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Measles vaccine effectiveness and duration of vaccine-induced immunity in the absence of boosting from exposure to measles virus.

BACKGROUND: It is unknown whether vaccine-induced immunity is lifelong in the absence of periodic exposure to measles virus. After 27 years of no known exposure to measles, an outbreak in Palau in 1993 offered the opportunity to study this issue and the measles vaccine effectiveness. METHODS: Household contacts of a sample of confirmed cases were interviewed for exposure, symptoms and vaccination status verified by records. Serum from symptomatic contacts was tested for measles antibodies. RESULTS: Among 78 contacts 4 of 5 (80%) unvaccinated, 4 of 35 (11%) 1-dose vaccine recipients and none of 38 (0%) > 1-dose recipients developed measles. Effectiveness of 1-dose vaccine was 86% (95% confidence interval, 60 to 95%). An additional dose significantly reduced the risk of measles (P = 0.048). Time since vaccination was not a significant risk factor for developing measles (relative risk, 1.6; 95% confidence interval, 0.3 to 9.4; persons vaccinated > 15 years ago vs. < 5 years ago). CONCLUSIONS: Similar to the estimates previously obtained in the area, measles vaccine effectiveness in Palau was lower than the estimates obtained in the US. A second dose of vaccine further reduced the risk for developing measles. We found no evidence that waning immunity was an important problem in this limited population with no known previous exposure to measles virus. The small number of vaccinated contacts precludes a definitive assessment.

Child↗

The impact of national measles immunization programme on measles admissions to the major children's hospital in Yangon.

To ascertain whether measles vaccination was associated with reduced measles associated mortality and morbidity in the Yangon Children's Hospital (YCH), the hospital records of children admitted to YCH in 1985 and 1989 with the diagnosis of measles or measles associated conditions, were analysed retrospectively. Measles vaccination was associated with a 90.7% reduction of deaths directly attributed to measles or ascribed to diarrhoea, respiratory illness, malnutrition or fits. An 85% reduction in the percentage of medical admissions related to measles and measles associated conditions was also seen. The case-fatality rate from measles declined from 25.3% to 15.6%. We conclude that measles immunization has been associated with a marked reduction in morbidity and mortality.

Child, Preschool↗

Increase of circulating CD8+CD57+ lymphocytes after measles infection but not after measles vaccination.

Natural measles virus infection is recognised to induce immunosuppression, contributing to an increased susceptibility to other infections. A cell population that could be involved in this process is the CD8CD57 double-positive lymphocyte subset (CD8+CD57+), known to be significantly expanded in some viral infections, e.g. human immunodeficiency virus (HIV) infection. We therefore studied the level of CD8+CD57+ lymphocytes during measles infection and measles vaccination. Twenty-two measles patients were examined 5-57 days after the onset of fever and several months later. Healthy, age-matched controls were examined twice. Eleven children receiving measles-mumps-rubella (MMR) vaccination were examined before, 9-19 days and 5-9 months afterwards. Blood samples were analysed for the proportion of peripheral blood mononuclear cells carrying both CD8 and CD57, and for other cell surface markers (CD4, CD14, CD3, CD16(CD56) or CD20). Elevated proportions of CD8CD57 double-positive cells were found in the peripheral blood of children with natural measles early after infection (p < 0.05), whereas the proportion of other cell surface markers remained stable. No corresponding change in CD8+CD57+ lymphocytes was noted in MMR-vaccinated children or in healthy controls. Since CD8+CD57+ lymphocytes could be related to the immunosuppression seen in some viral infections, our finding of elevated CD8CD57 double-positive lymphocytes during acute measles infection would suggest that this population of lymphocytes is involved in measles-induced immunosuppression. The absence of an increase of CD8CD57 in children vaccinated with the conventional live attenuated measles vaccine, in contrast to children with natural measles infection, would thus indicate that the vaccine does not induce immunosuppression as measured in our in vitro system.

Adolescent↗

Impact of a measles immunisation campaign on measles admissions to a Natal hospital.

During May and June 1990, a national mass measles immunisation campaign was undertaken in South Africa. This study is an assessment of the impact of the campaign on measles admissions to a provincial referral hospital that has specifically designated wards for children with communicable diseases. Data from the measles ward admissions book for the 18 months before the campaign (1 January 1989-30 June 1990) and 6 months after the campaign (1 July 1990-31 December 1990) were compared. Since the campaign, the average number of measles admissions has declined by 64.4% from 87 to 31 per month (P less than 0.01). Before the campaign, 21.3% of measles patients admitted were aged 7-9 months compared with 27.6% after the campaign, highlighting the urgent need to improve the measles vaccination coverage in this age group. An analysis of the geographical source of patients showed that measles continued to occur after the campaign in most of the areas where it existed before the campaign. It is concluded that important gains have been achieved by the campaign. These will be rapidly eroded and epidemics of measles may occur if measles vaccination efforts wane and slump back to pre-campaign levels. It is important to capitalise on the momentum generated through the campaign by continuing to support efforts of existing health care services to improve and maintain high levels of measles immunisation coverage.

Child↗

Examination of the immunological relationship between measles virus and canine distemper virus using monospecific measles antisera.

Indirect immunofluorescence titrations were performed with measles virus, the Rockborn strain of canine distemper virus (CDV), and a large plaque variant of the Onderstepoort strain of CDV (Ond-LP) using monospecific antisera prepared against either the haemagglutinin (anti-HA), the haemolysin (anti-HL), or the ribonucleoprotein (anti-RNP) of measles virus. Tests with anti-HA showed that the Rockborn strain of CDV was more closely related to measles virus than Ond-LP. The ribonucleoprotein antigens of the CDV strains were closely related to each other but were both related to and distinct from measles virus RNP. The use of measles anti-HL serum demonstrated that CDV possesses an antigenically related acetone-sensitive component equivalent to the haemolysin of measles virus. Absorption of human convalescent serum with excess quantities of acetone-fixed CDV antigens had no effect on measles-specific anti-HA, HL, or RNP activity in the serum. Absorption with measles antigens on the other hand, totally removed all measles and CDV-specific HA and RNP activity. CDV was not neutralised by any of the monospecific antisera when tested either as individual antisera or as mixtures. Our results demonstrate the occurrence of antigenic variation between different strains of CDV, they also reveal unique antigenic determinants in both measles virus and CDV.

Antigens, Viral↗

Atopic dermatitis is increased following vaccination for measles, mumps and rubella or measles infection.

The prevalence of atopic dermatitis increased markedly in the period 1960s to the 1990s. Earlier findings indicate that infections acquired in early life enhance or suppress the expression of atopic disease as a result of a change in immune reactivity. Our objectives were to examine the association between measles, mumps and rubella vaccination, measles infection and the risk of atopic dermatitis. A random sample of 9,744 children were followed up from birth to 3-15 years. Their parents responded to a questionnaire including highly structured questions on atopic dermatitis, measles, mumps and rubella vaccination and measles infection. Information on parental educational level was obtained from Statistics Denmark. The cumulative incidence of atopic dermatitis at age 14 was 19.7%. The confounder adjusted incidence ratio of atopic dermatitis among measles, mumps and rubella vaccinated children versus children not subjected to measles, mumps and rubella vaccination and measles infection was 1.86 (95% CI 1.25-2.79); the incidence ratio for measles-infected children was similar. The incidence of atopic dermatitis increased after measles, mumps and rubella vaccination and measles infection, which is surprising in view of the hygiene hypothesis. We suggest further study of the possible short-term and long-term effects of virus and bacteria on the immune responses and expression of atopic disease.

Adolescent↗

Measles in adults in Canada and the United States: implications for measles elimination and eradication.

BACKGROUND: Despite the implementation of mass school catch-up campaigns for measles in Canada, an outbreak of measles occurred in early 1997 mostly affecting the adult population. The higher incidence in Canada in adults led us to compare immunization policies and the evolution of measles among adults in Canada and the US. METHODS: Based on information gathered from both national immunization programmes and surveillance systems. RESULTS: Although the proportion of cases occurring in adults has increased tremendously in both countries in the past decade, there was no increase in measles incidence in these populations. The most likely factors to explain the higher rate of measles occurring in adults in Canada are the younger age at administration of first dose in Canada, the delay in implementation of a second dose policy in Canada compared with the US combined with the lack of prematriculation immunization requirements in Canadian colleges and universities, and the higher rate of overseas travel to and from Canada. The situation in Canada may also have been exacerbated by incomplete efforts to control measles for many years without attempting to eliminate the disease. CONCLUSIONS: In order to prevent measles in adults, high-risk groups must be identified and catch-up for selected groups considered. Vaccination of international travellers to endemic areas should be recommended until global elimination has been achieved. Appropriate measles control strategies in younger populations seem to be effective in preventing measles in adults. The experience in Canada and the US suggests that measles transmission in adults is unlikely to be a major impediment to regional elimination or global eradication.

Adult↗

Measles epidemic in Harare, Zimbabwe, despite high measles immunization coverage rates.

Despite rapidly increasing measles immunization coverage in Harare city, measles remains endemic, and regular outbreaks occur. The most recent occurred in 1988, when the measles immunization coverage was 83%. We have carried out a retrospective study of the clinical and epidemiological features of this outbreak to assess whether the present immunization policy needs to be changed. Of 4357 cases of measles seen at primary health care centres and hospitals in Harare during the outbreak, 1399 (32%) were severe or involved complications that required hospital admission. The peak incidence occurred among under-2-year-olds, followed by that among 5-7-year-olds. Poor nutritional status was significantly more frequent among children who were hospitalized and among those who died. A total of 59% of all cases aged 9-59 months had documented evidence of measles immunization. The most frequent complications, which occurred most often among under-5-year-olds, were diarrhoea with dehydration, pneumonia, laryngotracheobronchitis, and convulsions, which together affected 56% of hospitalized cases. The hospital case fatality rate was low (1.43%). In Harare, measles transmission remains a problem, despite high measles immunization coverage rates; the failure rate for the standard Schwarz measles vaccine also appears to be high. There is a need to reduce the number of measles cases among under-9-month-olds and young children. Further studies into alternative measles vaccines and schedules are required.

Adolescent↗

Nonclassic measles infections in an immune population exposed to measles during a college bus trip.

This study investigated the frequency of mild or asymptomatic measles infections among 44 persons exposed to a student with measles during a 3-day bus trip using two buses. Questionnaires and serum samples were obtained 26-37 days after the trip. All participants had detectable measles-neutralizing antibodies, and none developed classic measles symptoms. Ten persons (23%) were IgM positive for measles, indicating recent infection. Among previously vaccinated IgM-negative persons, those who rode on bus A with the index case-patient had significantly higher microneutralization titers than those on bus B (P= .001), suggesting that some persons on bus A were infected but were IgM negative at the time of the study. Mild or asymptomatic measles infections are probably very common among measles-immune persons exposed to measles cases and may be the most common manifestation of measles during outbreaks in highly immune populations.

Adolescent↗

Negative impact of clinical misdiagnosis of measles on health workers' confidence in measles vaccine.

We conducted a survey to determine the accuracy of the clinical diagnosis of measles in Zimbabwe. Between December 1996 and February 1997, we collected blood samples and clinical and demographic information from a sample of 105 children with a clinical diagnosis of measles. A clinical case of measles was defined as a person with a history of fever, rash for three or more days, and either cough, coryza, or conjunctivitis. A laboratory-confirmed case of measles or rubella had IgM antibodies against measles virus or rubella virus respectively. A total of 91% of children met the clinical case definition. Among those who met the clinical case definition for measles, 72% were IgM-positive for measles virus only, 23% were IgM-positive for rubella virus only, 3% were IgM-positive for both measles and rubella viruses, and 2% were IgM-negative for both viruses. This study demonstrates the importance of considering selective laboratory confirmation of measles in periods of high disease incidence when the effectiveness of the vaccine is questioned.

Adolescent↗

Increased protections during a measles outbreak of children previously vaccinated with a second dose of measles-mumps-rubella vaccine.

BACKGROUND: In 1989 a second dose of measles vaccine was recommended for US children to prevent school outbreaks of measles. Coverage of school age children with a second dose remains incomplete, and data on the effectiveness of this recommendation are limited. We investigated a measles outbreak in Mesa County, CO, in December, 1994, and evaluated the efficacy of preoutbreak immunizations at an elementary school (School A) where many students had received two doses. METHODS: All reported suspected cases of measles were investigated; cases that met a clinical case definition were tested by a measles IgM antibody assay. A confirmed case required laboratory confirmation or had to meet the clinical case definition and be epidemiologically linked to a confirmed case. Vaccination records of students at School A were reviewed. The effectiveness of one and two doses of measles vaccine was estimated using logistic regression. RESULTS: Sixty-two confirmed cases were reported, including 17 at School A. At School A the attack rate in unvaccinated children (7 of 16, 44%) was higher than in those with 1 dose (10 of 320, 3%) or 2 doses (0 of 289, 0%). Estimated vaccine effectiveness was 92% for 1 dose and 100% for 2 doses. Two doses were better than one dose in decreasing the likelihood of acquiring measles (P = 0.003). CONCLUSIONS: The lower attack rate among two dose recipients provides evidence that a two dose strategy can help prevent measles in schools. Administering the second dose at elementary school entry can help prevent the persistence of susceptible cohorts of children and is likely to be important in sustaining elimination of indigenous transmission of measles in the United States.

Adolescent↗

Changing levels of measles antibody titers in women and children in the United States: impact on response to vaccination. Kaiser Permanente Measles Vaccine Trial Team.

OBJECTIVES: In the United States, younger women are more likely to have immunity to measles from vaccination and are less likely to have been exposed to the wild virus than are older women. To evaluate changes in measles antibody titers in women in the United States and children's responses to measles vaccination, we analyzed data from a measles vaccine trial. METHODS: Sera collected from children before vaccination at 6, 9, or 12 months of age and from their mothers were assayed for measles antibodies by plaque reduction neutralization. Responses to vaccination with Merck Sharp & Dohme live measles virus vaccines at 9 months (Attenuvax) and 12 months (M-M-R II) were also analyzed. RESULTS: Among women born in the United States (n = 614), geometric mean titers (GMTs) of measles antibodies decreased with increasing birth year. For those born before 1957, 1957 through 1963, and after 1963, GMTs were 4798, 2665, and 989, respectively. Among women born outside of the United States (n = 394), there were no differences in GMTs by year of birth. Children of younger women born in the United States were less likely than those of older women to be seropositive at 6, 9, or 12 months. The response to the vaccines varied by maternal birth year for children of women born in the United States. Among 9-month-old children, 93% of those whose mothers were born after 1963 responded, compared with 77% and 60% of those whose mothers were born in 1957 through 1963 and before 1957, respectively. Among 12-month-old children, 98% of those born to the youngest mothers responded, compared with 90% and 83% of those whose mothers were born in 1957 through 1963 and before 1957. The responses of children of women born outside of the United States were not associated with maternal year of birth. CONCLUSIONS: An increasing proportion of children in the United States will respond to the measles vaccine at younger ages because of lower levels of passively acquired maternal measles antibodies.

Adult↗

Markedly elevated levels of beta2-microglobulin in urine with measles viruria in patients with measles.

BACKGROUND: Measles is a highly contagious infectious disease in children. However, the pathogenesis has not yet been fully defined since susceptible cells to measles virus (MV) had not been developed. Recently, B95a cells, which are very susceptible to MV, have been reported. OBJECTIVES: To evaluate measles viruria in patients with measles, isolation of MV from urine was performed using B95a cells. STUDY DESIGN: Isolation of MV from supernates or sediments of urine in patients with measles was performed using B95a cells. The levels of beta2-microglobulin (MG) in urine and serum were also measured. RESULTS: MV was isolated from either supernates or sediments of urine. MV was isolated from 10 of 11 samples (91%) within 2 days of the appearance of a rash. MV was isolated from supernates of urine for up to 4 days after the appearance of a rash, and from sediments for up to 5 days. The levels of urinary beta2-MG were elevated within 2 days of the appearance of a rash. The levels of urinary beta2-MG with measles viruria were significantly higher compared to those without measles viruria. CONCLUSIONS: Measles viruria may occur early in all patients with measles and elevated levels of urinary beta2-MG in patients with measles may be the consequence of tubular injury.

Journal Article↗

Immunogenicity of aerosol measles vaccine given as the primary measles immunization to nine-month-old Mexican children.

UNLABELLED: Aerosol measles vaccination has been found to be more immunogenic than subcutaneous administration as a booster in school aged children, and immunogenic in 12-month-old children as a primary dose. The objective of the study was to evaluate immunogenicity to aerosol measles vaccine in 9-month-old children. METHODS: Nine-months-old infants received Edmonston-Zagreb measles vaccine by aerosol (10(3.58) CCID50/0.1 mL, estimated retained dose 10(2.81) CCID50 or subcutaneous route (10(4.28) CCID50/0.5 mL); cellular and humoral immunity and adverse events were assessed. RESULTS: Measles-specific T cell proliferative responses developed in 42% of children given aerosolized vaccine compared with 67% of those who received subcutaneous vaccine (p = 0.01); the mean stimulation index (SI) was 4.4+/-0.7 versus 6.9+/-1, respectively, (p = 0.05). Seroconversion rates were 33 and 92% after aerosol or subcutaneous immunization (p < 0.001). Among infants who developed serologic responses, measles geometric mean titers (GMT; 95% CI) by neutralizing antibody assay were 215 mIU/mL (115-400) in aerosol vaccine recipients and 411 mIU/mL (345-490) in those given subcutaneous vaccine (p = 0.06). CONCLUSIONS: The proportion of 9-month-old infants who developed cellular and/or humoral immunity to measles was lower in the aerosol group but measles antibody and T cell responses were comparable among those who developed measles immunity. Differences in response rates are attributable to the lower aerosol dose. Improving aerosol delivery or increasing the dose may enhance immunogenicity of primary aerosol measles vaccination in this age group.

Aerosols↗

Atypical measles in a patient twice vaccinated against measles: transmission from an unvaccinated household contact.

Described are two cases within the same household that were involved in an outbreak of measles in Niterói, RJ. Measles diagnosis was confirmed serologically by specific IgM detection in Case 1 (classic measles) who was unvaccinated, and rising measles specific IgG in the absence of IgM in Case 2 (mild modified measles) who had a history of two vaccinations with measles-containing vaccines. Measles virus was detected by reverse transcriptase polymerase chain reaction (RT-PCR) in saliva samples from both cases. The nucleic acid amplified by RT-PCR was sequenced and showed identical measles sequence in the two cases. This study highlights the difficulty of diagnosing nonclassical measles infection on clinical and serological grounds, and the usefulness of PCR for viral RNA sequencing from noninvasive specimens for confirming epidemiologic links.

Adult↗

Reduced passive measles immunity in infants of mothers who have not been exposed to measles outbreaks.

Natural measles infection usually confers life-long immunity which is transferred from mothers to their offspring, protecting them from natural measles until the age of about 12 months. Recently, however, natural measles has been observed with increased frequency in infants under the age of 12 months. Natural measles outbreaks in the city of Sapporo have been suppressed by widely applied measles vaccination. Passive measles immunity in 160 neonates (cord blood), born during the last 17 y in Sapporo, Japan was determined by a neutralization (NT) antibody test. The mothers of these infants had had natural measles infection during childhood. Geometric mean titres (GMTs) of cord blood NT antibodies gradually decreased after 1989 and the GMTs of the most recently born infants were significantly lower than those of infants born in the first few years of the study. These observations suggest that even in mothers who experienced natural measles in childhood, recurrent exposure to natural measles is necessary in order to maintain adequate antibody levels for effective passive immunity of their infants.

Antibodies, Viral↗

Detection of measles virus genomic RNA in tear samples from a patient with measles keratitis.

PURPOSE: To report a case of measles keratitis, in which measles virus genomic RNA was detected in tear samples. METHODS: Samples of tears and pharyngeal mucus were obtained from a 19-year-old man with active systemic measles on day 7 after illness onset. These specimens were then subjected to reverse-transcriptase polymerase chain reaction (RT-PCR), using measles-specific primers. RESULTS: One week after systemic measles outbreak, the patient presented with a chief complaint of irritation in both eyes. Slit-lamp examination revealed bilateral superficial punctate keratopathy in the central cornea with small diffuse subepithelial infiltrations, and RT-PCR detected measles virus genomic RNA in tears and pharyngeal mucus. The patient was treated with topical 0.1% fluorometholone and 0.5% levofloxacin three times a day for 1 week, and the keratopathy resolved without sequelae. CONCLUSION: This report demonstrates for the first time the presence of measles virus genomic RNA in the tears of a patient with measles keratitis. It also highlights the utility of RT-PCR for rapid detection of measles RNA in tear or mucus samples. Furthermore, the presence of virus in bodily fluids and secretions signifies the potential contagiousness of this type of keratopathy.

Adult↗

Efficacy of measles vaccine during the 1993 measles epidemic in Korea.

Immunization to eliminate measles is recommended at 15 months of age with the option of giving vaccine at 6 to 9 months of age during measles outbreaks in Korea. Because of the recent resurgence of measles and concern about the possibility of reduced vaccine efficacy caused by genomic differences between vaccine virus and contemporary wild measles viruses, we conducted a measles vaccine efficacy study involving children with household exposure ages 1 to 5 years during measles outbreak that had occurred 1993 in Seoul and Seong-nam city, with the demographic analysis of patients brought to the hospitals. A total of 380 patients (M:F = 216:164) were included in this study. Two hundred nine cases (55.0%) occurred in children less than 5 years of age, and 167 (43.9%) were younger than 16 months of age. The recorded age-specific incidence rates showed bimodal patterns, i.e. highest peak in those below 16 months of age and second peak in those ages 6 to 9 years of age. Only 9.6% (16 of 167) of the measles cases less than 16 months, 59.5% (25 of 42) of those 16 months to 4 years and 91.8% (157 of 171) of the cases in school age children have been vaccinated. Attack rates among the 122 vaccinated siblings and 12 unvaccinated siblings ages 1 to 5 years who contacted measles were 5.7 and 75%, respectively, and the clinical vaccine efficacy was 92.4% (95% confidence interval, 83.6, 96.4). The high vaccine efficacy in household exposures suggests that measles outbreaks in Korea are not caused by reduced vaccine efficacy.

Adolescent↗