 months before, were admitted to hospital with this syndrome.The syndrome consists of a prodromal cough and high fever followed by a maculopapular rash appearing on the extremities and progressing centrally. Pulmonary consolidations with or without pleural effusions were evident, but these cleared rapidly in four or five days. Initial WBC and ESR values suggested a bacterial etiology, but no pathogens could be isolated.Complement fixation titres for rubeola are present in acute and convalescent sera and indicate a definite measles infection.Previous killed measles vaccination excites a delayed hypersensitivity which is activated by the natural measles infection to account for this syndrome.It is recommended that killed measles vaccine be no longer used in routine vaccinations.     

Real-time investigation of measles epidemics with estimate of vaccine efficacy

As part of measles elimination effort, evaluation of the vaccination program and real-time assessment of the epidemic dynamics constitute two important tasks to improve and strengthen the control. The present study aimed to develop an epidemiological modeling method which can be applied to estimating the vaccine efficacy at an individual level while conducting the timely investigation of the epidemic. The multivariate renewal process model was employed to describe the temporal evolution of infection by vaccination history, jointly estimating the time-dependent reproduction number and the vaccine efficacy. Analyzing the enhanced surveillance data of measles in Aichi prefecture, Japan from 2007-08, the vaccine efficacy was estimated at 96.7% (95% confidence interval: 95.8, 97.4). Using an age structured model, the vaccine efficacy among those aged from 5-19 years was shown to be smaller than that among those from 0-4 years. The age-dependent vaccine efficacy estimate informs the age-groups to be targeted for revaccination. Because the estimation method can rest on readily available epidemiological data, the proposed model has a potential to be integrated with routine surveillance.     

Seroprevalence of measles-, mumps- and rubella-specific IgG antibodies in german children and adolescents and predictors for seronegativity

We have undertaken a seroprevalence study with more than 13,000 children, who had been included in the German KIGGS survey, a representative sample of children and adolescents 0-17 years of age. The IgG titres against measles, mumps and rubella were determined in 1 to 17 year olds While 88.8% of the children were MMR-vaccinated at least once, 76.8% of children aged 1 to 17 years showed prevalence of antibodies to MMR. The highest seronegativity was seen with respect to mumps. Gender differences were most pronounced with regard to rubella IgG titres: girls aged 14 to 17 years were best protected, although seronegativity in 6.8% of this vulnerable group still shows the need of improvement. Search for predictors of missing seroprevalence identified young age to be the most important predictor. Children living in the former West and children born outside of Germany had a higher risk of lacking protection against measles and rubella, while children with a migration background but born in Germany were less often seronegative to measles antibodies than their German contemporaries. An association of seronegativity and early vaccination was seen for measles but not for mumps and rubella. A high maternal educational level was associated with seronegativity to measles and rubella. In vaccinated children, seronegativity was highest for mumps and lowest for rubella. For mumps, high differences were observed for seronegativity after one-dose and two-dose vaccination, respectively. Seronegativity increases as time since last vaccination passes thus indicating significant waning effects for all three components of MMR.     

Revisited measles and chickenpox dynamics through orthogonal transformation

The question addressed is whether or not childhood epidemics such as measles and chickenpox are characterized by low-dimensional chaos. We propose a new method for the detection and extraction of hidden periodic components embedded in an irregular cyclical series, and study the characterization of the epidemiological series in terms of the characteristic features or periodicity attributes of the extracted components. It is shown that the measles series possesses two periodic components each having a period of one year. Both the periodic components have time-varying pattern, and the process is nonlinear and deterministic; there is no evidence of strong chaoticity in the measles dynamics. The chickenpox series has one seasonal component with stable pattern, and the process is deterministic but linear, and hence non-chaotic. We also propose surrogate generators based on null hypotheses relating to the variability of the periodicity attributes to analyse the dynamics in the epidemic series. The process dynamics is also studied using seasonally forced SEIR epidemic model, and the characterization performance of the proposed schemes is assessed.