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。     

Neonatal immunization with a Sindbis virus-DNA measles vaccine induces adult-like neutralizing antibodies and cell-mediated immunity in the presence of maternal antibodies

Infants younger than age 9 mo do not respond reliably to the live attenuated measles vaccine due the immaturity of their immune system and the presence of maternal Abs that interfere with successful immunization. We evaluated the immune responses elicited by Sindbis virus replicon-based DNA vaccines encoding measles virus (MV) hemagglutinin (H, pMSIN-H) or both hemagglutinin and fusion (F, pMSINH-FdU) glycoproteins in neonatal mice born to naive and measles-immune mothers. Despite the presence of high levels of maternal Abs, neonatal immunization with pMSIN-H induced long-lasting, high-avidity MV plaque reduction neutralization (PRN) Abs, mainly IgG2a, that also inhibited syncytium formation in CD150(+) B95-8 cells. IgG secreting plasma cells were detected in spleen and bone marrow. Newborns vaccinated with pMSINH-FdU elicited PRN titers that surpassed the protective level (200 mIU/ml) but were short-lived, had low syncytium inhibition capacity, and lacked avidity maturation. This vaccine failed to induce significant PRN titers in the presence of placentally transferred Abs. Both pMSIN-H and pMSINH-FdU elicited strong Th1 type cell-mediated immunity, measured by T cell proliferation and IFN-gamma production, that was unaffected by maternal Abs. Newborns responded to measles DNA vaccines with similar or even higher PRN titers and cell-mediated immunity than adult mice. This study is the first demonstration that a Sindbis virus-based measles DNA vaccine can elicit robust MV immunity in neonates bypassing maternal Abs. Such a vaccine could be followed by the current live attenuated MV vaccine in a heterologous prime-boost to protect against measles early in life.     

Epidemiological situation of measles in Japan and measures for its control

In 2007, measles outbreak occurred mainly among teen/twenties in Japan, and many high-school, universities and colleges were closed to reduce spread of measles. Some high school students became measles when they were in foreign countries where measles has been eliminated, visited as school excursion. Since introducing measles vaccine as routine immunization, number of measles has been reduced remarkably in Japan. However, we had measles outbreak in 2001, and total annual patients number were estimated 200-300 thausands mainly among young infants. The main reason was low immunization coverage of measles at 1 year old, and operation to give measles vaccine as "the gift for 1 year old birthday" has been introduced widely. Then immunization coverage at this age was increased up from 50-60% (2001) to 80-90% (2006) and total measles number was estimated less than 10,000 at 2005 and 2006, however, measles outbreak occurred this time among teen/twenties in 2007. The total number of adult measles (more than 15 y.o.) were higher than the number of them at 2001 outbreak. To discontinue outbreak and to eliminate measles, enhancement of measles control activities has been introduced in Japan. Two doses policy with measles and rubella (MR) vaccine at 1 y.o. and before elementary school has been introduced since 2006 and further, supplementary immunization with MR at 1st grade in junior high school and 3rd grade in high school for 5 years from 2008 will start to eliminate measles by 2012. Reporting system will be also changed from sentinels system to notify to all measles cases system. In this paper, present epidemiological situation on measles in Japan, measles elimination strategy in WPRO, and plan for measles elimination in Japan are described.     

沪191麻疹疫苗免疫持久性和影响因素的评价

１９９１～１９９８年,我们对荆州区川店镇５０３名６～１５月龄儿童进行了现行沪１９１麻疹疫苗血清流行病学效果观察,结果表明,初次免疫后１个月麻疹ＩｇＧ抗体阳转率为９１６５％,ＧＭＴ为１∶２６６７４,达保护滴度者比例为４６５％。随着时间的推移,第４年上述指标迅速下降到４６８６％、１∶１２７４和１８５％,第６年时低至２９４３％、１∶４８９和１３６％。０２ｍｌ、０３ｍｌ和０５ｍｌ麻疹疫苗组的近期和远期效果是类似的,初免后１个月时ＩｇＧ滴度越高,其免疫持久性越好;初免月龄是影响麻苗免疫效果的主要原因,６月龄初免组的免疫效果明显低于≥８月龄组。结果提示麻苗８月龄初免是可行的。     

Effectiveness of measles immunoprophylaxis and the criteria for assessing its possible elimination

The study of measles morbidity in Donetsk Province in 1960-1984 and the study of antimeasles immunity in different groups of the population have shown that the problem of the liquidation of measles cannot be solved by immunizing the population in a single administration of the vaccine. To enhance the effectiveness of the immunoprophylaxis of measles and its influence on the epidemic process, a number of problems must be solved with the aim to improve the quality of the vaccine, especially its thermal stability, to establish the possibility of shifting the beginning of immunization from 15-17 months to 12 months of age, to increase the coverage of children with immunization against measles by decreasing the number of groundless exemptions from immunization and by immunizing children in risk groups according to individual schedules and dosage, to carry out selectively the booster immunization of persons who have lost their postvaccinal immunity, as revealed by laboratory test, or in whom such loss may be supposed, to introduce the objective method (indirect hemagglutination test) for controlling the state of immunity among different groups of the population into laboratory practice at sanitary and epidemiological stations. As to the possibility of the liquidation of measles, the statement of this problem is correct, but for its solution a complex of additional prophylactic and epidemic-control measures should be taken.     

Immunostructure of school-age children inoculated against measles

The mass serological survey of school children immunized against measles was carried out by means of the hemagglutination inhibition test. As a result, 20.4% of these school children were found to be seronegative, and in 9.5% of them even the minimum concentration of measles antihemagglutinins (when titrated with 1 hemagglutinating unit of the antigen) was not detected. The accumulation of a considerable seronegative (measles-susceptible) stratum among children of school age occurred due to the low immunogenic potency of some batches of live measles vaccine, used for immunization in 1973, as well as due to the formerly practiced immunization of children under 1 year of age. A direct and close dependence of focal measles morbidity among immunized children having had contacts with the source of infection on the number of children among them, found to be seronegative after titration with 1 hemagglutination unit of measles antigen, was established.     

梅州市两次麻疹疫苗强化免疫效果分析

目的综合评估分析梅州市两次麻疹疫苗强化免疫效果,为消除麻疹提供科学依据。方法综合分析麻疹疫苗强化免疫现场调查资料、评估法定传染病报告系统中麻疹发病率的变化;随机对辖区内1～12岁健康儿童216名,采用酶联免疫吸附试验(ELISA)进行强化免疫前及完成二次强化免疫后麻疹lgG抗体水平监测。结果监测人群完成二次强化免疫后麻疹IgG抗体阳性率达100.00%(216/216),2009年强化组、2010年强化组麻疹IgG抗体保护率和几何平均滴度(GMT)分别为82.08%、87.62%和1958.83、2050.26,均显著高于强化免疫前;2009年强化免疫后麻疹年发病率由强化免疫前五年平均发病率1.71/10万下降至0.22/10万,下降率87.13%,2010年强化后麻疹年发病率再次下降(0.039/10万),下降率82.27%。结论梅州市两次麻疹疫苗强化免疫效果显著,均大幅度降低了麻疹发病率、提高了人群麻疹抗体水平。     

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).     

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.     

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。     

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.     

Study of combined vaccination against yellow fever and measles in infants from six to nine months

A study has been carried out in the Ivory Coast to assess the efficacy of a combined vaccine against yellow fever and measles relative to that of each vaccine administered separately. Healthy children aged six to nine months were recruited and divided into two age groups: less than seven months (group I) and more than eight months (group II). In each group, they were randomly assigned to receive either yellow fever vaccine only (A), measles vaccine only (B), or the combined vaccine (C). The serological responses to measles and yellow fever were assessed in 219 initially seronegative children 45 days after immunization. More than 90% of the children developed yellow fever haemagglutination inhibiting antibodies. Neither age nor combination with measles vaccine influenced the responses to yellow fever vaccine. Measles haemagglutinational inhibiting antibodies were found in 97% of the children and the seroconversion rate was influenced neither by age nor by combination with yellow fever vaccine. Younger infants had lower titres of measles antibody. No particular adverse reactions were notified during the follow up. This study shows that combined yellow fever and measles vaccines are immunogenic in infants from the age of six months. Controlling yellow fever in endemic areas and the prevention of measles in young infants may greatly benefit by this combination.     

Characteristics of the immune response of children in the Arctic to live measles vaccine

The intensity of immune response to live measles vaccine varies in children living in different climatic and geographical regions. The least intensive immunogenesis is registered in children living in the Arctic regions. The level of seroconversion in children living in these regions rises in response to measles vaccine containing a 10-fold amount of the virus per immunization dose.     

Influence of genetic and phenotypical factors on the efficiency of the vaccination of young children against diphtheria and measles

The child's sex was shown to influence the character of antibody formation only after immunization against diphtheria with live measles vaccine: girls exhibited stronger reaction to vaccination than boys. Children of different gender were found to have characteristic HLA DR markers of humoral immune response to diphtheria toxoid and measles vaccine. HLA DR7 proved to be the marker of low production of antibodies to diphtheria toxoid and measles vaccine in boys.     

Experimental vaccines against measles in a world of changing epidemiology

Vaccination with the current live attenuated measles vaccine is one of the most successful and cost-effective medical interventions. However, as a result of persisting maternal antibodies and immaturity of the infant immune system, this vaccine is poorly immunogenic in children <9 months old. Immunity against the live vaccine is less robust than natural immunity and protection less durable. There may also be some concern about (vaccine) virus spread during the final stage of an eventual measles eradication program. Opinions may differ with respect to the potential threat that some of these concerns may be to the World Health Organisation goal of measles elimination, but there is a consensus that the development of new measles vaccines cannot wait. Candidate vaccines are based on viral or bacterial vectors expressing recombinant viral proteins, naked DNA, immune stimulating complexes or synthetic peptides mimicking neutralising epitopes. While some of these candidate vaccines have proven their efficacy in monkey studies, aerosol formulated live attenuated measles vaccine are evaluated in clinical trials.     

Successful DNA immunization against measles: neutralizing antibody against either the hemagglutinin or fusion glycoprotein protects rhesus macaques without evidence of atypical measles

Measles remains a principal cause of worldwide mortality, in part because young infants cannot be immunized effectively. Development of new vaccines has been hindered by previous experience with a formalin-inactivated vaccine that predisposed to a severe form of disease (atypical measles). Here we have developed and tested potential DNA vaccines for immunogenicity, efficacy and safety in a rhesus macaque model of measles. DNA protected from challenge with wild-type measles virus. Protection correlated with levels of neutralizing antibody and not with cytotoxic T lymphocyte activity. There was no evidence in any group, including those receiving hemagglutinin-encoding DNA alone, of 'priming' for atypical measles.     

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.     

宁夏2004—2007年麻疹监测分析

为了客观评价宁夏麻疹监测系统现状,探讨控制和消除麻疹的策略。对宁夏2004—2007年麻疹流行病学和实验室监测工作进行分析。结果显示,宁夏麻疹监测系统的灵敏性较高,疑似麻疹病例标本采集率和血清学诊断率等主要监测指标已达较高水平。同时,对监测到的36株麻疹野病毒基因型进行了探讨,全部为H1基因型H1a亚型,未发现其它基因亚型。因此,宁夏亟需加速控制麻疹,应继续做好麻疹监测和麻疹疫苗免疫接种。     

Immunological effectiveness of a booster inoculation against measles in children remaining seronegative after vaccination

Booster immunization against measles with a highly immunogenic vaccine leads to the development of prolonged postvaccinal immunity lasting at least 6-7 years (the term of observation) in the groups of children found to be seronegative after the titration of their blood sera with 1 hemagglutinating unit (HAU) of the antigen. The booster immunization of children in whose blood sera the minimal concentrations of antibodies can be determined in the presence of 1 HAU of the antigen (seronegative in the presence of 4 HAU) is less effective. The serological checks of immunized children entering preschool institutions and the primary grades at schools and the subsequent booster immunization of children found to be seronegative will lead to a further decrease in measles morbidity.     

An epidemiologic and immunologic study of measles under conditions of massive immunization against that infection]

Massive measles immunization in Riga led to a marked reduction of measles incidence and to a change of the principal regularities of the epidemic process in this infection. Among those who contracted the disease there was an increase in the percentage of schoolchildren; affection with measles of children attending creches and kindergartens and the intensity of the spread of the infection in them diminished. Selective examination of the immunological efficacy of the living measles vaccine prepared of the (see article) and applied in 1967--1972 demonstrated the presence of specific stimulation of the antibody formation in about 90% of the persons vaccinated. The intensity of humoral immunity in the persons vaccinated did not diminish with the advance of time after the vaccination, and 6--7 years after the vaccination over 90% of the vaccinated individuals were reliably protected from measles. The presence of numerous negative results in carrying out the vaccinations in individual institutions is apparently attributed chiefly to disturbances of the storage regimen of transportation and of the use of the vaccine.