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.     

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.     

Case Based Measles Surveillance in Pune: Evidence to Guide Current and Future Measles Control and Elimination Efforts in India

Background

According to WHO estimates, 35% of global measles deaths in 2011 occurred in India. In 2013, India committed to a goal of measles elimination by 2020. Laboratory supported case based measles surveillance is an essential component of measles elimination strategies. Results from a case-based measles surveillance system in Pune district (November 2009 through December 2011) are reported here with wider implications for measles elimination efforts in India.

Methods

Standard protocols were followed for case identification, investigation and classification. Suspected measles cases were confirmed through serology (IgM) or epidemiological linkage or clinical presentation. Data regarding age, sex, vaccination status were collected and annualized incidence rates for measles and rubella cases calculated.

Results

Of the 1011 suspected measles cases reported to the surveillance system, 76% were confirmed measles, 6% were confirmed rubella, and 17% were non-measles, non-rubella cases. Of the confirmed measles cases, 95% were less than 15 years of age. Annual measles incidence rate was more than 250 per million persons and nearly half were associated with outbreaks. Thirty-nine per cent of the confirmed measles cases were vaccinated with one dose of measles vaccine (MCV1).

Conclusion

Surveillance demonstrated high measles incidence and frequent outbreaks in Pune where MCV1 coverage in infants was above 90%. Results indicate that even high coverage with a single dose of measles vaccine was insufficient to provide population protection and prevent measles outbreaks. An effective measles and rubella surveillance system provides essential information to plan, implement and evaluate measles immunization strategies and monitor progress towards measles elimination.     

Single endemic genotype of measles virus continuously circulating in China for at least 16 years

The incidence of measles in China from 1991 to 2008 was reviewed, and the nucleotide sequences from 1507 measles viruses (MeV) isolated during 1993 to 2008 were phylogenetically analyzed. The results showed that measles epidemics peaked approximately every 3 to 5 years with the range of measles cases detected between 56,850 and 140,048 per year. The Chinese MeV strains represented three genotypes; 1501 H1, 1 H2 and 5 A. Genotype H1 was the predominant genotype throughout China continuously circulating for at least 16 years. Genotype H1 sequences could be divided into two distinct clusters, H1a and H1b. A 4.2% average nucleotide divergence was found between the H1a and H1b clusters, and the nucleotide sequence and predicted amino acid homologies of H1a viruses were 92.3%-100% and 84.7%-100%, H1b were 97.1%-100% and 95.3%-100%, respectively. Viruses from both clusters were distributed throughout China with no apparent geographic restriction and multiple co-circulating lineages were present in many provinces. Cluster H1a and H1b viruses were co-circulating during 1993 to 2005, while no H1b viruses were detected after 2005 and the transmission of that cluster has presumably been interrupted. Analysis of the nucleotide and predicted amino acid changes in the N proteins of H1a and H1b viruses showed no evidence of selective pressure. This study investigated the genotype and cluster distribution of MeV in China over a 16-year period to establish a genetic baseline before MeV elimination in Western Pacific Region (WPR). Continuous and extensive MeV surveillance and the ability to quickly identify imported cases of measles will become more critical as measles elimination goals are achieved in China in the near future. This is the first report that a single endemic genotype of measles virus has been found to be continuously circulating in one country for at least 16 years.     

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。     

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

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

Measles: immune suppression and immune responses

Measles is a highly contagious viral disease that remains the leading vaccine-preventable cause of child mortality worldwide. Deaths from measles are due largely to an increased susceptibility to secondary bacterial and viral infections, attributed to a prolonged state of immune suppression. Several abnormalities of the immune system have been described, including changes in lymphocyte number and function, shifts in cytokine responses, immunomodulatory effects of interleukin-10, down regulation of interleukin-12, impaired antigen presentation, and altered interferon alpha/beta signaling pathways. Although the current vaccine is very effective, knowledge of the molecular basis of the immune responses to measles virus could contribute to the development of a safer, more immunogenic measles vaccine. However, the safety of new measles vaccines must be carefully investigated, as two measles vaccines have resulted in unintended immunologic consequences: atypical measles following administration of the formalin-inactivated measles vaccine and increased mortality in girls following administration of high-titer measles vaccines.     

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。     

Impact of vaccination on selected diseases in Canada

Vaccination has dramatically reduced the morbidity and mortality rates of a number of diseases. The crucial element of vaccination programs is commitment to widespread coverage and to containment of outbreaks. Vaccines have led to virtual elimination of poliomyelitis and promise to eliminate measles. The incidence of congenital rubella syndrome will probably only be diminished if vaccination is extended to all 1-year-olds and susceptible prepubertal girls. The employment of diphtheria toxoid is one of the great success stories in public health. The incidence of pertussis has declined because of the diphtheria-pertussis-tetanus (DPT) vaccine given to infants, although elimination of the disease will probably have to await development of a more potent pertussis antigen. A remarkable reduction in the incidence of tetanus and tuberculosis has also been achieved.     

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.     

佛山市南海区2004—2010年麻疹流行病学特征分析及控制策略探讨

了解佛山市南海区2004—2010年麻疹流行病学特征,为进一步完善和制订消除麻疹策略与措施提供科学依据。采用流行病学方法对佛山市南海区2004—2010年麻疹发病资料进行分析。结果显示,佛山市南海区2004—2010年累计确诊麻疹病例1 376例,年平均发病率为9.24/10万;全年均有发病,3～8月是麻疹高发季节,但近年来随着麻疹防控措施的落实,季节性已不明显;麻疹发病以5岁以下儿童为主,占总发病数的55.7%,,近年来麻疹发病年龄趋势向<1岁人群组和≥15岁人群组发展,这两个年龄组发病数占总发病人数的62.8%;病例中无免疫史或免疫史不详者占92.2%。佛山市南海区麻疹发病年龄分布已逐步呈现"双向位移"现象,加强对重点人群、重点地区的免疫规划管理,提高麻疹疫苗接种率,是控制麻疹发病的有效措施。同时适时开展强化免疫接种是保护易感人群,进而实现消除麻疹的重要策略.     

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.     

潍坊市2007-2012年消除麻疹策略与效果评价

目的了解潍坊市2007-2012年麻疹疫情流行规律,为消除麻疹策略提供科学依据。方法采用描述性流行病学方法,研究探讨潍坊市2007-2012年麻疹流行规律。结果2007-2012年潍坊市报告麻疹确诊病例385例,均为散发病例,无死亡病例,年均发病率为0．72／10万,其中2008、2010年出现两个发病高峰,发病率分别为1．49／10万、1．17／10万,2012年发病率降至0．033／10万。3-5月为发病高峰,病例主要集中在寿光、诸城、安丘、青州四个市,占72．73％（280／385）。发病年龄最小2个月,最大63岁,病例年龄以〈1岁婴儿和20-44岁成年人为主。职业以民工、工人、农民和散居儿童为主,民工、工人和农民所占比例平均为52．47％（202／385）;散居儿童所占比例平均为22．08％（85／385）;民工、工人、农民和散居儿童发病人群所占比例逐渐升高,托幼儿童和学生逐渐降低。≥8月龄病例中有明确麻疹疫苗免疫史者96例,占26．74％;其中8月龄～14岁有明确麻疹免疫史者66例,占该年龄组病例的66％。结论潍坊市麻疹发病年龄构成以小于1岁婴儿和20～44岁成年人为主,出现向两极移动现象,1岁以下婴幼儿发病呈上升趋势。今后要提高常规免疫接种率和及时接种率,降低小年龄儿童麻疹发病率,适时对重点地区、重点人群开展麻疹疫苗强化免疫,消除免疫空白。     

克拉玛依市2008年麻疹监测与控制情况分析

分析克拉玛依市麻疹流行状况及预防控制措施,为消除麻疹提供依据。采用描述流行病学分析方法,对2008年克拉玛依市麻疹资料进行分析。结果显示,克拉玛依市2008年麻疹发病率为38.83/10万(138/355381),呈高度散发,较2007年有所上升。发病高峰在3～5月,发病数占全年的83.33%。年龄分布大年龄组高于小年龄组,>20岁年龄组病例占50.00%,<1岁病例占18.84%;流动人口发病占51.11%。应切实提高麻疹常规免疫接种率和做好入托、入学儿童查验预防接种证工作,加强麻疹监测,提高实验室确诊病例的比例。     

Evidence of recombination among early-vaccination era measles virus strains

Background  

The advent of live-attenuated vaccines against measles virus during the 1960'ies changed the circulation dynamics of the virus. Earlier the virus was indigenous to countries worldwide, but now it is mediated by a limited number of evolutionary lineages causing sporadic outbreaks/epidemics of measles or circulating in geographically restricted endemic areas of Africa, Asia and Europe. We expect that the evolutionary dynamics of measles virus has changed from a situation where a variety of genomic variants co-circulates in an epidemic with relatively high probabilities of co-infection of the individual to a situation where a co-infection with strains from evolutionary different lineages is unlikely.     

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。     

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.     

Are we protected? Imported measles - on the way to eradication

In accordance with the 2015 regional goal for measles and rubella elimination of the WHO European Region, only a few imported cases have been documented of both diseases in Hungary for years.This paper presents a case of a Hungarian woman, born in 1975, who received measles vaccination at age of 12 months and later at age of 11 years, according to her certificate of vaccination. In 2009, after arriving home from a vacation in Ireland, she developed acute measles infection with clinical symptoms. It was confirmed by the detection of measles specific IgM, IgA and IgG antibodies, and by detection of viral nucleic acid from throat swab in virus transport medium.Additionally, an outbreak occurred in December of 2011 among a family emigrated from Romania to Hungary. No new measles cases were diagnosed among the contact persons of neither the young Hungarian woman returning from Ireland, nor the family emigrated from Romania. This observation refers to the effectiveness of the Hungarian vaccination program.     

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。     

日照市2005—2011年麻疹监测分析

目的分析日照市2005—2011年麻疹流行病学特征,为制定消除麻疹策略及措施提供依据。方法对日照市2005—2011年麻疹监测系统资料进行描述流行病学分析。结果日照市2005—2011年共报告麻疹病例193例,其中2011年无病例报告,年平均报告发病率0.97/100 000。麻疹病例分布各区县,但不同区县之间存在差异,发病高峰在3—6月,以15岁以上大年龄组发病为主;散发和暴发并存,散发以本土病例为主,共暴发疫情3起,均为输入性病例。结论日照市消除麻疹已取得显著进展,应继续保持和巩固高水平儿童基础免疫接种率,高质量地完成MV SIA,加强监测和风险评估,做好暴发疫情的预警与控制工作,实现消除麻疹。