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Comparative efficacy of a canine distemper-measles and a standard measles vaccine for immunization of rhesus macaques (Macaca mulatta).

Measles virus (MV), a highly infective paramyxovirus, has caused sporadic epizootics characterized by high morbidity and increased mortality in nonhuman primates. Measles vaccines for human use, although effective, are cost prohibitive for use in primate colonies. We compared the efficacy of one or two doses of Vanguard D-M, a canine distemper-measles (CD-M) vaccine, with a single dose of Attenuvax, a human measles vaccine. Compared with 81% of animals inoculated with Attenuvax, all animals inoculated with one or two doses of Vanguard developed detectable MV antibodies. One year after immunization, six juveniles from each vaccine group, along with three unvaccinated controls, were challenged with pathogenic MV and were monitored for clinical signs of disease, viremia, viral shedding, and immune response. All uninoculated controls developed clinical disease and viremia, and shed virus in nasopharangeal secretions. Subclinical viremia without viral shedding was identified in two Attenuvax- and two single-dose Vanguard-inoculated animals. Viremia was not detected in any two-dose Vanguard-inoculated animals. Significantly higher neutralization antibody titers were observed in animals receiving Vanguard. Results of this study indicate that Vanguard is at least as efficacious as Attenuvax for protection of rhesus macaques. The considerably lower cost of Vanguard makes vaccination against measles in large breeding colonies economically feasible.

Animals↗

Difficulties in measles elimination: prevalence of measles antibodies before and after mass vaccination campaign in Laos.

Responding to the declaration of regional polio eradication in 2000, Western Pacific Region (WPR) has been strengthening the efforts for measles elimination. Nevertheless, we questioned the feasibility of the measles elimination in Laos, where measles was still endemic. This study was undertaken with the aim to examine the impact of mass measles vaccination campaign, by comparing the prevalence of measles antibodies between before and after the campaign in 2000, among the children aged 9 months to 4 years in the two pilot sites. The constraints of mass vaccination campaign have been explored in this study. It was also suggested that more efforts should be put on reconstruction of the existing routine immunization service in Laos, which had been weakened by aggressive eradication programme.

Age Factors↗

The epidemiology of measles in Poland: prevalence of measles virus antibodies in the population.

WHO has adopted a goal of eliminating indigenous measles from the European Region by the year 2007. The strategy focuses on reducing the proportion of susceptible individuals in the population to low levels and maintaining these low levels of susceptibility. Routine vaccination against measles for children aged 13-15 months was introduced in Poland in 1975, and a second dose added in 1991. High coverage (> 95%) is achieved with both doses. In order to assess progress towards measles elimination in Poland, a serological survey was performed to evaluate the impact of vaccination on the susceptibility profile of population. Three thousand residual serum samples from individuals aged 1-30 years were collected from hospitals in six selected voivodeships (administration units) in Poland. These were tested for measles-specific IgG using a commercial ELISA. Overall 4% (120/3000) were negative for measles virus antibody. The highest proportion of negatives (8.2%) occurred among cohorts born 1977-81--the only cohorts in which susceptibility exceeded the WHO targets. 'Catch-up' vaccination strategies should target these cohorts.

Adolescent↗

Successful DNA immunization against measles: neutralizing antibody against either the hemagglutinin or fusion glycoprotein protects rhesus macaques without evidence of atypical measles.

Measles remains a principal cause of worldwide mortality, in part because young infants cannot be immunized effectively. Development of new vaccines has been hindered by previous experience with a formalin-inactivated vaccine that predisposed to a severe form of disease (atypical measles). Here we have developed and tested potential DNA vaccines for immunogenicity, efficacy and safety in a rhesus macaque model of measles. DNA protected from challenge with wild-type measles virus. Protection correlated with levels of neutralizing antibody and not with cytotoxic T lymphocyte activity. There was no evidence in any group, including those receiving hemagglutinin-encoding DNA alone, of 'priming' for atypical measles.

Animals↗

Clinical features of measles according to age in a measles epidemic.

The purpose of this study was to retrospectively investigate the relationship between age and clinical manifestations and laboratory findings in patients with measles. The study included 216 patients admitted to a hospital in Daejeon, 1 of the largest cities in South Korea, during the 2000-2001 measles outbreak: very young children (<2 y old; 159 patients), school age children (9-11 y old; 34 patients), and young adults (>16 y old; 23 patients). Few of the very young children (9%), but most of the older children (86%) had a history of a prior measles-mumps-rubella vaccination. There were no statistical differences between the 3 groups in terms of the total duration of fever, length of hospitalization, occurrence of complications (defined as hospitalization for more than 7 d) or anti-measles IgM positivity. A reduction in the number of white blood cells and lymphocytes was observed in all age groups. The levels of C-reactive protein were not different between very young children and older children, but hepatic involvement was more prevalent in young adults. In conclusion, the clinical course including the complications experienced was similar in all the measles patients regardless of age.

Adolescent↗

Measles in England and Wales--II: The impact of the measles vaccination programme on the distribution of immunity in the population.

Measles notification and vaccination data for England and Wales are analysed to reveal trends in age-specific incidence and immunity levels in successive cohorts born since 1950. A method for cumulating infection and vaccination experience is described in detail. The analysis reveals that there was a trend towards lower incidence rates of measles, and towards younger average age of cases, for the 10 years prior to commencement of the national immunization programme in 1968. Since the immunization programme began, there has been a dramatic and complicated shift in the age pattern of measles immunity in the population, such that some young age groups are now better protected, but some older age groups less well protected, than they were before the programme. These trends are discussed with critical attention to the possibility that they may reflect biases in the available data. It is concluded that the number of susceptibles over 10 years of age is increasing, and that this could have appreciable public health implications in the years to come. It appears that the total number of individuals susceptible to measles has remained relatively constant, between 4 and 4.5 million, before and after the immunization programme. Though consistent with basic theory, this maintenance of constant overall number of susceptibles has not been demonstrated before. Because the implications of these analyses are important for the strategy of measles control, it is important that appropriate serological surveys be carried out in order to assess the validity of the findings.

Adolescent↗

Acute measles in patients with and without neurological involvement: distribution of measles virus antigen and RNA.

Using peroxidase immunohistochemistry and in situ hybridization to localize viral antigen and RNA, we studied autopsy tissues from 20 cases of acute fatal human measles (including seven patients with acute encephalomyelitis) and peripheral blood mononuclear cells from 16 patients with acute, nonfatal measles. In immunologically normal patients, virus was detected in five of nine who died five days or less after the onset of rash but in none of 11 who died later. Virus was localized to epithelial cells of lung, gut, bile duct, bladder, and skin and to lymphoid organs. Neither viral antigen nor RNA was detected in brain sections from 14 patients, including seven with acute encephalomyelitis and four with virus identified in other tissues, a finding supporting an indirect pathogenesis of post-measles encephalomyelitis. These data show that measles virus replicates in cells previously not recognized to be involved (capillary endothelium of lymph node and thymus, Hassall's corpuscles, and hepatic duct epithelium) and that invasion of the brain parenchyma during acute measles is uncommon.

Acute Disease↗

Clinical efficacy of measles vaccine during the 1990 measles epidemic.

Because of increased measles incidence in the United States during 1989 and 1990 and the recent finding of genomic differences between vaccine virus and contemporary wild measles viruses, we conducted a study to determine whether the current measles vaccine had become less effective. Household secondary attack rates for 203 California children ages 1 to 5 years were 4.2 and 77.8% for vaccinated and unvaccinated children, respectively, and the vaccine efficacy was 95% (95% confidence interval: 89%, 97%). The protective efficacy for postexposure vaccination and use of IG were both low, 4% (95% confidence interval: less than 0, 36%) and 8% (95% confidence interval: less than 0, 59%), respectively. The measles vaccine efficacy found in this study is similar to those obtained in previous years and indicates that the measles epidemic of 1989 to 1990 occurred despite high vaccine effectiveness.

California↗

Measles immunisation compliance: poor impact of bicentennial measles control campaigns on children under five.

A measles immunisation survey was conducted among children who enrolled in school kindergarten classes in the Eastern Sydney Area in 1989. Its aims were to determine baseline compliance rates, to identify subpopulations at risk of poor compliance and to evaluate the impact of the bicentennial measles control campaigns on compliance among children under five years. All 73 schools participated, questionnaires were returned by 2230 (81.4%) children, and compliance with immunisation was 91.3%. 89.1% of children attending public schools were immunised, compared to 91.9% of Catholic school pupils and 95.8% of independent school pupils (chi 2 = 21.4, P less than 0.001). Among public school children, 91.6% of pupils from English-speaking families were immunised in comparison to 81.4% of pupils from non-English-speaking backgrounds (chi 2 = 20.5, P less than or equal to 0.001). The fraction of previously unimmunised children who were known to have been immunised during each year of the measles control campaigns was 16% in 1986-87, 10% in 1987-88 and 9% in 1988-89. These small increments in immunisation uptake suggest that under-five-year-olds were not effectively targeted by the measles control campaigns. However, no control group was evaluated. Immunisation delivery systems must be designed which ensure that all children receive measles-mumps-rubella vaccine as soon as possible after the first birthday. Immunisation promotions and service providers will need to target specific language and socioeconomic groups.

Australia↗

[Real time observation of binding of measles virus to Vero cells and neutralization of measles virus by human immunoglobulin using optical biosensor--a new real time diagnosis system for viral infections].

An optical biosensor to monitor molecular intractions was developed. This system made possible to observe reactions with a few minutes. We tried to apply this system for rapid diagnosis of viral infections. Measles virus propagated in our laboratory and crude rabbit anti-measles antiserum were used. A commercially available human immunoglobulin was used as a representative of patient sera. A crude rabbit anti-measles antiserum was fixed on the reaction surface of aminosilane coated cuvette, and specific binding of measles virus to this antibody was monitored. Specific purified IgG antibody was known to give as high sensitivity as the conventional culture method. But the sensitivity by crude antibody was found to be 1/10 in the sensitivity. This might be caused by the masked effects on specific antibody to the contaminated high amounts of non-specific proteins. None purified polyclonal antisera for most of the viruses are commercially available, and 10-20 times highly concentrated antibody solutions could be used for this titrations. Estimated anti-measles antibody titer of the commercial available human immunoglobulin by biosensor system was found to be the same as that by the conventional culture method. It was suggested that 1 X 10(3) virus particles/ml in the test solutions could be detectable and titerable by using commercially available specific anti-viral antibody in real time, and the viral infections could be diagnosed within an hour.

Animals↗

Mothers' concept of measles and attitudes towards the measles vaccine in Ile-Ife, Nigeria.

The attitude of Nigerian mothers, mainly Yoruba, towards measles vaccine and other aspects of prevention are influenced by different perceptions of the cause of measles. There is a significant correlation between the literacy of mothers and their belief in the efficacy of measles vaccine but not between their ages and belief. The mothers' perception of measles is a function of their socioeconomic characteristics, with the lower socioeconomic group tending more to define measles within the supernatural context. The findings indicate the necessity for health education to be based on local culture when promoting vaccination.

Age Factors↗

Measles, mumps, rubella vaccine (Priorix; GSK-MMR): a review of its use in the prevention of measles, mumps and rubella.

GSK-MMR (Priorix) is a trivalent live attenuated measles, mumps and rubella (MMR) vaccine which contains the Schwarz measles, the RIT 4385 mumps (derived from the Jeryl Lynn mumps strain) and the Wistar RA 27/3 rubella strains. GSK-MMR as a primary vaccination demonstrated high immunogenicity in clinical trials in >7500 infants aged 9-27 months, and was as immunogenic as Merck-MMR (MMR II). However, antimumps seroconversion rates and geometric mean titres (GMTs) were significantly higher in infants receiving GSK-MMR compared with Berna-MMR (Triviraten trade mark ) recipients. Coadministration of GSK-MMR with a varicella vaccine (Varilrix; GSK-MMR/V) did not significantly affect the immunogenicity of GSK-MMR. A persistent immune response to GSK-MMR has been demonstrated in follow-up data from several randomised trials. GMTs for measles, mumps and rubella antibodies remained high in GSK-MMR recipients 1-2 years post-vaccination and were similar to those in Merck-MMR recipients. The immunogenicity of GSK-MMR was high, and similar to that of Merck-MMR, when used as a second dose in children aged 4-6 or 11-12 years who had received a primary vaccination with Merck-MMR in their second year of life. Although there are no protective efficacy data concerning the GSK-MMR vaccine to date, the rubella Wistar RA 27/3 rubella and Schwarz measles strains have well established protective efficacy; the new RIT 4385 mumps strain is expected to afford similar protection from mumps to that achieved with mumps vaccines that contain the Jeryl Lynn mumps strain (e.g. Merck-MMR). GSK-MMR was well tolerated as a primary or secondary vaccination, and in most clinical studies comparing GSK-MMR with Merck-MMR as a primary vaccination in infants, GSK-MMR was associated with significantly fewer local adverse events (e.g. pain, swelling and redness). The incidence of local adverse events with GSK-MMR, GSK-MMR/V or Berna-MMR was similar. GSK-MMR and Merck-MMR were associated with similar rates of fever, rash and parotid gland swelling, but Berna-MMR was associated with a lower incidence of fever. In conclusion, GSK-MMR is a highly immunogenic MMR vaccine with good tolerability. In clinical trials, the immunogenicity of GSK-MMR was similar to that of Merck-MMR, and the mumps component was more effective at eliciting seroprotection than that of Berna-MMR. Furthermore, GSK-MMR causes fewer injection-site adverse events than Merck-MMR. As such, GSK-MMR is an attractive alternative for immunisation against measles, mumps and rubella.

Child↗

The changing age ecology of measles and its implications on measles control.

In the City of Gweru measles vaccination was commenced in 1971. With the advent of the Expanded Programme on Immunisation in 1981-82, measles vaccination coverage was increased, reaching over 80 pc in 1985 and after. Despite this vaccination effort measles morbidity rates have remained high and epidemics continue to occur periodically. It is argued that the shift of the disease from young age groups to older children, coupled with the fact that there are more vaccinees amongst cases with the disease, will mean that transmission will continue uninterrupted. Possible reasons for persistent transmission in older children are explored. It is concluded that measles revaccination is required to interrupt measles transmission.

Child↗

[Current problems in the epidemiology and prevention of measles in the Ukrainian SSR. Reasons for the unfavorable epidemic situation with respect to measles which developed during the years of planned immunization].

In the first years of specific mass immunization (1969--1971) the epidemic situation in the Ukrainian SSR was more favorable than during the following period (1976--1977). With time after immunization the protection of the vaccinees decreased. The main reason of the measles virus circulation, of regular epidemics and the aggravation of the epidemic situation in 1976 and 1977 was the presence of 10% of seronegative children, which amounts to more than a million children unprotected against measles in the republic, and the decrease of the immune stratum of the children who had led measles (who played a definite role in the suppression of the epidemic process in 1969--1971) from 40% to 12%. The primary task of measles control is to improve the quality of the vaccine and the system of vaccination. The epidemiological parameters characteristic of measles at present and the results of the serological study of immunity suggest the absence of epidemiological indication for mass revaccination at the present moment.

Adolescent↗

MEASLES AND MEASLES VACCINATION IN AN AFRICAN VILLAGE.

Over the last five years, a number of reports have appeared drawing attention to the serious results of measles in young West African children. This is borne out by observations over a three-year period on children in the village of Imesi, which showed measles to be a severe and often fatal disease. The original live attenuated measles vaccine developed by Enders has been shown to give good protection and, in combination with immune serum, has been widely used in the USA. However, the need to combine it with immune serum severely limits its usefulness, owing to the small quantities of serum available and the high cost. In the present study, the reaction produced by the original vaccine with immune serum was compared with the reaction produced by a further attenuated vaccine without serum. The latter gave significantly fewer and less severe reactions, but produced a satisfactory serological response. This new vaccine should facilitate large-scale immunization of children in areas such as West Africa where protection against measles is urgently required.

Africa↗

Genomic characterization of wild-type measles viruses that circulated in different states in Brazil during the 1997 measles epidemic.

Despite the marked reduction in the incidence of measles in Brazil, a measles epidemic occurred in this country in 1997. The measles cases observed during this epidemic began to reappear in large numbers in São Paulo, and spread to Rio de Janeiro and other Brazilian states. In the present study molecular biology techniques were used for the detection and genomic characterization of measles viruses from clinical samples such as urine and nasopharyngeal secretions collected in the states of Rio de Janeiro, Minas Gerais and Paraná, during the 1997 epidemic. RT-PCR and nucleotide sequence analysis of part of the carboxyl-terminal region of the nucleoprotein gene of measles viruses obtained directly from clinical samples or from infected cell cultures during this epidemic classified all as wild-type of genotype D6. As the genotype D6 was identified in different Brazilian states, this study demonstrated that this genotype was circulating in Brazil during the 1997 epidemic.

Adult↗

Rapid diagnosis of measles using enzyme-linked immunosorbent assay for measles immunoglobulin M.

An enzyme-linked immunosorbent assay (ELISA) for measles-specific immunoglobulin M (MIgM) was developed for use as a rapid diagnostic test for acute measles. A titer greater than or equal to 1:20 in both the acute and convalescent sera was present in 100% of patients with measles and was diagnostic of acute measles infection in children. Interference by rheumatoid factor (RF) was avoided by pretesting sera for RF and absorption with aggregated gamma globulin. Ion exchange separation of IgM and IgG should eliminate RF interference. The ELISA MIgM assay can easily be used in any laboratory for the serologic confirmation of measles infection.

Adult↗

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

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.

Adolescent↗