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Measles-mumps-rubella immunization of susceptible hospital employees during a community measles outbreak: cost-effectiveness and protective efficacy.

OBJECTIVE: To determine cost-effectiveness and protective efficacy of a program to identify and immunize susceptible hospital employees during a measles outbreak. DESIGN: A cost analysis was made of blind measles-mumps-rubella (MMR) immunization versus directed MMR immunization based on 2,000 employees born after December 31, 1956. A directed MMR immunization program for susceptible employees was instituted. Actual costs of the program were calculated at the conclusion of the program. SETTING: A medical center complex with more than 4,000 employees, two acute care community hospitals, and a tertiary care children's hospital. RESULTS: A directed MMR immunization program was projected to be less expensive than blind immunization ($23,106 versus $70,720). MMR vaccine was administered to 169 of 188 susceptible employees. Actual cost of the directed MMR immunization program was $25,384. CONCLUSIONS: The directed MMR immunization program was cost-effective and prevented secondary cases among hospital employees during a community measles outbreak.

Community-Acquired Infections↗

Comparative evaluation of two combined measles-mumps-rubella vaccines based on AIK and Edmonston- Zagreb strains of measles virus.

In a previous paper, we have noticed the effectiveness of two further attenuated measles vaccines, i.e. AIK-HDC and Edmonston- Zagreb- HDC. In the present study the same strains are comparatively used for immunization of a limited number of children under 9 months of age. A seroconversion of 100% was observed. Following reimmunization, a significant increase of circulating antibodies for both strains was recorded. Two combined measles-mumps-rubella (MMR) vaccines were also produced by using the same measles strains. The seroconversion following utilisation of MMR prophylactics in susceptible children was 98.8 and 97.3 for AIK and Edmonston- Zagreb strains respectively.

Antibodies, Viral↗

Clinical trial of live measles vaccine given alone and live vaccine preceded by killed vaccine. Fourth report to the medical research council by the measles sub-committee of the committee on development of vaccines and immunisation procedures.

Follow-up of 5000 children given a single dose of live attenuated measles vaccine (Schwarz strain) when aged 10 months to 2 years shows a high level of protection in comparison with an unvaccinated group. This protection has been maintained for 12 years. Measles in vaccinated children was less severe as well as less frequent throughout the period. There is no evidence from the follow-up so far that a further injection of vaccine is needed; this has been confirmed by measles haemagglutination-inhibiting antibody estimations in a sample of the children.

Antibodies, Viral↗

Transfer of measles, mumps, and rubella antibodies from mother to infant. Its effect on measles, mumps, and rubella immunization.

Sera from 42 mother-infant pairs were examined to determine the effect of passively acquired enhanced neutralizing (ENt) antibody on immunization. The ENt antibodies to measles, mumps, and rubella were greater in term newborns than in their mothers, with mean ratio of 1.8:1, 1.3:1, and 1.2:1, respectively. In 21% to 25% of the children, these antibodies persisted until 12 months of age. When immunized with trivalent measles-mumps-rubella vaccine, children who had persisting ENt measles and rubella titers had significantly lower mean antibody responses than children without detectable antibodies to the two viruses. Persisting ENt mumps antibodies did not affect the postimmunization titers. Seroconversion rates to any of the three viruses were not different in children with or without preexisting ENt antibody.

Antibodies, Viral↗

Molecular analysis of measles virus genome derived from SSPE and acute measles patients in Papua, New Guinea.

A very high annual incidence of 56 per million population below the age of 20 years for subacute sclerosing panencephalitis (SSPE) has been reported from Papua New Guinea (PNG). In a more recent study, we have confirmed this unusual high incidence for Eastern Highlands Province (EHP) of PNG. In the study, it was observed that the vaccination rate among SSPE patients registered at Goroka Base General Hospital (GBGH) in EHP was higher than that of other infants in the province in recent years. To identify the measles virus (MV) responsible for SSPE in EHP, sequence analysis of hypervariable region of the N gene was performed from 13 MV genomes: 2 amplified from clinical specimens of SSPE patients and 11 from acute measles patients. In 2 cases among the 11 with acute measles, nucleotide sequence of the entire H gene derived from isolated viruses was determined. Both nucleotide sequence and phylogenetic tree analyses showed that the amplified MV cDNAs were closely related to one another and belonged to the D3 genotype though they were different from any previously reported MV sequences. No genome sequences of vaccine strains were detected. These findings suggest that the MV strains prevailing in the highlands of PNG belong to genotype D3 of the MV and this wild-type MV rather than the vaccine strains was likely to be responsible for SSPE in these patients.

Acute Disease↗

Fowlpox virus recombinant encoding the measles virus fusion protein: protection of mice against fatal measles encephalitis.

A recombinant Fowlpox virus engineered to encode the measles virus fusion protein was shown to protect mice against a challenge measles infection. A vaccine dose of about 10(6) p.f.u. was needed to protect nearly 100% of the animals. Mice failed to develop a significant level of antibodies directed against measles virus suggesting that other components of the immune system may be involved.

Animals↗

Characterization of measles viruses isolated after measles vaccination.

Seven measles virus (MV) strains were isolated from children who developed clinical signs of fever and rash 3-9 days after measles vaccination. The nucleotide sequence of the H gene, the molecular size of the H protein, the haemadsorption activity on African green monkey red blood cells, and antigenicity as determined by virus neutralization revealed that one strain was of the vaccine type and the remaining six were the wild virus type. Isolation of the virus directly from patients suspected of a vaccine-induced side-reaction and subsequent characterization of such isolated virus may be useful in differentiation between vaccine-induced side-reactions and natural measles.

Antibodies, Monoclonal↗

Measles and rubella antibody response after measles-mumps-rubella vaccination in children with afebrile upper respiratory tract infection.

The effect of concurrent afebrile viral upper respiratory tract infection (URI) on measles and rubella serum antibody response after measles-mumps-rubella (MMR) vaccination was determined in 580 1-year-old children, 369 with URI and 211 without URI, with the use of preimmunization and postimmunization sera. The presence of URI during the preceding 28 days, at the time of, or up to 7 days after immunization had no effect on the antibody response to either the measles or the rubella component of the vaccine. These findings support the recommendation that MMR vaccine be give to children at the recommended age regardless of the presence of afebrile viral URI.

Antibodies, Viral↗

Response to measles revaccination among toddlers in Saudi Arabia by the use of two different trivalent measles-mumps-rubella vaccines.

This trial confirmed the immunogenicity of a standard dose of measles vaccine Edmonston-Zagreb strain administered at the age of 6 months as evaluated serologically at 12 months of age in 94 healthy children in Saudi Arabia. The residual seropositivity rate for measles was 53.4 and 80.6% as measured by enzyme immunoassay (EIA) and plaque neutralization, respectively, and could be increased to virtually 100% seroprotection after immunization with 1 of 2 measles-mumps-rubella (MMR) vaccines (Triviraten Berna or MMR II MSD) at 12 months of age. In both groups, more than 90% of infants showed an immune response to the mumps and rubella vaccine strains at 14 months of age. There was a difference in the geometric mean titres of mumps antibodies in favour of MMR II (P < 0.001). The seroconversion rates for mumps antibodies differed between the 2 vaccines because of the different test systems and/or the different cut-off levels used. The study reconfirmed that for the assessment of Rubini mumps vaccine-induced antibodies the indirect immunofluorescence test is superior to the EIA. The systemic tolerability of both vaccines was excellent. Triviraten Berna is exclusively propagated on human diploid cell cultures and hence free of avian proteins.

Antibodies, Viral↗

Estimation of measles reproduction ratios and prospects for elimination of measles by vaccination in some Western European countries.

The objective of this study is to estimate the measles reproduction ratio for eight Western European vaccination programmes. Because many plausible age-structured transmission patterns result in a similar description of the observations, it is not possible to estimate a unique value of the reproduction ratio. A method is developed to estimate bounds and confidence intervals for plausible values of the reproduction ratios using maximum likelihood methods. Lower and upper bounds for plausible values of the basic reproduction ratio are estimated to be 7.17 (95% CI 7.14-7.20) and 45.41 (95% CI 9.77-49.57), corresponding to lower and upper bounds on critical vaccine coverage of 86.6% and 98.1%. Of the eight evaluated vaccination programmes, four have vaccine coverage below the lower bound and allow measles to persist, and four have vaccine coverage at the upper bound and may eventually eliminate measles.

Adolescent↗

Spectrum of anti-measles immunoglobulin G subclasses in convalescents after measles.

A simple semiquantitative method for measuring anti-measles IgG subclasses is developed on the basis of commercial diagnostic test system for measurements of anti-measles IgG and a kit of peroxidase-labeled monoclonal antibodies to human IgG subclasses. During the acute phase of the disease specific antibodies are presented mainly by IgG2 antibodies, while in subjects with a history of measles more than 10 years before 2 subgroups were detected, which responded by production of IgG2 or IgG1 subclasses.

Adult↗

Sequence analysis of the hemagglutinin gene of measles virus isolates in Denmark 1997-1998: no evidence of persistent circulation of measles virus in Denmark.

The hemagglutinin-coding region of 17 virus samples from 12 measles cases in Denmark during 1997-1998 was analysed by partial nucleotide sequencing. The cases appeared as three sporadic cases and two epidemics, both with a limited time course and geographical distribution. The measles strains identified from the three sporadic cases and two epidemics could be allocated to five different previously well-defined sequence groups consistent with the assumption that cases of measles in Denmark are due to repeated introduction from abroad rather than persistent circulation of strains in the population.

Antibodies, Viral↗

Evaluation of serological and virological tests in the diagnosis of clinical and subclinical measles virus infections during an outbreak of measles in The Netherlands.

We evaluated different approaches for diagnosing measles virus (MV) infection in unvaccinated children and in healthy contact persons (n=194) during a measles epidemic in The Netherlands. MV RNA was detected by reverse-transcriptase polymerase chain reaction in throat-swab specimens from 93% of the patients with clinical symptoms. MV RNA was detected from 5 days before until 12 days after the onset of symptoms. Most patients (88%) also secreted MV RNA in their urine until 5 weeks after the onset of symptoms. Oral fluid proved to be the most practical specimen for the simultaneous detection of MV-specific IgM antibody and viral RNA, which, together, confirmed 93% of measles cases. Viral RNA was also detected in oropharyngeal specimens from 3 healthy contact persons with serological proof of MV infection. The results of this study emphasize the feasibility of combined detection of viral RNA and MV-specific IgM antibodies in oropharyngeal specimens for the diagnosis of clinical and subclinical MV infection.

Adolescent↗

Elimination of measles and of disparities in measles childhood vaccine coverage among racial and ethnic minority populations in the United States.

The gap in measles vaccine coverage between white and nonwhite children was as large as 18% in 1970. During the measles epidemic of 1989-1991, attack rates among nonwhite children <5 years of age were 4- to 7-fold higher than rates among white children. Because of the epidemic and of the known disparity in vaccine coverage and risk of disease, a dual strategy to eliminate measles in the United States was implemented: universal interventions likely to reach the majority of children and targeted interventions more likely to reach nonwhite children. In 1992, the gap in coverage between white and nonwhite children was reduced to 6% (from 15% in 1985); the risk of disease among nonwhite children was narrowed to <or=4-fold the risk of white children. During the 1990s, further implementation of the dual strategy resulted in narrowing the gap in vaccine coverage to 2% and elimination of endemic disease in all racial and ethnic populations. This dual strategy deserves close scrutiny by health professionals and policy makers in devising programs to meet the Healthy People 2010 objectives for the elimination of other health disparities.

Black People↗

Changing epidemiology of measles in Hong Kong from 1961 to 1990--impact of a measles vaccination program.

With the use of measles vaccine since 1967, Hong Kong has experienced a low incidence of measles until a major outbreak in 1988. A shift in the distribution of susceptible children to older age groups was suddenly accelerated in the 1988 outbreak. The attack rate increased by 18.9-fold for children greater than 10 years old, while that for those in the best-protected age group of 1-4 years was only 2.2-fold. Of the cases during that outbreak, 56.3% would have been considered preventable with the present vaccination regimen, and vaccine failures accounted for only 20.4% of the cases. Present control strategies aim at increasing the coverage rate rather than introducing a two-dose regimen, which may be necessary when vaccine failures account for a larger proportion of measles cases.

Adolescent↗

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

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

Adolescent↗

Measles viruses on throat swabs from measles patients use signaling lymphocytic activation molecule (CDw150) but not CD46 as a cellular receptor.

Both CD46 and signaling lymphocytic activation molecule (SLAM) have been shown to act as cellular receptors for measles virus (MV). The viruses on throat swabs from nine patients with measles in Japan were titrated on Vero cells stably expressing human SLAM. Samples from all but two patients produced numerous plaques on SLAM-expressing Vero cells, whereas none produced any plaques on Vero cells endogenously expressing CD46. The Edmonston strain of MV, which can use either CD46 or SLAM as a receptor, produced comparable titers on these two types of cells. The results strongly suggest that the viruses in the bodies of measles patients use SLAM but probably not CD46 as a cellular receptor.

Animals↗