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Measles virus and subacute neurological disease: an unusual presentation of measles inclusion body encephalitis.

A 20-year-old girl developed a subacute neurological illness characterized by seizures and epilepsia partialis continua, which resulted in her death within 10 weeks of her first symptom. Although she had a history of unusual reactions to viral infections, there was no evidence of any underlying disorder resulting in immunosuppression. Histopathology demonstrated the presence of dense infection with measles virus. The unusual clinical features of this cases suggest that measles virus may be responsible for a wide spectrum of neurological disease ranging from measles inclusion body encephalitis on the one hand to subacute sclerosing panencephalitis on the other.

Adult↗

Loss of maternally acquired measles antibodies in well-nourished infants and response to measles vaccination, Peru.

Clinical, anthropometric, and serological evaluations were conducted at birth and at 3, 6, 9, and 10 months (post measles vaccination) in 34 well-nourished Peruvian infants. Seroconversion rate after measles vaccination was 94 percent. The rate of antibody loss was a direct function of birth titer; at age 9 months, all children had identical mean titers regardless of their titer at birth. Differences in maternally acquired measles antibodies at birth were important only during the first six months of life.

Aging↗

Measles control in Australia. Report of the Measles Control in Australia Workshop, 5 November 1997.

The proceedings of the Measles Control in Australia Workshop held on 5 November 1998 are presented in this report. Prompted by the possibility of a global elimination campaign in the near future the Workshop considered the factors involved in elimination of measles from Australia. Epidemiology, surveillance, laboratory diagnosis methods, mathematical modelling, and the cost and logistics were all addressed. Mass vaccination for all 2-18 year olds, and a routine 2-dose regimen with scheduled doses at 12 months and school entry were recommended. Intensified surveillance, based on a sensitive case definition and laboratory confirmation (measles specific IgM) of suspected cases was identified as a crucial component of the campaign. The continuation of high vaccination coverage for each of the two doses would be essential to maintain elimination once established.

Adolescent↗

Growth of measles virus in nervous tissues. IV. Neurovirulence of wild measles and SSPE viruses in monkeys.

Neurovirulence of in vivo-passed wild measles virus and that of the cell-associated SSPE virus were compared by intracerebral inoculation into monkeys. The wild measles virus was found to lack neutrovirulence without producing neurological signs or significant histological changes in the brains, whereas the virus was confirmed to preserve the properties characteristic of the wild virus. In contrast, inoculation of the SSPE virus induced rapid onset of neurological signs with mild but definite histological changes including degeneration of nerve cells. The fact that SSPE virus exhibited neurovirulence in monkeys indicated importance of the current assay system for neurovirulence of measles vaccine by intracerebral inoculation into monkeys.

Animals↗

Measles antibodies in nasal secretions and sera of children with measles.

Measles antibodies were determined, in the course of measles, in sera and nasal secretions of 54 and 27 children, respectively. The examinations were performed on the 3rd or 4th day (1st period) and between the 10th and 14th day (2nd period) after onset of rash in both sera and nasal secretions and after 25 to 60 days (3rd period) in sera only. Geometric mean titres of antibodies in sera determined by haemmagglutination inhibition (HI) and neutralization tests in the 1st period were 126.3 and 115.3 respectively. For the 2nd period the respective figures were 318.4 and 396.1 and for the 3rd period--388.0 and 445.6. Fractionation on Sephadex G-200 of sera from the 1st period revealed HI and neutralizaing antibodies associated mainly with the IgM serum globulin class. Measles HI and neutralizing antibodies were also found in nasal secretions of all 27 children, but their titres were much lower than in serum. The antibodies determined by indirect immunofluorescence in nasal secretions were associated with IgA in 26 and with IgG immunoglobulin in 15 of the 27 subjects. No IgM antibodies were found.

Antibodies, Viral↗

Age for measles immunization seroconversion after measles vaccination at 6-8 months of age--a randomized controlled trial.

The objective of the study was to compare the effectiveness of measles vaccine by seroconversion in vaccinated children with non-vaccinated children of 6 to 8 months age group in a city slum community so as to study the feasibility of advancing the age of immunization. Live attenuated lyophilized Schwartz strain of measles vaccine was used. Hemagglutination inhibition (HI) antibody was estimated. Seroconversion was defined as either the conversion of negative to positive or a two fold rise in titre. One hundred and thirty two children completed the study. There was no difference in the age, sex and nutritional status between vaccinated and non-vaccinated groups (p greater than 0.7). The seroconversion rate in the vaccinated group was 65% and in the non-vaccinated group was 26%. The age, sex and nutritional status did not significantly affect the seroconversion. Our data suggest that immunization with measles vaccine may be effective as early as 6 months of age. Immunization at 6 months may be needed at least for children in densely populated areas like cities and towns.

Age Factors↗

The predominance of CD8+ T cells after infection with measles virus suggests a role for CD8+ class I MHC-restricted cytotoxic T lymphocytes (CTL) in recovery from measles. Clonal analyses of human CD8+ class I MHC-restricted CTL.

Stimulation of PBMC, in children recovering from acute measles, with autologous EBV-transformed and measles virus (MV)-infected lymphoblastoid cell lines (B-LCL) expanded primarily MV-specific CD8+ T cells. A large number of CD8+ T cell clones were obtained either by passaging of bulk cultures at limiting dilutions or by direct cloning of PBMC without previous stimulation in bulk culture. The MV-specific CD8+ T cell clones responding in a proliferative and a CTL assay were found to be class I MHC restricted. In contrast, CD4+ MV-specific T cell clones, which were generated by the same protocol, recognized MV in association with class II MHC molecules. Analysis of processing requirements for Ag presentation to CD8+ and CD4+ T cell clones, measured by the effect of chloroquine in a proliferative T cell response, revealed that both types of T cells recognized MV Ag processed via the endogenous/cytoplasmic pathway. Thus, these studies indicate that, as in most other viral infections and in contrast to previous suggestions, the class I MHC-restricted CTL response by CD8+ T cells may be an important factor in the control and elimination of MV infection. Therefore, the role proposed for CD4+ class II-restricted T cells in recovery from measles needs to be reevaluated.

Antigen-Presenting Cells↗

Laboratory diagnosis of measles infection and monitoring of measles immunization: memorandum from a WHO meeting.

Measles infection continues to be a major global health problem, and in many countries the disease is frequently diagnosed on clinical grounds alone, although it is easily confused with other conditions. In order to discuss approaches to improving this situation, a WHO Consultation on Laboratory Diagnosis of Measles Infection and Monitoring of Measles Immunization was held in Glasgow on 7-8 August 1993. The discussions and recommendations made by the participants are summarized in this Memorandum.

Antibodies, Viral↗

Transient appearance of oligoclonal immunoglobulins and measles virus antibodies in the cerebrospinal fluid in a case of acute measles encephalitis.

Acute measles encephalitis with severe sequelae in a 25-year-old man was studied. A transient appearance of oligoclonal IgG in cerebrospinal fluid and of intrathecally produced measles antibodies was found during 2 months after the onset of the disease. On the basis of this finding of local hyperimmunization it is proposed that in the case studied the measles virus infection may have been directly responsible for the disease process in the central nervous system.

Adult↗

Measles-mumps-rubella and other measles-containing vaccines do not increase the risk for inflammatory bowel disease: a case-control study from the Vaccine Safety Datalink project.

CONTEXT: A link between measles virus-containing vaccines and inflammatory bowel disease (IBD) has been suggested by recent studies. OBJECTIVE: To address whether receipt or timing of measles-containing vaccine (MCV) increases risk for IBD. DESIGN: A case-control study. SETTING: Four large health maintenance organizations (HMOs) that are part of the Centers for Disease Control and Prevention's Vaccine Safety Datalink project. PATIENTS OR OTHER PARTICIPANTS: A total of 155 persons with codes from International Classification of Diseases, Ninth Revision specific for IBD, born between 1958 and 1989 and enrolled from birth to the onset of disease, were identified. Up to 5 controls were matched by sex, HMO, and birth year. INTERVENTION: None. MAIN OUTCOME MEASURES: Risk for IBD, Crohn's disease, and ulcerative colitis. RESULTS: Past vaccination was not associated with an increased risk for Crohn's disease (odds ratio [OR] for measles-mumps-rubella vaccine [MMR], 0.4; 95% confidence interval [CI], 0.08-2.0), ulcerative colitis (OR, 0.8; 95% CI, 0.18-3.56), or IBD (OR, 0.59; 95% CI, 0.21-1.68). Risk for IBD was not increased among children vaccinated who were younger than 12 months (OR for MMR, 0.61; 95% CI, 0.15-2.45) or aged 12 to 18 months (OR, 0.86; 95% CI, 0.28-2.59) relative to unvaccinated children. Children vaccinated with MMR who were older than 18 months were at significantly decreased risk for IBD (OR, 0.16; 95% CI, 0.04-0.68). Neither past vaccination nor age at vaccination with other MCV was associated with increased risk for Crohn's disease, ulcerative colitis, or IBD. Risk for Crohn's disease, ulcerative colitis, or IBD was not elevated in the time immediately following vaccination with either vaccine. CONCLUSIONS: Vaccination with MMR or other MCV, or the timing of vaccination early in life, did not increase the risk for IBD.

Adolescent↗

Monoclonal antibodies against five structural components of measles virus. I. Characterization of antigenic determinants on nine strains of measles virus.

Monoclonal antibodies against five structural proteins of measles virus were used to determine the degree of antigenic variation within these proteins amongst nine strains of measles virus (four fresh wild-type isolates, two vaccine and two laboratory strains, and a strain derived from a case of subacute sclerosing panencephalitis) giving lytic infections in cell culture. The major surface proteins showed limited variations in their epitopes between the nine strains. No variations in the fusion (F) protein and only three variations in the hemagglutinin (H) protein epitopes were detected by radioimmune precipitation assay and other serological tests using a panel of 11 monoclonal antibodies against each protein. These antibody panels consisted of at least nine and six different binding groups for the H and F proteins, respectively. The two innermost proteins, the nucleocapsid and polymerase proteins, also appeared to be antigenically stable as no variation was detected between strains using in each case a panel of six hybridomas. In sharp contrast, the epitopes on the matrix (M) protein of different strains showed extensive variation in their reactivity with the nine anti-M monoclonal antibodies. The possible use of M protein epitopic markers in classification of measles virus strains is discussed.

Antibodies, Monoclonal↗

Measles, mumps, rubella, and varicella combination vaccine: safety and immunogenicity alone and in combination with other vaccines given to children. Measles, Mumps, Rubella, Varicella Vaccine Study Group.

Eight hundred and twelve children, 12 months to 3.5 years of age, were enrolled in two clinical studies to evaluate the safety and immunogenicity of a live, attenuated combination vaccine for measles, mumps, rubella, and varicella (MMRV). Children were enrolled in one of two randomized, multicenter studies, involving administration of (1) MMRV and placebo vs. measles, mumps, and rubella vaccine (M-M-R(II)) and varicella-zoster virus vaccine (VARIVAX), given at separate anatomic sites at the same office visit; or (2) MMRV, DTaP (diphtheria, tetanus, and acellular pertussis vaccine) and OPV (oral polio vaccine) vs. M-M-R(II), DTaP, and OPV, with VARIVAX given 6 weeks later. All vaccine regimens were generally well tolerated. More than 95% of vaccinees seroconverted for measles, mumps, rubella, and varicella, regardless of the vaccine or regimen used. In each study, the level of antibody titer to varicella virus was significantly lower in vaccinees receiving MMRV than in those who received VARIVAX in a separate syringe.

Chickenpox Vaccine↗

Measles among the Amish: a comparative study of measles severity in primary and secondary cases in households.

An outbreak of measles among a predominantly unvaccinated and susceptible Amish population in Lebanon County, Pennsylvania, offered the opportunity to test the hypothesis that secondary cases in households are more severe than primary cases because the former have more intense exposure and receive a greater virus inoculum. Of 130 measles cases reported between April and June 1988, 119 (92%) constituted a study of disease severity. Severity was assessed by determining frequency and duration of symptoms, length of any hospitalization, and number of days in bed. In a univariate analysis, fewer secondary cases had conjunctivitis (relative risk [RR], 0.67; 95% confidence interval [CI], 0.48-0.96) and headache (RR, 0.37; CI, 0.15-0.86), but more had earache (RR, 9.69; CI, 1.8-202.9) compared with primary cases. Secondary cases had a shorter mean duration of coryza (4.0 vs. 5.0 days, Student's t test, P = .08). However, a logistic regression model that matched by family and controlled for age and sex indicated that there were no significant differences in measles severity among primary and secondary cases in households.

Adolescent↗

Cellular immunity in measles vaccine failure: demonstration of measles antigen-specific lymphoproliferative responses despite limited serum antibody production after revaccination.

Measles antigen-specific immune responses were evaluated 1 and 6 months after revaccination in 60 previously vaccinated subjects (9.4 +/- 3.4 years of age) who had either undetectable or low plaque reduction neutralization (PRN) titers (< 200). PRN titers were increased in all subjects at 1 month (590 +/- 61; range, 129-2513) but fell again in 66% of subjects by 6 months (214 +/- 29; range, 30-794). At 6 months, 23 (38%) had subprotective (< 120) or borderline (< 200) PRN titers. Lymphoproliferative responses to measles virus antigens were low overall before revaccination (mean stimulation index [SI], 2.6 +/- 0.4; range, 0.5-13.5) but were readily detectable at 1 (SI, 145.8 +/- 2.6; range, 1.4-80) and 6 months after revaccination (SI, 9.4 +/- 1.8; range, 1.1-87). Before revaccination, 10 of the subjects (50%) with low positive PRN titers had SIs > or = 3. At 6 months after revaccination, 18 subjects (78%) with PRN titers < or = 200 had SIs > or = 3. These data suggest that cellular responses to measles virus may be better sustained than antibody titers after vaccination and revaccination in some subjects.

Antibodies, Viral↗

Measles as a cause of fetal defects. A retrospective study of tem measles epidemics in Greenland.

In a retrospective study of ten epidemics of measles in virgin-soil populations in Greenland, 368 women were found to be pregnant at the time of their infection with measles. Information on the course of the pregnancies was obtained in 327 of these women and a clinical examination was made of 252 of their children. The risk of fetal death among women infected in the first trimester was found to be high. About half of 20 women infected during their first two months of pregnancy and a fifth of 31 women infected in the third month had abortions. 9% of 64 women infected in the first trimester and going to term had stillbirths. 28 women infected in the first two months of pregnancy had live children, but four of these had congenital malformations, three of extreme rarity and severity, leading to death. The rate of perinatal mortality and prematurity was equal among infants exposed to measles in the first, second and third trimester of fetal life.

Congenital Abnormalities↗

Implementing a system of enhanced surveillance for measles in Victoria. The Enhanced Measles Surveillance Working Party.

In response to identified deficiencies in the passive surveillance system for measles in Victoria and the move towards local disease elimination and global disease eradication, a system of enhanced measles surveillance was introduced in 1997. Each case is contacted and a structured telephone questionnaire is completed, collecting information on symptomatology and encouraging serological confirmation, if not already performed. The introduction of a paediatric phlebotomy service to collect serum specimens in the case's home, has led to a dramatic increase in the proportion of cases where testing is performed, reaching nearly 90 per cent by the end of 1998. The median time from notification to specimen collection is one day. The Victorian approach to the enhanced surveillance of measles provides a framework for similar systems as Australia approaches disease elimination.

Child↗

Further observations on subacute sclerosing encephalitis in adult hamsters: the effects of intranasal infections with Langat virus, measles virus and SSPE-measles virus.

Passage by i.c. inoculations of suckling hamsters enhanced the virulence for adult hamsters of Langat virus (TP21), neurotropic strain of measles virus (HNT) and SSPE-measles virus (HBS), not only for i.c. infections but also for intranasal instillations. The various viral strains passaged in hamsters showed a great similarity of behaviour including the ability of producing in a proportion of apparently unaffected survivors a subacute sclerosing encephalitis, leading to atrophy of parts of the brain especially the rhinencephalon. When large groups of animals were used for transmission experiments it became obvious that within one week after intranasal exposure, all the hamsters either died or became clinically affected, or did not show signs of disease but developed acute inflammatory brain lessions. tlater on, between 2-6 weeks following inoculations only 90% of hamsters were affected with either overt signs of disease or subacute brain lesions, suggesting that in about 10% of hamsters the initial infection did not progress further and that in these animals the early brain lesions disappeared. Passage levels, irrespective of the virus used, did not influence the total numbers of infected hamsters but showed a significant effect on the mortality in TP21 and HNT infections where the number of dead and clinically affected increased in the higher passes. In these higher passes the number of survivors with subacute brain lesions decreased. In SSPE-measles virus the number of clinically affected hamsters and those surviving but developing brain lesions remained constant throughout. Vacuolated neurons were present in the brains of hamsters that survived one of the above 3 viral infections. They were seen beginning from 6 weeks after infection only in animals that developed subacute sclerosing lesions and were most commonly found in the amygdaloid nuclei and in the pyriform cortex. There was a dramatic increase in the number of brains with vacuolated neurons in hamsters infected with the high viral passes; however, in the 36th hamster passage of TP21 no vacuolated neurons were present but the total number of survivors was small, the majority had no brain lesions and none had subacute sclerosing changes.

Age Factors↗

Serum complement concentrations, nutritional status and the outcome of measles and measles pneumonia.

A prospective study of children with measles has shown a significant association between malnutrition and a poor prognosis. Levels of a number of complement components bore no relationship to the severity of the disease or to its prognosis. Some of the children with acute measles had depressed serum concentrations of factor D, Clq or C3, but complement deficiency does not appear to be implicated in the heightened susceptibility to secondary bacterial and viral infection so commonly found after acute measles.

Body Weight↗