[Molecular epidemiological study of measles viruses isolated in Qinghai Province during 2000-2011].

PubMed

Fan, Li-Xia; Ba, Zhuo-Ma; Zhao, Sheng-Cang; Yi, Hu; Jiang, Shuang-Ying; Zhang, Yan; Wang, Hui-Ling; Xu, Wen-Bo

2013-08-01

To carry out the molecular epidemiological study of the wild-type measles virus isolated in Qinghai Province during 2000-2011, and provide a scientific basis for the measles elimination. Measles viruses were isolated using B95a cell line or Vero/SLAM cell line from throat swabs collected from suspected measles cases during measles outbreak and sporadic in 6 prefectures during 2000-2011. The fragment of 696 nucleotides of N gene carboxy terminal was amplified by using RT-PCR methods. The PCR products were sequenced and analyzed. The phylogenetic tree was conducted with the viruses isolated in viruses from other province. Total 19 measles viruses were isolated during 2000-2011 in Qinghai province and all belong to genotype H1a. The results of phylogenetic tree showed that viruses in 2000-2005 and in 2009-2011 were distributed in two different lineages, and it revealed that these strains belonged to at least 2 viral transmission chains and the viruses circulated during 2000-2005 were not detected after 2005. Genotype H1a was the predominant genotype circulated in Qinghai province during 2000-2011. Qinghai measles virus strains had not evolved independently, but coevolved with the measles virus strains in other provinces in mainland China. The variation of important amino acid sites of measles virus should be continuous monitored and provide the scientific strategy for the measles elimination.

Improving molecular tools for global surveillance of measles virus.

PubMed

Bankamp, Bettina; Byrd-Leotis, Lauren A; Lopareva, Elena N; Woo, Gibson K S; Liu, Chunyu; Jee, Youngmee; Ahmed, Hinda; Lim, Wilina W; Ramamurty, Nalini; Mulders, Mick N; Featherstone, David; Bellini, William J; Rota, Paul A

2013-09-01

The genetic characterization of wild-type measles viruses plays an important role in the description of viral transmission pathways and the verification of measles elimination. The 450 nucleotides that encode the carboxyl-terminus of the nucleoprotein (N-450) are routinely sequenced for genotype analysis. The objectives of this study were to develop improved primers and controls for RT-PCR reactions used for genotyping of measles samples and to develop a method to provide a convenient, safe, and inexpensive means to distribute measles RNA for RT-PCR assays and practice panels. A newly designed, genetically defined synthetic RNA and RNA isolated from cells infected with currently circulating genotypes were used to compare the sensitivity of primer pairs in RT-PCR and nested PCR. FTA® cards loaded with lysates of measles infected cells were tested for their ability to preserve viral RNA and destroy virus infectivity. A new primer pair, MeV216/MeV214, was able to amplify N-450 from viruses representing 10 currently circulating genotypes and a genotype A vaccine strain and demonstrated 100-fold increased sensitivity compared to the previously used primer set. A nested PCR assay further increased the sensitivity of detection from patient samples. A synthetic positive control RNA was developed that produced PCR products that are distinguishable by size from PCR products amplified from clinical samples. FTA® cards completely inactivated measles virus and stabilized RNA for at least six months. These improved molecular tools will advance molecular characterization of circulating measles viruses globally and provide enhanced quality control measures. Published by Elsevier B.V.

Single Endemic Genotype of Measles Virus Continuously Circulating in China for at Least 16 Years

PubMed Central

Wang, Huiling; Zhu, Zhen; Ji, Yixin; Liu, Chunyu; Zhang, Xiaojie; Sun, Liwei; Zhou, Jianhui; Lu, Peishan; Hu, Ying; Feng, Daxing; Zhang, Zhenying; Wang, Changyin; Fang, Xueqiang; Zheng, Huanying; Liu, Leng; Sun, Xiaodong; Tang, Wei; Wang, Yan; Liu, Yan; Gao, Hui; Tian, Hong; Ma, Jiangtao; Gu, Suyi; Wang, Shuang; Feng, Yan; Bo, Fang; Liu, Jianfeng; Si, Yuan; Zhou, Shujie; Ma, Yuyan; Wu, Shengwei; Zhou, Shunde; Li, Fangcai; Ding, Zhengrong; Yang, Zhaohui; Rota, Paul A.; Featherstone, David; Jee, Youngmee; Bellini, William J.; Xu, Wenbo

2012-01-01

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. PMID:22532829

Distinct Contributions of Autophagy Receptors in Measles Virus Replication.

PubMed

Petkova, Denitsa S; Verlhac, Pauline; Rozières, Aurore; Baguet, Joël; Claviere, Mathieu; Kretz-Remy, Carole; Mahieux, Renaud; Viret, Christophe; Faure, Mathias

2017-05-22

Autophagy is a potent cell autonomous defense mechanism that engages the lysosomal pathway to fight intracellular pathogens. Several autophagy receptors can recognize invading pathogens in order to target them towards autophagy for their degradation after the fusion of pathogen-containing autophagosomes with lysosomes. However, numerous intracellular pathogens can avoid or exploit autophagy, among which is measles virus (MeV). This virus induces a complete autophagy flux, which is required to improve viral replication. We therefore asked how measles virus interferes with autophagy receptors during the course of infection. We report that in addition to NDP52/CALCOCO₂ and OPTINEURIN/OPTN, another autophagy receptor, namely T6BP/TAXIBP1, also regulates the maturation of autophagosomes by promoting their fusion with lysosomes, independently of any infection. Surprisingly, only two of these receptors, NDP52 and T6BP, impacted measles virus replication, although independently, and possibly through physical interaction with MeV proteins. Thus, our results suggest that a restricted set of autophagosomes is selectively exploited by measles virus to replicate in the course of infection.

Will Synergizing Vaccination with Therapeutics Boost Measles Virus Eradication?

PubMed Central

Plemper, Richard K; Hammond, Anthea L

2014-01-01

Introduction Measles virus is a major human pathogen responsible for approximately 150,000 measles deaths annually. The disease is vaccine preventable and eradication of the virus is considered feasible in principle. However, a herd immunity exceeding 95% is required to prevent sporadic viral outbreaks in a population. Declining disease prevalence combined with public anxieties about vaccination safety has increased vaccine refusal especially in the European region, which has resulted in measles resurgence in some areas. Areas covered Here, we discuss whether synergizing effective measles therapeutics with vaccination could contribute to solving an endgame conundrum of measles elimination by accelerating the eradication effort. Based on an anticipated use for protection of high-risk contacts of confirmed measles cases through post-exposure prophylaxis, we identify key elements of the desirable drug profile, review current disease management strategies and the state of experimental inhibitor candidates, evaluate the risk associated with viral escape from inhibition, and consider the potential of measles therapeutics for the management of persistent viral infection of the CNS. Assuming a post-measles world with waning measles immunity, we contemplate the possible impact of therapeutics on controlling the threat imposed by closely related zoonotic pathogens of the same genus as measles virus. Expert opinion Efficacious therapeutics given for post-exposure prophylaxis of high-risk social contacts of confirmed index cases may aid measles eradication by closing herd immunity gaps due to vaccine refusal or failure in populations with overall good vaccination coverage. The envisioned primarily prophylactic application of measles therapeutics to a predominantly pediatric and/or adolescent patient population dictates the drug profile; the article must be safe and efficacious, orally available, shelf-stable at ambient temperature, and amenable to cost-effective manufacture

[Genetic characterization analysis on the first imported measles virus of genotype D8 in Chinese mainland].

PubMed

Sun, Xiao-Dong; Li, Chong-Shan; Tang, Xian; Li, Zhi; Zhang, Yan; Tang, Wei; Wang, Jing; Wang, Hui-Ling; Yang, Yan-Ji; Li, Jia; Yuan, Zheng-An; Xu, Wen-Bo

2013-11-01

This study analyzed the genetic characterization on first imported measles virus of genotype D8 in Chinese mainland. Serums were collected from the suspicious MV patients to detect IgM antibody in ELISA. Throat swabs were cultured in Vero/SLAM cell line to get measles virus isolates. Part of the nucleotide sequence of the 3' terminus of nucleoprotein (N) gene of these isolates were amplified by RT-PCR, and the amplicons were directly sequenced. The phylogenetic analysis was based on the nucleotide sequence about 456 base pairs of the 3' terminus of nucleoprotein (N) gene. Results showed that it reported 1 105 suspicious measles cases in shanghai, 2012, including 590 confirmed cases and 2 clinical case. The reported morbidity was 2.52 per one hundred thousand. 247 measles viruses were isolated from 984 throat swabs specimen. Most of them belonged to sub-genotype H1a except Shanghai12-239 was genotype D8. The homology of nucleotide and amino acid sequences were 97.8% and 98.6% respectively between Shanghai12-239 and WHO reference strain (Manchester. UNK30.94(D8)AF280803). Those were 89.6%-94.5% and 88.7%-95.3% between Shanghai12-239 and WHO reference strains of other genotypes.

[Circulating pattern analysis for endemic measles viruses in mainland of China].

PubMed

Zhang, Yan; Ji, Yi-Xin; Zhu, Zhen

2009-04-01

To analysis of the circulating pattern for endemic measles viruses in mainland of China (Hong Kong, Macao and Taiwan were excluded) between 1993 and 2006. To analyze the database of Measles laboratory network surveillance, and the database of virology surveillance of National laboratory for Measles in Chinese Centers for Disease Control and Prevention (CCDC). Total 748 positive measles isolates were available from 29 provinces of China. 743 were H1 genotypes, 1 was H2 genotype, 1 was A genotype and 3 were vaccine like A genotypes. Among H1 genotype, 684 were H1a subgenotypes, 50 were H1b subgenotypes, 9 were H1c subgenotypes. H1a was isolated from 29 provinces (Tibet and Hubei did not carry out virus isolation), H1b was isolated from 10 provinces, H1c was isolated from 4 provinces during 1993-1994. H1a became predominant subgenotype since 2000; H1b shrink annually, its circulating has been interrupted since 2006; H1c circulating has been interrupted since 1995. Molecular epidemiology of measles viruses between 1993 and 2006 showed the character of genetic variation and the geographic distribution of the measles viruses in different years, and revealed that genotype H1 was the predominant indigenous measles virus genotype in mainland China and H1a became the predominant subgenotype in recent years.

Measles virus genotypes circulating in India, 2011-2015.

PubMed

Vaidya, Sunil R; Chowdhury, Deepika T

2017-05-01

The Government of India is accepted to participate in the measles elimination and rubella control goal 2020, hence genetic characterization of measles viruses (MeV) becomes essential. At National Reference Laboratory (National Institute of Virology, Pune), the throat swabs/urine specimens (n = 380) or PCR products (n = 219) obtained from the suspected measles cases were referred for the molecular testing and subsequently, MeV nucleoprotein (N) gene sequencing/genotyping. In addition, 2,449 suspected measles cases, mainly from the Maharashtra state were referred for the laboratory diagnosis. A detailed study was performed on N gene sequences obtained during last two decades. Indian MeV sequences obtained during 2011-2015 were compared with 1996-2010 sequences and genetic divergence was studied. Circulation of measles genotypes B3 (n = 3), D4 (n = 49), and D8 (n = 351) strains were observed in 19 States and three Union Territories of India. In addition, 64 measles viruses were isolated from 253 throat swab or urine specimens obtained from the suspected measles cases. During 2011-2015, 67.9% (1,663/2,449) suspected measles cases were laboratory confirmed. Molecular studies showed circulation of measles genotype B3 in India along with prominently circulating genotypes D4 and D8 except D7 strains. The genetic diversion within Indian B3, D4, and D8 genotypes was 0.3%, 1.1%, and 2.1%, respectively. The genetic divergence of Indian B3, D4, and D8 measles strains with the WHO reference sequences was 2.5%, 2.6%, and 1.8%, respectively. It is crucial data for national immunization program. More measles/rubella genotyping studies are necessary to track transmission and to support measles elimination and rubella control. J. Med. Virol. 89:753-758, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Case-based surveillance enhanced with measles virus detection/genotyping is essential to maintain measles elimination in Aichi Prefecture, Japan.

PubMed

Minagawa, Hiroko; Yasui, Yoshihiro; Adachi, Hirokazu; Ito, Miyabi; Hirose, Emi; Nakamura, Noriko; Hata, Mami; Kobayashi, Shinichi; Yamashita, Teruo

2015-11-09

Japan was verified as having achieved measles elimination by the Measles Regional Verification Commission in the Western Pacific Region in March 2015. Verification of measles elimination implies the absence of continuous endemic transmission. After the last epidemic in 2007 with an estimated 18,000 cases, Japan introduced nationwide case-based measles surveillance in January 2008. Laboratory diagnosis for all suspected measles cases is essentially required by law, and virus detection tests are mostly performed by municipal public health institutes. Despite relatively high vaccination coverage and vigorous response to every case by the local health center staff, outbreak of measles is repeatedly observed in Aichi Prefecture, Japan. Measles virus N and H gene detection by nested double RT-PCR was performed with all specimens collected from suspected cases and transferred to our institute. Genotyping and further molecular epidemiological analyses were performed with the direct nucleotide sequence data of appropriate PCR products. Between 2010 and 2014, specimens from 389 patients suspected for measles were tested in our institute. Genotypes D9, D8, H1 and B3 were detected. Further molecular epidemiological analyses were helpful to establish links between patients, and sometimes useful to discriminate one outbreak from another. All virus-positive cases, including 49 cases involved in three outbreaks without any obvious epidemiological link with importation, were considered as import-related based on the nucleotide sequence information. Chain of transmission in the latest outbreak in 2014 terminated after the third generations, much earlier than the 2010-11 outbreak (6th generations). Since 2010, almost all measles cases reported in Aichi Prefecture are either import or import-related, based primarily on genotypes and nucleotide sequences of measles virus detected. In addition, genotyping and molecular epidemiological analyses are indispensable to prove the interruption

Structural virology. Near-atomic cryo-EM structure of the helical measles virus nucleocapsid.

PubMed

Gutsche, Irina; Desfosses, Ambroise; Effantin, Grégory; Ling, Wai Li; Haupt, Melina; Ruigrok, Rob W H; Sachse, Carsten; Schoehn, Guy

2015-05-08

Measles is a highly contagious human disease. We used cryo-electron microscopy and single particle-based helical image analysis to determine the structure of the helical nucleocapsid formed by the folded domain of the measles virus nucleoprotein encapsidating an RNA at a resolution of 4.3 angstroms. The resulting pseudoatomic model of the measles virus nucleocapsid offers important insights into the mechanism of the helical polymerization of nucleocapsids of negative-strand RNA viruses, in particular via the exchange subdomains of the nucleoprotein. The structure reveals the mode of the nucleoprotein-RNA interaction and explains why each nucleoprotein of measles virus binds six nucleotides, whereas the respiratory syncytial virus nucleoprotein binds seven. It provides a rational basis for further analysis of measles virus replication and transcription, and reveals potential targets for drug design. Copyright © 2015, American Association for the Advancement of Science.

Targeted entry of enveloped viruses: measles and herpes simplex virus I.

PubMed

Navaratnarajah, Chanakha K; Miest, Tanner S; Carfi, Andrea; Cattaneo, Roberto

2012-02-01

We compare the receptor-based mechanisms that a small RNA virus and a larger DNA virus have evolved to drive the fusion of viral and cellular membranes. Both systems rely on tight control over triggering the concerted refolding of a trimeric fusion protein. While measles virus entry depends on a receptor-binding protein and a fusion protein only, the herpes simplex virus (HSV) is more complex and requires four viral proteins. Nevertheless, in both viruses a receptor-binding protein is required for triggering the membrane fusion process. Moreover, specificity domains can be appended to these receptor-binding proteins to target virus entry to cells expressing a designated receptor. We discuss how principles established with measles and HSV can be applied to targeting other enveloped viruses, and alternatively how retargeted envelopes can be fitted on foreign capsids. Copyright © 2011 Elsevier B.V. All rights reserved.

Identification of different lineages of measles virus strains circulating in Uttar Pradesh, North India.

PubMed

Shakya, Akhalesh Kumar; Shukla, Vibha; Maan, Harjeet Singh; Dhole, Tapan N

2012-10-16

Genetic analysis of measles viruses associated with recent cases and outbreaks has proven to bridge information gaps in routine outbreak investigations and has made a substantial contribution to measles control efforts by helping to identify the transmission pathways of the virus. The present study describes the genetic characterization of wild type measles viruses from Uttar Pradesh, India isolated between January 2008 and January 2011. In the study, 526 suspected measles cases from 15 outbreaks were investigated. Blood samples were collected from suspected measles outbreaks and tested for the presence of measles specific IgM; throat swab and urine samples were collected for virus isolation and RT-PCR. Genotyping of circulating measles viruses in Uttar Pradesh was performed by sequencing a 450-bp region encompassing the nucleoprotein hypervariable region and phylogenetic analysis. Based on serological results, all the outbreaks were confirmed as measles. Thirty eight strains were obtained. Genetic analysis of circulating measles strains (n = 38) in Uttar Pradesh from 235 cases of laboratory-confirmed cases from 526 suspected measles cases between 2008 and 2011 showed that all viruses responsible for outbreaks were within clade D and all were genotype D8.Analysis of this region showed that it is highly divergent (up to 3.4% divergence in the nucleotide sequence and 4.1% divergence in the amino acid sequence between most distant strains). Considerable genetic heterogeneity was observed in the MV genotype D8 viruses in North India and underscores the need for continued surveillance and in particular increases in vaccination levels to decrease morbidity and mortality attributable to measles.

SUBCLINICAL INFECTION OF DOGS BY CANINE-ADAPTED MEASLES VIRUS EVIDENCED BY THEIR SUBSEQUENT IMMUNITY TO CANINE DISTEMPER VIRUS

PubMed Central

Moura, Roberto A.; Warren, Joel

1961-01-01

Moura, Roberto A. (Chas. Pfizer and Company, Inc., Terre Haute, Ind.) and Joel Warren. Subclinical infection of dogs by canine-adapted measles virus evidenced by their subsequent immunity to canine distemper virus. J. Bacteriol. 82:702–705. 1961.—Young dogs were inoculated with virulent measles virus which had been adapted to canine kidney or human amnion cell culture. None of the animals showed any clinical symptoms nor could virus be isolated from the blood, although measles-neutralizing and complement-fixing antibodies developed during convalescence. All dogs failed to develop antibody to canine distemper. However, when these and normal control animals were subsequently inoculated intracerebrally with virulent distemper virus, each of the controls succumbed to typical symptoms, whereas all of the measles-immune dogs survived. These results suggest that the cross-protection conferred by measles against canine distemper virus infection involves factors other than humoral antibody. The immunity persists for a considerable length of time. PMID:14476677

Absence of Measles Virus Detection from Stapes of Patients with Otosclerosis.

PubMed

Flores-García, María de Lourdes; Colín-Castro, Claudia Adriana; Hernández-Palestina, Mario Sabas; Sánchez-Larios, Roberto; Franco-Cendejas, Rafael

2018-01-01

Objective To determine molecularly the presence of measles virus genetic material in the stapes of patients with otosclerosis. Study Design A cross-sectional study. Setting A tertiary referral hospital. Subjects and Methods Genetic material was extracted from the stapes of patients with otosclerosis (n = 93) during the period from March 2011 to April 2012. The presence of viral measles sequences was evaluated by the real-time reverse transcriptase polymerase chain reaction (RT-PCR). The expression of the CD46 gene was determined. Results Ninety-three patients were included in the study. No sample was positive for any of 3 measles virus genes (H, N, and F). Measles virus RNA was not detected in any sample by real-time RT-PCR. CD46 levels were positive in 3.3% (n = 3) and negative in 96.7% (n = 90). Conclusion This study does not support the theory of measles virus as the cause of otosclerosis. It is necessary to do more research about other causal theories to clarify its etiology and prevention.

Genetic characterization of measles viruses isolated in Turkey during 2000 and 2001

PubMed Central

Korukluoglu, Gulay; Liffick, Stephanie; Guris, Dalya; Kobune, Fumio; Rota, Paul A; Bellini, William J; Ceylan, Ali; Ertem, Meliksah

2005-01-01

Background Molecular epidemiologic studies have made significant contributions to measles surveillance activities by helping to identify source and transmission pathways of the virus. This report describes the genetic characterization of wild-type measles viruses isolated in Turkey in 2000 and 2001. Results Wild-type measles viruses were isolated from 24 cases from five provinces in Turkey during 2001. The viruses were analyzed using the standard genotyping protocols. All isolates were classified as genotype D6, the same genotype that was identified in Turkey in previous outbreaks during 1998. Conclusion Turkey has begun implementation of a national program to eliminate measles by 2010. Therefore, this baseline genotype data will provide a means to monitor the success of the elimination program. PMID:16029506

Vaccine platform recombinant measles virus.

PubMed

Mühlebach, Michael D

2017-10-01

The classic development of vaccines is lengthy, tedious, and may not necessarily be successful as demonstrated by the case of HIV. This is especially a problem for emerging pathogens that are newly introduced into the human population and carry the inherent risk of pandemic spread in a naïve population. For such situations, a considerable number of different platform technologies are under development. These are also under development for pathogens, where directly derived vaccines are regarded as too complicated or even dangerous due to the induction of inefficient or unwanted immune responses causing considerable side-effects as for dengue virus. Among platform technologies are plasmid-based DNA vaccines, RNA replicons, single-round infectious vector particles, or replicating vaccine-based vectors encoding (a) critical antigen(s) of the target pathogens. Among the latter, recombinant measles viruses derived from vaccine strains have been tested. Measles vaccines are among the most effective and safest life-attenuated vaccines known. Therefore, the development of Schwarz-, Moraten-, or AIK-C-strain derived recombinant vaccines against a wide range of mostly viral, but also bacterial pathogens was quite straightforward. These vaccines generally induce powerful humoral and cellular immune responses in appropriate animal models, i.e., transgenic mice or non-human primates. Also in the recent first clinical phase I trial, the results have been quite encouraging. The trial indicated the expected safety and efficacy also in human patients, interestingly independent from the level of prevalent anti-measles immunity before the trial. Thereby, recombinant measles vaccines expressing additional antigens are a promising platform for future vaccines.

A systematic review of human-to-human transmission of measles vaccine virus.

PubMed

Greenwood, Kathryn P; Hafiz, Radwan; Ware, Robert S; Lambert, Stephen B

2016-05-17

Measles is one of the most contagious human diseases. Administration of the live attenuated measles vaccine has substantially reduced childhood mortality and morbidity since its licensure in 1963. The live but attenuated form of the vaccine describes a virus poorly adapted to replicating in human tissue, but with a replication yield sufficient to elicit an immune response for long-term protection. Given the high transmissibility of the wild-type virus and that transmission of other live vaccine viruses has been documented, we conducted a systematic review to establish if there is any evidence of human-to-human transmission of the live attenuated measles vaccine virus. We reviewed 773 articles for genotypic confirmation of a vaccine virus transmitted from a recently vaccinated individual to a susceptible close contact. No evidence of human-to-human transmission of the measles vaccine virus has been reported amongst the thousands of clinical samples genotyped during outbreaks or endemic transmission and individual case studies worldwide. Copyright © 2016 Elsevier Ltd. All rights reserved.

High titer oncolytic measles virus production process by integration of dielectric spectroscopy as online monitoring system.

PubMed

Grein, Tanja A; Loewe, Daniel; Dieken, Hauke; Salzig, Denise; Weidner, Tobias; Czermak, Peter

2018-05-01

Oncolytic viruses offer new hope to millions of patients with incurable cancer. One promising class of oncolytic viruses is Measles virus, but its broad administration to cancer patients is currently hampered by the inability to produce the large amounts of virus needed for treatment (10 10 -10 12 virus particles per dose). Measles virus is unstable, leading to very low virus titers during production. The time of infection and time of harvest are therefore critical parameters in a Measles virus production process, and their optimization requires an accurate online monitoring system. We integrated a probe based on dielectric spectroscopy (DS) into a stirred tank reactor to characterize the Measles virus production process in adherent growing Vero cells. We found that DS could be used to monitor cell adhesion on the microcarrier and that the optimal virus harvest time correlated with the global maximum permittivity signal. In 16 independent bioreactor runs, the maximum Measles virus titer was achieved approximately 40 hr after the permittivity maximum. Compared to an uncontrolled Measles virus production process, the integration of DS increased the maximum virus concentration by more than three orders of magnitude. This was sufficient to achieve an active Measles virus concentration of > 10 10 TCID 50 ml -1 . © 2017 Wiley Periodicals, Inc.

Monitoring progress toward measles elimination by genetic diversity analysis of measles viruses in China 2009-2010.

PubMed

Zhang, Y; Wang, H; Xu, S; Mao, N; Zhu, Z; Shi, J; Huang, G; Liu, C; Bo, F; Feng, D; Lu, P; Liu, Y; Wang, Y; Lei, Y; Chen, M; Chen, H; Wang, C; Fu, H; Li, C; He, J; Gao, H; Gu, S; Wang, S; Ling, H; Liu, Y; Ding, Z; Ba, Z; Feng, Y; Zheng, H; Tang, X; Lei, Y; Xiong, Y; Bellini, W J; Rota, P A; Jee, Y; Xu, W

2014-09-01

With the achievement of high coverage for routine immunization and supplementary immunization activities (SIAs), measles incidence in mainland China reached its lowest level in 2010. The proportion of measles cases in the vaccination-targeted population decreased during 2007-2010 after the SIAs. More than 60% of measles cases were in adults or infants, especially in the coastal and eastern provinces during 2009 and 2010. A total 567 isolates of measles virus were obtained from clinical specimens from 27 of 31 provinces in mainland China during 2009 and 2010. Except for two vaccine-associated cases, one genotype D4 strain, two genotype D9 strains, and four genotype D11 strains, the other 558 strains were genotype H1 cluster H1a. Genotype H1 has been the only endemic genotype detected in China since surveillance began in 1993. Only genotype H1 was found in mainland China during 1993-2008, except for one detection of genotype H2. More recently, multiple genotypes of imported measles were detected even with the background of endemic genetotype H1 viruses. Analysis of the 450-nucleotide sequencing window of the measles virus N gene showed that the overall genetic diversity of the recent geneotype H1 strains decreased between 2008 and 2010. The lower genetic diversity of H1 strains suggested that enhanced vaccination may have reduced the co-circulating lineages of endemic genotype H1 strains in mainland China. © 2014 The Authors Clinical Microbiology and Infection © 2014 European Society of Clinical Microbiology and Infectious Diseases.

Recombinant measles viruses expressing respiratory syncytial virus proteins induced virus-specific CTL responses in cotton rats.

PubMed

Yamaji, Yoshiaki; Nakayama, Tetsuo

2014-07-31

Respiratory syncytial virus (RSV) is a common cause of serious lower respiratory tract illnesses in infants. Natural infections with RSV provide limited protection against reinfection because of inefficient immunological responses that do not induce long-term memory. RSV natural infection has been shown to induce unbalanced immune response. The effective clearance of RSV is known to require the induction of a balanced Th1/Th2 immune response, which involves the induction of cytotoxic T lymphocytes (CTL). In our previous study, recombinant AIK-C measles vaccine strains MVAIK/RSV/F and MVAIK/RSV/G were developed, which expressed the RSV fusion (F) protein or glycoprotein (G). These recombinant viruses elicited antibody responses against RSV in cotton rats, and no infectious virus was recovered, but small amounts of infiltration of inflammatory cells were observed in the lungs following RSV challenge. In the present study, recombinant AIK-C measles vaccine strains MVAIK/RSV/M2-1 and MVAIK/RSV/NP were developed, expressing RSV M2-1 or Nucleoprotein (NP), respectively. These viruses exhibited temperature-sensitivity (ts), which was derived from AIK-C, and expressed respective RSV antigens. The intramuscular inoculation of cotton rats with the recombinant measles virus led to the induction of CD8(+) IFN-γ(+) cells. No infectious virus was recovered from a lung homogenate following the challenge. A Histological examination of the lungs revealed a significant reduction in inflammatory reactions without alveolar damage. These results support the recombinant measles viruses being effective vaccine candidates against RSV that induce RSV-specific CTL responses with or without the development of an antibody response. Copyright © 2014 Elsevier Ltd. All rights reserved.

Population immunity to measles virus and the effect of HIV-1 infection after a mass measles vaccination campaign in Lusaka, Zambia: a cross-sectional survey.

PubMed

Lowther, Sara A; Curriero, Frank C; Kalish, Brian T; Shields, Timothy M; Monze, Mwaka; Moss, William J

2009-03-21

Measles control efforts are hindered by challenges in sustaining high vaccination coverage, waning immunity in HIV-1-infected children, and clustering of susceptible individuals. Our aim was to assess population immunity to measles virus after a mass vaccination campaign in a region with high HIV prevalence. 3 years after a measles supplemental immunisation activity (SIA), we undertook a cross-sectional survey in Lusaka, Zambia. Households were randomly selected from a satellite image. Children aged 9 months to 5 years from selected households were eligible for enrolment. A questionnaire was administered to the children's caregivers to obtain information about measles vaccination history and history of measles. Oral fluid samples were obtained from children and tested for antibodies to measles virus and HIV-1 by EIA. 1015 children from 668 residences provided adequate specimens. 853 (84%) children had a history of measles vaccination according to either caregiver report or immunisation card. 679 children (67%) had antibodies to measles virus, and 64 (6%) children had antibodies to HIV-1. Children with antibodies to HIV-1 were as likely to have no history of measles vaccination as those without antibodies to HIV-1 (odds ratio [OR] 1.17, 95% CI 0.57-2.41). Children without measles antibodies were more likely to have never received measles vaccine than those with antibodies (adjusted OR 2.50, 1.69-3.71). In vaccinated children, 33 (61%) of 54 children with antibodies to HIV-1 also had antibodies to measles virus, compared with 568 (71%) of 796 children without antibodies to HIV-1 (p=0.1). 3 years after an SIA, population immunity to measles was insufficient to interrupt measles virus transmission. The use of oral fluid and satellite images for sampling are potential methods to assess population immunity and the timing of SIAs.

Host DNA Synthesis-Suppressing Factor in Culture Fluid of Tissue Cultures Infected with Measles Virus

PubMed Central

Minagawa, Tomonori; Nakaya, Chikako; Iida, Hiroo

1974-01-01

Host DNA synthesis is suppressed by the culture fluid of cell cultures infected with measles virus. This activity in the culture fluid is initiated somewhat later than the growth of infectious virus. Ninety percent of host DNA synthesis in HeLa cells is inhibited by culture fluid of 3-day-old cell cultures of Vero or HeLa cells infected with measles virus. This suppressing activity is not a property of the virion, but is due to nonvirion-associated component which shows none of the activities of measles virus such as hemagglutination, hemolysis, or cell fusion nor does it have the antigenicity of measles virus as tested by complement-fixation or hemagglutination-inhibiting antibody blocking tests. Neutralization of the activity of this component is not attained with the pooled sera of convalescent measles patients. This component has molecular weights of about 45,000, 20,000, and 3,000 and appears to be a heat-stable protein. The production of host DNA suppressing factor (DSF) is blocked by cycloheximide. Neither UV-inactivated nor antiserum-neutralized measles virus produce DSF. Furthermore, such activity of nonvirion-associated component is not detected in the culture fluid of cultures infected with other RNA viruses such as poliovirus, vesicular stomatitis virus, or Sindbis virus. PMID:4207526

Host DNA synthesis-suppressing factor in culture fluid of tissue cultures infected with measles virus

DOE Office of Scientific and Technical Information (OSTI.GOV)

Minagawa, T.; Nakaya, C.; Iida, H.

1974-05-01

Host DNA synthesis is suppressed by the culture fluid of cell cultures infected with measles virus. This activity in the culture fluid is initiated somewhat later than the growth of infectious virus. Ninety percent of host DNA synthesis in HeLa cells is inhibited by culture fluid of 3-day-old cell cultures of Vero or HeLa cells infected with measles virus. This suppressing activity is not a property of the virion, but is due to nonvirion-associated componentnent which shows none of the activities of measles virus such as hemagglutination, hemolysis, or cell fusion nor does it have the antigenicity of measles virusmore » as tested by complement-fixation or hemagglutination-inhibiting antibody blocking tests. Neutralization of the activity of this component is not attained with the pooled sera of convalescent measles patients. This component has molecular weights of about 45,000, 20,000, and 3,000 and appears to be a heat-stable protein. The production of host DNA suppressing factor (DSF) is blocked by cycloheximide. Neither uv-inactivated nor antiserum-neutralized measles virus produce DSF. Furthermore, such activity of nonvirion-associated component is not detected in the culture fluid of cultures infected with other RNA viruses such as poliovirus, vesicular stomatitis virus, or Sindbis virus. (auth)« less

[Antibody titers against measles, rubella, mumps and varicella-zoster viruses in medical students].

PubMed

Yoshida, Noriko; Tsumura, Naoki; Toyomasu, Koji; Sagawa, Kimitaka

2007-01-01

It is important to identify and immunize susceptible students who have clinical practice to prevent and control hospital infections. The antibody titers to measles, rubella, mumps and varicella viruses were measured in 1,139 students(417 men, 722 women, average age 21.3+/-2.7 yr old)including 510 medical students, 442 nursing students and 187 students of the School of Medical Technology in Kurume University. Antibodies against measles virus were detected by particle agglutination assay(PA), those against rubella virus by hemagglutination inhibition assay(HI), and those against mumps and varicella viruses by enzyme-linked immunosorbent assay(EIA). The serological susceptibilities to measles, rubella, mumps and varicella viruses were 112(9.8%), 112(9.8%), 163(14.3%)and 73(6.4%), respectively. The serological susceptibilities to measles, rubella and mumps viruses in male students were not different from those in female students. The susceptibility to varicella virus in female students was significantly higher than that in male students. After susceptible students were recommended to have vaccinations against each virus, the vaccination rate of the students without antibody was 99.1%. The history of infection and vaccination against the viruses were examined by self-recorded questionnaires in 406 students from all disciplines. The serological susceptibility of students with positive vaccination history was 11.1% for measles, 6.8% for rubella, 18.3% for mumps, and 4.9% for varicella. The serological susceptibility of students with a positive infection history was 5.7% for measles, 3.4% for rubella, 2.9% for mumps, and 4.9% for varicella. In the self-recorded questionnaire, the rate of unknown infection and vaccination histories were 57.5% and 71.6% for measles, 52.5% and 68.4% for rubella, 34.3% and 75.6% for mumps, and 27.1% and 80.5% for varicella, respectively. In conclusion, these data confirm that it is essential to assess immune status against measles, rubella

Wild-type Measles Virus in Brain Tissue of Children with Subacute Sclerosing Panencephalitis, Argentina

PubMed Central

Barrero, Paola Roxana; Grippo, Jorge; Viegas, Mariana

2003-01-01

We studied eight children who had measles at 6 to 10 months of age during the 1998 Argentine measles outbreak and in whom subacute sclerosing panencephalitis developed 4 years later. We report the genetic characterization of brain tissue–associated measles virus samples from three patients. Phylogenetic relationships clustered these viruses with the wild-type D6 genotype isolated during the 1998 outbreak. The children received measles vaccine; however, vaccinal strains were not found. PMID:14609476

The Measles Virus Receptor SLAMF1 Can Mediate Particle Endocytosis.

PubMed

Gonçalves-Carneiro, Daniel; McKeating, Jane A; Bailey, Dalan

2017-04-01

The signaling lymphocyte activation molecule F1 (SLAMF1) is both a microbial sensor and entry receptor for measles virus (MeV). Herein, we describe a new role for SLAMF1 to mediate MeV endocytosis that is in contrast with the alternative, and generally accepted, model that MeV genome enters cells only after fusion at the cell surface. We demonstrated that MeV engagement of SLAMF1 induces dramatic but transient morphological changes, most prominently in the formation of membrane blebs, which were shown to colocalize with incoming viral particles, and rearrangement of the actin cytoskeleton in infected cells. MeV infection was dependent on these dynamic cytoskeletal changes as well as fluid uptake through a macropinocytosis-like pathway as chemical inhibition of these processes inhibited entry. Moreover, we identified a role for the RhoA-ROCK-myosin II signaling axis in this MeV internalization process, highlighting a novel role for this recently characterized pathway in virus entry. Our study shows that MeV can hijack a microbial sensor normally involved in bacterial phagocytosis to drive endocytosis using a complex pathway that shares features with canonical viral macropinocytosis, phagocytosis, and mechanotransduction. This uptake pathway is specific to SLAMF1-positive cells and occurs within 60 min of viral attachment. Measles virus remains a significant cause of mortality in human populations, and this research sheds new light on the very first steps of infection of this important pathogen. IMPORTANCE Measles is a significant disease in humans and is estimated to have killed over 200 million people since records began. According to current World Health Organization statistics, it still kills over 100,000 people a year, mostly children in the developing world. The causative agent, measles virus, is a small enveloped RNA virus that infects a broad range of cells during infection. In particular, immune cells are infected via interactions between glycoproteins found

[Investigation of a measles outbreak caused by genotype D8 virus in Pinghu city of Zhejiang province, 2017].

PubMed

Yan, R; He, B; Yao, F Y; Xiang, Z L; He, H Q; Xie, S Y; Feng, Y

2018-03-10

Objective: To investigate the epidemiological characteristics of measles outbreak caused by genotype D8 virus in Pinghu city of Zhejiang province, and provide evidence for the control of the outbreak. Methods: The measles outbreak data were collected through National Measles Surveillance System. The outpatient records and admission records were checked, field investigation and outbreak response were conducted. Blood samples in acute phase and swab specimens were collected from the patients for laboratory testing, including serology test, RNA extraction and amplification, measles virus isolation and genotype identification. Software SPSS 17.0 and Excel 2016 were used for data analysis. Results: A total of 10 confirmed measles cases were reported in Pinghu city, and 8 cases were aged >40 years. Six blood samples were collected, in which 5 were measles D8 virus positive and 1 was negative in measles virus detection. There were epidemiological links among 10 cases which occurred in a factory, a hospital and a family at the same time. There was no statistical difference in symptoms among cases caused by D8 virus and H1a virus. After the emergent measles vaccination, the measles outbreak was effectively controlled. Conclusion: Untimely response due to the uneasy detection of measles cases in the early stage, nosocomial infection and weak barrier of measles immunity in adults might be the main reasons for this outbreak. Measles vaccination is effective in the prevention of measles D8 virus infection. It is necessary to strengthen measles genotype monitoring for the tracing of infection source and control of outbreaks.

The Plant-Derived Naphthoquinone Droserone Inhibits In Vitro Measles Virus Infection.

PubMed

Lieberherr, Christina; Zhang, Guoliang; Grafen, Anika; Singethan, Katrin; Kendl, Sabine; Vogt, Valentin; Maier, Jonathan; Bringmann, Gerhard; Schneider-Schaulies, Jürgen

2017-02-01

The naphthoquinone droserone ( 1 ) is a natural product occurring in dicotyledonous plants. We have now observed that the addition of 1 during infection of tissue culture cells with measles virus considerably reduced the infection. Interestingly, the infection was inhibited only when droserone ( 1 ) was added during virus entry, but not when added to the cells prior to virus uptake or after virus uptake. These findings suggest that 1 interacts with viral particles to reduce infectivity. The formation of progeny measles virus particles was inhibited to 50 % by droserone ( 1 ) at a concentration (IC 50 ) of approximately 2 µM with a half-maximal cytotoxicity (CC 50 ) of about 60 µM for Vero cells. Other tested naphthoquinone derivatives, among them the likewise natural plumbagin ( 2 ), but also synthetic analogs, were either more cytotoxic or not as effective as 1 . Thus, our data do not support the development of naphthoquinone derivatives into antiviral compounds, but suggest that they may be interesting research tools to study measles virus entry into cells. Georg Thieme Verlag KG Stuttgart · New York.

Measles in Mexico, 1941-2001: interruption of endemic transmission and lessons learned.

PubMed

Santos, Jose Ignacio; Nakamura, Miguel Angel; Godoy, Miriam Veras; Kuri, Pablo; Lucas, Carlos Alvarez; Conyer, Roberto Tapia

2004-05-01

In Mexico, measles occurred in a cyclical endemic-epidemic pattern until the early 1970s. Beginning in 1973, routine vaccination augmented by mass vaccination campaigns led to a decrease in the incidence of measles until the 1989-1990 regional pandemic, when the measles attack rate rose to 80 cases per 100000, resulting in 5899 deaths. Since the pandemic, measles elimination efforts in Mexico have resulted in increasing coverage to >95% among children aged 1-6 years with 2 doses of either measles or measles-mumps-rubella vaccine since 1996 and in coverage of 97.6% among children aged 6-10 since 1999. Surveillance data suggest that the transmission of indigenous measles virus was interrupted in 1997. After almost 4 years without measles cases, in April 2000, measles virus was reintroduced into Mexico and 30 laboratory-confirmed cases were reported. Detection of relatively few cases in nonprogrammatic age groups affirms the high immunization coverage and the sensitivity of measles surveillance in Mexico. We conclude that the specific strategies adopted for measles elimination have enabled Mexico to eliminate the endemic transmission of measles.

Recombinant Measles AIK-C Vaccine Strain Expressing the prM-E Antigen of Japanese Encephalitis Virus.

PubMed

Higuchi, Akira; Toriniwa, Hiroko; Komiya, Tomoyoshi; Nakayama, Tetsuo

2016-01-01

An inactivated Japanese encephalitis virus (JEV) vaccine, which induces neutralizing antibodies, has been used for many years in Japan. In the present study, the JEV prM-E protein gene was cloned, inserted at the P/M junction of measles AIK-C cDNA, and an infectious virus was recovered. The JEV E protein was expressed in B95a cells infected with the recombinant virus. Cotton rats were inoculated with recombinant virus. Measles PA antibodies were detected three weeks after immunization. Neutralizing antibodies against JEV developed one week after inoculation, and EIA antibodies were detected three weeks after immunization. The measles AIK-C-based recombinant virus simultaneously induced measles and JEV immune responses, and may be a candidate for infant vaccines. Therefore, the present strategy of recombinant viruses based on a measles vaccine vector would be applicable to the platform for vaccine development.

Measles to the Rescue: A Review of Oncolytic Measles Virus

PubMed Central

Aref, Sarah; Bailey, Katharine; Fielding, Adele

2016-01-01

Oncolytic virotherapeutic agents are likely to become serious contenders in cancer treatment. The vaccine strain of measles virus is an agent with an impressive range of oncolytic activity in pre-clinical trials with increasing evidence of safety and efficacy in early clinical trials. This paramyxovirus vaccine has a proven safety record and is amenable to careful genetic modification in the laboratory. Overexpression of the measles virus (MV) receptor CD46 in many tumour cells may direct the virus to preferentially enter transformed cells and there is increasing awareness of the importance of nectin-4 and signaling lymphocytic activation molecule (SLAM) in oncolysis. Successful attempts to retarget MV by inserting genes for tumour-specific ligands to antigens such as carcinoembryonic antigen (CEA), CD20, CD38, and by engineering the virus to express synthetic microRNA targeting sequences, and “blinding” the virus to the natural viral receptors are exciting measures to increase viral specificity and enhance the oncolytic effect. Sodium iodine symporter (NIS) can also be expressed by MV, which enables in vivo tracking of MV infection. Radiovirotherapy using MV-NIS, chemo-virotherapy to convert prodrugs to their toxic metabolites, and immune-virotherapy including incorporating antibodies against immune checkpoint inhibitors can also increase the oncolytic potential. Anti-viral host immune responses are a recognized barrier to the success of MV, and approaches such as transporting MV to the tumour sites by carrier cells, are showing promise. MV Clinical trials are producing encouraging preliminary results in ovarian cancer, myeloma and cutaneous non-Hodgkin lymphoma, and the outcome of currently open trials in glioblastoma multiforme, mesothelioma and squamous cell carcinoma are eagerly anticipated. PMID:27782084

Measles to the Rescue: A Review of Oncolytic Measles Virus.

PubMed

Aref, Sarah; Bailey, Katharine; Fielding, Adele

2016-10-22

Oncolytic virotherapeutic agents are likely to become serious contenders in cancer treatment. The vaccine strain of measles virus is an agent with an impressive range of oncolytic activity in pre-clinical trials with increasing evidence of safety and efficacy in early clinical trials. This paramyxovirus vaccine has a proven safety record and is amenable to careful genetic modification in the laboratory. Overexpression of the measles virus (MV) receptor CD46 in many tumour cells may direct the virus to preferentially enter transformed cells and there is increasing awareness of the importance of nectin-4 and signaling lymphocytic activation molecule (SLAM) in oncolysis. Successful attempts to retarget MV by inserting genes for tumour-specific ligands to antigens such as carcinoembryonic antigen (CEA), CD20, CD38, and by engineering the virus to express synthetic microRNA targeting sequences, and "blinding" the virus to the natural viral receptors are exciting measures to increase viral specificity and enhance the oncolytic effect. Sodium iodine symporter (NIS) can also be expressed by MV, which enables in vivo tracking of MV infection. Radiovirotherapy using MV-NIS, chemo-virotherapy to convert prodrugs to their toxic metabolites, and immune-virotherapy including incorporating antibodies against immune checkpoint inhibitors can also increase the oncolytic potential. Anti-viral host immune responses are a recognized barrier to the success of MV, and approaches such as transporting MV to the tumour sites by carrier cells, are showing promise. MV Clinical trials are producing encouraging preliminary results in ovarian cancer, myeloma and cutaneous non-Hodgkin lymphoma, and the outcome of currently open trials in glioblastoma multiforme, mesothelioma and squamous cell carcinoma are eagerly anticipated.

Temperature-sensitive mutants of measles virus produced from persistently infected HeLa cells.

PubMed

Armen, R C; Evermann, J F; Truant, A L; Laughlin, C A; Hallum, J V

1977-01-01

A persistent infection with the Edmonston strain of measles virus was established in HeLa cells in the absence of measles virus antibody (HeLaPI cells). By hemadsorption or immunofluoresnce virtually 100 per cent of the cells possessed measles virus components. HeLaPI cells produced no interferon and were not resistant to superinfection with Newcastle disease virus. HeLaPI cells contained both smooth (15--18 nm) and rought (20--35 nm) nucleocapsids as detected by electron microscopy. The virus produced from the HeLaPI cells (MVPI) varied in titer between 1.5 X 10(2) and 5.5 X10(4) PFU/ml, had a smaller plque size and was more heat resistant than wild-type measles virus. MVPI was also found to be temperature-sensitive. The temperature-sensitivity of MVPI was determined by the efficiency of plaquing at 33 degrees and 39 degrees C in Vero cell monolayers. When HeLaPI cells were incubated at 33 degrees C, there was a 50-fold increase in virus production as well as a slight increase in the percentage of cells forming infectious centers compared to HeLaPI cells grown at 37 degrees C. MVPI readily established a persistent infection in HeLa cells which also rleased temperature-sensitive virus.

Pathological consequences of systemic measles virus infection.

PubMed

Ludlow, Martin; McQuaid, Stephen; Milner, Dan; de Swart, Rik L; Duprex, W Paul

2015-01-01

The identification of poliovirus receptor-like 4 (PVRL4) as the second natural receptor for measles virus (MV) has closed a major gap in our understanding of measles pathogenesis, and explains how this predominantly lymphotropic virus breaks through epithelial barriers to transmit to a susceptible host. Advances in the development of wild-type, recombinant MVs which express fluorescent proteins making infected cells readily detectable in living tissues and animals, has also increased our understanding of this important and highly transmissible human disease. Thus, it is timely to review how these advances have provided new insights into MV infection of immune, epithelial and neural cells. This demands access to primate samples that help us understand the early and acute stages of the disease, which are challenging to dissect due to the mild/self-limiting nature of the infection. It also requires well-characterized and rather rare human tissue samples from patients who succumb to neurological sequelae to help study the consequences of the long-term persistence of this RNA virus in vivo. Collectively, these studies have provided unique insights into how the use of two cellular receptors, CD150 and PVRL4, governs the in vivo tissue-specific temporal patterns of virus spread and resulting pathological lesions. Analysis of tissue samples has also demonstrated the importance of differing mechanisms of virus cell-to-cell spread within lymphoid, epithelial and neural tissues in the dissemination of MV during acute and long-term persistent infections. Given the incentive to eradicate MV globally, and the inevitable question as to whether or not vaccination should cease in light of the existence of closely related morbilliviruses, a thorough understanding of measles pathological lesions is essential. Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Seroepidemiology and phylogenetic characterisation of measles virus in Ireland, 2004-2013.

PubMed

O' Riordan, Bernadette; Carr, Michael J; Connell, Jeff; Dunford, Linda; Hall, William W; Hassan, Jaythoon

2014-08-01

Ireland is classified as an area of high measles incidence. A World Health Organisation-European Region strategic plan exists for measles elimination by 2015. To retrospectively investigate measles outbreaks using all patient samples (sera and oral fluid) received for measles laboratory diagnosis and characterise the genetic diversity of circulating measles genotypes in Ireland. 704 cases of acute measles infection as determined by the presence of measles specific IgM in sera and oral fluids were confirmed at the National Virus Reference Laboratory. Measles positive samples (n=116) were examined by genotyping, sequence analysis and phylogenetic characterisation. Three measles outbreaks occurred over the study period: 2004, 2009/2010 and 2011. Measles IgM positivity ranged from 22-29% in outbreak years to 5-10% in the intervening years. Age profile analysis revealed that whereas individuals >10 years accounted for only 8% of cases in the 2004 outbreak, this increased to 33% and 29% in the 2009/2010 and 2011 outbreaks, respectively. The <1 year cohort accounted for 18-20% of cases in all outbreaks. Phylogenetic analysis demonstrated both indigenous transmission and also importation events. Clade D viruses were exclusively found circulating in Ireland, with autochthonous transmission of diverse genotype D4 strains associated with large outbreaks across Europe. More recently, genotype D8 was identified and these were associated with importation events. This study provides a comprehensive genetic analysis of circulating measles genotypes in Ireland and discriminated between indigenous and imported viral strains. Notably, an increase in laboratory-confirmed measles cases in the greater than 10 years of age group was seen over the study period. This information is valuable to inform vaccination strategies with a focus on those populations who remain susceptible to measles infection. Copyright © 2014 Elsevier B.V. All rights reserved.

Persistent measles virus infection of the intestine: confirmation by immunogold electron microscopy.

PubMed Central

Lewin, J; Dhillon, A P; Sim, R; Mazure, G; Pounder, R E; Wakefield, A J

1995-01-01

This study sought to investigate persistent measles virus infection of the intestine: a novel protocol for immunogold electron microscopy was developed using a polyclonal anti-measles nucleoprotein antibody on reprocessed, formalin fixed paraffin wax embedded tissue sections. Antibody binding was detected using both immunoperoxidase and light microscopy on tissue sections, and 10 nm gold conjugated secondary antibody and electron microscopy on ultrathin sections. The techniques were validated using both measles infected vero cells and human tissues with established measles infection: these included brain affected by subacute sclerosing panencephalitis and acute measles appendicitis. The technique was applied subsequently to six untreated cases of granulomatous Crohn's disease, and two cases of ileocaecal tuberculosis, a granulomatous control. Mumps primary antibody--applied to both mumps infected vero cells, and measles infected vero cells and tissues studied by immunoperoxidase, and measles antibody on mumps infected cells studied by immunoperoxidase and immunogold--were used as specificity controls: the primary antibodies identified their respective target antigen and there was no antibody cross reactivity. Measles virus nucleocapsids labelled with gold conjugated antibody in both infected cells and tissues, including foci of granulomatous inflammation in five of six cases of Crohn's disease: in the fifth case, the granuloma could not be identified in ultrathin section. In one of the tuberculosis cases, a low level of signal was noted while the second case was negative. Labelling adopted a characteristic pattern in all infected tissues, strengthening the specificity of these findings. This study provides the first direct confirmation of persistent measles virus infection of the intestine. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 PMID:7737565

Molecular Epidemiology of Measles Viruses in the United States, 1997–2001

PubMed Central

Liffick, Stephanie L.; Rota, Jennifer S.; Katz, Russell S.; Redd, Susan; Papania, Mark; Bellini, William J.

2002-01-01

From 1997 to 2001, sequence data from 55 clinical specimens were obtained from confirmed measles cases in the United States, representing 21 outbreaks and 34 sporadic cases. Sequence analysis indicated the presence of 11 of the recognized genotypes. The most common genotypes detected were genotype D6, usually identified from imported cases from Europe, and genotype D5, associated with importations from Japan. A number of viruses belonging to genotype D4 were imported from India and Pakistan. Overall, viral genotypes were determined for 13 chains of transmission with an unknown source of virus, and seven different genotypes were identified. Therefore, the diversity of Measles virus genotypes observed in the United States from 1997 to 2001 reflected multiple imported sources of virus and indicated that no strain of measles is endemic in the United States. PMID:12194764

Measles resurgence associated with continued circulation of genotype H1 viruses in China, 2005.

PubMed

Ji, Yixin; Zhang, Yan; Xu, Songtao; Zhu, Zhen; Zuo, Shuyan; Jiang, Xiaohong; Lu, Peishan; Wang, Changyin; Liang, Yong; Zheng, Huanying; Liu, Yang; Mao, Naiying; Liang, Xiaofeng; Featherstone, David Alexander; Rota, Paul A; Bellini, William J; Xu, Wenbo

2009-09-08

Measles morbidity and mortality decreased significantly after measles vaccine was introduced into China in 1965. From 1995 to 2004, average annual measles incidence decreased to 5.6 cases per 100,000 population following the establishment of a national two-dose regimen. Molecular characterization of wild-type measles viruses demonstrated that genotype H1 was endemic and widely distributed throughout the country in China during 1995-2004. A total of 124,865 cases and 55 deaths were reported from the National Notifiable Diseases Reporting System (NNDRS) in 2005, which represented a 69.05% increase compared with 2004. Over 16,000 serum samples obtained from 914 measles outbreaks and the measles IgM positive rate was 81%. 213 wild-type measles viruses were isolated from 18 of 31 provinces in China during 2005, and all of the isolates belonged to genotype H1. The ranges of the nucleotide sequence and predicted amino acid sequence homologies of the 213 genotype H1 strains were 93.4%-100% and 90.0%-100%, respectively. H1-associated cases and outbreaks caused the measles resurgence in China in 2005. H1 genotype has the most inner variation within genotype, it could be divided into 2 clusters, and cluster 1 viruses were predominant in China throughout 2005.

Measles Resurgence Associated with Continued Circulation of Genotype H1 Viruses in China, 2005

PubMed Central

Ji, Yixin; Zhang, Yan; Xu, Songtao; Zhu, Zhen; Zuo, Shuyan; Jiang, Xiaohong; Lu, Peishan; Wang, Changyin; Liang, Yong; Zheng, Huanying; Liu, Yang; Mao, Naiying; Liang, Xiaofeng; Featherstone, David Alexander; Rota, Paul A; Bellini, William J; Xu, Wenbo

2009-01-01

Measles morbidity and mortality decreased significantly after measles vaccine was introduced into China in 1965. From 1995 to 2004, average annual measles incidence decreased to 5.6 cases per 100,000 population following the establishment of a national two-dose regimen. Molecular characterization of wild-type measles viruses demonstrated that genotype H1 was endemic and widely distributed throughout the country in China during 1995-2004. A total of 124,865 cases and 55 deaths were reported from the National Notifiable Diseases Reporting System (NNDRS) in 2005, which represented a 69.05% increase compared with 2004. Over 16,000 serum samples obtained from 914 measles outbreaks and the measles IgM positive rate was 81%. 213 wild-type measles viruses were isolated from 18 of 31 provinces in China during 2005, and all of the isolates belonged to genotype H1. The ranges of the nucleotide sequence and predicted amino acid sequence homologies of the 213 genotype H1 strains were 93.4%-100% and 90.0%-100%, respectively. H1-associated cases and outbreaks caused the measles resurgence in China in 2005. H1 genotype has the most inner variation within genotype, it could be divided into 2 clusters, and cluster 1 viruses were predominant in China throughout 2005. PMID:19737391

Isolation of vaccine-derived measles viruses from children with acute respiratory infection.

PubMed

Aoki, Yoko; Mizuta, Katsumi; Ikeda, Tatsuya; Abiko, Chieko; Itagaki, Tsutomu; Ahiko, Tadayuki

2013-06-01

The measles elimination project led by the World Health Organization (WHO) has been moving toward the target of eliminating measles in the WHO Western Pacific Region. In Japan, prefectural public health institutes play a key role for the laboratory diagnosis of measles virus (MV) infection, which is based on PCR, virus isolation, and genotyping. Microscopic examination of viral-sensitive cell lines during routine virus isolation from nasopharyngeal specimens has been used to detect the morphological changes typical for the growth of respiratory viruses. Here, we describe the unexpected isolation of vaccine-derived MVs from the two unrelated 1-year-old boys with acute respiratory infection. The nasopharyngeal specimens were obtained from one patient in February 2007 and from another in December 2012. Incidentally, the two children had received measles-rubella vaccination 9 or 11 days before the sampling. The isolates from two children induced morphological changes of the viral-sensitive cell lines, such as syncythia formation (cell fusion). We finally identified the isolates as vaccine-derived MVs by sequence analysis and immunological methods with anti-measles nucleoprotein antibodies. As no typical symptoms of MV infection were observed in either patient, the vaccine-derived MVs were isolated not as causative pathogens but by chance. In fact, there was no suspected case of secondary MV infection in either patient, thereby excluding the possibility that vaccine-derived MVs spread from human to human. Our experiences suggest the possibility of vaccine-derived MV isolation by cell cultures and the difficulty in identifying MVs in specimens from patients other than clinically suspected measles cases.

External Quality Assessment for the Detection of Measles Virus by Reverse Transcription-PCR Using Armored RNA

PubMed Central

Jia, Tingting; Zhang, Lei; Wang, Guojing; Zhang, Rui; Zhang, Kuo; Lin, Guigao; Xie, Jiehong; Wang, Lunan; Li, Jinming

2015-01-01

In recent years, nucleic acid tests for detection of measles virus RNA have been widely applied in laboratories belonging to the measles surveillance system of China. An external quality assessment program was established by the National Center for Clinical Laboratories to evaluate the performance of nucleic acid tests for measles virus. The external quality assessment panel, which consisted of 10 specimens, was prepared using armored RNAs, complex of noninfectious MS2 bacteriophage coat proteins encapsulated RNA of measles virus, as measles virus surrogate controls. Conserved sequences amplified from a circulating measles virus strain or from a vaccine strain were encapsulated into these armored RNAs. Forty-one participating laboratories from 15 provinces, municipalities, or autonomous regions that currently conduct molecular detection of measles virus enrolled in the external quality assessment program, including 40 measles surveillance system laboratories and one diagnostic reagent manufacturer. Forty laboratories used commercial reverse transcription-quantitative PCR kits, with only one laboratory applying a conventional PCR method developed in-house. The results indicated that most of the participants (38/41, 92.7%) were able to accurately detect the panel with 100% sensitivity and 100% specificity. Although a wide range of commercially available kits for nucleic acid extraction and reverse transcription polymerase chain reaction were used by the participants, only two false-negative results and one false-positive result were generated; these were generated by three separate laboratories. Both false-negative results were obtained with tests performed on specimens with the lowest concentration (1.2 × 104 genomic equivalents/mL). In addition, all 18 participants from Beijing achieved 100% sensitivity and 100% specificity. Overall, we conclude that the majority of the laboratories evaluated have reliable diagnostic capacities for the detection of measles virus

External Quality Assessment for the Detection of Measles Virus by Reverse Transcription-PCR Using Armored RNA.

PubMed

Zhang, Dong; Sun, Yu; Jia, Tingting; Zhang, Lei; Wang, Guojing; Zhang, Rui; Zhang, Kuo; Lin, Guigao; Xie, Jiehong; Wang, Lunan; Li, Jinming

2015-01-01

In recent years, nucleic acid tests for detection of measles virus RNA have been widely applied in laboratories belonging to the measles surveillance system of China. An external quality assessment program was established by the National Center for Clinical Laboratories to evaluate the performance of nucleic acid tests for measles virus. The external quality assessment panel, which consisted of 10 specimens, was prepared using armored RNAs, complex of noninfectious MS2 bacteriophage coat proteins encapsulated RNA of measles virus, as measles virus surrogate controls. Conserved sequences amplified from a circulating measles virus strain or from a vaccine strain were encapsulated into these armored RNAs. Forty-one participating laboratories from 15 provinces, municipalities, or autonomous regions that currently conduct molecular detection of measles virus enrolled in the external quality assessment program, including 40 measles surveillance system laboratories and one diagnostic reagent manufacturer. Forty laboratories used commercial reverse transcription-quantitative PCR kits, with only one laboratory applying a conventional PCR method developed in-house. The results indicated that most of the participants (38/41, 92.7%) were able to accurately detect the panel with 100% sensitivity and 100% specificity. Although a wide range of commercially available kits for nucleic acid extraction and reverse transcription polymerase chain reaction were used by the participants, only two false-negative results and one false-positive result were generated; these were generated by three separate laboratories. Both false-negative results were obtained with tests performed on specimens with the lowest concentration (1.2 × 104 genomic equivalents/mL). In addition, all 18 participants from Beijing achieved 100% sensitivity and 100% specificity. Overall, we conclude that the majority of the laboratories evaluated have reliable diagnostic capacities for the detection of measles virus.

Transmission and molecular characterisation of wild measles virus in Romania, 2008 to 2012.

PubMed

Necula, G; Lazar, M; Stanescu, A; Pistol, A; Santibanez, S; Mankertz, A; Lupulescu, E

2013-12-12

Molecular characterisation of measles virus is a powerful tool for tracing transmission. Genotyping may prove the absence of endemic circulation of measles virus, i.e. transmission for more than 12 months, which is one of the criteria for verifying elimination of the disease. We have genetically characterised measles viruses detected in Romania from 2008 to 2012, focusing on the recent outbreaks from 2010 to 2012 that affected mainly groups with limited access to healthcare and schools. The findings emphasise the importance of genotyping during the different phases of an outbreak. A total of 8,170 cases were notified, and 5,093 (62%) of the 7,559 possible cases were serologically confirmed. RT-PCR was performed for 104 samples: from the 101 positive samples obtained from sporadic measles cases or clusters from different counties, 73 were genotyped. Sporadic measles cases associated with D4 and D5 viruses were observed from2008 to 2009. Genotype D4-Manchester was predominant in 2011 and 2012. In addition, the related variant D4-Maramures and MVs/Limoges.FRA/17.10[D4] and a few D4-Hamburg strains were detected. The detection of several distinct MV-D4 genotypes suggests multiple virus importations to Romania. The outbreak associated with D4 genotype is the second largest outbreak in Romania in less than 10 years.

Review of the temporal and geographical distribution of measles virus genotypes in the prevaccine and postvaccine eras

PubMed Central

Riddell, Michaela A; Rota, Jennifer S; Rota, Paul A

2005-01-01

Molecular epidemiological investigation of measles outbreaks can document the interruption of endemic measles transmission and is useful for establishing and clarifying epidemiological links between cases in geographically distinct clusters. To determine the distribution of measles virus genotypes in the prevaccine and postvaccine eras, a literature search of biomedical databases, measles surveillance websites and other electronic sources was conducted for English language reports of measles outbreaks or genetic characterization of measles virus isolates. Genotype assignments based on classification systems other than the currently accepted WHO nomenclature were reassigned using the current criteria. This review gives a comprehensive overview of the distribution of MV genotypes in the prevaccine and postvaccine eras and describes the geographically diverse distribution of some measles virus genotypes and the localized distributions of other genotypes. PMID:16303052

Measles virus-induced suppression of immune responses.

PubMed

Griffin, Diane E

2010-07-01

Measles is an important cause of child mortality that has a seemingly paradoxical interaction with the immune system. In most individuals, the immune response is successful in eventually clearing measles virus (MV) infection and in establishing life-long immunity. However, infection is also associated with persistence of viral RNA and several weeks of immune suppression, including loss of delayed type hypersensitivity responses and increased susceptibility to secondary infections. The initial T-cell response includes CD8+ and T-helper 1 CD4+ T cells important for control of infectious virus. As viral RNA persists, there is a shift to a T-helper 2 CD4+ T-cell response that likely promotes B-cell maturation and durable antibody responses but may suppress macrophage activation and T-helper 1 responses to new infections. Suppression of mitogen-induced lymphocyte proliferation can be induced by lymphocyte infection with MV or by lymphocyte exposure to a complex of the hemagglutinin and fusion surface glycoproteins without infection. Dendritic cells (DCs) are susceptible to infection and can transmit infection to lymphocytes. MV-infected DCs are unable to stimulate a mixed lymphocyte reaction and can induce lymphocyte unresponsiveness through expression of MV glycoproteins. Thus, multiple factors may contribute both to measles-induced immune suppression and to the establishment of durable protective immunity.

Expression of TNF-α, OPG, IL-1β and the presence of the measles virus RNA in the stapes of the patients with otosclerosis.

PubMed

Potocka-Bakłażec, Małgorzata; Sakowicz-Burkiewicz, Monika; Kuczkowski, Jerzy; Pawełczyk, Tadeusz; Stankiewicz, Czesław; Sierszeń, Wojciech; Jankowski, Zbigniew; Buczny, Jacek

2015-08-01

Persistent measles virus infections play a crucial role in the pathomechanism of otosclerosis. The study was undertaken to investigate the role of tumor necrosis factor-α (TNF-α), interleukin 1β (IL-1β) and osteoprotegerin (OPG) in otosclerotic bone remodeling and to assess the relation of TNF-α, OPG and IL-1β expression levels in otosclerotic stape footplates to the occurrence of measles virus infection. 61 patients with otosclerosis were treated surgically. Thirty-one stapes obtained from cadavers of people, who had died from a sudden cause were used as a control group. The presence of measles virus RNA and the expression levels of TNF-α, IL-1β and OPG in otosclerotic foci were assessed using one-step RT-PCR. The presence of measles virus RNA was noted in 80.3 % of otosclerotic stapes (49 out of 61) and 9.7 % of normal tissues (3 out of 31). Transcript of TNF-α, IL-1β and OPG was detected in 40, 46 and 18 virus-positive stapes, respectively. The transcript level of TNF-α and IL-1β was significantly higher in otosclerotic tissues comparing to normal tissue. The OPG expression level was significantly lower in otosclerotic tissues comparing to controls. The presence of measles virus RNA in the stapes may indicate its role in the pathogenesis of otosclerosis. The presence of TNF-α and IL-1β mRNA in the virus-positive stapes could be the result of viral antigen stimulation and may be a marker of inflammation the otosclerotic focus. The lack of OPG mRNA and the presence of TNF-α and IL-1β mRNA in the majority of otosclerotic tissues reflect the bone remodeling process occurring in the stapes.

What assay is optimal for the diagnosis of measles virus infection? An evaluation of the performance of a measles virus real-time reverse transcriptase PCR using the Cepheid SmartCycler(®) and antigen detection by immunofluorescence.

PubMed

Chua, Kyra Y L; Thapa, Kiran; Yapa, Chaturangi M; Somerville, Lucy K; Chen, Sharon C-A; Dwyer, Dominic E; Sheppeard, Vicky; Kok, Jen

2015-09-01

Despite the World Health Organization (WHO)-reported elimination of measles in Australia, importation of cases especially in travellers from Asia continues in Sydney, Australia's largest city. Laboratory confirmation supports clinico-epidemiological evidence of measles virus infection, and is needed to establish elimination. To evaluate the performance of a random access real-time reverse transcriptase polymerase chain reaction (RT-PCR) assay using the moderate complexity SmartCycler(®) platform, and measles antigen detection by immunofluorescence (IFA), for the detection of measles virus in patient samples. One hundred samples comprising nose and throat swabs, nasopharyngeal aspirates and urine, collected from patients with suspected measles were tested in parallel using IFA and nucleic acid testing using the SmartCycler(®) and LightCycler(®) RT-PCR platforms. The LightCycler(®) RT-PCR was used as the reference assay against which the SmartCycler(®) RT-PCR and IFA were compared. Using the LightCycler(®) RT-PCR, measles virus was detected in 35 clinical samples. There was 100% concordance between the results of the SmartCycler(®) and the LightCycler(®)-based RT-PCR. Measles genotypes detected included B3, D8, and D9. Testing urine in addition to NTS did not improve diagnostic yield. In contrast, the sensitivity and specificity of IFA compared to the reference LightCycler(®) RT-PCR was 34.3% and 96.7%, respectively. The performance of the SmartCycler(®) is comparable to the LightCycler(®) for the detection of measles virus. However, IFA had poor sensitivity and should not be used to confirm measles virus infection where nucleic acid testing is available. Copyright © 2015 Elsevier B.V. All rights reserved.

Molecular epidemiology of measles virus infection in Shanghai in 2000-2012: the first appearance of genotype D8.

PubMed

Li, Shuhua; Qian, Xiaohua; Yuan, Zhengan; Sun, Xiaodong; Li, Chongshan; Tang, Xian; Yang, Yanji; Gong, Xiangzhen; Cao, Guangwen

2014-01-01

The purpose of this study was to identify measles virus in Shanghai in 2012 and study the genotype trend of measles virus epidemic strains during 2000-2012. Nose and throat swab specimens were collected from 34 suspected measles cases in Shanghai. Measles virus was isolated using Vero-SLAM cells (African green monkey kidney cells/lymphoid signal activating factor-transfected African green monkey kidney cells). The 450 bp of C terminus of the N gene and the entire hemagglutinin gene sequence was amplified using RT-PCR. Phylogenetic analysis was performed by comparing the seven measles strains in Shanghai with the reference strains for H1a, H1b and D8 genotypes, as well as the Chinese measles virus vaccine strain. Seven measles viruses strains were isolated from the 34 throat swap specimens. Six strains were genotype H1a, which is the predominant strain in China and one strain was genotype D8, which is the first imported strain since 2000. All these seven strains maintained most of the glycosylation sites except subtype H1a, which lost one glycosylation site. Since 2000, measles virus strains in Shanghai are consistent with measles virus from other provinces in China with H1a being the predominant genotype. This study is also the first report of genotype D8 strain in Shanghai. All strains maintained their glycosylation sites except H1a that lost one glycosylation site. These strains could still be neutralized by the Chinese measles vaccine. We suggest that Shanghai Center for Disease Control laboratories should strengthen their approaches to monitor measles cases to prevent further spread of imported strains. Copyright © 2014 Elsevier Editora Ltda. All rights reserved.

Identification of measles virus genotype B3 associated with outbreaks in Islamabad, Pakistan, 2013-2015.

PubMed

Zaidi, Syed Sohail Zahoor; Hameed, Abdul; Suleman Rana, Muhammad; Alam, Muhammad Masroor; Umair, Massab; Aamir, Uzma Bashir; Hussain, Maqbool; Sharif, Salmaan; Shaukat, Shahzad; Angez, Mehar; Khurshid, Adnan

2017-11-09

Measles virus infection remains a significant cause of childhood mortality and morbidity despite continued global efforts and the availability of a safe and effective vaccine. Molecular analysis of indigenous measles viruses could provide critical information on outbreak linkages and transmission pathways that can aid the implementation of appropriate control programs in Pakistan. Blood samples and throat swabs were collected from subjects suspected with measles in Islamabad, Pakistan from 2013 to 2015. Serum samples were tested for the presence of measles immunoglobulin M (IgM) antibodies using enzyme-linked immunosorbent assay (ELISA) while throat swabs were used for the isolation (Vero/SLAM cell line) and subsequent characterization and phylogenetic analysis of measles strains. Of 373 blood samples, 66% tested positive for measles IgM. Male subjects were more often infected (58%) than female (42%) with the highest frequency of positive cases (63%) in the 0-5-years age group. Among the positive cases, only 13% had received one or two doses of the measles vaccine, while 87% were unvaccinated. Of 80 throat swabs, 29 (36%) showed a measles virus-specific cytopathic effect (CPE) and were characterized as genotype B3 through partial sequencing of the nucleoprotein (N) gene. Phylogenetic analysis revealed the Pakistani B3 strains to be closely related to strains from neighboring countries (Iran and Afghanistan) as well as with B3 viruses from the USA, Germany, and the UK. The study results showed that despite the availability of an effective vaccine, the burden of measles infections is very high in Pakistan due to poor routine immunization coverage even in major cities, including the capital city of Islamabad. It is imperative that national health authorities take urgent strategic steps to improve routine immunization and implement adequate molecular identification methods to tackle future measles outbreaks. Copyright © 2017 The Authors. Published by Elsevier Ltd

Measles Vaccination of Nonhuman Primates Provides Partial Protection against Infection with Canine Distemper Virus

PubMed Central

de Vries, Rory D.; Ludlow, Martin; Verburgh, R. Joyce; van Amerongen, Geert; Yüksel, Selma; Nguyen, D. Tien; McQuaid, Stephen; Osterhaus, Albert D. M. E.; Duprex, W. Paul

2014-01-01

ABSTRACT Measles virus (MV) is being considered for global eradication, which would likely reduce compliance with MV vaccination. As a result, children will grow up without MV-specific immunity, creating a potential niche for closely related animal morbilliviruses such as canine distemper virus (CDV). Natural CDV infection causing clinical signs has never been reported in humans, but recent outbreaks in captive macaques have shown that CDV can cause disease in primates. We studied the virulence and tropism of recombinant CDV expressing enhanced green fluorescent protein in naive and measles-vaccinated cynomolgus macaques. In naive animals CDV caused viremia and fever and predominantly infected CD150+ lymphocytes and dendritic cells. Virus was reisolated from the upper and lower respiratory tracts, but infection of epithelial or neuronal cells was not detectable at the time points examined, and the infections were self-limiting. This demonstrates that CDV readily infects nonhuman primates but suggests that additional mutations are necessary to achieve full virulence in nonnatural hosts. Partial protection against CDV was observed in measles-vaccinated macaques, as demonstrated by accelerated control of virus replication and limited shedding from the upper respiratory tract. While neither CDV infection nor MV vaccination induced detectable cross-reactive neutralizing antibodies, MV-specific neutralizing antibody levels of MV-vaccinated macaques were boosted by CDV challenge infection, suggesting that cross-reactive VN epitopes exist. Rapid increases in white blood cell counts in MV-vaccinated macaques following CDV challenge suggested that cross-reactive cellular immune responses were also present. This study demonstrates that zoonotic morbillivirus infections can be controlled by measles vaccination. IMPORTANCE Throughout history viral zoonoses have had a substantial impact on human health. Given the drive toward global eradication of measles, it is essential to

Measles vaccination of nonhuman primates provides partial protection against infection with canine distemper virus.

PubMed

de Vries, Rory D; Ludlow, Martin; Verburgh, R Joyce; van Amerongen, Geert; Yüksel, Selma; Nguyen, D Tien; McQuaid, Stephen; Osterhaus, Albert D M E; Duprex, W Paul; de Swart, Rik L

2014-04-01

Measles virus (MV) is being considered for global eradication, which would likely reduce compliance with MV vaccination. As a result, children will grow up without MV-specific immunity, creating a potential niche for closely related animal morbilliviruses such as canine distemper virus (CDV). Natural CDV infection causing clinical signs has never been reported in humans, but recent outbreaks in captive macaques have shown that CDV can cause disease in primates. We studied the virulence and tropism of recombinant CDV expressing enhanced green fluorescent protein in naive and measles-vaccinated cynomolgus macaques. In naive animals CDV caused viremia and fever and predominantly infected CD150(+) lymphocytes and dendritic cells. Virus was reisolated from the upper and lower respiratory tracts, but infection of epithelial or neuronal cells was not detectable at the time points examined, and the infections were self-limiting. This demonstrates that CDV readily infects nonhuman primates but suggests that additional mutations are necessary to achieve full virulence in nonnatural hosts. Partial protection against CDV was observed in measles-vaccinated macaques, as demonstrated by accelerated control of virus replication and limited shedding from the upper respiratory tract. While neither CDV infection nor MV vaccination induced detectable cross-reactive neutralizing antibodies, MV-specific neutralizing antibody levels of MV-vaccinated macaques were boosted by CDV challenge infection, suggesting that cross-reactive VN epitopes exist. Rapid increases in white blood cell counts in MV-vaccinated macaques following CDV challenge suggested that cross-reactive cellular immune responses were also present. This study demonstrates that zoonotic morbillivirus infections can be controlled by measles vaccination. Throughout history viral zoonoses have had a substantial impact on human health. Given the drive toward global eradication of measles, it is essential to understand the

Expression of defective measles virus genes in brain tissues of patients with subacute sclerosing panencephalitis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Baczko, K.; Liebert, U.G.; Billeter, M.

1986-08-01

The persistence of measles virus in selected areas of the brains of four patients with subacute sclerosing panencephalitis (SSPE) was characterized by immunohistological and biochemical techniques. The five measles virus structural proteins were never simultaneously detectable in any of the bran sections. Nucleocapsid proteins and phosphoproteins were found in every diseased brain area, whereas hemagglutinin protein was detected in two cases, fusion protein was detected in three cases, and matrix protein was detected in only one case. Also, it could be shown that the amounts of measles virus RNA in the brains differed from patient to patient and in themore » different regions investigated. In all patients, plus-strand RNAs specific for these five viral genes could be detected. However, the amounts of fusion and hemagglutinin mRNAs were low compared with the amounts in lytically infected cells. The presence of particular measles virus RNAs in SSPE-infected brains did not always correlate with mRNA activity. In in vitro translations, the matrix protein was produced in only one case, and the hemagglutinin protein was produced in none. These results indicate that measles virus persistence in SSPE is correlated with different defects of several genes which probably prevent assembly of viral particles in SSPE-infected brain tissue.« less

Structure of the measles virus hemagglutinin bound to its cellular receptor SLAM.

PubMed

Hashiguchi, Takao; Ose, Toyoyuki; Kubota, Marie; Maita, Nobuo; Kamishikiryo, Jun; Maenaka, Katsumi; Yanagi, Yusuke

2011-02-01

Measles virus, a major cause of childhood morbidity and mortality worldwide, predominantly infects immune cells using signaling lymphocyte activation molecule (SLAM) as a cellular receptor. Here we present crystal structures of measles virus hemagglutinin (MV-H), the receptor-binding glycoprotein, in complex with SLAM. The MV-H head domain binds to a β-sheet of the membrane-distal ectodomain of SLAM using the side of its β-propeller fold. This is distinct from attachment proteins of other paramyxoviruses that bind receptors using the top of their β-propeller. The structure provides templates for antiviral drug design, an explanation for the effectiveness of the measles virus vaccine, and a model of the homophilic SLAM-SLAM interaction involved in immune modulations. Notably, the crystal structures obtained show two forms of the MV-H-SLAM tetrameric assembly (dimer of dimers), which may have implications for the mechanism of fusion triggering.

Towards measles elimination: Phylogenetic analysis of measles viruses in Turkey (2012-2013) and identification of genotype D8.

PubMed

Kalaycioglu, Atila T; Yolbakan, Sultan; Guldemir, Dilek; Korukluoglu, Gulay; Coskun, Aslihan; Cosgun, Yasemin; Durmaz, Riza

2016-11-01

Molecular characterization of different measles virus (MV) strains is essential to combat the disease. Sixty measles MV strains were obtained from throat swabs or urine of patients in Turkey between 2012 and 2013 and characterized. MV RNA sequences (n = 60) were analysed for 456 nucleotides representing hypervariable domain of the nucleoprotein (N) gene. Of the 60 strains analysed 53 were the D8 genotype, 6 were B3, 1 was D4, and 1 was A. This report describes MV genotype D8 that was involved in a measles outbreak in Turkey. Sequences of most genotype D8 strains (n = 51) were identical to the sequence of variant D8-Frankfurt-Main, which has been associated with outbreaks throughout Europe. Despite the lack of epidemiologic information, a phylogenetic analysis suggested that the genotype D8 MV may have been brought to Turkey from elsewhere. Phylogenetic and epidemiological findings suggested that strains identified in tourists and associated with importation included one strain of genotype D8, one strain of genotype B3, and one strain of genotype D4. These findings from the 2012 to 2013 outbreak in Turkey confirm that pockets of unimmunised individuals are making the country susceptible to measles outbreaks. To prevent further outbreaks, deliberate and sustained effort must be made to reach, and immunise susceptible age groups. Towards measles elimination process, continued molecular surveillance of measles strains in Turkey will help identify transmission patterns of virus and evaluate vaccination efforts. J. Med. Virol. 88:1867-1873, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Measles.

PubMed

Rota, Paul A; Moss, William J; Takeda, Makoto; de Swart, Rik L; Thompson, Kimberly M; Goodson, James L

2016-07-14

Measles is an infectious disease in humans caused by the measles virus (MeV). Before the introduction of an effective measles vaccine, virtually everyone experienced measles during childhood. Symptoms of measles include fever and maculopapular skin rash accompanied by cough, coryza and/or conjunctivitis. MeV causes immunosuppression, and severe sequelae of measles include pneumonia, gastroenteritis, blindness, measles inclusion body encephalitis and subacute sclerosing panencephalitis. Case confirmation depends on clinical presentation and results of laboratory tests, including the detection of anti-MeV IgM antibodies and/or viral RNA. All current measles vaccines contain a live attenuated strain of MeV, and great progress has been made to increase global vaccination coverage to drive down the incidence of measles. However, endemic transmission continues in many parts of the world. Measles remains a considerable cause of childhood mortality worldwide, with estimates that >100,000 fatal cases occur each year. Case fatality ratio estimates vary from <0.01% in industrialized countries to >5% in developing countries. All six WHO regions have set goals to eliminate endemic transmission of MeV by achieving and maintaining high levels of vaccination coverage accompanied by a sensitive surveillance system. Because of the availability of a highly effective and relatively inexpensive vaccine, the monotypic nature of the virus and the lack of an animal reservoir, measles is considered a candidate for eradication.

Molecular analysis of rubella virus in travelers suspected of measles infection in São Paulo, Brazil.

PubMed

Figueiredo, Cristina A; Yu, Ana Lucia Frugis; Afonso, Ana Maria S; Curti, Suely P; Oliveira, Maria I

2012-01-01

To identify measles virus genotypes in three cases of travelers suspected of measles infection. Samples (blood and urine) were collected for serology, virus isolation, and genotyping. Sera were analyzed for IgM antibodies against measles virus and rubella virus by enzyme-linked immunosorbent assay (ELISA) (Siemens - Marburg, Germany). Clinical samples (lymphocytes and urine) were inoculated into Statens Serum Institute rabbit corneal epithelial cell line- ATCC CL 60 (SIRC) and Vero Slam cells. RNA was extracted from clinical samples and cell culture was inoculated and processed by polymerase chain reaction (PCR) with oligonucleotides specific for measles virus (MV) and rubella virus (RV). All patients showed IgM negative serology for MV and positive IgM for RV. RV belonging to genotypes 1B, 1C, and 1E were isolated from patients who came from Finland, Peru, and Germany, respectively. Genotype 1B has been found in Europe and on the East Coast of South America; 1C has been found in Peru and the West Coast of South America, and 1E, first identified in 1997, now appears to have worldwide distribution. Information about RV and MV genotypes circulating in São Paulo is essential for the control of measles, rubella, and congenital rubella syndrome (CRS) in Brazil.

Genetic characterization of measles virus in the Philippines, 2008-2011.

PubMed

Centeno, Rex; Fuji, Naoko; Okamoto, Michiko; Dapat, Clyde; Saito, Mariko; Tandoc, Amado; Lupisan, Socorro; Oshitani, Hitoshi

2015-06-03

Large outbreaks of measles occurred in the Philippines in 2010 and 2011. Genetic analysis was performed to identify the genotype of measles virus (MeV) that was responsible for the large outbreaks. A total of 114 representative MeVs that were detected in the Philippines from 2008 to 2011 were analyzed by sequencing the C-terminal region of nucleocapsid (N) gene and partial hemagglutinin (H) gene and by inferring the phylogenetic trees. Genetic analysis showed that genotype D9 was the predominant circulating strain during the 4-year study period. Genotype D9 was detected in 23 samples (92%) by N gene sequencing and 93 samples (94%) by H gene analysis. Sporadic cases of genotype G3 MeV were identified in 2 samples (8%) by N gene sequencing and 6 samples (6%) by H gene analysis. Genotype G3 MeV was detected mainly in Panay Island in 2009 and 2010. Molecular clock analysis of N gene showed that the recent genotype D9 viruses that caused the big outbreaks in 2010 and 2011 diverged from a common ancestor in 2005 in one of the neighboring Southeast Asian countries, where D9 was endemic. These big outbreaks of measles resulted in a spillover and were associated with genotype D9 MeV importation to Japan and the USA. Genotype D9 MeV became endemic and caused two big outbreaks in the Philippines in 2010 and 2011. Genotype G3 MeV was detected sporadically with limited geographic distribution. This study highlights the importance of genetic analysis not only in helping with the assessment of measles elimination program in the country but also in elucidating the transmission dynamics of measles virus.

Safety Study: Intraventricular Injection of a Modified Oncolytic Measles Virus into Measles-Immune, hCD46-Transgenic, IFNαRko Mice.

PubMed

Lal, Sangeet; Peng, Kah-Whye; Steele, Michael B; Jenks, Nathan; Ma, Hong; Kohanbash, Gary; Phillips, Joanna J; Raffel, Corey

2016-12-01

The modified Edmonston vaccine strain of measles virus (MV) has shown potent oncolytic efficacy against various tumor types and is being investigated in clinical trials. Our laboratory showed that MV effectively kills medulloblastoma tumor cells in both localized disease and when tumor cells are disseminated through cerebrospinal fluid (CSF). Although the safety of repeated intracerebral injection of modified MV in rhesus macaques has been established, the safety of administering MV into CSF has not been adequately investigated. In this study, we assessed the safety of MV-NIS (MV modified to express the human sodium iodide symporter protein) injected into the CSF of measles-immunized and measles virus-susceptible transgenic (CD46, IFNαRko) mice. Treated animals were administered a single intraventricular injection of 1 × 10 5 or 1 × 10 6 TCID 50 (50% tissue culture infective dose) of MV-NIS. Detailed clinical observation was performed over a 90-day period. Clinically, we did not observe any measles-related toxic effects or behavioral abnormality in animals of any treated cohort. The complete blood count and blood chemistry analysis results were found to be within normal range for all the cohorts. Histologic examination of brains and spinal cords revealed inflammatory changes, mostly related to the needle track; these resolved by day 21 postinjection. To assess viral biodistribution, quantitative RT-PCR to detect the measles virus N-protein was performed on blood and brain samples. Viral RNA was not detectable in the blood as soon as 2 days after injection, and virus cleared from the brain by 45 days postadministration in all treatment cohorts. In conclusion, our data suggest that a single injection of modified MV into the CSF is safe and can be used in future therapeutic applications.

Measles Virus Neutralizing Antibodies in Intravenous Immunoglobulins: Is an Increase by Revaccination of Plasma Donors Possible?

PubMed

Modrof, Jens; Tille, Björn; Farcet, Maria R; McVey, John; Schreiner, Jessica A; Borders, Charles M; Gudino, Maria; Fitzgerald, Peter; Simon, Toby L; Kreil, Thomas R

2017-11-15

We report a screen of plasma donors confirming that widespread use of childhood measles vaccination since 1963 resulted in a decrease in average measles virus antibody titers among plasma donors, which is reflected in intravenous immunoglobulins (IVIGs). The measles virus antibody titer, however, is a potency requirement for IVIGs, as defined in a Food and Drug Administration regulation. To mitigate the decline in measles virus antibody titers in IVIGs and to ensure consistent product release, revaccination of plasma donors was investigated as a means to boost titers. However, revaccination-induced titer increases were only about 2-fold and short-lived. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Detection of measles, mumps, and rubella viruses.

PubMed

Tipples, Graham; Hiebert, Joanne

2011-01-01

Measles, mumps, and rubella are infections caused by RNA viruses of the same name and are vaccine preventable. The vaccines are frequently administered in a trivalent form. Laboratory diagnostic methods can include indirect detection via antibody (IgM and IgG) detection methods and direct detection by viral culture or viral genome detection. There are challenges for the laboratory in areas with low prevalence due to high vaccine uptake. In those areas, routine serological methods such as IgM detection may have a reduced positive predictive value and thus require confirmation by other methods. Direct detection of viral genomic material using reverse transcription polymerase chain reaction (RT-PCR) methodologies can play an important role for laboratory confirmation of acute infections. Furthermore, genotyping of these three viruses provides useful molecular epidemiological data for differentiating vaccine from wild-type strains, linking cases and outbreaks, and tracking geographic spread and elimination. The purpose of this chapter is to provide guidance for the laboratory diagnosis of measles, mumps, and rubella virus infections. Where assays are commercially available or previously published, the appropriate references are provided as well as brief comments on the interpretation of results. Detailed protocols are provided for the molecular assays which have been developed and more commonly applied in recent years.

Rapid Titration of Measles and Other Viruses: Optimization with Determination of Replication Cycle Length

PubMed Central

Grigorov, Boyan; Rabilloud, Jessica; Lawrence, Philip; Gerlier, Denis

2011-01-01

Background Measles virus (MV) is a member of the Paramyxoviridae family and an important human pathogen causing strong immunosuppression in affected individuals and a considerable number of deaths worldwide. Currently, measles is a re-emerging disease in developed countries. MV is usually quantified in infectious units as determined by limiting dilution and counting of plaque forming unit either directly (PFU method) or indirectly from random distribution in microwells (TCID50 method). Both methods are time-consuming (up to several days), cumbersome and, in the case of the PFU assay, possibly operator dependent. Methods/Findings A rapid, optimized, accurate, and reliable technique for titration of measles virus was developed based on the detection of virus infected cells by flow cytometry, single round of infection and titer calculation according to the Poisson's law. The kinetics follow up of the number of infected cells after infection with serial dilutions of a virus allowed estimation of the duration of the replication cycle, and consequently, the optimal infection time. The assay was set up to quantify measles virus, vesicular stomatitis virus (VSV), and human immunodeficiency virus type 1 (HIV-1) using antibody labeling of viral glycoprotein, virus encoded fluorescent reporter protein and an inducible fluorescent-reporter cell line, respectively. Conclusion Overall, performing the assay takes only 24–30 hours for MV strains, 12 hours for VSV, and 52 hours for HIV-1. The step-by-step procedure we have set up can be, in principle, applicable to accurately quantify any virus including lentiviral vectors, provided that a virus encoded gene product can be detected by flow cytometry. PMID:21915289

Measles Virus Fusion Protein: Structure, Function and Inhibition

PubMed Central

Plattet, Philippe; Alves, Lisa; Herren, Michael; Aguilar, Hector C.

2016-01-01

Measles virus (MeV), a highly contagious member of the Paramyxoviridae family, causes measles in humans. The Paramyxoviridae family of negative single-stranded enveloped viruses includes several important human and animal pathogens, with MeV causing approximately 120,000 deaths annually. MeV and canine distemper virus (CDV)-mediated diseases can be prevented by vaccination. However, sub-optimal vaccine delivery continues to foster MeV outbreaks. Post-exposure prophylaxis with antivirals has been proposed as a novel strategy to complement vaccination programs by filling herd immunity gaps. Recent research has shown that membrane fusion induced by the morbillivirus glycoproteins is the first critical step for viral entry and infection, and determines cell pathology and disease outcome. Our molecular understanding of morbillivirus-associated membrane fusion has greatly progressed towards the feasibility to control this process by treating the fusion glycoprotein with inhibitory molecules. Current approaches to develop anti-membrane fusion drugs and our knowledge on drug resistance mechanisms strongly suggest that combined therapies will be a prerequisite. Thus, discovery of additional anti-fusion and/or anti-attachment protein small-molecule compounds may eventually translate into realistic therapeutic options. PMID:27110811

Measles Virus Fusion Protein: Structure, Function and Inhibition.

PubMed

Plattet, Philippe; Alves, Lisa; Herren, Michael; Aguilar, Hector C

2016-04-21

Measles virus (MeV), a highly contagious member of the Paramyxoviridae family, causes measles in humans. The Paramyxoviridae family of negative single-stranded enveloped viruses includes several important human and animal pathogens, with MeV causing approximately 120,000 deaths annually. MeV and canine distemper virus (CDV)-mediated diseases can be prevented by vaccination. However, sub-optimal vaccine delivery continues to foster MeV outbreaks. Post-exposure prophylaxis with antivirals has been proposed as a novel strategy to complement vaccination programs by filling herd immunity gaps. Recent research has shown that membrane fusion induced by the morbillivirus glycoproteins is the first critical step for viral entry and infection, and determines cell pathology and disease outcome. Our molecular understanding of morbillivirus-associated membrane fusion has greatly progressed towards the feasibility to control this process by treating the fusion glycoprotein with inhibitory molecules. Current approaches to develop anti-membrane fusion drugs and our knowledge on drug resistance mechanisms strongly suggest that combined therapies will be a prerequisite. Thus, discovery of additional anti-fusion and/or anti-attachment protein small-molecule compounds may eventually translate into realistic therapeutic options.

Protection of Mice from Fatal Measles Encephalitis by Vaccination with Vaccinia Virus Recombinants Encoding Either the Hemagglutinin or the Fusion Protein

NASA Astrophysics Data System (ADS)

Drillien, Robert; Spehner, Daniele; Kirn, Andre; Giraudon, Pascale; Buckland, Robin; Wild, Fabian; Lecocq, Jean-Pierre

1988-02-01

Vaccinia virus recombinants encoding the hemagglutinin or fusion protein of measles virus have been constructed. Infection of cell cultures with the recombinants led to the synthesis of authentic measles proteins as judged by their electrophoretic mobility, recognition by antibodies, glycosylation, proteolytic cleavage, and presentation on the cell surface. Mice vaccinated with a single dose of the recombinant encoding the hemagglutinin protein developed antibodies capable of both inhibiting hemagglutination activity and neutralizing measles virus, whereas animals vaccinated with the recombinant encoding the fusion protein developed measles neutralizing antibodies. Mice vaccinated with either of the recombinants resisted a normally lethal intracerebral inoculation of a cell-associated measles virus subacute sclerosing panencephalitis strain.

Evaluation of Measles Vaccine Virus as a Vector to Deliver Respiratory Syncytial Virus Fusion Protein or Epstein-Barr Virus Glycoprotein gp350

PubMed Central

Mok, Hoyin; Cheng, Xing; Xu, Qi; Zengel, James R; Parhy, Bandita; Zhao, Jackie; Wang, C. Kathy; Jin, Hong

2012-01-01

Live attenuated recombinant measles vaccine virus (MV) Edmonston-Zagreb (EZ) strain was evaluated as a viral vector to express the ectodomains of fusion protein of respiratory syncytial virus (RSV F) or glycoprotein 350 of Epstein-Barr virus (EBV gp350) as candidate vaccines for prophylaxis of RSV and EBV. The glycoprotein gene was inserted at the 1st or the 3rd position of the measles virus genome and the recombinant viruses were generated. Insertion of the foreign gene at the 3rd position had a minimal impact on viral replication in vitro. RSV F or EBV gp350 protein was secreted from infected cells. In cotton rats, EZ-RSV F and EZ-EBV gp350 induced MV- and insert-specific antibody responses. In addition, both vaccines also induced insert specific interferon gamma (IFN-γ) secreting T cell response. EZ-RSV F protected cotton rats from pulmonary replication of RSV A2 challenge infection. In rhesus macaques, although both EZ-RSV F and EZ-EBV gp350 induced MV specific neutralizing antibody responses, only RSV F specific antibody response was detected. Thus, the immunogenicity of the foreign antigens delivered by measles vaccine virus is dependent on the nature of the insert and the animal models used for vaccine evaluation. PMID:22383906

Molecular epidemiology of measles viruses in China, 1995–2003

PubMed Central

Zhang, Yan; Zhu, Zhen; Rota, Paul A; Jiang, Xiaohong; Hu, Jiayu; Wang, Jianguo; Tang, Wei; Zhang, Zhenying; Li, Congyong; Wang, Changyin; Wang, Tongzhan; Zheng, Lei; Tian, Hong; Ling, Hua; Zhao, Chunfang; Ma, Yan; Lin, Chunyan; He, Jilan; Tian, Jiang; Ma, Yan; Li, Ping; Guan, Ronghui; He, Weikuan; Zhou, Jianhui; Liu, Guiyan; Zhang, Hong; Yan, Xinge; Yang, Xuelei; Zhang, Jinlin; Lu, Yiyu; Zhou, Shunde; Ba, Zhuoma; Liu, Wei; Yang , Xiuhui; Ma, Yujie; Liang, Yong; Li, Yeqiang; Ji, Yixin; Featherstone, David; Bellini, William J; Xu, Songtao; Liang, Guodong; Xu, Wenbo

2007-01-01

This report describes the genetic characterization of 297 wild-type measles viruses that were isolated in 24 provinces of China between 1995 and 2003. Phylogenetic analysis of the N gene sequences showed that all of the isolates belonged to genotype H1 except 3 isolates, which were genotype A. The nucleotide sequence and predicted amino acid homologies of the 294-genotype H1 strains were 94.7%–100% and 93.3%–100%, respectively. The genotype H1 isolates were divided into 2 clusters, which differed by approximately 2.9% at the nucleotide level. Viruses from both clusters were distributed throughout China with no apparent geographic restriction and multiple co-circulating lineages were present in many provinces. Even though other measles genotypes have been detected in countries that border China, this report shows that genotype H1 is widely distributed throughout the country and that China has a single, endemic genotype. This important baseline data will help to monitor the progress of measles control in China. PMID:17280609

Measles

MedlinePlus

Measles is an infectious disease caused by a virus. It spreads easily from person to person. It ... down Tiny white spots inside the mouth Sometimes measles can lead to serious problems. There is no ...

Immunogenicity of peptides of measles virus origin and influence of adjuvants.

PubMed

Halassy, Beata; Mateljak, Sanja; Bouche, Fabienne B; Pütz, Mike M; Muller, Claude P; Frkanec, Ruza; Habjanec, Lidija; Tomasić, Jelka

2006-01-12

Epitope-based peptide antigens have been under development for protection against measles virus. The immunogenicity of five peptides composed of the same B cell epitope (BCE) (H236-250 of the measles virus hemagglutinin), and different T cell epitopes of measles virus fusion protein (F421-435, F256-270, F288-302) and nucleoprotein (NP335-345) was studied in mice (subcutaneous immunisation). The adjuvant effects of peptidoglycan monomer (PGM), Montanide ISA 720 and 206 were also investigated. Results showed basic differences in peptide immunogenicity that were consistent with already described structural differences. PGM elevated peptide-specific IgG when applied together with four of five tested peptides. A strong synergistic effect was observed after co-immunisation of mice with a mixture containing all five chimeric peptides in small and equal amounts. Results revealed for the first time that immunisation with several peptides having the common BCE generated significantly higher levels of both anti-peptide and anti-BCE IgG in comparison to those obtained after immunisation with a single peptide in much higher quantity. Further improvement of immune response was obtained after incorporation of such a peptide mixture into oil-based adjuvants.

Implementation of a national measles elimination program in Iran: Phylogenetic analysis of measles virus strains isolated during 2010-2012 outbreaks.

PubMed

Salimi, Vahid; Abbasi, Simin; Zahraei, Seyed Mohsen; Fatemi-Nasab, Ghazal; Adjaminezhad-Fard, Fatemeh; Shadab, Azadeh; Ghavami, Nastaran; Zareh-Khoshchehre, Raziyeh; Soltanshahi, Rambod; Bont, Louis; Mokhtari-Azad, Talat

2014-01-01

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.

No evidence of persisting measles virus in peripheral blood mononuclear cells from children with autism spectrum disorder.

PubMed

D'Souza, Yasmin; Fombonne, Eric; Ward, Brian J

2006-10-01

Despite epidemiologic evidence to the contrary, claims of an association between measles-mumps-rubella vaccination and the development of autism have persisted. Such claims are based primarily on the identification of measles virus nucleic acids in tissues and body fluids by polymerase chain reaction. We sought to determine whether measles virus nucleic acids persist in children with autism spectrum disorder compared with control children. Peripheral blood mononuclear cells were isolated from 54 children with autism spectrum disorder and 34 developmentally normal children, and up to 4 real-time polymerase chain reaction assays and 2 nested polymerase chain reaction assays were performed. These assays targeted the nucleoprotein, fusion, and hemagglutinin genes of measles virus using previously published primer pairs with detection by SYBR green I. Our own real-time assay targeted the fusion gene using novel primers and an internal fluorescent probe. Positive reactions were evaluated rigorously, and amplicons were sequenced. Finally, anti-measles antibody titers were measured by enzyme immunoassay. The real-time assays based on previously published primers gave rise to a large number of positive reactions in both autism spectrum disorder and control samples. Almost all of the positive reactions in these assays were eliminated by evaluation of melting curves and amplicon band size. The amplicons for the remaining positive reactions were cloned and sequenced. No sample from either autism spectrum disorder or control groups was found to contain nucleic acids from any measles virus gene. In the nested polymerase chain reaction and in-house assays, none of the samples yielded positive results. Furthermore, there was no difference in anti-measles antibody titers between the autism and control groups. There is no evidence of measles virus persistence in the peripheral blood mononuclear cells of children with autism spectrum disorder.

[Genetic Characterization of Hemagglutinin on Measles Virus Epidemic Strain Genotype H1a in Liaoning Province (China) from 1997 to 2014].

PubMed

Wang, Yan; Ma, Yan; Xu, Xiaoting; Hao, Shuang; Han, Yue; Yao, Wenqing; Zhao, Zhuo

2015-07-01

To wished to characterize the hemagglutinin (H) gene of the measles virus epidemic strain H1a in Liaoning Province (China) from 1997-2014 to provide a basis for the control and elimination of measles. All 63 measles virus strains were the H1a genotype. Fragments of the H gene (1854 nucleotides) and nucleoprotein (N) gene (450 nucleotides) were amplified by reverse transcription-polymerase chain reaction (RT-PCR) and the PCR products sequenced and analyzed. Phylogenetic-trees were constructed with reference strains of the genotype-H measles virus downloaded from GenBank, including Chinese measles virus strains isolated in 1993-1994 and the vaccine reference strains S-191 and C-47. Sixty-three strains of the measles virus in 1997-2014 belonged to genotype H1a. The mean evolutionary rate for gene N-450 was higher than that for the H gene. All 63 strains of the measles virus were mutated from: serine (Ser S) to asparagine (Asn N) in the 240th amino acid; arginine (Arg R) to glycine (Gly G) in the 243th; and tyrosine (Tyr Y) to Asn N in the 481th amino acid. All measles virus strains in cluster 2 were mutated from proline (Pro P) to leucine (Leu L) in the 397th amino acid. The other neutralization sites showed no apparent difference when comparing the nucleotides/amino acids of the H gene of S191 vaccine strains.

Extreme mortality after first introduction of measles virus to the polynesian island of Rotuma, 1911.

PubMed

Shanks, G Dennis; Lee, Seung-Eun; Howard, Alan; Brundage, John F

2011-05-15

Rotuma is an isolated Polynesian island. In January 1911, most residents of Rotuma (population approximately 2,600) were exposed to measles virus for the first time. The official mortality register documented 491 deaths due to all causes among Rotumans during 1911 (cumulative measles-related mortality: 12.8%); most deaths occurred in April-May and were attributed to measles and its sequelae. Measles-related mortality rates were higher among young children (23.4 per 100 person-years) and young adults (17.1 per 100 person-years) than among adolescents (11.0 per 100 person-years) and older adults (5.6 per 100 person-years); females (16.2 per 100 person-years) died at a higher rate than males (13.2 per 100 person-years). Gastrointestinal complications (75%), not respiratory complications, were the predominant clinical manifestations of fatal measles cases; tuberculosis mortality was unusually high during the year of the epidemic. In 1911, measles-related mortality varied by nearly 3-fold across geographic districts (range, 7.4%-21.6%). The extreme mortality due to measles on Rotuma typifies the experiences of isolated populations after first encounters with measles; it suggests that prior exposures to a narrow range of microbes and genetic homogeneity predispose isolated populations to lethal outcomes when they are first exposed to highly contagious and pathogenic viruses (e.g., measles, influenza).

Phylogenetic analysis of the nucleoprotein gene of measles viruses prevalent in Nantong, Jiangsu Province, China, during 2010.

PubMed

Li, H; Spencer, S D; Lian, L; Zhang, Z; Lu, P

2012-09-01

Measles control in China is monitored in part by surveillance of circulating wild-type viruses. The objective of this study was genetic characterization and phylogenetic analysis of measles strains in the Nantong City region of Jiangsu province, China, during 2010. Sera from suspected cases were tested for IgM antibodies and measles virus isolated by inoculation of transport medium onto Vero/SLAM cells. Isolated strains were phylogenetically analysed according to the nucleotide sequence of the C-terminal region of the nucleoprotein gene amplified by RT-PCR. The results revealed 34 cases confirmed by positive IgM, for an incidence of 0·45/100 000. Six isolates identified were all clustered within genotype H1. The findings reported here support continued endemic transmission of measles virus in China.

Occurrence of measles in a country with elimination status: Amplifying measles infection in hospitalized children due to imported virus.

PubMed

Eom, HyeEun; Park, YoungJoon; Kim, JooWhee; Yang, Jeong-Sun; Kang, HaeJi; Kim, Kisoon; Chun, Byung Chul; Park, Ok; Hong, Jeong Ik

2018-01-01

The Republic of Korea declared measles elimination in 2006. However, a measles outbreak occurred in 2013. This study aimed to identify the epidemiological characteristics of the sources of infection and the pattern of measles transmission in 2013 in South Korea. We utilized surveillance data, epidemiological data, immunization registry data, and genetic information. We describe the epidemiological characteristics of all measles case patients (sex, age distribution, vaccination status, sources of infection) as well as details of the outbreak (the pattern of transmission, duration, mean age of patients, and generation time). In 2013, a total of 107 measles cases were notified. Most patients were infants (43.0%) and unvaccinated individuals (60.7%). We identified 4 imported and 103 import-related cases. A total of 105 cases were related to four outbreaks that occurred in Gyeongnam, northern Gyeonggi, southern Gyeonggi, and Seoul. The predominant circulating genotype was B3 type, which was identified in the Gyeongnam, northern Gyeonggi, and southern Gyeonggi outbreaks. The B3 type had not been in circulation in South Korea in the previous 3 years; virologic evidence suggests that these outbreaks were import-related. Most measles cases in South Korea have been associated with imported measles virus. Although Korea has maintained a high level of herd immunity, clustering of susceptible people can cause such measles outbreaks.

Occurrence of measles in a country with elimination status: Amplifying measles infection in hospitalized children due to imported virus

PubMed Central

Eom, HyeEun; Park, YoungJoon; Kim, JooWhee; Yang, Jeong-Sun; Kang, HaeJi; Kim, Kisoon; Chun, Byung Chul; Park, Ok; Hong, Jeong Ik

2018-01-01

The Republic of Korea declared measles elimination in 2006. However, a measles outbreak occurred in 2013. This study aimed to identify the epidemiological characteristics of the sources of infection and the pattern of measles transmission in 2013 in South Korea. We utilized surveillance data, epidemiological data, immunization registry data, and genetic information. We describe the epidemiological characteristics of all measles case patients (sex, age distribution, vaccination status, sources of infection) as well as details of the outbreak (the pattern of transmission, duration, mean age of patients, and generation time). In 2013, a total of 107 measles cases were notified. Most patients were infants (43.0%) and unvaccinated individuals (60.7%). We identified 4 imported and 103 import-related cases. A total of 105 cases were related to four outbreaks that occurred in Gyeongnam, northern Gyeonggi, southern Gyeonggi, and Seoul. The predominant circulating genotype was B3 type, which was identified in the Gyeongnam, northern Gyeonggi, and southern Gyeonggi outbreaks. The B3 type had not been in circulation in South Korea in the previous 3 years; virologic evidence suggests that these outbreaks were import-related. Most measles cases in South Korea have been associated with imported measles virus. Although Korea has maintained a high level of herd immunity, clustering of susceptible people can cause such measles outbreaks. PMID:29447169

Simultaneous co-detection of wild-type and vaccine strain measles virus using the BD MAX system.

PubMed

Thapa, Kiran; Ellem, Justin A; Basile, Kerri; Carter, Ian; Olma, Tom; Chen, Sharon C-A; Dwyer, Dominic E; Kok, Jen

2018-06-01

Despite the reported elimination of measles virus in Australia, importation of cases from endemic countries continues to lead to secondary local transmission and outbreaks. Rapid laboratory confirmation of measles is paramount for individual patient management and outbreak responses. Further, it is important to rapidly distinguish infection from wild-type virus or vaccine strains to guide public health responses. We developed a high throughput, TaqMan-based multiplex reverse-transcription-polymerase chain reaction (PCR) assay using the BD MAX platform (Becton Dickinson) that simultaneously detects measles virus and differentiates between wild-type and vaccine strains without the need for sequencing. Copyright © 2018 Royal College of Pathologists of Australasia. Published by Elsevier B.V. All rights reserved.

Assessment of humoral and cell-mediated immune response to measles-mumps-rubella vaccine viruses among patients with asthma.

PubMed

Yoo, Kwang Ha; Agarwal, Kanishtha; Butterfield, Michael; Jacobson, Robert M; Poland, Gregory A; Juhn, Young J

2010-01-01

Little is known about the influence of asthma status on humoral and cell-mediated immune responses to measles-mumps-rubella (MMR) vaccine viruses. We compared the virus-specific IgG levels and lymphoproliferative response of peripheral blood mononuclear cells to MMR vaccine viruses between asthmatic and nonasthmatic patients. The study subjects included 342 healthy children aged 12-18 years who had received two doses of the MMR vaccine. We ascertained asthma status by applying predetermined criteria. Of the 342 subjects, 230 were available for this study of whom 25 were definite asthmatic patients (10.9%) and the rest of subjects were nonasthmatic patients. The mean of the log-transformed lymphoproliferative responses between definite asthma and nonasthma who had a family history of asthma were for measles, 0.92 ± 0.31 versus 1.54 ± 0.17 (p = 0.125); for mumps, 0.98 ± 0.64 versus 2.20 ± 0.21 (p = 0.035); and for rubella, 0.12 ± 0.37 versus 0.97 ± 0.16 (p = 0.008), respectively, adjusting for the duration between the first MMR vaccination and determination of the immune responses. There were no such differences among children without a family history of asthma. MMR virus-specific IgG levels were not different between study subjects with or without asthma. The study findings suggest asthmatic patients may have a suboptimal cell-mediated immune response to MMR vaccine viruses and a family history of asthma modifies this effect.

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

PubMed Central

Salimi, Vahid; Abbasi, Simin; Zahraei, Seyed Mohsen; Fatemi-Nasab, Ghazal; Adjaminezhad-Fard, Fatemeh; Shadab, Azadeh; Ghavami, Nastaran; Zareh-Khoshchehre, Raziyeh; Soltanshahi, Rambod; Bont, Louis; Mokhtari-Azad, Talat

2014-01-01

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. PMID:24736720

The Host Cell Receptors for Measles Virus and Their Interaction with the Viral Hemagglutinin (H) Protein

PubMed Central

Lin, Liang-Tzung; Richardson, Christopher D.

2016-01-01

The hemagglutinin (H) protein of measles virus (MeV) interacts with a cellular receptor which constitutes the initial stage of infection. Binding of H to this host cell receptor subsequently triggers the F protein to activate fusion between virus and host plasma membranes. The search for MeV receptors began with vaccine/laboratory virus strains and evolved to more relevant receptors used by wild-type MeV. Vaccine or laboratory strains of measles virus have been adapted to grow in common cell lines such as Vero and HeLa cells, and were found to use membrane cofactor protein (CD46) as a receptor. CD46 is a regulator that normally prevents cells from complement-mediated self-destruction, and is found on the surface of all human cells, with the exception of erythrocytes. Mutations in the H protein, which occur during adaptation and allow the virus to use CD46 as a receptor, have been identified. Wild-type isolates of measles virus cannot use the CD46 receptor. However, both vaccine/laboratory and wild-type strains can use an immune cell receptor called signaling lymphocyte activation molecule family member 1 (SLAMF1; also called CD150) and a recently discovered epithelial receptor known as Nectin-4. SLAMF1 is found on activated B, T, dendritic, and monocyte cells, and is the initial target for infections by measles virus. Nectin-4 is an adherens junction protein found at the basal surfaces of many polarized epithelial cells, including those of the airways. It is also over-expressed on the apical and basal surfaces of many adenocarcinomas, and is a cancer marker for metastasis and tumor survival. Nectin-4 is a secondary exit receptor which allows measles virus to replicate and amplify in the airways, where the virus is expelled from the body in aerosol droplets. The amino acid residues of H protein that are involved in binding to each of the receptors have been identified through X-ray crystallography and site-specific mutagenesis. Recombinant measles “blind” to

The Host Cell Receptors for Measles Virus and Their Interaction with the Viral Hemagglutinin (H) Protein.

PubMed

Lin, Liang-Tzung; Richardson, Christopher D

2016-09-20

The hemagglutinin (H) protein of measles virus (MeV) interacts with a cellular receptor which constitutes the initial stage of infection. Binding of H to this host cell receptor subsequently triggers the F protein to activate fusion between virus and host plasma membranes. The search for MeV receptors began with vaccine/laboratory virus strains and evolved to more relevant receptors used by wild-type MeV. Vaccine or laboratory strains of measles virus have been adapted to grow in common cell lines such as Vero and HeLa cells, and were found to use membrane cofactor protein (CD46) as a receptor. CD46 is a regulator that normally prevents cells from complement-mediated self-destruction, and is found on the surface of all human cells, with the exception of erythrocytes. Mutations in the H protein, which occur during adaptation and allow the virus to use CD46 as a receptor, have been identified. Wild-type isolates of measles virus cannot use the CD46 receptor. However, both vaccine/laboratory and wild-type strains can use an immune cell receptor called signaling lymphocyte activation molecule family member 1 (SLAMF1; also called CD150) and a recently discovered epithelial receptor known as Nectin-4. SLAMF1 is found on activated B, T, dendritic, and monocyte cells, and is the initial target for infections by measles virus. Nectin-4 is an adherens junction protein found at the basal surfaces of many polarized epithelial cells, including those of the airways. It is also over-expressed on the apical and basal surfaces of many adenocarcinomas, and is a cancer marker for metastasis and tumor survival. Nectin-4 is a secondary exit receptor which allows measles virus to replicate and amplify in the airways, where the virus is expelled from the body in aerosol droplets. The amino acid residues of H protein that are involved in binding to each of the receptors have been identified through X-ray crystallography and site-specific mutagenesis. Recombinant measles "blind" to each of

Understanding the causes and consequences of measles virus persistence

PubMed Central

Griffin, Diane E.; Lin, Wen-Hsuan W.; Nelson, Ashley N.

2018-01-01

Measles is an acute systemic viral disease with initial amplification of infection in lymphoid tissue and subsequent spread over 10–14 days to multiple organs. Failure of the innate response to control initial measles virus (MeV) replication is associated with the ability of MeV to inhibit the induction of type I interferon and interferon-stimulated antiviral genes. Rather, the innate response is characterized by the expression of proteins regulated by nuclear factor kappa B and the inflammasome. With eventual development of the adaptive response, the rash appears with immune cell infiltration into sites of virus replication to initiate the clearance of infectious virus. However, MeV RNA is cleared much more slowly than recoverable infectious virus and remains present in lymphoid tissue for at least 6 months after infection. Persistence of viral RNA and protein suggests persistent low-level replication in lymphoid tissue that may facilitate maturation of the immune response, resulting in lifelong protection from reinfection, while persistence in other tissues (for example, the nervous system) may predispose to development of late disease such as subacute sclerosing panencephalitis. Further studies are needed to identify mechanisms of viral clearance and to understand the relationship between persistence and development of lifelong immunity. PMID:29560260

Understanding the causes and consequences of measles virus persistence.

PubMed

Griffin, Diane E; Lin, Wen-Hsuan W; Nelson, Ashley N

2018-01-01

Measles is an acute systemic viral disease with initial amplification of infection in lymphoid tissue and subsequent spread over 10-14 days to multiple organs. Failure of the innate response to control initial measles virus (MeV) replication is associated with the ability of MeV to inhibit the induction of type I interferon and interferon-stimulated antiviral genes. Rather, the innate response is characterized by the expression of proteins regulated by nuclear factor kappa B and the inflammasome. With eventual development of the adaptive response, the rash appears with immune cell infiltration into sites of virus replication to initiate the clearance of infectious virus. However, MeV RNA is cleared much more slowly than recoverable infectious virus and remains present in lymphoid tissue for at least 6 months after infection. Persistence of viral RNA and protein suggests persistent low-level replication in lymphoid tissue that may facilitate maturation of the immune response, resulting in lifelong protection from reinfection, while persistence in other tissues (for example, the nervous system) may predispose to development of late disease such as subacute sclerosing panencephalitis. Further studies are needed to identify mechanisms of viral clearance and to understand the relationship between persistence and development of lifelong immunity.

A measles outbreak in Sindh, Pakistan caused by a genotype B3 virus.

PubMed

Zaidi, Syed Sohail Zahoor; Hameed, Abdul; Ali, Naeem; Umair, Massab; Alam, Muhammad Masroor; Rana, Muhammad Suleman; Sharif, Salmaan; Aamir, Uzma Bashir; Shaukat, Shahzad; Angez, Mehar; Khurshid, Adnan; Akhtar, Ribqa; Mehmood, Nayab; Badar, Nazish

2017-12-01

Measles continues to be a major public health issue causing substantial outbreaks worldwide, mostly affecting young children. Molecular analysis of measles viruses provides important information on outbreak linkages and transmission pathways that can be helpful towards implementation of appropriate control programs. In Pakistan, the control of measles is still tenuous, and progress towards elimination has been irregular and challenging. In the 2013 measles outbreak we received 4,682 sera collected from suspected patients in 23 districts across Sindh. A total of 3,283 samples were confirmed measles positive using IgM ELISA with the highest infection rate in children aged 1-12 months. Males were more affected than females and a visible peak was observed from January to April. Among the 3,283 cases, 59.1% were unvaccinated, 29.6% had received 1 dose and 10.3% had received 2 doses of measles vaccine while 0.85% had an unknown vaccination status. For genotype detection and phylogenetic analysis, 60 throat swab samples were collected from suspected patients below 15 years of age in eight districts of Sindh province. Forty four (73%; 44/60) throat swab samples were successfully genotyped using RT-PCR. Phylogenetic analyses based on partial sequences of the nucleocapsid protein gene revealed that all Pakistani measles virus strains belonged to genotype B3 and were closely related to those isolated from neighboring countries such as Iran, Afghanistan (99.1-100%) and India with 98.6 - 99.6% nucleotide homology. This is the first report on the phylogenetic analysis of measles B3 genotype strains from Pakistan and highlights the need for strengthening the surveillance systems and improving immunization coverage across the country.

Susceptibility to measles, rubella, mumps, and varicella-zoster viruses among healthcare workers.

PubMed

Aypak, Cenk; Bayram, Yasemin; Eren, Hayriye; Altunsoy, Adalet; Berktaş, Mustafa

2012-01-01

It is important to identify and immunize susceptible healthcare workers to prevent and control hospital infections. Our aim was to evaluate the specific antibodies against the measles, mumps, and rubella viruses and the varicella zoster virus among healthcare workers in a tertiary-care hospital. A total of 284 healthcare workers (89 men and 195 women; mean age, 33.5 ± 11 years), including 111 nurses, 87 physicians, 34 laboratory technicians, and 52 members of the housekeeping staff, of Van Training and Research Hospital were enrolled in this study. Antibodies were detected with an enzyme-linked immunosorbent assay. The numbers of workers with serological susceptibility to mumps, measles, rubella, or chicken pox were 26 (9.2%), 18 (6.3%), 7 (2.5%), and 5 (1.8%), respectively. Although the difference was not statistical significant, the rate of seroprevalence of antibodies was lowest for measles (90.8%; p>0.05). Susceptibility to measles, mumps, and rubella, and chicken pox was more prevalent among young healthcare workers (p<0.001). Not all healthcare workers born before 1957 were immune to these vaccine-preventable diseases. These data confirm that screening and vaccination of susceptible healthcare workers is essential regardless of age.

Sequence and immunogenicity of a clinically approved novel measles virus vaccine vector

PubMed Central

Zuniga, Amando; Liniger, Mathias; Morin, Teldja Neige Azzouz; Marty, René R.; Wiegand, Marian; Ilter, Orhan; Weibel, Sara; Billeter, Martin A.; Knuchel, Marlyse C.; Naim, Hussein Y.

2013-01-01

The measles virus vaccine (MVbv) is a clinically certified and well-tolerated vaccine strain that has been given both parenterally and mucosally. It has been extensively used in children and has proven to be safe and effective in eliciting protective immunity. This specific strain was therefore chosen to generate a measles viral vector. The genome of the commercial MVbv vaccine strain was isolated, sequenced and a plasmid, p(+)MVb, enabling transcription of the viral antigenome and rescue of MVb, was constructed. Phylogenic and phenotypic analysis revealed that MVbv and the rescued MVb constitute another evolutionary branch within the hitherto classified measles vaccines. Plasmid p(+)MVb was modified by insertion of artificial MV-type transcription units (ATUs) for the generation of recombinant viruses (rMVb) expressing additional proteins. Replication characteristics and immunogenicity of rMVb vectors were similar to the parental MVbv and to other vaccine strains. The expression of the additional proteins was stable over 10 serial virus transfers, which corresponds to an amplification greater than 1020. The excellent safety record and its efficient application as aerosol may add to the usefulness of the derived vectors. PMID:23324616

Wild type measles virus attenuation independent of type I IFN.

PubMed

Druelle, Johan; Sellin, Caroline I; Waku-Kouomou, Diane; Horvat, Branka; Wild, Fabian T

2008-02-03

Measles virus attenuation has been historically performed by adaptation to cell culture. The current dogma is that attenuated virus strains induce more type I IFN and are more resistant to IFN-induced protection than wild type (wt). The adaptation of a measles virus isolate (G954-PBL) by 13 passages in Vero cells induced a strong attenuation of this strain in vivo. The adapted virus (G954-V13) differs from its parental strain by only 5 amino acids (4 in P/V/C and 1 in the M gene). While a vaccine strain, Edmonston Zagreb, could replicate equally well in various primate cells, both G954 strains exhibited restriction to the specific cell type used initially for their propagation. Surprisingly, we observed that both G954 strains induced type I IFN, the wt strain inducing even more than the attenuated ones, particularly in human plasmacytoid Dendritic Cells. Type I IFN-induced protection from the infection of both G954 strains depended on the cell type analyzed, being less efficient in the cells used to grow the viral strain. Thus, mutations in M and P/V/C proteins can critically affect MV pathogenicity, cellular tropism and lead to virus attenuation without interfering with the alpha/beta IFN system.

Wild type measles virus attenuation independent of type I IFN

PubMed Central

Druelle, Johan; Sellin, Caroline I; Waku-Kouomou, Diane; Horvat, Branka; Wild, Fabian T

2008-01-01

Background Measles virus attenuation has been historically performed by adaptation to cell culture. The current dogma is that attenuated virus strains induce more type I IFN and are more resistant to IFN-induced protection than wild type (wt). Results The adaptation of a measles virus isolate (G954-PBL) by 13 passages in Vero cells induced a strong attenuation of this strain in vivo. The adapted virus (G954-V13) differs from its parental strain by only 5 amino acids (4 in P/V/C and 1 in the M gene). While a vaccine strain, Edmonston Zagreb, could replicate equally well in various primate cells, both G954 strains exhibited restriction to the specific cell type used initially for their propagation. Surprisingly, we observed that both G954 strains induced type I IFN, the wt strain inducing even more than the attenuated ones, particularly in human plasmacytoid Dendritic Cells. Type I IFN-induced protection from the infection of both G954 strains depended on the cell type analyzed, being less efficient in the cells used to grow the viral strain. Conclusion Thus, mutations in M and P/V/C proteins can critically affect MV pathogenicity, cellular tropism and lead to virus attenuation without interfering with the α/β IFN system. PMID:18241351

Measles-mumps-rubella vaccination and respiratory syncytial virus-associated hospital contact.

PubMed

Sørup, Signe; Benn, Christine Stabell; Stensballe, Lone Graff; Aaby, Peter; Ravn, Henrik

2015-01-01

The live measles vaccine has been associated with lower non-measles mortality and admissions in low-income countries. The live measles-mumps-rubella vaccine has also been associated with lower rate of admissions with any type of infection in Danish children; the association was strongest for admissions with lower respiratory infections. To examine whether measles, mumps, and rubella (MMR) vaccination was associated with reduced rate of hospital contact related to respiratory syncytial virus (RSV) in a high-income country. Nationwide cohort study of laboratory-confirmed RSV hospital contacts at age 14-23 months in all children born in Denmark 1997-2002 who had already received the vaccine against diphtheria, tetanus, pertussis (acellular), polio, and Haemophilus influenzae type b (DTaP-IPV-Hib) at the recommended ages of 3, 5, and 12 months. The study included 888 RSV hospital contacts in 128,588 person years of follow up (rate 6.8/1000 person years). Having MMR as the most recent vaccine was associated with a reduced rate of RSV hospital contacts compared with having DTaP-IPV-Hib as the most recent vaccine (Incidence rate ratio (IRR), 0.75; 95% confidence interval (CI), 0.63-0.89). After adjustment for potential confounders including exact age in days the IRR was 0.78 (95% CI, 0.66-0.93). The adjusted IRR was 0.74 (95% CI, 0.60-0.92) in males and 0.84 (95% CI, 0.66-1.06) in females (P Interaction, 0.42). There was no association in the first month after MMR vaccination (adjusted IRR, 0.97; 95% CI, 0.76-1.24) but the adjusted IRR was 0.70 (95% CI, 0.58-0.85) from one month after MMR vaccination. MMR vaccination was associated with reduced rate of hospital contacts related to laboratory-confirmed RSV infection. Further research on the association between MMR vaccination and other unrelated pathogens are warranted. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

21 CFR 866.3520 - Rubeola (measles) virus serological reagents.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Rubeola (measles) virus serological reagents. 866.3520 Section 866.3520 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Serological Reagents § 866.3520...

21 CFR 866.3520 - Rubeola (measles) virus serological reagents.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Rubeola (measles) virus serological reagents. 866.3520 Section 866.3520 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Serological Reagents § 866.3520...

21 CFR 866.3520 - Rubeola (measles) virus serological reagents.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Rubeola (measles) virus serological reagents. 866.3520 Section 866.3520 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Serological Reagents § 866.3520...

21 CFR 866.3520 - Rubeola (measles) virus serological reagents.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Rubeola (measles) virus serological reagents. 866.3520 Section 866.3520 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Serological Reagents § 866.3520...

21 CFR 866.3520 - Rubeola (measles) virus serological reagents.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Rubeola (measles) virus serological reagents. 866.3520 Section 866.3520 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Serological Reagents § 866.3520...

Spotlight on measles 2010: An epidemiological overview of measles outbreaks in Poland in relation to the measles elimination goal.

PubMed

Rogalska, J; Santibanez, S; Mankertz, A; Makowka, A; Szenborn, L; Stefanoff, P

2010-04-29

The objective of this study was to describe transmission chains of measles observed in Poland during 2008-2009. A decade ago, the incidence of measles in Poland declined and approached one case per million inhabitants one of the World Health Organization's criteria for measles elimination. Following a period of very few reported measles cases (2003 to 2005), an increase in incidence was observed in 2006. Since then, the incidence has constantly exceeded one case per million inhabitants. Of 214 measles cases reported in 2008 and 2009 in Poland, 164 (77%) were linked to 19 distinct outbreaks, with 79% of cases belonging to the Roma ethnic group. Outbreaks in the non-Roma Polish population had different dynamics compared to those in the Roma population. On average, measles outbreaks in Roma communities involved 10 individuals, seven of whom were unvaccinated, while outbreaks in the non-Roma Polish population involved five individuals, half of whom were incompletely vaccinated. The majority of outbreaks in Roma communities were related to importation of virus from the United Kingdom. In six outbreaks, the epidemiologic investigation was confirmed by identification of genotype D4 closely related to measles viruses detected in the United Kingdom and Germany. Our data indicate that Poland is approaching measles elimination, but measles virus circulation is still sustained in a vulnerable population. More efforts are needed to integrate the Roma ethnic group into the Polish healthcare system and innovative measures to reach vulnerable groups should be explored.

Decay of Passively Acquired Maternal Antibodies against Measles, Mumps, and Rubella Viruses

PubMed Central

Nicoara, Corina; Zäch, Kristina; Trachsel, Daniel; Germann, Daniel; Matter, Lukas

1999-01-01

The decay of maternally derived antibodies to measles, mumps, and rubella viruses in Swiss infants was studied in order to determine the optimal time for vaccination. A total of 500 serum or plasma samples from infants up to 2 years of age were tested by enzyme-linked immunosorbent assay and fluorescent-antibody testing. The decline of antibody prevalence was slowest against the measles virus. By 9 to 12 months of age, only 5 of 58 (8.6%; 95% CI, 2.9 to 19.0) infants were antibody positive for the measles virus, and only 2 had levels above 200 mIU/ml. Mumps and rubella virus antibody seropositivity was lowest at 9 to 12 months of age with 3 of 58 (5.2%; 95% CI, 1.1 to 14.4) infants and at 12 to 15 months with 1 of 48 (2.1%; 95% CI, 0.1 to 11.1) infants, respectively. Concentrations of passively acquired antibodies decreased rapidly within the first 6 months of life. We observed no significant differences in antibody prevalence or concentration according to gender in any age group. In conclusion, MMR vaccination at 12 instead of 15 months of age could reduce the pool of susceptible subjects in infancy and support the efforts to eliminate these infections, particularly in combination with a second vaccine dose before school entry. PMID:10548578

Genetic analysis of Asian measles virus strains--new endemic genotype in Nepal.

PubMed

Truong, A T; Mulders, M N; Gautam, D C; Ammerlaan, W; de Swart, R L; King, C C; Osterhaus, A D; Muller, C P

2001-07-01

In many parts of Asia measles virus (MV) continues to be endemic. However, little is known about the genetic characteristics of viruses circulating on this continent. This study reports the molecular epidemiological analysis based on the entire nucleocapsid (N) and hemagglutinin (H) genes of the first isolates from Nepal and Taiwan, as well as of recent MV strains from India, Indonesia, and China. Four isolates collected in various regions in Nepal during 1999 belonged to a new genotype, tentatively called D8. Another Nepalese isolate and one from India belonged to genotype D4. The diversity of the Nepalese strains indicated that measles continues to be endemic in this country. The isolate from Taiwan grouped with D3 viruses and one Chinese strain isolated in The Netherlands was assigned to the previously described clade H, known to be endemic in Mainland China. Molecular characterization emerges as an important tool for monitoring virus endemicity and vaccination efforts.

Spread of Measles Virus D4-Hamburg, Europe, 2008–2011

PubMed Central

Mihneva, Zefira; Gold, Hermann; Baumgarte, Sigrid; Baillot, Armin; Helble, Rudolph; Roggendorf, Hedwig; Bosevska, Golubinka; Nedeljkovic, Jasminka; Makowka, Agata; Hutse, Veronik; Holzmann, Heidemarie; Aberle, Stefan W.; Cordey, Samuel; Necula, Gheorghe; Mentis, Andreas; Korukluoğlu, Gulay; Carr, Michael; Brown, Kevin E.; Hübschen, Judith M.; Muller, Claude P.; Mulders, Mick N.; Santibanez, Sabine

2011-01-01

A new strain of measles virus, D4-Hamburg, was imported from London to Hamburg in December 2008 and subsequently spread to Bulgaria, where an outbreak of >24,300 cases was observed. We analyzed spread of the virus to demonstrate the importance of addressing hard-to-reach communities within the World Health Organization European Region regarding access to medical care and vaccination campaigns. The D4-Hamburg strain appeared during 2009–2011 in Poland, Ireland, Northern Ireland, Austria, Greece, Romania, Turkey, Macedonia, Serbia, Switzerland, and Belgium and was repeatedly reimported to Germany. The strain was present in Europe for >27 months and led to >25,000 cases in 12 countries. Spread of the virus was prevalently but not exclusively associated with travel by persons in the Roma ethnic group; because this travel extends beyond the borders of any European country, measures to prevent the spread of measles should be implemented by the region as a whole. PMID:21801615

Measles virus antibody responses in children randomly assigned to receive standard-titer edmonston-zagreb measles vaccine at 4.5 and 9 months of age, 9 months of age, or 9 and 18 months of age.

PubMed

Martins, Cesario; Garly, May-Lill; Bale, Carlitos; Rodrigues, Amabelia; Njie-Jobe, Jainaba; Benn, Christine S; Whittle, Hilton; Aaby, Peter

2014-09-01

The World Health Organization recommends administration of measles vaccine (MV) at age 9 months in low-income countries. We tested the measles virus antibody response at 4.5, 9, 18, and 24 months of age for children randomly assigned to receive standard-titer Edmonston-Zagreb MV at 4.5 and 9 months, at 9 months, or at 9 and 18 months of age. At 4.5 months of age, 75% had nonprotective measles virus antibody levels. Following receipt of MV at 4.5 months of age, 77% (316/408) had protective antibody levels at 9 months of age; after a second dose at 9 months of age, 97% (326/337) had protective levels at 24 months of age. In addition, the response at both 9 and 24 months of age was inversely correlated with the antibody level at receipt of the first dose of MV, and the second dose of MV, received at 9 months of age, provided a significant boost in antibody level to children who had low antibody levels. In the group of 318 children who received MV at 9 months of age, with or without a second dose at 18 months of age, 99% (314) had protective levels at 24 months of age. The geometric mean titer at 24 months of age was significantly lower in the group that received MV at 4.5 and 9 months of age than in the group that received MV at 9 months of age (P = .0001). In conclusion, an early 2-dose MV schedule was associated with protective measles virus antibody levels at 24 months of age in nearly all children. Clinical Trials Registration. NCT00168558. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Long-term transmission of measles virus in Central and continental Western Europe.

PubMed

Santibanez, S; Hübschen, J M; Muller, C P; Freymuth, F; Mosquera, M M; Mamou, M Ben; Mulders, M N; Brown, K E; Myers, R; Mankertz, A

2015-02-01

The World Health Organization (WHO) has adopted an elimination goal for measles and rubella, which is supposed to be met in the WHO European Region (EUR) by 2015. For verification of elimination, it is required that the genotyping data of detected measles viruses provide evidence for the interruption of endemic transmission. In order to record and assess the extent of endemic measles virus (MV) circulation in a part of the EUR, we analyzed transmission chains of the epidemiologically most relevant MV variants identified in Central and continental Western Europe (CCWE) from 2006 to 2013. Based on MV sequence data deposited in the WHO global database for molecular surveillance of measles (MeaNS), the circulation period was calculated for each MV variant at the country-level and for the entire region of CCWE. The MV variants "D5-Okinawa," "D4-Hamburg," "D4-Manchester," and "D8-Frankfurt-Main" spread widely in CCWE; they caused large and long-lasting outbreaks with secondary spread that resulted in additional outbreaks. Nation-wide outbreaks (epidemics) with thousands of measles cases occurred in four countries (Switzerland, France, Bulgaria, and Romania) and were characterized by continuous detection of the same MV variant for more than 12 months suggesting endemic transmission. In the entire region of CCWE, the circulation period of the four predominant MV variants ranged from 18 to 44 months. The long-lasting MV transmission which affected predominantly unvaccinated individuals in different hard-to-reach groups and in the general population is not consistent with the measles elimination goal. Additional efforts are necessary to meet the elimination target in the EUR.

Structural basis of efficient contagion: measles variations on a theme by parainfluenza viruses.

PubMed

Mateo, Mathieu; Navaratnarajah, Chanakha K; Cattaneo, Roberto

2014-04-01

A quartet of attachment proteins and a trio of fusion protein subunits play the cell entry concert of parainfluenza viruses. While many of these viruses bind sialic acid to enter cells, wild type measles binds exclusively two tissue-specific proteins, the lymphatic receptor signaling lymphocytic activation molecule (SLAM), and the epithelial receptor nectin-4. SLAM binds near the stalk-head junction of the hemagglutinin. Nectin-4 binds a hydrophobic groove located between blades 4 and 5 of the hemagglutinin β-propeller head. The mutated vaccine strain hemagglutinin binds in addition the ubiquitous protein CD46, which explains attenuation. The measles virus entry concert has four movements. Andante misterioso: the virus takes over the immune system. Allegro con brio: it rapidly spreads in the upper airway's epithelia. 'Targeting' fugue: the versatile orchestra takes off. Presto furioso: the virus exits the host with thunder. Be careful: music is contagious. Copyright © 2014 Elsevier B.V. All rights reserved.

Genetic variability of wild-type measles viruses, circulating in the Russian Federation during the implementation of the National Measles Elimination Program, 2003-2007.

PubMed

Shulga, S V; Rota, P A; Kremer, J R; Naumova, M A; Muller, C P; Tikhonova, N T; Lopareva, E N; Mamaeva, T A; Tsvirkun, O V; Mulders, M N; Lipskaya, G Y; Gerasimova, A G

2009-06-01

Genetic characterization of wild-type measles viruses (MVs) is an important component of laboratory surveillance of measles. In this study, a phylogenetic analysis was performed of the nucleoprotein gene sequences of 228 MVs isolated in the Russian Federation between 2003 and 2007. Five genotypes, D4, D5, D6, D8, and H1, were detected. From 1999 through the first 6 months of 2003, the most prevalent genotype in the European part of Russia was D4. All genotype D4-type viruses were closely related to each other (with overall sequence diversity of viruses with closely related sequences within genotype D6 (viruses were imported from neighbouring countries, which led to the identification of two lineages of genotype D6, i.e. D6a and D6b. Lineage D6a was closely related to viruses isolated in Turkey, Kazakhstan, and Uzbekistan, whereas lineage D6b was linked to a large outbreak in Ukraine in 2005-2006. Genotypes H1, D5 and D8 were associated with sporadic cases and clusters of transmission linked to importations. Enhanced vaccination interrupted the transmission of the previous endemic lineage D4 in 2003 and of lineage D6a in 2005, although an accumulation of susceptible individuals in the population allowed for prolonged circulation of lineage D6b. These data on MV genotype distribution, in conjunction with the epidemiological data for measles, show considerable progress in measles control and suggest that regional elimination is possible.

Specific elimination of CD133+ tumor cells with targeted oncolytic measles virus.

PubMed

Bach, Patricia; Abel, Tobias; Hoffmann, Christopher; Gal, Zoltan; Braun, Gundula; Voelker, Iris; Ball, Claudia R; Johnston, Ian C D; Lauer, Ulrich M; Herold-Mende, Christel; Mühlebach, Michael D; Glimm, Hanno; Buchholz, Christian J

2013-01-15

Tumor-initiating cells (TIC) are critical yet evasive targets for the development of more effective antitumoral strategies. The cell surface marker CD133 is frequently used to identify TICs of various tumor entities, including hepatocellular cancer and glioblastoma. Here, we describe oncolytic measles viruses (MV) retargeted to CD133. The viruses, termed MV-141.7 and MV-AC133, infected and selectively lysed CD133(+) tumor cells. Both viruses exerted strong antitumoral effects on human hepatocellular carcinoma growing subcutaneously or multifocally in the peritoneal cavity of nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice. Notably, the CD133-targeted viruses were more effective in prolonging survival than the parental MV-NSe, which is currently assessed as oncolytic agent in clinical trials. Interestingly, target receptor overexpression or increased spreading kinetics through tumor cells were excluded as being causative for the enhanced oncolytic activity of CD133-targeted viruses. MV-141.7 was also effective in mouse models of orthotopic glioma tumor spheres and primary colon cancer. Our results indicate that CD133-targeted measles viruses selectively eliminate CD133(+) cells from tumor tissue, offering a key tool for research in tumor biology and cancer therapy.

Global Transmission Dynamics of Measles in the Measles Elimination Era.

PubMed

Furuse, Yuki; Oshitani, Hitoshi

2017-04-16

Although there have been many epidemiological reports of the inter-country transmission of measles, systematic analysis of the global transmission dynamics of the measles virus (MV) is limited. In this study, we applied phylogeographic analysis to characterize the global transmission dynamics of the MV using large-scale genetic sequence data (obtained for 7456 sequences) from 115 countries between 1954 and 2015. These analyses reveal the spatial and temporal characteristics of global transmission of the virus, especially in Australia, China, India, Japan, the UK, and the USA in the period since 1990. The transmission is frequently observed, not only within the same region but also among distant and frequently visited areas. Frequencies of export from measles-endemic countries, such as China, India, and Japan are high but decreasing, while the frequencies from countries where measles is no longer endemic, such as Australia, the UK, and the USA, are low but slightly increasing. The world is heading toward measles eradication, but the disease is still transmitted regionally and globally. Our analysis reveals that countries wherein measles is endemic and those having eliminated the disease (apart from occasional outbreaks) both remain a source of global transmission in this measles elimination era. It is therefore crucial to maintain vigilance in efforts to monitor and eradicate measles globally.

Viral Oncolysis — Can Insights from Measles Be Transferred to Canine Distemper Virus?

PubMed Central

Lapp, Stefanie; Pfankuche, Vanessa M.; Baumgärtner, Wolfgang; Puff, Christina

2014-01-01

Neoplastic diseases represent one of the most common causes of death among humans and animals. Currently available and applied therapeutic options often remain insufficient and unsatisfactory, therefore new and innovative strategies and approaches are highly needed. Periodically, oncolytic viruses have been in the center of interest since the first anecdotal description of their potential usefulness as an anti-tumor treatment concept. Though first reports referred to an incidental measles virus infection causing tumor regression in a patient suffering from lymphoma several decades ago, no final treatment concept has been developed since then. However, numerous viruses, such as herpes-, adeno- and paramyxoviruses, have been investigated, characterized, and modified with the aim to generate a new anti-cancer treatment option. Among the different viruses, measles virus still represents a highly interesting candidate for such an approach. Numerous different tumors of humans including malignant lymphoma, lung and colorectal adenocarcinoma, mesothelioma, and ovarian cancer, have been studied in vitro and in vivo as potential targets. Moreover, several concepts using different virus preparations are now in clinical trials in humans and may proceed to a new treatment option. Surprisingly, only few studies have investigated viral oncolysis in veterinary medicine. The close relationship between measles virus (MV) and canine distemper virus (CDV), both are morbilliviruses, and the fact that numerous tumors in dogs exhibit similarities to their human counterpart, indicates that both the virus and species dog represent a highly interesting translational model for future research in viral oncolysis. Several recent studies support such an assumption. It is therefore the aim of the present communication to outline the mechanisms of morbillivirus-mediated oncolysis and to stimulate further research in this potentially expanding field of viral oncolysis in a highly suitable

Clinical safety issues of measles, mumps and rubella vaccines.

PubMed Central

Afzal, M. A.; Minor, P. D.; Schild, G. C.

2000-01-01

The clinical safety of measles and measles-mumps-rubella vaccines has been questioned in recent reports that propose a possible link between measles virus or measles vaccines and the occurrence of juvenile Crohn disease and autism. This article reviews the outcomes of several laboratory investigations which were carried out independently to identify the presence or absence of measles virus in the intestinal tissues derived from cases of inflammatory bowel disease. One research group reported the presence of measles virus particles and genomic RNA in inflammatory bowel disease tissues, but this could not be confirmed by other groups, despite use of techniques that are highly specific and sensitive for the detection of measles virus nucleic acid in clinical specimens down to the molecular level. Based on the published data reviewed here, it can be concluded that there is no direct association between measles virus or measles vaccines and the development of Crohn disease, a conclusion which is supported by most epidemiological findings. PMID:10743285

Epidemiology of two large measles virus outbreaks in Catalonia

PubMed Central

Torner, Núria; Anton, Andres; Barrabeig, Irene; Lafuente, Sara; Parron, Ignasi; Arias, César; Camps, Neus; Costa, Josep; Martínez, Ana; Torra, Roser; Godoy, Pere; Minguell, Sofia; Ferrús, Glòria; Cabezas, Carmen; Domínguez, Ángela; Elimination Program Surveillance Network of Spain, the Measles

2013-01-01

Measles cases in the European Region have been increasing in the last decade; this illustrates the challenge of what we are now encountering in the form of pediatric preventable diseases. In Catalonia, autochthonous measles was declared eliminated in the year 2000 as the result of high measles-mumps-rubella vaccine (MMR) coverage for first and second dose (15 mo and 4 y) since the mid-1990s. From then on, sporadic imported cases and small outbreaks appeared, until in 2006–2007 a large measles outbreak affecting mostly unvaccinated toddlers hit the Barcelona Health Region. Consequently, in January 2008, first dose administration of MMR was lowered from 15 to 12 mo of age. A new honeymoon period went by until the end of 2010, when several importations of cases triggered new sustained transmission of different wild measles virus genotypes, but this time striking young adults. The aim of this study is to show the effect of a change in MMR vaccination schedule policy, and the difference in age incidence and hospitalization rates of affected individuals between both outbreaks. Epidemiologic data were obtained by case interviews and review of medical records. Samples for virological confirmation and genotyping of cases were collected as established in the Measles Elimination plan guidelines. Incidence rate (IR), rate ratio (RR) and their 95% CI and hospitalization rate (HR) by age group were determined. Statistic z was used for comparing proportions. Total number of confirmed cases was 305 in the 2010 outbreak and 381 in the 2006–2007 outbreak; mean age 20 y (SD 14.8 y; 3 mo to 51 y) vs. 15 mo (SD 13.1 y; 1 mo to 50 y). Highest proportion of cases was set in ≥ 25 y (47%) vs. 24.2% in 2006 (p < 0.001). Differences in IR for ≤ 15 mo (49/100,000 vs. 278.2/100,000; RR: 3,9; 95%CI 2,9–5.4) and in overall HR 29.8% vs. 15.7% were all statistically significant (p < 0.001). The change of the month of age for the administration of the first MMR dose proved successful to

In vivo evaluation of the antiviral activity of Cajanus cajan on measles virus.

PubMed

Nwodo, U U; Ngene, A A; Iroegbu, C U; Onyedikachi, O A L; Chigor, V N; Okoh, A I

2011-09-01

Cajanus cajan, a tropical shrub, serves as source of food and traditional medicines. The evaluation of aqueous and ethanol extracts for activity against measles virus and toxicity to embryonated chicken eggs was carried out in this study. In vivo and in vitro assay techniques using embryonated chicken eggs and tissue culture (Hep-2 cell lines) as media for both virus cultivation and anti-virus assay showed that a hot-water extract yielded higher activity against measles virus. The hot-water extract of the stem yielded a Log(2) titre of 0.1 for the in vivo assay and an inhibition of cytopathic effect (CPE) in Hep-2 cells by 100% for the in vitro assay. At all concentrations of the extracts, there was a lowering of virus concentration (p = 0.05), indicated by hemagglutination (HA) titration, which is the advantage of HA titration over the tissue culture technique using CPE. This study validates embryonated chicken eggs as suitable media for anti-virus assay and the use of C. cajan in the treatment of some diseases of viral origin.

Evolutionary genetics of genotype H1 measles viruses in China from 1993 to 2012

PubMed Central

Xu, Songtao; Zhang, Yan; Rivailler, Pierre; Wang, Huiling; Ji, Yixin; Zhen, Zhu; Mao, Naiying; Li, Chongshan; Bellini, William J.

2014-01-01

Virologic surveillance is a critical component of measles management. One of the criteria for verification of elimination of endemic measles is genetic analysis of wild-type viruses to demonstrate lack of an indigenous genotype. Measles is yet to be eliminated in China, and genotype H1 has been detected continuously since virologic surveillance was initiated in 1993. Virologic surveillance has been very active in China, providing a unique opportunity to conduct a detailed study of the evolution of a single, endemic genotype over a timespan of nearly two decades. Phylogenetic analysis performed on the 450 nt coding sequence for the C-terminal 150 amino acids of the nucleoprotein (N-450), fusion (F) gene and haemagglutinin (H) gene confirmed the continued circulation of genotype H1 viruses for 19 years. No evidence of selective pressure for the H protein was found. The substitution rates ranged from 0.75×10−3 substitutions site−1 year−1 for H to 1.65×10−3 substitutions site−1 year−1 for N-450. The time of most recent common ancestor (TMRCA) for genotype H1 was estimated as approximately 1985 (95 % highest probability density, 1979–1989). Finally, the overall diversity of measles sequences from China decreased from 2005 to 2012, coincident with a substantial decrease in measles cases. The results suggest that detailed evolutionary analyses should facilitate the documentation of eventual measles elimination in China. Moreover, the molecular approaches used in this study can be applied in other countries approaching measles elimination. PMID:24914068

Evolutionary genetics of genotype H1 measles viruses in China from 1993 to 2012.

PubMed

Xu, Songtao; Zhang, Yan; Rivailler, Pierre; Wang, Huiling; Ji, Yixin; Zhen, Zhu; Mao, Naiying; Li, Chongshan; Bellini, William J; Xu, Wenbo; Rota, Paul A

2014-09-01

Virologic surveillance is a critical component of measles management. One of the criteria for verification of elimination of endemic measles is genetic analysis of wild-type viruses to demonstrate lack of an indigenous genotype. Measles is yet to be eliminated in China, and genotype H1 has been detected continuously since virologic surveillance was initiated in 1993. Virologic surveillance has been very active in China, providing a unique opportunity to conduct a detailed study of the evolution of a single, endemic genotype over a timespan of nearly two decades. Phylogenetic analysis performed on the 450 nt coding sequence for the C-terminal 150 amino acids of the nucleoprotein (N-450), fusion (F) gene and haemagglutinin (H) gene confirmed the continued circulation of genotype H1 viruses for 19 years. No evidence of selective pressure for the H protein was found. The substitution rates ranged from 0.75×10(-3) substitutions site(-1) year(-1) for H to 1.65×10(-3) substitutions site(-1) year(-1) for N-450. The time of most recent common ancestor (TMRCA) for genotype H1 was estimated as approximately 1985 (95 % highest probability density, 1979-1989). Finally, the overall diversity of measles sequences from China decreased from 2005 to 2012, coincident with a substantial decrease in measles cases. The results suggest that detailed evolutionary analyses should facilitate the documentation of eventual measles elimination in China. Moreover, the molecular approaches used in this study can be applied in other countries approaching measles elimination.

9 CFR 113.313 - Measles Vaccine.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Measles Vaccine. 113.313 Section 113... Vaccines § 113.313 Measles Vaccine. Measles Vaccine shall be prepared from virus-bearing cell culture... for preparing the production seed virus for vaccine production. All serials of vaccine shall be...

9 CFR 113.313 - Measles Vaccine.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Measles Vaccine. 113.313 Section 113... Vaccines § 113.313 Measles Vaccine. Measles Vaccine shall be prepared from virus-bearing cell culture... for preparing the production seed virus for vaccine production. All serials of vaccine shall be...

9 CFR 113.313 - Measles Vaccine.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 9 Animals and Animal Products 1 2013-01-01 2013-01-01 false Measles Vaccine. 113.313 Section 113... Vaccines § 113.313 Measles Vaccine. Measles Vaccine shall be prepared from virus-bearing cell culture... for preparing the production seed virus for vaccine production. All serials of vaccine shall be...

9 CFR 113.313 - Measles Vaccine.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false Measles Vaccine. 113.313 Section 113... Vaccines § 113.313 Measles Vaccine. Measles Vaccine shall be prepared from virus-bearing cell culture... for preparing the production seed virus for vaccine production. All serials of vaccine shall be...

9 CFR 113.313 - Measles Vaccine.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false Measles Vaccine. 113.313 Section 113... Vaccines § 113.313 Measles Vaccine. Measles Vaccine shall be prepared from virus-bearing cell culture... for preparing the production seed virus for vaccine production. All serials of vaccine shall be...

Structural and mechanistic studies of measles virus illuminate paramyxovirus entry.

PubMed

Plemper, Richard K; Brindley, Melinda A; Iorio, Ronald M

2011-06-01

Measles virus (MeV), a member of the paramyxovirus family of enveloped RNA viruses and one of the most infectious viral pathogens identified, accounts for major pediatric morbidity and mortality worldwide although coordinated efforts to achieve global measles control are in place. Target cell entry is mediated by two viral envelope glycoproteins, the attachment (H) and fusion (F) proteins, which form a complex that achieves merger of the envelope with target cell membranes. Despite continually expanding knowledge of the entry strategies employed by enveloped viruses, our molecular insight into the organization of functional paramyxovirus fusion complexes and the mechanisms by which the receptor binding by the attachment protein triggers the required conformational rearrangements of the fusion protein remain incomplete. Recently reported crystal structures of the MeV attachment protein in complex with its cellular receptors CD46 or SLAM and newly developed functional assays have now illuminated some of the fundamental principles that govern cell entry by this archetype member of the paramyxovirus family. Here, we review these advances in our molecular understanding of MeV entry in the context of diverse entry strategies employed by other members of the paramyxovirus family.

Detection of measles, mumps and rubella viruses by immuno-colorimetric assay and its application in focus reduction neutralization tests.

PubMed

Vaidya, Sunil R; Kumbhar, Neelakshi S; Bhide, Vandana S

2014-12-01

Measles, mumps and rubella are vaccine-preventable diseases; however limited epidemiological data are available from low-income or developing countries. Thus, it is important to investigate the transmission of these viruses in different geographical regions. In this context, a cell culture-based rapid and reliable immuno-colorimetric assay (ICA) was established and its utility studied. Twenty-three measles, six mumps and six rubella virus isolates and three vaccine strains were studied. Detection by ICA was compared with plaque and RT-PCR assays. In addition, ICA was used to detect viruses in throat swabs (n = 24) collected from patients with suspected measles or mumps. Similarly, ICA was used in a focus reduction neutralization test (FRNT) and the results compared with those obtained by a commercial IgG enzyme immuno assay. Measles and mumps virus were detected 2 days post-infection in Vero or Vero-human signaling lymphocytic activation molecule cells, whereas rubella virus was detected 3 days post-infection in Vero cells. The blue stained viral foci were visible by the naked eye or through a magnifying glass. In conclusion, ICA was successfully used on 35 virus isolates, three vaccine strains and clinical specimens collected from suspected cases of measles and mumps. Furthermore, an application of ICA in a neutralization test (i.e., FRNT) was documented; this may be useful for sero-epidemiological, cross-neutralization and pre/post-vaccine studies. © 2014 The Societies and Wiley Publishing Asia Pty Ltd.

Successful respiratory immunization with dry powder live-attenuated measles virus vaccine in rhesus macaques.

PubMed

Lin, Wen-Hsuan; Griffin, Diane E; Rota, Paul A; Papania, Mark; Cape, Stephen P; Bennett, David; Quinn, Brian; Sievers, Robert E; Shermer, Charles; Powell, Kenneth; Adams, Robert J; Godin, Steven; Winston, Scott

2011-02-15

Measles remains an important cause of childhood mortality worldwide. Sustained high vaccination coverage is the key to preventing measles deaths. Because measles vaccine is delivered by injection, hurdles to high coverage include the need for trained medical personnel and a cold chain, waste of vaccine in multidose vials and risks associated with needle use and disposal. Respiratory vaccine delivery could lower these barriers and facilitate sustained high coverage. We developed a novel single unit dose, dry powder live-attenuated measles vaccine (MVDP) for respiratory delivery without reconstitution. We tested the immunogenicity and protective efficacy in rhesus macaques of one dose of MVDP delivered either with a mask or directly intranasal with two dry powder inhalers, PuffHaler and BD Solovent. MVDP induced robust measles virus (MeV)-specific humoral and T-cell responses, without adverse effects, which completely protected the macaques from infection with wild-type MeV more than one year later. Respiratory delivery of MVDP was safe and effective and could aid in measles control.

Interferon production by cells infected with subacute sclerosing panencephalitis (SSPE) virus or measles virus.

PubMed

Hasegawa, Shunji; Mori, Natsumi; Satomi, Mika; Jiang, Da-Peng; Hotta, Hak; Matsushige, Takeshi; Ichiyama, Takashi

2011-12-01

Subacute sclerosing panencephalitis (SSPE) is a rare progressive neurodegenerative encephalitis caused by some variants of measles virus (MV). The structure of SSPE virus in the brains of SSPE patients is different from that of MV. The difference in interferon (IFN) production between cells infected with SSPE virus and those infected with MV remains unclear. We measured the concentrations of IFN-α, β, γ, and λ1 (interleukin (IL)-29) from MV- or SSPE virus-infected B95a cells (a marmoset B-lymphoblastoid cell line). SSPE virus-infected B95a cells produced significantly higher levels of IFN-α and λ1 than did MV-infected or mock-infected cells. Our results suggest that SSPE virus and MV induce different IFN production profiles. Copyright © 2011 Elsevier Ltd. All rights reserved.

[Measles pathogenic surveillance from 2005 to 2007 in Guangdong Province].

PubMed

Liu, Leng; Zheng, Huan-ying; Guo, Xue; Zhu, Jian-qiong; Ji, Yi-xin; Xu, Wen-bo

2008-12-01

To develop pathogenic surveillance on measles and to effectively isolate measles virus. To know the genetic characterizations and molecular epidemiology of wildtype measles viruses from 2005 to 2007 in Guangdong Province, and provide the scientific basis for measles control and eradication. Vero/Slam cell line were used, measles viruses were isolated from throat swabs or urine specimens collected from uspected measles patients in outbreaks and sporadic patients. A 450 nucleotides fragment of the C-terminal of the nucleoprotein (N) gene was amplified and by RT-PCR and subjected to sequence and phylogenetic analysis using Bio-Edit software. 82 wild-type measels virus were obtained from 377 throat swabs and urine specimens from 2005 to 2007 in Guangdong Province measles lab. The measles isolation rate was 23.58% in 2005, 17.11% in 2006, 39.13% in 2007. The succeed rate of virus isolation is related to the quality of specimens collected and the days after rash occurrence. We have grasped the technicalability of measles virus isolation and confirm action, and got higher isolation ratio. The wild-type measles virus isolated from Guangdong Province is of H1 genotype from 2005 to 2007, which is the same as the dominant genotype circulation.

Measles-induced encephalitis.

PubMed

Fisher, D L; Defres, S; Solomon, T

2015-03-01

Encephalitis is the most frequent neurological complication of measles virus infection. This review examines the pathophysiology of measles infection and the presentations, diagnosis and treatment of the four types of measles-induced encephalitis including primary measles encephalitis, acute post-measles encephalitis, measles inclusion body encephalitis and subacute sclerosing panencephalitis. The early symptoms of encephalitis may be non-specific and can be mistakenly attributed to a systemic infection leading to a delay in diagnosis. This review provides a summary of the symptoms that should cause health care workers to suspect measles-induced encephalitis. © The Author 2014. Published by Oxford University Press on behalf of the Association of Physicians. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Antigenic Drift Defines a New D4 Subgenotype of Measles Virus.

PubMed

Muñoz-Alía, Miguel Ángel; Muller, Claude P; Russell, Stephen J

2017-06-01

The measles virus hemagglutinin (MeV-H) protein is the main target of protective neutralizing antibodies. Using a panel of monoclonal antibodies (MAbs) that recognize known major antigenic sites in MeV-H, we identified a D4 genotype variant that escapes neutralization by MAbs targeting the neutralizing epitope (NE) antigenic site. By site-directed mutagenesis, L249P was identified as the critical mutation disrupting the NE in this genotype D4 variant. Forty-two available D4 genotype gene sequences were subsequently analyzed and divided into 2 groups according to the presence or absence of the L249P MeV-H mutation. Further analysis of the MeV-N gene sequences of these 2 groups confirmed that they represent clearly definable, sequence-divergent D4 subgenotypes, which we named subgenotypes D4.1 and D4.2. The subgenotype D4.1 MeVs were isolated predominantly in Kenya and Ethiopia, whereas the MAb-resistant subgenotype D4.2 MeVs were isolated predominantly in France and Great Britain, countries with higher vaccine coverage rates. Interestingly, D4.2 subgenotype viruses showed a trend toward diminished susceptibility to neutralization by human sera pooled from approximately 60 to 80 North American donors. Escape from MAb neutralization may be a powerful epidemiological surveillance tool to monitor the evolution of new MeV subgenotypes. IMPORTANCE Measles virus is a paradigmatic RNA virus, as the antigenic composition of the vaccination has not needed to be updated since its discovery. The vaccine confers protection by inducing neutralizing antibodies that interfere with the function of the hemagglutinin protein. Viral strains are indistinguishable serologically, although characteristic nucleotide sequences differentiate 24 genotypes. In this work, we describe a distant evolutionary branch within genotype D4. Designated subgenotype D4.2, this virus is distinguishable by neutralization with vaccine-induced monoclonal antibodies that target the neutralizing epitope (NE

Antigenic Drift Defines a New D4 Subgenotype of Measles Virus

PubMed Central

Muller, Claude P.

2017-01-01

ABSTRACT The measles virus hemagglutinin (MeV-H) protein is the main target of protective neutralizing antibodies. Using a panel of monoclonal antibodies (MAbs) that recognize known major antigenic sites in MeV-H, we identified a D4 genotype variant that escapes neutralization by MAbs targeting the neutralizing epitope (NE) antigenic site. By site-directed mutagenesis, L249P was identified as the critical mutation disrupting the NE in this genotype D4 variant. Forty-two available D4 genotype gene sequences were subsequently analyzed and divided into 2 groups according to the presence or absence of the L249P MeV-H mutation. Further analysis of the MeV-N gene sequences of these 2 groups confirmed that they represent clearly definable, sequence-divergent D4 subgenotypes, which we named subgenotypes D4.1 and D4.2. The subgenotype D4.1 MeVs were isolated predominantly in Kenya and Ethiopia, whereas the MAb-resistant subgenotype D4.2 MeVs were isolated predominantly in France and Great Britain, countries with higher vaccine coverage rates. Interestingly, D4.2 subgenotype viruses showed a trend toward diminished susceptibility to neutralization by human sera pooled from approximately 60 to 80 North American donors. Escape from MAb neutralization may be a powerful epidemiological surveillance tool to monitor the evolution of new MeV subgenotypes. IMPORTANCE Measles virus is a paradigmatic RNA virus, as the antigenic composition of the vaccination has not needed to be updated since its discovery. The vaccine confers protection by inducing neutralizing antibodies that interfere with the function of the hemagglutinin protein. Viral strains are indistinguishable serologically, although characteristic nucleotide sequences differentiate 24 genotypes. In this work, we describe a distant evolutionary branch within genotype D4. Designated subgenotype D4.2, this virus is distinguishable by neutralization with vaccine-induced monoclonal antibodies that target the neutralizing epitope

Upon Infection the Cellular WD Repeat-containing Protein 5 (WDR5) Localizes to Cytoplasmic Inclusion Bodies and Enhances Measles Virus Replication.

PubMed

Ma, Dzwokai; George, Cyril X; Nomburg, Jason; Pfaller, Christian K; Cattaneo, Roberto; Samuel, Charles E

2017-12-13

Replication of negative-strand RNA viruses occurs in association with discrete cytoplasmic foci called inclusion bodies. Whereas inclusion bodies represent a prominent subcellular structure induced by viral infection, our knowledge of the cellular protein components involved in inclusion body formation and function is limited. Using measles virus-infected HeLa cells, we found that the WD repeat-containing protein 5 (WDR5), a subunit of histone H3 lysine 4 methyltransferases, was selectively recruited to virus-induced inclusion bodies. Furthermore, WDR5 was found in complexes containing viral proteins associated with RNA replication. WDR5 was not detected with mitochondria, stress granules, or other known secretory or endocytic compartments of infected cells. WDR5 deficiency decreased both viral protein production and infectious virus yields. Interferon production was modestly increased in WDR5 deficient cells. Thus, our study identifies WDR5 as a novel viral inclusion body-associated cellular protein and suggests a role for WDR5 in promoting viral replication. IMPORTANCE Measles virus is a human pathogen that remains a global concern with more than 100,000 measles-related deaths annually despite the availability of an effective vaccine. As measles continues to cause significant morbidity and mortality, understanding the virus-host interactions at the molecular level that affect virus replication efficiency is important for development and optimization of treatment procedures. Measles virus is an RNA virus that encodes six genes and replicates in the cytoplasm of infected cells in discrete cytoplasmic replication bodies, though little is known of the biochemical nature of these structures. Here we show that the cellular protein WDR5 is enriched in the cytoplasmic viral replication factories and enhances virus growth. WDR5-containing protein complex includes viral proteins responsible for viral RNA replication. Thus, we have identified WDR5 as a host factor that

Progress toward the 2012 measles elimination goal--Western Pacific Region, 1990-2008.

PubMed

2009-06-26

In 2003, the World Health Organization (WHO) Regional Committee of the Western Pacific Region (WPR) formally declared a measles elimination goal, and in 2005, the committee established a target date of 2012 for regional measles elimination. Key strategies recommended by WHO for achievement of measles elimination include 1) very high (>or=95%) vaccination coverage with 2 doses of measles-containing vaccine (MCV1 and MCV2) through routine vaccination and/or supplemental immunization activities (SIAs); 2) high-quality case-based measles surveillance; and 3) access to an accredited measles laboratory network for testing of suspected measles cases and identification of measles virus genotypes. This report describes progress toward measles elimination in the WPR through 2008. Measles likely has been eliminated or nearly eliminated in 24 of the 37 countries and areas in the WPR (referred to in this report as countries). However, large numbers of measles cases continue to be reported from several countries. During 2008, a total of 131,441 confirmed measles cases (98.4 per million population) were reported from China and 11,015 cases (86.1 per million population) from Japan, two countries that account for 82% of the region's population and >97% of its confirmed measles cases. Intensified efforts by WPR countries, particularly China and Japan, will be required to achieve the 2012 goal.

Measles & rubella outbreaks in Maharashtra State, India.

PubMed

Vaidya, Sunil R; Kamble, Madhukar B; Chowdhury, Deepika T; Kumbhar, Neelakshi S

2016-02-01

Under the outbreak-based measles surveillance in Maharashtra State the National Institute of Virology at Pune receives 3-5 serum samples from each outbreak and samples from the local hospitals in Pune for laboratory diagnosis. This report describes one year data on the measles and rubella serology, virus isolation and genotyping. Maharashtra State Health Agencies investigated 98 suspected outbreaks between January-December 2013 in the 20 districts. Altogether, 491 serum samples were received from 20 districts and 126 suspected cases from local hospitals. Samples were tested for the measles and rubella IgM antibodies by commercial enzyme immunoassay (EIA). To understand the diagnostic utility, a subset of serum samples (n=53) was tested by measles focus reduction neutralization test (FRNT). Further, 37 throat swabs and 32 urine specimens were tested by measles reverse transcription (RT)-PCR and positive products were sequenced. Virus isolation was performed in Vero hSLAM cells. Of the 98 suspected measles outbreaks, 61 were confirmed as measles, 12 as rubella and 21 confirmed as the mixed outbreaks. Four outbreaks remained unconfirmed. Of the 126 cases from the local hospitals, 91 were confirmed for measles and three for rubella. Overall, 93.6 per cent (383/409) confirmed measles cases were in the age group of 0-15 yr. Measles virus was detected in 18 of 38 specimens obtained from the suspected cases. Sequencing of PCR products revealed circulation of D4 (n=9) and D8 (n=9) strains. Four measles viruses (three D4 & one D8) were isolated. Altogether, 94 measles and rubella outbreaks were confirmed in 2013 in the State of Maharasthra indicating the necessity to increase measles vaccine coverage in the State.

[Measles, mumps and rubella virus infection in pregnancy. Possible adverse effects on pregnant women, pregnancy outcome and the fetus].

PubMed

Enders, M; Biber, M; Exler, S

2007-11-01

Measles, mumps and rubella are common childhood diseases. Therefore, frequent and intense contact with children of preschool age may be associated with a higher infection risk for childcare providers. This overview summarizes current knowledge on possible adverse effects of these infections on pregnant women, pregnancy outcome and the fetus. Acute rubella or mumps virus infections are apparently not more severe in pregnant than non-pregnant women. In contrast, measles virus infection in pregnancy is linked to a higher incidence of pneumonitis and hospitalization. Evidence of congenital defects due to fetal infection is only provided in case of rubella virus infection in early pregnancy. Following rubella virus infection in the first trimester an increased fetal loss rate was reported. In 1966, a prospective study showed also a significant association between maternal mumps in the first trimester and an increased risk of abortion. But other investigators could not confirm this association. Measles and rubella but not mumps virus infections are linked to an increased premature birth rate. Occurring in late pregnancy, all three infections can result in birth of an infected infant. But severe disease occurs rarely and is mostly reported for premature infants with early neonatal measles. Preventive measures, aimed to reduce the risk of infection or severe complications for pregnant childcare providers, should consider the individual history of the employee (e.g. previous immunizations or antibody test results), the current epidemiological situation and possible interventions like passive immunization in case of exposure to measles.

Facts about Measles for Adults

MedlinePlus

... residents should be immune to measles before international travel. Symptoms Symptoms of measles include high fever, generalized rash, runny nose, pink, watery eyes, coughing, diarrhea, and earache. The average time between exposure to the measles virus and development ...

Estimating the force of measles virus infection from hospitalised cases in Lusaka, Zambia.

PubMed

Scott, Susana; Mossong, Joel; Moss, William J; Cutts, Felicity T; Kasolo, Francis; Sinkala, Moses; Cousens, Simon

2004-12-21

Estimates of the force of infection (the rate at which susceptible individuals acquire infection) are essential for modelling the transmission dynamics of infectious diseases and can be a useful tool in evaluating mass vaccination strategies. Few estimates exist of the force of infection of measles virus in sub-Saharan Africa. A mathematical model was applied to age-specific recorded hospital admissions between September 1996 and September 1999 to estimate the force of measles virus infection in Lusaka, Zambia. The average force of infection was estimated to be 20% per year (95% confidence intervals (CI) 16.5, 23.5) which was insensitive to varying assumptions about vaccine coverage. The force of infection varied from year to year (P < 0.001) reflecting the cyclic pattern of measles incidence. The estimated probability of a case being hospitalised decreased with age, consistent with less severe disease in older children. Estimates of the force of infection using routinely available data were consistent with those based upon serological surveys in other sub-Saharan African countries.

Epidemiology of laboratory confirmed measles virus cases in the southern nations of Ethiopia, 2007-2014.

PubMed

Getahun, Mekonen; Beyene, Berhane; Ademe, Ayesheshem; Teshome, Birke; Tefera, Mesfin; Afework, Aklog; HaileMariam, Yoseph; Assefa, Esete; Hailegiorgis, Yonas; Asha, Anjelo

2017-01-19

In Ethiopia, measles case-based surveillance was introduced in 2004 as one strategy for measles control by laboratory confirmation of suspected cases. In this article, epidemiological distribution of laboratory-confirmed measles cases were reported from the Southern Nation Nationalities and Peoples Region (SNNPR) of Ethiopia between 2007 and 2014, as the region is one of the highly measles affected areas in Ethiopia. A serum sample was collected from all measles suspected cases, and patient information was captured by case reporting format (CRF). Samples were transported to the National Measles Laboratory for Measles IgM testing by ELISA technique. Data entry and analysis were done using Epi-Info 3.5.4 software. A total of 4810 samples were tested for measles IgM using ELISA technique and 1507 (31.3%) were found positive during 2007-2014 in SNNPR of Ethiopia. Patients with age 1-4 years were the most affected regardless of sex. The incidence of measles confirmed cases increased from 15 in 2007 to 180 in 2013 per million population. The highest percentage of laboratory-confirmed cases were found in 2014. Measles was found distributed throughout the regional state. Measles was found a public health important disease in SNNPR of Ethiopia, mostly affecting children 1-4 years. The incidence of measles cases is increasing from time to time. Additional research to determine the genotype of circulating measles virus, knowledge, attitude and practice of professionals and the population for measles vaccination and infection in the region is important. A wide age group measles vaccination campaign is highly recommended.

Genetic characterization of Measles Viruses in China, 2004

PubMed Central

Zhang, Yan; Ji, Yixin; Jiang, Xiaohong; Xu, Songtao; Zhu, Zhen; Zheng, Lei; He, Jilan; Ling, Hua; Wang, Yan; Liu, Yang; Du, Wen; Yang, Xuelei; Mao, Naiying; Xu, Wenbo

2008-01-01

Genetic characterization of wild-type measles virus was studied using nucleotide sequencing of the C-terminal region of the N protein gene and phylogenetic analysis on 59 isolates from 16 provinces of China in 2004. The results showed that all of the isolates belonged to genotype H1. 51 isolates were belonged to cluster 1 and 8 isolates were cluster 2 and Viruses from both clusters were distributed throughout China without distinct geographic pattern. The nucleotide sequence and predicted amino acid homologies of the 59 H1 strains were 96.5%–100% and 95.7%–100%, respectively. The report showed that the transmission pattern of genotype H1 viruses in China in 2004 was consistent with ongoing endemic transmission of multiple lineages of a single, endemic genotype. Multiple transmission pathways leaded to multiple lineages within endemic genotype. PMID:18928575

Successful respiratory immunization with dry powder live-attenuated measles virus vaccine in rhesus macaques

PubMed Central

Lin, Wen-Hsuan; Griffin, Diane E.; Rota, Paul A.; Papania, Mark; Cape, Stephen P.; Bennett, David; Quinn, Brian; Sievers, Robert E.; Shermer, Charles; Powell, Kenneth; Adams, Robert J.; Godin, Steven; Winston, Scott

2011-01-01

Measles remains an important cause of childhood mortality worldwide. Sustained high vaccination coverage is the key to preventing measles deaths. Because measles vaccine is delivered by injection, hurdles to high coverage include the need for trained medical personnel and a cold chain, waste of vaccine in multidose vials and risks associated with needle use and disposal. Respiratory vaccine delivery could lower these barriers and facilitate sustained high coverage. We developed a novel single unit dose, dry powder live-attenuated measles vaccine (MVDP) for respiratory delivery without reconstitution. We tested the immunogenicity and protective efficacy in rhesus macaques of one dose of MVDP delivered either with a mask or directly intranasal with two dry powder inhalers, PuffHaler and BD Solovent. MVDP induced robust measles virus (MeV)-specific humoral and T-cell responses, without adverse effects, which completely protected the macaques from infection with wild-type MeV more than one year later. Respiratory delivery of MVDP was safe and effective and could aid in measles control. PMID:21282608

Proof-of-principle that a decoy virus protects oncolytic measles virus against neutralizing antibodies.

PubMed

Xu, Chun; Goß, Annika Verena; Dorneburg, Carmen; Debatin, Klaus-Michael; Wei, Jiwu; Beltinger, Christian

2018-01-01

Attenuated oncolytic measles virus (OMV) is a promising antitumor agent in early-phase clinical trials. However, pre-existing immunity against measles might be a hurdle for OMV therapy. OMV was inactivated with short-wavelength ultraviolet light (UV-C). Loss of replication and oncolytic activity of UV-inactivated OMV were confirmed by tissue culture infective dose 50 (TCID 50 ) assay using Vero cells and by flow cytometry using Jurkat cells. An enzyme-linked immunosorbent assay was performed to verify that UV-inactivated OMV remained antigenic. Different doses of UV-inactivated OMV were pre-cultured in media supplemented with measles immune serum. The mixture was transferred to Jurkat cells and active OMV was added. Active OMV-induced death of Jurkat cells was monitored by flow cytometry. UV-inactivation abrogates OMV replication while maintaining its antigenicity. UV-inactivated OMV sequesters pre-existing anti-MV antibodies in Jurkat cell culture, thereby protecting active OMV from neutralization and preserving oncolytic activity. We prove the principle that a non-replicating OMV can serve as a "decoy" for neutralizing anti-MV antibodies, thereby allowing antitumor activity of OMV.

Measles & rubella outbreaks in Maharashtra State, India

PubMed Central

Vaidya, Sunil R.; Kamble, Madhukar B.; Chowdhury, Deepika T.; Kumbhar, Neelakshi S.

2016-01-01

Background & objectives: Under the outbreak-based measles surveillance in Maharashtra State the National Institute of Virology at Pune receives 3-5 serum samples from each outbreak and samples from the local hospitals in Pune for laboratory diagnosis. This report describes one year data on the measles and rubella serology, virus isolation and genotyping. Methods: Maharashtra State Health Agencies investigated 98 suspected outbreaks between January-December 2013 in the 20 districts. Altogether, 491 serum samples were received from 20 districts and 126 suspected cases from local hospitals. Samples were tested for the measles and rubella IgM antibodies by commercial enzyme immunoassay (EIA). To understand the diagnostic utility, a subset of serum samples (n=53) was tested by measles focus reduction neutralization test (FRNT). Further, 37 throat swabs and 32 urine specimens were tested by measles reverse transcription (RT)-PCR and positive products were sequenced. Virus isolation was performed in Vero hSLAM cells. Results: Of the 98 suspected measles outbreaks, 61 were confirmed as measles, 12 as rubella and 21 confirmed as the mixed outbreaks. Four outbreaks remained unconfirmed. Of the 126 cases from the local hospitals, 91 were confirmed for measles and three for rubella. Overall, 93.6 per cent (383/409) confirmed measles cases were in the age group of 0-15 yr. Measles virus was detected in 18 of 38 specimens obtained from the suspected cases. Sequencing of PCR products revealed circulation of D4 (n=9) and D8 (n=9) strains. Four measles viruses (three D4 & one D8) were isolated. Interpretation & conclusions: Altogether, 94 measles and rubella outbreaks were confirmed in 2013 in the State of Maharasthra indicating the necessity to increase measles vaccine coverage in the State. PMID:27121521

Measles vaccination: Threat from related veterinary viruses and need for continued vaccination post measles eradication.

PubMed

Cosby, Sara Louise; Weir, Leanne

2018-01-02

Measles virus (MV) is the only human virus within the morbillivirus genus of the Paramyxoviridae. The veterinary members are canine distemper virus (CDV), peste des petits ruminants virus (PPRV), Rinderpest Virus (RPV) as well as the marine morbilliviruses phocine distemper virus (PDV), dolphin morbillivirus (DMV) and porpoise morbillivirus (PMV). Morbilliviruses have a severe impact on humans and animal species. They confer diseases which have contributed to morbidity and mortality of the population on a global scale. There is substantial evidence from both natural and experimental infections that morbilliviruses can readily cross species barriers. Of most concern with regard to zoonosis is the more recently reported fatal infection of primates in Japan and China with strains of CDV which have adapted to this host. The close genetic relationship, shared cell entry receptors and similar pathogenesis between the morbilliviruses highlights the potential consequences of complete withdrawal of MV vaccination after eradication. Therefore, it would be prudent to continue the current MV vaccination. Ultimately development of novel, safe vaccines which have higher efficacy against the veterinary morbilliviruses is a priority. These would to protect the human population long term against the threat of zoonosis by these veterinary viruses.

Changes in Measles Serostatus Among HIV-Infected Zambian Children Initiating Antiretroviral Therapy Before and After the 2010 Measles Outbreak and Supplemental Immunization Activities

PubMed Central

Rainwater-Lovett, Kaitlin; Nkamba, Hope C.; Mubiana-Mbewe, Mwangelwa; Bolton-Moore, Carolyn; Moss, William J.

2013-01-01

Background. In 2010, Zambia had a large measles outbreak, providing an opportunity to measure changes in measles serostatus following highly active antiretroviral therapy (HAART), exposure to measles virus, and revaccination among children infected with human immunodeficiency virus (HIV). Methods. A prospective cohort study of 169 HIV-infected Zambian children aged 9–60 months with a history of measles vaccination was conducted to characterize the effects of HAART and revaccination on measles immunoglobulin G (IgG) serostatus by enzyme immunoassay. Results. Prior to the measles outbreak, only 23% of HIV-infected children were measles IgG seropositive at HAART initiation. After adjusting for 6-month changes in baseline age and 5% changes in nadir CD4+ T-cell percentage, HAART was not associated with measles IgG seroconversion. However, 18 of 19 children seroconverted after revaccination. Eight children seroconverted during the outbreak without revaccination and were likely exposed to wild-type measles virus, but none were reported to have had clinical measles. Conclusions. Immune reconstitution after HAART initiation did not restore protective levels of measles IgG antibodies, but almost all children developed protective antibody levels after revaccination. Some previously vaccinated HIV-infected children had serological evidence of exposure to wild-type measles virus without a reported history of measles. PMID:23911708

A chimeric measles virus with a lentiviral envelope replicates exclusively in CD4+/CCR5+ cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mourez, Thomas; APHP, GH Saint-Louis-Lariboisiere, Laboratoire de Bacteriologie-Virologie, F-75010 Paris; Universite Paris 7 Denis Diderot, F-75010 Paris

2011-10-25

We generated a replicating chimeric measles virus in which the hemagglutinin and fusion surface glycoproteins were replaced with the gp160 envelope glycoprotein of simian immunodeficiency virus (SIVmac239). Based on a previously cloned live-attenuated Schwarz vaccine strain of measles virus (MV), this chimera was rescued at high titers using reverse genetics in CD4+ target cells. Cytopathic effect consisted in the presence of large cell aggregates evolving to form syncytia, as observed during SIV infection. The morphology of the chimeric virus was identical to that of the parent MV particles. The presence of SIV gp160 as the only envelope protein on chimericmore » particles surface altered the cell tropism of the new virus from CD46+ to CD4+ cells. Used as an HIV candidate vaccine, this MV/SIVenv chimeric virus would mimic transient HIV-like infection, benefiting both from HIV-like tropism and the capacity of MV to replicate in dendritic cells, macrophages and lymphocytes.« less

Characteristics of Viruses Derived from Nude Mice with Persistent Measles Virus Infection

PubMed Central

Hashimoto, Koichi; Watanabe, Masahiro; Ohara, Shinichiro; Sato, Masatoki; Kawasaki, Yukihiko; Hashimoto, Yuko; Hosoya, Mitsuaki

2013-01-01

Measles virus (MV) isolates from patients with subacute sclerosing panencephalitis (SSPE) differ from wild-type MV virologically. However, few animal models have reported viruses with characteristics of the SSPE virus. The MV Edmonston strain was inoculated into the subarachnoid space of nude mice. All nude mice displayed weight loss and required euthanasia, with a mean survival duration of 73.2 days. The viral load in the brain was 4- to 400-fold higher than the inoculated load, and brain infection was confirmed by immunostaining. Gene sequencing of the viruses revealed that amino acid mutations occurred more frequently in matrix proteins. The most common mutation was a uridine-to-cytosine transition. The virus exhibited lower free virus particle formation ability than the Edmonston strain. When nude mice were challenged with 2 × 102 PFU of the brain-derived virus, the mean survival duration was 34.7 days, which was significantly shorter than that of the mice challenged with 4 × 104 PFU of the Edmonston strain (P < 0.01). This study indicated that MV in a nude mouse model of persistent infection exhibited characteristics of the SSPE virus. This model may prove useful in elucidating the pathogenic mechanism of SSPE and developing potential therapeutics. PMID:23345518

Characteristics of viruses derived from nude mice with persistent measles virus infection.

PubMed

Abe, Yusaku; Hashimoto, Koichi; Watanabe, Masahiro; Ohara, Shinichiro; Sato, Masatoki; Kawasaki, Yukihiko; Hashimoto, Yuko; Hosoya, Mitsuaki

2013-04-01

Measles virus (MV) isolates from patients with subacute sclerosing panencephalitis (SSPE) differ from wild-type MV virologically. However, few animal models have reported viruses with characteristics of the SSPE virus. The MV Edmonston strain was inoculated into the subarachnoid space of nude mice. All nude mice displayed weight loss and required euthanasia, with a mean survival duration of 73.2 days. The viral load in the brain was 4- to 400-fold higher than the inoculated load, and brain infection was confirmed by immunostaining. Gene sequencing of the viruses revealed that amino acid mutations occurred more frequently in matrix proteins. The most common mutation was a uridine-to-cytosine transition. The virus exhibited lower free virus particle formation ability than the Edmonston strain. When nude mice were challenged with 2 × 10(2) PFU of the brain-derived virus, the mean survival duration was 34.7 days, which was significantly shorter than that of the mice challenged with 4 × 10(4) PFU of the Edmonston strain (P < 0.01). This study indicated that MV in a nude mouse model of persistent infection exhibited characteristics of the SSPE virus. This model may prove useful in elucidating the pathogenic mechanism of SSPE and developing potential therapeutics.

Mechanism of Polykaryocytosis Associated with Noncytopathic Infection by Measles Virus

PubMed Central

Atherton, John G.; Chaparas, Sotiros D.; Cremer, Martha; Gordon, Irving

1965-01-01

Atherton, John G. (University of Southern California, Los Angeles), Sotiros G. Chaparas, Martha Cremer, and Irving Gordon. Mechanism of polykaryocytosis associated with noncytopathic infection by measles virus. J. Bacteriol. 90:213–219. 1965.—Infection with a measles virus variant resulted not only in formation of polykaryocytes (PK) but also in formation of multicellular immunofluorescent foci (IFF) in which no cytopathic effect could be detected. The ratio of IFF to PK changed from 27 to 4 during the first passage and remained 4 after a second passage. PK were plaques. Plaque assay was linear in the presence of IFF. To investigate the mechanism of PK formation, radioautography was done on cells pulse-labeled with tritiated thymidine before virus multiplication began. The results showed that PK were formed by fusion; there were no PK whose nuclei contained no label, and the proportion of labeled nuclei (32%) and distribution of grain counts was the same in PK as in uninvolved cells, ruling out nuclear replication without concomitant cytoplasmic membrane formation as the mechanism of formation of these PK. Early in PK development, neutral red uptake was markedly increased (“red” plaques). As PK matured, hyperchromicity disappeared (“white” plaques). This sequence provided an index of rate of evolution of PK. Rate of PK maturation was more rapid at 37 than at 32 C. Images PMID:16562019

Isolation of measles virus in primary rhesus monkey cells from a child with acute interstitial pneumonia who cytologically had giant-cell pneumonia without a rash.

PubMed

Siegel, C; Johnston, S; Adair, S

1990-10-01

The isolation of measles virus in primary Rhesus monkey kidney cells (PRMK) in patients with documented giant-cell pneumonia who have presented without a rash is limited. The diagnosis usually is made by cytologic examination of nasal or bronchial secretions in which characteristic multinucleated giant cells with intranuclear and intracytoplasmic inclusion bodies are observed. The diagnosis of giant-cell pneumonia has been associated with measles virus but not exclusively. Canine distemper, herpes group viruses, and parainfluenza infections have been associated with these cells. In addition, vitamin A deficiency also has been cytologically associated with multinucleated giant cells. The authors describe the isolation of measles virus from bronchial washing and sputum in PRMK cells at 4 days from an 11-year-old child with acute interstitial pneumonia who was in remission for acute lymphocytic leukemia. Classic cytopathologic effect (CPE) consisting of syncytial and hole formation on the PRMK monolayer was apparent. In addition, a foamy appearance of the monolayer was noted in an otherwise clean lot of monkey cells. Confirmatory testing with measles antibody of the infected areas of the monolayer by indirect immunofluorescence (IFA) was positive for measles antigen and negative for mumps, parainfluenza (types I, II, and III) and influenza A and B virus. Serologic studies for measles antibody revealed an IFA IgG titer of greater than 1:10,240, and an IgM titer of 1:128. Cytologic examination of the same bronchial fluid revealed the typical giant cells with characteristic inclusions associated with measles virus. Because this disease usually is severe, and often fatal, prompt recognition of this virus is essential, not only to the patient, who can be treated with immunoglobulin and/or antiviral therapy, but also to prevent the spread of the virus to other patients and medical personnel. These findings also support direct evidence for the etiologic role of measles virus

[Measles and pregnancy].

PubMed

Anselem, Olivia; Tsatsaris, Vassilis; Lopez, Emmanuel; Krivine, Anne; Le Ray, Camille; Loulergue, Pierre; Floret, Daniel; Goffinet, Francois; Launay, Odile

2011-11-01

Because of insufficient vaccine coverage, there is an outbreak of measles since 2008 in France with an increasing incidence of cases, most of them among children less than 1 year old or young adults. When measles occurs during pregnancy, maternal and fetal morbidity is increased. Particularly pregnant women are exposed to a higher risk of severe respiratory distress that might cause death. Measles virus can be detected in the placenta. Placental infection appears to be involved in some cases of fetal death. The virus is not responsible for congenital defects but can induce histologic damages inside the placenta which may lead to fetal death. Major perinatal risks are also miscarriage and prematurity. When measles occurs in late pregnancy, congenital infection is possible with variable expression and a risk of subacute sclerosing panencephalitis. Non immune pregnant women or neonates exposed to measles should receive an immunoglobulin prophylaxis within 6 days after contact in order to reduce the risk of infection and severe morbidity. In case of declared measles infection, symptomatic treatment can be proposed and tocolysis can be used if preterm labor is associated. Daily fetal monitoring during the 14 days following the beginning of the eruption can be offered when the fetus is viable. Vaccination is recommended for the people born in France after 1980 with 2 doses of vaccine against measles, rubeola and mumps. Measles vaccine, an attenuated living vaccine, should not be administered during pregnancy but must be proposed before pregnancy or during the post-partum period. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

Seroprevalence of antibodies to measles, mumps, and rubella, and serologic responses after vaccination among human immunodeficiency virus (HIV)-1 infected adults in Northern Thailand.

PubMed

Chaiwarith, Romanee; Praparattanapan, Jutarat; Nuket, Khanuengnit; Kotarathitithum, Wilai; Supparatpinyo, Khuanchai

2016-04-30

After the global implementation of national immunization programs for prevention of measles, mumps, and rubella (MMR), the prevalences of protective antibodies to these viruses are high in general population. However, there are limited data among human immunodeficiency virus (HIV)-1 infected individuals. This study aimed to determine the seroprevalence of antibodies to these viruses, and the serologic responses after vaccination among HIV-infected adults in Northern Thailand. A cross-sectional study was conducted in 500 HIV-infected adults, aged 20-59 years, receiving combination antiretroviral therapy, CD4 cell count ≥200 cells/mm(3), and plasma HIV-1 RNA <50 copies/mL, and 132 HIV-uninfected controls, aged 20-59 years, at Chiang Mai University Hospital during July and August 2011. Prevalences of protective antibodies to these viruses as well as serologic responses after MMR vaccination in those without protective antibody to at least one of the three viruses were compared between groups. The prevalences of protective antibodies to measles, mumps, and rubella were 94.2, 55.0, and 84.6 % among HIV-infected adults, and 97.7, 67.5, and 89.4 % among HIV-uninfected controls, respectively. The prevalence of protective antibody to mumps was significantly lower in HIV-infected adults (p-value = 0.010). MMR vaccination was done in 249 HIV-infected and 46 HIV-uninfected controls; at week 8 to 12 after vaccination, the seroprotective rates against measles, mumps, and rubella in HIV-infected adults were 96.4, 70.7, and 98.0 %, respectively, whereas those in HIV-uninfected controls were 100, 87, and 100 %, respectively. No serious adverse effects were observed. In contrast to measles and rubella, the prevalence of protective antibody to mumps was low in both HIV-infected adults and HIV-uninfected controls in northern Thailand. The seroprotective rates after MMR vaccination in both groups were considerably high, except only for mumps. Therefore, MMR vaccination

Proof-of-principle that a decoy virus protects oncolytic measles virus against neutralizing antibodies

PubMed Central

Dorneburg, Carmen; Debatin, Klaus-Michael; Wei, Jiwu; Beltinger, Christian

2018-01-01

Background Attenuated oncolytic measles virus (OMV) is a promising antitumor agent in early-phase clinical trials. However, pre-existing immunity against measles might be a hurdle for OMV therapy. Methods OMV was inactivated with short-wavelength ultraviolet light (UV-C). Loss of replication and oncolytic activity of UV-inactivated OMV were confirmed by tissue culture infective dose 50 (TCID50) assay using Vero cells and by flow cytometry using Jurkat cells. An enzyme-linked immunosorbent assay was performed to verify that UV-inactivated OMV remained antigenic. Different doses of UV-inactivated OMV were pre-cultured in media supplemented with measles immune serum. The mixture was transferred to Jurkat cells and active OMV was added. Active OMV-induced death of Jurkat cells was monitored by flow cytometry. Results UV-inactivation abrogates OMV replication while maintaining its antigenicity. UV-inactivated OMV sequesters pre-existing anti-MV antibodies in Jurkat cell culture, thereby protecting active OMV from neutralization and preserving oncolytic activity. Conclusion We prove the principle that a non-replicating OMV can serve as a “decoy” for neutralizing anti-MV antibodies, thereby allowing antitumor activity of OMV. PMID:29750140

Measles in suburban Khartoum: an epidemiological and clinical study.

PubMed

Ibrahim, S A; Mustafa, O M; Mukhtar, M M; Saleh, E A; El Mubarak, H S; Abdallah, A; El-Hassan, A M; Osterhaus, A D M E; Groen, J; De Swart, R L; Zijlstra, E E

2002-05-01

Clinical and epidemiological data were collected from 187 clinically diagnosed measles patients in Haj Yousif area, suburban Khartoum. Laboratory tests confirmed the diagnosis in 141 (75%) of the cases, but demonstrated that in 46 (25%) patients the clinical symptoms were not caused by an acute measles virus (MV) infection. According to their vaccination card, 59% of the laboratory-confirmed measles cases had been vaccinated for measles. Compared with non-measles rash disease cases, confirmed measles cases more often had severe illness (P < 0.0001), were dehydrated (P=0.01) at presentation and less likely to recover without complications [OR 0.19 (95% CI 0.09, 0.39)]. There was no difference in death rate (P=0.20). Underweight [weight-for-age Z score (WAZ) measles cases (those who developed diarrhoea, pneumonia, otitis media, encephalitis or haemorrhagic rash) had similar vaccination rates and time intervals since vaccination as uncomplicated measles cases. Although severe measles had lower WAZ-scores (P=0.004), none of the nutritional parameters studied were predictive of outcome. Mortality was higher in the severe measles group [OR 8.8 (95% CI 1.7, 85.2)]. In 11 of 141 confirmed measles cases serological evidence of a recent infection with another virus was found, most commonly varicella zoster virus and dengue virus; spotted fever and rubella were among the most frequent diagnoses in 17 of 47 cases of the non-measles cases.

German Measles (Rubella)

MedlinePlus

... the world. German measles is caused by the rubella virus, which is not the same virus that causes ... days after a child is infected with the virus. What You Can Do Make ... tired. Children with rubella should not attend school or child care for ...

Measles resurgence in southern Africa: challenges to measles elimination.

PubMed

Shibeshi, Messeret E; Masresha, Balcha G; Smit, Sheilagh B; Biellik, Robin J; Nicholson, Jennifer L; Muitherero, Charles; Shivute, Nestor; Walker, Oladapo; Reggis, Katsande; Goodson, James L

2014-04-01

In seven southern African countries (Botswana, Lesotho, Malawi, Namibia, South Africa, Swaziland and Zimbabwe), following implementation of a measles mortality reduction strategy starting in 1996, the number of annually reported measles cases decreased sharply to less than one per million population during 2006-2008. However, during 2009-2010, large outbreaks occurred in these countries. In 2011, a goal for measles elimination by 2020 was set in the World Health Organization (WHO) African Region (AFR). We reviewed the implementation of the measles control strategy and measles epidemiology during the resurgence in the seven southern African countries. Estimated coverage with routine measles vaccination, supplemental immunization activities (SIA), annually reported measles cases by country, and measles surveillance and laboratory data were analyzed using descriptive analysis. In the seven countries, coverage with the routine first dose of measles-containing vaccine (MCV1) decreased from 80% to 65% during 1996-2004, then increased to 84% in 2011; during 1996-2011, 79,696,523 people were reached with measles vaccination during 45 SIAs. Annually reported measles cases decreased from 61,160 cases to 60 cases and measles incidence decreased to <1 case per million during 1996-2008. During 2009-2010, large outbreaks that included cases among older children and adults were reported in all seven countries, starting in South Africa and Namibia in mid-2009 and in the other five countries by early 2010. The measles virus genotype detected was predominantly genotype B3. The measles resurgence highlighted challenges to achieving measles elimination in AFR by 2020. To achieve this goal, high two-dose measles vaccine coverage by strengthening routine immunization systems and conducting timely SIAs targeting expanded age groups, potentially including young adults, and maintaining outbreak preparedness to rapidly respond to outbreaks will be needed. Published by Elsevier Ltd.

Morbillivirus Experimental Animal Models: Measles Virus Pathogenesis Insights from Canine Distemper Virus

PubMed Central

da Fontoura Budaszewski, Renata; von Messling, Veronika

2016-01-01

Morbilliviruses share considerable structural and functional similarities. Even though disease severity varies among the respective host species, the underlying pathogenesis and the clinical signs are comparable. Thus, insights gained with one morbillivirus often apply to the other members of the genus. Since the Canine distemper virus (CDV) causes severe and often lethal disease in dogs and ferrets, it is an attractive model to characterize morbillivirus pathogenesis mechanisms and to evaluate the efficacy of new prophylactic and therapeutic approaches. This review compares the cellular tropism, pathogenesis, mechanisms of persistence and immunosuppression of the Measles virus (MeV) and CDV. It then summarizes the contributions made by studies on the CDV in dogs and ferrets to our understanding of MeV pathogenesis and to vaccine and drugs development. PMID:27727184

Measles eradication: experience in the Americas.

PubMed Central

de Quadros, C. A.; Hersh, B. S.; Nogueira, A. C.; Carrasco, P. A.; da Silveira, C. M.

1998-01-01

In 1994, the Ministers of Health from the Region of the Americas targeted measles for eradication from the Western Hemisphere by the year 2000. To achieve this goal, the Pan American Health Organization (PAHO) developed an enhanced measles eradication strategy. First, a one-time-only "catch-up" measles vaccination campaign is conducted among children aged 9 months to 14 years. Efforts are then made to vaccinate through routine health services ("keep-up") at least 95% of each newborn cohort at 12 months of age. Finally, to assure high population immunity among preschool-aged children, indiscriminate "follow-up" measles vaccination campaigns are conducted approximately every 4 years. These vaccination activities are accompanied by improvements in measles surveillance, including the laboratory testing of suspected measles cases. The implementation of the PAHO strategy has resulted in a marked reduction in measles incidence in all countries of the Americas. Indeed, in 1996 the all-time regional record low of 2109 measles cases was reported. There was a relative resurgence of measles in 1997 with over 20,000 cases, due to a large measles outbreak among infants, preschool-aged children and young adults in São Paulo, Brazil. Contributing factors for this outbreak included: low routine infant vaccination coverage, failure to conduct a "follow-up" campaign, presence of susceptible young adults, and the importation of measles virus, apparently from Europe. PAHO's strategy has been effective in interrupting measles virus circulation. This experience demonstrates that global measles eradication is an achievable goal using currently available measles vaccines. PMID:10063674

Measles virus genetic evolution throughout an imported epidemic outbreak in a highly vaccinated population.

PubMed

Muñoz-Alía, Miguel Ángel; Fernández-Muñoz, Rafael; Casasnovas, José María; Porras-Mansilla, Rebeca; Serrano-Pardo, Ángela; Pagán, Israel; Ordobás, María; Ramírez, Rosa; Celma, María Luisa

2015-01-22

Measles virus circulates endemically in African and Asian large urban populations, causing outbreaks worldwide in populations with up-to-95% immune protection. We studied the natural genetic variability of genotype B3.1 in a population with 95% vaccine coverage throughout an imported six month measles outbreak. From first pass viral isolates of 47 patients we performed direct sequencing of genomic cDNA. Whilst no variation from index case sequence occurred in the Nucleocapsid gene hyper-variable carboxy end, in the Hemagglutinin gene, main target for neutralizing antibodies, we observed gradual nucleotide divergence from index case along the outbreak (0% to 0.380%, average 0.138%) with the emergence of transient and persistent non-synonymous and synonymous mutations. Little or no variation was observed between the index and last outbreak cases in Phosphoprotein, Nucleocapsid, Matrix and Fusion genes. Most of the H non-synonymous mutations were mapped on the protein surface near antigenic and receptors binding sites. We estimated a MV-Hemagglutinin nucleotide substitution rate of 7.28 × 10-6 substitutions/site/day by a Bayesian phylogenetic analysis. The dN/dS analysis did not suggest significant immune or other selective pressures on the H gene during the outbreak. These results emphasize the usefulness of MV-H sequence analysis in measles epidemiological surveillance and elimination programs, and in detection of potentially emergence of measles virus neutralization-resistant mutants. Copyright © 2014 Elsevier B.V. All rights reserved.

Progress Toward Measles Elimination - Western Pacific Region, 2013-2017.

PubMed

Hagan, José E; Kriss, Jennifer L; Takashima, Yoshihiro; Mariano, Kayla Mae L; Pastore, Roberta; Grabovac, Varja; Dabbagh, Alya J; Goodson, James L

2018-05-04

In 2005, the Regional Committee for the World Health Organization (WHO) Western Pacific Region (WPR)* established a goal for measles elimination † by 2012 (1). To achieve this goal, the 37 WPR countries and areas implemented the recommended strategies in the WPR Plan of Action for Measles Elimination (2) and the Field Guidelines for Measles Elimination (3). The strategies include 1) achieving and maintaining ≥95% coverage with 2 doses of measles-containing vaccine (MCV) through routine immunization services and supplementary immunization activities (SIAs), when required; 2) conducting high-quality case-based measles surveillance, including timely and accurate testing of specimens to confirm or discard suspected cases and detect measles virus for genotyping and molecular analysis; and 3) establishing and maintaining measles outbreak preparedness to ensure rapid response and appropriate case management. This report updates the previous report (4) and describes progress toward measles elimination in WPR during 2013-2017. During 2013-2016, estimated regional coverage with the first MCV dose (MCV1) decreased from 97% to 96%, and coverage with the routine second MCV dose (MCV2) increased from 91% to 93%. Eighteen (50%) countries achieved ≥95% MCV1 coverage in 2016. Seven (39%) of 18 nationwide SIAs during 2013-2017 reported achieving ≥95% administrative coverage. After a record low of 5.9 cases per million population in 2012, measles incidence increased during 2013-2016 to a high of 68.9 in 2014, because of outbreaks in the Philippines and Vietnam, as well as increased incidence in China, and then declined to 5.2 in 2017. To achieve measles elimination in WPR, additional measures are needed to strengthen immunization programs to achieve high population immunity, maintain high-quality surveillance for rapid case detection and confirmation, and ensure outbreak preparedness and prompt response to contain outbreaks.

A point-of-care test for measles diagnosis: detection of measles-specific IgM antibodies and viral nucleic acid.

PubMed

Warrener, Lenesha; Slibinskas, Rimantas; Chua, Kaw Bing; Nigatu, Wondatir; Brown, Kevin E; Sasnauskas, Kestutis; Samuel, Dhanraj; Brown, David

2011-09-01

To evaluate the performance of a newly developed point-of-care test (POCT) for the detection of measles-specific IgM antibodies in serum and oral fluid specimens and to assess if measles virus nucleic acid could be recovered from used POCT strips. The POCT was used to test 170 serum specimens collected through measles surveillance or vaccination programmes in Ethiopia, Malaysia and the Russian Federation: 69 were positive for measles immunoglobulin M (IgM) antibodies, 74 were positive for rubella IgM antibodies and 7 were positive for both. Also tested were 282 oral fluid specimens from the measles, mumps and rubella (MMR) surveillance programme of the United Kingdom of Great Britain and Northern Ireland. The Microimmune measles IgM capture enzyme immunoassay was the gold standard for comparison. A panel of 24 oral fluids was used to investigate if measles virus haemagglutinin (H) and nucleocapsid (N) genes could be amplified by polymerase chain reaction directly from used POCT strips. With serum POCT showed a sensitivity and specificity of 90.8% (69/76) and 93.6% (88/94), respectively; with oral fluids, sensitivity and specificity were 90.0% (63/70) and 96.2% (200/208), respectively. Both H and N genes were reliably detected in POCT strips and the N genes could be sequenced for genotyping. Measles virus genes could be recovered from POCT strips after storage for 5 weeks at 20-25 °C. The POCT has the sensitivity and specificity required of a field-based test for measles diagnosis. However, its role in global measles control programmes requires further evaluation.

Measles virus infection of human keratinocytes: Possible link between measles and atopic dermatitis.

PubMed

Gourru-Lesimple, Geraldine; Mathieu, Cyrille; Thevenet, Thomas; Guillaume-Vasselin, Vanessa; Jégou, Jean-François; Boer, Cindy G; Tomczak, Katarzyna; Bloyet, Louis-Marie; Giraud, Celine; Grande, Sophie; Goujon, Catherine; Cornu, Catherine; Horvat, Branka

2017-05-01

Measles virus (MV) infection is marked with a skin rash in the acute phase of the disease, which pathogenesis remains poorly understood. Moreover, the association between measles and progression of skin diseases, such as atopic dermatitis (AD), is still elusive. We have thus analysed the susceptibility of human keratinocytes to MV infection and explore the potential relationship between MV vaccination and the pathogenesis the AD. We performed immunovirological characterisation of MV infection in human keratinocytes and then tested the effect of live attenuated measles vaccine on the progression of AD in adult patients, in a prospective, double-blind study. We showed that both human primary keratinocytes and the keratinocyte cell line HaCaT express MV receptors and could be infected by MV. The infection significantly modulated the expression of several keratinocyte-produced cytokines, known to be implicated in the pathogenesis of inflammatory allergic diseases, including AD. We then analysed the relationship between exposure to MV by vaccination and the progression of AD in 20 adults during six weeks. We found a significant decrease in CCL26 and thymic stromal lymphopoietin (TSLP) mRNA in biopsies from acute lesions of vaccinated patients, suggesting MV-induced modulation of skin cytokine expression. Clinical analysis revealed a transient improvement of SCORAD index in vaccinated compared to placebo-treated patients, two weeks after vaccination. Altogether, these results clearly demonstrate that keratinocytes are susceptible to MV infection, which could consequently modulate their cytokine production, resulting with a beneficial effect in the progression of AD. This study provides thus a proof of concept for the vaccination therapy in AD and may open new avenues for the development of novel strategies in the treatment of this allergic disease. Copyright © 2017 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.

Molecular characterization of wild-type measles viruses in Tamil Nadu, India, during 2005-2006: relationship of genotype D8 strains from Tamil Nadu to global strains.

PubMed

Duraisamy, Raja; Rota, Paul A; Palani, Gunasekaran; Elango, Varalakshmi; Sambasivam, Mohana; Lowe, Luis; Lopareva, Elena; Ramamurty, Nalini

2012-02-01

Molecular characterization of measles viruses is a valuable tool for measuring the effectiveness of measles control and elimination programmes. WHO recommends that virological surveillance be conducted during all phases of measles control to document circulation of indigenous strains and trace future importation. This report describes the genetic characterization of wild type measles viruses from Tamil Nadu, India isolated between January 2005 and January 2006. In the study, 304 suspected measles cases (292 from 56 outbreaks and 12 sporadic cases) were investigated. Blood samples were collected from suspected measles outbreaks and 11 suspected sporadic cases and tested for the presence of measles and rubella specific IgM. Based on serological results, 53 outbreaks were confirmed as measles, 2 as a combination of measles and rubella, and 1 negative for both. Eight sporadic cases were confirmed as measles and one as rubella. Throat swab and urine samples were collected for virus isolation and 28 isolates were obtained. Sequencing and analysis showed that 3 isolates belonged to genotype D4 and 25 to genotype D8. Comparison of the genotype D8 sequences from Tamil Nadu with previously reported genotype D8 sequences from India and abroad showed six distinct clusters with Tamil Nadu strains forming two clusters. This study has established baseline molecular data and is the first report that describes genetic diversity of circulating measles strains in Tamil Nadu, a state in India. D8 has multiple lineages and this has been linked with importation of measles into the USA and UK. Copyright © 2011 Wiley Periodicals, Inc.

Genetic characterization of the hemagglutinin genes of wild-type measles virus circulating in china, 1993-2009.

PubMed

Xu, Songtao; Zhang, Yan; Zhu, Zhen; Liu, Chunyu; Mao, Naiying; Ji, Yixin; Wang, Huiling; Jiang, Xiaohong; Li, Chongshan; Tang, Wei; Feng, Daxing; Wang, Changyin; Zheng, Lei; Lei, Yue; Ling, Hua; Zhao, Chunfang; Ma, Yan; He, Jilan; Wang, Yan; Li, Ping; Guan, Ronghui; Zhou, Shujie; Zhou, Jianhui; Wang, Shuang; Zhang, Hong; Zheng, Huanying; Liu, Leng; Ma, Hemuti; Guan, Jing; Lu, Peishan; Feng, Yan; Zhang, Yanjun; Zhou, Shunde; Xiong, Ying; Ba, Zhuoma; Chen, Hui; Yang, Xiuhui; Bo, Fang; Ma, Yujie; Liang, Yong; Lei, Yake; Gu, Suyi; Liu, Wei; Chen, Meng; Featherstone, David; Jee, Youngmee; Bellini, William J; Rota, Paul A; Xu, Wenbo

2013-01-01

China experienced several large measles outbreaks in the past two decades, and a series of enhanced control measures were implemented to achieve the goal of measles elimination. Molecular epidemiologic surveillance of wild-type measles viruses (MeV) provides valuable information about the viral transmission patterns. Since 1993, virologic surveillnace has confirmed that a single endemic genotype H1 viruses have been predominantly circulating in China. A component of molecular surveillance is to monitor the genetic characteristics of the hemagglutinin (H) gene of MeV, the major target for virus neutralizing antibodies. Analysis of the sequences of the complete H gene from 56 representative wild-type MeV strains circulating in China during 1993-2009 showed that the H gene sequences were clustered into 2 groups, cluster 1 and cluster 2. Cluster1 strains were the most frequently detected cluster and had a widespread distribution in China after 2000. The predicted amino acid sequences of the H protein were relatively conserved at most of the functionally significant amino acid positions. However, most of the genotype H1 cluster1 viruses had an amino acid substitution (Ser240Asn), which removed a predicted N-linked glycosylation site. In addition, the substitution of Pro397Leu in the hemagglutinin noose epitope (HNE) was identified in 23 of 56 strains. The evolutionary rate of the H gene of the genotype H1 viruses was estimated to be approximately 0.76×10(-3) substitutions per site per year, and the ratio of dN to dS (dN/dS) was <1 indicating the absence of selective pressure. Although H genes of the genotype H1 strains were conserved and not subjected to selective pressure, several amino acid substitutions were observed in functionally important positions. Therefore the antigenic and genetic properties of H genes of wild-type MeVs should be monitored as part of routine molecular surveillance for measles in China.

Whole-Genome Sequencing of Measles Virus Genotypes H1 and D8 During Outbreaks of Infection Following the 2010 Olympic Winter Games Reveals Viral Transmission Routes.

PubMed

Gardy, Jennifer L; Naus, Monika; Amlani, Ashraf; Chung, Walter; Kim, Hochan; Tan, Malcolm; Severini, Alberto; Krajden, Mel; Puddicombe, David; Sahni, Vanita; Hayden, Althea S; Gustafson, Reka; Henry, Bonnie; Tang, Patrick

2015-11-15

We used whole-genome sequencing to investigate a dual-genotype outbreak of measles occurring after the XXI Olympic Winter Games in Vancouver, Canada. By sequencing 27 complete genomes from H1 and D8 genotype measles viruses isolated from outbreak cases, we estimated the virus mutation rate, determined that person-to-person transmission is typically associated with 0 mutations between isolates, and established that a single introduction of H1 virus led to the expansion of the outbreak beyond Vancouver. This is the largest measles genomics project to date, revealing novel aspects of measles virus genetics and providing new insights into transmission of this reemerging viral pathogen. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Live attenuated measles vaccine expressing HIV-1 Gag virus like particles covered with gp160DELTAV1V2 is strongly immunogenic

DOE Office of Scientific and Technical Information (OSTI.GOV)

Guerbois, Mathilde; Moris, Arnaud; Combredet, Chantal

Although a live attenuated HIV vaccine is not currently considered for safety reasons, a strategy inducing both T cells and neutralizing antibodies to native assembled HIV-1 particles expressed by a replicating virus might mimic the advantageous characteristics of live attenuated vaccine. To this aim, we generated a live attenuated recombinant measles vaccine expressing HIV-1 Gag virus-like particles (VLPs) covered with gp160DELTAV1V2 Env protein. The measles-HIV virus replicated efficiently in cell culture and induced the intense budding of HIV particles covered with Env. In mice sensitive to MV infection, this recombinant vaccine stimulated high levels of cellular and humoral immunity tomore » both MV and HIV with neutralizing activity. The measles-HIV virus infected human professional antigen-presenting cells, such as dendritic cells and B cells, and induced efficient presentation of HIV-1 epitopes and subsequent activation of human HIV-1 Gag-specific T cell clones. This candidate vaccine will be next tested in non-human primates. As a pediatric vaccine, it might protect children and adolescents simultaneously from measles and HIV.« less

Measles Virus Hemagglutinin Protein Epitopes: The Basis of Antigenic Stability.

PubMed

Tahara, Maino; Bürckert, Jean-Philippe; Kanou, Kazuhiko; Maenaka, Katsumi; Muller, Claude P; Takeda, Makoto

2016-08-02

Globally eliminating measles using available vaccines is biologically feasible because the measles virus (MV) hemagglutinin (H) protein is antigenically stable. The H protein is responsible for receptor binding, and is the main target of neutralizing antibodies. The immunodominant epitope, known as the hemagglutinating and noose epitope, is located near the receptor-binding site (RBS). The RBS also contains an immunodominant epitope. Loss of receptor binding correlates with an escape from the neutralization by antibodies that target the epitope at RBS. Another neutralizing epitope is located near RBS and is shielded by an N-linked sugar in certain genotype strains. However, human sera from vaccinees and measles patients neutralized all MV strains with similar efficiencies, regardless of the N-linked sugar modification or mutations at these epitopes. Two other major epitopes exist at a distance from RBS. One has an unstructured flexible domain with a linear neutralizing epitope. When MV-H forms a tetramer (dimer of dimers), these epitopes may form the dimer-dimer interface, and one of the two epitopes may also interact with the F protein. The neutralization mechanisms of antibodies that recognize these epitopes may involve inhibiting the H-F interaction or blocking the fusion cascade after MV-H binds to its receptors.

Measles Virus Hemagglutinin Protein Epitopes: The Basis of Antigenic Stability

PubMed Central

Tahara, Maino; Bürckert, Jean-Philippe; Kanou, Kazuhiko; Maenaka, Katsumi; Muller, Claude P.; Takeda, Makoto

2016-01-01

Globally eliminating measles using available vaccines is biologically feasible because the measles virus (MV) hemagglutinin (H) protein is antigenically stable. The H protein is responsible for receptor binding, and is the main target of neutralizing antibodies. The immunodominant epitope, known as the hemagglutinating and noose epitope, is located near the receptor-binding site (RBS). The RBS also contains an immunodominant epitope. Loss of receptor binding correlates with an escape from the neutralization by antibodies that target the epitope at RBS. Another neutralizing epitope is located near RBS and is shielded by an N-linked sugar in certain genotype strains. However, human sera from vaccinees and measles patients neutralized all MV strains with similar efficiencies, regardless of the N-linked sugar modification or mutations at these epitopes. Two other major epitopes exist at a distance from RBS. One has an unstructured flexible domain with a linear neutralizing epitope. When MV-H forms a tetramer (dimer of dimers), these epitopes may form the dimer-dimer interface, and one of the two epitopes may also interact with the F protein. The neutralization mechanisms of antibodies that recognize these epitopes may involve inhibiting the H-F interaction or blocking the fusion cascade after MV-H binds to its receptors. PMID:27490564

Seroprevalence survey of varicella, measles, rubella, and hepatitis A and B viruses in a multinational healthcare workforce in Saudi Arabia.

PubMed

Almuneef, M A; Memish, Z A; Balkhy, H H; Otaibi, B; Helmi, M

2006-11-01

To determine the prevalence of the vaccine-preventable diseases caused by varicella, measles, rubella, and hepatitis A and B viruses in a multinational healthcare workforce. Prospective cohort study. A 750-bed tertiary care center located in Riyadh, Saudi Arabia. In compliance with hospital policy, newly recruited healthcare workers (HCWs) were enrolled in the study from September 2001 to March 2005. Serum samples were collected from all HCWs during the initial hiring process and tested for IgG antibodies against each of the 5 viral agents. Nonimmune HCWs were subsequently vaccinated at the earliest opportunity. A total of 4,006 newly hired (international and local) employees were included in the study. All underwent serologic testing for IgG antibodies against varicella, measles, rubella, hepatitis A, and hepatitis B viruses. Of the total, 63% were female and 37% were male. Middle Eastern employees comprised 47% of the total, followed by employees from the Far East (35%), the West (10%), and Africa (8%). Forty-two percent were nurses, 27% were in administration, 18% were medical technicians, and 13% were physicians. Among the 4,006 newly hired HCWs, 14% had negative IgG antibody test results for varicella virus, 13% for measles virus, 10% for rubella virus, 33% for hepatitis A virus, and 43% for hepatitis B virus. More women than men were susceptible to hepatitis A (40% vs. 24%; P<.001), whereas more men were susceptible to hepatitis B (55% vs. 35%; P<.001). Varicella susceptibility was more common among HCWs from the Far East (19%), whereas susceptibility to measles, rubella, hepatitis A, and hepatitis B was highest among HCWs from the Middle East. Both relative youth and male sex were associated with lack of antibodies against hepatitis B virus and rubella virus. In contrast, female sex and younger age were associated with lack of antibodies against hepatitis A virus (P<.001). Seroprevalence surveys of vaccine-preventable diseases among HCWs, although labor

Nectin-4 Interactions Govern Measles Virus Virulence in a New Model of Pathogenesis, the Squirrel Monkey (Saimiri sciureus).

PubMed

Delpeut, Sébastien; Sawatsky, Bevan; Wong, Xiao-Xiang; Frenzke, Marie; Cattaneo, Roberto; von Messling, Veronika

2017-06-01

In addition to humans, only certain nonhuman primates are naturally susceptible to measles virus (MeV) infection. Disease severity is species dependent, ranging from mild to moderate for macaques to severe and even lethal for certain New World monkey species. To investigate if squirrel monkeys ( Saimiri sciureus ), which are reported to develop a course of disease similar to humans, may be better suited than macaques for the identification of virulence determinants or the evaluation of therapeutics, we infected them with a green fluorescent protein-expressing MeV. Compared to cynomolgus macaques ( Macaca fascicularis ) infected with the same virus, the squirrel monkeys developed more-severe immunosuppression, higher viral load, and a broader range of clinical signs typical for measles. In contrast, infection with an MeV unable to interact with the epithelial receptor nectin-4, while causing immunosuppression, resulted in only a mild and transient rash and a short-lived elevation of the body temperature. Similar titers of the wild-type and nectin-4-blind MeV were detected in peripheral blood mononuclear cells and lymph node homogenates, but only the wild-type virus was found in tracheal lavage fluids and urine. Thus, our study demonstrates the importance of MeV interactions with nectin-4 for clinical disease in the new and better-performing S. sciureus model of measles pathogenesis. IMPORTANCE The characterization of mechanisms underlying measles virus clinical disease has been hampered by the lack of an animal model that reproduces the course of disease seen in human patients. Here, we report that infection of squirrel monkeys ( Saimiri sciureus ) fulfills these requirements. Comparative infection with wild-type and epithelial cell receptor-blind viruses demonstrated the importance of epithelial cell infection for clinical disease, highlighting the spread to epithelia as an attractive target for therapeutic strategies. Copyright © 2017 American Society for

Molecular detection and genetic characterization of circulating measles virus in northern Italy.

PubMed

Piccirilli, Giulia; Chiereghin, Angela; Pascucci, Maria Grazia; Frasca, Gabriella; Zuntini, Roberta; Ferrari, Simona; Gabrielli, Liliana; Landini, Maria Paola; Lazzarotto, Tiziana

2016-08-01

Laboratory diagnosis of measles virus (MV) infection and genetic characterization of circulating MV play an essential role in measles surveillance, allowing proper interventions to interrupt endemic transmission. We describe results obtained using serological and molecular methods to confirm MV infection among suspected cases reported in a large region in the north of Italy during 2010-2014 and the genotyping of the MV strains detected. Three hundred seventy-two samples (361 urine and 11 oral fluids) were tested for MV-RNA detection. In 281 cases, the serological results for MV-IgM detection were also available. A total of 276 cases were classified as confirmed measles and MV-RNA detection resulted positive for 239/276 cases. Nucleotide sequence analysis revealed sporadic cases of genotypes D9 and different circulations of endemic MV strains (D8, D4 and B3). This data suggests that there is still an unvaccinated part of the population maintaining the endemic circulation of MV in Italy. Copyright © 2016 Elsevier B.V. All rights reserved.

The Immune Response in Measles: Virus Control, Clearance and Protective Immunity.

PubMed

Griffin, Diane E

2016-10-12

Measles is an acute systemic viral infection with immune system interactions that play essential roles in multiple stages of infection and disease. Measles virus (MeV) infection does not induce type 1 interferons, but leads to production of cytokines and chemokines associated with nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) signaling and activation of the NACHT, LRR and PYD domains-containing protein (NLRP3) inflammasome. This restricted response allows extensive virus replication and spread during a clinically silent latent period of 10-14 days. The first appearance of the disease is a 2-3 day prodrome of fever, runny nose, cough, and conjunctivitis that is followed by a characteristic maculopapular rash that spreads from the face and trunk to the extremities. The rash is a manifestation of the MeV-specific type 1 CD4⁺ and CD8⁺ T cell adaptive immune response with lymphocyte infiltration into tissue sites of MeV replication and coincides with clearance of infectious virus. However, clearance of viral RNA from blood and tissues occurs over weeks to months after resolution of the rash and is associated with a period of immunosuppression. However, during viral RNA clearance, MeV-specific antibody also matures in type and avidity and T cell functions evolve from type 1 to type 2 and 17 responses that promote B cell development. Recovery is associated with sustained levels of neutralizing antibody and life-long protective immunity.

Measles vaccination before the measles-mumps-rubella vaccine.

PubMed

Hendriks, Jan; Blume, Stuart

2013-08-01

At the beginning of the 1960s, it was clear that a vaccine against measles would soon be available. Although measles was (and remains) a killer disease in the developing world, in the United States and Western Europe this was no longer so. Many parents and many medical practitioners considered measles an inevitable stage of a child's development. Debating the desirability of measles immunization, public health experts reasoned differently. In the United States, introduction of the vaccine fit well with Kennedy's and Johnson's administrations' political commitments. European policymakers proceeded cautiously, concerned about the acceptability of existing vaccination programs. In Sweden and the Netherlands, recent experience in controlling polio led researchers to prefer an inactivated virus vaccine. Although in the early 1970s attempts to develop a sufficiently potent inactivated vaccine were abandoned, we have argued that the debates and initiatives of the time during the vaccine's early history merit reflection in today's era of standardization and global markets.

New Measles Genotype, Uganda

PubMed Central

Muwonge, Apollo; Nanyunja, Miriam; Bwogi, Josephine; Lowe, Luis; Liffick, Stephanie L.; Bellini, William J.; Sylvester, Sempala

2005-01-01

We report the first genetic characterization of wildtype measles viruses from Uganda. Thirty-six virus isolates from outbreaks in 6 districts were analyzed from 2000 to 2002. Analyses of sequences of the nucleoprotein (N) and hemagglutinin (H) genes showed that the Ugandan isolates were all closely related, and phylogenetic analysis indicated that these viruses were members of a unique group within clade D. Sequences of the Ugandan viruses were not closely related to any of the World Health Organization reference sequences representing the 22 currently recognized genotypes. The minimum nucleotide divergence between the Ugandan viruses and the most closely related reference strain, genotype D2, was 3.1% for the N gene and 2.6% for the H gene. Therefore, Ugandan viruses should be considered a new, proposed genotype (d10). This new sequence information will expand the utility of molecular epidemiologic techniques for describing measles transmission patterns in eastern Africa. PMID:16318690

Genetic Characterization of the Hemagglutinin Genes of Wild-Type Measles Virus Circulating in China, 1993–2009

PubMed Central

Zhu, Zhen; Liu, Chunyu; Mao, Naiying; Ji, Yixin; Wang, Huiling; Jiang, Xiaohong; Li, Chongshan; Tang, Wei; Feng, Daxing; Wang, Changyin; Zheng, Lei; Lei, Yue; Ling, Hua; Zhao, Chunfang; Ma, Yan; He, Jilan; Wang, Yan; Li, Ping; Guan, Ronghui; Zhou, Shujie; Zhou, Jianhui; Wang, Shuang; Zhang, Hong; Zheng, Huanying; Liu, Leng; Ma, Hemuti; Guan, Jing; Lu, Peishan; Feng, Yan; Zhang, Yanjun; Zhou, Shunde; Xiong, Ying; Ba, Zhuoma; Chen, Hui; Yang, Xiuhui; Bo, Fang; Ma, Yujie; Liang, Yong; Lei, Yake; Gu, Suyi; Liu, Wei; Chen, Meng; Featherstone, David; Jee, Youngmee; Bellini, William J.; Rota, Paul A.; Xu, Wenbo

2013-01-01

Background China experienced several large measles outbreaks in the past two decades, and a series of enhanced control measures were implemented to achieve the goal of measles elimination. Molecular epidemiologic surveillance of wild-type measles viruses (MeV) provides valuable information about the viral transmission patterns. Since 1993, virologic surveillnace has confirmed that a single endemic genotype H1 viruses have been predominantly circulating in China. A component of molecular surveillance is to monitor the genetic characteristics of the hemagglutinin (H) gene of MeV, the major target for virus neutralizing antibodies. Principal Findings Analysis of the sequences of the complete H gene from 56 representative wild-type MeV strains circulating in China during 1993–2009 showed that the H gene sequences were clustered into 2 groups, cluster 1 and cluster 2. Cluster1 strains were the most frequently detected cluster and had a widespread distribution in China after 2000. The predicted amino acid sequences of the H protein were relatively conserved at most of the functionally significant amino acid positions. However, most of the genotype H1 cluster1 viruses had an amino acid substitution (Ser240Asn), which removed a predicted N-linked glycosylation site. In addition, the substitution of Pro397Leu in the hemagglutinin noose epitope (HNE) was identified in 23 of 56 strains. The evolutionary rate of the H gene of the genotype H1 viruses was estimated to be approximately 0.76×10−3 substitutions per site per year, and the ratio of dN to dS (dN/dS) was <1 indicating the absence of selective pressure. Conclusions Although H genes of the genotype H1 strains were conserved and not subjected to selective pressure, several amino acid substitutions were observed in functionally important positions. Therefore the antigenic and genetic properties of H genes of wild-type MeVs should be monitored as part of routine molecular surveillance for measles in China. PMID

DARPin-targeting of Measles Virus: Unique Bispecificity, Effective Oncolysis, and Enhanced Safety

PubMed Central

Friedrich, Katrin; Hanauer, Jan RH; Prüfer, Steffen; Münch, Robert C; Völker, Iris; Filippis, Christodoulos; Jost, Christian; Hanschmann, Kay-Martin; Cattaneo, Roberto; Peng, Kah-Whye; Plückthun, Andreas; Buchholz, Christian J; Cichutek, Klaus; Mühlebach, Michael D

2013-01-01

Oncolytic virotherapy is an emerging treatment modality that uses replication-competent viruses to destroy cancers. Many naturally occurring viruses have a preferential, although nonexclusive, tropism for tumors and tumor cells. In addition, specific targeting of cancer cells can be achieved at the virus entry level. We optimized retargeting of cell entry by elongating the measles virus attachment protein with designed ankyrin repeat proteins (DARPins), while simultaneously ablating entry through the natural receptors. DARPin-targeted viruses were strongly attenuated in off-target tissue, thereby enhancing safety, but completely eliminated tumor xenografts. Taking advantage of the unique properties of DARPins of being fused without generating folding problems, we generated a virus simultaneous targeting two different tumor markers. The bispecific virus retained the original oncolytic efficacy, while providing proof of concept for a strategy to counteract issues of resistance development. Thus, DARPin-targeting opens new prospects for the development of personalized, targeted therapeutics. PMID:23380817

Improving molecular tools for global surveillance of measles virus⋆

PubMed Central

Bankamp, Bettina; Byrd-Leotis, Lauren A.; Lopareva, Elena N.; Woo, Gibson K.S.; Liu, Chunyu; Jee, Youngmee; Ahmed, Hinda; Lim, Wilina W.; Ramamurty, Nalini; Mulders, Mick N.; Featherstone, David; Bellini, William J.; Rota, Paul A.

2017-01-01

Background The genetic characterization of wild-type measles viruses plays an important role in the description of viral transmission pathways and the verification of measles elimination. The 450 nucleotides that encode the carboxyl-terminus of the nucleoprotein (N-450) are routinely sequenced for genotype analysis. Objectives The objectives of this study were to develop improved primers and controls for RT-PCR reactions used for genotyping of measles samples and to develop a method to provide a convenient, safe, and inexpensive means to distribute measles RNA for RT-PCR assays and practice panels. Study design A newly designed, genetically defined synthetic RNA and RNA isolated from cells infected with currently circulating genotypes were used to compare the sensitivity of primer pairs in RT-PCR and nested PCR. FTA® cards loaded with lysates of measles infected cells were tested for their ability to preserve viral RNA and destroy virus infectivity. Results A new primer pair, MeV216/MeV214, was able to amplify N-450 from viruses representing 10 currently circulating genotypes and a genotype A vaccine strain and demonstrated 100-fold increased sensitivity compared to the previously used primer set. A nested PCR assay further increased the sensitivity of detection from patient samples. A synthetic positive control RNA was developed that produced PCR products that are distinguishable by size from PCR products amplified from clinical samples. FTA® cards completely inactivated measles virus and stabilized RNA for at least six months. Conclusions These improved molecular tools will advance molecular characterization of circulating measles viruses globally and provide enhanced quality control measures. PMID:23806666

Measles re-emergence in Northern Italy: Pathways of measles virus genotype D8, 2013-2014.

PubMed

Amendola, Antonella; Bianchi, Silvia; Lai, Alessia; Canuti, Marta; Piralla, Antonio; Baggieri, Melissa; Ranghiero, Alberto; Piatti, Alessandra; Tanzi, Elisabetta; Zehender, Gianguglielmo; Magurano, Fabio; Baldanti, Fausto

2017-03-01

Molecular surveillance and advanced phylogenetic methods are important tools to track the pathways of Measles virus (MV) genotypes, provide evidence for the interruption of endemic transmission and verify the elimination of the disease. The aims of this study were to describe the genetic profile of MV genotype D8 (D8-MV) strains circulating in Northern Italy (Lombardy Region) during the 2013-2014 period and to analyze the transmission chains and estimate the introduction time points using a phylogenetic approach. Forty-four strains of D8-MV identified from 12 outbreaks and 28 cases reported as sporadic were analyzed. Molecular analysis was performed by sequencing the highly variable 450nt region of the N gene of MV genome (N-450), as recommended by the WHO. Phylogenetic analyses and tree time-scaled reconstruction were performed with BEAST software. We could trace back the transmission pathways that resulted in three chains of transmission, two introductions with limited spread (two familiar outbreaks), and two single introductions (true sporadic cases). The D8-Taunton transmission chain, which was involved in 7 outbreaks and 13 sporadic cases, was endemic during the studied period. Furthermore, two novel local variants emerged independently in March 2014 and caused two transmission chains linked to at least 3 outbreaks. Overall, viral diversity was high and strains belonging to 5 different variants were identified. The results of this study clearly demonstrate that multiple lineages of D8-MV co-circulated in Northern Italy. Measles can be considered a re-emerging disease in Italy and additional efforts are necessary to achieve measles elimination goal. Copyright © 2016 Elsevier B.V. All rights reserved.

Proteome profiling of virus-host interactions of wild type and attenuated measles virus strains.

PubMed

Billing, Anja M; Kessler, Julia R; Revets, Dominique; Sausy, Aurélie; Schmitz, Stephanie; Barra, Claire; Muller, Claude P

2014-08-28

Quantitative gel-based proteomics (2D DIGE coupled to MALDI-TOF/TOF MS) has been used to investigate the effects of different measles virus (MV) strains on the host cell proteome. A549/hSLAM cells were infected either with wild type MV strains, an attenuated vaccine or a multiple passaged Vero cell adapted strain. By including interferon beta treatment as a control it was possible to distinguish between the classical antiviral response and changes induced specifically by the different strains. Of 38 differentially expressed proteins in total (p-value ≤0.05, fold change ≥2), 18 proteins were uniquely modulated following MV infection with up to 9 proteins specific per individual strain. Interestingly, wt strains displayed distinct protein patterns particularly during the late phase of infection. Proteins were grouped into cytoskeleton, metabolism, transcription/translation, immune response and mitochondrial proteins. Bioinformatics analysis revealed mostly changes in proteins regulating cell death and apoptosis. Surprisingly, wt strains affected the cytokeratin system much stronger than the vaccine strain. To our knowledge, this is the first study on the MV-host proteome addressing interstrain differences. In the present study we investigated the host cell proteome upon measles virus (MV) infection. The novelty about this study is the side-by side comparison of different strains from the same virus, which has not been done at the proteome level for any other virus including MV. We used different virus strains including a vaccine strain, wild type isolates derived from MV-infected patients as well as a Vero cell adapted strain, which serves as an intermediate between vaccine and wild type strain. We observed differences between vaccine and wild type strains as well as common features between different wild type strains. Perhaps one of the most surprising findings was that differences did not only occur between wild type and vaccine or Vero cell adapted strains but

Clinical Trials with Oncolytic Measles Virus: Current Status and Future Prospects.

PubMed

Msaouel, Pavlos; Opyrchal, Mateusz; Dispenzieri, Angela; Peng, Kah Whye; Federspiel, Mark J; Russell, Stephen J; Galanis, Evanthia

2018-01-01

Attenuated Edmonston lineage measles virus (MV-Edm) vaccine strains can preferentially infect and lyse a wide variety of cancer cells. Oncolytic MV-Edm derivatives are genetically engineered to express the human carcinoembryonic antigen (MV-CEA virus) or the human sodium iodide symporter (MV-NIS virus) and are currently being tested in clinical trials against ovarian cancer, glioblastoma multiforme, multiple myeloma, mesothelioma, head and neck cancer, breast cancer and malignant peripheral nerve sheath tumors. This review describes the basic and preclinical data that facilitated the clinical translation of MV-Edm strains, and summarizes the clinical results of this oncolytic platform to date. Furthermore, we discuss the latest clinically relevant MV-Edm vector developments and creative strategies for future translational steps. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Seroconversion rates to combined measles-mumps-rubella-varicella vaccine of children with upper respiratory tract infection.

PubMed

Dennehy, P H; Saracen, C L; Peter, G

1994-10-01

To determine if upper respiratory tract infection (URI) affects the seroconversion rate or quantitative response to each component of a combined measles-mumps-rubella-varicella vaccine. One hundred forty-nine children between 15 and 18 months of age were prospectively divided into two groups according to the presence of URI or recent history of URI symptoms within the 4 weeks before vaccination. Once stratified, 74 children in the healthy group and 75 children in the URI group were randomly assigned to receive one of three lots of measles-mumps-rubella varicella vaccine by subcutaneous injection into the deltoid area. Serum was obtained from each child just before vaccination and 4 to 6 weeks later for measuring antibody levels against each virus. Prevaccination antibody levels against each virus in the URI and healthy groups did not differ. Nine children had pre-existing antibodies to varicella and six to mumps; no child had positive serologies for measles or rubella before vaccination. Children with pre-existing antibody were excluded from analysis of seroconversion for that virus. Seroconversion to measles, mumps, and rubella occurred in 100% of children in both groups. Mean antibody levels did not differ between the healthy and URI groups for measles (111 vs 122), mumps (97 vs 108), or rubella (96 vs 102). Three (4%) of 70 children with URIs in whom varicella serologies were available failed to seroconvert to varicella vaccine although none of the 69 healthy children had vaccine failure (P = .24). The mean varicella antibody level was 11.3 +/- 1.4 in the healthy children, which did not differ significantly from the level of 9.5 +/- 0.9 in the URI group. Seroconversion to measles, mumps, rubella, and varicella was not significantly affected by the presence of a concurrent or recent URI in 15- to 18-month-old children.

Ten-Year Surveillance of Measles Virus from 2007-2016 in Osaka City, Japan.

PubMed

Kaida, Atsushi; Iritani, Nobuhiro; Kanbayashi, Daiki; Yamamoto, Seiji P; Hirai, Yuki; Hakui, Noritaka; Fujimori, Ryoko; Mori, Hiromi; Hirokawa, Hidetetsu; Ogasawara, Jun; Kubo, Hideyuki

2018-03-22

Measles is a highly contagious infection caused by the measles virus (MV). This study performed long-term surveillance in order to survey the prevalence of MV. A total of 417 patients diagnosed with or suspected of having measles were tested for MV between January 2007 and December 2016 in Osaka City, Japan. Reverse transcription-polymerase chain reaction-based testing of clinical specimens showed that 54 patients (12.9%) were MV-positive. An MV epidemic occurred in 2007, in which all detected MV strains were genotype D5, an epidemic strain in Japan at that time. The detected wild-type MV strains in sporadic or outbreak-associated cases since 2011 included genotypes D4, D8, B3, and H1. Three vaccine strains (all genotype A) were also detected. Children ＜10 years of age accounted for 90.0% of the MV-positive patients in 2007. In contrast, adults (≥ 20 years of age) accounted for the majority of MV-positive cases since 2011, as follows: 100%, 50%, 71.4%, 100%, and 87.5% of cases in 2011, 2013, 2014, 2015, and 2016, respectively. The recent high rate of two-dose MV vaccination coverage among children in Japan may have contributed to the reduced risk of MV infection and onset of measles in young persons.

Virucidal activity of a scorpion venom peptide variant mucroporin-M1 against measles, SARS-CoV and influenza H5N1 viruses.

PubMed

Li, Qiaoli; Zhao, Zhenhuan; Zhou, Dihan; Chen, Yaoqing; Hong, Wei; Cao, Luyang; Yang, Jingyi; Zhang, Yan; Shi, Wei; Cao, Zhijian; Wu, Yingliang; Yan, Huimin; Li, Wenxin

2011-07-01

Outbreaks of SARS-CoV, influenza A (H5N1, H1N1) and measles viruses in recent years have raised serious concerns about the measures available to control emerging and re-emerging infectious viral diseases. Effective antiviral agents are lacking that specifically target RNA viruses such as measles, SARS-CoV and influenza H5N1 viruses, and available vaccinations have demonstrated variable efficacy. Therefore, the development of novel antiviral agents is needed to close the vaccination gap and silence outbreaks. We previously identified mucroporin, a cationic host defense peptide from scorpion venom, which can effectively inhibit standard bacteria. The optimized mucroporin-M1 can inhibit gram-positive bacteria at low concentrations and antibiotic-resistant pathogens. In this investigation, we further tested mucroporin and the optimized mucroporin-M1 for their antiviral activity. Surprisingly, we found that the antiviral activities of mucroporin-M1 against measles, SARS-CoV and influenza H5N1 viruses were notably increased with an EC₅₀ of 7.15 μg/ml (3.52 μM) and a CC₅₀ of 70.46 μg/ml (34.70 μM) against measles virus, an EC₅₀ of 14.46 μg/ml (7.12 μM) against SARS-CoV and an EC₅₀ of 2.10 μg/ml (1.03 μM) against H5N1, while the original peptide mucroporin showed no antiviral activity against any of these three viruses. The inhibition model could be via a direct interaction with the virus envelope, thereby decreasing the infectivity of virus. This report provides evidence that host defense peptides from scorpion venom can be modified for antiviral activity by rational design and represents a practical approach for developing broad-spectrum antiviral agents, especially against RNA viruses. Copyright © 2011 Elsevier Inc. All rights reserved.

[Effectiveness of a combined live mumps-measles vaccine].

PubMed

Unanov, S S; Korzh, Iu N; Dorofeev, V M; Iuminova, N V; Myshliaeva, L A

1987-01-01

The reactogenic and areactogenic properties of a live combined mumps-measles vaccine (MMV) prepared in primary cultures of Japanese quail embryo cells from attenuated strains of mumps (L-3) and measles (L-16) viruses were under study. The observations involved 648 infants varying in ages from 1 to 3 years, seronegative to measles and mumps viruses, without the history of the disease and vaccinations against these infections or contraindications to vaccinations. The infants were vaccinated with 5 batches of MMV with different portions of the mumps and measles components. The vaccinees and controls (placebo injections) were observed for 30 days postvaccination. The live MMV was shown to be a safe, well tolerated preparation with low reactogenicity and a high antigenic activity.

Measles virus C protein suppresses gamma-activated factor formation and virus-induced cell growth arrest

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yokota, Shin-ichi; Okabayashi, Tamaki; Fujii, Nobuhiro, E-mail: fujii@sapmed.ac.j

2011-05-25

Measles virus (MeV) produces two accessory proteins, V and C, from the P gene. These accessory proteins have been reported to contribute to efficient virus proliferation through the modulation of host cell events. Our previous paper described that Vero cell-adapted strains of MeV led host cells to growth arrest through the upregulation of interferon regulatory factor 1 (IRF-1), and wild strains did not. In the present study, we found that C protein expression levels varied among MeV strains in infected SiHa cells. C protein levels were inversely correlated with IRF-1 expression levels and with cell growth arrest. Forced expression ofmore » C protein released cells from growth arrest. C-deficient recombinant virus efficiently upregulated IRF-1 and caused growth arrest more efficiently than the wild-type virus. C protein preferentially bound to phosphorylated STAT1 and suppressed STAT1 dimer formation. We conclude that MeV C protein suppresses IFN-{gamma} signaling pathway via inhibition of phosphorylated STAT1 dimerization.« less

Outbreak of measles in medical students and determination of immune status to measles-mumps-rubella viruses.

PubMed

Yalçin, Songül S; Kanra, Güler; Pehlivan, Tamer

2006-01-01

We conducted an investigation after a measles outbreak in medical students to determine the immunity of the medical students, the correlation between history and seropositivity, and measles-mumps-rubella vaccine effectiveness. After a preliminary study done during measles outbreak, a cross-sectional study was planned. Serum samples from 322 medical students were tested by enzyme-linked immunosorbent assay, vaccinated volunteers, then re-tested vaccinees. Histories of measles, mumps and rubella were taken. Of 322 students, seven students (2.2%) were seronegative to measles, 13 (4.0%) to mumps, and 13 (4.0%) to rubella. Historical information revealed 30.4% of sensitivity in measles and 34.3% in mumps, whereas 5.2% in rubella. Among those seronegative on admission and vaccinated, seroconversion rates were 100% (5/5), 90.9% (10/11), 100% (8/8) in measles, mumps and rubella vaccine, respectively. Of 265 vaccinated students parotitis was detected in one female student, arthralgia was observed in three students (1.1%) and myalgia in two (0.7%), and 240 students reported no side effects. We detected the unreliable historical screening and high seroprevalence of measles, mumps and rubella in prevaccine era for mumps and rubella and, safety of MMR vaccination in medical students in Turkey.

Modified measles versus rubella versus atypical measles: One and same thing

PubMed Central

Gupta, Surender Nikhil; Gupta, Naveen; Gupta, Shivani

2015-01-01

Introduction: In outbreak settings, more than one virus may be infecting the given population. In twin or triple outbreak of measles, German measles (rubella), and varicella in highly immunized hilly areas, maximal number of the case patients in all the hilly villages belonged to the older age group. It suggested an obvious shift to the higher age group, warranting second dose opportunity in such case scenario. The clinical presentations of viral diseases are too similar to differentiate. The aim is to clearly categorize the case patients of modified measles, rubella, and atypical measles in outbreak settings. Results: Four outbreaks are listed. In the first one, sixty case patients were identified from 1026 people in 5 villages. Of these, 41 were diagnosed by clinically, 8 were laboratory confirmed as measles and 11 were epidemiologically linked German measles case patients. Seventy percent of the cases were vaccinated for measles. In second case, we identified 29/35 measles and 6/35 were confirmed as epidemiologically linked unvaccinated chickenpox case patients. In third one, we identified 116 cases in eight villages (112/116 clinically and 04/116 laboratory confirmed). Majority of cases were immunized against measles, but only minor cases for rubella. In fourth case, we identified 505 case patients from mixed outbreaks of varicella, measles and rubella (30/505 clinically, 467/505 epidemiologically linked and 8/505 laboratory confirmed case patients from a study population of 3280). In all the four outbreaks, prima facie, the clinical presentations of both rubella and modified measles were difficult to differentiate. Discussion: On the basis of outbreak investigation and analytical inference, it has been observed that the symtomatology of modified measles and laboratory confirmed rubella case patients/epidemiologically linked cases are so similar placed that many a time, it becomes much difficult to line list the cases in one section of modified measles or

Modified measles versus rubella versus atypical measles: One and same thing.

PubMed

Gupta, Surender Nikhil; Gupta, Naveen; Gupta, Shivani

2015-01-01

In outbreak settings, more than one virus may be infecting the given population. In twin or triple outbreak of measles, German measles (rubella), and varicella in highly immunized hilly areas, maximal number of the case patients in all the hilly villages belonged to the older age group. It suggested an obvious shift to the higher age group, warranting second dose opportunity in such case scenario. The clinical presentations of viral diseases are too similar to differentiate. The aim is to clearly categorize the case patients of modified measles, rubella, and atypical measles in outbreak settings. Four outbreaks are listed. In the first one, sixty case patients were identified from 1026 people in 5 villages. Of these, 41 were diagnosed by clinically, 8 were laboratory confirmed as measles and 11 were epidemiologically linked German measles case patients. Seventy percent of the cases were vaccinated for measles. In second case, we identified 29/35 measles and 6/35 were confirmed as epidemiologically linked unvaccinated chickenpox case patients. In third one, we identified 116 cases in eight villages (112/116 clinically and 04/116 laboratory confirmed). Majority of cases were immunized against measles, but only minor cases for rubella. In fourth case, we identified 505 case patients from mixed outbreaks of varicella, measles and rubella (30/505 clinically, 467/505 epidemiologically linked and 8/505 laboratory confirmed case patients from a study population of 3280). In all the four outbreaks, prima facie, the clinical presentations of both rubella and modified measles were difficult to differentiate. On the basis of outbreak investigation and analytical inference, it has been observed that the symtomatology of modified measles and laboratory confirmed rubella case patients/epidemiologically linked cases are so similar placed that many a time, it becomes much difficult to line list the cases in one section of modified measles or rubella or atypical cases. Similarities

Measles Vaccine.

PubMed

Griffin, Diane E

2018-03-01

Measles remains an important cause of child morbidity and mortality worldwide despite the availability of a safe and efficacious vaccine. The current measles virus (MeV) vaccine was developed empirically by attenuation of wild-type (WT) MeV by in vitro passage in human and chicken cells and licensed in 1963. Additional passages led to further attenuation and the successful vaccine strains in widespread use today. Attenuation is associated with decreased replication in lymphoid tissue, but the molecular basis for this restriction has not been identified. The immune response is age dependent, inhibited by maternal antibody (Ab) and involves induction of both Ab and T cell responses that resemble the responses to WT MeV infection, but are lower in magnitude. Protective immunity is correlated with levels of neutralizing Ab, but the actual immunologic determinants of protection are not known. Because measles is highly transmissible, control requires high levels of population immunity. Delivery of the two doses of vaccine needed to achieve >90% immunity is accomplished by routine immunization of infants at 9-15 months of age followed by a second dose delivered before school entry or by periodic mass vaccination campaigns. Because delivery by injection creates hurdles to sustained high coverage, there are efforts to deliver MeV vaccine by inhalation. In addition, the safety record for the vaccine combined with advances in reverse genetics for negative strand viruses has expanded proposed uses for recombinant versions of measles vaccine as vectors for immunization against other infections and as oncolytic agents for a variety of tumors.

Measles, immune suppression and vaccination: direct and indirect nonspecific vaccine benefits.

PubMed

Mina, Michael J

2017-06-01

The measles virus is among the most transmissible viruses known to infect humans. Prior to measles vaccination programs, measles infected over 95% of all children and was responsible for over 4 million deaths each year. Measles vaccination programs have been among the greatest public health achievements reducing, eliminating endemic measles in the whole of the Americas and across much of the globe. Where measles vaccines are introduced, unexpectedly large reductions in all-cause childhood mortality have been observed. These gains appear to derive in part from direct heterologous benefits of measles vaccines that enhance innate and adaptive immune responses. Additionally, by preventing measles infections, vaccination prevents measles-associated short- and long-term immunomodulating effects. Before vaccination, these invisible hallmarks of measles infections increased vulnerability to non-measles infections in nearly all children for weeks, months, or years following acute infections. By depleting measles incidence, vaccination has had important indirect benefits to reduce non-measles mortality. Delineating the relative importance of these two modes of survival benefits following measles vaccine introduction is of critical public health importance. While both support continued unwavering global commitments to measles vaccination programs until measles eradication is complete, direct heterologous benefits of measles vaccination further support continued commitment to measles vaccination programs indefinitely. We discuss what is known about direct and indirect nonspecific measles vaccine benefits, and their implications for continued measles vaccination programs. © 2017 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

Assessment of measles incidence, measles-related complications and hospitalisations during an outbreak in a southern Italian region.

PubMed

Ciofi Degli Atti, Marta Luisa; Filia, Antonietta; Massari, Marco; Pizzuti, Renato; Nicoletti, Loredana; D'Argenzio, Angelo; de Campora, Enrico; Marchi, Antonella; Lombardo, Assunta; Salmaso, Stefania

2006-02-27

A large measles epidemic occurred in 2002 in Campania, a region of southern Italy with inadequate vaccination coverage. We evaluated the burden of the outbreak in children <15 years of age using different data sources. The measles standardized incidence rate was 5,757/100,000, corresponding to 63,368 estimated cases (95% CI: 59,544--67,373). Measles virus strains were identified as belonging to the D7 genotype. The estimated complication rate was 7.6%. A total of 972 measles hospitalisations were detected, giving a hospitalisation rate of 88.3/100,000. Three deaths occurred. These results show that measles can still represent a serious health threat even in industrialized countries.

Molecular characterisation of measles virus strains among refugees from Central African Republic in Cameroon in 2014.

PubMed

Ndombo, P K; Ndze, V N; Mbarga, F D; Anderson, R; Acho, A; Ebua Chia, J; Njamnshi, A K; Rota, P A; Waku-Kouomou, D

2018-02-01

Measles is a highly infectious human viral disease caused by measles virus (MeV). An estimated 114 900 measles deaths occurred worldwide in 2014. There are currently eight clades (A-H) comprised 24 MeV genotypes. We sought to characterise MeVs among Central African Republic (CAR) refugees during the 2014 measles epidemic in Cameroon. Samples were collected from children <15 years with suspected measles infections in two refugee camps in the east region of Cameroon. Viral RNA was extracted directly from urine samples. RNA detection of MeV RNA was performed with real-time reverse transcription polymerase chain reaction (PCR) to amplify a 634 bp nucleotide fragment of the N gene. The sequence of the PCR product was obtained to determine the genotype. MeV RNA was detected in 25 out of 30 samples from suspected cases, and among the 25 positive samples, MeV sequences were obtained from 20. The MeV strains characterised were all genotype B3. The MeV strains from genotype B3 found in this outbreak were more similar to those circulating in Northern Cameroon in 2010-2011 than to MeV strains circulating in the CAR in 2011. Surveillance system should be improved to focus on refugees for early detection of and response to outbreaks.

A recombinant measles virus unable to antagonize STAT1 function cannot control inflammation and is attenuated in rhesus monkeys.

PubMed

Devaux, Patricia; Hudacek, Andrew W; Hodge, Gregory; Reyes-Del Valle, Jorge; McChesney, Michael B; Cattaneo, Roberto

2011-01-01

Measles remains a leading cause of death worldwide among children because it suppresses immune function. The measles virus (MV) P gene encodes three proteins (P, V, and C) that interfere with innate immunity, controlling STAT1, STAT2, mda5, and perhaps other key regulators of immune function. We identified here three residues in the shared domain of the P and V proteins-tyrosine 110, valine 112, and histidine 115-that function to retain STAT1 in the cytoplasm and inhibit interferon transcription. This information was used to generate a recombinant measles virus unable to antagonize STAT1 function (STAT1-blind MV) differing only in these three residues from a wild-type strain of well-defined virulence. This virus was used to assess the relevance of P and V interactions with STAT1 for virulence in primates. When a group of six rhesus monkeys (Macaca mulatta) was inoculated intranasally with STAT1-blind MV, viremia was short-lived, and the skin rash and other clinical signs observed with wild-type MV were absent. The STAT1-blind virus less efficiently controlled the inflammatory response, as measured by enhanced transcription of interleukin-6 and tumor necrosis factor alpha in peripheral blood mononuclear cells from infected hosts. Importantly, neutralizing antibody titers and MV-specific T-cell responses were equivalent in hosts infected with either virus. These findings indicate that efficient MV interactions with STAT1 are required to sustain virulence in a natural host by controlling the inflammatory response against the virus. They also suggest that selectively STAT1-blind MV may have utility as vectors for targeted oncolysis and vaccination.

Measles Cases during Ebola Outbreak, West Africa, 2013-2106.

PubMed

Colavita, Francesca; Biava, Mirella; Castilletti, Concetta; Quartu, Serena; Vairo, Francesco; Caglioti, Claudia; Agrati, Chiara; Lalle, Eleonora; Bordi, Licia; Lanini, Simone; Guanti, Michela Delli; Miccio, Rossella; Ippolito, Giuseppe; Capobianchi, Maria R; Di Caro, Antonino

2017-06-01

The recent Ebola outbreak in West Africa caused breakdowns in public health systems, which might have caused outbreaks of vaccine-preventable diseases. We tested 80 patients admitted to an Ebola treatment center in Freetown, Sierra Leone, for measles. These patients were negative for Ebola virus. Measles virus IgM was detected in 13 (16%) of the patients.

Synergizing vaccinations with therapeutics for measles eradication.

PubMed

Plemper, Richard K; Hammond, Anthea L

2014-02-01

The measles virus is a major human pathogen responsible for approximately 150,000 deaths annually. The disease is vaccine preventable and eradication of the virus is considered feasible, in principle. However, a herd immunity exceeding 95% is required to prevent sporadic viral outbreaks in a population. Declining disease prevalence, combined with public anxiety over the vaccination's safety, has led to increased vaccine refusal, especially in Europe. This has led to the resurgence of measles in some areas. This article discusses whether synergizing effective measles therapeutics with the measles vaccination could contribute to finally eradicating measles. The authors identify key elements in a desirable drug profile and review current disease management strategies and the state of experimental inhibitor candidates. The authors also evaluate the risk associated with viral escape from inhibition, and consider the potential of measles therapeutics in the management of persistent central nervous system (CNS) viral infection. Finally, the authors contemplate the possible impact of therapeutics in controlling the threat imposed by closely related zoonotic pathogens of the same genus as measles. Efficacious therapeutics used for post-exposure prophylaxis of high-risk social contacts of confirmed index cases may aid measles eradication by closing herd immunity gaps; this is due to vaccine refusal or failure in populations with overall good vaccination coverage. The envisioned primarily prophylactic application of measles therapeutics to a predominantly pediatric and/or adolescent population, dictates the drug profile. It also has to be safe and efficacious, orally available, shelf-stable at ambient temperature and amenable to cost-effective manufacturing.

A chimeric measles virus with canine distemper envelope protects ferrets from lethal distemper challenge.

PubMed

Rouxel, Ronan Nicolas; Svitek, Nicholas; von Messling, Veronika

2009-08-06

CDV infects a broad range of carnivores, and over the past decades it has caused outbreaks in a variety of wild carnivore populations. Since the currently available live-attenuated vaccine is not sufficiently safe in these highly susceptible species, we produced a chimeric virus combining the replication complex of the measles Moraten vaccine strain with the envelope of a recent CDV wild type isolate. The resulting virus did not cause disease or immunosuppression in ferrets and conferred protection from challenge with a lethal wild type strain, demonstrating its potential value for wildlife conservation efforts.

[Study on the neutralization capacity of different types of human measles virus vaccine and the epidemic strains].

PubMed

Feng, Yan; Lu, Yi-yu; Yan, Ju-ying; Jiang, Xiao-hui; Shi, Wen; Xu, Chang-ping; Li, Zhen

2007-11-01

To explore the neutralization capacities of different types of human serum to measles virus epidemic strains and vaccine strain. Neutralization antibody (NT) to Shanghai 191 and measles virus isolates in 2005 were tested using acute and convalescent serum samples from diagnosed measles patients, children serum samples collected before and after vaccination and serum samples of migrant residents, from 3 different regions. Additionally, animal immune serum referring to vaccine strain and 3 epidemic strains were prepared and used to undergo crossing neutralization test with corresponding strains mentioned-above. Antigenic ratios were calculated. GMT value of NT of after-immune serum to vaccine strains was 50.82,1.86 times higher than that to MVi/ZJ/05/7 (GMT was 27.35), whereas GMT value of convalescent serum to MVi/ZJ/05/7 (GMT was 386.95) was obviously higher than that to vaccine strain (GMT was 1:151.83),and GMT value of migrant residents' serum in 3 regions to MVi/ZJ/05/7 were 2.22-4.17 times lower than that to vaccine strain. Meanwhile,the antigenic ratios between MVi/ZJ/ 99/1, MVi/ZJ/04/1, MVi/ZJ/05/7 and vaccine strain were found to be 4.28,5.24 and 5.66 respectively. Additionally,low NT titers to vaccine strain were found in patients' acute sera and GMT value was over 1:4. There were obvious differences on neutralization antibody of different types of serum to measles vaccine strain and epidemic strains which indicating the antigenic diversity of epidemic strains had influenced the protective effectiveness of vaccine antibody to epidemic strains. It was of significance to carry on research projects on the antigenic diversity and effectiveness of measles vaccine.

Progress toward measles elimination--Western Pacific Region, 2009-2012.

PubMed

2013-06-07

In 2005, the World Health Organization (WHO) Regional Committee for the Western Pacific Region (WPR) resolved that WPR should aim to eliminate measles by 2012. The recommended measles elimination strategies in WPR include 1) achieving and maintaining high (≥95%) coverage with 2 doses of measles-containing vaccine (MCV) through routine immunization services and by implementing supplementary immunization activities (SIAs), when required; 2) conducting high-quality, case-based measles surveillance; 3) ensuring high-quality laboratory surveillance, with timely and accurate testing of specimens to confirm or discard suspected cases and detect measles virus for genotyping and molecular analysis; and 4) establishing and maintaining measles outbreak preparedness for rapid response and ensuring appropriate case management. This report updates the previous report and describes progress toward eliminating measles in WPR during 2009-2012. During this period, measles incidence reached a historic low, decreasing by 83%, from 34.0 to 5.9 cases per million population. However, to achieve measles elimination in WPR, additional efforts are needed to strengthen routine immunization services in countries and areas with <95% coverage with the routine first (MCV1) or second dose of MCV (MCV2), to introduce a MCV2 dose in the four remaining countries and areas that do not yet have a routine 2-dose MCV schedule, and to use SIAs to close immunity gaps among measles-susceptible populations in countries and areas that have ongoing measles virus transmission.

HSP90 Chaperoning in Addition to Phosphoprotein Required for Folding but Not for Supporting Enzymatic Activities of Measles and Nipah Virus L Polymerases

PubMed Central

Bloyet, Louis-Marie; Welsch, Jérémy; Enchery, François; Mathieu, Cyrille; de Breyne, Sylvain

2016-01-01

ABSTRACT Nonsegmented negative-stranded RNA viruses, or members of the order Mononegavirales, share a conserved gene order and the use of elaborate transcription and replication machinery made up of at least four molecular partners. These partners have coevolved with the acquisition of the permanent encapsidation of the entire genome by the nucleoprotein (N) and the use of this N-RNA complex as a template for the viral polymerase composed of the phosphoprotein (P) and the large enzymatic protein (L). Not only is P required for polymerase function, but it also stabilizes the L protein through an unknown underlying molecular mechanism. By using NVP-AUY922 and/or 17-dimethylaminoethylamino-17-demethoxygeldanamycin as specific inhibitors of cellular heat shock protein 90 (HSP90), we found that efficient chaperoning of L by HSP90 requires P in the measles, Nipah, and vesicular stomatitis viruses. While the production of P remains unchanged in the presence of HSP90 inhibitors, the production of soluble and functional L requires both P and HSP90 activity. Measles virus P can bind the N terminus of L in the absence of HSP90 activity. Both HSP90 and P are required for the folding of L, as evidenced by a luciferase reporter insert fused within measles virus L. HSP90 acts as a true chaperon; its activity is transient and dispensable for the activity of measles and Nipah virus polymerases of virion origin. That the cellular chaperoning of a viral polymerase into a soluble functional enzyme requires the assistance of another viral protein constitutes a new paradigm that seems to be conserved within the Mononegavirales order. IMPORTANCE Viruses are obligate intracellular parasites that require a cellular environment for their replication. Some viruses particularly depend on the cellular chaperoning apparatus. We report here that for measles virus, successful chaperoning of the viral L polymerase mediated by heat shock protein 90 (HSP90) requires the presence of the viral

Detection and genotyping of rubella virus from exanthematous patients suspected of having measles using reverse transcription-PCR.

PubMed

Yasui, Yoshihiro; Mori, Yoshio; Adachi, Hirokazu; Kobayashi, Shinichi; Yamashita, Teruo; Minagawa, Hiroko

2014-01-01

Between July 2012 and March 2013, a total of 133 clinical specimens from 47 patients suspected of having measles were collected for virological surveillance in Aichi Prefecture, Japan. Facing the rubella epidemic, the reverse transcription (RT)-PCR protocol for measles virus (MeV) was modified to simultaneously detect rubella virus (RUBV) in these clinical specimens. As a result, 30 specimens from 15 patients were positive for RUBV and 8 specimens from 3 patients were positive for MeV. The RUBV genotype analysis for the samples from 13 patients revealed 12 samples as 2B and 1 sample as 1E. The results provided additional evidence for the difficulty in the diagnosis of exanthematous diseases based on clinical manifestations alone and the necessity of virological diagnosis to maintain the accuracy of case-based surveillance. Furthermore, the results indicated that the modified RT-PCR protocol could be useful as a routine procedure to simultaneously detect MeV and RUBV in clinical specimens of patients suspected of having exanthematous disease caused by these viruses.

Decline of measles-specific immunoglobulin M antibodies after primary measles, mumps, and rubella vaccination.

PubMed

Helfand, R F; Gary, H E; Atkinson, W L; Nordin, J D; Keyserling, H L; Bellini, W J

1998-03-01

Detection of measles-specific immunoglobulin M (IgM) has become the standard diagnostic method for laboratory confirmation of measles. In outbreaks, the interpretation of an IgM-positive result can be complicated when persons with suspected measles receive a dose of measles vaccine as part of outbreak control measures. This investigation evaluated the decay of measles-specific IgM antibodies 1 to 4 months after primary vaccination with measles, mumps, and rubella vaccine (MMRII). Serum samples were obtained from 536 infants vaccinated when they were 15 months old as part of a study to assess primary and secondary measles vaccine failure. Sixty serum specimens per week were selected from specimens collected between 4 and 9 weeks after MMRII vaccination; all 176 available serum specimens collected between 10 and > or = 16 weeks were included. Specimens were tested for the presence of measles-specific IgM by an antibody-capture enzyme immunoassay. The proportion of IgM-positive specimens dropped from 73% at 4 weeks after vaccination to 52% at 5 weeks after vaccination and then declined to 7% by 8 weeks after vaccination. Less than 10% of children remained IgM positive between 9 and 11 weeks. An IgM-negative result helps rule out the diagnosis of measles in a person with suspected infection and a history of recent vaccination. The interpretation of a positive IgM result from a person with a clinically suspected case of measles and a recent history of measles vaccination (especially within 8 weeks) is problematic, and the diagnosis of measles should be based on epidemiologic linkage to a confirmed case or on detection of wild-type measles virus.

Do HIV-positive adult immigrants need to be screened for measles-mumps-rubella and varicella zoster virus immunization?

PubMed

Llenas-García, Jara; Rubio, Rafael; Hernando, Asunción; Arrazola, Pilar; Pulido, Federico

2013-08-01

A systematic screening for measles, mumps, rubella (MMR) and varicella zoster virus (VZV) in HIV-positive adult immigrants in Spain was evaluated, and factors associated with MMR and VZV vaccines' indication were studied. Every HIV-positive immigrant was tested for VZV and MMR-IgG. MMR vaccine was indicated to patients with lymphocytes CD4+ >200 cells/mm³ and a negative measles-IgG, a negative mumps-IgG and/or a negative rubella-IgG. VZV vaccine was indicated to every VZV-IgG negative patient with CD4+ >400 cells/mm³. In total, 289 patients were screened; seroprevalence was 95.2%, 92.2%, 70.3% and 89.3% for VZV, measles, mumps and rubella IgG, respectively. Having a negative VZV-IgG was statistically associated with coming from sub-Saharan Africa (prevalence ratio [PR]: 6.52; 95% CI: 1.71-24.84; p=0.006), while having secondary education was a protective factor (PR: 0.25; 95% CI: 0.07-0.97; p=0.045). Fourteen patients (4.8%) had indication of VZV vaccine; vaccination was feasible in 21.4% of them at first visit. Eighty-one patients (29.7%) had indication of MMR vaccine, most of them due to mumps-IgG negative (53.1%) or rubella-IgG negative (24.7%). Age < 30 years at first visit was the only factor statistically associated with MMR vaccine indication (PR: 1.47; 95% CI: 1.02-2.11; p=0.04). According to CD4+ cell counts, vaccination was feasible in 71.6% of patients at first visit. In conclusion, more than a third of HIV-infected immigrant patients are susceptible to at least one easily preventable infectious disease. Especial attention should be given to immigrant women of childbearing age.

Dried venous blood samples for the detection and quantification of measles IgG using a commercial enzyme immunoassay.

PubMed Central

Riddell, Michaela A.; Byrnes, Graham B.; Leydon, Jennie A.; Kelly, Heath A.

2003-01-01

OBJECTIVES: To determine whether samples of dried venous blood (DVB) were an acceptable alternative to serum for detecting measles-specific IgG in a commercial enzyme immunoassay. METHODS: Paired samples of serum and DVB were collected from 98 suspected cases of measles and 1153 schoolchildren in Victoria, Australia. All samples were tested using the Dade Behring Enzygnost Anti-Measles-Virus/IgG immunoassay. DVB samples were eluted using either the sample buffer provided with the kit or 5% dry milk powder in phosphate-buffered saline-Tween 20. FINDINGS: DVB samples eluted by sample buffer showed significantly better linear correlation to the serum samples than did DVB samples eluted in 5% dry milk in phosphate-buffered saline-Tween 20. To improve the comparability of serum and DVB samples an adjustment factor of 1.28 was applied to the optical density (OD) values of DVB. This adjustment also enabled quantification of the titre of measles IgG in mIU/ml directly from the OD value using the alpha calculation as specified by the kit protocol. For DVB samples stored for less than six months at 4 degrees C, the assay showed an overall sensitivity of 98.4% and a specificity of 97.2% compared with the results of serum testing. CONCLUSION: These results illustrate the potential for DVB samples to be widely used with the Dade Behring enzyme immunoassay system for determining the immunity of the individual and the population to the measles virus. PMID:14758429

Comparison of monoplex and duplex RT-PCR assays for the detection of measles virus.

PubMed

Binkhamis, Khalifa; Gillis, Hayley; Lafreniere, Joseph Daniel; Hiebert, Joanne; Mendoza, Lillian; Pettipas, Janice; Severini, Alberto; Hatchette, Todd F; LeBlanc, Jason J

2017-01-01

Rapid and accurate detection of measles virus is important for case diagnosis and public health management. This study compared the performance of two monoplex RT-PCR reactions targeting the H and N genes to a duplex RT-PCR targeting both genes simultaneously. The duplex simplified processing without compromising assay performance characteristic. Copyright © 2016 Elsevier B.V. All rights reserved.

Persistence of measles neutralizing antibody related to vaccine and natural infection acquired before HIV infection.

PubMed

Isa, M B; Pavan, J V; Sicilia Don, P; Grutadauria, S; Martinez, L C; Giordano, M O; Masachessi, G; Barril, P A; Nates, S V

2014-08-01

Little is known about long-lasting measles protective immunity when exposure to wild-type or vaccine measles virus precedes HIV infection. The results obtained suggest that measles immunity wanes and the lowest measles geometric mean titres (GMT) were significantly associated with measles vaccine-induced immunity in individuals that later developed HIV infection (86% prevalence, GMT 164 mIU/ml) compared to naturally induced immunity in HIV-infected adults (100% prevalence, GMT 340 mIU/ml, P = 0·0082) or non-HIV infected adults (100%, GMT 724 mIU/ml, P = 0·0001), and vaccine-induced immunity in non-HIV-infected adults (100%, GMT 347 mIU/ml, P = 0·017). The study was conducted in an area without wild-type virus circulation since 2000. The absence of virus circulating may alter the paradigm of lifelong immunity to measles virus after vaccination. As the proportion of HIV-infected individuals possessing only vaccine-induced immunity continues to grow, checking the status of measles immunity in this group is strongly recommended.

[Measles vaccination].

PubMed

Floret, Daniel

2010-12-20

France is facing since 2008 a re-emerging measles outbreak affecting a high proportion of adults currently not or not correctly vaccinated. The non application since 30 years of the immunization program on measles mumps and rubella is the cause of this situation, despite the efficacy and the good tolerance of this vaccine has been demonstrated. The present epidemic is expected to go on, as long as the millions of measles susceptible people have not been either affected or vaccinated. A 95% protection rate is needed to interrupt the circulation of the virus. So, the objective of the French Plan for elimination of measles and congenital rubella is to reach at least a 95% vaccination coverage for the first dose and 80% for the second dose. The immunization recommendations should be strictly respected: first dose of MMR vaccine at 12 months and second dose within the second year of life. In this context, catch up immunization of children, adolescents and young adults (up to 30 year) not or not correctly vaccinated is particularly important, as well as the post exposure prophylactic measures, including vaccination.

In Vivo Ligands of MDA5 and RIG-I in Measles Virus-Infected Cells

PubMed Central

Hembach, Katharina; Baum, Alina; García-Sastre, Adolfo; Söding, Johannes; Conzelmann, Karl-Klaus

2014-01-01

RIG-I-like receptors (RLRs: RIG-I, MDA5 and LGP2) play a major role in the innate immune response against viral infections and detect patterns on viral RNA molecules that are typically absent from host RNA. Upon RNA binding, RLRs trigger a complex downstream signaling cascade resulting in the expression of type I interferons and proinflammatory cytokines. In the past decade extensive efforts were made to elucidate the nature of putative RLR ligands. In vitro and transfection studies identified 5′-triphosphate containing blunt-ended double-strand RNAs as potent RIG-I inducers and these findings were confirmed by next-generation sequencing of RIG-I associated RNAs from virus-infected cells. The nature of RNA ligands of MDA5 is less clear. Several studies suggest that double-stranded RNAs are the preferred agonists for the protein. However, the exact nature of physiological MDA5 ligands from virus-infected cells needs to be elucidated. In this work, we combine a crosslinking technique with next-generation sequencing in order to shed light on MDA5-associated RNAs from human cells infected with measles virus. Our findings suggest that RIG-I and MDA5 associate with AU-rich RNA species originating from the mRNA of the measles virus L gene. Corresponding sequences are poorer activators of ATP-hydrolysis by MDA5 in vitro, suggesting that they result in more stable MDA5 filaments. These data provide a possible model of how AU-rich sequences could activate type I interferon signaling. PMID:24743923

Live attenuated measles virus vaccine induces apoptosis and promotes tumor regression in lung cancer.

PubMed

Zhao, Danhua; Chen, Ping; Yang, Huiqiang; Wu, Yonglin; Zeng, Xianwu; Zhao, Yu; Wen, Yanjun; Zhao, Xia; Liu, Xiaolin; Wei, Yuquan; Li, Yuhua

2013-01-01

Although the treatment of lung carcinoma has improved, at least 65% of patients with this tumor succumb to progressive disease. Measles virus oncolytic therapy has been reported to be effective in reducing tumor burden in immunocompetent or nude mice; however, its potential to reduce tumor burden in lung carcinoma remains to be determined. Herein, we report the potent antitumor effects of a live attenuated measles vaccine virus Hu-191 strain (MV) against lung carcinoma. Immunocompetent C57BL/6 mice bearing Lewis lung carcinoma (LLC) cells were treated with MV (1x104 to 1x106 CCID50/ml) once every other day for 10 days. Our results showed that treatment with MV effectively suppressed tumor growth and significantly prolonged the survival time of tumor-bearing animals. Histological examination revealed that the antitumor effects of MV therapy may result from increased induction of apoptosis, tumor necrosis and elevated lymphocyte infiltration. Our data suggest that MV, one of the widely used vaccines in China, has the ability to inhibit the growth of mouse lung carcinoma and may prove useful in the further exploration of the application of this approach in the treatment of human advanced lung cancer.

A review of measles.

PubMed

Dardis, Melissa R

2012-02-01

Measles, once a common childhood illness that many older school nurses could recognize without difficulty, needs review again after reemerging from Europe and other continents. A highly contagious disease, which has been referenced since the seventh century, the virus can cause serious illness and death, despite the fact that it is vaccine preventable. School nurses are wise to review the pathogenesis, occurrences, incubation, and communicability as well as methods to diagnose and treat measles in order to prevent an outbreak.

Detection and sequencing of measles virus from peripheral mononuclear cells from patients with inflammatory bowel disease and autism.

PubMed

Kawashima, H; Mori, T; Kashiwagi, Y; Takekuma, K; Hoshika, A; Wakefield, A

2000-04-01

It has been reported that measles virus may be present in the intestine of patients with Crohn's disease. Additionally, a new syndrome has been reported in children with autism who exhibited developmental regression and gastrointestinal symptoms (autistic enterocolitis), in some cases soon after MMR vaccine. It is not known whether the virus, if confirmed to be present in these patients, derives from either wild strains or vaccine strains. In order to characterize the strains that may be present, we have carried out the detection of measles genomic RNA in peripheral mononuclear cells (PBMC) in eight patients with Crohn's disease, three patients with ulcerative colitis, and nine children with autistic enterocolitis. As controls, we examined healthy children and patients with SSPE, SLE, HIV-1 (a total of eight cases). RNA was purified from PBMC by Ficoll-paque, followed by reverse transcription using AMV; cDNAs were subjected to nested PCR for detection of specific regions of the hemagglutinin (H) and fusion (F) gene regions. Positive samples were sequenced directly, in nucleotides 8393-8676 (H region) or 5325-5465 (from noncoding F to coding F region). One of eight patients with Crohn disease, one of three patients with ulcerative colitis, and three of nine children with autism, were positive. Controls were all negative. The sequences obtained from the patients with Crohn's disease shared the characteristics with wild-strain virus. The sequences obtained from the patients with ulcerative colitis and children with autism were consistent with being vaccine strains. The results were concordant with the exposure history of the patients. Persistence of measles virus was confirmed in PBMC in some patients with chronic intestinal inflammation.

Seroprevalence of measles, mumps, rubella, varicella-zoster and hepatitis A-C in Emirati medical students.

PubMed

Sheek-Hussein, Mohamud; Hashmey, Rayhan; Alsuwaidi, Ahmed R; Al Maskari, Fatima; Amiri, Leena; Souid, Abdul-Kader

2012-12-05

The aims of this study were to assess the seroprevalence of vaccine-preventable infections in Emirati medical students, and to provide scientific evidence for implementation of a cost-effective immunization guideline and policy for medical school admission. This prospective cohort study involved 261 (61% female) Emirati medical students (preclinical and clinical) attending the College of Medicine and Health Sciences at UAE University. Data on vaccination and history of infectious diseases were collected from participants. Blood samples were collected between July 1, 2011 and May 30, 2012 for serological testing and QuantiFERON®-TB assay. All students tested negative for infection with hepatitis C virus and human immunodeficiency virus. The prevalence of seropositivity to rubella virus was 97%, varicella-zoster virus 88%, mumps virus 84%, measles virus 54%, hepatitis B virus (HBV) 48%, and hepatitis A virus 21%. The QuantiFERON®-TB test was positive in 8% and indeterminate in 2%. Forty percent of students received HBV vaccine at birth; their HBV titers (mean ± SD) were 17.2 ± 62.9 mIU/mL (median = 1.64). The remaining 60% received it at school and their titers were 293.4 ± 371.0 mIU/mL (median = 107.7, p = 0.000). About 50% of students were susceptible to HBV and measles virus; therefore, pre-matriculation screening for antibodies against these viruses is highly recommended. Moreover, tuberculosis screening is necessary because of the high influx of expatriates from endemic areas. Students with inadequate protection should be reimmunized prior to contact with patients.

Biosafety considerations for attenuated measles virus vectors used in virotherapy and vaccination

PubMed Central

Baldo, Aline; Galanis, Evanthia; Tangy, Frédéric; Herman, Philippe

2016-01-01

ABSTRACT Attenuated measles virus (MV) is one of the most effective and safe vaccines available, making it attractive candidate vector to prevent infectious diseases. Attenuated MV have acquired the ability to use the complement regulator CD46 as a major receptor to mediate virus entry and intercellular fusion. Therefore, attenuated MV strains preferentially infect and destroy a wide variety of cancer cells making them also attractive oncolytic vectors. The use of recombinant MV vector has to comply with various regulatory requirements, particularly relating to the assessment of potential risks for human health and the environment. The present article highlights the main characteristics of MV and recombinant MV vectors used for vaccination and virotherapy and discusses these features from a biosafety point of view. PMID:26631840

Biosafety considerations for attenuated measles virus vectors used in virotherapy and vaccination.

PubMed

Baldo, Aline; Galanis, Evanthia; Tangy, Frédéric; Herman, Philippe

2016-05-03

Attenuated measles virus (MV) is one of the most effective and safe vaccines available, making it attractive candidate vector to prevent infectious diseases. Attenuated MV have acquired the ability to use the complement regulator CD46 as a major receptor to mediate virus entry and intercellular fusion. Therefore, attenuated MV strains preferentially infect and destroy a wide variety of cancer cells making them also attractive oncolytic vectors. The use of recombinant MV vector has to comply with various regulatory requirements, particularly relating to the assessment of potential risks for human health and the environment. The present article highlights the main characteristics of MV and recombinant MV vectors used for vaccination and virotherapy and discusses these features from a biosafety point of view.

Measles in Poland in 2013.

PubMed

Rogalska, Justyna

2015-01-01

Since 1998, Poland has been actively participating in the Measles Elimination Program, coordinated by the World Health Organization (WHO). It requires achieving and maintaining very high vaccine coverage (>95%), recording all cases and suspected cases of measles, and laboratory testing of all suspected measles cases in the WHO Reference Laboratory. In Poland it is a Laboratory of Department of Virology, NIPH-NIH. In order to confirm or exclude the case of measles specific measles IgM antibodies should be measured using Elisa test, or molecular testing (PCR) should be performed to detect the presence measles virus RNA in biological material. To assess epidemiological situation of measles in Poland in 2013, including vaccination coverage in Polish population, and Measles Elimination Program implementation status. The descriptive analysis was based on data retrieved from routine mandatory surveillance system and published in the annual bulletins "Infectious diseases and poisonings in Poland in 2013" and "Vaccinations in Poland in 2013", and measles case-based reports from 2013 sent to the Department of Epidemiology NIPH-NIH by Sanitary-Epidemiological Stations. In total, there were 84 measles cases registered in Poland in 2013 (incidence 0.22 per 100,000). The highest incidence rate was observed among infants (2.18 per 100,000) and children aged 1 year (1.27 per 100,000). In 2013, 56 cases (66.7%) were hospitalized due to measles. No deaths from measles were reported. Vaccination coverage of children and youth aged 2-11 years ranged from 82.8% do 99.5% (primary vaccination in children born in 2012-2007) and from 73.6% to 93.2% (booster dose in children born in 2004-2001). In 2013, 127 measles-compatible cases were reported (67% of expected reports). Two hundred seven cases (80%) were confirmed by IgM ELISA test. In 2013, the epidemiological situation of measles deteriorated in comparison to proceding year. The sensitivity of measles surveillance improved but is still

Replication of transformation-defective mutants of the Prague strain of Rous sarcoma virus and isolation of a td mutant from duck-adapted PR-RSV-C.

PubMed

Geryk, J; Mazo, A; Svoboda, J; Hlozánek, I

1980-01-01

The replication of transformation-defective mutants of the Prague strain of Rous sarcoma virus subgroup C was studied using roller cultures. Under such conditions, 10(5)--10(6) infectous units of virus per 0.2 ml were produced, as revealed in both the reverse transcriptase and 16Q complementation tests. A new td daPR-RSV-C mutant was isolated from duck-adapted PR-RSV-C. This mutant replicated in roller cultures with equal efficiency as the original td PR-RSV-C. It was verified that td daPR-RSV-C does not transform chicken fibroblasts, is not oncogenic for 3-week-old chickens and has subgroup C host-range specificity. Both td mutants replicate in duck cells and reach the same titres.

Experience with live rubella virus vaccine combined with live vaccines against measles and mumps*

PubMed Central

Smorodintsev, A. A.; Nasibov, M. N.; Jakovleva, N. V.

1970-01-01

Vaccination of pre-school children in the 1-7-years age-group for the specific prophylaxis of mumps and rubella is often difficult to arrange because of the already large number of inoculations given to these children. Combined vaccines to protect against measles, mumps and rubella should therefore be a valuable development. The existence of effective live vaccines for each of these 3 diseases makes possible the production of a single preparation suitable for subcutaneous inoculation. Tests on vaccine strains of measles (Leningrad-16), mumps (Leningrad-3) and rubella (Leningrad-8) viruses in various combinations have established that divalent or trivalent vaccines remain clinically harmless, highly immunogenic and epidemiologically effective. Single subcutaneous administrations of live measles vaccine combined with mumps or rubella vaccines or both, when given to children aged 1-8 years, brough about a high percentage of serological conversions and an increase in antibodies to a level comparable with that achieved with the corresponding monovalent vaccines. Morbidity from the 3 diseases was reduced among those vaccinated with the trivalent vaccine by 10 or more times, i.e., by about the same factor as when monovalent or divalent vaccines were used. PMID:5310140

Measles, mumps, rubella vaccine induced subacute sclerosing panencephalitis.

PubMed

Belgamwar, R B; Prasad, S; Appaya, P

1997-11-01

The incidence of subacute sclerosing panencephalitis (SSPE), a progressive and fatal neurodegenerative disease caused by the measles virus, has declined with widespread use of measles vaccine. The risk of SSPE after measles vaccination has been estimated at 0.7/million doses. This paper reports the case of a 15-year-old girl from India who developed SSPE presumably as a result of a delayed effect of measles, mumps, and rubella (MMR) vaccine. She presented with a 2-month history of behavioral disturbances, a deterioration in school performance, forgetfulness, silly smiling, handwriting changes, social withdrawal, and ataxia. The girl had received MMR vaccine at 9 months of age and had no past history of measles. Her measles antibody titre was 1:625 in both serum and cerebrospinal fluid.

Association between seroprevalence of measles and various social determinants in the year following a measles outbreak in Turkey.

PubMed

Emek, M; Islek, D; Atasoylu, G; Ozbek, O A; Ceylan, A; Acikgoz, A; Tay, Z; Demiral, Y; Oktem, M A; Unal, B

2017-06-01

Despite an ongoing measles elimination programme, a measles outbreak occurred in 2013 in Turkey. Population-based seroprevalence studies are needed to determine seronegativity and explore the reasons for this outbreak. This study aimed to explore the seroprevalence of measles and its association with various social determinants in a provincial population in Turkey in the year following a measles outbreak. Cross-sectional study. This study was conducted in Manisa Province in 2014 in a sample of 1740 people aged >2 years. The dependent variable was the seroprevalence of measles. Independent variables were sex, age, migration, household size, household density, income, education level, existence of chronic disease and occupational class. Blood samples were collected from participants at family health centres. The presence of specific measles antibodies in serum samples was determined using an anti-measles virus IgG enzyme-linked immunosorbent assay test. Chi-squared test and logistic regression analysis were performed. Overall, data from 1250 people were analysed. The seroprevalence of measles in the whole study population was 82.2% (95% confidence interval 80.0-84.2). Seroprevalence was 55.4% among subjects aged 2-9 years, 48.7% among subjects aged 10-19 years, 74.1% among subjects aged 20-29 years and 93.6% among subjects aged 30-39 years (P < 0.01). Seroprevalence in subjects aged >40 years was >95%. The lowest seroprevalence was found in primary school children (40.2%), followed by those below the age for primary education (69.8%) and secondary school graduates (75.1%). The prevalence of measles seronegativity was not associated with any of the social determinants when adjusted for age. The seroprevalence of measles was lower than expected in the study population and was particularly low in subjects aged <30 years of age despite previous vaccination. Seroprevalence was not associated with social determinants of health that confirmed either an even distribution

HSP90 Chaperoning in Addition to Phosphoprotein Required for Folding but Not for Supporting Enzymatic Activities of Measles and Nipah Virus L Polymerases.

PubMed

Bloyet, Louis-Marie; Welsch, Jérémy; Enchery, François; Mathieu, Cyrille; de Breyne, Sylvain; Horvat, Branka; Grigorov, Boyan; Gerlier, Denis

2016-08-01

Nonsegmented negative-stranded RNA viruses, or members of the order Mononegavirales, share a conserved gene order and the use of elaborate transcription and replication machinery made up of at least four molecular partners. These partners have coevolved with the acquisition of the permanent encapsidation of the entire genome by the nucleoprotein (N) and the use of this N-RNA complex as a template for the viral polymerase composed of the phosphoprotein (P) and the large enzymatic protein (L). Not only is P required for polymerase function, but it also stabilizes the L protein through an unknown underlying molecular mechanism. By using NVP-AUY922 and/or 17-dimethylaminoethylamino-17-demethoxygeldanamycin as specific inhibitors of cellular heat shock protein 90 (HSP90), we found that efficient chaperoning of L by HSP90 requires P in the measles, Nipah, and vesicular stomatitis viruses. While the production of P remains unchanged in the presence of HSP90 inhibitors, the production of soluble and functional L requires both P and HSP90 activity. Measles virus P can bind the N terminus of L in the absence of HSP90 activity. Both HSP90 and P are required for the folding of L, as evidenced by a luciferase reporter insert fused within measles virus L. HSP90 acts as a true chaperon; its activity is transient and dispensable for the activity of measles and Nipah virus polymerases of virion origin. That the cellular chaperoning of a viral polymerase into a soluble functional enzyme requires the assistance of another viral protein constitutes a new paradigm that seems to be conserved within the Mononegavirales order. Viruses are obligate intracellular parasites that require a cellular environment for their replication. Some viruses particularly depend on the cellular chaperoning apparatus. We report here that for measles virus, successful chaperoning of the viral L polymerase mediated by heat shock protein 90 (HSP90) requires the presence of the viral phosphoprotein (P). Indeed

Determining infants' age for measles vaccination based on persistence of protective level of maternal measles antibody.

PubMed

Shilpi, Tanjida; Sattar, Humayun; Miah, Md Ruhul Amin

2009-12-01

The present study was conducted over a period of one year to find the right time for measles vaccination when maternal antibody titer in infants was decayed rendering them susceptible to wild virus infection. Blood samples were collected from the cord of new born (147), 2-5 months (47) and 5 to 7.5 months (24) of age. The mean measles IgG antibody titer detected in cord blood at birth (0 months) was 348.8 mlU/mL which steeply decreased to 155.6 mlU/mL by the age of 2-3 months. After that the fall in antibody becomes relatively slower and decreased to 101.6 mIU/mL by the age of 3-5 months and 38.8 mlU/mL by the age of 5-6 months and to 19.2 mIU/mL between the age of 6 to 7.5 months. The fall in antibody level with the advance of age was statistically significant (p < 0.001 ). Majority of the subjects (97.6%) exhibited protective level of antibody at birth. But only a little above one-quarter (25.5%) of them persisted the protective level between the age of 2-5 months and none had protective level from 5 months onwards.

Measles, mumps, and rubella.

PubMed

White, Sarah J; Boldt, Kristi L; Holditch, Sara J; Poland, Gregory A; Jacobson, Robert M

2012-06-01

Measles, mumps, and rubella are viral diseases that may adversely affect nonimmune pregnant women and their fetuses/neonates. Prevention of these diseases and their complications can be achieved through measles-mumps-rubella (MMR) vaccination before pregnancy. The vaccine is contraindicated during pregnancy, because it contains live, attenuated viruses that pose a theoretical risk to the fetus. However, accidental receipt of MMR vaccination is not known to cause maternal/fetal complications. MMR immunization is recommended to nonimmune obstetric patients upon completion or termination of pregnancy.

Expression of interleukin-2 (IL-2) receptor alpha and CD45RO antigen on T-lymphocytes cultured with measles virus antigens, compared with humoral immunity in measles vaccinees.

PubMed

Toyoda, M; Ihara, T; Nakano, T; Ito, M; Kamiya, H

1999-03-17

In response to two types of measles virus (MV) antigens, a vaccine strain CAM and a wild strain isolated in 1994, the expression of IL-2 receptor alpha (CD25)(+)CD45RO(+)CD4(+) T-lymphocytes (T-cell activation) was analyzed by flow cytometry. In 75 healthy subjects with measles hemagglutination inhibition tests > or =1:16, the percentage of T-cell activation was significantly increased compared with that in seronegative individuals (p) < 0.05). Moreover, the T-cell expression was not significantly different among the vaccinated (n = 38), the naturally infected (n = 28) and the subclinically infected (exposed with wild type without history of measles infection and HI titers > or =1:16) (n = 10) groups. T-cell activation stimulated with MV antigens and HI antibody titers persisted for almost 30 years in the vaccinated group. These results suggest that cell-mediated immunity persists for long periods after vaccination and does not be influenced by antigenic drift.

Epitope Dampening Monotypic Measles Virus Hemagglutinin Glycoprotein Results in Resistance to Cocktail of Monoclonal Antibodies

PubMed Central

Lech, Patrycja J.; Tobin, Gregory J.; Bushnell, Ruth; Gutschenritter, Emily; Pham, Linh D.; Nace, Rebecca; Verhoeyen, Els; Cosset, François-Loïc; Muller, Claude P.; Russell, Stephen J.; Nara, Peter L.

2013-01-01

The measles virus (MV) is serologically monotypic. Life-long immunity is conferred by a single attack of measles or following vaccination with the MV vaccine. This is contrary to viruses such as influenza, which readily develop resistance to the immune system and recur. A better understanding of factors that restrain MV to one serotype may allow us to predict if MV will remain monotypic in the future and influence the design of novel MV vaccines and therapeutics. MV hemagglutinin (H) glycoprotein, binds to cellular receptors and subsequently triggers the fusion (F) glycoprotein to fuse the virus into the cell. H is also the major target for neutralizing antibodies. To explore if MV remains monotypic due to a lack of plasticity of the H glycoprotein, we used the technology of Immune Dampening to generate viruses with rationally designed N-linked glycosylation sites and mutations in different epitopes and screened for viruses that escaped monoclonal antibodies (mAbs). We then combined rationally designed mutations with naturally selected mutations to generate a virus resistant to a cocktail of neutralizing mAbs targeting four different epitopes simultaneously. Two epitopes were protected by engineered N-linked glycosylations and two epitopes acquired escape mutations via two consecutive rounds of artificial selection in the presence of mAbs. Three of these epitopes were targeted by mAbs known to interfere with receptor binding. Results demonstrate that, within the epitopes analyzed, H can tolerate mutations in different residues and additional N-linked glycosylations to escape mAbs. Understanding the degree of change that H can tolerate is important as we follow its evolution in a host whose immunity is vaccine induced by genotype A strains instead of multiple genetically distinct wild-type MVs. PMID:23300970

Poor recall of prior exposure to varicella zoster, rubella, measles, or mumps in patients with IBD.

PubMed

Naganuma, Makoto; Nagahori, Masakazu; Fujii, Toshimitsu; Morio, Junko; Saito, Eiko; Watanabe, Mamoru

2013-02-01

Few studies have measured the levels of antibodies specific for measles, mumps, rubella, and varicella zoster/chickenpox viruses in inflammatory bowel disease (IBD) patients undergoing treatment with immunomodulators/biologics. We prospectively recruited 139 IBD outpatients. Enzyme-linked immunosorbent assays were used as the serological tests for measles, mumps, rubella, and varicella zoster. We defined anti-rubella IgG < 10 IU/mL, anti-measles IgG < 16 IU/mL, and anti-mumps/varicella zoster IgG <4 IU/mL as seronegative for viruses. We also asked participants about past immunizations against or infections with measles, mumps, rubella, and varicella zoster viruses. The proportion of patients with seronegative levels of antibodies specific for varicella zoster, rubella, measles, and mumps viruses was 5%, 30%, 34%, and 37%, respectively. Approximately 40% of the IBD patients did not remember whether they had previously been infected with any of the viruses, and almost one-third of the patients could not remember whether they had previously been vaccinated. Almost 30% of the patients with a past history of rubella or measles did not have seropositive antibody levels. A total of 54% of the patients being treated with immunosuppressant displayed seronegative levels of antibodies specific for at least one of the viruses. Many IBD patients were unaware of whether they had previously been vaccinated against or infected with the viruses causing varicella zoster, rubella, measles, or mumps. Therefore, measuring the current levels of antibodies specific for such viruses is useful for determining whether patients have seropositive antibody levels before immunomodulators/biologics are used for therapy.

[Measles in Germany: An Epidemiological Analysis and First Measures for Containment].

PubMed

Matysiak-Klose, Dorothea; Wicker, Sabine

2017-11-01

Measles are one of the most contagious diseases of mankind. Measles incidence has declined worldwide since the introduction of vaccinations. Due to low numbers of measles cases in countries with high vaccination rates the population is not aware of possible complications of measles any more. Measles elimination is an important goal set by all regions of the World Health Organization. However, it remains a challenge for Germany and other European countries. Because of a high proportion of susceptibles in specific population and age groups outbreaks take place in Germany every year after importation of the virus. More than 50 % of measles cases are 20 years and older. However, the highest incidences have been seen in two-year-olds since several years. In addition to epidemiological findings such as case numbers and risk groups, genotyping permits e. g. an assessment of the endemic circulation of viruses. Suspicion of a measles case should result in immediate and consistent measures. © Georg Thieme Verlag KG Stuttgart · New York.

[Measles in France].

PubMed

Mortamet, G; Dina, J; Freymuth, F; Guillois, B; Vabret, A

2012-11-01

Measles is one of the most contagious diseases implicated in an outbreak in Western Europe for a few years. In France, the outbreak began in 2008, especially in the southern regions. Most of the cases are mild but deleterious effects can occur in infants, during the pregnancy, or in immunosuppressive patients. Pneumonia and encephalitis are the major complications in these patients. Measles illness during pregnancy results in a higher risk of premature labor, spontaneous abortion, and low-birthweight infants. Death from measles was reported in approximately 0.3% of cases. The National Reference Center for measles and paramyxoviridae is implicated in biological confirmation of cases and epidemiologic surveillance. Virologic diagnosis consists in a direct detection of viral RNA (real time PCR), or indirect detection of the immune response (IgM and IgG) in saliva samples. The measles genotype is determined by sequencing a 450 nucleotids fragment of the N gene, as the World Health Organization (WHO) recommendation. This molecular analysis helps determine the geographic origin of the virus and the viral strains circulating in the country. In 2011, 3105 specimens were received. PCR was positive for 1990 patients (64%), with a large majority of children younger than 2 years of age and young adults. The most important cause of measles resurgence is low vaccination coverage. The role of pediatricians is important in order to achieve the goal of 95% of vaccination coverage established by the WHO. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Investigation of measles and rubella outbreaks in Tamil Nadu, India-2003.

PubMed

Ramamurty, Nalini; Raja, Duraisamy; Gunasekaran, Palani; Varalakshmi, Elango; Mohana, Sambasivam; Jin, Li

2006-04-01

The aims of the present study were to confirm measles outbreaks by detection of measles-specific IgM antibodies, isolation of measles virus, and genetic characterization to document the circulating genotypes in Tamil Nadu. Eight outbreaks were reported from six districts of Tamil Nadu, India during the period Jan-Dec 2003. Blood samples were collected for serology, urine, and throat swabs for virus isolation. Genotypic characterization of measles isolates was based on the sequence of the N gene. All the clinically suspected outbreaks (n = 8) were confirmed by serology; six out of the eight as measles and two as combination of measles and rubella highlighting the need to carry out rubella serology on measles-negative samples. Genetic characterization of three isolates obtained revealed one as genotype D4 and two as D8. Measles genotypes D4 and D8 were found to circulate in three districts of Tamil Nadu. It is necessary to be aware of the circulating genotypes within the geographical area. The information would be valuable to evaluate control measures and identify viral transmission and importation. Copyright 2006 Wiley-Liss, Inc.

Maintaining high rates of measles immunization in Africa.

PubMed

Lessler, J; Moss, W J; Lowther, S A; Cummings, D A T

2011-07-01

Supplementary immunization activities (SIAs) are important in achieving high levels of population immunity to measles virus. Using data from a 2006 survey of measles vaccination in Lusaka, Zambia, we developed a model to predict measles immunity following routine vaccination and SIAs, and absent natural infection. Projected population immunity was compared between the current programme and alternatives, including supplementing routine vaccination with a second dose, or SIAs at 1-, 2-, 3-, 4- and 5-year intervals. Current routine vaccination plus frequent SIAs could maintain high levels of population immunity in children aged <5 years, even if each frequent SIA has low coverage (e.g. ≥ 72% for bi-annual 60% coverage SIAs vs. ≥ 69% for quadrennial 95% coverage SIAs). A second dose at 12 months with current coverage could achieve 81% immunity. Circulating measles virus will only increase population immunity. Public health officials should consider frequent SIAs when resources for a two-dose strategy are unavailable.

Eradication of measles: remaining challenges.

PubMed

Holzmann, Heidemarie; Hengel, Hartmut; Tenbusch, Matthias; Doerr, H W

2016-06-01

Measles virus (MeV) is an aerosol-borne and one of the most contagious pathogenic viruses known. Almost every MeV infection becomes clinically manifest and can lead to serious and even fatal complications, especially under conditions of malnutrition in developing countries, where still 115,000 to 160,000 patients die from measles every year. There is no specific antiviral treatment. In addition, MeV infections cause long-lasting memory B and T cell impairment, predisposing people susceptible to opportunistic infections for years. A rare, but fatal long-term consequence of measles is subacute sclerosing panencephalitis. Fifteen years ago (2001), WHO has launched a programme to eliminate measles by a worldwide vaccination strategy. This is promising, because MeV is a human-specific morbillivirus (i.e. without relevant animal reservoir), safe and potent vaccine viruses are sufficiently produced since decades for common application, and millions of vaccine doses have been used globally without any indications of safety and efficacy issues. Though the prevalence of wild-type MeV infection has decreased by >90 % in Europe, measles is still not eliminated and has even re-emerged with recurrent outbreaks in developed countries, in which effective vaccination programmes had been installed for decades. Here, we discuss the crucial factors for a worldwide elimination of MeV: (1) efficacy of current vaccines, (2) the extremely high contagiosity of MeV demanding a >95 % vaccination rate based on two doses to avoid primary vaccine failure as well as the installation of catch-up vaccination programmes to fill immunity gaps and to achieve herd immunity, (3) the implications of sporadic cases of secondary vaccine failure, (4) organisation, acceptance and drawbacks of modern vaccination campaigns, (5) waning public attention to measles, but increasing concerns from vaccine-associated adverse reactions in societies with high socio-economic standards and (6) clinical

Demographic transition and the dynamics of measles in six provinces in China: A modeling study

PubMed Central

Su, Qiru; An, Zhijie; Ma, Fubao; Xie, Shuyun; Xu, Aiqiang; Zhang, Yanyang; Ding, Zhengrong; Li, Hui; Wang, Huaqing; Luo, Huiming; Wang, Ning; Li, Li; Ferrari, Matthew J.

2017-01-01

Background Industrialization and demographic transition generate nonstationary dynamics in human populations that can affect the transmission and persistence of infectious diseases. Decades of increasing vaccination and development have led to dramatic declines in the global burden of measles, but the virus remains persistent in much of the world. Here we show that a combination of demographic transition, as a result of declining birth rates, and reduced measles prevalence, due to improved vaccination, has shifted the age distribution of susceptibility to measles throughout China. Methods and findings We fit a novel time-varying catalytic model to three decades of age-specific measles case reporting in six provinces in China to quantify the change in the age-specific force of infection for measles virus over time. We further quantified the impact of supplemental vaccination campaigns on the reduction of susceptible individuals. The force of infection of measles has declined dramatically (90%–97% reduction in transmission rate) in three industrialized eastern provinces during the last decade, driving a concomitant increase in both the relative proportion and absolute number of adult cases, while three central and western provinces exhibited dynamics consistent with endemic persistence (24%–73% reduction in transmission rate). The reduction in susceptible individuals due to supplemental vaccination campaigns is frequently below the nominal campaign coverage, likely because campaigns necessarily vaccinate those who may already be immune. The impact of these campaigns has significantly improved over time: campaigns prior to 2005 were estimated to have achieved less than 50% reductions in the proportion susceptible in the target age classes, but campaigns from 2005 onwards reduced the susceptible proportion by 32%–87%. A limitation of this study is that it relies on case surveillance, and thus inference may be biased by age-specific variation in measles reporting

Healthcare-associated Measles Following a Nationwide Outbreak in Mongolia.

PubMed

Lake, Jason G; Luvsansharav, Ulzii-Orshikh; Hagan, José E; Goodson, James L; Jigjidsuren, Nyamsuren; Gombojamts, Narantuya; Park, Benjamin J; Smith, Rachel

2018-01-31

Measles virus is highly infectious and can spread rapidly through healthcare settings where vaccine coverage is low and isolation precautions are suboptimal. We describe healthcare-associated measles transmission during the large 2015-2016 measles outbreak in Mongolia, describe observed infection prevention gaps, and outline practical strategies to prevent healthcare-associated measles transmission. Published by Oxford University Press for the Infectious Diseases Society of America 2018. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Complications of Measles (Rubeola)

MedlinePlus

... more depth. Top of Page Long-term Complications Subacute sclerosing panencephalitis (SSPE) is a very rare, but fatal disease of ... a measles virus infection acquired earlier in life. SSPE generally develops 7 to 10 years after a ...

Measles Virus Infection of Epithelial Cells in the Macaque Upper Respiratory Tract Is Mediated by Subepithelial Immune Cells

PubMed Central

Ludlow, Martin; Lemon, Ken; de Vries, Rory D.; McQuaid, Stephen; Millar, Emma L.; van Amerongen, Geert; Yüksel, Selma; Verburgh, R. Joyce; Osterhaus, Albert D. M. E.; Duprex, W. Paul

2013-01-01

Measles virus (MV), one of the most contagious viruses infecting humans, causes a systemic infection leading to fever, immune suppression, and a characteristic maculopapular rash. However, the specific mechanism or mechanisms responsible for the spread of MV into the respiratory epithelium in the late stages of the disease are unknown. Here we show the crucial role of PVRL4 in mediating the spread of MV from immune to epithelial cells by generating a PVRL4 “blind” recombinant wild-type MV and developing a novel in vitro coculture model of B cells with primary differentiated normal human bronchial epithelial cells. We utilized the macaque model of measles to analyze virus distribution in the respiratory tract prior to and at the peak of MV replication. Expression of PVRL4 was widespread in both the lower and upper respiratory tract (URT) of macaques, indicating MV transmission can be facilitated by more than only epithelial cells of the trachea. Analysis of tissues collected at early time points after experimental MV infection demonstrated the presence of MV-infected lymphoid and myeloid cells contacting respiratory tract epithelium in the absence of infected epithelial cells, suggesting that these immune cells seed the infection in vivo. Thereafter, lateral cell-to-cell spread of MV led to the formation of large foci of infected cells in the trachea and high levels of MV infection in the URT, particularly in the nasal cavity. These novel findings have important implications for our understanding of the high transmissibility of measles. PMID:23365435

The pathogenesis of measles.

PubMed

de Vries, Rory D; Mesman, Annelies W; Geijtenbeek, Teunis B H; Duprex, W Paul; de Swart, Rik L

2012-06-01

Measles is an important cause of childhood morbidity and mortality in developing countries. Measles virus (MV) is transmitted via the respiratory route and causes systemic disease. Over the last decade, identification of new cellular receptors and studies in animal models have challenged the historic concepts of measles pathogenesis. It is thought that MV enters the host by infection of alveolar macrophages and/or dendritic cells in the airways, and is amplified in local lymphoid tissues. Viremia mediated by infected CD150+ lymphocytes results in systemic dissemination. Infection of lymphocytes and dendritic cells in the respiratory submucosa facilitates basolateral infection of epithelial cells via the newly identified receptor Nectin-4. Concomitant and extensive epithelial damage may contribute to efficient transmission to the next host. Copyright © 2012 Elsevier B.V. All rights reserved.

An oncolytic measles virus-sensitive Group 3 medulloblastoma model in immune-competent mice.

PubMed

Lal, Sangeet; Carrera, Diego; Phillips, Joanna J; Weiss, William A; Raffel, Corey

2018-06-14

Oncolytic measles virus (MV) is effective in xenograft models of many tumor types in immune-compromised mice. However, no murine cell line exists that is tumorigenic, grows in immune-competent mice, and is killed by MV. The lack of such a model prevents an examination of the effect of the immune system on MV oncotherapy. Cerebellar stem cells from human CD46-transgenic immunocompetent mice were transduced to express Sendai virus C-protein, murine C-Myc, and Gfi1b proteins. The resultant cells were injected into the brain of NSG mice, and a cell line, called CSCG, was prepared from the resulting tumor. CSCG cells are highly proliferative, and express stem cell markers. These cells are permissive for replication of MV and are killed by the virus in a dose- and time-dependent manner. CSCG cells form aggressive tumors that morphologically resemble medulloblastoma when injected into the brains of immune-competent mice. On the molecular level, CSCG tumors overexpress natriuretic peptide receptor 3 and gamma-aminobutyric acid type A receptor alpha 5, markers of Group 3 medulloblastoma. A single intratumoral injection of MV‒green fluorescent protein resulted in complete tumor regression and prolonged survival of animals compared with treatments with phosphate buffered saline (P = 0.0018) or heat-inactivated MV (P = 0.0027). This immune-competent model provides the first platform to test therapeutic regimens of oncolytic MV for Group 3 medulloblastoma in the presence of anti-measles immunity. The strategy presented here can be used to make MV-sensitive murine models of any human tumor for which the driving mutations are known.

Measles mortality reduction--West Africa, 1996-2002.

PubMed

2004-01-23

The World Health Organization (WHO) estimates that, during 2000, measles accounted for approximately 777,000 deaths worldwide, of which 452,000 (58%) occurred in Africa. In response, in 2000, WHO's African Regional Office (AFRO) adopted a plan to reduce measles mortality >50% by 2005. The plan recommended 1) increasing measles vaccination by strengthening routine health services; 2) providing a second opportunity for measles vaccination for all children, primarily through wide--age-range supplemental immunization activities (SIAs); 3) enhancing measles surveillance; and 4) improving management of measles cases. The initial wide--age-range SIA targets all children aged 9 months-14 years, regardless of history of measles disease or vaccination. Follow-up SIAs are needed 3-5 years after the initial SIA to provide a second opportunity for vaccination to children born since the previous SIA (i.e., those aged 9 months-4 years). During the 1990s, the countries of the Americas and seven countries in southern Africa used this strategy to reduce the number of measles deaths to near zero. This report describes the recent implementation of this strategy in three West African countries, where reported measles cases declined 83%-97% during the first year after SIAs. Successful implementation of this strategy by other African countries should result in achieving the goal of >50% reduction in measles mortality by 2005.

Characterization of measles virus strains circulating in Southern Italy (Palermo area, Sicily) between 2010 and 2011.

PubMed

Urone, Noemi; Colomba, Claudia; Ferraro, Donatella

2016-03-01

Measles virus (MV) was classified in 24 genotypes that show a distinct geographic distribution. Genotypes contain multiple distinct lineages. In 2011 large outbreaks of measles occurred in Italy and in many European countries. Aims of this study are to analyze the intra-genotype variability and to follow the importation and the spread of new MV strains in Sicily. A fragment of 450 bps of MV C-terminal nucleoprotein was sequenced from sera of 73 Sicilian patients with symptomatic measles infections, occurred between 2010 and 2011. Five MV strains were D4 genotype and 68 were D8 genotype. The MV/D4 sequences were related to MV/D4-Enfield variant. Two lineages of MV/D8 genotypes, related to MV/D8-Villupuram variant and to a strain found in Birmingham in 2006 respectively, were identified. This is the first study that reports the co-circulation of different MV genotypes and lineages in Sicily suggesting multiple origins of the outbreak that occurred during 2010 and 2011 years. Copyright © 2016 Elsevier B.V. All rights reserved.

The 2014 measles outbreak in Osaka An epidemiological study for the elimination of measles.

PubMed

Yagi, Yoshina; Higashino, Hirohiko; Yoshida, Hideki; Hirokawa, Hidetetsu; Okumachi, Akinori; Takano, Masako; Nobuta, Mari; Matuoka, Taro; Sasai, Yasunori; Fukushima, Wakaba; Tanaka, Tomoyuki

2015-01-01

To examine and analyze the spread of measles in Osaka in 2014 and determine effective measures to prevent such occurrences. We analyzed 47 cases of measles reported in Osaka, including one measles patient living in another prefecture where there was an outbreak. We focused on age distribution, the number of patients reported each week, estimated infection routes, history of measles vaccination, detection of viruses, and number of days it took to report the case after the onset of measles. Patients aged 20-39 years accounted for 24 cases (51.1%). The number of patients reported started from 2nd week with relatively broad peak to 27(th) week, and the measles epidemic was brought under control in the 47(th) week. Among the 47 cases, no source could be identified in 16 cases (34.0%). Household exposure was the main cause of the infection (25.5%), followed by imported cases (21.3%). Eighty-three percent of the overall patients had not received a measles vaccination at all or it was unclear whether they previously had been vaccinated. Genotype B3, H1, and D8 were detected in our patients and these genotypes originated overseas. It took significantly more days, from the onset of measles, for the case to be reported in patients aged 15 years and over compared with those aged under 15 years (P=0.001). For eradicating measles in Osaka, it is important to raise awareness about this issue among medical institutions, especially institutions for adults, in order for them to report cases as soon as possible, upon discovery in their patients. In addition, "catch-up" supplementary immunizations are effective for all people, including adults who are susceptible to measles.

EpiReview: Measles in NSW, 2002-2011.

PubMed

Rosewell, Alexander; Reinten-Reynolds, Tracie; Spokes, Paula J

2012-12-01

Measles has been eliminated in NSW for more than a decade; however outbreaks associated with international travel do occur. This EpiReview describes the epidemiology of measles in NSW from 2002-2011. A total of 281 cases of measles were notified during the period, an average annual notification rate of 0.41 notifications per 100 000 population (range: 0.06-1.25). There were 139 hospitalisations recorded with a measles diagnosis in the 10-year reporting period, corresponding to a rate of 0.20 hospitalisations per 100 000 population. Of the 80 measles virus specimens genotyped, five genotypes were identified: D9 (38%), D8 (24%), D4 (16%), D5 (14%) with H1 identified less frequently (9%). No single genotype was associated with local transmission across successive years. To sustain good measles control, children should be vaccinated against measles on time through routine childhood immunisation, and all young adults who travel internationally should be vaccinated. Clinician awareness remains important in the early identification and control of measles to avoid further transmission during outbreaks and to enable the timely implementation of public health measures.

Measles Virus Nucleocapsid (MVNP) Gene Expression and RANK Receptor Signaling in Osteoclast Precursors,Osteoclast Inhibitors Peptide Therapy for Pagets Disease

DTIC Science & Technology

2004-10-01

Anderson DC, Sharpe PT. 1992. Canine distemper virus transcripts sequenced from pagetic bone. Bone Miner 19:159–174. Gori F, Hofbauer LC, Dunstan CR...clast formation in Paget’s disease. QJM 95:233–240. Ooi CG, Walsh CA, Gallagher JA, Fraser WD. 2000. Absence of measles virus and canine distemper virus...techniques. Furthermore, it has also been de- monstrated that infecting canine bone marrow cells with CDV results in development of multi- nucleated cells

CD147/EMMPRIN acts as a functional entry receptor for measles virus on epithelial cells.

PubMed

Watanabe, Akira; Yoneda, Misako; Ikeda, Fusako; Terao-Muto, Yuri; Sato, Hiroki; Kai, Chieko

2010-05-01

Measles is a highly contagious human disease caused by measles virus (MeV) and remains the leading cause of death in children, particularly in developing countries. Wild-type MeV preferentially infects lymphocytes by using signaling lymphocytic activation molecule (SLAM), whose expression is restricted to hematopoietic cells, as a receptor. MeV also infects other epithelial and neuronal cells that do not express SLAM and causes pneumonia and diarrhea and, sometimes, serious symptoms such as measles encephalitis and subacute sclerosing panencephalitis. The discrepancy between the tissue tropism of MeV and the distribution of SLAM-positive cells suggests that there are unknown receptors other than SLAM for MeV. Here we identified CD147/EMMPRIN (extracellular matrix metalloproteinase inducer), a transmembrane glycoprotein, which acts as a receptor for MeV on epithelial cells. Furthermore, we found the incorporation of cyclophilin B (CypB), a cellular ligand for CD147, in MeV virions, and showed that inhibition of CypB incorporation significantly attenuated SLAM-independent infection on epithelial cells, while it had no effect on SLAM-dependent infection. To date, MeV infection was considered to be triggered by binding of its hemagglutinin (H) protein and cellular receptors. Our present study, however, indicates that MeV infection also occurs via CD147 and virion-associated CypB, independently of MeV H. Since CD147 is expressed in a variety of cells, including epithelial and neuronal cells, this molecule possibly functions as an entry receptor for MeV in SLAM-negative cells. This is the first report among members of the Mononegavirales that CD147 is used as a virus entry receptor via incorporated CypB in the virions.

Measles and Rubella Seroprevalence Among HIV-infected and Uninfected Zambian Youth.

PubMed

Sutcliffe, Catherine G; Searle, Kelly; Matakala, Hellen K; Greenman, Michelle P; Rainwater-Lovett, Kaitlin; Thuma, Philip E; Moss, William J

2017-03-01

Measles and congenital rubella syndrome remain significant causes of morbidity and mortality despite available vaccines. HIV-infected youth may be at increased risk of measles because of greater waning immunity after vaccination. At a population level, they constitute a potentially large pool of susceptibles to measles and rubella. More data among HIV-infected youth in sub-Saharan Africa are needed to guide vaccination policy and control strategies. This cross-sectional study was nested within 2 ongoing studies of malaria and HIV in Zambia. Dried blood spot cards from youth (5-15 years) in these studies from 2009 to 2013 were tested for IgG antibodies to measles and rubella viruses. HIV-uninfected youth, HIV-infected treatment-naive youth and HIV-infected youth receiving antiretroviral therapy (ART) were compared. A total of 617 HIV-uninfected, 144 HIV-infected treatment-naive and 128 HIV-infected youth receiving ART were included in this study. The proportion seropositive for measles virus was significantly higher among HIV-uninfected youth (92.5%) compared with HIV-infected treatment-naive youth (74.1%) and HIV-infected youth receiving ART (71.9%). No differences by age were observed. The proportion seropositive for rubella virus was significantly higher among HIV-uninfected youth (54.7%) compared with HIV-infected treatment-naive youth (41.7%) and HIV-infected youth receiving ART (49.6%), with increases observed by age for all groups. Measles seroprevalence was lower among HIV-infected than uninfected youth, consistent with waning immunity after measles vaccination. HIV-infected youth would benefit from revaccination. Half of all youth in rural Zambia were susceptible to rubella and may need targeting for catch-up rubella campaigns when measles-rubella vaccine is introduced.

[EIA-IgG antibody measles prevention level estimated from measles neutralizing, particle agglutination and hemagglutination-inhibition antibody titer].

PubMed

Takayama, Naohide; Saika, Shizuko; Ichinohe, Sadato

2009-09-01

Measles hemagglutination inhibition (HI) antibody titer, widely used in clinical practice to simply and easily determine the measles immunity level has, in recent years, been increasingly replaced by measles IgG-antibody titer determined by enzyme-immunoassay (EIA). HI antibody titer appears to reflect this protective level, because HI measures the antibody against H protein required for the measles virus to adhere to host cells. EIA-IgG antibody titer does not correlate with the protective level, similar to particle agglutination (PA) titer, because EIA measures different antibodies, including those unrelated to measles protection. After determining HI, PA, neutralizing test (NT) results, and EIA-IgG antibody titer for individual specimens, we compared EIA-IgG antibody titer obtained using an EIA-Kit (Denka Seiken) to HI, PA, and NT titer with the following results: (1) Subjects with EIA-IgG titer of > or = 12.0 may be protected against measles: (2) Subjects with EIA-IgG titer of 4.0 to 8.0 appear to be protected insufficiently requiring a booster dose against measles: (3) Subjects with EIA-IgG titer of 8.0 to 12.0 may benefit from booster vaccination.

The 2011 measles outbreak in Tokyo. An analysis of surveillance data.

PubMed

Nadaoka, Yoko; Hayata, Noriko; Sugishita, Yoshiyuki; Kajiwara, Toshiko; Watanabe, Yu; Yoshida, Michihiko; Hasegawa, Michiya; Hayashi, Yukinao; Ochi, Masayo; Kai, Akemi; Sumitomo, Masami

2014-01-01

The study was conducted with the intention of establishing a strategy to eliminate measles on the basis of an analysis of the epidemiological profile of measles cases reported in Tokyo during the year 2011. We investigated measles cases reported to the Tokyo Metropolitan Government in 2011, recorded as part of the National Epidemiological Surveillance of Infectious Diseases. Factors analyzed included age, vaccination status for each patient, cases for which records were discarded after laboratory confirmation, genotype of the measles virus and relationships between dates of specimen collection and results of polymerase chain reaction (PCR) and IgM antibody tests. A total of 178 measles cases were reported in Tokyo during 2011, and the majority of cases (128, 71.9%) were reported during the peak period from epiweeks 13 to 24. The largest age group reported was one to four years of age (40, 22.5%) followed by groups of 20-29 and 30-39 years of age (both 34, 19.1%). Most cases were sporadic, with only six outbreaks occurring. Even then, the numbers of cases for each outbreak was less than five. More than half of the patients in all age groups, except for the 1-4-year-old group, had not been vaccinated or did not have a record of vaccination. Genotypes D4 and D9 of measles virus were detected in most cases. However, genotype D5, which had been circulating in Japan before 2008, was not detected. Imported viruses were the cause of measles cases reported in Tokyo during 2011. The disease control was better than that in 2007 and 2008 because of the swift and appropriate responses to the occurrences. It is also possible that there has been an increase in the proportion of people with immunity to measles. Increasing the rate of immunization, performing effective surveillance, and confirming suspicious measles cases by using molecular methods are important for achieving the elimination of measles.

Measles in Poland in 2014

PubMed

Paradowska-Stankiewicz, Iwona; Rogalska, Justyna

Since 1998, Poland has been actively participating in the Measles Elimination Program, coordinated by the World Health Organization (WHO). It requires achieving and maintaining very high vaccine coverage (>95%), recording all cases and suspected cases of measles, and laboratory testing of all suspected measles cases in the WHO Reference Laboratory. In Poland it is a Laboratory of Department of Virology, NIPHNIH. In order to confirm or exclude the case of measles specific measles IgM antibodies should be measured using Elisa test, or molecular testing (PCR) should be performed to detect the presence measles virus RNA in biological material. To assess epidemiological situation of measles in Poland in 2014, including vaccination coverage in Polish population, and Measles Elimination Program implementation status. The descriptive analysis was based on data retrieved from routine mandatory surveillance system, measles case-based reports from 2014 sent to the Department of Epidemiology NIPH-NIH by Sanitary-Epidemiological Stations and data published in the annual bulletins “Infectious diseases and poisonings in Poland in 2014” and “Vaccinations in Poland in 2014” (MP Czarkowski et all., Warszawa 2015, NIZP-PZH, GIS). In total, there were 110 measles cases registered in Poland in 2014 (incidence 0.29 per 100,000), from which 87 cases (79%) were confirmed with laboratory test. That was more than in 2013 - when 84 cases were reported and incidence was 0,22. The highest incidence rate was observed among children aged 1 year (3,43 per 100,000). In 2014, 76 cases (69%) were hospitalized due to measles. No deaths from measles were reported. Vaccination coverage of children and youth aged 2-11 years ranged from 79.7% do 94.8% (primary vaccination in children born in 2004-2013) and from 77.7% to 85.8% (booster dose in children born in 2005-2011). In 2013, 127 measles-compatible cases were reported (67% of expected reports). In whole country the total number of suspects

Measles transmission from an anthroposophic community to the general population, Germany 2008

PubMed Central

2011-01-01

Background In Germany, measles vaccination coverage with two doses is not yet sufficient to prevent regional outbreaks. Among the 16 German federal states, vaccination coverage was lowest in Bavaria with 85% in 2008. From March to mid-April 2008, four neighbouring Bavarian counties reported 55 measles-cases mostly linked to an ongoing measles outbreak in an anthroposophic school in Austria. We investigated this outbreak to guide future public health action. Methods We applied the German national case-definition for measles and collected data using the national surveillance system and a questionnaire. Measles cases with disease onset a maximum of 18 days apart and spatial contact (e.g. same household, same school) were summed up in clusters. Two different interventions, which were implemented in schools and kindergartens in Bavaria, were compared by their impact on the size and duration of measles clusters. Susceptible persons were excluded from schools or kindergartens either with the first (intervention A) or second (intervention B) measles case occurring in the respective institution. Results Among the 217 Bavarian measles cases identified from March-July 2008, 28 (13%) cases were attendees of the anthroposophic school in Austria. In total, vaccination status was known in 161 (74%) cases and 156 (97%) of them were not vaccinated. The main factor for non-vaccination was "fear of vaccine-related adverse events" (33%). Twenty-nine (18%) of 161 cases suffered complications. Exclusively genotype D5 was detected. Overall, 184 cases could be epidemiologically grouped into 59 clusters. Of those, 41 clusters could be linked to households and 13 to schools or kindergartens. The effect of intervention A and B was analysed in 10 school or kindergarten clusters. Depending on the respective intervention A or B, the median number of cases per cluster was 3 versus 13 (p = 0.05), and the median duration of a cluster was 3 versus 26 days (p = 0.13). Conclusions Introduction of

The measles virus N(TAIL)-XD complex: an illustrative example of fuzziness.

PubMed

Longhi, Sonia

2012-01-01

In this chapter, I focus on the biochemical and structural characterization of the complex between the intrinsically disordered C-terminal domain of the measles virus nucleoprotein (N(TAIL)) and the C-terminal X domain (XD) of the viral phosphoprotein (P). I summarize the main experimental data available so far pointing out the prevalently disordered nature of N(TAIL) even after complex formation and the role of the flexible C-terminal appendage in the binding reaction. I finally discuss the possible functional role of these residual disordered regions within the complex in terms of their ability to capture other regulatory, binding partners.

Predicting receptor functionality of signaling lymphocyte activation molecule for measles virus hemagglutinin by docking simulation.

PubMed

Suzuki, Yoshiyuki

2017-05-01

Predicting susceptibility of various species to a virus assists assessment of risk of interspecies transmission. Evaluation of receptor functionality may be useful in screening for susceptibility. In this study, docking simulation was conducted for measles virus hemagglutinin (MV-H) and immunoglobulin-like variable domain of signaling lymphocyte activation molecule (SLAM-V). It was observed that the docking scores for MV-H and SLAM-V correlated with the activity of SLAM as an MV receptor. These results suggest that the receptor functionality may be predicted from the docking scores of virion surface proteins and cellular receptor molecules. © 2017 The Societies and John Wiley & Sons Australia, Ltd.

Susceptibility to measles in migrant population: implication for policy makers.

PubMed

Ceccarelli, Giancarlo; Vita, Serena; Riva, Elisabetta; Cella, Eleonora; Lopalco, Maurizio; Antonelli, Francesca; De Cesaris, Marina; Fogolari, Marta; Dicuonzo, Giordano; Ciccozzi, Massimo; Angeletti, Silvia

2018-01-01

Despite a large measles outbreak is taking place in WHO European region, currently no data are available on measles immunization coverage in the asylum seeker and migrants hosted in this area. Two hundred and fifty-six migrants upon their arrival in Italy on March, April and May 2016 were screened for measles virus IgG antibodies by chemiluminescence immunoassay (Liaison XL analyzer, Diasorin, Italy). The virus susceptibility in this cohort, the differences between the official country reported and the observed measles immunization coverage and the impact of current measles outbreak on the asylum seekers hosted in the largest Asylum Seeker centres of Italy, were evaluated. The prevalence of subjects with positive result for measles IgG antibodies ranged between 79.9% and 100%. In Senegal, Mali, Nigeria, Pakistan and Bangladesh, the measles IgG seroprevalence observed was greater than the vaccinal coverage reported by WHO after I dose of vaccine. Based on data regarding the II dose coverage, the ASs population presented a seroprevalence greater to that expected. On the basis of the results obtained, extraordinary screening and vaccination campaigns in the migrant population, especially in the course of large outbreaks, could represent a resource to reach an adequate measles immunization coverage and to control this infectious disease. © International Society of Travel Medicine, 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com

Measles, mumps, rubella, and human parvovirus B19 infections and neurologic disease.

PubMed

Bale, James F

2014-01-01

While the systemic disorders associated with measles, mumps, and rubella viruses and human parvovirus B19 tend to be mild, each virus can produce potentially life-threatening neurologic disease in human hosts, especially when these viruses infect young children. Two of the viruses, rubella and parvovirus B19, can be vertically transmitted to fetuses during maternal infection and cause congenital infection. Neurologic complications are common after intrauterine infection with the rubella virus, a condition known as the congenital rubella syndrome. Two, measles and rubella viruses, can induce "slow viral" infections, serious, disorders that can occur several years after the initial exposure to the virus and typically have fatal outcomes. © 2014 Elsevier B.V. All rights reserved.

Prior DNA vaccination does not interfere with the live-attenuated measles vaccine.

PubMed

Premenko-Lanier, Mary; Rota, Paul; Rhodes, Gary; Bellini, William; McChesney, Michael

2004-01-26

The currently used live-attenuated measles vaccine is very effective although maternal antibody prevents its administration prior to 6 months of age. We are investigating the ability of a DNA vaccine encoding the measles viral hemagglutinin, fusion and nucleoprotein to protect newborn infants from measles. Here, we show that a measles DNA vaccine protects juvenile macaques from pathogenic measles virus challenge and that macaques primed and boosted with this DNA vaccine have anemnestic antibody and cell-mediated responses after vaccination with a live-attenuated canine distemper-measles vaccine. Therefore, this DNA vaccine administered to newborn infants may not hinder the subsequent use of live-attenuated measles vaccine.

Evaluating the impact of the HIV pandemic on measles control and elimination.

PubMed

Helfand, Rita F; Moss, William J; Harpaz, Rafael; Scott, Susana; Cutts, Felicity

2005-05-01

To estimate the impact of the HIV pandemic on vaccine-acquired population immunity to measles virus because high levels of population immunity are required to eliminate transmission of measles virus in large geographical areas, and HIV infection can reduce the efficacy of measles vaccination. A literature review was conducted to estimate key parameters relating to the potential impact of HIV infection on the epidemiology of measles in sub-Saharan Africa; parameters included the prevalence of HIV, child mortality, perinatal HIV transmission rates and protective immune responses to measles vaccination. These parameter estimates were incorporated into a simple model, applicable to regions that have a high prevalence of HIV, to estimate the potential impact of HIV infection on population immunity against measles. The model suggests that the HIV pandemic should not introduce an insurmountable barrier to measles control and elimination, in part because higher rates of primary and secondary vaccine failure among HIV-infected children are counteracted by their high mortality rate. The HIV pandemic could result in a 2-3% increase in the proportion of the birth cohort susceptible to measles, and more frequent supplemental immunization activities (SIAs) may be necessary to control or eliminate measles. In the model the optimal interval between SIAs was most influenced by the coverage rate for routine measles vaccination. The absence of a second opportunity for vaccination resulted in the greatest increase in the number of susceptible children. These results help explain the initial success of measles elimination efforts in southern Africa, where measles control has been achieved in a setting of high HIV prevalence.

Biased hypermutation occurred frequently in a gene inserted into the IC323 recombinant measles virus during its persistence in the brains of nude mice.

PubMed

Otani, Sanae; Ayata, Minoru; Takeuchi, Kaoru; Takeda, Makoto; Shintaku, Haruo; Ogura, Hisashi

2014-08-01

Measles virus (MV) is the causative agent of measles and its neurological complications, subacute sclerosing panencephalitis (SSPE) and measles inclusion body encephalitis (MIBE). Biased hypermutation in the M gene is a characteristic feature of SSPE and MIBE. To determine whether the M gene is the preferred target of hypermutation, an additional transcriptional unit containing a humanized Renilla reniformis green fluorescent protein (hrGFP) gene was introduced into the IC323 MV genome, and nude mice were inoculated intracerebrally with the virus. Biased hypermutation occurred in the M gene and also in the hrGFP gene when it was inserted between the leader and the N gene, but not between the H and L gene. These results indicate that biased hypermutation is usually found in a gene whose function is not essential for viral proliferation in the brain and that the location of a gene in the MV genome can affect its mutational frequency. Copyright © 2014 Elsevier Inc. All rights reserved.

Molecular characterization of measles viruses that circulated in Cameroon between 2010 and 2011.

PubMed

Demanou, Maurice; Ratsitoharana, Rajhonson; Yonga, Martial; Dosseh, Annick; Anya, Blanche; Kobela, Marie; Njouom, Richard

2013-03-04

Measles virus (MeV) is monotypic, but genetic variation in the hemagglutinin H and nucleoprotein N genes can be analyzed by molecular epidemiologic techniques and used to study virus transmission patterns. The World Health Organization currently recognizes 8 clades (A-H) within which are 24 genotypes of MeV and one provisional genotype, d11. Genotype B3 is clearly the endemic genotype in most of African continent where it is widely distributed. We provide an update on the molecular characterization of wild-type MeVs that circulated in Cameroon between 2010 and 2011. Viral RNA was extracted directly from samples obtained from clinically diagnosed measles patients using QIAamp viral RNA Mini Kit. Reverse transcription and PCR amplification of 634 nucleotides of the N gene was performed using the SuperScript™ III One-Step. Sequence analysis of 450 of the 634 nucleotides using Clustal X 2.0 program for multiple alignments and Mega version 5 for phylogenic analysis indicated that all the viruses belonged to genotype B3 with two distinct clusters. Twenty three (77%) belonged to subgroup B3.1 and the other 7 (23%) belonged to B3.3 a recently described subtype. Circulation of cluster 3 was detected in the Far-North Region (5/7) particularly along the Chad-Cameroon border in 2010 and later in Yaounde (2/7 in Biyem-assi Health District) the capital city of Cameroon in 2011. This study highlights the endemic circulation in Cameroon of MeV B3 subtype 1, which probably has its source in the neighboring Nigeria, and the presence of the new subtype B3.3, suggesting a possible importation from Northern Africa where it was first described between 2008 and 2009.

Measles and Rubella Seroprevalence Among HIV- Infected And Uninfected Zambian Youth

PubMed Central

Sutcliffe, Catherine G.; Searle, Kelly; Matakala, Hellen K.; Greenman, Michelle; Rainwater-Lovett, Kaitlin; Thuma, Philip E.; Moss, William J.

2016-01-01

Background Measles and congenital rubella syndrome remain significant causes of morbidity and mortality despite available vaccines. HIV-infected youth may be at increased risk of measles because of greater waning immunity following vaccination. At a population level, they constitute a potentially large pool of susceptibles to measles and rubella. More data among HIV-infected youth in sub-Saharan Africa are needed to guide vaccination policy and control strategies. Methods This cross-sectional study was nested within two ongoing studies of malaria and HIV in Zambia. Dried blood spot cards from youth (5–15 years) in these studies from 2009–2013 were tested for IgG antibodies to measles and rubella viruses. HIV-uninfected youth, HIV-infected treatment-naïve youth, and HIV-infected youth receiving antiretroviral therapy (ART) were compared. Results 617 HIV-uninfected, 144 HIV-infected treatment-naïve, and 128 HIV-infected youth receiving ART were included in the study. The proportion seropositive for measles virus was significantly higher among HIV-uninfected youth (92.5%) compared to HIV-infected treatment-naïve youth (74.1%) and HIV-infected youth receiving ART (71.9%). No differences by age were observed. The proportion seropositive for rubella virus was significantly higher among HIV-uninfected youth (54.7%) compared with HIV-infected treatment-naïve youth (41.7%) and HIV-infected youth receiving ART (49.6%), with increases observed by age for all groups. Conclusions Measles seroprevalence was lower among HIV-infected than uninfected youth, consistent with waning immunity following measles vaccination. HIV-infected youth would likely benefit from revaccination. Half of all youth in rural Zambia were susceptible to rubella and may need targeting for catch-up rubella campaigns when measles-rubella vaccine is introduced. PMID:27879554

Towards eradication of measles virus: global progress and strategy evaluation.

PubMed

Nokes, D J; Williams, J R; Butler, A R

1995-05-01

Despite an increase in global measles vaccine coverage from under 20% in 1980 to around 80% in 1990, measles remains a major cause of morbidity and mortality world-wide. This paper addresses a number of issues relating to efforts to control measles, namely, (i) at the global level, how might we assess the impact of measles vaccination on the incidence of infection and associated disease, and, (ii), at the strategic level, how can we utilise an understanding of the transmission dynamics of childhood viral infections to aid the design of optimal immunisation programmes? Based on WHO vaccine coverage data, and organising countries according to similarities in demographic and epidemiological parameters, an age-structured model of measles transmission is used to capture the non-linear dynamics of infection and mass vaccination and to generate projections of the impact of measles immunization world-wide. The results provide a crude indication of the percentage reduction in measles cases by year 2000 (compared with no immunization) and suggest an approximately 70% reduction in cases over all ages, and 77% reduction in cases under 5 years (where there is the greatest risk of case fatality); these suggest that WHO targets for 1995 are unlikely to be achieved. In the second part of the paper, examples are given to illustrate the usefulness of a modelling approach in evaluating measles immunization policy. The introduction of MMR vaccine in the UK in 1988 has resulted in measles incidence falling to an all time low and attention has turned to the requirements of elimination. A realistic age structured model, validated using extensive serological data, is used to compare the merits of single or two dose strategies. Based upon recent estimates of vaccine efficacy (90%) and coverage (92% by end of second year of life) it is suggested that a two-dose policy with a pre-school second dose given irrespective of vaccine history is required to prevent the build up of susceptibles to

Measles, mumps, and rubella vaccines.

PubMed

Wharton, M; Cochi, S L; Williams, W W

1990-03-01

With widespread use of the live virus vaccines for measles, mumps, and rubella, there has been a dramatic decrease in the incidence of all three diseases. At the same time, an increasing proportion of the remaining cases are occurring in adolescents and adults. Thus, vaccinations for these three diseases of childhood must be included in a comprehensive program for adult immunization. The vaccines have a proven history of safety and efficacy and are usually administered together as combined measles-mumps-rubella (MMR) vaccine. Vaccination for measles, mumps, and rubella is particularly important for susceptible adults likely to come in contact with infected children. Adults at particularly high risk for exposure may include daycare center workers, teachers and other school employees, college students, medical personnel, and those planning to travel outside the United States.

CD147/EMMPRIN Acts as a Functional Entry Receptor for Measles Virus on Epithelial Cells▿

PubMed Central

Watanabe, Akira; Yoneda, Misako; Ikeda, Fusako; Terao-Muto, Yuri; Sato, Hiroki; Kai, Chieko

2010-01-01

Measles is a highly contagious human disease caused by measles virus (MeV) and remains the leading cause of death in children, particularly in developing countries. Wild-type MeV preferentially infects lymphocytes by using signaling lymphocytic activation molecule (SLAM), whose expression is restricted to hematopoietic cells, as a receptor. MeV also infects other epithelial and neuronal cells that do not express SLAM and causes pneumonia and diarrhea and, sometimes, serious symptoms such as measles encephalitis and subacute sclerosing panencephalitis. The discrepancy between the tissue tropism of MeV and the distribution of SLAM-positive cells suggests that there are unknown receptors other than SLAM for MeV. Here we identified CD147/EMMPRIN (extracellular matrix metalloproteinase inducer), a transmembrane glycoprotein, which acts as a receptor for MeV on epithelial cells. Furthermore, we found the incorporation of cyclophilin B (CypB), a cellular ligand for CD147, in MeV virions, and showed that inhibition of CypB incorporation significantly attenuated SLAM-independent infection on epithelial cells, while it had no effect on SLAM-dependent infection. To date, MeV infection was considered to be triggered by binding of its hemagglutinin (H) protein and cellular receptors. Our present study, however, indicates that MeV infection also occurs via CD147 and virion-associated CypB, independently of MeV H. Since CD147 is expressed in a variety of cells, including epithelial and neuronal cells, this molecule possibly functions as an entry receptor for MeV in SLAM-negative cells. This is the first report among members of the Mononegavirales that CD147 is used as a virus entry receptor via incorporated CypB in the virions. PMID:20147391

Progress Toward Measles Elimination - Nepal, 2007-2014.

PubMed

Khanal, Sudhir; Sedai, Tika Ram; Choudary, Ganga Ram; Giri, Jagat Narain; Bohara, Rajendra; Pant, Rajendra; Gautam, Mukunda; Sharapov, Umid M; Goodson, James L; Alexander, James; Dabbagh, Alya; Strebel, Peter; Perry, Robert T; Bah, Sunil; Abeysinghe, Nihal; Thapa, Arun

2016-03-04

In 2013, the 66th session of the Regional Committee of the World Health Organization (WHO) South-East Asia Region (SEAR) established a goal to eliminate measles and to control rubella and congenital rubella syndrome (CRS) in SEAR by 2020. Current recommended measles elimination strategies in the region include 1) achieving and maintaining ≥95% coverage with 2 doses of measles-containing vaccine (MCV) in every district, delivered through the routine immunization program or through supplementary immunization activities (SIAs); 2) developing and sustaining a sensitive and timely measles case-based surveillance system that meets minimum recommended performance indicators; 3) developing and maintaining an accredited measles laboratory network; and 4) achieving timely identification, investigation, and response to measles outbreaks. In 2013, Nepal, one of the 11 SEAR member states, adopted a goal for national measles elimination by 2019. This report updates a previous report and summarizes progress toward measles elimination in Nepal during 2007-2014. During 2007-2014, estimated coverage with the first MCV dose (MCV1) increased from 81% to 88%. Approximately 3.9 and 9.7 million children were vaccinated in SIAs conducted in 2008 and 2014, respectively. Reported suspected measles incidence declined by 13% during 2007-2014, from 54 to 47 cases per 1 million population. However, in 2014, 81% of districts did not meet the measles case-based surveillance performance indicator target of ≥2 discarded non-measles cases per 100,000 population per year. To achieve and maintain measles elimination, additional measures are needed to strengthen routine immunization services to increase coverage with MCV1 and a recently introduced second dose of MCV (MCV2) to ≥95% in all districts, and to enhance sensitivity of measles case-based surveillance by adopting a more sensitive case definition, expanding case-based surveillance sites nationwide, and ensuring timely transport of

Genetic characterization of clade B measles viruses isolated in Tunisia and Libya 2002-2009 and a proposed new subtype within the B3 genotype.

PubMed

Haddad-Boubaker, Sondes; Rezq, Moftah; Smeo, Mohamed-Najeb; Ben Yahia, Ahlem; Abudher, Abdulhafid; Slim, Amin; Ben Ghorbel, Mohamed; Ahmed, Hinda; Rota, Paul; Triki, Hinda

2010-11-01

Genetic characterization was conducted on 18 wild-type measles viruses, detected in Tunisia and Libya from 2002 to 2009. Sequence analysis of the 456 nucleotides in the carboxy terminus of the nucleoprotein (N) gene and the entire hemagglutinin (H) gene indicated that all isolates were in genotype B3. All of the viruses from 2002 to 2007 and some of the isolates from 2009 belonged to subtype B3.1. In contrast, 7 of the viruses isolated during 2008 and 2009 were quite divergent from all B3 isolates. The nucleotide sequences of the N gene of these 7 isolates differed from the sequences of the Ibadan and New York reference strain by an average of 3.1 and 4.4%, respectively. The H gene sequences differed by 1.1 and 2.6% with the same reference strains. This is the first report describing the genetic characteristics of measles viruses from clade B isolated in North Africa; the results suggest that these viruses represent a new subtype of genotype B3. Copyright © 2010 Elsevier B.V. All rights reserved.

Phase I Trial of Intratumoral Administration of NIS-Expressing Strain of Measles Virus in Unresectable or Recurrent Malignant Peripheral Nerve Sheath Tumor

DTIC Science & Technology

2017-10-01

Distribution Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT Study approved by Mayo IRB on April 18 , 2016, and by USAMRMC/ORP/HRPO on May 6, 2016. All...Sheath Tumor(MPNST), MV-NIS, Oncolytic Virus, Measles Virus 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18 . NUMBER OF PPAGES 19a. NAME...virus incorporation and persistence in MPNST after injection Subtask 2: Assess viremia and viral shedding 1. Received Mayo IRB approval on 04/ 18 /2016

Occurrence of measles genotype D8 during a 2014 outbreak in Banjarmasin, South Kalimantan, Indonesia.

PubMed

Hartoyo, Edi; Wiyatno, Ageng; Jaya, Ungke Anton; Ma'roef, Chairin Nisa; Monagin, Corina; Myint, Khin Saw; Safari, Dodi

2017-01-01

An outbreak of measles symptoms occurring in children in Banjarmasin, South Kalimantan, Indonesia in 2014 was investigated. Nasal swabs were collected from 23 children (median age 41 months) with fever and other symptoms of measles hospitalized in Ulin General Hospital and Islamic Hospital, Banjarmasin, South Kalimantan. Viral RNA was extracted for cDNA synthesis, followed by PCR and sequencing using paramyxovirus family consensus and N-gene primers. Sixteen measles-positive patients (70%) were identified. Fifteen virus strains belonged to genotype D8 and the remaining one strain was confirmed as belonging to genotype D9. Measles virus genotype D8 was detected in an outbreak of measles in South Kalimantan, Indonesia, in 2014. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Toward measles elimination in Bahrain--a Middle East country experience.

PubMed

Jawad, Jaleela S; Al-Sayyad, Adel S; Sataih, Fathiya; Naouri, Boubker; Alexander, James P

2011-07-01

Measles was a leading cause of infant and child morbidity and mortality in Bahrain before the introduction of measles vaccine in 1974. With the establishment of the Expanded Program on Immunization (EPI) in 1981 and the introduction of a second dose of measles vaccine in 1985, coverage for first and second doses of measles vaccine increased to 94% by 1997 and has been sustained >97% since 2001. Measles, mumps, and rubella (MMR) immunization campaigns targeting 12-year-old students were conducted annually during 1998-2006 and achieved coverage of >95%. As a result, the incidence of measles in Bahrain has declined markedly over the past 4 decades, to 2.7 cases per million persons in 2009. Recent confirmed measles cases have occurred sporadically, in undervaccinated children or in infants too young or adults too old to receive measles vaccine. Bahrain has made significant progress toward measles elimination by sustaining high immunization coverage and strengthening case-based measles surveillance activities. Further success will depend on improved identification and immunization of undervaccinated expatriate workers and their families. Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2011.

Immunogenicity of recombinant measles vaccine expressing fusion protein of respiratory syncytial virus in cynomolgus monkeys.

PubMed

Sawada, Akihito; Yunomae, Kiyokazu; Nakayama, Tetsuo

2018-02-01

Respiratory syncytial virus (RSV) is a common cause of respiratory infections in infants. Effective vaccines are currently being sought, but no vaccine is thus far available. In our previous study, recombinant AIK-C measles vaccine expressing the RSV fusion protein (MVAIK/RSV/F) was developed and protective immunity against RSV demonstrated in cotton rats. In the present study, the immunogenicity and protective effects were investigated in three cynomolgus monkeys immunized with MVAIK/RSV/F. Neutralizing test antibodies against RSV were detected and no infectious virus was recovered from the lungs of monkeys immunized with MVAIK/RSV/F after challenge. MVAIK/RSV/F has the potential to inhibit RSV infection. © 2018 The Societies and John Wiley & Sons Australia, Ltd.

Molecular Characterization of Wild Type Measles Virus from Adult Patients in Northern China, 2014.

PubMed

Xu, Wen; Zhang, Ming-Xiang; Qin, En-Qiang; Yan, Ying-Chun; Li, Feng-Yi; Xu, Zhe; Tian, Xia; Fan, Rong; Tu, Bo; Chen, Wei-Wei; Zhao, Min

2016-04-01

In this study, we studied the N and H genes from wild type measles viruses (MeVs) isolated during the 2013-2014 outbreak. Clinical samples were collected, and the genotyping, phylogenetic analysis were performed. The vaccination rate of the study population was 4%. Genotype H1a was the predominant genotype. Wild type viruses were classified into clusters A and B, C and may have different origins. N-450 sequences from wild type viruses were highly homologous with, and likely evolved from MeVs circulating in Tianjing and Henan in 2012. MVs/Shenyang.CHN/18.14/3 could have evolved from MeVs from Liaoning, Beijing, Hebei, Heilongjiang, Henan, Jilin, and Tianjin. Our data suggested that one or more of the same viruses circulated between Beijing, Shenyang, Hong Kong, Taiwan and Berlin. Important factors contributing to outbreaks could include weak vaccination coverage, poor vaccination strategies, and migration of adult workers between cities, countries, and from rural areas to urban areas. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Measles virus induces persistent infection by autoregulation of viral replication.

PubMed

Doi, Tomomitsu; Kwon, Hyun-Jeong; Honda, Tomoyuki; Sato, Hiroki; Yoneda, Misako; Kai, Chieko

2016-11-24

Natural infection with measles virus (MV) establishes lifelong immunity. Persistent infection with MV is likely involved in this phenomenon, as non-replicating protein antigens never induce such long-term immunity. Although MV establishes stable persistent infection in vitro and possibly in vivo, the mechanism by which this occurs is largely unknown. Here, we demonstrate that MV changes the infection mode from lytic to non-lytic and evades the innate immune response to establish persistent infection without viral genome mutation. We found that, in the persistent phase, the viral RNA level declined with the termination of interferon production and cell death. Our analysis of viral protein dynamics shows that during the establishment of persistent infection, the nucleoprotein level was sustained while the phosphoprotein and large protein levels declined. The ectopic expression of nucleoprotein suppressed viral replication, indicating that viral replication is self-regulated by nucleoprotein accumulation during persistent infection. The persistently infected cells were able to produce interferon in response to poly I:C stimulation, suggesting that MV does not interfere with host interferon responses in persistent infection. Our results may provide mechanistic insight into the persistent infection of this cytopathic RNA virus that induces lifelong immunity.

Epidemiological and molecular investigation of a measles outbreak in Punjab, Pakistan, 2013-2015.

PubMed

Zaidi, Syed Sohail Zahoor; Hameed, Abdul; Ali, Naeem; Rana, Muhammad Suleman; Umair, Massab; Alam, Muhammad Masroor; Aamir, Uzma Bashir; Khurshid, Adnan; Sharif, Salmaan; Shaukat, Shahzad; Angez, Mehar; Mujtaba, Ghulam; Arshad, Yasir; Akthar, Ribqa; Sufian, Mian Muhammad; Mehmood, Nayab

2018-04-28

Despite the availability of an effective vaccine, the measles virus continues to cause significant morbidity and mortality in children worldwide. Molecular characterization of wild-type measles strains is an invaluable component of epidemiological studies or surveillance systems that provides important information pertinent to outbreak linkages and transmission pathways. Serum samples and throat swabs were collected from suspected measles cases from the Punjab province of Pakistan (2013-2015) and further tested for measles immunoglobulin M (IgM) through enzyme-linked immunosorbent assay and reverse-transcriptase polymerase chain reaction for molecular characterization. Among the total of 5415 blood samples, 59% tested positive for measles IgM. Males had a higher infection rate (55%) than females (45%), and the highest frequency of positive cases (63%) was found in the age group of 0 to 5 years. Partial sequencing of the nucleoprotein gene showed that 27 strains belonged to the B3 genotype, whereas 2 viruses were identified as D4. On phylogenetic analysis, Pakistani B3 strains were found to be closely related to previously reported indigenous strains and those from neighboring countries of Iran and Qatar. This is the first report on the detection of the measles B3 genotype from Punjab, Pakistan. The current study shows a high burden of measles infections in Punjab province owing to poor routine immunization coverage in major cities. It is imperative that national health authorities adopt strategic steps on an urgent basis for improvement of routine immunization coverage. Molecular epidemiology of the measles viruses circulating in different parts of the country can provide useful data to manage future outbreaks. © 2018 Wiley Periodicals, Inc.

A Review of Measles

ERIC Educational Resources Information Center

Dardis, Melissa R.

2012-01-01

Measles, once a common childhood illness that many older school nurses could recognize without difficulty, needs review again after reemerging from Europe and other continents. A highly contagious disease, which has been referenced since the seventh century, the virus can cause serious illness and death, despite the fact that it is vaccine…

Structures of the prefusion form of measles virus fusion protein in complex with inhibitors.

PubMed

Hashiguchi, Takao; Fukuda, Yoshinari; Matsuoka, Rei; Kuroda, Daisuke; Kubota, Marie; Shirogane, Yuta; Watanabe, Shumpei; Tsumoto, Kouhei; Kohda, Daisuke; Plemper, Richard Karl; Yanagi, Yusuke

2018-03-06

Measles virus (MeV), a major cause of childhood morbidity and mortality, is highly immunotropic and one of the most contagious pathogens. MeV may establish, albeit rarely, persistent infection in the central nervous system, causing fatal and intractable neurodegenerative diseases such as subacute sclerosing panencephalitis and measles inclusion body encephalitis. Recent studies have suggested that particular substitutions in the MeV fusion (F) protein are involved in the pathogenesis by destabilizing the F protein and endowing it with hyperfusogenicity. Here we show the crystal structures of the prefusion MeV-F alone and in complex with the small compound AS-48 or a fusion inhibitor peptide. Notably, these independently developed inhibitors bind the same hydrophobic pocket located at the region connecting the head and stalk of MeV-F, where a number of substitutions in MeV isolates from neurodegenerative diseases are also localized. Since these inhibitors could suppress membrane fusion mediated by most of the hyperfusogenic MeV-F mutants, the development of more effective inhibitors based on the structures may be warranted to treat MeV-induced neurodegenerative diseases.

Measles virus fusion machinery activated by sialic acid binding globular domain.

PubMed

Talekar, Aparna; Moscona, Anne; Porotto, Matteo

2013-12-01

Paramyxoviruses, including the human pathogen measles virus (MV) and the avian Newcastle disease virus (NDV), enter host cells through fusion of the viral envelope with the target cell membrane. This fusion is driven by the concerted action of two viral envelope glycoproteins: the receptor binding protein and the fusion protein (F). The MV receptor binding protein (hemagglutinin [H]) attaches to proteinaceous receptors on host cells, while the receptor binding protein of NDV (hemagglutinin-neuraminidase [HN]) interacts with sialic acid-containing receptors. The receptor-bound HN/H triggers F to undergo conformational changes that render it competent to mediate fusion of the viral and cellular membranes. The mechanism of fusion activation has been proposed to be different for sialic acid-binding viruses and proteinaceous receptor-binding viruses. We report that a chimeric protein containing the NDV HN receptor binding region and the MV H stalk domain can activate MV F to fuse, suggesting that the signal to the stalk of a protein-binding receptor binding molecule can be transmitted from a sialic acid binding domain. By engineering the NDV HN globular domain to interact with a proteinaceous receptor, the fusion activation signal was preserved. Our findings are consistent with a unified mechanism of fusion activation, at least for the Paramyxovirinae subfamily, in which the receptor binding domains of the receptor binding proteins are interchangeable and the stalk determines the specificity of F activation.

Successful public health response to four cases of imported measles in Panama.

PubMed

Sosa, Nestor; Guerra, Ilka; Abrego, Leyda; Cisneros, Julio; Castillo, Juan; Nieto-Guevara, Javier; Gálvez, Carlos; Moltó, Yadira; Smith, Rebecca E; Pascale, Juan Miguel

2012-08-21

In Panama, the last endemic cases of measles occurred in 1995. In this paper, we report four cases of imported measles in three girls and one boy after they returned from a trip to Poland and Israel between 28 April and 11 May 2011. The etiologic diagnosis of the four cases was confirmed by detection of IgM antibodies against measles virus and positive polymerase chain reaction using measles-specific primers. All cases had genotype D4 with close genetic similarity to virus reported from Poland. Public health interventions included isolation of the cases in their homes and an extensive search for and vaccination of contacts of the four cases, regardless of their vaccination status. A nationwide vaccination campaign was also implemented after the first case was identified. A total of 70,950 measles vaccine doses were administered in Panama in the two months following the identification of these cases. In addition, 94,179 persons were confirmed to have their immunization schedule up-to-date and did not receive the vaccine. No secondary cases were detected in Panama in the following six months.

Multigenic Control of Measles Vaccine Immunity Mediated by Polymorphisms in Measles Receptor, Innate Pathway, and Cytokine Genes

PubMed Central

Kennedy, Richard B.; Ovsyannikova, Inna G.; Haralambieva, Iana H.; O’Byrne, Megan; Jacobson, Robert M.; Pankratz, V. Shane; Poland, Gregory A.

2012-01-01

Measles infection and vaccine response are complex biological processes that involve both viral and host genetic factors. We have previously investigated the influence of genetic polymorphisms on vaccine immune response, including measles vaccines, and have shown that polymorphisms in HLA, cytokine, cytokine receptor, and innate immune response genes are associated with variation in vaccine response but do not account for all of the inter-individual variance seen in vaccinated populations. In the current study we report the findings of a multigenic analysis of measles vaccine immunity, indicating a role for the measles virus receptor CD46, innate pattern-recognition receptors (DDX58, TLR2, 4, 5,7 and 8) and intracellular signaling intermediates (MAP3K7, NFKBIA), and key antiviral molecules (VISA, OAS2, MX1, PKR) as well as cytokines (IFNA1, IL4, IL6, IL8, IL12B) and cytokine receptor genes (IL2RB, IL6R, IL8RA) in the genetic control of both humoral and cellular immune responses. This multivariate approach provided additional insights into the genetic control of measles vaccine responses over and above the information gained by our previous univariate SNP association analyses. PMID:22265947

[Subacute sclerosing panencephalitis cases diagnosed by increased CSF/serum measles antibody indices].

PubMed

Samlıoğlu, Pınar; Unalp, Aycan; Gökçay, Ahmet; Altuğlu, Imre; Oztürk, Aysel; Zeytinoğlu, Ayşın

2012-10-01

Subacute sclerosing panencephalitis (SSPE) caused by persistent defective measles virus strains, is a progressive neurological disorder of children and adolescents. The aim of this letter was to share the data from SSPE-suspected cases who were definitely diagnosed by the detection of increased antibody index in serum and cerebrospinal fluid (CSF) samples. A total of 11 patients (mean age: 14.3 years) with suspected SSPE between February 2006 to August 2008, were included in the study. Simultaneously obtained serum and CSF samples from patients were analyzed in terms of albumin, total IgG and measles-specific IgG levels (Measles Virus IgG ELISA for CSF Diagnostics, Euroimmun, Germany). The value of CSQrel (relative CSF/serum quotient) ≥ 1.5 was accepted indicative for intrathecal measles antibody synthesis. Seven (63.6%) of the 11 patients' diagnosis were confirmed with the demonstration of elevated CSF/serum indices (CSQrel range: 2.3-36.9; mean: 12.9). Mean age of those seven cases was 12.3 years (age range: 7-21) and four of them were male. The history of patients with high antibody indices indicated that three of four patients who had measles infection had not been vaccinated against measles. These three unvaccinated patients had measles infection at 3rd, 8th and 30th months of age, respectively, and the period of SSPE development were 15, 6 and 4.5 years, respectively. With this letter we would like to emphasize once more that effective measles vaccination is the only way for the prevention of measles and SSPE and the demonstration of increased measles antibody index in simultaneously obtained serum and CSF samples is crucial for the diagnosis of SSPE.

Epidemiology of measles in Southwest Nigeria: an analysis of measles case-based surveillance data from 2007 to 2012.

PubMed

Fatiregun, Akinola A; Adebowale, Ayodeji S; Fagbamigbe, Adeniyi F

2014-03-01

In Nigeria, a system of measles case-based surveillance with laboratory confirmation of suspected cases was introduced in 2005 as one of the strategies for the control of measles morbidity and mortality. In this report, we provide an epidemiological distribution of confirmed cases of measles reported from the southwest of the country between 2007 and 2012, and predict the expected number of cases for the ensuing years. A descriptive analysis of persons and place and time of confirmed measles cases (laboratory and epidemiological link) reported in the case-based surveillance data was carried out. Using an additive time series model, we predicted the expected number of cases to the year 2015, assuming that current interventional efforts were sustained. From the 10 187 suspected cases investigated during the time period, 1631 (16.0%) cases of measles were confirmed. The annual incidence rose from <1 case per million in 2007 to 23 cases per million in 2011. Cases were confirmed from all six states within the zone and most (97.4%) were in individuals aged less than 20 years. Seasonal variation existed with peaks of infection in the first and second quarters of the year. There was an increasing trend in the number of expected cases based on projections. Case-based surveillance provided an insight into understanding the epidemiology of measles infection in Southwest Nigeria. There is a need to work out alternate strategies for control of measles and to strengthen the surveillance system.

[Analysis of measles immunity level and serological susceptibility among Yunnan residents aged ≥20 years].

PubMed

Zhao, Z X; Zhou, R R; Li, L Q; Yu, W; Li, Q F; Hu, P

2018-01-06

Objective: To evaluate the population immunity to measles and explore the factors associated with measles susceptibility in Yunnan residents aged ≥20 years. Methods: 2 689 residents aged ≥20 years were selected by multistage stratified systematic randomized sampling in 252 villages of 42 counties in Yunnan Province between June and September in 2015. Each subject was surveyed by the same questionnaire, including general information, measles contained vaccine history, measles history, and 5 ml blood sample of each subject was collected. Serum IgG antibodies against measles virus were measured by ELISA. Positive was defined as the antibody concentration ≥250 mU/ml, and negative as <250 mU/ml. Non-conditional logistic regression model was used analyze the factors associated with measles susceptibility in adults. Results: Among 2 689 subjects, 1 214 were males (45.15%), and the overall positive rate of measles IgG antibody was 89.77%. Compared with subjects from the region where economic development was low, subjects from the region where economic development was moderate were likely to be susceptible to measles virus ( OR= 1.81, 95 %CI: 1.33-2.47). Four age groups had higher risk of being susceptible to measles virus (compared with ≥40 years: 20-24 years old, OR= 2.04, 95 %CI: 1.26-3.31; 25-29 years old, OR= 3.72, 95 %CI: 2.37-5.86; 30-34 years old, OR= 1.94, 95 %CI: 1.22-3.09; 35-39 years old, OR= 1.81, 95 %CI: 1.07-3.05). Conclusion: Our results suggest that the serological susceptibility in adults (20-39 years), especially adults from the regions where the economic development was moderate, should be concerned. The additional vaccination strategy targeting young adults is important for reducing the risk of measles infection.

Progress toward measles elimination—Philippines, 1998-2014.

PubMed

Takashima, Yoshihiro; Schluter, W William; Mariano, Kayla Mae L; Diorditsa, Sergey; de Quiroz Castro, Maricel; Ou, Alan C; Ducusin, Maria Joyce U; Garcia, Luzviminda C; Elfa, Dulce C; Dabbagh, Alya; Rota, Paul; Goodson, James L

2015-04-10

In 2005, the Regional Committee for the World Health Organization (WHO) Western Pacific Region (WPR) established a goal to eliminate measles by 2012.The recommended elimination strategies in WPR include 1) ≥95% 2-dose coverage with measles-containing vaccine (MCV) through routine immunization services and supplementary immunization activities (SIAs); 2) high-quality case-based measles surveillance; 3) laboratory surveillance with timely and accurate testing of specimens to confirm or discard suspected cases and detect measles virus genotypes; and 4) measles outbreak preparedness, rapid response, and appropriate case management. In the WPR, the Philippines set a national goal in 1998 to eliminate measles by 2008. This report describes progress toward measles elimination in the Philippines during 1998-2014 and challenges remaining to achieve the goal. WHO-United Nations Children's Fund (UNICEF)-estimated coverage with the routine first dose of MCV (MCV1) increased from 80% in 1998 to 90% in 2013, and coverage with the routine second dose of MCV (MCV2) increased from 10% after nationwide introduction in 2010 to 53% in 2013. After nationwide SIAs in 1998 and 2004, historic lows in the numbers and incidence of reported measles cases occurred in 2006. Despite nationwide SIAs in 2007 and 2011, the number of reported cases and incidence generally increased during 2007-2012, and large measles outbreaks occurred during 2013-2014 that affected infants, young children, older children, and young adults and that were prolonged by delayed and geographically limited outbreak response immunization activities during 2013-2014. For the goal of measles elimination in WPR to be achieved, sustained investments are required in the Philippines to strengthen health systems, implement the recommended elimination strategies, and develop additional strategies to identify and reduce measles susceptibility in specific geographic areas and older age groups.

Measles epidemic from 1951 to 2012 and vaccine effectiveness in Guangzhou, Southern China

PubMed Central

Yang, Zhicong; Xu, Jianxiong; Wang, Ming; Di, Biao; Tan, Huifeng; He, Qing; Cai, Yanshan; Liang, Jianhua; Hu, Wensui; Dong, Zhiqiang; Yang, Yunqing; Fu, Chuanxi

2014-01-01

Background Since the National Expanded Program on Immunization was implemented in China, considerable progress has been made in reducing the incidence of measles. However, the incidence of measles increased again in 2004. Few post-marketing studies on measles vaccine effectiveness were reported in China. In this study, we aimed to describe the measles epidemic and to evaluate the effectiveness of the measles vaccine in Guangzhou, southern China. Methods Based on the surveillance data for measles, we investigated the epidemiology during different periods between 1951 and 2012. We analyzed the clinical characteristics of laboratory-confirmed cases of measles between 2009 and 2012 and conducted a case-control study using test-negative cases as controls. We determined the protective effect of measles vaccine. Results The highest annual incidence in Guangzhou was 2187.15/100 000 in 1964, and the lowest was 0.32/100 000 in 2011. The average incidence of measles from 1951 to 2012 was 306.27/100 000. There was a significant tendency of decline in recent years. From 2009 to 2012, there are 700 laboratory-confirmed cases reported with an average onset age of 2.5 (median) years. The non-vaccinated target population (age <8 months and ≥15 years) accounted for 56.7% of the cases. The transient (non-resident) population accounted for 51.3% of the cases. Fewer cases were observed in the population targeted for measles vaccine (aged 8 months to 14 years). The effectiveness of a single dose of the measles vaccine was 89.1% (95% confidence interval (CI), 44.5–97.9), and the effectiveness of ≥2 doses of the measles vaccine was 97.8% (95% CI, 88.3–99.6) in children aged 8 months to 14 years old. Conclusions There is a significant overall decline in the incidence of measles (including clinical and laboratory confirmed cases) in the measles vaccine targeted population in Guangzhou. Two doses of measles vaccine are more effective than one dose in preventing measles in China

Progress Toward Regional Measles Elimination - Worldwide, 2000-2016.

PubMed

Dabbagh, Alya; Patel, Minal K; Dumolard, Laure; Gacic-Dobo, Marta; Mulders, Mick N; Okwo-Bele, Jean-Marie; Kretsinger, Katrina; Papania, Mark J; Rota, Paul A; Goodson, James L

2017-10-27

The fourth United Nations Millennium Development Goal, adopted in 2000, set a target to reduce child mortality by two thirds by 2015. One indicator of progress toward this target was measles vaccination coverage (1). In 2010, the World Health Assembly (WHA) set three milestones for measles control by 2015: 1) increase routine coverage with the first dose of a measles-containing vaccine (MCV1) among children aged 1 year to ≥90% at the national level and to ≥80% in every district; 2) reduce global annual measles incidence to <5 cases per million population; and 3) reduce global measles mortality by 95% from the 2000 estimate (2).* In 2012, WHA endorsed the Global Vaccine Action Plan, † with the objective of eliminating measles in four World Health Organization (WHO) regions by 2015 and in five regions by 2020. Countries in all six WHO regions have adopted goals for measles elimination by or before 2020. Measles elimination is defined as the absence of endemic measles virus transmission in a region or other defined geographic area for ≥12 months, in the presence of a high quality surveillance system that meets targets of key performance indicators. This report updates a previous report (3) and describes progress toward global measles control milestones and regional measles elimination goals during 2000-2016. During this period, annual reported measles incidence decreased 87%, from 145 to 19 cases per million persons, and annual estimated measles deaths decreased 84%, from 550,100 to 89,780; measles vaccination prevented an estimated 20.4 million deaths. However, the 2015 milestones have not yet been met; only one WHO region has been verified as having eliminated measles. Improved implementation of elimination strategies by countries and their partners is needed, with focus on increasing vaccination coverage through substantial and sustained additional investments in health systems, strengthening surveillance systems, using surveillance data to drive

High seroprevalence of varicella, measles, mumps, rubella and pertussis antibodies in first-grade medical students.

PubMed

Socan, Maja; Berginc, Natasa

2008-01-01

The aim of the study was to investigate seropositivity for five vaccine-preventable communicable diseases - varicella, measles, mumps, rubella and pertussis - in a sample of first-grade medical students. A total of 256 students were tested for varicella IgG antibodies. In addition, 138 of the students were serologically screened for measles, mumps, rubella and pertussis antibodies. Data on vaccination and history of measles, mumps, rubella and pertussis were collected. Immunity to varicella, measles, mumps and rubella was established in 97.6%, 96.4%, 97.8% and 99.3% participants, respectively. Anti-pertussis toxin antibodies were detected in 81.2% of the students. The rates of varicella, measles, mumps and rubella immunity in first-grade medical students are very high. To identify those students who need vaccination before commencing practical work in healthcare facilities, a meticulous disease and vaccination history should be taken and medical records should be reviewed. Medical students providing no written evidence of adequate vaccination status should be serologically tested and vaccinated if necessary.

Phase I Trial of Intratumoral Administration of NIS Expressing Strain of Measles Virus in Unresectable or Recurrent Malignant Peripheral Nerve Sheath Tumor

DTIC Science & Technology

2016-10-01

Release; Distribution Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT Study approved by Mayo IRB on April 18 , 2016, and by USAMRMC/ORP/HRPO on May 6...MV-NIS, Oncolytic Virus, Measles Virus 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18 . NUMBER OF PPAGES 19a. NAME OF...1. Received Mayo IRB approval on 04/ 18 /2016 2. The US Army Medical Research and Materiel Command (USAMRMC), Office of Research Protections (ORP

Transmission of measles among healthcare Workers in Hospital W, Xinjiang Autonomous Region, China, 2016.

PubMed

Jia, Haimei; Ma, Chao; Lu, Mengting; Fu, Jianping; Rodewald, Lance E; Su, Qiru; Wang, Huaqin; Hao, Lixin

2018-01-12

As China approaches the elimination of measles, outbreaks of measles continue to occur. Healthcare workers (HCWs) are known to be at high risk of infection and transmission of measles virus. A measles outbreak occurred in a hospital in Xinjiang Uighur Autonomous Region of the People's Republic of China. We report an investigation of this outbreak and its implications for measles elimination and outbreak preparedness. We conducted a retrospective search for measles cases using hospital records. Information on cases was collected by interview, and was used to determine epidemiological linkages. We surveyed HCWs to determine their demographic characteristics, disease history and vaccination status, and knowledge about measles. We identified 19 cases, ages 18 to 45 years, in Hospital W between December 2015 and January 2016; 14 were laboratory-confirmed, and 5 were epidemiologically linked. The primary case was a 25-year-old neurology department nurse who developed a rash on 22 December 2015 that was reported on 11 January 2016. She continued working and living with her workmates in a dormitory during her measles transmission period. Among the 19 infected HCWs, 2 had received a dose of measles-containing vaccine (MCV) before the outbreak, and 16 had unknown vaccination status. Outbreak response immunization activities were started on 8 January in a non-selective manner by offering vaccine regardless of vaccination history; 605(68%) of 890 HCWs were vaccinated. The HCW survey had a 73% response rate (646/890); 41% of HCWs reported that they had received MCV before outbreak, and 56% exhibited good knowledge of measles symptoms, transmission, complications, and vaccination. Low MCV coverage, low measles knowledge among HCWs, delayed reporting of measles cases, and absence of proper case management were associated with this outbreak. Training and vaccinating HCWs against measles are essential activities to prevent measles virus transmission among HCWs.

Molecular characterization of measles viruses in Turkey (2010-2011): first report of genotype D9 involved in an outbreak in 2011.

PubMed

Kalaycioglu, Atila T; Baykal, Atakan; Guldemir, Dilek; Bakkaloglu, Zekiye; Korukluoglu, Gulay; Coskun, Aslihan; Torunoglu, Mehmet Ali; Ertek, Mustafa; Durmaz, Riza

2013-12-01

Genetic characterization of measles viruses (MVs) combined with acquisition of epidemiologic information is essential for measles surveillance programs used in determining transmission pathways. This study describes the molecular characterization of 26 MV strains (3 from 2010, 23 from 2011) obtained from urine or throat swabs harvested from patients in Turkey. MV RNA samples (n = 26) were subjected to sequence analysis of 450 nucleotides comprising the most variable C-terminal region of the nucleoprotein (N) gene. Phylogenetic analysis revealed 20 strains from 2011 belonged to genotype D9, 3 to D4, 2 strains from 2010 to genotype D4 and 1 to genotype B3. This study represents the first report describing the involvement of MV genotype D9 in an outbreak in Turkey. The sequence of the majority of genotype D9 strains was identical to those identified in Russia, Malaysia, Japan, and the UK. Despite lack of sufficient epidemiologic information, the presence of variants observed following phylogenetic analysis suggested that exposure to genotype D9 might have occurred due to importation more than once. Phylogenetic analysis of five genotype D4 strains revealed the presence of four variants. Epidemiological information and phylogenetic analysis suggested that three genotype D4 strains and one genotype B3 strain were associated with importation. This study suggests the presence of pockets of unimmunized individuals making Turkey susceptible to outbreaks. Continuing molecular surveillance of measles strains in Turkey is essential as a means of acquiring epidemiologic information to define viral transmission patterns and determine the effectiveness of measles vaccination programs designed to eliminate this virus. © 2013 Wiley Periodicals, Inc.

The significance for epidemiological studies anti-measles antibody detection examined by enzyme immunoassay (EIA) and plaque reduction neutralization test (PRNT).

PubMed

Siennicka, Joanna; Częścik, Agnieszka; Trzcińska, Agnieszka

2014-01-01

The paper discusses the role of anti-measles antibodies for protection and significance for epidemiological studies determination of antibodies by different serological methods. The comparison of anti-measles virus antibodies levels measured by enzyme immunoassay (EIA) and Plaque Reduction Neutralization Test (PRNT) was described. It was found that the 200 mIU/ml of anti-measles activity measured by PRNT (level protection against symp- tomatic disease) is equivalent of 636 mIU/ml measured by EIA (Enzygnost®Anti-Measles Virus/IgG, Simens).

Constraints on the Genetic and Antigenic Variability of Measles Virus.

PubMed

Beaty, Shannon M; Lee, Benhur

2016-04-21

Antigenic drift and genetic variation are significantly constrained in measles virus (MeV). Genetic stability of MeV is exceptionally high, both in the lab and in the field, and few regions of the genome allow for rapid genetic change. The regions of the genome that are more tolerant of mutations (i.e., the untranslated regions and certain domains within the N, C, V, P, and M proteins) indicate genetic plasticity or structural flexibility in the encoded proteins. Our analysis reveals that strong constraints in the envelope proteins (F and H) allow for a single serotype despite known antigenic differences among its 24 genotypes. This review describes some of the many variables that limit the evolutionary rate of MeV. The high genomic stability of MeV appears to be a shared property of the Paramyxovirinae, suggesting a common mechanism that biologically restricts the rate of mutation.

Constraints on the Genetic and Antigenic Variability of Measles Virus

PubMed Central

Beaty, Shannon M.; Lee, Benhur

2016-01-01

Antigenic drift and genetic variation are significantly constrained in measles virus (MeV). Genetic stability of MeV is exceptionally high, both in the lab and in the field, and few regions of the genome allow for rapid genetic change. The regions of the genome that are more tolerant of mutations (i.e., the untranslated regions and certain domains within the N, C, V, P, and M proteins) indicate genetic plasticity or structural flexibility in the encoded proteins. Our analysis reveals that strong constraints in the envelope proteins (F and H) allow for a single serotype despite known antigenic differences among its 24 genotypes. This review describes some of the many variables that limit the evolutionary rate of MeV. The high genomic stability of MeV appears to be a shared property of the Paramyxovirinae, suggesting a common mechanism that biologically restricts the rate of mutation. PMID:27110809

Measles

MedlinePlus

... Staying Safe Videos for Educators Search English Español Measles KidsHealth / For Parents / Measles What's in this article? ... the Doctor? Print en español Sarampión What Is Measles? Measles is a very contagious respiratory infection. It ...

Measles, mumps, and rubella virus vaccine (M-M-R™II): a review of 32 years of clinical and postmarketing experience.

PubMed

Lievano, Fabio; Galea, Susan A; Thornton, Michele; Wiedmann, Richard T; Manoff, Susan B; Tran, Trung N; Amin, Manisha A; Seminack, Margaret M; Vagie, Kristen A; Dana, Adrian; Plotkin, Stanley A

2012-11-06

M-M-R™II (measles, mumps, and rubella virus vaccine live; Merck, Sharp, & Dohme Corp.) is indicated for simultaneous vaccination against measles, mumps, and rubella in individuals ≥ 12 months of age. Before the vaccine era, these viruses infected most exposed individuals, with subsequent morbidity and mortality. One of the greatest achievements of public health has been to eliminate these 3 diseases in large geographic areas. The safety profile of M-M-R™II is described using data from routine global postmarketing surveillance. Postmarketing surveillance has limitations (including incomplete reporting of case data), but allows collection of real-world information on large numbers of individuals, who may have concurrent medical problems excluding them from clinical trials. It can also identify rare adverse experiences (AEs). Over its 32-year history, ≈ 575 million doses of M-M-R™II have been distributed worldwide, with 17,536 AEs voluntarily reported for an overall rate of 30.5 AEs/1,000,000 doses distributed. This review provides evidence that the vaccine is safe and well-tolerated. Copyright © 2012 Elsevier Ltd. All rights reserved.

The Receptor-Binding Site of the Measles Virus Hemagglutinin Protein Itself Constitutes a Conserved Neutralizing Epitope

PubMed Central

Ohno, Shinji; Sakai, Kouji; Ito, Yuri; Fukuhara, Hideo; Komase, Katsuhiro; Brindley, Melinda A.; Rota, Paul A.; Plemper, Richard K.; Maenaka, Katsumi; Takeda, Makoto

2013-01-01

Here, we provide direct evidence that the receptor-binding site of measles virus (MV) hemagglutinin protein itself forms an effective conserved neutralizing epitope (CNE). Several receptor-interacting residues constitute the CNE. Thus, viral escape from neutralization has to be associated with loss of receptor-binding activity. Since interactions with both the signaling lymphocyte activation molecule (SLAM) and nectin4 are critical for MV pathogenesis, its escape, which results from loss of receptor-binding activity, should not occur in nature. PMID:23283964

Measles outbreak in the Republic of the Marshall Islands, 2003.

PubMed

Hyde, Terri B; Dayan, Gustavo H; Langidrik, Justina R; Nandy, Robin; Edwards, Russell; Briand, Kennar; Konelios, Mailynn; Marin, Mona; Nguyen, Huong Q; Khalifah, Anthony P; O'leary, Michael J; Williams, Nobia J; Bellini, William J; Bi, Daoling; Brown, Cedric J; Seward, Jane F; Papania, Mark J

2006-04-01

Measles is a highly contagious viral infection. Measles transmission can be prevented through high population immunity (>or=95%) achieved by measles vaccination. In the Republic of the Marshall Islands (RMI), no measles cases were reported during 1989-2002; however, a large measles outbreak occurred in 2003. Reported 1-dose measles vaccine coverage among children aged 12-23 months varied widely (52-94%) between 1990 and 2000. RMI is a Pacific island nation (1999 population: 50,840). A measles case was defined as fever, rash, and cough, or coryza, or conjunctivitis, in an RMI resident between July 13 and November 7, 2003. A vaccination campaign was used for outbreak control. Of the 826 reported measles cases, 766 (92%) occurred in the capital (Majuro). There were 186 (23%) cases in infants aged <1 year and 309 (37%) of cases in persons aged >or=15 years. The attack rate was highest among infants (Majuro atoll: 213 cases/1,000 infants). Among cases aged 1-14 years, 281 (59%) reported no measles vaccination before July 2003. There were 100 hospitalizations and 3 deaths. The measles H1 genotype was identified. The vaccination campaign resulted in 93% coverage among persons aged 6 months to 40 years. Interpretation Populations without endemic measles transmission can accumulate substantial susceptibility and be at risk for large outbreaks when measles virus is imported. 'Islands' of measles susceptibility may develop in infants, adults, and any groups with low vaccine coverage. To prevent outbreaks, high population immunity must be sustained by maintaining and documenting high vaccine coverage.

Acute measles encephalitis in partially vaccinated adults.

PubMed

Fox, Annette; Hung, Than Manh; Wertheim, Heiman; Hoa, Le Nguyen Minh; Vincent, Angela; Lang, Bethan; Waters, Patrick; Ha, Nguyen Hong; Trung, Nguyen Vu; Farrar, Jeremy; Van Kinh, Nguyen; Horby, Peter

2013-01-01

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. 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. 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

Measles Vaccine Strain Genotype A from the Skin Rash of a DiGeorge Patient on a TNF Inhibitor

PubMed Central

Tam, Pui-Ying Iroh; Hanisch, Benjamin R.; Klammer, Kate; DeVries, Aaron S.

2015-01-01

Isolation of measles virus is typically from respiratory, blood or urine specimens. We describe the first known case of measles vaccine-associated disease in a patient on TNF inhibitor therapy in which genotype A Edmonston vaccine strain virus was identified from skin scrapings of the patient’s rash. PMID:24346604

A Microneedle Patch for Measles and Rubella Vaccination Is Immunogenic and Protective in Infant Rhesus Macaques.

PubMed

Joyce, Jessica C; Carroll, Timothy D; Collins, Marcus L; Chen, Min-Hsin; Fritts, Linda; Dutra, Joseph C; Rourke, Tracy L; Goodson, James L; McChesney, Michael B; Prausnitz, Mark R; Rota, Paul A

2018-04-26

New methods to increase measles and rubella (MR) vaccination coverage are needed to achieve global and regional MR elimination goals. Here, we developed microneedle (MN) patches designed to administer MR vaccine by minimally trained personnel, leave no biohazardous sharps waste, remove the need for vaccine reconstitution, and provide thermostability outside the cold chain. This study evaluated the immunogenicity of MN patches delivering MR vaccine to infant rhesus macaques. Protective titers of measles neutralizing antibodies (>120 mIU/mL) were detected in 100% of macaques in the MN group and 75% of macaques in the subcutaneous (SC) injection group. Rubella neutralizing antibody titers were >10 IU/mL for all groups. All macaques in the MN group were protected from challenge with wild-type measles virus, whereas 75% were protected in the SC group. However, vaccination by the MN or SC route was unable to generate protective immune responses to measles in infant macaques pretreated with measles immunoglobulin to simulate maternal antibody. These results show, for the first time, that MR vaccine delivered by MN patch generated protective titers of neutralizing antibodies to both measles and rubella in infant rhesus macaques and afforded complete protection from measles virus challenge.

[Monitoring of implementation of international programs of poliomyelitis eradication and measles and rubella elimination in the Republic of Belarus].

PubMed

2012-01-01

Monitoring of implementation of international programs of poliomyelitis eradication, and measles and rubella elimination in the Republic of Belarus based on results of molecular-epidemiologic studies of 2009 - 2010. 271 viral agents isolated from children with acute flaccid paralysis syndrome, other diseases, healthy children and from sewage water within the framework of poliomyelitis control implementation were identified by serological and molecular methods. Blood sera of 528 patients with fever and rash were examined for the presence of IgM to measles and rubella virus, 418 - for the presence of IgM to parvovirus B19 and parvovirus DNA. Blood sera of 33 pregnant women and 64 children with signs of intrauterine infection were studied for IgM and IgG antibodies to rubella virus. Measles virus was isolated, N-gene sequence and phylogenetic analysis carried out. The studies performed confirmed that indigenous wild polioviruses in the country do not circulate, imported wild or vaccine-related polioviruses were also not detected. Measles and rubella morbidity in the Republic of Belarus was less than 1 in 1 000 000. 2 cases of rubella (2009) and 1 case of measles (2010) was detected during adequate control level: the rate of detection of patients with fever and rash, in whom measles and rubella diagnosis was excluded by the results of laboratory examination, was more than 2 in 100 000 of the population. The etiologic agent in more than 20% of diseases with fever and rash was parvovirus B19. A single case of measles was caused by genotype D8 virus imported from India. The data obtained give evidence to conformance of the poliomyelitis, measles, rubella, innate rubella syndrome control implemented in the Republic of Belarus to WHO recommendations; maintenance of status of country as free from poliomyelitis and achievement of main criteria of elimination of both measles and rubella by 2010.

Disruption of Akt kinase activation is important for immunosuppression induced by measles virus.

PubMed

Avota, E; Avots, A; Niewiesk, S; Kane, L P; Bommhardt, U; ter Meulen, V; Schneider-Schaulies, S

2001-06-01

Surface-contact-mediated signaling induced by the measles virus (MV) fusion and hemagglutinin glycoproteins is necessary and sufficient to induce T-cell unresponsiveness in vitro and in vivo. To define the intracellular pathways involved, we analyzed interleukin (IL)-2R signaling in primary human T cells and in Kit-225 cells. Unlike IL-2-dependent activation of JAK/STAT pathways, activation of Akt kinase was impaired after MV contact both in vitro and in vivo. MV interference with Akt activation was important for immunosuppression, as expression of a catalytically active Akt prevented negative signaling by the MV glycoproteins. Thus, we show here that MV exploits a novel strategy to interfere with T-cell activation during immunosuppression.

In Vitro Measles Virus Infection of Human Lymphocyte Subsets Demonstrates High Susceptibility and Permissiveness of both Naive and Memory B Cells

PubMed Central

Laksono, Brigitta M.; Grosserichter-Wagener, Christina; de Vries, Rory D.; Langeveld, Simone A. G.; Brem, Maarten D.; van Dongen, Jacques J. M.; Koopmans, Marion P. G.

2018-01-01

ABSTRACT Measles is characterized by a transient immune suppression, leading to an increased risk of opportunistic infections. Measles virus (MV) infection of immune cells is mediated by the cellular receptor CD150, expressed by subsets of lymphocytes, dendritic cells, macrophages, and thymocytes. Previous studies showed that human and nonhuman primate memory T cells express higher levels of CD150 than naive cells and are more susceptible to MV infection. However, limited information is available about the CD150 expression and relative susceptibility to MV infection of B-cell subsets. In this study, we assessed the susceptibility and permissiveness of naive and memory T- and B-cell subsets from human peripheral blood or tonsils to in vitro MV infection. Our study demonstrates that naive and memory B cells express CD150, but at lower frequencies than memory T cells. Nevertheless, both naive and memory B cells proved to be highly permissive to MV infection. Furthermore, we assessed the susceptibility and permissiveness of various functionally distinct T and B cells, such as helper T (TH) cell subsets and IgG- and IgA-positive memory B cells, in peripheral blood and tonsils. We demonstrated that TH1TH17 cells and plasma and germinal center B cells were the subsets most susceptible and permissive to MV infection. Our study suggests that both naive and memory B cells, along with several other antigen-experienced lymphocytes, are important target cells of MV infection. Depletion of these cells potentially contributes to the pathogenesis of measles immune suppression. IMPORTANCE Measles is associated with immune suppression and is often complicated by bacterial pneumonia, otitis media, or gastroenteritis. Measles virus infects antigen-presenting cells and T and B cells, and depletion of these cells may contribute to lymphopenia and immune suppression. Measles has been associated with follicular exhaustion in lymphoid tissues in humans and nonhuman primates, emphasizing

Attenuated Salmonella enterica serovar Typhi and Shigella flexneri 2a strains mucosally deliver DNA vaccines encoding measles virus hemagglutinin, inducing specific immune responses and protection in cotton rats.

PubMed

Pasetti, Marcela F; Barry, Eileen M; Losonsky, Genevieve; Singh, Mahender; Medina-Moreno, Sandra M; Polo, John M; Ulmer, Jeffrey; Robinson, Harriet; Sztein, Marcelo B; Levine, Myron M

2003-05-01

Measles remains a leading cause of child mortality in developing countries. Residual maternal measles antibodies and immunologic immaturity dampen immunogenicity of the current vaccine in young infants. Because cotton rat respiratory tract is susceptible to measles virus (MV) replication after intranasal (i.n.) challenge, this model can be used to assess the efficacy of MV vaccines. Pursuing a new measles vaccine strategy that might be effective in young infants, we used attenuated Salmonella enterica serovar Typhi CVD 908-htrA and Shigella flexneri 2a CVD 1208 vaccines to deliver mucosally to cotton rats eukaryotic expression plasmid pGA3-mH and Sindbis virus-based DNA replicon pMSIN-H encoding MV hemagglutinin (H). The initial i.n. dose-response with bacterial vectors alone identified a well-tolerated dosage (1 x 10(9) to 7 x 10(9) CFU) and a volume (20 micro l) that elicited strong antivector immune responses. Animals immunized i.n. on days 0, 28, and 76 with bacterial vectors carrying DNA plasmids encoding MV H or immunized parenterally with these naked DNA vaccine plasmids developed MV plaque reduction neutralizing antibodies and proliferative responses against MV antigens. In a subsequent experiment of identical design, cotton rats were challenged with wild-type MV 1 month after the third dose of vaccine or placebo. MV titers were significantly reduced in lung tissue of animals immunized with MV DNA vaccines delivered either via bacterial live vectors or parenterally. Since attenuated serovar Typhi and S. flexneri can deliver measles DNA vaccines mucosally in cotton rats, inducing measles immune responses (including neutralizing antibodies) and protection, boosting strategies can now be evaluated in animals primed with MV DNA vaccines.

Epidemiology and Genetic Characterization of Measles Strains in Senegal, 2004-2013

PubMed Central

Dia, Ndongo; Fall, Ameth; Ka, Rouguiyatou; Fall, Amary; Kiori, David E.; Goudiaby, Deborah G.; Fall, Aichatou D.; Faye, El Hadj Abdourahmane; Dosseh, Annick; Ndiaye, Kader; Diop, Ousmane M.; Niang, Mbayame Nd.

2015-01-01

Background In Senegal, with the variable routine vaccination coverage, the risk for illness and death from measles still exists as evidenced by the measles epidemic episode in 2009. Since 2002 a laboratory-based surveillance system of measles was established by the Ministry of Health and the Institut Pasteur de Dakar. The present study analysed the data collected over the 10 years inclusive between 2004-2013 in order to define a measles epidemiological profile in Senegal, and we carried out a phylogenetic analysis of measles virus circulating in Senegal over the period 2009-2012. Methodology and Results A total number of 4580 samples were collected from suspected cases, with the most cases between 2008 and 2010 (2219/4580; 48.4%). The majority of suspected cases are found in children from 4-6 years old (29%). 981 (21.4%) were measles laboratory-confirmed by IgM ELISA. The measles confirmation rate per year is very high during 2009-2010 periods (48.5% for each year). Regarding age groups, the highest measles IgM-positivity rate occurred among persons aged over 15 years with 39.4% (115/292) followed by 2-3 years old age group with 30.4% (323/1062) and 30% (148/494) in children under one year old group. The majority of suspected cases were collected between February and June and paradoxically confirmed cases rates increased from July (77/270; 28.6%) and reached a peak in November with 60% (93/155). Phylogenetic analysis showed that all the 29 sequences from strains that circulated in Senegal between 2009 and 2012 belong to the B3 genotype and they are clustered in B3.1 (2011-2012) and B3.3 (2009-2011) sub-genotypes according to a temporal parameter. Conclusion Improvements in the measles surveillance in Senegal are required and the introduction of oral fluid and FTA cards as an alternative to transportation of sera should be investigated to improve surveillance. The introduction of a national vaccine database including number of doses of measles-containing vaccine

A Recombinant Measles Vaccine with Enhanced Resistance to Passive Immunity.

PubMed

Julik, Emily; Reyes-Del Valle, Jorge

2017-09-21

Current measles vaccines suffer from poor effectiveness in young infants due primarily to the inhibitory effect of residual maternal immunity on vaccine responses. The development of a measles vaccine that resists such passive immunity would strongly contribute to the stalled effort toward measles eradication. In this concise communication, we show that a measles virus (MV) with enhanced hemagglutinin (H) expression and incorporation, termed MVvac2-H2, retained its enhanced immunogenicity, previously established in older mice, when administered to very young, genetically modified, MV-susceptible mice in the presence of passive anti-measles immunity. This immunity level mimics the sub-neutralizing immunity prevalent in infants too young to be vaccinated. Additionally, toward a more physiological small animal model of maternal anti-measles immunity interference, we document vertical transfer of passive anti-MV immunity in genetically-modified, MV susceptible mice and show in this physiological model a better MVvac2-H2 immunogenic profile than that of the parental vaccine strain. In sum, these data support the notion that enhancing MV hemagglutinin incorporation can circumvent in vivo neutralization. This strategy merits additional exploration as an alternative pediatric measles vaccine.

A Recombinant Measles Vaccine with Enhanced Resistance to Passive Immunity

PubMed Central

Julik, Emily; Reyes-del Valle, Jorge

2017-01-01

Current measles vaccines suffer from poor effectiveness in young infants due primarily to the inhibitory effect of residual maternal immunity on vaccine responses. The development of a measles vaccine that resists such passive immunity would strongly contribute to the stalled effort toward measles eradication. In this concise communication, we show that a measles virus (MV) with enhanced hemagglutinin (H) expression and incorporation, termed MVvac2-H2, retained its enhanced immunogenicity, previously established in older mice, when administered to very young, genetically modified, MV-susceptible mice in the presence of passive anti-measles immunity. This immunity level mimics the sub-neutralizing immunity prevalent in infants too young to be vaccinated. Additionally, toward a more physiological small animal model of maternal anti-measles immunity interference, we document vertical transfer of passive anti-MV immunity in genetically-modified, MV susceptible mice and show in this physiological model a better MVvac2-H2 immunogenic profile than that of the parental vaccine strain. In sum, these data support the notion that enhancing MV hemagglutinin incorporation can circumvent in vivo neutralization. This strategy merits additional exploration as an alternative pediatric measles vaccine. PMID:28934110

Detection of Measles Virus Genotypes B3, D4, D5, D8, and H1 in the Surveillance System in Hokkaido, Japan, 2006-2015, the Last Decade toward the Elimination.

PubMed

Miyoshi, Masahiro; Komagome, Rika; Yamaguchi, Hiroki; Ohnishi, Asami; Kikuchi, Masayuki; Ishida, Setsuko; Nagano, Hideki; Okano, Motohiko

2017-05-24

Measles is an acute and highly contagious disease caused by measles virus (MeV). The government of Japan, following the last epidemic in 2007 and 2008, which was caused by genotype D5 strains, introduced a catch-up-vaccination program for teenagers during Japan fiscal years 2008-2012 and a mandatory case-based reporting system for the nationwide elimination. Furthermore, laboratory confirmation of measles cases by genotyping of isolates has been performed to clarify the source of infection and support the interruption of measles cases. Owing to these preventive measures, the number of measles cases has been steadily decreasing after the last epidemic. In March 2015, Japan was internationally verified as having achieved measles elimination by the World Health Organization Regional Office for the Western Pacific. The continuous elimination of measles and high levels of vaccination coverage for MeV have been maintained nationally. However, imported or import-associated cases of measles have sporadically occurred during this time. After the last nationwide epidemic, 17 imported or import-associated measles cases (MeV strains identified as genotypes H1, D4, D8, and B3) were reported in Hokkaido, the northern islands of Japan. In this study, we present the occurrence of measles and surveillance activities in Hokkaido during 2006-2015.

Macrophages and Dendritic Cells Are the Predominant Cells Infected in Measles in Humans

PubMed Central

Allen, Ingrid V.; McQuaid, Stephen; Penalva, Rosana; Ludlow, Martin; Duprex, W. Paul

2018-01-01

ABSTRACT Characterization of human measles cases is essential in order to better assess the data generated in model systems of morbillivirus infection. To this end, we collected formalin-fixed tissue samples from 23 natural measles cases from different areas in the world and different phases of disease ranging from prodromal and acute measles to a persistent infection in an immunocompromised subject. We show that the vast majority of measles virus (MV)-infected cells in epithelia were intraepithelial immune cells that were, in most cases, positive for the CD11c myeloid cell marker. Small numbers of measles virus-infected cytokeratin-positive epithelial cells were also detected in bronchial and appendix epithelia. Dissolution and disruption of uninfected and MV-infected alveolar and bronchial epithelia were prominent features of the measles cases, especially in the established and late phases of the disease. In some instances, this was associated with the formation of MV-infected multinucleated giant cells which expressed CD11c and/or macrophage cell marker 68, a pathological feature also prominently observed in closely associated mucosa-associated lymphoid tissue. Collectively, these data show that resident and inflammatory infiltrating immune cells alter the architecture of respiratory tract epithelia and highlight the necessity for additional research into the function(s) and expression of nectin-4 in human tissues. IMPORTANCE We have brought together a unique collection of 23 human cases of measles infection and studied the types of cells that are infected. This work has not been done with modern technologies such as double labeling with antibodies and confocal microscopy in human cases primarily due to the fact that it is difficult to obtain the material because, fortunately, measles is fatal in only a very small fraction of infected patients. During the past decades, the receptors for measles virus have been elucidated and monkey models have been developed. We

Macrophages and Dendritic Cells Are the Predominant Cells Infected in Measles in Humans.

PubMed

Allen, Ingrid V; McQuaid, Stephen; Penalva, Rosana; Ludlow, Martin; Duprex, W Paul; Rima, Bertus K

2018-01-01

Characterization of human measles cases is essential in order to better assess the data generated in model systems of morbillivirus infection. To this end, we collected formalin-fixed tissue samples from 23 natural measles cases from different areas in the world and different phases of disease ranging from prodromal and acute measles to a persistent infection in an immunocompromised subject. We show that the vast majority of measles virus (MV)-infected cells in epithelia were intraepithelial immune cells that were, in most cases, positive for the CD11c myeloid cell marker. Small numbers of measles virus-infected cytokeratin-positive epithelial cells were also detected in bronchial and appendix epithelia. Dissolution and disruption of uninfected and MV-infected alveolar and bronchial epithelia were prominent features of the measles cases, especially in the established and late phases of the disease. In some instances, this was associated with the formation of MV-infected multinucleated giant cells which expressed CD11c and/or macrophage cell marker 68, a pathological feature also prominently observed in closely associated mucosa-associated lymphoid tissue. Collectively, these data show that resident and inflammatory infiltrating immune cells alter the architecture of respiratory tract epithelia and highlight the necessity for additional research into the function(s) and expression of nectin-4 in human tissues. IMPORTANCE We have brought together a unique collection of 23 human cases of measles infection and studied the types of cells that are infected. This work has not been done with modern technologies such as double labeling with antibodies and confocal microscopy in human cases primarily due to the fact that it is difficult to obtain the material because, fortunately, measles is fatal in only a very small fraction of infected patients. During the past decades, the receptors for measles virus have been elucidated and monkey models have been developed. We found

A Measles Outbreak in an Underimmunized Amish Community in Ohio.

PubMed

Gastañaduy, Paul A; Budd, Jeremy; Fisher, Nicholas; Redd, Susan B; Fletcher, Jackie; Miller, Julie; McFadden, Dwight J; Rota, Jennifer; Rota, Paul A; Hickman, Carole; Fowler, Brian; Tatham, Lilith; Wallace, Gregory S; de Fijter, Sietske; Parker Fiebelkorn, Amy; DiOrio, Mary

2016-10-06

Although measles was eliminated in the United States in 2000, importations of the virus continue to cause outbreaks. We describe the epidemiologic features of an outbreak of measles that originated from two unvaccinated Amish men in whom measles was incubating at the time of their return to the United States from the Philippines and explore the effect of public health responses on limiting the spread of measles. We performed descriptive analyses of data on demographic characteristics, clinical and laboratory evaluations, and vaccination coverage. From March 24, 2014, through July 23, 2014, a total of 383 outbreak-related cases of measles were reported in nine counties in Ohio. The median age of case patients was 15 years (range, <1 to 53); a total of 178 of the case patients (46%) were female, and 340 (89%) were unvaccinated. Transmission took place primarily within households (68% of cases). The virus strain was genotype D9, which was circulating in the Philippines at the time of the reporting period. Measles-mumps-rubella (MMR) vaccination coverage with at least a single dose was estimated to be 14% in affected Amish households and more than 88% in the general (non-Amish) Ohio community. Containment efforts included isolation of case patients, quarantine of susceptible persons, and administration of the MMR vaccine to more than 10,000 persons. The spread of measles was limited almost exclusively to the Amish community (accounting for 99% of case patients) and affected only approximately 1% of the estimated 32,630 Amish persons in the settlement. The key epidemiologic features of a measles outbreak in the Amish community in Ohio were transmission primarily within households, the small proportion of Amish people affected, and the large number of people in the Amish community who sought vaccination. As a result of targeted containment efforts, and high baseline coverage in the general community, there was limited spread beyond the Amish community. (Funded by the

Photos of Measles and People with Measles

MedlinePlus

... children. Viewing discretion is advised. Measles Clinical Features Video CDC’s Dr. Raymond Strikas, MD, describes clinical features of measles infection. Video, 3:15 minutes Video transcript [1 page] Measles ...

USA supports measles elimination.

PubMed

1996-06-01

The United States, through the United States Agency for International Development (USAID), has approved an $8 million grant in support of the Pan American Health Organization (PAHO) goal to eliminate measles in the Americas by the year 2000. From 1996 to 2001, the grant will complement regional efforts to stop the disease. Mrs. Hillary Clinton had pledged the support on World Health Day 1995. Although record low levels of measles cases were reported in 1995 for the region, the virus could be imported from elsewhere in the world. A major obstacle is the accumulation of susceptible preschool-aged children. As the proportion of susceptibles expands, the risk of a measles outbreak increases, if the virus is reintroduced. To prevent this, follow-up campaigns are being conducted throughout the region, focusing on all children aged 1-4 years, regardless of previous vaccination or disease history. PAHO recommends follow-up whenever the number of susceptible preschool children approaches the size of an average birth cohort. The interval between these campaigns and the specific age group targeted will depend on the vaccination coverage obtained through routine services since the last campaign. Follow-up campaigns were conducted in Cuba in 1993; in Belize, Brazil, Columbia, and Jamaica in 1995; and in Chile and the countries of Central America during April 1996. 19 million children were reached. Follow-up campaigns are planned for the remaining countries of the English-speaking Caribbean later in 1996. USAID played a key role in the successful completion of the 1994 poliomyelitis eradication initiative; the agency contributed approximately 60% of the external costs associated with the hemispheric campaign.

High Genetic Diversity of Measles Virus, World Health Organization European Region, 2005–2006

PubMed Central

Brown, Kevin E.; Jin, Li; Santibanez, Sabine; Shulga, Sergey V.; Aboudy, Yair; Demchyshyna, Irina V.; Djemileva, Sultana; Echevarria, Juan E.; Featherstone, David F.; Hukic, Mirsada; Johansen, Kari; Litwinska, Bogumila; Lopareva, Elena; Lupulescu, Emilia; Mentis, Andreas; Mihneva, Zefira; Mosquera, Maria M.; Muscat, Mark; Naumova, M.A.; Nedeljkovic, Jasminka; Nekrasova, Ljubov S.; Magurano, Fabio; Fortuna, Claudia; Rebelo de Andrade, Helena; Richard, Jean-Luc; Robo, Alma; Rota, Paul A.; Samoilovich, Elena O.; Sarv, Inna; Semeiko, Galina V.; Shugayev, Nazim; Utegenova, Elmira S.; van Binnendijk, Rob; Vinner, Lasse; Waku-Kouomou, Diane; Wild, T. Fabian; Brown, David W.G.; Mankertz, Annette; Muller, Claude P.; Mulders, Mick N.

2008-01-01

During 2005–2006, nine measles virus (MV) genotypes were identified throughout the World Health Organization European Region. All major epidemics were associated with genotypes D4, D6, and B3. Other genotypes (B2, D5, D8, D9, G2, and H1) were only found in limited numbers of cases after importation from other continents. The genetic diversity of endemic D6 strains was low; genotypes C2 and D7, circulating in Europe until recent years, were no longer identified. The transmission chains of several indigenous MV strains may thus have been interrupted by enhanced vaccination. However, multiple importations from Africa and Asia and virus introduction into highly mobile and unvaccinated communities caused a massive spread of D4 and B3 strains throughout much of the region. Thus, despite the reduction of endemic MV circulation, importation of MV from other continents caused prolonged circulation and large outbreaks after their introduction into unvaccinated and highly mobile communities. PMID:18258089

Broadly Neutralizing Immune Responses against Hepatitis C Virus Induced by Vectored Measles Viruses and a Recombinant Envelope Protein Booster

PubMed Central

Reyes-del Valle, Jorge; de la Fuente, Cynthia; Turner, Mallory A.; Springfeld, Christoph; Apte-Sengupta, Swapna; Frenzke, Marie E.; Forest, Amelie; Whidby, Jillian; Marcotrigiano, Joseph; Rice, Charles M.

2012-01-01

Hepatitis C virus (HCV) infection remains a serious public health problem worldwide. Treatments are limited, and no preventive vaccine is available. Toward developing an HCV vaccine, we engineered two recombinant measles viruses (MVs) expressing structural proteins from the prototypic HCV subtype 1a strain H77. One virus directs the synthesis of the HCV capsid (C) protein and envelope glycoproteins (E1 and E2), which fold properly and form a heterodimer. The other virus expresses the E1 and E2 glycoproteins separately, with each one fused to the cytoplasmic tail of the MV fusion protein. Although these hybrid glycoproteins were transported to the plasma membrane, they were not incorporated into MV particles. Immunization of MV-susceptible, genetically modified mice with either vector induced neutralizing antibodies to MV and HCV. A boost with soluble E2 protein enhanced titers of neutralizing antibody against the homologous HCV envelope. In animals primed with MV expressing properly folded HCV C-E1-E2, boosting also induced cross-neutralizating antibodies against two heterologous HCV strains. These results show that recombinant MVs retain the ability to induce MV-specific humoral immunity while also eliciting HCV neutralizing antibodies, and that anti-HCV immunity can be boosted with a single dose of purified E2 protein. The use of MV vectors could have advantages for pediatric HCV vaccination. PMID:22896607

Postpartum live virus vaccination: lessons from veterinary medicine.

PubMed

Yazbak, F Edward; Diodati, Catherine J M

2002-09-01

Pregnant rubella-susceptible women are often revaccinated during the postpartum period with the Measles, Mumps, and Rubella vaccine (MMR). It is known that the rubella virus from vaccine is secreted in breast milk and persists in the nose and throat for up to 28 days but it is not known whether the measles and mumps viruses are similarly secreted. It is probable the measles virus from vaccine is.

Case-based surveillance of measles in Sicily during 2012-2017: The changing molecular epidemiology and implications for vaccine strategies

PubMed Central

Maida, Carmelo Massimo; Pojero, Fanny; Colomba, Giuseppina Maria Elena; Casuccio, Alessandra; Restivo, Vincenzo; Vitale, Francesco

2018-01-01

Following the indication of the World Health Organization, a national plan for the elimination of measles was approved in Italy and this included the improvement of the molecular surveillance of measles viruses and the interruption of indigenous transmission of the disease. Nevertheless, large outbreaks continue to occur in almost all regions of the country, including Sicily. Here we describe the epidemiology and molecular dynamics of measles viruses as a result of the measles surveillance activity carried out by the “Reference Laboratory for Measles and Rubella” in Sicily over a 5-year period. Biological samples of 259 suspected measles cases were tested for viral RNA detection and a total of 223 (86.1%) were classified as laboratory confirmed. The median age of confirmed measles cases was 21.0 years and about half of them were adults aged 19 years and older. Overall, one-third of the patients showed clinical complications and these latter were more common among adults than children (44.9% vs. 25.7%). The vast majority of measles cases were unvaccinated (94.2%, n = 210). The phylogenetic analysis of 221 measles virus nucleotide sequences revealed sporadic detections of genotypes D4 and H1, while endemic circulation of genotypes D8 and B3 was documented. Genotype D8 was associated with epidemics occurred between 2013 and 2016, whereas genotype B3 was more recently introduced into Sicily characterizing the current measles outbreak. The results of this study confirm the autochthonous co-circulation of viral variants belonging to different genotypes during the study period, and emphasizes the need of measles surveillance programmes in order to investigate the viral dynamics, the pathways of disease transmission, and to eventually adapt the development of successfull vaccine formulations. PMID:29617454

Case-based surveillance of measles in Sicily during 2012-2017: The changing molecular epidemiology and implications for vaccine strategies.

PubMed

Tramuto, Fabio; Maida, Carmelo Massimo; Pojero, Fanny; Colomba, Giuseppina Maria Elena; Casuccio, Alessandra; Restivo, Vincenzo; Vitale, Francesco

2018-01-01

Following the indication of the World Health Organization, a national plan for the elimination of measles was approved in Italy and this included the improvement of the molecular surveillance of measles viruses and the interruption of indigenous transmission of the disease. Nevertheless, large outbreaks continue to occur in almost all regions of the country, including Sicily. Here we describe the epidemiology and molecular dynamics of measles viruses as a result of the measles surveillance activity carried out by the "Reference Laboratory for Measles and Rubella" in Sicily over a 5-year period. Biological samples of 259 suspected measles cases were tested for viral RNA detection and a total of 223 (86.1%) were classified as laboratory confirmed. The median age of confirmed measles cases was 21.0 years and about half of them were adults aged 19 years and older. Overall, one-third of the patients showed clinical complications and these latter were more common among adults than children (44.9% vs. 25.7%). The vast majority of measles cases were unvaccinated (94.2%, n = 210). The phylogenetic analysis of 221 measles virus nucleotide sequences revealed sporadic detections of genotypes D4 and H1, while endemic circulation of genotypes D8 and B3 was documented. Genotype D8 was associated with epidemics occurred between 2013 and 2016, whereas genotype B3 was more recently introduced into Sicily characterizing the current measles outbreak. The results of this study confirm the autochthonous co-circulation of viral variants belonging to different genotypes during the study period, and emphasizes the need of measles surveillance programmes in order to investigate the viral dynamics, the pathways of disease transmission, and to eventually adapt the development of successfull vaccine formulations.

Cloning the Antibody Response in Humans with Chronic Inflammatory Disease: Immunopanning of Subacute Sclerosing Panencephalitis (SSPE) Brain Sections with Antibody Phage Libraries Prepared from SSPE Brain Enriches for Antibody Recognizing Measles Virus Antigens In Situ

PubMed Central

Owens, Gregory P.; Williamson, R. Anthony; Burgoon, Mark P.; Ghausi, Omar; Burton, Dennis R.; Gilden, Donald H.

2000-01-01

In central nervous system (CNS) infectious and inflammatory diseases of known cause, oligoclonal bands represent antibody directed against the causative agent. To determine whether disease-relevant antibodies can be cloned from diseased brain, we prepared an antibody phage display library from the brain of a human with subacute sclerosing panencephalitis (SSPE), a chronic encephalitis caused by measles virus, and selected the library against SSPE brain sections. Antibodies that were retrieved reacted strongly with measles virus cell extracts by enzyme-linked immunosorbent assay and were specific for the measles virus nucleocapsid protein. These antibodies immunostained cells in different SSPE brains but not in control brain. Our data provide the first demonstration that diseased brain can be used to select in situ for antibodies directed against the causative agent of disease and point to the potential usefulness of this approach in identifying relevant antibodies in chronic CNS or systemic inflammatory diseases of unknown cause. PMID:10627565

Challenges in managing a school-based measles outbreak in Melbourne, Australia, 2014.

PubMed

Gibney, Katherine B; Brahmi, Aicha; O'Hara, Miriam; Morey, Rosemary; Franklin, Lucinda

2017-02-01

To identify barriers to control of a Victorian primary school-based measles outbreak. Confirmed measles cases notified in Victoria in 2014 were reviewed. Surveillance data, correspondence, and investigation notes for the school-based outbreak were assessed regarding timeliness of diagnosis and notification, and adequacy of school-based immunisation records. Twenty-three (31%) of the 75 measles cases notified in 2014 were school-aged (5-18 years); three had documentation of measles vaccination, 17 were unvaccinated, and three had unknown vaccination history. Eight measles outbreaks were identified, including a primary school-based outbreak with ten cases. Of the six unvaccinated pupils in the affected school, five (83%) contracted measles. The proportion of the school's prep students with documented vaccination records, as required by law, ranged from 39% in 2013 to 97% in 2014. Inadequately vaccinated students constitute a vulnerable population and schools are a potential site for measles outbreaks. Inadequate enforcement of school-based immunisation records impact the management and control of school-based measles outbreaks. Implications for Public Health: There is a need to educate clinicians on measles diagnosis and notification, and schools on the requirement to maintain up-to-date vaccination records. School entry is an opportunity to review student vaccination history and offer immunisations. © 2016 The Authors.

Evaluation of the mass measles vaccination campaign in Guangdong Province, China.

PubMed

Peng, Zhi Qiang; Chen, Wei Shi; He, Qun; Peng, Guo Wen; Wu, Cheng Gang; Xu, Ning; Zhao, Zhan Jie; Shu, Jun; Tan, Qiu; Zheng, Hui Zhen; Lin, Li Feng; Deng, Hui Hong; Lin, Jin Yan; Zhang, Yong Hui

2012-02-01

To evaluate the mass measles vaccination campaign of 2009 in Guangdong Province, China. Data on the campaign implementation, measles surveillance, and serological surveillance were reviewed and analyzed by statistical methods. Rapid coverage surveys showed that 98.09% of children were vaccinated during the campaign. The coverage of migrant children increased significantly from 67.10% to 97.32% (p<0.01). From May to December 2009, after the campaign, the number of measles cases was reduced by 93.04% compared with the same period of 2008. The antibody positive rate in children aged less than 15 years reached above 95%. More than 1 million migrant children were identified and vaccinated during the campaign. Flyers, notices of information from doctors, and television programs were the best methods to inform parents of the campaign. Awareness of the campaign by residents increased significantly from 91.86% to 97.10% (p<0.01) through the use of social mobilization materials. A massive vaccination campaign approach for controlling measles in a developing region like Guangdong Province with a vast migrant population has proved effective. Comprehensive mobilization, communication with the mass media, and support from government departments were critical to the success of the campaign. Copyright © 2011 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Measles virus attachment proteins with impaired ability to bind CD46 interact more efficiently with the homologous fusion protein

DOE Office of Scientific and Technical Information (OSTI.GOV)

Corey, Elizabeth A.; Iorio, Ronald M.; Program in Immunology and Virology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655

2009-01-05

Fusion promotion by measles virus (MV) depends on an interaction between the hemagglutinin (H) and fusion (F) glycoproteins. Amino acid substitutions in MV H that drastically reduce hemagglutinating activity result in an increase in the amount of H (primarily the 74 kDa isoform) detectable in a complex with F at the cell surface. This is in direct contrast to the loss of the ability to detect a complex between the fusion protein of Newcastle disease virus and most attachment proteins that lack receptor binding activity. These opposing results provide support for the existence of different mechanisms for the regulation ofmore » fusion by these two paramyxoviruses.« less

Measles

MedlinePlus

... Issues Listen Español Text Size Email Print Share Measles Page Content Article Body Measles was once a common disease among preschool and ... of growing up. This is no longer true. Measles has not been completely eliminated as a childhood ...

Imported case of measles in a university setting leading to an outbreak of measles in Edinburgh, Scotland from September to December 2016.

PubMed

Kirolos, A; Waugh, C; Templeton, K; McCormick, D; Othieno, R; Willocks, L J; Stevenson, J

2018-04-01

In September 2016, an imported case of measles in Edinburgh in a university student resulted in a further 17 confirmed cases during October and November 2016. All cases were genotype D8 and were associated with a virus strain most commonly seen in South East Asia. Twelve of the 18 cases were staff or students at a university in Edinburgh and 17 cases had incomplete or unknown measles mumps rubella (MMR) vaccination status. The public health response included mass follow-up of all identified contacts, widespread communications throughout universities in Edinburgh and prompt vaccination clinics at affected campuses. Imported cases of measles pose a significant risk to university student cohorts who may be undervaccinated, include a large number of international students and have a highly mobile population. Public health departments should work closely with universities to promote MMR uptake and put in place mass vaccination plans to prevent rapidly spreading measles outbreaks in higher educational settings in future.

The epidemiological and serological characteristics of measles in Dongguan, China, 2005-2014.

PubMed

Han, Ke; Chen, Shaoli; Tang, Cuifei; Wen, Jinjun; Li, Jingquan; Ni, Jindong; Zheng, Xueli

2016-08-02

This study examined the epidemiological and serological characteristics of measles in Dongguan, China. From 2005 to 2014, a total of 8,224 measles cases were reported in Dongguan, 33.5% of which were aged <1 y and 30.6% >14 y. From 2005 to 2014, the proportion of the <1 y measles cases increased year by year from 24.3% to 47.9%. Of the cases aged ≥8 months (n = 6,768 cases), only 11.6% had been immunized with at least one dose of measles vaccine. Of the 2,213 cases who had never been immunized with measles vaccine, immigrants accounted for 82.4%. 52.4% of the measles cases were diagnosed with pneumonia, and 12 cases died from respiratory failure. Seroprevalence rate in women and their newborns was 86.0% and 82.5%, respectively. Measurement of serum measles antibody levels for infants aged less than 8 months indicated that seroprevalence rate dramatically declined from 97.3% at birth to 9.3% and 13.2% at 6- and 7- month old. The existence of a sufficient pool of unvaccinated people (especially immigrants) and decreased level of passively transferred measles antibodies in infants from vaccinated mothers contributed to the sustained transmission observed in Dongguan. In addition to high routine vaccination coverage, new strategies and innovations for measles vaccination are needed to eliminate measles.

[Seroprevalence of antibodies to measles, rubella, mumps, hepatitis B viruses and all three poliovirus serotypes among children in Quindío, Colombia].

PubMed

González, María M; Sarmiento, Luis; Giraldo, Alejandra M; Padilla, Leonardo; Rey-Benito, Gloria; Castaño, Jhon C

2016-02-01

Objective The main goal of this research was to assess the seroprevalence of antibodies against measles, rubella, mumps, hepatitis B and all three poliovirus serotypes among children in the Quindío Department, Colombia. Methods Blood samples were obtained from 170 healthy children aged 5-9 years from nine municipalities in Quindío. The presence of serum IgG antibodies against measles, rubella, mumps and Hepatitis B were determined using commercial indirect ELISA kits. Immunity to poliomyelitis was assessed through the presence of neutralizing antibodies following the method recommended by the World Health Organization. Results Among the 170 children enrolled, 169 (99.41%), 170 (100 %), and 167 (98.2 %) were seropositive to poliovirus 1, poliovirus 2, and poliovirus 3, respectively. The average reciprocal antibody titers were 178 for poliovirus type 1, 120 for type 2 and 56 for type 3. Of the 170 children, 96.47 % were protected against mumps and rubella, and 86.47 % against measles. Only 106 (62.35 %) of the studied subjects were proved to be seropositive to hepatitis B. Conclusion The immunization program in Quindío has provided seroprotection against all three poliomyelitis serotypes, rubella and mumps. However, the child population is not fully protected against measles and hepatitis B virus infections.

Patterns of measles transmission among airplane travelers.

PubMed

Edelson, Paul J

2012-09-01

With advanced air handling systems on modern aircraft and the high level of measles immunity in many countries, measles infection in air travelers may be considered a low-risk event. However, introduction of measles into countries where transmission has been controlled or eliminated can have substantial consequences both for the use of public health resources and for those still susceptible. In an effort to balance the relatively low likelihood of disease transmission among largely immune travelers and the risk to the public health of the occurrence of secondary cases resulting from importations, criteria in the United States for contact investigations for measles exposures consider contacts to be those passengers who are seated within 2 rows of the index case. However, recent work has shown that cabin air flow may not be as reliable a barrier to the spread of measles virus as previously believed. Along with these new studies, several reports have described measles developing after travel in passengers seated some distance from the index case. To understand better the potential for measles virus to spread on an airplane, reports of apparent secondary cases occurring in co-travelers of passengers with infectious cases of measles were reviewed. Medline™ was searched for articles in all languages from 1946 to week 1 of March 2012, using the search terms "measles [human] or rubeola" and ("aircraft" or "airplane" or "aeroplane" or "aviation" or "travel" or "traveler" or "traveller"); 45 citations were returned. Embase™ was searched from 1988 to week 11 2012, using the same search strategy; 95 citations were returned. Papers were included in this review if they reported secondary cases of measles occurring in persons traveling on an airplane on which a person or persons with measles also flew, and which included the seating location of both the index case(s) and the secondary case(s) on the plane. Nine reports, including 13 index cases and 23 apparent secondary cases

Towards ambient temperature-stable vaccines: the identification of thermally stabilizing liquid formulations for measles virus using an innovative high-throughput infectivity assay.

PubMed

Schlehuber, Lisa D; McFadyen, Iain J; Shu, Yu; Carignan, James; Duprex, W Paul; Forsyth, William R; Ho, Jason H; Kitsos, Christine M; Lee, George Y; Levinson, Douglas A; Lucier, Sarah C; Moore, Christopher B; Nguyen, Niem T; Ramos, Josephine; Weinstock, B André; Zhang, Junhong; Monagle, Julie A; Gardner, Colin R; Alvarez, Juan C

2011-07-12

As a result of thermal instability, some live attenuated viral (LAV) vaccines lose substantial potency from the time of manufacture to the point of administration. Developing regions lacking extensive, reliable refrigeration ("cold-chain") infrastructure are particularly vulnerable to vaccine failure, which in turn increases the burden of disease. Development of a robust, infectivity-based high throughput screening process for identifying thermostable vaccine formulations offers significant promise for vaccine development across a wide variety of LAV products. Here we describe a system that incorporates thermal stability screening into formulation design using heat labile measles virus as a prototype. The screening of >11,000 unique formulations resulted in the identification of liquid formulations with marked improvement over those used in commercial monovalent measles vaccines, with <1.0 log loss of activity after incubation for 8h at 40°C. The approach was shown to be transferable to a second unrelated virus, and therefore offers significant promise towards the optimization of formulation for LAV vaccine products. Copyright © 2011 Elsevier Ltd. All rights reserved.

Frequently Asked Questions about Measles in the U.S.

MedlinePlus

... by at least 28 days. These adults include students at post-high school education institutions, healthcare personnel, ... requested by states. using Advanced Molecular Detection (AMD) methods to determine measles virus genotypes and strains. providing ...

Measles Elimination Activities in the Western Pacific Region: Experience from the Republic of Korea

PubMed Central

Choe, Young June; Jee, Youngmee; Oh, Myoung-don

2015-01-01

We describe the global status of measles control and elimination, including surveillance and vaccination coverage data provided by the World Health Organization (WHO). Since 2000, two doses of measles vaccine (MCV2) became recommended globally and the achievement of high vaccination coverage has led to dramatic decrease in the measles incidence. Our finding indicates that, in the Western Pacific Region (WPR), substantial progress has been made to control measles transmission in some countries; however, the measles virus continues to circulate, causing outbreaks. The Republic of Korea (ROK) experienced a series of resurgence of measles due to the importation and healthcare-associated transmission in infants, however overall incidence and surveillance indicators met the WHO criteria for measles elimination. The ROK was verified to be measles-free along with Australia, Mongolia, and Macau, China in 2014. One of the effective elimination activities was the establishment of solid keep-up vaccination system in school settings. The lessons learnt from the measles elimination activities in Korea may contribute to enhancing the surveillance schemes and strengthening of vaccination programs in member countries and areas of WPR. PMID:26617443

Measles Elimination Activities in the Western Pacific Region: Experience from the Republic of Korea.

PubMed

Choe, Young June; Jee, Youngmee; Oh, Myoung-don; Lee, Jong-Koo

2015-11-01

We describe the global status of measles control and elimination, including surveillance and vaccination coverage data provided by the World Health Organization (WHO). Since 2000, two doses of measles vaccine (MCV2) became recommended globally and the achievement of high vaccination coverage has led to dramatic decrease in the measles incidence. Our finding indicates that, in the Western Pacific Region (WPR), substantial progress has been made to control measles transmission in some countries; however, the measles virus continues to circulate, causing outbreaks. The Republic of Korea (ROK) experienced a series of resurgence of measles due to the importation and healthcare-associated transmission in infants, however overall incidence and surveillance indicators met the WHO criteria for measles elimination. The ROK was verified to be measles-free along with Australia, Mongolia, and Macau, China in 2014. One of the effective elimination activities was the establishment of solid keep-up vaccination system in school settings. The lessons learnt from the measles elimination activities in Korea may contribute to enhancing the surveillance schemes and strengthening of vaccination programs in member countries and areas of WPR.

In Vitro Measles Virus Infection of Human Lymphocyte Subsets Demonstrates High Susceptibility and Permissiveness of both Naive and Memory B Cells.

PubMed

Laksono, Brigitta M; Grosserichter-Wagener, Christina; de Vries, Rory D; Langeveld, Simone A G; Brem, Maarten D; van Dongen, Jacques J M; Katsikis, Peter D; Koopmans, Marion P G; van Zelm, Menno C; de Swart, Rik L

2018-04-15

Measles is characterized by a transient immune suppression, leading to an increased risk of opportunistic infections. Measles virus (MV) infection of immune cells is mediated by the cellular receptor CD150, expressed by subsets of lymphocytes, dendritic cells, macrophages, and thymocytes. Previous studies showed that human and nonhuman primate memory T cells express higher levels of CD150 than naive cells and are more susceptible to MV infection. However, limited information is available about the CD150 expression and relative susceptibility to MV infection of B-cell subsets. In this study, we assessed the susceptibility and permissiveness of naive and memory T- and B-cell subsets from human peripheral blood or tonsils to in vitro MV infection. Our study demonstrates that naive and memory B cells express CD150, but at lower frequencies than memory T cells. Nevertheless, both naive and memory B cells proved to be highly permissive to MV infection. Furthermore, we assessed the susceptibility and permissiveness of various functionally distinct T and B cells, such as helper T (T H ) cell subsets and IgG- and IgA-positive memory B cells, in peripheral blood and tonsils. We demonstrated that T H 1T H 17 cells and plasma and germinal center B cells were the subsets most susceptible and permissive to MV infection. Our study suggests that both naive and memory B cells, along with several other antigen-experienced lymphocytes, are important target cells of MV infection. Depletion of these cells potentially contributes to the pathogenesis of measles immune suppression. IMPORTANCE Measles is associated with immune suppression and is often complicated by bacterial pneumonia, otitis media, or gastroenteritis. Measles virus infects antigen-presenting cells and T and B cells, and depletion of these cells may contribute to lymphopenia and immune suppression. Measles has been associated with follicular exhaustion in lymphoid tissues in humans and nonhuman primates, emphasizing the

A Two-Center Randomized Trial of an Additional Early Dose of Measles Vaccine: Effects on Mortality and Measles Antibody Levels.

PubMed

Fisker, Ane B; Nebie, Eric; Schoeps, Anja; Martins, Cesario; Rodrigues, Amabelia; Zakane, Alphonse; Kagone, Moubassira; Byberg, Stine; Thysen, Sanne M; Tiendrebeogo, Justin; Coulibaly, Boubacar; Sankoh, Osman; Becher, Heiko; Whittle, Hilton C; van der Klis, Fiona R M; Benn, Christine S; Sie, Ali; Müller, Olaf; Aaby, Peter

2018-05-02

In addition to protecting against measles, measles vaccine (MV) may have beneficial nonspecific effects. We tested the effect of an additional early MV on mortality and measles antibody levels. Children aged 4-7 months at rural health and demographic surveillance sites in Burkina Faso and Guinea-Bissau were randomized 1:1 to an extra early standard dose of MV (Edmonston-Zagreb strain) or no extra MV 4 weeks after the third diphtheria-tetanus-pertussis-hepatitis B-Haemophilus influenzae type b vaccine. All children received routine MV at 9 months. We assessed mortality through home visits and compared mortality from enrollment to age 3 years using Cox proportional hazards models, censoring for subsequent nontrial MV. Subgroups of participants had blood sampled to assess measles antibody levels. Among 8309 children enrolled from 18 July 2012 to 3 December 2015, we registered 145 deaths (mortality rate: 16/1000 person-years). The mortality was lower than anticipated and did not differ by randomization group (hazard ratio, 1.05; 95% confidence interval, 0.75-1.46). At enrollment, 4% (16/447) of children in Burkina Faso and 21% (90/422) in Guinea-Bissau had protective measles antibody levels. By age 9 months, no measles-unvaccinated/-unexposed child had protective levels, while 92% (306/333) of early MV recipients had protective levels. At final follow-up, 98% (186/189) in the early MV group and 97% (196/202) in the control group had protective levels. Early MV did not reduce all-cause mortality. Most children were susceptible to measles infection at age 4-7 months and responded with high antibody levels to early MV. NCT01644721.

Measles Virus Persistent Infection of Human Induced Pluripotent Stem Cells.

PubMed

Naaman, Hila; Rabinski, Tatiana; Yizhak, Avi; Mizrahi, Solly; Avni, Yonat Shemer; Taube, Ran; Rager, Bracha; Weinstein, Yacov; Rall, Glenn; Gopas, Jacob; Ofir, Rivka

2018-02-01

In this study, we found that the measles virus (MV) can infect human-induced pluripotent stem cells (hiPSCs). Wild-type MV strains generally use human signaling lymphocyte activation molecule (SLAM; CD150) as a cellular receptor, while vaccine strains such as the Edmonston strain can use both CD150 and CD46 as receptors. It is not yet known how early in the embryonal differentiation stages these receptors are expressed. We established two hiPSCs (BGU-iPSCs and EMF-iPSCs) which express CD46 and CD150. Both cell types can be infected by MV to form persistent, noncytopathic cell lines that release infectious MV particles. Following MV persistent infection, BGU-iPSCs and EMF-iPSCs remain pluripotent and can differentiate in vitro into the three germ layers. This includes cells expressing the neuronal differentiation markers: NF68 and miRNA-124. Since the MV does not integrate into the cell's genome, it can be utilized as a vehicle to systematically introduce genes into iPSC, to dissect and to define factors regulating lineage differentiation.

An increasing, potentially measles-susceptible population over time after vaccination in Korea.

PubMed

Kang, Hae Ji; Han, Young Woo; Kim, Su Jin; Kim, You-Jin; Kim, A-Reum; Kim, Joo Ae; Jung, Hee-Dong; Eom, Hye Eun; Park, Ok; Kim, Sung Soon

2017-07-24

In Korea, measles occurs mainly in infants <12months of age, who are unvaccinated. In addition, vaccine populations, including adolescents and young adults, can become infected though importation. Thus, the question arises whether the current level of herd immunity in Korea is now insufficient for protecting against measles infection. Age-specific measles seroprevalence was evaluated by performing enzyme immunoassays and plaque reduction-neutralization tests on 3050 subjects aged 0-50years (birth cohort 1964-2014) and 480 subjects aged 2-30years (birth cohort 1984-2012). The overall seropositivity and measles antibody concentrations were 71.5% and 1366mIU/mL, respectively. Progressive decline in antibody levels and seropositivity were observed over time after vaccination in infants, adolescents, and young adults. The accumulation of potentially susceptible individuals in the population was confirmed by comparing data from 2010 and 2014 seroprevalence surveys. The statistical correlation between measles incidence and measles seronegativity was determined. Waning levels of measles antibodies with increasing time post-vaccination suggests that measles susceptibility is potentially increasing in Korea. This trend may be related to limitations of vaccine-induced immunity in the absence of natural boosting by the wild virus, compared to naturally acquired immunity triggered by measles infection. This study provides an important view into the current measles herd immunity in Korea. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Modulation of Re-initiation of Measles Virus Transcription at Intergenic Regions by PXD to NTAIL Binding Strength.

PubMed

Bloyet, Louis-Marie; Brunel, Joanna; Dosnon, Marion; Hamon, Véronique; Erales, Jenny; Gruet, Antoine; Lazert, Carine; Bignon, Christophe; Roche, Philippe; Longhi, Sonia; Gerlier, Denis

2016-12-01

Measles virus (MeV) and all Paramyxoviridae members rely on a complex polymerase machinery to ensure viral transcription and replication. Their polymerase associates the phosphoprotein (P) and the L protein that is endowed with all necessary enzymatic activities. To be processive, the polymerase uses as template a nucleocapsid made of genomic RNA entirely wrapped into a continuous oligomer of the nucleoprotein (N). The polymerase enters the nucleocapsid at the 3'end of the genome where are located the promoters for transcription and replication. Transcription of the six genes occurs sequentially. This implies ending and re-initiating mRNA synthesis at each intergenic region (IGR). We explored here to which extent the binding of the X domain of P (XD) to the C-terminal region of the N protein (NTAIL) is involved in maintaining the P/L complex anchored to the nucleocapsid template during the sequential transcription. Amino acid substitutions introduced in the XD-binding site on NTAIL resulted in a wide range of binding affinities as determined by combining protein complementation assays in E. coli and human cells and isothermal titration calorimetry. Molecular dynamics simulations revealed that XD binding to NTAIL involves a complex network of hydrogen bonds, the disruption of which by two individual amino acid substitutions markedly reduced the binding affinity. Using a newly designed, highly sensitive dual-luciferase reporter minigenome assay, the efficiency of re-initiation through the five measles virus IGRs was found to correlate with NTAIL/XD KD. Correlatively, P transcript accumulation rate and F/N transcript ratios from recombinant viruses expressing N variants were also found to correlate with the NTAIL to XD binding strength. Altogether, our data support a key role for XD binding to NTAIL in maintaining proper anchor of the P/L complex thereby ensuring transcription re-initiation at each intergenic region.

Modulation of Re-initiation of Measles Virus Transcription at Intergenic Regions by PXD to NTAIL Binding Strength

PubMed Central

Hamon, Véronique; Erales, Jenny; Bignon, Christophe; Roche, Philippe

2016-01-01

Measles virus (MeV) and all Paramyxoviridae members rely on a complex polymerase machinery to ensure viral transcription and replication. Their polymerase associates the phosphoprotein (P) and the L protein that is endowed with all necessary enzymatic activities. To be processive, the polymerase uses as template a nucleocapsid made of genomic RNA entirely wrapped into a continuous oligomer of the nucleoprotein (N). The polymerase enters the nucleocapsid at the 3’end of the genome where are located the promoters for transcription and replication. Transcription of the six genes occurs sequentially. This implies ending and re-initiating mRNA synthesis at each intergenic region (IGR). We explored here to which extent the binding of the X domain of P (XD) to the C-terminal region of the N protein (NTAIL) is involved in maintaining the P/L complex anchored to the nucleocapsid template during the sequential transcription. Amino acid substitutions introduced in the XD-binding site on NTAIL resulted in a wide range of binding affinities as determined by combining protein complementation assays in E. coli and human cells and isothermal titration calorimetry. Molecular dynamics simulations revealed that XD binding to NTAIL involves a complex network of hydrogen bonds, the disruption of which by two individual amino acid substitutions markedly reduced the binding affinity. Using a newly designed, highly sensitive dual-luciferase reporter minigenome assay, the efficiency of re-initiation through the five measles virus IGRs was found to correlate with NTAIL/XD KD. Correlatively, P transcript accumulation rate and F/N transcript ratios from recombinant viruses expressing N variants were also found to correlate with the NTAIL to XD binding strength. Altogether, our data support a key role for XD binding to NTAIL in maintaining proper anchor of the P/L complex thereby ensuring transcription re-initiation at each intergenic region. PMID:27936158

Epidemiology of two large measles virus outbreaks in Catalonia: what a difference the month of administration of the first dose of vaccine makes.

PubMed

Torner, Núria; Anton, Andres; Barrabeig, Irene; Lafuente, Sara; Parron, Ignasi; Arias, César; Camps, Neus; Costa, Josep; Martínez, Ana; Torra, Roser; Godoy, Pere; Minguell, Sofia; Ferrús, Glòria; Cabezas, Carmen; Domínguez, Ángela; Spain

2013-03-01

Measles cases in the European Region have been increasing in the last decade; this illustrates the challenge of what we are now encountering in the form of pediatric preventable diseases. In Catalonia, autochthonous measles was declared eliminated in the year 2000 as the result of high measles-mumps-rubella vaccine (MMR) coverage for first and second dose (15 mo and 4 y) since the mid-1990s. From then on, sporadic imported cases and small outbreaks appeared, until in 2006-2007 a large measles outbreak affecting mostly unvaccinated toddlers hit the Barcelona Health Region. Consequently, in January 2008, first dose administration of MMR was lowered from 15 to 12 mo of age. A new honeymoon period went by until the end of 2010, when several importations of cases triggered new sustained transmission of different wild measles virus genotypes, but this time striking young adults. The aim of this study is to show the effect of a change in MMR vaccination schedule policy, and the difference in age incidence and hospitalization rates of affected individuals between both outbreaks.   Epidemiologic data were obtained by case interviews and review of medical records. Samples for virological confirmation and genotyping of cases were collected as established in the Measles Elimination plan guidelines. Incidence rate (IR), rate ratio (RR) and their 95% CI and hospitalization rate (HR) by age group were determined. Statistic z was used for comparing proportions. Total number of confirmed cases was 305 in the 2010 outbreak and 381 in the 2006-2007 outbreak; mean age 20 y (SD 14.8 y; 3 mo to 51 y) vs. 15 mo (SD 13.1 y; 1 mo to 50 y). Highest proportion of cases was set in ≥ 25 y (47%) vs. 24.2% in 2006 (p < 0.001). Differences in IR for ≤ 15 mo (49/100,000 vs. 278.2/100,000; RR: 3,9; 95%CI 2,9-5.4) and in overall HR 29.8% vs. 15.7% were all statistically significant (p < 0.001). The change of the month of age for the administration of the first MMR dose proved successful to

Similar Antibody Levels in 3-Year-Old Children Vaccinated Against Measles, Mumps, and Rubella at the Age of 12 Months or 18 Months.

PubMed

Kontio, Mia; Palmu, Arto A; Syrjänen, Ritva K; Lahdenkari, Mika; Ruokokoski, Esa; Davidkin, Irja; Vaarala, Outi; Melin, Merit

2016-06-15

Measles-mumps-rubella (MMR) vaccinations have been offered to Finnish children at 14-18 months and 6 years of age. In May 2011, the recommended age for the first vaccine dose was lowered to 12 months because of the European measles epidemic. Fingertip capillary blood samples were collected from 3-year-old Finnish children vaccinated once with MMR vaccine at 11-19 months of age. The immunoglobulin G (IgG) antibodies to all 3 MMR antigens were measured with enzyme-linked immunosorbent assay. Neutralizing antibodies and the avidity of antibodies were measured for measles virus. From April through October 2013, 187 children were enrolled. Equally high proportions of the samples were seropositive for measles virus, mumps virus, or rubella virus antibodies, and there were no significant differences in the IgG antibody concentrations in children vaccinated at 11-13 months of age, compared with those vaccinated at 17-19 months of age. However, among children vaccinated at 11-13 months of age, boys had lower antibody concentrations than girls. Neutralizing measles virus antibody titers were above the threshold for protective immunity in all 78 samples analyzed. The measles virus antibody avidity indexes were high for all children. MMR induces similar antibody responses in 12-month-old children as compared to 18-month-old children, but in boys increasing age appears to improve the antibody responses. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

Rubella elimination programme strengthened through measles elimination programme in Catalonia.

PubMed

Domínguez, Angela; Torner, Nuria; Martínez, Ana; Costa, Josep; Plans, Pere; Ciruela, Pilar; Salleras, Lluís

2006-02-27

The drastic fall in rubella cases recorded in Catalonia from 1988 on, when the second dose of Measles-Mumps-Rubella (MMR) vaccine was implemented, and especially from 1998, when the measles elimination programme began, led to the introduction, in May 2002, of the rubella and congenital rubella syndrome elimination by 2005 programme. From May 2002 to May 2004, 13 suspected rubella cases were reported to the Statutory Disease Reporting System; of these, one postnatal case and one congenital rubella case were confirmed (15.4%), both being imported cases. Through the screening of viruses established in the measles elimination programme, 28 possible cases were analyzed and six (21.4%) confirmed imported postnatal rubella cases were detected. The small number and imported nature of the cases of rubella and the detection of the majority of the confirmed cases through the measles elimination programme, strongly suggests that both programmes should continue.

Measles Virus Defective Interfering RNAs Are Generated Frequently and Early in the Absence of C Protein and Can Be Destabilized by Adenosine Deaminase Acting on RNA-1-Like Hypermutations

PubMed Central

Pfaller, Christian K.; Mastorakos, George M.; Matchett, William E.; Ma, Xiao; Samuel, Charles E.

2015-01-01

ABSTRACT Defective interfering RNAs (DI-RNAs) of the viral genome can form during infections of negative-strand RNA viruses and outgrow full-length viral genomes, thereby modulating the severity and duration of infection. Here we document the frequent de novo generation of copy-back DI-RNAs from independent rescue events both for a vaccine measles virus (vac2) and for a wild-type measles virus (IC323) as early as passage 1 after virus rescue. Moreover, vaccine and wild-type C-protein-deficient (C-protein-knockout [CKO]) measles viruses generated about 10 times more DI-RNAs than parental virus, suggesting that C enhances the processivity of the viral polymerase. We obtained the nucleotide sequences of 65 individual DI-RNAs, identified breakpoints and reinitiation sites, and predicted their structural features. Several DI-RNAs possessed clusters of A-to-G or U-to-C transitions. Sequences flanking these mutation sites were characteristic of those favored by adenosine deaminase acting on RNA-1 (ADAR1), which catalyzes in double-stranded RNA the C-6 deamination of adenosine to produce inosine, which is recognized as guanosine, a process known as A-to-I RNA editing. In individual DI-RNAs the transitions were of the same type and occurred on both sides of the breakpoint. These patterns of mutations suggest that ADAR1 edits unencapsidated DI-RNAs that form double-strand RNA structures. Encapsidated DI-RNAs were incorporated into virus particles, which reduced the infectivity of virus stocks. The CKO phenotype was dominant: DI-RNAs derived from vac2 with a CKO suppressed the replication of vac2, as shown by coinfections of interferon-incompetent lymphatic cells with viruses expressing different fluorescent reporter proteins. In contrast, coinfection with a C-protein-expressing virus did not counteract the suppressive phenotype of DI-RNAs. IMPORTANCE Recombinant measles viruses (MVs) are in clinical trials as cancer therapeutics and as vectored vaccines for HIV-AIDS and

Wild-Type Measles Viruses with Non-Standard Genome Lengths

PubMed Central

Bankamp, Bettina; Liu, Chunyu; Rivailler, Pierre; Bera, Jayati; Shrivastava, Susmita; Kirkness, Ewen F.; Bellini, William J.; Rota, Paul A.

2014-01-01

The length of the single stranded, negative sense RNA genome of measles virus (MeV) is highly conserved at 15,894 nucleotides (nt). MeVs can be grouped into 24 genotypes based on the highly variable 450 nucleotides coding for the carboxyl-terminus of the nucleocapsid protein (N-450). Here, we report the genomic sequences of 2 wild-type viral isolates of genotype D4 with genome lengths of 15,900 nt. Both genomes had a 7 nt insertion in the 3′ untranslated region (UTR) of the matrix (M) gene and a 1 nt deletion in the 5′ UTR of the fusion (F) gene. The net gain of 6 nt complies with the rule-of-six required for replication competency of the genomes of morbilliviruses. The insertions and deletion (indels) were confirmed in a patient sample that was the source of one of the viral isolates. The positions of the indels were identical in both viral isolates, even though epidemiological data and the 3 nt differences in N-450 between the two genomes suggested that the viruses represented separate chains of transmission. Identical indels were found in the M-F intergenic regions of 14 additional genotype D4 viral isolates that were imported into the US during 2007–2010. Viral isolates with and without indels produced plaques of similar size and replicated efficiently in A549/hSLAM and Vero/hSLAM cells. This is the first report of wild-type MeVs with genome lengths other than 15,894 nt and demonstrates that the length of the M-F UTR of wild-type MeVs is flexible. PMID:24748123

Polio and Measles Down the Drain: Environmental Enterovirus Surveillance in the Netherlands, 2005 to 2015.

PubMed

Benschop, Kimberley S M; van der Avoort, Harrie G; Jusic, Edin; Vennema, Harry; van Binnendijk, Rob; Duizer, Erwin

2017-07-01

Polioviruses (PVs) are members of the genus Enterovirus In the Netherlands, the exclusion of PV circulation is based on clinical enterovirus (EV) surveillance (CEVS) of EV-positive cases and routine environmental EV surveillance (EEVS) conducted on sewage samples collected in the region of the Netherlands where vaccination coverage is low due to religious reasons. We compared the EEVS data to those of the CEVS to gain insight into the relevance of EEVS for poliovirus and nonpolio enterovirus surveillance. Following the polio outbreak in Syria, EEVS was performed at the primary refugee center in Ter Apel in the Netherlands, and data were compared to those of CEVS and EEVS. Furthermore, we assessed the feasibility of poliovirus detection by EEVS using measles virus detection in sewage during a measles outbreak as a proxy. Two Sabin-like PVs were found in routine EEVS, 11 Sabin-like PVs were detected in the CEVS, and one Sabin-like PV was found in the Ter Apel sewage. We observed significant differences between the three programs regarding which EVs were found. In 6 sewage samples collected during the measles outbreak in 2013, measles virus RNA was detected in regions where measles cases were identified. In conclusion, we detected PVs, nonpolio EVs, and measles virus in sewage and showed that environmental surveillance is useful for poliovirus detection in the Netherlands, where live oral poliovirus vaccine is not used and communities with lower vaccination coverage exist. EEVS led to the detection of EV types not seen in the CEVS, showing that EEVS is complementary to CEVS. IMPORTANCE We show that environmental enterovirus surveillance complements clinical enterovirus surveillance for poliovirus detection, or exclusion, and for nonpolio enterovirus surveillance. Even in the presence of adequate surveillance, only a very limited number of Sabin-like poliovirus strains were detected in a 10-year period, and no signs of transmission of oral polio vaccine (OPV) strains

Polio and Measles Down the Drain: Environmental Enterovirus Surveillance in the Netherlands, 2005 to 2015

PubMed Central

Benschop, Kimberley S. M.; van der Avoort, Harrie G.; Jusic, Edin; Vennema, Harry; van Binnendijk, Rob

2017-01-01

ABSTRACT Polioviruses (PVs) are members of the genus Enterovirus. In the Netherlands, the exclusion of PV circulation is based on clinical enterovirus (EV) surveillance (CEVS) of EV-positive cases and routine environmental EV surveillance (EEVS) conducted on sewage samples collected in the region of the Netherlands where vaccination coverage is low due to religious reasons. We compared the EEVS data to those of the CEVS to gain insight into the relevance of EEVS for poliovirus and nonpolio enterovirus surveillance. Following the polio outbreak in Syria, EEVS was performed at the primary refugee center in Ter Apel in the Netherlands, and data were compared to those of CEVS and EEVS. Furthermore, we assessed the feasibility of poliovirus detection by EEVS using measles virus detection in sewage during a measles outbreak as a proxy. Two Sabin-like PVs were found in routine EEVS, 11 Sabin-like PVs were detected in the CEVS, and one Sabin-like PV was found in the Ter Apel sewage. We observed significant differences between the three programs regarding which EVs were found. In 6 sewage samples collected during the measles outbreak in 2013, measles virus RNA was detected in regions where measles cases were identified. In conclusion, we detected PVs, nonpolio EVs, and measles virus in sewage and showed that environmental surveillance is useful for poliovirus detection in the Netherlands, where live oral poliovirus vaccine is not used and communities with lower vaccination coverage exist. EEVS led to the detection of EV types not seen in the CEVS, showing that EEVS is complementary to CEVS. IMPORTANCE We show that environmental enterovirus surveillance complements clinical enterovirus surveillance for poliovirus detection, or exclusion, and for nonpolio enterovirus surveillance. Even in the presence of adequate surveillance, only a very limited number of Sabin-like poliovirus strains were detected in a 10-year period, and no signs of transmission of oral polio vaccine (OPV

Measles elimination in Italy: projected impact of the National Elimination Plan.

PubMed Central

Manfredi, P.; Williams, J. R.; Ciofi Degli Atti, M. L.; Salmaso, S.

2005-01-01

A mathematical model was used to evaluate the impact of the Italian Measles National Elimination Plan (NEP), and possible sources of failure in achieving its targets. The model considered two different estimates of force of infection, and the possible effect on measles transmission of the current Italian demographic situation, characterized by a below-replacement fertility. Results suggest that reaching all NEP targets will allow measles elimination to be achieved. In addition, the model suggests that achieving elimination by reaching a 95 % first-dose coverage appears unlikely; and that conducting catch-up activities, reaching high vaccination coverage, could interrupt virus circulation, but could not prevent the infection re-emerging before 2020. Also, the introduction of the second dose of measles vaccine seems necessary for achieving and maintaining elimination. Furthermore, current Italian demography appears to be favourable for reaching elimination. PMID:15724715

Highly sensitive and robust peroxidase-like activity of Au-Pt core/shell nanorod-antigen conjugates for measles virus diagnosis.

PubMed

Long, Lin; Liu, Jianbo; Lu, Kaishun; Zhang, Tao; Xie, Yunqing; Ji, Yinglu; Wu, Xiaochun

2018-05-02

As a promising candidate for artificial enzymes, catalytically active nanomaterials show several advantages over natural enzymes, such as controlled synthesis at low cost, tunability of catalytic activities, and high stability under stringent conditions. Rod-shaped Au-Pt core/shell nanoparticles (Au@Pt NRs), prepared by Au nanorod-mediated growth, exhibit peroxidase-like activities and could serve as an inexpensive replacement for horseradish peroxidase, with potential applications in various bio-detections. The determination of measles virus is accomplished by a capture-enzyme-linked immunosorbent assay (ELISA) using Au@Pt NR-antigen conjugates. Based on the enhanced catalytic properties of this nanozyme probe, a linear response was observed up to 10 ng/mL measles IgM antibodies in human serum, which is 1000 times more sensitive than commercial ELISA. Hence, these findings provide positive proof of concept for the potential of Au@Pt NR-antigen conjugates in the development of colorimetric biosensors that are simple, robust, and cost-effective.

Tyrosine 110 in the measles virus phosphoprotein is required to block STAT1 phosphorylation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Devaux, Patricia; Messling, Veronika von; Songsungthong, Warangkhana

2007-03-30

The measles virus (MV) P gene encodes three proteins: P, an essential polymerase cofactor, and C and V, which have multiple functions including immune evasion. We show here that the MV P protein also contributes to immune evasion, and that tyrosine 110 is required to block nuclear translocation of the signal transducer and activator of transcription factors (STAT) after interferon type I treatment. In particular, MV P inhibits STAT1 phosphorylation. This is shown not only by transient expression but also by reverse genetic analyses based on a new functional infectious cDNA derived from a MV vaccine vial (Moraten strain). Ourmore » study also identifies a conserved sequence around P protein tyrosine 110 as a candidate interaction site with a cellular protein.« less

Annexin A2 Mediates the Localization of Measles Virus Matrix Protein at the Plasma Membrane.

PubMed

Koga, Ritsuko; Kubota, Marie; Hashiguchi, Takao; Yanagi, Yusuke; Ohno, Shinji

2018-02-28

Annexins are a family of structurally related proteins that bind negatively charged membrane phospholipids in a Ca 2+ -dependent manner. Annexin A2 (AnxA2), a member of the family, has been implicated in a variety of cellular functions including the organization of membrane domains, vesicular trafficking and cell-cell adhesion. AnxA2 generally forms the heterotetrameric complex with a small Ca 2+ -binding protein S100A10. Measles virus (MV), a member of the family Paramyxoviridae , is an enveloped virus with a nonsegmented negative strand RNA genome. Knockdown of AnxA2 greatly reduced MV growth in cells, without affecting its entry and viral RNA production. In MV-infected, AnxA2-knockdown cells, the expression level of the matrix (M) protein, but not other viral proteins, was reduced compared with that in control cells, and the distribution of the M protein at the plasma membrane was decreased. The M protein lines the inner surface of the envelope and plays an important role in virus assembly by connecting the nucleocapsid to the envelope proteins. The M protein bound to AnxA2 independently of AnxA2's phosphorylation or its association with S100A10, and was co-localized with AnxA2 within cells. Truncation of the N-terminal 10 amino acid residues, but not the N-terminal 5 residues, compromised the ability of the M protein to interact with AnxA2 and localize at the plasma membrane. These results indicate that AnxA2 mediates the localization of the MV M protein at the plasma membrane by interacting with its N-terminal region (especially residues at positions 6-10), thereby aiding in MV assembly. IMPORTANCE Measles virus (MV) is an important human pathogen, still claiming ∼ 100,000 lives per year despite the presence of effective vaccines, and causes occasional outbreaks even in developed countries. Replication of viruses largely relies on the functions of host cells. Our study revealed that the reduction of the host protein annexin A2 compromises the replication of

High Concentrations of Measles Neutralizing Antibodies and High-Avidity Measles IgG Accurately Identify Measles Reinfection Cases

PubMed Central

Rota, Jennifer S.; Hickman, Carole J.; Mercader, Sara; Redd, Susan; McNall, Rebecca J.; Williams, Nobia; McGrew, Marcia; Walls, M. Laura; Rota, Paul A.; Bellini, William J.

2016-01-01

In the United States, approximately 9% of the measles cases reported from 2012 to 2014 occurred in vaccinated individuals. Laboratory confirmation of measles in vaccinated individuals is challenging since IgM assays can give inconclusive results. Although a positive reverse transcription (RT)-PCR assay result from an appropriately timed specimen can provide confirmation, negative results may not rule out a highly suspicious case. Detection of high-avidity measles IgG in serum samples provides laboratory evidence of a past immunologic response to measles from natural infection or immunization. High concentrations of measles neutralizing antibody have been observed by plaque reduction neutralization (PRN) assays among confirmed measles cases with high-avidity IgG, referred to here as reinfection cases (RICs). In this study, we evaluated the utility of measuring levels of measles neutralizing antibody to distinguish RICs from noncases by receiver operating characteristic curve analysis. Single and paired serum samples with high-avidity measles IgG from suspected measles cases submitted to the CDC for routine surveillance were used for the analysis. The RICs were confirmed by a 4-fold rise in PRN titer or by RT-quantitative PCR (RT-qPCR) assay, while the noncases were negative by both assays. Discrimination accuracy was high with serum samples collected ≥3 days after rash onset (area under the curve, 0.953; 95% confidence interval [CI], 0.854 to 0.993). Measles neutralizing antibody concentrations of ≥40,000 mIU/ml identified RICs with 90% sensitivity (95% CI, 74 to 98%) and 100% specificity (95% CI, 82 to 100%). Therefore, when serological or RT-qPCR results are unavailable or inconclusive, suspected measles cases with high-avidity measles IgG can be confirmed as RICs by measles neutralizing antibody concentrations of ≥40,000 mIU/ml. PMID:27335386

Multicenter Safety and Immunogenicity Trial of an Attenuated Measles Vaccine for NHP

PubMed Central

Yee, JoAnn L; McChesney, Michael B; Christe, Kari L

2015-01-01

Measles is a highly contagious viral disease in NHP. The infection can range from asymptomatic to rapidly fatal, resulting in significant morbidity and mortality in captive populations. In addition to appropriate quarantine practices, restricted access, the immunization of all personnel in contact with NHP, and the wearing of protective clothing including face masks, measles immunization further reduces the infection risk. Commercially available measles vaccines are effective for use in NHP, but interruptions in their availability have prevented the implementation of ongoing, consistent vaccination programs. This need for a readily available vaccine led us to perform a broad, multicenter safety and immunogenicity study of another candidate vaccine, MVac (Serum Institute of India), a monovalent measles vaccine derived from live Edmonston–Zagreb strain virus that had been attenuated after 22 passages on human diploid cells. PMID:26473350

Utility of a stressed-SNP real-time PCR assay for the rapid identification of measles vaccine strain in patient samples.

PubMed

Tran, Thomas; Kostecki, Renata; Catton, Michael; Druce, Julian

2018-05-09

Rapid differentiation of wild-type measles virus from measles vaccine strains is crucial during a measles outbreak and in a measles elimination setting. A real-time RT-PCR for the rapid detection of measles vaccine strains was developed with high specificity and greater sensitivity than when compared to traditional measles genotyping methods. The "stressed" minor grove binder TaqMan probe design approach achieves specificity to vaccine strains only, without compromising sensitivity. This assay has proven to be extremely useful in outbreak settings, without requiring sequence genotyping, for over 4 years at the Regional Measles Reference Laboratory for the Western Pacific Region. Copyright © 2018 Tran et al.

Role of health determinants in a measles outbreak in Ecuador: a case-control study with aggregated data.

PubMed

Rivadeneira, María F; Bassanesi, Sérgio L; Fuchs, Sandra C

2018-02-20

In 2011-2012, an outbreak of measles occurred in Ecuador. This study sought to ascertain which population characteristics were associated. Case-control study of aggregate data. The unit of analysis was the parish (smallest geographic division). The national communicable disease surveillance database was used to identify 52 case parishes (with at least one confirmed case of measles) and 972 control parishes (no cases of measles). A hierarchical model was used to determine the association of measles with population characteristics and access to health care. Case parishes were mostly urban and had a higher proportion of children under 1 year of age, heads of household with higher educational attainment, larger indigenous population, lower rates of measles immunization, and lower rates of antenatal care visit attendance. On multivariate analysis, associations were found with educational attainment of head of household ≥8 years (OR: 0.29; 95%CI 0.15-0.57) and ≥1.4% indigenous population (OR: 3.29; 95%CI 1.63-6.68). Antenatal care visit attendance had a protective effect against measles (OR: 0.98; 95%CI 0.97-0.99). Measles vaccination was protective of the outbreak (OR: 0.97; 95%CI 0.95-0.98). The magnitude of these associations was modest, but represents the effect of single protective factors, capable of acting at the population level regardless of socioeconomic, biological, and environmental confounding factors. In Ecuador, the parishes with the highest percentage of indigenous populations and those with the lowest vaccination coverage were the most vulnerable during the measles outbreak.

New Insights into the Hendra Virus Attachment and Entry Process from Structures of the Virus G Glycoprotein and Its Complex with Ephrin-B2

DTIC Science & Technology

2012-11-05

organization of measles virus fusion complexes. J Virol 83: 10480–10493. 24. Bishop KA, Hickey AC, Khetawat D, Patch JR, Bossart KN, et al. (2008...its receptor, sialyllactose. Structure 13: 803–815. 38. Colf LA, Juo ZS, Garcia KC (2007) Structure of the measles virus hemagglutinin. Nat Struct Mol...Biol 14: 1227–1228. 39. Hashiguchi T, Kajikawa M, Maita N, Takeda M, Kuroki K, et al. (2007) Crystal structure of measles virus hemagglutinin provides

A unique measles B3 cluster in the United Kingdom and the Netherlands linked to air travel and transit at a large international airport, February to April 2014.

PubMed

Nic Lochlainn, Laura; Mandal, Sema; de Sousa, Rita; Paranthaman, Karthik; van Binnendijk, Rob; Ramsay, Mary; Hahné, Susan; Brown, Kevin E

2016-01-01

This report describes a joint measles outbreak investigation between public health officials in the United Kingdom (UK) and the Netherlands following detection of a measles cluster with a unique measles virus strain. From 1 February to 30 April 2014, 33 measles cases with a unique measles virus strain of genotype B3 were detected in the UK and the Netherlands, of which nine secondary cases were epidemiologically linked to an infectious measles case travelling from the Philippines. Through a combination of epidemiological investigation and sequence analysis, we found that measles transmission occurred in flight, airport and household settings. The secondary measles cases included airport workers, passengers in transit at the same airport or travelling on the same flight as the infectious case and also household contacts. This investigation highlighted the particular importance of measles genotyping in identifying transmission networks and the need to improve vaccination, public health follow-up and management of travellers and airport staff exposed to measles.

Computational Analysis of the Interaction Energies between Amino Acid Residues of the Measles Virus Hemagglutinin and Its Receptors.

PubMed

Xu, Fengqi; Tanaka, Shigenori; Watanabe, Hirofumi; Shimane, Yasuhiro; Iwasawa, Misako; Ohishi, Kazue; Maruyama, Tadashi

2018-05-03

Measles virus (MV) causes an acute and highly devastating contagious disease in humans. Employing the crystal structures of three human receptors, signaling lymphocyte-activation molecule (SLAM), CD46, and Nectin-4, in complex with the measles virus hemagglutinin (MVH), we elucidated computationally the details of binding energies between the amino acid residues of MVH and those of the receptors with an ab initio fragment molecular orbital (FMO) method. The calculated inter-fragment interaction energies (IFIEs) revealed a number of significantly interacting amino acid residues of MVH that played essential roles in binding to the receptors. As predicted from previously reported experiments, some important amino-acid residues of MVH were shown to be common but others were specific to interactions with the three receptors. Particularly, some of the (non-polar) hydrophobic residues of MVH were found to be attractively interacting with multiple receptors, thus indicating the importance of the hydrophobic pocket for intermolecular interactions (especially in the case of Nectin-4). In contrast, the electrostatic interactions tended to be used for specific molecular recognition. Furthermore, we carried out FMO calculations for in silico experiments of amino acid mutations, finding reasonable agreements with virological experiments concerning the substitution effect of residues. Thus, the present study demonstrates that the electron-correlated FMO method is a powerful tool to search exhaustively for amino acid residues that contribute to interactions with receptor molecules. It is also applicable for designing inhibitors of MVH and engineered MVs for cancer therapy.

Immunogenic Subviral Particles Displaying Domain III of Dengue 2 Envelope Protein Vectored by Measles Virus

PubMed Central

Harahap-Carrillo, Indira S.; Ceballos-Olvera, Ivonne; Reyes-del Valle, Jorge

2015-01-01

Vaccines against dengue virus (DV) are commercially nonexistent. A subunit vaccination strategy may be of value, especially if a safe viral vector acts as biologically active adjuvant. In this paper, we focus on an immunoglobulin-like, independently folded domain III (DIII) from DV 2 envelope protein (E), which contains epitopes that elicits highly specific neutralizing antibodies. We modified the hepatitis B small surface antigen (HBsAg, S) in order to display DV 2 DIII on a virus-like particle (VLP), thus generating the hybrid antigen DIII-S. Two varieties of measles virus (MV) vectors were developed to express DIII-S. The first expresses the hybrid antigen from an additional transcription unit (ATU) and the second additionally expresses HBsAg from a separate ATU. We found that this second MV vectoring the hybrid VLPs displaying DIII-S on an unmodified HBsAg scaffold were immunogenic in MV-susceptible mice (HuCD46Ge-IFNarko), eliciting robust neutralizing responses (averages) against MV (1:1280 NT90), hepatitis B virus (787 mIU/mL), and DV2 (1:160 NT50) in all of the tested animals. Conversely, the MV vector expressing only DIII-S induced immunity against MV alone. In summary, DV2 neutralizing responses can be generated by displaying E DIII on a scaffold of HBsAg-based VLPs, vectored by MV. PMID:26350592

[Drug clinics. Drug of the month. A new measles-rubella-mumps vaccine (Priorix)].

PubMed

Senterre, J

1999-02-01

A novel measles-mumps-rubella vaccine (Priorix) has been marketed by SmithKline Beecham. It contains live attenuated virus with measles and mumps strains slightly different from those present in MMR VAX (Pasteur Merieux MSD). The indications and contraindications are similar for both vaccines. Immunogenicity is also equivalent as well as general reactogenicity. By contrast local symptoms were reported significantly less frequently after Priorix.

Combination of Vaccine-Strain Measles and Mumps Viruses Enhances Oncolytic Activity against Human Solid Malignancies.

PubMed

Son, Ho Anh; Zhang, LiFeng; Cuong, Bui Khac; Van Tong, Hoang; Cuong, Le Duy; Hang, Ngo Thu; Nhung, Hoang Thi My; Yamamoto, Naoki; Toan, Nguyen Linh

2018-02-07

Oncolytic measles and mumps viruses (MeV, MuV) have a potential for anti-cancer treatment. We examined the anti-tumor activity of MeV, MuV, and MeV-MuV combination (MM) against human solid malignancies (HSM). MeV, MuV, and MM targeted and significantly killed various cancer cell lines of HSM but not normal cells. MM demonstrated a greater anti-tumor effect and prolonged survival in a human prostate cancer xenograft tumor model compared to MeV and MuV. MeV, MuV, and MM significantly induced the expression of immunogenic cell death markers and enhanced spleen-infiltrating immune cells. In conclusion, MM combination significantly improves the treatment of human solid malignancies.

Predicting and comparing long-term measles antibody profiles of different immunization policies.

PubMed

Lee, M S; Nokes, D J

2001-01-01

Measles outbreaks are infrequent and localized in areas with high coverage of measles vaccine. The need is to assess long-term effectiveness of coverage. Since 1991, no measles epidemic affecting the whole island has occurred in Taiwan, China. Epidemiological models are developed to predict the long-term measles antibody profiles and compare the merits of different immunization policies on the island. The current measles immunization policy in Taiwan, China, is 1 dose of measles vaccine at 9 months of age and 1 dose of measles, mumps and rubella (MMR) vaccine at 15 months of age, plus a 'mop-up' of MMR-unvaccinated schoolchildren at 6 years of age. Refinements involve a change to a two-dose strategy. Five scenarios based on different vaccination strategies are compared. The models are analysed using Microsoft Excel. First, making the assumption that measles vaccine-induced immunity will not wane, the predicted measles IgG seroprevalences in preschool children range from 81% (lower bound) to 94% (upper bound) and in schoolchildren reach 97-98% in all strategy scenarios. Results are dependent on the association of vaccine coverage between the first and second dose of vaccine. Second, if it is assumed that vaccine-induced antibody titres decay, the long-term measles seroprevalence will depend on the initial titres post vaccination, decay rates of antibody titres and cut-off of seropositivity. If MMR coverage at 12 months of age can reach > 90%, it would be worth changing the current policy to 2 doses at 12 months and 6 years of age to induce higher antibody titres. These epidemiological models could be applied wherever a similar stage of measles elimination has been reached.

The epidemiological and serological characteristics of measles in Dongguan, China, 2005–2014

PubMed Central

Han, Ke; Chen, Shaoli; Tang, Cuifei; Wen, Jinjun; Li, Jingquan; Ni, Jindong; Zheng, Xueli

2016-01-01

ABSTRACT This study examined the epidemiological and serological characteristics of measles in Dongguan, China. From 2005 to 2014, a total of 8,224 measles cases were reported in Dongguan, 33.5% of which were aged <1 y and 30.6% >14 y. From 2005 to 2014, the proportion of the <1 y measles cases increased year by year from 24.3% to 47.9%. Of the cases aged ≥8 months (n = 6,768 cases), only 11.6% had been immunized with at least one dose of measles vaccine. Of the 2,213 cases who had never been immunized with measles vaccine, immigrants accounted for 82.4%. 52.4% of the measles cases were diagnosed with pneumonia, and 12 cases died from respiratory failure. Seroprevalence rate in women and their newborns was 86.0% and 82.5%, respectively. Measurement of serum measles antibody levels for infants aged less than 8 months indicated that seroprevalence rate dramatically declined from 97.3% at birth to 9.3% and 13.2% at 6- and 7- month old. The existence of a sufficient pool of unvaccinated people (especially immigrants) and decreased level of passively transferred measles antibodies in infants from vaccinated mothers contributed to the sustained transmission observed in Dongguan. In addition to high routine vaccination coverage, new strategies and innovations for measles vaccination are needed to eliminate measles. PMID:27003239

Quantification of measles, mumps and rubella viruses using real-time quantitative TaqMan-based RT-PCR assay.

PubMed

Ammour, Y; Faizuloev, E; Borisova, T; Nikonova, A; Dmitriev, G; Lobodanov, S; Zverev, V

2013-01-01

In this study, a rapid quantitative method using TaqMan-based real-time reverse transcription-polymerase chain reaction (qPCR-RT) has been developed for estimating the titers of measles, mumps and rubella (MMR) viruses in infected cell culture supernatants. The qPCR-RT assay was demonstrated to be a specific, sensitive, efficient and reproducible method. For MMR viral samples obtained during MMR viral propagations in Vero cells at a different multiplicity of infection, titers determined by the qPCR-RT assay have been compared with estimates of infectious virus obtained by a traditional commonly used method for MMR viruses - 50% cell culture infective dose (CCID(50)) assay, in paired samples. Pearson analysis evidenced a significant correlation between both methods for a certain period after viral inoculation. Furthermore, the established qPCR-RT assay was faster and less-laborious. The developed method could be used as an alternative method or a supplementary tool for the routine titer estimation during MMR vaccine production. Copyright © 2012 Elsevier B.V. All rights reserved.

Reduced immunity to measles in adults with major depressive disorder.

PubMed

Ford, Bart N; Yolken, Robert H; Dickerson, Faith B; Teague, T Kent; Irwin, Michael R; Paulus, Martin P; Savitz, Jonathan

2018-03-19

Depression can impair the immunogenicity of vaccine administration in adults. Whereas many vaccinations are administered in childhood, it is not known whether adolescent or adult onset depression is associated with impairments in the maintenance of protection of childhood vaccines. This study tested the hypothesis that individuals with adolescent or adult onset mood disorders would display compromised immunity to measles, a target of childhood vaccination. IgG antibodies to measles were quantified using a solid phase immunoassay in volunteers with bipolar disorder (BD, n = 64, mean age of onset = 16.6 ± 5.6), currently depressed individuals with major depressive disorder (cMDD, n = 85, mean age of onset = 17.9 ± 7.0), remitted individuals with a history of MDD (rMDD, n = 82, mean age of onset = 19.2 ± 8.6), and non-depressed comparison controls (HC, n = 202), all born after the introduction of the measles vaccine in the USA in 1963. Relative to HC, both the cMDD group (p = 0.021, adjusted odds ratios (OR) = 0.47, confidence interval (CI) = 0.24-0.90), and the rMDD group (p = 0.038, adjusted OR = 0.50, CI = 0.26-0.97) were less likely to test seropositive for measles. Compared with unmedicated MDD participants, currently medicated MDD participants had a longer lifetime duration of illness and were less likely to test seropositive for measles. Individuals with adolescent or adult onset MDD are less likely to test seropositive for measles. Because lower IgG titers are associated with increased risk of measles infection, MDD may increase the risk and severity of infection possibly because of impaired maintenance of vaccine-related protection from measles.

Measles Virus Defective Interfering RNAs Are Generated Frequently and Early in the Absence of C Protein and Can Be Destabilized by Adenosine Deaminase Acting on RNA-1-Like Hypermutations.

PubMed

Pfaller, Christian K; Mastorakos, George M; Matchett, William E; Ma, Xiao; Samuel, Charles E; Cattaneo, Roberto

2015-08-01

Defective interfering RNAs (DI-RNAs) of the viral genome can form during infections of negative-strand RNA viruses and outgrow full-length viral genomes, thereby modulating the severity and duration of infection. Here we document the frequent de novo generation of copy-back DI-RNAs from independent rescue events both for a vaccine measles virus (vac2) and for a wild-type measles virus (IC323) as early as passage 1 after virus rescue. Moreover, vaccine and wild-type C-protein-deficient (C-protein-knockout [CKO]) measles viruses generated about 10 times more DI-RNAs than parental virus, suggesting that C enhances the processivity of the viral polymerase. We obtained the nucleotide sequences of 65 individual DI-RNAs, identified breakpoints and reinitiation sites, and predicted their structural features. Several DI-RNAs possessed clusters of A-to-G or U-to-C transitions. Sequences flanking these mutation sites were characteristic of those favored by adenosine deaminase acting on RNA-1 (ADAR1), which catalyzes in double-stranded RNA the C-6 deamination of adenosine to produce inosine, which is recognized as guanosine, a process known as A-to-I RNA editing. In individual DI-RNAs the transitions were of the same type and occurred on both sides of the breakpoint. These patterns of mutations suggest that ADAR1 edits unencapsidated DI-RNAs that form double-strand RNA structures. Encapsidated DI-RNAs were incorporated into virus particles, which reduced the infectivity of virus stocks. The CKO phenotype was dominant: DI-RNAs derived from vac2 with a CKO suppressed the replication of vac2, as shown by coinfections of interferon-incompetent lymphatic cells with viruses expressing different fluorescent reporter proteins. In contrast, coinfection with a C-protein-expressing virus did not counteract the suppressive phenotype of DI-RNAs. Recombinant measles viruses (MVs) are in clinical trials as cancer therapeutics and as vectored vaccines for HIV-AIDS and other infectious

Supplementary immunization activities to achieve measles elimination: experience of the European Region.

PubMed

Khetsuriani, Nino; Deshevoi, Sergei; Goel, Ajay; Spika, John; Martin, Rebecca; Emiroglu, Nedret

2011-07-01

Supplementary immunization activities (SIAs) using measles-containing vaccine (MCV) have had a substantial impact on reducing mortality associated with measles worldwide. To assess impact of SIAs on measles incidence in the World Health Organization European Region and their role at the final stages of measles elimination efforts in Europe, we reviewed information on SIAs, measles surveillance, and routine vaccination coverage during 2000-2009. During 2000-2009, >57 million persons received MCV through SIAs in 16 countries. The Region primarily focused on catch-up campaigns with wider target age groups than in other regions and subsequently relied on routine vaccination rather than periodic follow-up SIAs for the second MCV dose. In addition, the concept of SIAs has been expanded from short-term (<30 days) mass campaigns implemented in other regions to incorporate vaccination efforts over longer periods and outbreak response vaccination. In 2009, 14 of 16 countries that conducted SIAs reported no measles cases or <1 case per 1,000,000 population, reflecting the post-SIA decrease in incidence. SIAs have made a substantial contribution to the success of measles elimination efforts and will likely remain an important strategy for interrupting measles virus transmission in the European Region, although specific approaches will vary by country. Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2011.

Neurokinin-1 enables measles virus trans-synaptic spread in neurons

DOE Office of Scientific and Technical Information (OSTI.GOV)

Makhortova, Nina R.; Askovich, Peter; Patterson, Catherine E.

2007-05-25

Measles virus (MV), a morbillivirus that remains a significant human pathogen, can infect the central nervous system, resulting in rare but often fatal diseases, such as subacute sclerosing panencephalitis. Previous work demonstrated that MV was transmitted trans-synaptically and that, while a cellular receptor for the hemagglutinin (H) protein was required for MV entry, it was dispensable for subsequent cell-to-cell spread. Here, we explored what role the other envelope protein, fusion (F), played in trans-synaptic transport. We made the following observations: (1) MV-F expression in infected neurons was similar to that seen in infected fibroblasts; (2) fusion inhibitory peptide (FIP), anmore » inhibitor of MV fusion, prevented both infection and spread in primary neurons; (3) Substance P, a neurotransmitter with the same active site as FIP, also blocked neuronal MV spread; and (4) both genetic deletion and pharmacological inhibition of the Substance P receptor, neurokinin-1 (NK-1), reduced infection of susceptible mice. Together, these data implicate a role for NK-1 in MV CNS infection and spread, perhaps serving as an MV-F receptor or co-receptor on neurons.« less

The genetic basis for interindividual immune response variation to measles vaccine: new understanding and new vaccine approaches

PubMed Central

Haralambieva, Iana H; Ovsyannikova, Inna G; Pankratz, V Shane; Kennedy, Richard B; Jacobson, Robert M; Poland, Gregory A

2013-01-01

The live-attenuated measles vaccine is effective, but measles outbreaks still occur in vaccinated populations. This warrants elucidation of the determinants of measles vaccine-induced protective immunity. Interindividual variability in markers of measles vaccine-induced immunity, including neutralizing antibody levels, is regulated in part by host genetic factor variations. This review summarizes recent advances in our understanding of measles vaccine immunogenetics relative to the perspective of developing better measles vaccines. Important genetic regulators of measles vaccine-induced immunity, such as HLA class I and HLA class II genotypes, single nucleotide polymorphisms in cytokine/cytokine receptor genes (IL12B, IL12RB1, IL2, IL10) and the cell surface measles virus receptor CD46 gene, have been identified and independently replicated. New technologies present many opportunities for identification of novel genetic signatures and genetic architectures. These findings help explain a variety of immune response-related phenotypes and promote a new paradigm of ‘vaccinomics’ for novel vaccine development. PMID:23256739

In Vivo Efficacy of Measles Virus Fusion Protein-Derived Peptides Is Modulated by the Properties of Self-Assembly and Membrane Residence

PubMed Central

Figueira, T. N.; Palermo, L. M.; Veiga, A. S.; Huey, D.; Alabi, C. A.; Santos, N. C.; Welsch, J. C.; Mathieu, C.; Niewiesk, S.; Moscona, A.

2016-01-01

ABSTRACT Measles virus (MV) infection is undergoing resurgence and remains one of the leading causes of death among young children worldwide despite the availability of an effective measles vaccine. MV infects its target cells by coordinated action of the MV hemagglutinin (H) and fusion (F) envelope glycoproteins; upon receptor engagement by H, the prefusion F undergoes a structural transition, extending and inserting into the target cell membrane and then refolding into a postfusion structure that fuses the viral and cell membranes. By interfering with this structural transition of F, peptides derived from the heptad repeat (HR) regions of F can inhibit MV infection at the entry stage. In previous work, we have generated potent MV fusion inhibitors by dimerizing the F-derived peptides and conjugating them to cholesterol. We have shown that prophylactic intranasal administration of our lead fusion inhibitor efficiently protects from MV infection in vivo. We show here that peptides tagged with lipophilic moieties self-assemble into nanoparticles until they reach the target cells, where they are integrated into cell membranes. The self-assembly feature enhances biodistribution and the half-life of the peptides, while integration into the target cell membrane increases fusion inhibitor potency. These factors together modulate in vivo efficacy. The results suggest a new framework for developing effective fusion inhibitory peptides. IMPORTANCE Measles virus (MV) infection causes an acute illness that may be associated with infection of the central nervous system (CNS) and severe neurological disease. No specific treatment is available. We have shown that fusion-inhibitory peptides delivered intranasally provide effective prophylaxis against MV infection. We show here that specific biophysical properties regulate the in vivo efficacy of MV F-derived peptides. PMID:27733647

In Vivo Efficacy of Measles Virus Fusion Protein-Derived Peptides Is Modulated by the Properties of Self-Assembly and Membrane Residence.

PubMed

Figueira, T N; Palermo, L M; Veiga, A S; Huey, D; Alabi, C A; Santos, N C; Welsch, J C; Mathieu, C; Horvat, B; Niewiesk, S; Moscona, A; Castanho, M A R B; Porotto, M

2017-01-01

Measles virus (MV) infection is undergoing resurgence and remains one of the leading causes of death among young children worldwide despite the availability of an effective measles vaccine. MV infects its target cells by coordinated action of the MV hemagglutinin (H) and fusion (F) envelope glycoproteins; upon receptor engagement by H, the prefusion F undergoes a structural transition, extending and inserting into the target cell membrane and then refolding into a postfusion structure that fuses the viral and cell membranes. By interfering with this structural transition of F, peptides derived from the heptad repeat (HR) regions of F can inhibit MV infection at the entry stage. In previous work, we have generated potent MV fusion inhibitors by dimerizing the F-derived peptides and conjugating them to cholesterol. We have shown that prophylactic intranasal administration of our lead fusion inhibitor efficiently protects from MV infection in vivo We show here that peptides tagged with lipophilic moieties self-assemble into nanoparticles until they reach the target cells, where they are integrated into cell membranes. The self-assembly feature enhances biodistribution and the half-life of the peptides, while integration into the target cell membrane increases fusion inhibitor potency. These factors together modulate in vivo efficacy. The results suggest a new framework for developing effective fusion inhibitory peptides. Measles virus (MV) infection causes an acute illness that may be associated with infection of the central nervous system (CNS) and severe neurological disease. No specific treatment is available. We have shown that fusion-inhibitory peptides delivered intranasally provide effective prophylaxis against MV infection. We show here that specific biophysical properties regulate the in vivo efficacy of MV F-derived peptides. Copyright © 2016 American Society for Microbiology.

Inter-operator variation in ELISPOT analysis of measles virus-specific IFN-gamma-secreting T cells.

PubMed

Ryan, J E; Ovsyannikova, I G; Dhiman, N; Pinsky, N A; Vierkant, R A; Jacobson, R M; Poland, G A

2005-01-01

The ELISPOT assay is a highly sensitive technique used for the detection of individual cytokine releasing cells. We have developed an IFN-gamma ELISPOT assay utilizing unfractionated frozen peripheral blood mononuclear cells (PBMC) to quantify the frequency of measles virus (MV)-specific IFN-gamma-secreting T cells in 117 healthy children who had been previously immunized with two doses of the measles-mumps-rubella vaccine. We have also estimated the variability associated with the quantification of ELISPOT plates and compared the number of MV-specific IFN-gamma-secreting T cells for each subject as determined by two different operators of an ELISPOT reader. The median frequency of MV-specific IFN-gamma-producing memory T cells detected by this assay was 0.005 % and 0.01 % as determined by an in-house and commercial operator, respectively. Although we found a significant correlation (r = 0.83, p<0.0001) between the number of spots counted by the commercial and in-house operators of an ELISPOT reader, the median number of spots counted by the commercial operator was twice the number of spots counted by an in-house operator (p<0.001). This demonstrates the importance of using a common ELISPOT reader and operator, among other parameters, to quantify the number of spots when a large volume of plates are being scanned and analyzed.

Progress towards Rapid Detection of Measles Vaccine Strains: a Tool To Inform Public Health Interventions

PubMed Central

2016-01-01

ABSTRACT Rapid differentiation of vaccine from wild-type strains in suspect measles cases is a valuable epidemiological tool that informs the public health response to this highly infectious disease. Few public health laboratories sequence measles virus-positive specimens to determine genotype, and the vaccine-specific real-time reverse transcriptase PCR (rRT-PCR) assay described by F. Roy et al. (J. Clin. Microbiol. 55:735–743, 2017, https://doi.org/10.1128/JCM.01879-16) offers a rapid, easily adoptable method to identify measles vaccine strains in suspect cases. PMID:28003421

Progress towards Rapid Detection of Measles Vaccine Strains: a Tool To Inform Public Health Interventions.

PubMed

Hacker, Jill K

2017-03-01

Rapid differentiation of vaccine from wild-type strains in suspect measles cases is a valuable epidemiological tool that informs the public health response to this highly infectious disease. Few public health laboratories sequence measles virus-positive specimens to determine genotype, and the vaccine-specific real-time reverse transcriptase PCR (rRT-PCR) assay described by F. Roy et al. (J. Clin. Microbiol. 55:735-743, 2017, https://doi.org/10.1128/JCM.01879-16) offers a rapid, easily adoptable method to identify measles vaccine strains in suspect cases. Copyright © 2017 American Society for Microbiology.

Measles

MedlinePlus

... it in its tracks. Doctors call this "herd immunity." Measles isn't very common, but it is ... get the vaccine get some protection through herd immunity. During a measles outbreak, some people who haven' ...

Enhanced lysis by bispecific oncolytic measles viruses simultaneously using HER2/neu or EpCAM as target receptors

PubMed Central