Expanded program on immunization and its implementation in the Czech Socialist Republic

National immunization programs carried out in the CSR are here confronted with the EPI regional targets for Europe, a component of the WHO global program "Health for all by the year 2000". The EPI target diseases to be brought under control in Europe by 1990 include measles, poliomyelitis, diphtheria and neonatal tetanus; control of congenital rubella infection is to be achieved by the year 2000. The presented data show that Czechoslovakia has succeeded in implementing this program much ahead of the WHO time schedule. The elimination of measles infection was achieved in 1982, poliomyelitis was brought under control in 1961, and the effective diphtheria control has been in effect since the mid-1960s. Cases of neonatal tetanus are absent in the CSR since 1965, the annual incidence of postnatal tetanus is permanently 0.1-0.2 per 100,000 population. The goal of achieving the rubella-free status and thus the elimination of congenital rubella cases at country level is expected to be reached in the early 1990s. Implementation of the remaining WHO recommendations pertinent to infections other than EPI target diseases appears also satisfactory. Regular immunization against whooping cough, one of the oldest immunization programs in Czechoslovakia, succeeded in effectively eliminating this infection in the early 1970s. Selective immunization campaigns against influenza infection, introduced many years ago, help protect, together with a large-scale use of available chemoprophylactics, some 200,000 individuals every year in CSR. The hepatitis B immunization program was started in 1983 and is primarily limited to health service staff, which is in line with the existing WHO recommendations. Inception of the regular immunization program against mumps is planned for the beginning of 1987.     

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.     

Swedish experience of two dose vaccination programme aiming at eliminating measles,mumps, and rubella.

In 1982 a two dose regimen was introduced in Sweden for the combined vaccination against measles, mumps, and rubella of children aged 18 months and 12 years. Since 1977 about half of the preschool children were vaccinated against measles annually, and since 1974 about 80% of 12 year old girls were vaccinated against rubella. During the period 1982 to 1985 90-93% of the eligible age cohorts of 18 month old children and 88-91% of the 12 year old children were immunised with the new combined vaccine. A study in 1982 of about 140 18 month old children who were nearly all seronegative before vaccination showed that 96%, 92%, and 99% seroconverted against measles, mumps, and rubella, respectively. A second study was carried out in 1983 of 247 12 year old children, of whom 11% lacked antibodies to measles, 27% to mumps, and 45% to rubella. This showed seroconversion in 82% and 80% against measles and mumps, respectively, and all children seroconverted against rubella. In the latest study in 1985 of 496 12 year olds 9% and 13% were seronegative against measles and mumps before vaccination, and 41% against rubella. Of these, 88% seroconverted to measles and 80% to mumps, and all converted to rubella when sera were tested by the haemolysis in gel method. After a neutralisation test against measles as well all children showed immunity to the disease. A low incidence of measles and declining figures for mumps and rubella were reported in 1984 to 1986. An outbreak of rubella during 1985 affected mainly boys in age cohorts in which only the girls had been vaccinated during the 1970s.     

佛山市2004—2009年麻疹流行病学分析和防治措施探讨

通过分析近年来佛山市麻疹流行病学特征,为探讨麻疹控制措施提供理论依据。对2004—2009年麻疹发病情况进行描述性流行病学分析。结果显示,佛山市2004—2009年共报告麻疹病例3 599例,年平均发病率为10.19/10万;发病数前3位的区为顺德区、南海区、禅城区,占全市病例数的94.50%;4～8月为高发季节,占总病例数的66.60%;6岁以下儿童及15岁以上人群是麻疹发病主要人群,分别占总病例数的62.86%、31.54%;8月龄以下儿童发病数占14.48%;病例以流动人口为主,占总病例数的94.78%;有明确免疫史病例仅占总病例数10.22%。佛山市麻疹发病有回升趋势,疫情形势严峻。实施麻疹疫苗强化免疫和查漏补种是控制麻疹的有效措施;同时应采取加强流动人口管理,提高麻疹疫苗常规免疫接种率和及时率,加强麻疹监测和入学、入托查验证管理,控制医院内感染,强化疫区处理等综合防控措施。     

Deciphering the relative weights of demographic transition and vaccination in the decrease of measles incidence in Italy

In Italy, during the course of the past century to the present-day, measles incidence underwent a remarkable decreasing trend that started well before the introduction of the national immunization programme. In this work, we aim at examining to what extent both the demographic transition, characterized by declining mortality and fertility rates over time, and the vaccination programme are responsible for the observed epidemiological pattern. Making use of a non-stationary, age-structured disease transmission model, we show that in the pre-vaccination era, from 1901 to 1982, the decline in birth rates has resulted in a drastic decrease in the effective transmission rate, which in turn has determined a declining trend of measles incidence (from 25.2 to 10.3 infections per 1000 individuals). However, since 1983, vaccination appears to have become the major contributing factor in the decrease of measles incidence, which otherwise would have remained stable as a consequence of the nearly constant birth rates. This led to a remarkable decrease in the effective transmission rate, to a level well below the critical threshold for disease persistence. These findings call for the adoption of epidemiological models, which deviate the age structure from stationary equilibrium solutions, to better understand the biology of infectious diseases and evaluate immunization programmes.     

The duration and strength of postvaccinal measles immunity

A prolonged immunoepidemiological follow-up of a large group of children immunized against measles revealed a high epidemiological efficacy of a single vaccination. Cases of measles were registered only among those vaccinees in whose blood sera no specific hemagglutinins were detectable by titration with 4 hemagglutinating units of measles antigen prior to the disease. The study showed that groups of children seronegative with respect to measles appeared, as a rule, after unsatisfactory immunization and not due to loss of postvaccinal immunity with time. Properly immunized children in whom the formation of antimeasles antibodies had occurred in response to the injection of live measles vaccine retained postvaccinal immunity for more that 15 years (the term of observation).     

The control of viral diseases in the developing countries with the use of existing vaccines]

In developing countries, every year about 70 million measles cases occur with 1.5 million deaths, over 200,000 children contract paralytic poliomyelitis, 50 million people get infected with viral B hepatitis causing over 1 million deaths, and several thousand people perish because of yellow fever according to WHO data. At the present time, there are 12 vaccines against viruses: vaccines against German measles and mumps in addition to the above. The universal immunization program (UIP) of WHO targets measles and polio. In 1989, a WHO resolution envisioned a 90% immunization coverage by the year 2000. Measles vaccination is recommended for children aged 9-23 months, since most children have maternal antibodies during the first 3-13 months of age. The Edmonston-Zagreb vaccine provided seroconversion of 92, 96, and 98% for 18 months vs. the 66, 76, and 91% rate of the Schwarz vaccine. In the US, measles incidence increased from 1497 cases in 1983 to 6382 cases in 1988 to over 14,000 cases in 1989, prompting second vaccination in children of school age. The highest incidence of polio was registered in Southeast Asia, although it declined from 1 case/100,000 population in 1975 to .5/100,000 in 1988. Oral poliomyelitis vaccine (OPV) provides protection: there is only 1 case/2.5 million vaccinations. Hepatitis B has infected over 2 billion people. About 300 million are carriers, with a prevalence of 20% in African, Asian, and Pacific region populations. Plasmatic and bioengineered recombinant vaccine type have been used in 30 million people. The first dose is given postnatally, the second at 1-2 months of age, and the 3rd at 1 year of age. Yellow fever vaccine was 50 years old in 1988, yet during 1986-1988 there were 5395 cases with 3172 deaths in Africa and South America. Vaccination provides 90-95% seroconversion, and periodic follow-up vaccinations under UIP could eradicate these infections and their etiologic agents.     

Catch-up immunization programs will eliminate measles threat for most schoolchildren.

The threat of measles will be eliminated for 72% of Canadian schoolchildren this spring as seven provinces/territories establish routine two-dose schedules for measles-mumps-rubella vaccination, including five jurisdictions that are undertaking universal catch-up immunization programs. The initiatives move the country closer to its commitment to eradicate measles by the year 2000.     

我们离麻疹消除还有多远?

中国麻疹发病率自2008年起出现大幅度下降,但2012年底以来麻疹发病疫情呈上升趋势,部分城市出现了以成人为主的疫情暴发。导致麻疹疫情再次上升的一个可能原因是中国的麻疹疫苗实际接种率低于报告接种率,常规免疫有不到位的情况。同时,中国存在部分麻疹免疫空缺人群,既未接种过麻疹常规疫苗,也没有参加过2004—2010年的补充免疫活动。这类人群积累到一定程度后,可引起聚集性的疫情暴发。中国在消除麻疹方面虽已取得显著进展,但近年来疫情再次抬头值得警惕。进一步增加常规麻疹两剂疫苗接种率,对重点地区和人群适当增加补充免疫活动,更好地落实麻疹应急预案等,将有助于控制并消除麻疹疫情。     

A long-term follow-up study on the efficacy of further attenuated live measles vaccine, Biken CAM vaccine

Antibody persistence was measured in 39 children in an open community 12-13 years after immunization against measles with further attenuated live vaccine, Biken CAM. Serum samples of the children taken every two or three years after vaccination had higher, lower, or the same HI antibody titers as those in samples taken 6 weeks after vaccination. These differences reflected a decrease in the titer in some children and subclinical natural reinfection in others. However, all the children still retained detectable antibody in 12 or 13 years after vaccination, indicating long-term persistence of immunity after immunization with Biken CAM vaccine. For evaluation of the protective efficacy of the vaccine, matched controls were studied during the same period. Serological examination revealed that 97.5% of the controls were infected with measles and contracted the disease. In contrast, none of the vaccinees developed clinical infection after close contact with measles patients.     

A dynamic,multi‐level analysis of recent immunization trends in Colombia

Abstract

During 1985–91, Latin American ministries of health carried out the ultimately successful Regional Polio Eradication Initiative. Unprecedented vaccine coverage levels were attained through a combination of mass campaigns, house‐to‐house vaccinations, and improvements in routine immunization services. Little is known, however, about the effects of these interventions on immunization demand; whether they reached so‐called high‐risk households and, if so, whether program effects were sufficient to offset the household risk factors. This paper examines the probability and timing of full immunization over this period in one case country, Colombia. Information on the immunization status of 3,609 vaccine‐eligible children born 1985–90 was extracted from Colombia's 1990 Demographic and Health Survey. Annual immunization coverage estimates from the Colombian Ministry of Health for 1985–90 for 148 sample municipios were appended to each child record, along with household‐level data. Initial non‐parametric regressions showed that five of six observed risk factors negatively influenced full immunization probability. Multivariate logit models showed that parents who had already lost a child were significantly less likely to obtain immunization cards (a proxy for exposure to the routine immunization program), despite rising cardholdership rates over the period. Among 1,376 immunization cardholders, waiting times to full immunization fell monotonically over the period. Local program coverage of 80 per cent or higher and prior use of prenatal services both increased the probability of full immunization. However, three of five maternal occupational categories decreased the probability, as did three of six observed household risk factors. The results show that demand for routine immunizations rose over the period, that only the highest‐risk households were not exposed to the routine program, and that routine program participation partially offset negative risk factor effects on the probability of full immunization. While targeted PHC interventions may increase health production by recruiting high‐risk households into the routine PHC services, further health production increases will require more intensive follow‐up of such households through routine PHC services.     

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.     

甘肃省麻疹监测系统报告病例的流行病学分析

目的分析甘肃省近年来麻疹报告发病特点,为实现消除麻疹目标措施的制定提供参考依据。方法对甘肃省2009—2010年疾病监测信息报告系统和麻疹监测系统报告的疑似麻疹病例进行分析。结果 2009—2010年报告麻疹病例1 463例,主要集中在15岁以下年龄组,占病例总数的74.16%,≥15岁病例占病例总数的25.91%。4～7月为发病的高峰季节。对15岁以下进行流行病学调查的病例分析,20.86%的病例未接种过麻疹类疫苗,32.71%的病例免疫史不详。对病例的接触史分析,在发病前7～21d有5.82%的病例明确接触过发热出疹性病人,有12.43%的病例曾去过医院。分离出麻疹病毒H1a基因型,对麻疹疫苗免疫和疫情的防控有指导意义。结论根据麻疹发病年龄构成及免疫史分析,个别地区常规免疫接种不足是造成麻疹发病的主要原因,同时要注意控制院内感染的发生。需要在提高麻疹疫苗常规免疫覆盖率的基础上,进一步深入和规范监测工作,提高监测调查质量。     

郑州市麻疹疫苗强化免疫前后麻疹流行病学特征分析

目的了解郑州市麻疹疫苗强化免疫对疾病流行特征的影响,为消除麻疹采取针对性措施提供科学依据。方法对郑州市麻疹强化免疫活动前后的2010年和2011年麻疹发病情况进行描述性流行病学分析。结果郑州市强化免疫后麻疹病例大幅减少,2011年较2010年病例数减少90%;全年病例散发,无明显季节性高峰出现;病例构成仍以1岁以下儿童和无免疫史者为主;城区发病高于农村。结论此次麻疹强化免疫活动效果明显,致使麻疹发病率显著下降。     

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.     

河南省漯河市2005—2010年麻疹流行病学分析

目的掌握河南省漯河市麻疹流行特征与规律,探讨漯河市麻疹防治对策与措施。方法收集漯河市2005—2010年麻疹疫情及监测资料,用Excel统计软件进行分析。结果漯河市2005—2010年共报告麻疹病例683例,平均发病率为4.55/10万,2005—2007年发病率逐年上升,2008—2010年逐年下降,3—5月份为发病高峰,发病年龄以≤3岁散居儿童为主。结论提高麻疹疫苗常规免疫接种覆盖率及8月龄儿童麻疹疫苗及时接种率是控制和消除麻疹的关键。     

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。     

Acute Measles Encephalitis in Partially Vaccinated Adults

Background

The pathogenesis of acute measles encephalitis (AME) is poorly understood. Treatment with immune-modulators is based on theories that post-infectious autoimmune responses cause demyelination. The clinical course and immunological parameters of AME were examined during an outbreak in Vietnam.

Methods and Findings

Fifteen measles IgM-positive patients with confusion or Glasgow Coma Scale (GCS) score below 13, and thirteen with uncomplicated measles were enrolled from 2008–2010. Standardized clinical exams were performed and blood collected for lymphocyte and measles- and auto-antibody analysis. The median age of AME patients was 21 years, similar to controls. Eleven reported receiving measles vaccination when aged one year. Confusion developed a median of 4 days after rash. Six patients had GCS <8 and four required mechanical ventilation. CSF showed pleocytosis (64%) and proteinorrhachia (71%) but measles virus RNA was not detected. MRI revealed bilateral lesions in the cerebellum and brain stem in some patients. Most received dexamethasone +/− IVIG within 4 days of admission but symptoms persisted for ≥3 weeks in five. The concentration of voltage gated calcium channel-complex-reactive antibodies was 900 pM in one patient, and declined to 609 pM ∼ 3 months later. Measles-reactive IgG antibody avidity was high in AME patients born after vaccine coverage exceeded 50% (∼ 25 years earlier). AME patients had low CD4 (218/µl, p = 0.029) and CD8 (200/µl, p = 0.012) T-cell counts compared to controls.

Conclusion

Young adults presenting with AME in Vietnam reported a history of one prior measles immunization, and those aged <25 years had high measles-reactive IgG avidity indicative of prior vaccination. This suggests that one-dose measles immunization is not sufficient to prevent AME in young adults and reinforces the importance of maintaining high coverage with a two-dose measles immunization schedule. Treatment with corticosteroids and IVIG is common practice, and should be assessed in randomized clinical trials.     

Immunization

Vaccines have eliminated or substantially reduced the incidence in Canada of smallpox, poliomyelitis, measles, mumps, rubella, diphtheria, tetanus and pertussis. The Canadian Medical Association (CMA) advocates a single immunization schedule, complete for all age groups and diseases where immunization is indicated and available. CMA has endorsed in principle (1984), the second edition of the Guide to Immunization for Canadians compiled by the National Advisory Committee on Immunization and requested that it be disseminated to all practising physicians in Canada. CMA also firmly endorses the concept of a readily accessible nationwide method of recording immunization status. In keeping with the World Health Organization''s commitment to global control of measles, CMA (1981) supports and encourages mandatory vaccination against measles for children. The association advocates a much more aggressive and sustained public education program to promote public awareness and acceptance of immunization.