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Measles virus-specific functional antibody responses and viremia during acute measles.

Antibody titers measured in functional and immunofluorescent assays were compared with proportions of peripheral blood mononuclear cells infected with measles virus in 8 adults with measles. In addition, a syncytium inhibition assay (SIA) for measuring neutralizing antibody using low-passage virus was compared with a standard plaque neutralization test (PNT). Antibody-dependent cellular cytotoxicity (ADCC) antibody rose later but attained higher titer than neutralizing, antibody-dependent complement-mediated lysis, IgM, or IgG antibodies. When titer changes between specimens from each patient obtained on different days were compared, only ADCC (r = .81, P = .026) and IgM (r = .81, P = .027) antibodies correlated with reductions in viremia. SIA and PNT correlated well (r = .93, P < .001). ADCC may be an important defense against measles. The delay in ADCC antibody relative to other antibodies is unique among viruses studied. The SIA is a useful alternative to the PNT for measuring measles neutralizing antibody.

Acute Disease↗

A novel sensitive approach for frequency analysis of measles virus-specific memory T-lymphocytes in healthy adults with a childhood history of natural measles.

Measles virus (MV), a single-stranded negative-sense RNA virus, is an important pathogen causing almost 1 million deaths annually. Acute MV infection induces immunity against disease throughout life. The immunological factors which are responsible for protection against measles are still poorly understood. However, T-cell-mediated immune responses seem to play a central role. The emergence of new single-cell methods for quantification of antigen-specific T-cells directly ex vivo has prompted us to measure frequencies of MV-specific memory T-cells. As an indicator for T-cell activation IFN-gamma production was measured. PBMC were analysed by intracellular staining and ELISPOT assay after stimulation with MV-infected autologous B-lymphoblastoid cell lines or dendritic cells. T-cell responses were exclusively seen with PBMC from MV-seropositive healthy adults with a history of natural measles in childhood. The median frequency of MV-specific T-cells was 0.35% for CD3(+)CD4(+) and 0.24% for the CD3(+)CD8(+) T-cell subset. These frequencies are comparable with T-cell numbers reported by other investigators for persistent virus infections such as Epstein-Barr virus, cytomegalovirus or human immunodeficiency virus. Hence, this study illustrates that MV-specific CD4(+) and CD8(+) T-cells are readily detectable long after the acute infection, and thus are probably contributing to long-term immunity. Furthermore, this new approach allows efficient analysis of T-cell responses from small samples of blood and could therefore be a useful tool to further elucidate the role of cell-mediated immunity in measles as well as in other viral infections.

Adult↗

Evasion of host defenses by measles virus: wild-type measles virus infection interferes with induction of Alpha/Beta interferon production.

Measles is a highly contagious disease currently responsible for over one million childhood deaths, particularly in the developing world. Since alpha/beta interferons (IFNs) are pivotal players both in nonspecific antiviral immunity and in specific cellular responses, their induction or suppression by measles virus (MV) could influence the outcome of a viral infection. In this study we compare the IFN induction and sensitivity of laboratory-passaged attenuated MV strains Edmonston and Moraten with those of recent wild-type viruses isolated and passaged solely on human peripheral blood mononuclear cells (PBMC) or on the B958 marmoset B-cell line. We report that two PBMC-grown wild-type measles isolates and two B958-grown strains of MV induce 10- to 80-fold-lower production of IFN by phytohemagglutinin-stimulated peripheral blood lymphocytes (PBL) compared to Edmonston and Moraten strains of measles. Preinfection of PBL with these non-IFN-inducing MV isolates prevents Edmonston-induced but not double-stranded-RNA-induced IFN production. This suggests that the wild-type viruses can actively inhibit Edmonston-induced IFN synthesis and that this is not occurring by double-stranded RNA. Furthermore, the wild-type MV is more sensitive than Edmonston MV to the effect of IFN. MV is thus able to suppress the synthesis of the earliest mediator of antiviral immunity, IFN-alpha/beta. This could have important implications in the virulence and spread of MV.

Animals↗

Should all children receive two measles vaccinations? A study of measles susceptibility in a suburban New Jersey private practice.

Because of the rising incidence of rubeola, we tested all our patients who were vaccinated prior to 15 months of age and those vaccinated after 15 months, if requested, for susceptibility to measles (IgG, ELISA). Those found to be susceptible were revaccinated. Of 1,228 tested, 264 (21.5%) were susceptible. In the group vaccinated before 1980, 237 of 901 (26.3%) were susceptible, whereas only 27 of 327 (8.3%) vaccinated after 1980 were not immune. Susceptibility was sharply divided by month of age at vaccination at the 14-month mark. Less than 5% of those vaccinated after age 15 months in the 1980s (one of 22, or 4.5%) were susceptible. Waning immunity (secondary vaccine failure) was not found to be a factor in our patients. Despite outbreaks of measles in surrounding communities and in our area, none of our patients developed measles. Identification of high-risk groups and selective measles revaccination should be considered as an alternative to universal revaccination in populations such as ours, since it is more cost-effective and may prove equally successful.

Analysis of Variance↗

Subacute sclerosing panencephalitis after passive immunization and natural measles infection: role of antibody in persistence of measles virus.

Subacute sclerosing panencephalitis (SSPE) developed in a patient in whom natural measles infection was anteceded by immunization with measles immune serum globulin (ISG). This observation prompted experimental studies of the role of antibody in viral persistence. When Balb/c mice were infected with the hamster neurotropic measles virus, acute encephalopathy was fatal in 80% of the animals. When measles antibody was administered 3 days after virus inoculation, the acute disease was abolished and subacute encephalitis had a 30% mortality. The subacute disease was characterized by the presence of neuronal viral antigen, meningitis, and encephalitis. Induction of viral persistence was therefore a consequence of antibody transfer during viral infection. Caution is advised in human prophylaxis with immune globulin.

Animals↗

[Intranasal vaccination with live measles vaccines within the framework of measles eradication strategy].

The authors discuss the possibility of intranasal revaccination with live measles vaccine. Intranasal vaccination is no less effective than subcutaneous. It induces generalized immune response and formation of anti-measles IgA in the nasopharyngeal mucosa. Immunomodulating side effects of intranasal vaccination are less pronounced than those of subcutaneous one. The intranasal method of vaccination is safer than the inhalation method, which involves exposure of the bronchial mucosa to the live measles virus. The efficiency of mucosal measles vaccine can be increased by adding this or that adjuvant to the vaccine.

Administration, Intranasal↗

[Measles in two children and one adult--outbreak of measles genotype B3].

Measles virus genotype B3 was isolated from patients during a measles outbreak in Copenhagen starting January 2006. Here we describe three cases: two children aged 9 and 22 months, respectively, and a 29-year-old man. All three patients were hospitalised. Several doctors examined both the children before the diagnosis of measles was established. The patients were not vaccinated against measles. They had not been abroad within the last three weeks. Genotype B3 is endemic in West and Central Africa. The genotype B3 detected in these cases was different from the B3 seen in recent outbreaks in Europe.

Adult↗

[Loss of maternal measles antibodies acquired by vaccination against measles].

The objective of the investigation was to assess whether children of mothers who acquired measles antibodies resp. immunity by vaccination are at least for the first six months of their life protected by maternal antibodies. A group of fifty pregnant women mean age 18 years incl. their umbilical blood and blood of their children, mostly 5-6 months after birth, were examined by the haemagglutination inhibition and immunoenzymatic test. The levels of measles antibodies were detected in 11 women immunized against measles in cca 1970 and in 26 revaccinated women mostly after 5 to 11 years. In once vaccinated mothers and their umbilical bloods the mean HI titres were 1:8.5 and 1:14 resp. and the mean EIA titres were 1:3600 and 1:3040 resp. As to the eight newborn children at the age of 5 and 6 months 6 children did not have any protective antibodies. In twice vaccinated women and their umbilical bloods the mean HI titre was 1:10 and 1:16.4 resp. and EIA titres were 1:2937 and 1:3784 resp. Of the 15 newborn infants at the age of 4 to 6 months 11 infants did not have any protective antibodies. In 8 mothers without vaccination records and their umbilical bloods the mean HI titre was 1:7.5 and 1:25.5 and mean EIA titres were 1:8229 and 1:7360 resp. In none of their children at the age of 6 months measles antibodies were found. The finding of the lack of protection in children older than 6 months stimulates further research of the problem.

Antibodies, Viral↗

Measles complications: the importance of their management in reducing mortality attributed to measles.

OBJECTIVE: To determine the effect of rates of complications among cases and management of complicated cases on measles case fatality rates. DESIGN: Measles disease surveillance. SETTING: City of Gweru, Department of Health. SUBJECTS: Children aged zero to 15 years. MAIN OUTCOME MEASURES: Case fatality rates. RESULTS: Measles case fatality rates declined from 47.6 in 1967 to zero in 1989. Between 1967 and 1978 respiratory infections were the predominant complications (66.5%), while after 1979 diarrhoea was the predominant complications (60.6%). A significant partial correlation coefficient was observed between rates of mortality among complicated cases and case fatality rates (r = 0.89, df = 20, p < 0.001). CONCLUSION: Good management of complicated cases may have contributed towards the decline in measles case fatality rates.

Adolescent↗

Monoclonal antibodies against five structural components of measles virus. II. Characterization of five cell lines persistently infected with measles virus.

Groups of monoclonal antibodies against measles virus nucleoprotein (NP), phosphoprotein (P), matrix (M), hemagglutinin (H) and fusion (F) components were used for characterization of 5 persistently infected cell lines. In four of these lines (Lu106 carrier, MaSSPE, MaPi, HEpPi) all cells were infected but the cells mostly produced noninfectious virus products. The fifth line (HNT in vero cells) did not produce any infectious virus and only a fraction of the cells were infected in most passages. In agreement with earlier findings the virus strains showed marked variations in the M epitope pattern and also some variation in the H epitope pattern. In addition epitope variations were found in both NP and P protein, which contrasted with conserved antigen characteristics of these components in lytically replicating virus. Restriction of fusion in the persistent infections was studied further. HNT and Lu 106 cells showed selective quantitative restriction in F protein synthesis. Lu106 cells were found to contain distinct epitopic F species. In contrast MaSSPE cells produced readily detectable cleaved F protein and in addition extracellular virus products carried hemolytic activity. The fact that no cell fusion occurred was interpreted to be due to particular properties of the Ma 106 cells, a concept supported by the absence of fusion of these cells when infected with syncytiogenic measles virus. It is concluded that (a) under conditions of persistence of measles-virus without requirement for synthesis of complete virions a more pronounced variation in epitope characteristics of virus components is encountered than in lytic infections; and b) that persistence of measles virus shows individualistic characteristics which may reflect changes in the virus and/or innate properties of the host cells.

Animals↗

Persistent infection of cells in culture by measles virus. II. Effect of measles antibody on persistently infected HeLa sublines and recovery of a HeLa clonal line persistently infected with incomplete virus.

Rustigian, Robert (Tufts University School of Medicine, Boston, Mass.). Persistent infection of cells in culture by measles virus. II. Effect of measles antibody on persistently infected HeLa clonal line persistently infected with incomplete virus. J. Bacteriol. 92:1805-1811. 1966.-The effect of viral antibody on persistent infection of HeLa cells by the Edmonston strain of measles virus was investigated by culturing cells from three persistently infected clones in medium supplemented with human immune globulin. The three infected HeLa clones were isolated from a persistently infected parent line. Two sublines which were grown in the presence of measles antibody developed a nonyielder state, wherein there is no detectable virus infectious for normal HeLa cultures. There is, however, continued synthesis of intracellular viral antigen and formation of viral intracytoplasmic inclusion bodies. The development of a nonyielder state was associated with a marked decrease in the degree of hemadsorption in cultures of both sublines. Further studies of the viral properties of non-yielder HeLa cell populations were made with a clone obtained from one of these sublines by plating under antibody. Persistent infection in this line was characterized by synthesis of incomplete virus even when the cells were cultured thereafter in anti-body-free medium. This was evidenced by (i) failure to recover infectious virus from the clonal population despite continued formation of intracellular viral antigen and viral intracytoplasmic inclusion bodies in a majority of the cells, (ii) the presence of only a few cells with surface viral antigen(s) including hemagglutinin, and (iii) the relatively weak antibody response to viral envelope antigen(s) after injection of cells into guinea pigs.

Animals↗

Alterations in immune responsiveness in acute measles and chronic post-measles chest disease.

Immune responses in 24 children with acute measles (AM) were compared with those in 20 children who had chronic pulmonary complications (CPMC) following measles. The immuno-suppressive effects of acute measles were extensive: total white cells were reduced and this reduction was accounted for entirely by lymphopenia which was equally expressed among the major lymphocyte sub-populations studied; the function of 'T' cells, assessed by radio-isotope incorporation into phytohaemagglutin (PHA) transformed lymphocytes and delayed skin hypersensitivity (DHR) to dinitrochlorobenzene (DNCB), was depressed. Serum IgA was reduced in AM patients. In contrast there was a relative sparing of the measured indices of immunity in patients with chronic post-measles chest disease, with the major defect being an impaired DHR to DNCB. There were minor alterations of complement components in both groups of patients.

Acute Disease↗

[Nucleotide sequence of the noncoding regions of measles virus stain CC-47 and comparison with other measles viruses].

BACKGROUND: To determine the nucleotide sequence of noncoding regions of Measles virus strain Changchun-47 (CC-47) and to compare them with other measles virus for revealing some vaccine-related information. METHODS: Six overlapped fragments, that covers complete genome of CC-47 were amplified by using RT-PCR, all of the amplified fragments have been cloned and sequenced. RESULTS: Seven noncoding regions lie in the genome sequence of CC-47 separated by six structure genes. The noncoding regions of CC-47 contain 1791 nucleotides totally. Comparing of the noncoding regions of CC-47 with other wild type strains and five Edmonston-derived vaccine strains, four nucleotide substitutions were shared by nearly all vaccine strains. Two of these were in the genomic 3 terminal transcriptional control region: position 26 (U->G), 42 (U->G); the other were in the F mRNA 5 -untranslated region of M/F intergenic region. These site substitutions may influence the efficiency of mRNA synthesis, processing, and translation, as wel l as genome replication and encapsidation. CONCLUSIONS: The nucleotide substitutions shared by different genotype measles virus vaccine strains may be related to virus growth in semipermissive cell or process of attenuation, which provide useful data for molecular epidemiology of measles virus. The nucleotide substitutions for attenuation were involved in several regions other than one definite region.

3' Untranslated Regions↗

Measles, measles vaccination, and risk of subacute sclerosing panencephalitis (SSPE).

Between the years 1968 and 1979, 87 cases of subacute sclerosing panencephalitis (SSPE) appeared among the Israeli-born population. The incidence of SSPE dropped sharply in 1977, 10 years (the median age at onset of SSPE) after introduction of mass antimeasles vaccination, and remained low in 1978 and 1979. Most of the SSPE cases reported measles at an age significantly younger than that of the general population. This pattern did not change after introduction of antimeasles vaccination. Incidence was significantly lower (p less than 10(-9) in the vaccinated population than in the unvaccinated population. Occurrence of SSPE in some children who were vaccinated against measles could be explained by incomplete vaccine efficacy, or by older age at vaccination, which allows the possibility of prior exposure to measles. There was no indication that measles vaccine can induce SSPE.

Adolescent↗

Measles vaccination status, delay in recognizing measles outbreaks and outbreak outcome.

From July to October 1994, Mashonaland East Province in Zimbabwe experienced measles outbreaks in which 2118 cases were reported. According to routine statistics, 69 pc of these patients were previously vaccinated against measles, 22 pc were not vaccinated and 9 pc had an unknown vaccination status. The measles vaccine coverages in the nine districts of this province during the year prior to the outbreak ranged from 58 pc to 87 pc with a provincial average of 72 pc. Three hundred and fifty eight patients who came in contact with health services during one month were investigated further. The prevalence of measles related complications among vaccinated and unvaccinated patients was 18,5 pc and 51,7 pc respectively (X2 = 56,01, p < 0,001; df = 2. While no death occurred among vaccinated patients, the case fatality rate among unvaccinated patients was 27,3 pc (X2 = 45,15, p < 0,001; df = 2). The later an outbreak was recognized the longer it was likely to last and the higher the case fatality rate was (Correlation coefficient = 0,76; 95 pc CI 0,02 - 0,96). It is concluded that the Expanded Programme on Immunization in this area is not a failure and that for outbreak control measures to be effective, they have to be implemented as early as possible, preferably within one week of the onset of an outbreak. District managers should put more emphasis on the use of data by Rural Health Centre staff in order to recognize outbreaks early.

Adolescent↗

Adverse events following measles-mumps-rubella and measles vaccinations in college students.

We studied adverse events reported by 401 measles, mumps and rubella (MMR) vaccinees and 391 unvaccinated controls at one college, and 133 measles (M) vaccinees and 352 unvaccinated controls at an adjacent college during a measles outbreak in Massachusetts in 1985. Rates of symptoms and signs experienced by MMR vaccinees, M vaccinees, and controls were essentially similar. No serious adverse events were detected.

Adolescent↗

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.

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.

Adolescent↗

Suboptimal measles-mumps-rubella vaccination coverage facilitates an imported measles outbreak in ireland.

The year 2000 saw a dramatic increase in the incidence of measles infections in Ireland, with >1500 cases documented. Initial cases were reported from an area of Dublin with low vaccine uptake and a large immigrant population. Molecular epidemiologic findings revealed that the strain of measles virus responsible for this outbreak was the genotype D2 strain, which is closely related to strains initially identified in South Africa. It is suggested that suboptimal vaccine uptake facilitated the spread of imported measles infection.

Diagnostic Errors↗