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[Serological evidence of persistent elimination of measles in Czechoslovakia].

The authors report on the elimination surveillance programme initiated in 1969 with the introduction of mass vaccination. In 1982 the elimination of measles was achieved. It included serological surveillance or/and annual serological reports, which considerably contributed to the optimum effect of vaccination and re-vaccination strategies. Within the frame work of this programme, from 1971 to 1987, approximately 40,000 probands from all regions of the Czech Socialist Republic were examined. Proof was supplied as regards low vaccination and high post-vaccination seropositivity in children. Since the elimination of measles, seropositivity in children's and adult age has been in the range of approximately 95%. The paper gives an illustration of the vaccination history in children born in the Czech Socialist Republic in 1960-1986. It also analyzes the average levels of HI antibodies in non-vaccinated persons (1:54.9) with measles infection, in vaccinated and non-vaccinated newborns (1:20.4) and in persons after a single-dose vaccination (1:12.0). From 1982, when measles was eliminated, up to 1987, 126 sporadically occurring cases with measles were reported. In some of these cases, the exact diagnosis of measles was made with the aid of serological tests (HI test, CF reaction, EIA, IF IgM tests and SPIT-HI test).

Adolescent↗

Effect of simultaneous administration of live measles vaccine on the "take rate" of live mumps vaccine.

During the course of clinical studies to develop a new bivalent measles-mumps vaccine, it was established that simultaneous administration of live measles and mumps vaccines at doses contained in the monovalent vaccines resulted in a reduced seroconversion rate against mumps but not against measles. This one-way interference was resolved by increasing the dose of the mumps component in the bivalent measles-mumps and the trivalent measles-mumps-rubella vaccines above that in the monovalent mumps vaccine. On the other hand, it was not necessary to adjust the doses of the measles and rubella components in the combined vaccines. This observation requires that not only the titres of vaccine viruses must be carefully adjusted in combined live mumps vaccines but also that the heat-stability of each component in such vaccines be carefully determined to ensure that interference is not a problem during the complete shelf-life of the product. The relative doses at release of combined mumps vaccines using the Urabe Am 9 strain and the heat-stability characteristics of these products will be presented and discussed.

Antibodies, Viral↗

Agents affecting health of mother and child in a rural area of Kenya. III. The epidemiology of measles.

Between April 1974 and March 1976 surveillance of measles has been conducted by 12 fieldworkers making fortnightly home visits among a total population of 24,000 living in nearly 4000 households scattered in variable density throughout an area of 87 sq km in the northern division of the Machakos district, Kenya. The diagnosis of measles was verified by one of the project's physicians according to standardized procedures and was, whenever possible, supported by virus isolation and serum antibody level determination. Because not all reported patients were actually seen during the period of clinical manifestations, the diagnosis remained doubtful in a number of cases. Incidence and mortality figures have been estimated with 95% confidence limits based on the assumption that doubtful cases represent a probability of measles of .33 and probable cases a probability of .67. The estimated attack rate for the susceptible population 0-15 years of age was 13.5%. When related to all children--susceptible or not--the attack rate was highest in the 1-2 years age group (11%). Almost 15% of cases occurred below the age of one year, 1% below 6 months of age and 6% between 6 and 8 months. The estimated case fatality rate was 6.5%, fatality being highest between 1 and 2 years of age. For the age group 0-15 years measles accounted for 16.7% of all deaths. The estimated death rate per 100,000 total population was 113. The epidemiological pattern of measles suggests continuous re-introduction of the measles virus in a dispersed population causing micro-outbreaks of the disease in geographically widely separated spots throughout the year which tends to keep the proportion of susceptibles down and the attack rate during a protracted epidemic relatively low.

Adolescent↗

Measles vaccine in the People's Republic of China.

The strains of measles virus and the method used in the production of further attenuated live-virus vaccine in the People's Republic of China were studied. Observation of clinical reactions and serologic responses to immunization with Shanghai-191 measles vaccine, which is produced on a large scale with a locally isolated viral strain, revealed that this vaccine is adequately safe and immunogenic. Epidemiologic data showed a significant decrease in measles-associated morbidity after the introduction of mass vaccination in 1965. The duration of immunity induced by Shanghai-191 measles vaccine was studied for eight years in a region in which interference due to natural measles infection had been minimized by mass vaccination of children. Although immunity appeared to persist for at least eight years, the results suggested that primary vaccination does not confer lifelong immunity. Reactions and antibody responses to this vaccine were compared with those to two vaccines from abroad, the Schwarz and Leningrad-16 strains. The hemagglutination-inhibiting (HAI) antibody titer induced by Shanghai-191 vaccine was higher than that induced by Leningrad-16 vaccine and lower than that induced by Schwarz vaccine; however, these differences were not significant. Preliminary studies on the preparation of measles vaccine in human diploid cells have yielded promising results.

Animals↗

Prevalence of hepatitis B markers and measles, mumps, and rubella antibodies among Jewish refugees from the former Soviet Union.

OBJECTIVE: To assess the prevalence of hepatitis B virus (HBV) infection and immunity to measles, mumps, and rubella among refugees from the former Soviet Union (FSU). DESIGN: Descriptive study. SETTING: Soviet Immigrant Health Care Program, Sinai Samaritan Hospital, Milwaukee, Wis. PATIENTS: Consecutive sample of 496 Jewish refugees from the FSU presenting for new arrival screening from December 1, 1990, through January 11, 1993. OUTCOME MEASURES: Hepatitis B surface antigen (HBsAg), hepatitis B core antibody, hepatitis B surface antibody, and measles, mumps, and rubella antibodies. RESULTS: At least one hepatitis B marker was detected in 22% of the refugees, and HBsAg was detected in 0.4%. The rate of HBV infection (any marker present) increased with increasing age, ranging from 4% among those aged 0 through 19 years to 31% among those aged 50 through 59 years (chi 2 test for trend, 13.5; P < .001). Among those aged 0 through 19 years, 19% lacked antibody to measles, 8% lacked antibody to mumps, and 13% lacked antibody to rubella. Refugees who were less than 30 years of age were more than twice as likely to lack antibodies to measles, mumps, or rubella compared with those who were 30 years of age or older (relative risk, 2.8; 95% confidence interval, 1.8 to 4.2; P < .001). CONCLUSIONS: In our sample of Jewish refugees from the FSU (primarily Ukraine, Russia, and Belorussia), the rate of HBsAg positivity was low, suggesting that routine screening for HBV infection is not needed. Seronegativity to measles, mumps, and rubella was relatively common among those less than 30 years old. Those refugees who were born after 1957 should be given combined measles, mumps, and rubella vaccine unless their written documentation indicates previous receipt of these antigens according to the immunization schedule recommended in the United States.

Adolescent↗

Seroconversion rates to combined measles-mumps-rubella-varicella vaccine of children with upper respiratory tract infection.

OBJECTIVE: To determine if upper respiratory tract infection (URI) affects the seroconversion rate or quantitative response to each component of a combined measles-mumps-rubella-varicella vaccine. SUBJECTS AND METHODS: One hundred forty-nine children between 15 and 18 months of age were prospectively divided into two groups according to the presence of URI or recent history of URI symptoms within the 4 weeks before vaccination. Once stratified, 74 children in the healthy group and 75 children in the URI group were randomly assigned to receive one of three lots of measles-mumps-rubella varicella vaccine by subcutaneous injection into the deltoid area. Serum was obtained from each child just before vaccination and 4 to 6 weeks later for measuring antibody levels against each virus. RESULTS: Prevaccination antibody levels against each virus in the URI and healthy groups did not differ. Nine children had pre-existing antibodies to varicella and six to mumps; no child had positive serologies for measles or rubella before vaccination. Children with pre-existing antibody were excluded from analysis of seroconversion for that virus. Seroconversion to measles, mumps, and rubella occurred in 100% of children in both groups. Mean antibody levels did not differ between the healthy and URI groups for measles (111 vs 122), mumps (97 vs 108), or rubella (96 vs 102). Three (4%) of 70 children with URIs in whom varicella serologies were available failed to seroconvert to varicella vaccine although none of the 69 healthy children had vaccine failure (P = .24). The mean varicella antibody level was 11.3 +/- 1.4 in the healthy children, which did not differ significantly from the level of 9.5 +/- 0.9 in the URI group. CONCLUSIONS: Seroconversion to measles, mumps, rubella, and varicella was not significantly affected by the presence of a concurrent or recent URI in 15- to 18-month-old children.

Antibodies, Viral↗

Booster vaccination with further live attenuated measles vaccine.

Revaccination with live attenuated measles vaccine was evaluated in a large group of children to determine (1) if protective antibody to measles infection could be augmented and (2) after what interval will the revaccination yield optimal results. The rate of decline in measles hemagglutination-inhibition (HI) antibody was observed to be directly related to the time interval since the previous vaccination, and individuals with declining titers became increasingly responsive to revaccination with a maximal response approximately four to six years after previous vaccination. Six-month follow-up studies demonstrated sustained elevations in measles HI antibody titers. Measles-neutralizing antibody showed less tendency to sustain a titer increase with revaccination. The observations suggest that revaccination with live, further attenuated measles vaccine is safe and may augment immunity.

Adolescent↗

Progress toward elimination of measles from the Americas.

In 1994, the Pan American Health Organization (PAHO) established the goal of eliminating measles from the Western Hemisphere by 2000. To reach this goal, PAHO developed a measles-elimination strategy that includes three vaccination components ("catch-up," "keep-up," and "follow-up") and integrated epidemiologic and laboratory surveillance. The aim of the strategy is to achieve and maintain high levels of measles immunity among infants and children and detect all chains of transmission of measles virus through careful surveillance. This report updates measles surveillance data through February 1998 and summarizes the impact of elimination strategies on measles in the Americas.

Americas↗

[Age-related seroprevalence of measles, mumps and rubella antibodies in 1996].

In 1996 the effects on the immunity profile of a Swiss population exposed to MMR vaccination, which has been recommended since 1985, were evaluated with an age-stratified seroprevalence study for measles, mumps and rubella (MMR). At the age of 1.5-2.5 years, seroprevalence attained 76% for measles and rubella, which is respectively 17% and 24% above the values observed in 1992. The seroprevalence for mumps attained only 55% at the same age, which could reflect the poor immunogenicity of this component of the MMR vaccine. The seroprevalence for measles IgG showed a slow but steady increase from vaccination age to adulthood, attaining nearly 100%. The concentrations of measles IgG were about 700 IU/l into adolescence and rose to a plateau at about 1500 IU/l during young adulthood. These observations are compatible with low endemic activity of measles in the last 20 years and a predominance of vaccine-induced immunity up to about 20 years of age. This corresponds to the time period when measles vaccines--single or as MMR--have been in use. In 1992, at the peak of epidemic activity, seroprevalence for mumps rose substantially faster than in 1996. In addition, the rapid increase in quantitative values during preschool age mirrors the ongoing wild virus circulation with minimal vaccine effect. In the vaccine cohort (2-12 years of age) the seroprevalence of rubella IgG reached 70-80%. That there is no rise in the curve during school age shows that the recommended catch-up vaccinations before or during school age have been neglected. The median concentrations of rubella IgG were about 65 IU/ml at vaccination, declined to 40-50 IU/ml during preschool age, and rose again during school age, suggesting wild virus circulation. These data show that the MMR vaccine cover in Swiss children is insufficient to interrupt virus circulation, and administration of a second dose of MMR for catch-up immunisation has been omitted. The poor efficacy of the mumps component of the MMR vaccine that has mainly been used in Switzerland is also evident. The average age at infection is therefore expected to rise, thus involving a risk of increasing age-dependent complications. Efforts to implement the MMR vaccination program in Switzerland should be improved.

Adolescent↗

Comparison of subacute sclerosing panencephalitis and measles viruses: an electron microscope study.

The ultrastructure of CV-1 cells infected with subacute sclerosing panencephalitis (SSPE) viruses was compared with that of CV-1 cells infected with the wild or Edmonston strain of measles virus. Both SSPE viruses and the measles viruses produced two types of nucleocapsid structures: smooth filaments, 15 to 17 nm in diameter, and granular filaments, 22 to 25 nm. The smooth and granular filaments produced by SSPE and measles virus did not differ in appearance. In CV-1 cells infected with SSPE viruses, smooth filaments formed large intranuclear inclusions and granular filaments occupied a large area of the cytoplasm, but always spared the area under the cell membrane. Particles budding from the surface of these cells contained no nucleocapsids. In CV-1 cells infected with measles virus, only small aggregates of smooth filaments were seen in the nuclei. Granular filaments in the cytoplasm predominantly occupied the area under the cell membrane, and were aligned beneath the cell membrane in a parallel fashion and assembled into budding particles. These differences between SSPE and measles virus may be regarded as quantitative, but they do distinguish SSPE viruses from measles virus. Moreover, the formation of large nuclear inclusions filled with smooth filaments appears to be a characteristic process of SSPE, but not of measles, since this type of inclusion is invariably seen in SSPE brain tissues, brain cultures derived from them, and CV-1 cells infected with SSPE viruses.

Antigens↗

Assessment of coverage levels of single dose measles vaccine.

OBJECTIVE: To study the consequences of low coverage levels of a single dose of measles vaccine. DESIGN: Case series. PLACE AND DURATION OF STUDY: The study was conducted in the Department of Paediatrics, Rawalpindi General Hospital (RGH) from January 2001 to August 2001. PATIENTS AND METHODS: Information about 68 admitted cases of measles was collected on a structured proforma with reference to epidemiological profile, vaccination history and comorbidities. RESULTS: Mean age observed in measles cases was 2 years and 8 months with a range from 3 months to 8 years. Maximum number of cases reported were <1 year of age (n=22, 32%). Fifty percent of cases were seen among vaccinated children. Seventy-five percent (n=51) had history of contact with a measles case. Pneumonia was the commonest complication followed by acute gastroenteritis, encephalitis, febrile convulsions, oral ulcers, oral thrush, eye changes of vitamin-A deficiency and pulmonary tuberculosis (T.B.) in descending order of frequency. Fifty-four cases were successfully treated for complications of measles and discharged. Nine cases left against medical advice. Five patients died--all of them had encephalitis either alone (n=1) or in combination with pneumonia and acute gastroenteritis (n=4). CONCLUSION: There is a dire need to increase the immunization coverage to reduce the rate of vaccine failure and achieve effective control of measles.

Child↗

Measles revaccination. Persistence and degree of antibody titer by type of immune response.

During a measles immunization campaign 203 children were enrolled in an antibody response study. Of this group, follow-up clinical data and sera samples were available from 125 children three weeks after immunization and from 90 children ten months later. Seventy-six of the children had been previously vaccinated, ten had a history of measles and 39 denied vaccination or illness. Twenty-six of the children had prevaccination hemagglutination inhibiting antibody titers of less than 5. Of this group 12 had a primary immune response (IgM measles antibody) with geometric mean titers (GMT) of 90 and 40 three weeks and ten months respectively after vaccination. In contrast, the other 14 children with initial titers of less than 5 had secondary immune responses (only IgG measles antibody) with GMTs of 28 and 9 three weeks and ten months after vaccination. Since the antibody responses in these children who had previously been stimulated by measles antigen were modest and transient, it is suggested that booster immunization may not be effective in preventing future secondary vaccine failures. Also noted in this study was a poor correlation between historical data and actual measles antibody.

Adolescent↗

Measles elimination in the Americas. Evolving strategies.

The strategy currently used to control measles in most countries has been to immunize each successive birth cohort through the routine health services delivery system. While measles vaccine coverage has increased markedly, significant measles outbreaks have continued to recur. During the past 5 years, experience in the Americas suggests that measles transmission has been interrupted in a number of countries (Cuba, Chile, and countries in the English-speaking Caribbean and successfully controlled in all remaining countries. Since 1991 these countries have implemented one-time "catch-up" vaccination campaigns (conducted during a short period, usually 1 week to 1 month, and targeting all children 9 months through 14 years of age, regardless of previous vaccination status or measles disease history). These campaigns have been followed by improvements in routine vaccination services and in surveillance systems, so that the progress of the measles elimination efforts can be sustained and monitored. Follow-up mass vaccination campaigns for children younger than 5 years are planned to take place every 3 to 5 years.

Americas↗

Encephalitis after inhalation of measles virus: a pathogenetic study in hamsters.

A neuroadapted strain of measles virus (HNT) was administered by inhalation to newborn hamsters. Primary replication of virus in the lung was followed by the transient appearance of virus in spleen within 7 to 9 days of inoculation. A terminal encephalitis occurred between 6 and 60 days in 31% of infected hamsters, and virus was recovered by explant culture of these brains. Virus could not be cultured directly from brain or tissue homogenates. At least 7% of hamsters that had survived the infection for two months had antibody to measles virus. The histopathological change in morbid animals was limited to the central nervous system (CNS) and consisted of small foci of necrosis, perivascular mononuclear cell infiltrates, intracytoplasmic and intranuclear inclusions, and vacuolated pyknotic neurons. Immunofluorescent studies disclosed measles antigen in the lungs and brain. This hamster model of measles encephalitis following a "natural" route of inoculation appears to represent a faithful reproduction of certain CNS complications of natural measles infection in humans, i.e., measles encephalitis and subacute sclerosing panencephalitis.

Animals↗

Manganese superoxide dismutase induction during measles virus infection.

Measles virus infection of B-cells results in marked alterations in proliferation and immunoglobulin production. Very little is known about the changes of gene expression, if any, during acute measles virus infection. To elucidate cellular genes that are induced during measles virus infection, we carried out a subtraction technique, representational differential analysis. The mitochondrial protein, manganese superoxide dismutase (MnSOD), was upregulated in B-cells during measles virus infection. Although measles virus-infected B-cells did not secrete MnSOD into the environment, it was found, using an MnSOD mimetic, that intracellular MnSOD did inhibit proliferation of the B-cells. MnSOD also decreases the titer of virus produced from infected cells. Therefore, MnSOD seems to play a role in the alteration of immune function seen upon infection of B-cells with measles virus.

B-Lymphocytes↗

Genetic and antigenic characterization of measles viruses that circulated in Korea during the 2000-2001 epidemic.

Despite the marked reduction in the incidence of measles in Korea by the introduction of measles vaccine, a large measles epidemic occurred during 2000-2001. During the epidemic, more than 55,000 measles cases were reported and at least 7 children were dead. In this study, we analyzed the genetic and antigenic properties of 15 measles viruses that isolated during the epidemic. Sequence analyses of entire hemagglutinin (H) and nucleoprotein (N) genes of the viruses indicated that all Korean isolates had a high degree of homology (>99.8%) when compared with each other. They differed from other wild-type viruses by as much as 6.8% in the H gene and 6.5% in the N gene at the nucleotide level. The deduced amino acid variability was up to 6.4% for the H protein and up to 6.5% for the N protein. Phylogenetic analysis of nucleotide sequences and deduced amino acid sequences of the H and N genes revealed that all Korean viruses were grouped into the genotype H1. This strongly demonstrated that single genotype of measles virus has been circulated in Korea during the 2000-2001 epidemic. Plaque reduction neutralizing antibody titers against vaccine strains, Edmonston and Schwarz, and recently isolated Korean strains were measured using sera from vaccinees and recently infected children. Although sera of recently infected children demonstrated higher neutralizing antibody titers against wild-type strains than against vaccine strains, both sera neutralized both strains and the reciprocal geometric mean titers (GMTs) were not significantly different against both strains.

Adolescent↗

A simple method for the detection of measles virus genome by loop-mediated isothermal amplification (LAMP).

Approximately 20,000-30,000 measles patients were reported in a surveillance of infectious diseases because of low vaccine coverage of 80% in Japan. Among them, some were thought to be secondary vaccine failure (SVF) with generally mild or non-typical measles illness and sometimes became a source of further transmission. We have developed a new, sensitive, and rapid method to detect the measles virus genome by reverse transcription loop-mediated isothermal amplification (RT-LAMP). We examined 50 nasopharyngeal secretion (NPS) samples that were obtained during the 1999 outbreak and stored at -70 degrees C and fresh NPS, lymphocytes and sera from 11 patients in 2003. Total RNA was extracted from the samples and subjected to reverse transcription-polymerase chain reaction (RT-PCR) and RT-LAMP. We detected the genomic RNA corresponding to at least 0.01-0.04 TCID50, 30-100 copies in samples by RT-LAMP within 60 min after extraction of RNA, and all four genotypes isolated in Japan were equally amplified. Specific DNA amplification was monitored spectrophotometrically by real time turbidimeter and the quantity of RNA was calculated. Measles virus genome was detected in 44 of 50 stored NPS by RT-PCR and in 49 by RT-LAMP. The vaccine strain was discriminated from wild strains after sequencing the LAMP products. RT-LAMP is a useful rapid diagnostic method for the detection of measles virus without any special apparatus, showing higher sensitivity than RT-PCR, and expected to be applied for hospital-based infection control and for laboratory-based measles surveillance.

Base Sequence↗

Measles virus strains circulating in Ethiopia in 1998-1999: molecular characterisation using oral fluid samples and identification of a new genotype.

A measles outbreak in December 1998 in Bedelle (vaccine coverage <40%) and two sporadic cases in Addis Ababa, Ethiopia, were investigated. Paired serum and oral fluid samples were collected 2-8 days after the onset of symptoms. A total of 53 of 55 outbreak cases and both sporadic cases were positive for serum measles virus-specific IgM. Oral fluid measles-specific IgM was positive in 71% of cases collected up to 5 days after onset and in 90% collected at 6-8 days. By contrast, 100% of oral fluid samples were positive for measles virus RNA by RT-PCR, suggesting that early collection of samples favoured the detection of measles virus RNA by RT-PCR. The measles virus strain in the outbreak was identified as genotype D4. One strain from a sporadic case was also genotype D4; the strain from the other sporadic case was assigned to clade D but was distinct. The degree of divergence from recognised clade D strains suggested that, together with three strains from the United Kingdom, it represents an additional genotype of clade D (GenBank accession numbers AF280800-280807).

Adolescent↗