Global measles elimination

Measles remains a leading vaccine-preventable cause of child mortality worldwide, particularly in sub-Saharan Africa where almost half of the estimated 454,000 measles deaths in 2004 occurred. However, great progress in measles control has been made in resource-poor countries through accelerated measles-control efforts. The global elimination of measles has been debated since measles vaccines were first licensed in the 1960's, and this debate is likely to be renewed if polio virus is eradicated. This review discusses the pathogenesis of measles and the likelihood of the worldwide elimination of this disease.     

Cell-associated immunity to measles (rubeola): The demonstration of in vitro lymphocyte tritiated thymidine incorporation in response to measles complement fixation antigen

Lack of a reliable in vitro assay for lymphocyte responsiveness to measles (rubeola) has hampered our understanding of the cell-associated response in diseases caused by, or related to, the measles virus. We report a reliable and reproducible system for demonstrating specific lymphocyte incorporation of ³H-thymidine in response to measles complement fixation antigen (CFA). Seventeen patients with positive histories of measles as children demonstrated a dose-response curve that varied between individuals but was constant for each individual. Kinetic data disclosed maximal responsiveness on day 7, and viral inactivation experiments disclosed that live virus was neither necessary for nor inhibitory to the reaction. The implications of this assay in terms of our understanding of the cell-associated response to measles virus in clinical measles and SSPE are discussed. The concept is explored that membrane-associated antigen is crucial in demonstrating the host's cellular immune response to viruses that can grow by cell-to-contiguous cell spread.     

Characterization of an RNA-dependent RNA polymerase activity associated with measles virus

An RNA-dependent RNA polymerase activity has been found copurifying with measles virus infectivity and complement-fixing antigen in three Vero cell-grown variants of measles virus: the attenuated Edmonston B strain, the natural non-attenuated Edmonston strain, and a subacute sclerosing panencephalitis isolate, IP-3. Incubation of purified measles virions with immunoglobulin G derived from sera of monkeys hyperimmunized against measles specifically removes activity sedimenting in the density region of measles virions. The requirements of the reaction, which is RNase sensitive, are similar to those reported for other paramyxovirus-associated activities, including detergent, divalent cation, ribonucleoside triphosphates, and a reducing agent. The size classes of RNA synthesized correspond to those found in measles-infected cells, including 50, 35, and 16 to 20S. The product RNA of the Edmonston B virus-stimulated reaction was rendered RNase resistant by annealing with RNA extracted from purified Edmonston B virions. RNA from uninfected Vero cells was ineffective in the annealing reaction.     

Use of the leukocyte adherence inhibition reaction for assessing the effectiveness of vaccination against measles

The reaction of the inhibition of leukocyte adhesion to a glass slide under the action of measles antigen may be used for the evaluation of the activity of antigen-specific T-lymphocytes in the process of immunization against measles and recommended, along with serological studies, for finding out persons susceptible to measles among vaccinees. The immunological effect of booster immunizations against measles can be evaluated by the degree of the inhibition of leukocyte agglutination to a glass slide.     

Leucocyte migration inhibition test as an index of immunological response to measles virus II. Immunogenic activity of measles virus.

Experiments discussed in this paper aimed at obtaining, using Cercopithecus aethiops monkeys information on immunogenic activity of measles virus as well as kinetic and persistence of immunological reaction at active and inactivated virus.     

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.     

麻疹77例临床分析

目的 分析2005年77例麻疹病人的发病与流行病学特征。方法 回顾性分析我院2005年收治的77例麻疹病人的年龄、预防接种史、发病时间、临床表现、并发症、实验室检查及预后等资料。结果 麻疹发病高峰时间集中在3～6月份,发病年龄主要在20～49岁(94．8％),高热持续1周的病人数多(62．3％),有扁桃体炎(10．9％)、血尿(8．2％)、腹泻(5．5％)、口腔溃疡(4．1％)、心悸(2．7％)等临床表现;并发症表现为:肝功能异常(63．6％)和肺部感染(16．9％);77例麻疹患者中75例麻疹抗体IgM阳性;预后良好。结论 麻疹该年出现的高峰时间在3～6月份,以成人发病为主,并以外来人群居多,高热持续时间长,并发症以肝功能异常最多见,麻疹抗体IgM仍是实验室诊断的主要指标。     

Sputum cytology in measles infection. A case report

A resurgence of measles, a highly infectious viral infection, has occurred in the United States. In this report the sputum cytology from a case of measles pneumonia is described and discussed. Only a few recent reports have described the cytopathologic changes of measles. Familiarity with the typical cytologic changes of measles will assist in the diagnosis of this infection.     

The measles virus

Summary Measles is one of widely spread virus infections that is a major cause of deaths in some tropical areas. The measles virus is a member of the genus of Morbillivirus of the family of Paramyxoviridae. The virions contain six polypeptides, including one glycoprotein; two of them are surface proteins that possess hemagglutinating and hemolytic activities, one of them is polymerase. Replication of the measles virus is similar to that of other Paramyxoviruses. Besides the acute infection for measles virus a persistent infection is characteristic that affects central nervous system and inner organs. Molecular mechanisms of it were studied and the results are discussed to explain the pathogenesis of subacute sclerosing panencephalitis, systemic lupus erythematosus and other diseasis in which measles or measles-like virus may be involved.     

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。     

104例麻疹病例的流行病学分析

目的分析平顶山市麻疹病例发生的原因,为加速控制和消除麻疹提供科学依据。方法对平顶山市2013年法定传染病疫情报告资料和麻疹监测资料进行流行病学分析。结果平顶山市2013年共报告麻疹104例,年发病率为2.11/10万,2~4月为发病高峰;男女发病率差异有统计学意义,发病以3岁以下儿童居多,占发病总数的86.54%;其中8月龄~1岁者最多,占39.42%;14岁以上者9例,占8.65%,其他年龄组发病率随年龄增大而逐步下降。从病例就诊、住院时间上推断其感染方式可能以医院内感染为主。结论常规免疫接种率和首针及时接种率不高是麻疹高发的主要原因,医院内交叉感染是麻疹的传播因素,提高易感人群麻疹疫苗接种率,控制院内感染是控制、消除麻疹的有效手段。     

Molecular epidemiology of measles virus

Genetic analysis of viruses associated with recent outbreaks of measles in the United States indicated that at least four genotypes were present during 1994 and 1995. None of these more recent genotypes were related to the genotype responsible for the resurgence of measles cases in the United States between 1989 and 1992. The sequence data confirmed that the majority of measles cases that occurred in the United States between 1994 and 1995 were the result of international importation of virus. The data also suggested that transmission of the genotype associated with the resurgence had been interrupted by aggressive control measures. Therefore, molecular epidemiologic studies will provide a powerful means to measure the success of measles control strategies.     

Isolation and study of the immunobiological properties of the recombinant proteins of measles virus

Recombinant proteins rN (nucleocapsid) and rH/Nh (hemagglutinin) of the measles virus strain NovO/96 of genotype A were obtained. The immunobiological properties of the proteins were studied in the reaction with a panel of positive and negative sera. Mice of the line Balb/C were immunized with recombinant proteins and native antigen of the measles virus strain NovO/96 in order to obtain hyperimmune serum and its analysis using ELISA (enzyme-linked immunosorbent assay) and PRN (plaque reduction neutralization). The hyperimmune serum against recombinant proteins and native antigen of the measles virus strain NovO/96 were found to be highly active in ELISA. The antibodies against the proteins rN and rH/Nh were found to be able to neutralize the virus in titer 1:13.5 and 1:22.9, respectively. The neutralization titer of the antibodies generated against native antigen of the measles virus strain NovO/96 was 1:25.7.     

A role for nonprotective complement-fixing antibodies with low avidity for measles virus in atypical measles

In the 1960s, a formalin-inactivated measles vaccine (FIMV) predisposed recipients to atypical measles, an immune complex-mediated disease. To identify characteristics of the immune priming that leads to atypical measles, responses of monkeys to FIMV were compared with responses to live attenuated virus (LAV) and hemagglutinin (H-DNA) vaccines that do not prime for atypical measles. Antibodies induced by FIMV were transient and avidity did not mature. Antibodies induced by LAV and H-DNA vaccines were sustained and avidity matured over time. After challenge with measles virus, FIMV and H-DNA recipients developed high titers of complement-fixing antibodies. In FIMV recipients, the antibodies were of low avidity, whereas in H-DNA vaccine recipients, the antibodies were of high avidity. Neutralizing capacity in B958 cells correlated with avidity. Only FIMV recipients had immune complex deposition. Failure of FIMV to induce affinity maturation results in anamnestic production of nonprotective, complement-fixing antibodies, immune complex deposition and atypical measles.     

Development of antibody to measles virus polypeptides during complicated and uncomplicated measles virus infections.

Immune precipitation of 181 sera from 152 patients with natural measles was studied to determine the temporal course and frequency of antibody responses to nucleocapsid, fusion, hemagglutinin, and matrix proteins of measles virus. Large amounts of antibody to nucleocapsid protein developed in all patients by day one of the rash. Antibody to hemagglutinin and fusion proteins developed in all patients over the next 3 weeks, the former to high levels and the latter to low levels. Antibody to matrix protein developed to very low levels and was detectable in only 41% of the patients; this poor response to matrix protein was not correlated with the age of the patient or the acute neurological complications of measles.     

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.     

Immunoepidemiological observations on the duration of post-vaccinal immunity in children vaccinated against measles

In the course of 4 years the authors carried out an immunological and epidemiological observation over 4719 children which attended creches, kindergartens and schools, and were vaccinated with live measles vaccines L-16 and ASC in 1967--1972. A stable persistence of immunity was revealed in the majority of children vaccinated against measles which responded to the vaccination by the formation of humoral antibodies. Among these groups an insignificant number of persons with the appearance of measles sensitivity was noted during the observation period. The quality of the preparation, conditions of its storage, use, and different errors during the vaccination influenced the efficacy of the vaccination. Children immunized with the low-immunogenic series of the vaccine whose blood sera failed to display any specific antibodies in the reaction with 1 AU of the antigen, as a rule, were the ones that contracted the disease.     

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.     

Equilibrium centrifugation of measles virus

Measles virus has been centrifuged on different density gradients. It sediments at densities of 1,20 g/cm³ in K-tartrate, of 1,18–1,21 g/cm³ in sucrose, 1,19–1,23 g/cm³ in CsCl and 1,19 g/cm³ in metrizamide gradients. Metrizamide reduced measles virus infectivity. In sucrose gradients sometimes more than one infectious peak was observed. Control Vero cells produced particles of the same densities as measles virus peaks. These peaks did contain actin as the major protein. The relevance of this finding in relation to the presence of actin in measles virus is discussed.