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Detection of measles virus genome in bronchoalveolar lavage cells in a patient with measles pneumonia.

Measles is frequently complicated with pneumonia that could be fatal in numerous occasions. However, a prompt and precise diagnosis of measles is not easily made particularly in the early stage of the disease, or in immunocompromised individuals because of the lack of typical clinical features or the defect in antigen-specific antibody production. In the present paper, we describe a 27-yr-old male who developed fever, skin rash typical of measles, and diffuse pulmonary infiltrates associated with respiratory failure. Infection of lung cells with measles virus was proved by detection of viral genome ribonucleic acid within alveolar macrophages and lymphocytes recovered by bronchoalveolar lavage using reverse transcription-polymerase chain reaction amplification. These techniques may offer a useful tool to make the swift and precise diagnosis of measles pneumonia, thus allowing appropriate therapeutic approaches to the disease.

Adult↗

Effect of measles virus antibodies on a measles SSPE virus persistently infected C6 rat glioma cell line.

Maintenance of measles (SSPE-Lec) virus persistently infected C6 rat glioma cells in medium containing polyclonal measles antiserum resulted in the loss of detectable expression of all measles virus proteins. Removal of these cells from antiserum, however, led to a re-expression of virus proteins and the production of infectious virus. Cloning of antibody-modulated non-expressing cells in the presence of antiserum showed that re-expression of virus proteins was not due to an incomplete curing process following the addition of antiserum, as a large number of non-expressing cell clones developed the capacity to express measles virus antigen at different periods after removal of antiserum. Irradiation of persistently infected cells to give a non-growing culture showed that modulation was not mediated by a selection and outgrowth of a small percentage of non-expressing cells originally present in the culture. Antibody directed against C6 membrane proteins did not lead to modulation and it was also shown that only monoclonal antibodies with neutralizing activity could affect intracellular antigen expression. Immunoglobulin Fab fragments with neutralizing activity also had modulating activity. Although all modulated cell clones were more susceptible to homologous virus infection than control C6 cells, it was not possible to rescue any defective measles virus which may have been maintained in the culture.

Animals↗

Estimation of measles vaccination coverage and longer-term vaccine efficacy in a Queensland State High School during the 1993-94 measles epidemic.

The parents of 470 students randomly selected from 1321 students attending a state high school were surveyed during the 1993-94 measles epidemic, by means of a take-home questionnaire. The response rate was 87%. Thirty stated that their child had measles during this epidemic; nine of these 30 gave a history of previous vaccination. Overall, 312 of the 470 (76%) stated that their child had been vaccinated, but only 34% indicated that they had vaccination records. There were no measles cases during this epidemic in the group with records. Those not vaccinated were at 10 times increased risk of contracting measles compared to those who had been vaccinated with or without records. Vaccine efficacy estimated in general a decade after vaccination based on parental recall of vaccination status regardless of whether they had vaccination records or not was 91% (95% CI 80%-96%). This calculation excluded 123 who claimed to have had measles prior to 1993 and 30 uncertain of their vaccination status.

Adolescent↗

The Measles Initiative to control measles in Kenya.

PURPOSE: To describe the epidemiology of measles in Kenya and evaluate the Measles Initiative's (MI's) mass immunization campaign and its impact on measles control in Kenya. METHODS: This descriptive study focused on evaluating the MI's simultaneous mass campaigns in the provinces of Kenya, the implementation process of the campaign strategy, post-campaign impact data, and pre-campaign measles trends. Secondary data were obtained from the Kenya Ministry of Health and MI documentation involving vaccine coverage, and morbidity and mortality rates. Analysis focused on program achievement with a comparison of immunization coverage results and program goals. OUTCOMES: Campaign goals of vaccination coverage were successfully achieved, and subsequent surveillance data indicate significant decreases in measles morbidity and mortality. Barriers to participation, sociocultural factors, and environmental demographics were identified and addressed. IMPLICATIONS: The success of the MI immunization program was the result of the commitment of expert international public health agencies in partnership with the Kenyan government. The strategies used for this successful public health activity can be applied to improve vaccination programs in other countries.

Adolescent↗

Genetic characterization of wild-type measles viruses isolated during the 1998 measles epidemic in Argentina.

This study reports on genomic characterization of six measles virus (MV) isolates obtained from a measles epidemic in Argentina in 1998. Reverse transcription-polymerase chain reaction (RT-PCR) and nucleotide sequence analysis of the carboxyl-terminal region of the nucleoprotein (N) gene of these isolates classified all of them as wild type MV of D6 genotype. MVs of D6 genotype with identical nucleotide sequences in the region analyzed were also identified during the 1997 measles epidemic in Brazil and the 1999 measles outbreak in Uruguai. These results suggest that the MVs associated with the 1998 measles epidemic in Argentina might have originated from Brazil. As the D6 genotype is also widely distributed in Europe, it is possible that this genotype was brought to South America from Europe.

Adult↗

Atypical measles in adolescent siblings 16 years after killed measles virus vaccine.

The history of killed and live measles vaccine administration and exposure to natural disease is detailed in four adolescent siblings over a 16-year period. In two of these siblings, atypical measles developed 16 years after killed measles virus vaccine was administered, despite intercurrent doses of live measles virus vaccine.

Adolescent↗

Measles--Puerto Rico, 1993, and the measles elimination program.

In the Commonwealth of Puerto Rico, a resurgence of measles peaked in 1990 when 1805 cases (51.3 cases per 100,000 population) and 12 measles-related deaths were reported. This report summarizes the persistence of measles transmission in Puerto Rico in 1993 and describes the Puerto Rico Measles Elimination Program.

Adolescent↗

Measles immunization strategy: measles antibody response following MMR II vaccination of children at one year of age.

Measles antibody levels were determined by the plaque reduction neutralization (PRN) test in 580 one-year-old children before vaccination and four to six weeks after MMR II vaccination. Fifty-one (8.8%) had maternally derived measles antibody at prevaccination, and this was more common among children of women born before 1967 (10.6%) vs. 4.3%; p < 0.01). Among those with maternal antibody, only 22 (43.1%) responded with a protective PRN titre of over 120, in contrast to 463 (87.5%) of the 529 without maternal antibody at prevaccination (p < 0.0001). Also, the geometric mean titre was significantly lower for the former (114.1 vs. 378.5; p < 0.0001). Overall, 15 (2.6%) of the 580 children had no antibody response after vaccination, and a further 80 (13.8%) had a subprotective response (PRN titre < 120). This lack of response could not be attributed entirely to the presence of maternal measles antibody at the time of vaccination. The MMR II vaccine may not be sufficiently immunogenic in inducing adequate measles antibody response after a single dose given at one year of age.

Age Factors↗

Measles, mumps, and rubella--vaccine use and strategies for elimination of measles, rubella, and congenital rubella syndrome and control of mumps: recommendations of the Advisory Committee on Immunization Practices (ACIP).

These revised recommendations of the Advisory Committee on Immunization Practices (ACIP) on measles, mumps, and rubella prevention supersede recommendations published in 1989 and 1990. This statement summarizes the goals and current strategies for measles, rubella, and congenital rubella syndrome (CRS) elimination and for mumps reduction in the United States. Changes from previous recommendations include: Emphasis on the use of combined MMR vaccine for most indications; A change in the recommended age for routine vaccination to 12-15 months for the first dose of MMR, and to 4-6 years for the second dose of MMR; A recommendation that all states take immediate steps to implement a two dose MMR requirement for school entry and any additional measures needed to ensure that all school-aged children are vaccinated with two doses of MMR by 2001; A clarification of the role of serologic screening to determine immunity; A change in the criteria for determining acceptable evidence of rubella immunity; A recommendation that all persons who work in health-care facilities have acceptable evidence of measles and rubella immunity; Changes in the recommended interval between administration of immune globulin and measles vaccination; and Updated information on adverse events and contraindications, particularly for persons with severe HIV infection, persons with a history of egg allergy or gelatin allergy, persons with a history of thrombocytopenia, and persons receiving steroid therapy.

Adolescent↗

Detection of measles antigen in conjunctival epithelial lesions staining by lissamine green during measles virus infection.

In a study in Kenya of corneal lesions occurring in children with measles virus infection, conjunctival lesions of a characteristic appearance were seen concomitant with the rash. The lesions became visible after staining by Lissamine green or Rose Bengal. In order to investigate whether these lesions were virus-induced, paired biopsies were performed on the conjunctiva of five measles patients. One biopsy was taken of a staining lesion; the other one, taken of nonstaining conjunctiva of the same eye, served as control. Measles-specific immunofluorescence on cryostate sections of the biopsies showed that in all patients the antigen occurred in the conjunctival epithelial cell layer in the staining lesions only. The coincidence of epithelial staining and presence of measles antigen suggests a viral origin of the conjunctival lesion. Fluorescent antibody technique on cryostate sections proved to be a suitable method to demonstrate the presence of virus where isolation fails and serology is not applicable.

Antigens, Viral↗

The use of a measles latex reagent for the determination of measles antibodies and in a specific test for multiple sclerosis.

Measles virus antigens covalently linked to latex spheres were used for measuring measles-specific antibodies in a direct agglutination test either in microtitre plates or as a rapid slide-agglutination test. The titres were compared to that obtained by conventional assays. The measles-latex spheres were also used as the antigen for a radio-immuno assay. By incorporating a 14C-radioactive marker into the measles-latex spheres their interaction with lymphocytes from multiple sclerosis and control patients was determined. Lymphocytes from multiple sclerosis patients reacted with a higher percentage of beads at low bead/lymphocyte ratios compared with controls, whereas the reverse was found when the ratio of beads was increased.

Antibodies, Viral↗

Expression of measles virus RNA in peripheral blood mononuclear cells of patients with measles, SSPE, and autoimmune diseases.

In order to characterize measles virus (MV) infection in peripheral blood mononuclear cells (PBMCs), RNA was isolated from PBMCs after PHA-stimulation for 72 hr of 9 patients with acute measles, 16 patients with subacute sclerosing panencephalitis (SSPE), 13 patients with various autoimmune diseases, and 16 healthy control donors. The RNA obtained was screened for the presence of MV N (nucleocapsid) gene specific transcripts of either positive or negative orientation in a S1 nuclease protection assay. The sensitivity of this assay allowed us to detect one infected cell in 20,000 PBMCs or 0.1 to 0.05 copies of MV-specific RNA per cell. Using single-stranded DNA or RNA probes expression of MV genomic RNA of negative polarity could be detected in only one case of acute measles and one healthy control donor. Conversely, N-specific transcripts of positive polarity, indicating active transcription, could only be detected in patients with acute measles. In addition, in infected PBMCs and in a persistently MV-infected B cell line positive stranded N-specific transcripts containing leader usually present at very low frequency have been found in relatively increased amounts in comparison with transcripts lacking leader. Whereas the ratio of these RNA species during lytic infection with MV in Vero cells is about 1:50, the ratio found here ranges from 1:3 to 1:10. This altered ratio indicates a specific regulation of MV specific transcription in cells of lymphoid origin that has not been found in any other cell system analyzed.

Animals↗

Passive immunity against measles during the first 8 months of life of infants born to vaccinated mothers or to mothers who sustained measles.

Neutralizing antibody titers of 47 infants whose mothers sustained measles (measles group) and 70 whose mothers were vaccinated (vaccine group) were compared at birth, 4 and 8 months of age. All children had antibodies at birth and 88% at 4 months. At 8 months, 49% had antibodies in the measles group and 15% in the vaccine group (P < 0.001). The geometric mean titers were significantly lower in the vaccine group than in the measles group and the difference corresponded to the antibody loss occurring in only 1.5 months of life. This small difference may reflect past exposure to wild virus of many vaccinated mothers.

Adult↗

Impact of the Australian Measles Control Campaign on immunity to measles and rubella.

To evaluate the impact of the 1998 Australian Measles Control Campaign on immunity to measles and rubella, 4400 opportunistically-collected sera, submitted to diagnostic laboratories across Australia from subjects aged 1-49 years, and 3000 from subjects aged 1-18 years, were tested before and after the campaign, respectively. The proportion of individuals aged 1-18 years who were immune to measles rose from 85% before, to 90% after, the campaign (P < 0.001). The greatest increase was in preschool (7%, P < 0.001) and primary school (10%, P < 0.001) children, who were actively targeted by the campaign. Rubella immunity in 1-18 year-olds rose from 83% to 91% (P < 0.0001), again with significant increases in preschool (4%, P = 0.002) and primary school (16%, P < 0.001) children. 94% of individuals aged 19-49 years were immune to rubella. These serosurveys confirm other evidence of the effectiveness of the Australian Measles Control Campaign and demonstrate the value of serosurveillance using opportunistically collected sera.

Adolescent↗

The effect of timing of sample collection on the detection of measles-specific IgM in serum and oral fluid samples after primary measles vaccination.

This study compares the timing of the rise and decline of measles-specific IgM in serum samples and in oral fluid samples. Two hundred and eighty 9-month-old infants presenting for routine measles vaccination in Addis Ababa, Ethiopia, were enrolled. Paired serum and oral fluid samples were collected before and 1, 2, 3 or 4 weeks after measles vaccination. Samples were tested by using a modified antibody-capture enzyme immunoassay. For the 321 IgM-negative pre- and post-vaccination serum samples, 317 (99 %) of their corresponding oral fluid samples were IgM-negative. Among the 130 IgM-positive serum samples, 75% of their paired oral fluid samples were IgM-positive, with the percentage rising to 87% after oral fluid samples collected > or =3.5 weeks after vaccination were excluded. Among the post-vaccination serum samples, the percent IgM-positive peaked in week 3 and declined to 79% in week 4. For post-vaccination oral fluid samples, the percent IgM-positive peaked in weeks 2 and 3, and then declined to 43% in week 4. This modified antibody-capture enzyme immunoassay appears to detect vaccine-induced measles-specific IgM in the first 3 weeks after vaccination.

Female↗

Th1 and Th2 cytokine responses after measles antigen stimulation in vitro in bone marrow transplant patients: response to measles vaccination.

In seronegative autologous bone marrow transplanted (ABMT) patients, a sustained cell-mediated immunity (CMI) has been shown to impair the antibody response after measles vaccination. To investigate if this might be caused by a preferential Th1 cytokine response, interferon (IFN)-gamma and interleukin (IL)-10 production of peripheral blood mononuclear cells (PBMC) was analyzed after measles antigen (M-ag) stimulation in vitro. The non-specific immune response was measured by IFN-alpha, and IL-12 analyses. Fifty non-vaccinated patients following ABMT or allogeneic bone marrow transplantation (BMT) were included. IFN-gamma production was significantly higher in patients with a retained CMI to measles than in patients without (2.3 vs 0.8 IU/ml; P = 0.01). Only a non-significant tendency was seen in IL-10 production (48.6 vs 26.7 pg/ml; NS), whereas no difference was found in IFN-alpha or IL-12 production. A positive correlation between IFN-gamma and IL-10 production was found (r(s) = 0.49; P < 0.001). After vaccination of 14 ABMT children, there was an increase in PBMC IFN-gamma production in vitro (2.5 vs <0.1 IU/ml; P < 0.05), whereas no changes were seen in the IL-10, IFN-alpha, or antibody levels. These results suggest that both Th1 and Th2 cytokine production are increased by M-ag stimulation in patients with a retained CMI to measles, but the Th1 response seems to be stronger. The preferential Th1 stimulation and increase in IFN-gamma production after vaccination may lead to a reduction in the humoral immune response which may explain the negative correlation between antibody production and T cell reactivity prior to vaccination.

Adolescent↗

Etiology of measles- and rubella-like illnesses in measles, mumps, and rubella-vaccinated children.

The viral etiology of measles- or rubella-like illnesses after MMR (measles, mumps, and rubella) vaccination was studied prospectively in 993 acutely ill Finnish children with fever and rash in 1983-1995. Their sera were tested for adeno-, entero-, and parvovirus B19 antibodies. Sera of 300 children <4 years old were also tested for human herpesvirus 6 (HHV-6) antibodies. Measles and rubella had been excluded by previous antibody testing. Serologic diagnosis of adeno-, entero-, or parvovirus infection was based on EIA (IgM or IgG antibodies) and that of HHV-6 on indirect immunofluorescence. A viral etiology was verified in 368 cases, most commonly parvovirus (20%), followed by enterovirus (9%) and adenovirus (4%). Among young children, HHV-6 infection was found in 37 (12%). Thirty-eight children (4%) had double infections. This study confirms that measles- or rubella-like illnesses in MMR-vaccinated children are often caused by other viruses. Each suspected vaccine failure requires laboratory confirmation to maintain reliable surveillance and control and to establish the specific etiology of the disease.

Adenoviruses, Human↗

Failure of targeted urban supplemental measles vaccination campaigns (1997-1999) to prevent measles epidemics in Mozambique (1998-2001).

This study assessed the effect of urban supplemental measles vaccination campaigns (1997-1999) in Mozambique that targeted children aged 9-59 months. Reported measles cases were analyzed to the end of 2001 to determine campaign impact. Hospital inpatient data were collected in the national capital and in three provincial capitals where epidemics occurred the year after the campaigns. Measles epidemics followed campaigns in the capital city, in 4 of 9 provincial capitals, and in 39 of 126 districts. Reasons for limited campaign impact included a low proportion of urban dwellers, the geographic location of some provincial capitals, the limited target age group, and low routine and campaign coverage. Routine immunization and disease surveillance should be strengthened and campaigns must achieve >90% coverage and target wider age groups and geographic areas in order to reach a high proportion of persons susceptible to measles.

Child, Preschool↗