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PubMed1971

Effect of measles vaccination on incidence of measles in the community.

A study of the effect of measles vaccination on the incidence of the disease in eight separate areas of England and Wales was begun in 1966. It showed an inverse association between the proportion of children vaccinated and the incidence of measles in the area in the following year, but measles epidemics occurred in several of the areas in subsequent years, despite continuing vaccinations.Measles vaccination was introduced on a large scale in Britain in 1968. Analysis of the notification and vaccination statistics shows that the vaccination of about 10% of the child population (under 15 years) in 1968 sufficed to "replace" the measles epidemic which had been expected in the period October 1968 to September 1969 by a low incidence of the disease, typical of that in previous "interepidemic" years. Further, the effect of the vaccinations was to prevent the development of natural measles in susceptible unvaccinated children as well as in the vaccinated subjects. Thus the number of immune subjects in the community was increased by the vaccinations, but as a result there was a reduction in the number of subjects who acquired immunity from natural measles. These opposed results can therefore explain why vaccination may be effective in the community for only a year or two, though vaccination protects the individual for much longer.It is estimated that a continuing vaccination rate of 40 to 50% of the children born each year would be necessary to replace the regular biennial measles epidemics in Britain by a continuous endemic incidence, and might perhaps lead to the disappearance of the disease without a further major epidemic, but that a continuing vaccination rate of 80 to 90% of children born each year would then be necessary to prevent its reintroduction. The long-term control of measles by vaccination will thus probably prove more difficult than for any other infectious disease.

Adolescent↗

PubMed1999

Twice vaccinated recipients are better protected against epidemic measles than are single dose recipients of measles containing vaccine.

OBJECTIVE: To study measles risk after revaccination. DESIGN: A population-based case-control study during an epidemic season. MAIN OUTCOME MEASURE: Relative serologically confirmed measles risk. PARTICIPANTS AND METHODS: 153 vaccinated cases, mostly from rural areas, were serologically confirmed as measles at the central laboratory in 1988-89. A randomly selected group of 453 controls from either municipalities of vaccinated cases or from areas where measles attack rate was > 600/10(5), was identified via the population registry. Vaccination and measles histories of cases and controls were determined from official vaccination cards. RESULTS: Once and twice vaccinated had crude relative risk 15.6 and 2.3 compared with thrice vaccinated. When cases who had received their first vaccination at less than 14 months of age were omitted from analysis, once vaccinated had 4.0 (95% CI 1.2, 16.6) times higher age adjusted measles risk compared with twice vaccinated. When, omission was extended to cases from one particular municipality where even revaccinees had high measles risk during an explosive outbreak the corresponding risk ratio was 17.8 (2.8, 67.8). CONCLUSIONS: Twice vaccinated have better protection against epidemic measles compared with single dose recipients.

Adolescent↗

PubMed1978

Measles vaccination after exposure to natural measles.

When an extensive measles epidemic broke out in Turku in late 1975, the availability of a previous study on measles vaccination reactions in 442 children permitted a comparative evaluation to be made on reactions to and the efficacy of measles vaccine (Schwartz strain) administered after exposure to natural measles. In a preliminary study, nine children were vaccinated one to 14 days after exposure to natural measles but before prodromal symptoms appeared. Only one of these nine children developed symptoms and signs comparable to those of the natural disease. In five day-care centers the children were vaccinated when five or more children out of 30 to 40 at each center had measles. In only five of 74 exposed children were the signs and symptoms comparable to those of natural measles. No marked differences in signs and symptoms after the vaccinations were observed between the exposed and nonexposed children. It is concluded that vaccination is safe, can usually prevent measles, even when administered after a prolonged interval following exposure to natural disease, and can usually control an epidemic in progress.

Adolescent↗

PubMed2002

Severe infantile measles encephalitis occurred three months after neonatal measles.

A 3-month-old girl who developed severe measles encephalitis after neonatal measles is reported. Her mother had measles when she was ten days old and she was admitted to our hospital with low grade fever, Koplik spot, and mild exanthema seventeen days after birth, and she recovered in 7 days without any complication. At three months of age, she was readmitted because of intractable seizures. The levels of IgM and IgG antibodies against measles in the cerebrospinal fluid were elevated. The measles virus genome, amplifying the region encoding the nucleocapsid protein, was detected from the brain specimen by reverse transcriptase-polymerase chain reaction. Magnetic resonance imaging showed a focal destructive lesion and diffuse cerebral atrophy. The electroencephalogram did not show periodic synchronous discharges. Although the neonatal measles was believed to be relatively mild in severity, the possible development of measles encephalitis should be carefully monitored in an infant who had neonatal measles.

Encephalitis, Viral↗

PubMed1983

Post-measles corneal ulceration in children in northern Nigeria: the role of vitamin A, malnutrition and measles.

This work was prompted by the observation that corneal ulceration was apparently more common in young children in the guinea savannah area of northern Nigeria than in children in the tropical rainforest areas of southern Nigeria, where the intake of vitamin A, as the provitamin in red palm oil, is higher. Since corneal ulceration was usually seen in association with measles, a study was carried out to clarify the relationship between nutritional status, measles infection and vitamin A status in young children. The concentration of total retinol was measured in the plasma of well-nourished and malnourished children under three years of age, with or without a clinical record of recent measles. One hundred and twenty children were studied of whom 17 had corneal lesions. Malnutrition and measles were both found to depress the plasma concentrations of retinol and albumin. Measles depressed retinol levels (-20 to -30%) more than did malnutrition (-4 to -12%) while malnutrition had a greater depressing effect on albumin concentration (-23 to -30%) than did measles (-11 to -23%). The results support the hypothesis that corneal ulceration found in association with measles in northern Nigeria, although clinically similar to xerophthalmia, is not simply mediated through an effect of measles on the concentrations of vitamin A in plasma.

Adolescent↗

PubMed1985

Low molecular weight measles immunoglobulin M in subacute sclerosing panencephalitis and acute measles.

Thirty eight patients with subacute sclerosing panencephalitis (SSPE) were investigated. Five patients who previously had measles immunoglobulin M (IgM) detected in unfractionated serum and cerebrospinal fluid (CSF) had measles IgM exclusively in the low molecular weight (LMW) fractions of serum and CSF. Measles IgM had previously not been found in unfractionated serum from 33 patients but was detected exclusively in the LMW fractions of serum from 30 patients. Seven children with acute measles had the expected high molecular weight (HMW) measles IgM in serum but 5 also had LMW measles IgM. Four young adults who had had measles in childhood had neither HMW nor LMW measles IgM in their sera.

Acute Disease↗

PubMed2005

Measles virus genotype circulation in Spain after implementation of the national measles elimination plan 2001-2003.

Molecular characterization of measles virus is important for disease surveillance and for monitoring elimination of the virus throughout the world. Furthermore, knowledge of genotype distribution in as many countries as possible, is useful for tracing the origin of a strain, especially in countries without endemic measles disease, where most cases are imported. Data on genotypes circulating in Spain from 1970 to 1997 showed the prevalence of genotypes C1, C2, and D6, with subsequent replacement of each other. After the establishment of the Spanish Measles Elimination Plan, genotyping with a new retrotranscriptase polymerase chain reaction (RT-PCR) was undertaken directly on 92 specimens, corresponding to 90 patients, which were positive for measles by a different diagnostic RT-PCR. Genotypes B3, D4, D8, A, C2, H1, and D7 were found in different autonomous communities (Madrid, Balearic Islands, Valencia Community, Extremadura, Andalusia, Canary Islands and Murcia) between 2001 and 2003 with none of these genotypes being prevalent. After the introduction of the vaccine in 1978, the incidence of the disease decreased from 150,000 cases in 1977 to 64 in 2002. This could be the reason for the change observed in the pattern of measles genotype circulation, since this pattern was reported in countries at an advanced stage of eradication of measles. This report considers that Spain is on the way to eradicating measles.

Base Sequence↗

PubMed1995

Reduced seroconversion to measles in infants given vitamin A with measles vaccination.

Administration of 100,000 IU vitamin A at the time of measles immunisation is currently recommended for infants in developing countries. However, the safety and value of giving vitamin A, a potent immune enhancer, with live measles virus vaccines are unknown. We conducted a randomised, double-blind, placebo-controlled clinical trial in Indonesia to evaluate the effect of simultaneous vitamin A supplementation on the immune response to measles immunisation at six months of age. 336 infants received either vitamin A (100,000 IU) or placebo when immunised with standard-titre Schwarz measles vaccine. 82% of infants seroconverted to measles. In a multiple logistic regression model adjusting for maternal antibody titres, vitamin A supplementation was associated with a lower likelihood of seroconversion to measles (odds ratio 0.40, 95% CI 0.19-0.88), and girls were less likely to seroconvert than boys (0.34, 0.15-0.76). Immunisation with standard-titre Schwarz vaccine at six months of age in this study population is characterised by high seroconversion rates. However, simultaneous high-dose vitamin A may interfere with seroconversion to live measles vaccine in infants with maternal antibody.

Antibodies, Viral↗

PubMed2004

Identification of primary and secondary measles vaccine failures by measurement of immunoglobulin G avidity in measles cases during the 1997 São Paulo epidemic.

Despite almost universal use of measles vaccines in recent decades, epidemics of the disease continue to occur. Understanding the role of primary vaccine failure (failure to seroconvert after vaccination) and secondary vaccine failures (waning immunity after seroconversion) in measles epidemics is important for the evaluation of measles control programs in developing countries. After a measles epidemic in São Paulo, Brazil, 159 cases previously confirmed by detection of specific immunoglobulin M (IgM) antibodies were tested for IgG avidity, and a secondary immune response, defined by an IgG avidity index of at least 30%, was established in 30 of 159 (18.9%) patients. Among the 159 patients, 107 (67.3%) had not been vaccinated and 52 (32.7%) had received one or more doses of measles vaccine. Of the 107 unvaccinated patients, 104 (97.2%) showed a primary immune response, defined as an IgG avidity index of less than 30%. Among the 52 patients with documented vaccination, 25 (48.1%) showed a primary immune response and 27 (51.9%) showed a secondary immune response, thereby constituting a secondary vaccine failure. Primary vaccine failure was observed in 13 of 13 patients vaccinated prior to 1 year of age and in 43.5 and 12.5%, respectively, of patients receiving one or two doses after their first birthdays. These results provide evidence that measurement of IgG avidity can be used to distinguish between primary and secondary vaccine failures in vaccinated patients with measles; the method can also be a useful tool for the evaluation of measles control programs.

Adolescent↗

PubMed2000

Human parainfluenza virus type 3 (PIV3) expressing the hemagglutinin protein of measles virus provides a potential method for immunization against measles virus and PIV3 in early infancy.

Recombinant human parainfluenza virus type 3 (PIV3) was used as a vector to express the major protective antigen of measles virus, the hemagglutinin (HA) glycoprotein, in order to create a bivalent PIV3-measles virus that can be administered intranasally. The measles virus HA open reading frame (ORF) was inserted as an additional transcriptional unit into the N-P, P-M, or HA-neuraminidase (HN)-L gene junction of wild-type PIV3 or into the N-P or P-M gene junction of an attenuated derivative of PIV3, termed rcp45L. The recombinant PIV3 (rPIV3) viruses bearing the HA inserts replicated more slowly in vitro than their parental viruses but reached comparable peak titers of >/=10(7.5) 50% tissue culture infective doses per ml. Each of the wild-type or cold-passaged 45L (cp45L) PIV3(HA) chimeric viruses replicated 5- to 10-fold less well than its respective parent virus in the upper respiratory tract of hamsters. Thus, insertion of the approximately 2-kb ORF itself conferred attenuation, and this attenuation was additive to that conferred by the cp45L mutations. The attenuated cp45L PIV3(HA) recombinants induced a high level of resistance to replication of PIV3 challenge virus in hamsters and induced very high levels of measles virus neutralizing antibodies (>1:8,000) that are well in excess of those known to be protective in humans. rPIV3s expressing the HA gene in the N-P or P-M junction induced about 400-fold more measles virus-neutralizing antibody than did the rPIV3 with the HA gene in the HN-L junction, indicating that the N-P or P-M junction appears to be the preferred insertion site. Previous studies indicated that the PIV3 cp45 virus, a more attenuated version of rcp45L, replicates efficiently in the respiratory tract of monkeys and is immunogenic and protective even when administered in the presence of very high titers of passively transferred PIV3 antibodies (A. P. Durbin, C. J. Cho, W. R. Elkins, L. S. Wyatt, B. Moss, and B. R. Murphy, J. Infect. Dis. 179:1345-1351, 1999). This suggests that this intranasally administered PIV3(HA) chimeric virus can be used to immunize infants with maternally acquired measles virus antibodies in whom the current parenterally administered live measles virus vaccine is ineffective.

Animals↗

PubMedDate not supplied

Measles HI-antibody levels in Lagos children, Nigeria: a follow-up study to resurgence of measles in Lagos metropolis.

A total of 138 children aged between 0-36 months were bled and screened for measles haemagglutination inhibiting (HI)-antibody. Twenty seven children were from age group (0-4) months with 16 (59.3%) seropositive while, 67 and 44 were bled in the group (5-9) and > or = 12 months with 29 (43.3%) and 31 (70.5%) sero positive sera respectively. The distribution of the antibody titre pattern among various age groups suggest vaccination against measles should be at age 9 month. The antibody titres pattern of seroconverted vaccinees also showed that the vaccine administered at our study centre were potent enough to elicit good and protective immune response in vaccinees when given at age 9 month. Our study agrees with the current policy of vaccinating children against measles at age 9 months in Nigeria and should therefore be continued. Based on observations in this study, we suggest; continued administration of the Edmonston-Zagreb strain of measle vaccine currently-in-use in Nigeria, mother's breast-feeding of children for a longer period before the apporpriate age for vaccination, and the possible administration of Vitamin A-a potent immune enhancer, as a supplement during immunization programmes in Nigeria. The introduction of a booster dose of measles vaccine at elementary school age in order to care for the residual unvaccinated children may be a good strategy for measles eradication necessary to be considered in Nigeria and might probably forestall instances of measles outbreaks in children during their second year in school.

Antibodies, Viral↗

PubMed1996

Detection by polymerase chain reaction of wild-type measles virus genome in the cerebrospinal fluid of a patient with SSPE who had received measles vaccine.

BACKGROUND: Previous studies have reported that approximately 4-5% of patients with subacute sclerosing panencephalitis (SSPE) were given measles vaccination but had no history of natural measles. However, in the case who received measles vaccine, it has been extremely difficult to determine whether the actual cause of SSPE is the inoculated vaccine virus or not. OBJECTIVES: To detect the measles virus genome in a patient with SSPE and to analyze its nucleotide and deduced amino acid sequence. STUDY DESIGN: We applied the polymerase chain reaction (PCR) to detect the measles virus genome in specimens from a 12-year-old boy with SSPE who had received measles vaccine 10 years before and had no history of apparent natural measles. The oligonucleotide primers for PCR were prepared based on the nucleotide sequence of the F and NP genes of the measles virus Edmonston strain. RESULTS: F and NP genes were detected in both the cerebrospinal fluid and peripheral blood lymphocytes. Nucleotide and deduced amino acid sequence analysis of the F gene showed that the patient's virus was different from that of the vaccine strain. Judging from these results, it was likely that the SSPE-associated strain in this case was derived from the wild-type rather than the vaccine strain. CONCLUSIONS: PCR is a useful method to establish a definitive diagnosis of SSPE and to study the nature of the SSPE-associated virus.

Journal Article↗

PubMed2004

The laboratory confirmation of suspected measles cases in settings of low measles transmission: conclusions from the experience in the Americas.

The Americas have set a goal of interrupting indigenous transmission of measles using a strategy developed by the Pan American Health Organization (PAHO). This strategy includes recommendations for vaccination activities to achieve and sustain high immunity in the population and is complemented by sensitive epidemiological surveillance systems developed to monitor illnesses characterized by febrile rash, and to provide effective virological and serological surveillance. A key component in ensuring the success of the programme has been a laboratory network comprising 22 national laboratories including reference centres. Commercially available indirect enzyme immunoassay kits (EIA) for immunoglobulin M (IgM)-class antibodies are currently being used throughout the region. However, because there are few or no true measles cases in the region, the positive predictive value of these diagnostic tests has decreased. False-positive results of IgM tests can also occur as a result of testing suspected measles cases with exanthemata caused by Parvovirus B19, rubella and Human herpesvirus 6, among others. In addition, as countries maintain high levels of vaccination activity and increased surveillance of rash and fever, the notification of febrile rash illness in recently vaccinated people can be anticipated. Thus, managers in the measles elimination programme must be prepared to address the interpretation of a positive result of a laboratory test for measles IgM when clinical and epidemiological data may indicate that the case is not measles. The interpretation of an IgM-positive test under different circumstances and the definition of a vaccine-related rash illness in a setting of greatly reduced, or absent, transmission of measles is discussed.

Antibodies, Viral↗

PubMed2004

Influence of HLA-DRB1 alleles on lymphoproliferative responses to a naturally processed and presented measles virus phosphoprotein in measles immunized individuals.

Identification of stimulatory T-cell epitopes recognized by CD4+ T lymphocytes is important for vaccine development. Our previous studies using mass spectrometry identified a naturally processed HLA class II restricted DRB1*0301 T cell epitope in the measles virus phosphoprotein, MV-P1 (residues 179-197). Here we provide lymphocyte proliferation data from peripheral blood mononuclear cells (PBMC) obtained from 131 HLA-DRB1*0301-positive and HLA-DRB1*0301-negative (HLA discordant) individuals previously immunized against measles and report that a single amino acid substitution in the MV-P1 T cell epitope can reduce T cell proliferation and CD4+ T-cell recognition. Measles virus and measles peptide-specific lymphoproliferative responses and HLA-DRB1 allele associations reveal that the DRB1*0701 allele provided suggestive evidence of association with both measles virus (p = 0.03) and MV-P1 peptide (p = 0.06) lymphoproliferation. A marginally significant increase in the frequency of the *0301 allele (p = 0.10) was found among subjects who demonstrated low cellular responses to the measles virus. We found no associations between proliferation levels to the MV-P1 and MV-P2 peptides with *0301 alleles. We speculate that the glutamic acid at position 192 of the measles phosphoprotein is a critical immunogenicity factor and may influence the antigenicity of the naturally processed HLA class II MV-P1 epitope.

Alleles↗

PubMed1998

Immune response to measles vaccine in 6-month-old infants of measles seronegative mothers.

Determinants of measles vaccine-induced immune response in infancy include maternal immune status and the infant's age at immunization. In a previously published study, 74% of 19 6-month-old infants developed neutralizing antibody. Two of the infants were born to measles seronegative mothers. In order to (1) assess the prevalence of measles seronegativity in a population of US mothers born after 1960 and (2) assess the immunogenicity of standard titer measles vaccine in 6-month-old infants of measles seronegative mothers, mothers with healthy term (> or = 37 weeks gestation) infants attending well child care clinics at MetroHealth Medical Center were prospectively screened for measles antibody by EIA. If negative, maternal samples were retested for neutralization (NT) antibody. Fifteen of 169 women were seronegative by both assays. Six-month-old infants of 9 of these 15 seronegative mothers were enrolled in the pediatric vaccine study. Serological response of these 9 infants to monovalent measles vaccine (Attenuvax) was compared to the responses of 17 6-month-old infants of seropositive mothers and 15 15-month-old toddlers from our previous study. All 9 infants of seronegative mothers became EIA seropositive after the vaccine compared to 9 of 17 6-month-old infants born to seropositive mothers (p = 0.02). Differences in NT seroconversion rates (100% vs 70.6%) were not statistically significant. The comparison group of 15-month-old vaccinees showed 100% seroconversion by both assays. The NT geometric mean titer (GMT) was higher in the 15-month-old toddlers than in the 6-month-old infants born to seronegative mothers (87.2 vs 33.9, p < 0.01), suggesting age-related differences in humoral immune response unrelated to passively transferred maternal antibody.

Antibodies, Viral↗

PubMed2001

Altered synthesis of interleukin-12 and type 1 and type 2 cytokinesin rhesus macaques during measles and atypical measles.

Immunosuppression during and after measles results in increased susceptibility to other infections and 1 million deaths annually. The mechanism by which measles virus (MV) induces immune suppression is incompletely understood, but a type 2 skewing of the cytokine response after infection has been documented. In vitro studies suggest that lack of interleukin (IL)-12 production by monocytes and dendritic cells plays an early role in the skewed response. In addition, immunization with an inactivated measles vaccine before measles develops appears to lead to an even stronger type 2 skewing of the cytokine response and atypical measles. In this study, the cytokine responses in rhesus macaques were compared after vaccination with live and formalin-inactivated vaccines and after challenge with MV. In vivo production of IL-12 was decreased during the viremic phase of the illness, and production of IL-4 was increased during and after atypical measles, compared with measles.

Animals↗

PubMed2003

Progress toward measles elimination in Romania after a mass vaccination campaign and implementation of enhanced measles surveillance.

In response to an outbreak of >33,000 measles cases in 1996-1998 and to prevent an outbreak predicted for 2002, Romania conducted a nationwide measles-rubella vaccination campaign in October 1998. Some 2.1 million children aged 7-18 years were vaccinated. Data from national surveillance and seroprevalence studies conducted in three districts were used to assess the campaign and status of measles control. Surveillance data showed a dramatic drop in measles despite enhanced surveillance starting in October 1999. From October 1999 to December 2001, 400 suspected measles cases were reported, down from about 5000 cases annually in non-outbreak years. Only 29 (8%) of 386 cases with specimens were laboratory confirmed; 14 were clinically confirmed. Seroprevalence estimates showed high measles antibody levels before (92.9%) and after (94.4%) the campaign. The low number of laboratory-confirmed cases and high population immunity suggest that interruption of indigenous measles virus transmission is a real possibility for Romania.

Adolescent↗

PubMed2003

Determining measles-containing vaccine demand and supply: an imperative to support measles mortality reduction efforts.

Measles remains a major cause of mortality with an estimated 745,000 deaths in 2001. The timely, sustained, and uninterrupted supply of affordable vaccines is critical for global efforts to reduce measles mortality. The measles vaccine supply needs to be considered in the context of vaccine security. In 2000, the World Health Organization (WHO) and United Nations Children's Fund (UNICEF) issued a number of new recommendations for measles control that resulted in a two-fold increase in the number of measles-containing vaccine (MCV) doses administered between 2000 and 2002. Any additional increments in mass campaigns must be duly planned and have time lines so that vaccine production capacities are increased to optimal levels. The cornerstone of vaccine security efforts remains at the country level. WHO and UNICEF, with major partners, will review progress on measles mortality reduction and assess the feasibility of global measles eradication. Strong collaboration by all key stakeholders will be invaluable.

Child, Preschool↗