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[Diagnosis of adult measles pneumonia from bronchoalveolar lavage fluid by reverse-transcriptase polymerase chain reaction].

The case was a 32 years old female who contracted measles. Two days after the appearance of skin eruptions, ground-glass opacities and small nodular opacities were detected in both lung fields on a X-ray and a chest computed tomography (CT). CT seems to be a useful method to detect measles pneumonia. Pneumonia complicating measles may be caused by either the measles virus itself or by a secondary bacterial infection. Culture of the bronchoalveolar lavage fluid (BALF) was negative for bacteria, acid-fast bacilli, and mycetes, and polymerase chain reaction (PCR) analysis did not detect mycoplasma, but reverse transcriptase PCR detected the measles virus. The demonstration of measles virus RNA in BALF by the reverse transcriptase PCR technique was useful for definitive diagnosis of measles pneumonia.

Adult↗

[Vaccination against rubella, measles, chickenpox, and mumps in nursing students].

The past history of infection and vaccination, and serum antibodies against rubella, measles, chickenpox, and mumps were investigated, before vaccine was inoculated in the susceptible nursing students. The subjects were 221 nursing students (208 women, 13 men, the average age 18.4 +/- 1.8 years old) who entered Nagasaki University from 2001 to 2003. The positive rates of the past history of rubella, measles, chickenpox, and mumps were 49.8%, 28.1%, 86.4%, 50.7%, and that of previous vaccination were 31.7%, 69.2%, 10.9%, 5.3%, respectively. The serum antibody was measured with HI assay for rubella, or with EIA assay for measles, chickenpox, and mumps. The positive rates for the antibodies against rubella, measles, chickenpox, and mumps were 92.8%, 90.0%, 82.3%, and 85.0%, respectively. The rates for vaccine inoculation to the students without antibody were 92.8% in rubella, 100.0% in measles, 66.7% in chickenpox, 85.0% in mumps, and that to the low titer antibody (2.0 < or = EIA-IgG < 4.0) students were 70.6% in measles, 48.0% in chickenpox, 93.8% in mumps, respectively. Susceptible nursing students, as well as the medical stuff, should be vaccinated in order to prevent hospital infection of rubella, measles, chickenpox, and mumps.

Adolescent↗

Immunoglobulin G avidity testing in serum and cerebrospinal fluid for analysis of measles virus infection.

We studied a variety of patients with measles virus infection by using avidity testing for measles virus-specific immunoglobulin G (IgG) in serum and cerebrospinal fluid samples. For the avidity testing, an Enzygnost measles IgG enzyme-linked immunosorbent assay kit was used with an 8 M urea denaturing method. With this method, low-avidity IgG (acute primary infection, avidity of < 30% within 15 days of the onset of rash) and high-avidity IgG (subacute sclerosing panencephalitis, avidity of > 75%) could be clearly distinguished by using serum samples. One patient, who developed a typical course of measles despite a previous vaccination, showed a positive IgM response with an initial low titer of measles virus-specific IgG of low avidity, but a later sample revealed a high titer of IgG of intermediate (40%) avidity, suggesting previous immunological priming. Two patients with breakthrough infection (secondary vaccine failure), both having central nervous system involvement, showed a positive IgM response with initial high titers of serum IgG of high avidity. In addition, one of the patients had a detectable level of measles-specific IgG in cerebrospinal fluid. In this patient, the avidity of both serum and cerebrospinal fluid IgG decreased during the short follow-up period. This phenomenon has never before been reported. In subacute sclerosing panencephalitis patients, the avidity of cerebrospinal fluid IgG was consistently lower than that of serum IgG. The difference in avidity between cerebrospinal fluid and serum IgG may be used as a direct indicator of intrathecal production of IgG. In conclusion, the avidity testing is simple to perform, reliable, and highly informative in the analysis of measles virus infection.

Adolescent↗

Detection of measles virus RNA in urine specimens from vaccine recipients.

Analysis of urine specimens by using reverse transcriptase-PCR was evaluated as a rapid assay to identify individuals infected with measles virus. For the study, daily urine samples were obtained from either 15-month-old children or young adults following measles immunization. Overall, measles virus RNA was detected in 10 of 12 children during the 2-week sampling period. In some cases, measles virus RNA was detected as early as 1 day or as late as 14 days after vaccination. Measles virus RNA was also detected in the urine samples from all four of the young adults between 1 and 13 days after vaccination. This assay will enable continued studies of the shedding and transmission of measles virus and, it is hoped, will provide a rapid means to identify measles infection, especially in mild or asymptomatic cases.

Adult↗

Immunosorbent assay based on recombinant hemagglutinin protein produced in a high-efficiency mammalian expression system for surveillance of measles immunity.

Recombinant hemagglutinin (H) protein of the measles virus (MV) was produced in mammalian cells with a high-yield expression system based on the Semliki Forest virus replicon. Crude membrane preparations of H protein-transfected BHK-21 cells were used to coat microtiter plates to measure specific immunoglobulin G antibodies in 228 serologically defined serum samples mainly from measles late-convalescent adults. The titers by the enzyme-linked immunosorbent assay for the H protein (H-ELISA) closely correlated with neutralization test (NT) titers (R2 = 0.66), hemagglutination inhibition test (HI) titers (R2 = 0.64), with the titers from a certified commercial ELISA based on whole MV-infected cells (MV-ELISA; R2 = 0.45). The correlations described above were better than those of the commercial MV-ELISA titers with the NT (R2 = 0.52) or HI (R2 = 0.48) titers. By using the 2nd International Standard for anti-measles serum, the detection level of the assay corresponds to 215 mIU/ml for undiluted serum, which corresponds to the estimated threshold for protective immunity. The specificity, accuracy, and positive predictive value were, in general, better for the H-ELISA than for a commercial MV-ELISA, independent of whether HI, NT, or HI and NT were used as "gold standards." In contrast, the H-ELISA proved to be slightly less sensitive than the MV-ELISA (sensitivities, 98.6 versus 99.5%, respectively; P was not significant). The assays did not differ significantly in the number of serum samples with positive HI and NT results (n = 212) which measured false negative (H-ELISA, 2 of 212 [0.94%]; MV-ELISA, 1 of 212 [0.47%]), but the H-ELISA detected significantly more measles-susceptible individuals than the MV-ELISA (10 of 11 versus 3 of 11, respectively; P < 0.05) among the individuals whose sera had negative HI and NT results. Our data demonstrate that the H-protein preparation that we describe could be a cost-effective alternative to current whole-virus-based ELISAs for surveillance for immunity to measles and that such an assay could be more efficient in detecting susceptibility to measles. Furthermore, unlike whole MV-based antigens, H-protein would also be suitable for use in the development of a simple field test for the diagnosis of measles.

Adolescent↗

No evidence of measles virus in stapes samples from patients with otosclerosis.

Otosclerosis is a localized bone dystrophy of unknown etiology mainly involving the stapes. The hypothesis of a persistent infection by the measles virus was based on the inconstant detection of the virus by various methods, including reverse transcription-PCR (RT-PCR) of patients' stapes samples. The aim of this work was to investigate the presence of the measles virus in stapedial otosclerosis foci by different sensitive methods. Pathologic stapes samples were obtained from 35 patients suffering from otosclerosis. Measles virus detection was performed by (i) cocultures of Vero cells and primary cell cultures of bone samples (n = 7), (ii) immunofluorescence study of these cocultures (n = 3), and (iii) RT-PCR on RNA directly obtained from fresh frozen samples (n = 28) and on RNA extracted from the primary cell cultures (n = 2). Viral genomic regions coding for N (nucleoprotein) and M (matrix) proteins were separately amplified. PCR sensitivity was optimized on the measles virus Edmonston strain. Glyceraldehyde-3-phosphate dehydrogenase mRNA was used as a marker of total RNA recovery. PCR products were tested by Southern blot hybridization technique to improve sensitivity and specificity. PCRs amplifying the M and the N protein genes were able to detect the control measles virus RNA at titers as low as 0.1 and 0.01 50% tissue culture infective dose, respectively. With these highly sensitive methods, we could not evidence the presence of the measles virus in any of our bone samples or primary bone cell cultures. Our results do not confirm the hypothesis of persistent measles virus infection in otosclerosis.

Adult↗

Evaluation of diagnostic markers for measles virus infection in the context of an outbreak in Spain.

A measles outbreak occurred from January to July 2003 in Spain, despite the fact that the Plan of Eradication of Measles and its surveillance program had been set up in 2001. Different diagnostic markers for measles virus infection were compared for 246 patients in tests of serum, urine, and pharyngeal exudate specimens. Measles virus immunoglobulin M (IgM) and IgG and rubella virus and parvovirus IgM levels in serum were assayed. Multiplex PCR was done on urine, serum, and pharyngeal exudates, and isolation of measles virus in the B 95 a cell line from urine was attempted. At least one positive marker for measles virus was obtained from 165 patients (67.1%; total number of patients, 246). A total of 136 cases (82.4% of the patients showing positive markers) were diagnosed by PCR and/or isolation and IgM detection methods. The results for 27 patients (16.4%) were positive only by direct methods. The results for two patients (1.2%) were positive only by IgM detection. In the case of the first group (136 cases), the time elapsed from appearance of the rash was significantly longer than in the case of the group which was only positive by PCR. Besides, 8 out of 27 PCR-positive IgM-negative cases showed specific IgG results, suggesting either secondary vaccine failure or reinfection. Numbers resulting from PCR performed with pharyngeal exudates proved to be significantly higher than those obtained with other specimens. Phylogenetic analysis showed the presence of genotype B3. The results strongly back the World Health Organization recommendation that detection of IgM should be supplemented by PCR and isolation for the diagnosis of measles virus infection.

Adolescent↗

Antigenic determinants of measles virus hemagglutinin associated with neurovirulence.

The biological activity of monoclonal antibodies specific for the hemagglutinin protein of measles virus strain CAM recognizing six epitope groups according to their binding properties to measles virus strain CAM/R401 was investigated in vivo in our rat model of measles encephalitis. When injected intraperitoneally into measles virus-infected suckling rats, some monoclonal antibodies modified the disease process and prevented the necrotizing encephalopathy seen in untreated animals. The analysis of measles virus brain isolates revealed emergence of variants that resisted neutralization with the passively transferred selecting monoclonal antibody but not with other monoclonal antibodies. Monoclonal antibody escape mutants were also isolated in vitro, and their neurovirulence varied in the animal model. Sequence data from the hemagglutinin gene of measles virus localize a major antigenic surface determinant of the hemagglutinin protein between amino acid residues 368 and 396, which may be functionally important for neurovirulence. The data indicate that the interaction of antibodies with the measles virus H protein plays an important role in the selection of neurovirulent variants. These variants have biological properties different from those of the parent CAM virus.

Animals↗

Measles immunoglobulins in subacute sclerosing panencephalitis.

Normal responses of measles specific immunoglobulins M and G (IgM and IgG) were defined in 10 children with measles. Abnormal responses of measles IgM and IgG were found in both sera and cerebrospinal fluids from three cases of subacute sclerosing panencephalitis. In two patients the serum titres of measles IgM and IgG were abnormally high. The measles IgM was present during prolonged illnesses in serum and cerebrospinal fluid, which suggested a correlation with the known persistence of measles virus antigen in the brain of the three patients. It was concluded that both measles IgM and IgG may be produced within the central nervous system in subacute sclerosing panencephalitis.

Antigens↗

Cell-mediated immunity during natural measles infection.

Natural measles causes prolonged depression of cell-mediated immunity yet little is known as to how the infection influences lymphocyte function. Therefore, we studied the properties and function of lymphocytes during and after measles. The number and proportion of circulating thymus-derived lymphocytes was low during the acute stage of measles, and at this time 37% of these cells showed positive immunofluorescent staining for measles virus after stimulation with phytohemagglutinin. 7% of B cells were shown to contain virus but their numbers did not alter during the infection. Acute-phase lymphocytes, when stimulated, yielded infective virus and half were killed on incubation with autologous serum and complement. In acute measles the increase in [(3)H]-thymidine uptake of lymphocytes when stimulated with an optimal dose of PHA was normal in media with 10% fetal calf serum and low in media containing 10% autologous serum: the mean values were 56.8+/-34.1 and 23.7+/-25.9 cpm x 10(3) per 10(6) lymphocytes, respectively. Stimulation of acute-phase lymphocytes by Candida antigen was also low in media containing autologous serum averaging 1.2 x 10(3) cpm per 10(6) lymphocytes. On recovery 4-6 wk later this rose significantly to 18.9+/-19.8. The mean migration index of leukocytes to heat-killed candida cells in acute measles was 0.84+/-SD 0.08, and this fell significantly to 0.75+/-SD 0.08 4 wk later. Thus, depletion of T cells, an inhibitor of lymphocyte proliferation in the serum and a possible defect in antigen processing, interacts to depress cell-mediated immunity in measles.

Antigens, Fungal↗

Measles outbreak in Juneau, Alaska, 1996: implications for future outbreak control strategies.

OBJECTIVE: To determine the most effective outbreak control strategy for school-based measles outbreaks as the proportion of children with two doses of measles-containing vaccine (MCV) increases. SETTING: A school-based measles outbreak during 1996 involving 63 cases in Juneau, Alaska (population 29 288), where systematic revaccination with MCV was not implemented. DESIGN: A retrospective evaluation using chain-of-transmission data of three possible outbreak control strategies: no school revaccination, targeted school revaccination (affected schools only), and community-wide school revaccination (all schools). Two-dose MCV coverage among students was estimated from school vaccination records and a survey issued to parents. PRIMARY OUTCOME MEASURES: Potentially preventable cases of measles and doses of MCV administered per case prevented. RESULTS: Two-dose MCV coverage among Juneau students was estimated to be 44% and 53% immediately before and after the outbreak, respectively. Of all the measles cases, an estimated 24 to 28 and 27 to 31 were potentially preventable by the targeted and community-wide school revaccination strategies, respectively. Either strategy might have optimally decreased the outbreak duration by 1 month, sparing one of seven affected schools and 10 of 12 unvaccinated children who had measles. Approximately 133 to 155 and 139 to 160 doses of MCV per case prevented would have been required for targeted and community-wide school revaccination, respectively. CONCLUSIONS: Either targeted or community-wide school revaccination would have been effective control strategies for this outbreak. Targeted school revaccination is probably the intervention of choice for school-based measles outbreaks in larger communities with higher two-dose MCV coverage. As two-dose MCV coverage continues to increase in the United States, public health control measures to respond to outbreaks need to be reevaluated.

Adolescent↗

Why we need to know whether prophylactic antibiotics can reduce measles-related morbidity.

In some parts of the world, measles vaccination has resulted in very substantial reductions in measles-related morbidity and mortality. Even so, it has been estimated that 30 million people still contract the disease every year, that nearly 1 million of these die, and that measles-related deaths account for about 10% of all deaths in children under the age of 5 in developing countries. Existing evidence from controlled trials suggests that antibiotic prophylaxis in measles can result in important reductions in measles-related morbidity, and, at a World Health Organization meeting convened in 1993 to decide on research priorities for the treatment of measles, highest priority was accorded to additional controlled trials of prophylactic antibiotics. As controlled trials of vitamin A in measles have made clear, such trials are feasible. Continued acquiescence in uncertainties about the effects of prophylactic antibiotics in a disease that continues to afflict so many children worldwide is unacceptable.

Anti-Bacterial Agents↗

[Measles epidemiology in the State of Santa Catarina, Brazil, 1996-2000].

This ecological study, based on an analysis of secondary data from epidemiological surveillance and using the municipality (county) as the unit of analysis, showed that measles vaccine coverage was lower than necessary for eradication (95%) and control (90%) in many municipalities in the State of Santa Catarina, Brazil, both before and during the last epidemic in 1997, particularly regarding the second dose of the vaccine, applied as a component of the MMR vaccine, scheduled at 15 months of age. Low vaccine coverage was associated with higher measles incidence. However, during the 1997 epidemic small-scale measles outbreaks were recorded even in municipalities with first-dose coverage of 95% or higher, particularly among those which also had low second-dose coverage for MMR. Approximately 80% of all measles cases during 1996-2000 occurred among schoolchildren and young adults. Measles virus circulation in the municipality in the previous year and population density increased the risk of measles. Two imported cases of measles in Santa Catarina in 2004 illustrate that it would be premature to describe the current situation as one of eradication.

Adolescent↗

Otosclerosis: a measles virus associated inflammatory disease.

The etiology of otosclerosis is still unknown. Immunohistochemical studies have revealed the characteristics of chronic inflammation in the otospongiotic area. Paramyxoviral structures have been identified by electron microscopy and the expression of measles virus antigen has been observed by immunohistochemistry in active otosclerotic tissue. By use of the polymerase chain reaction, measles virus related sequences have been detected in otosclerotic bone tissue but not in control specimens. The aim of our study was i) to detect measles virus genome in affected patients using a more sensitive PCR system and ii) to search for anti-measles virus IgG in the perilymph. In 13 out of 14 specimens of bone fragments from surgically removed stapedes of patients suffering from otosclerosis, measles virus RNA sequences could be detected while other tissues from the same patients and from a negative control group lacked such sequences. Furthermore, IgG anti-measles virus antibodies were detected in the perilymph of 6 patients. Our results support our previously stated hypothesis that otosclerosis is a measles virus associated disease which provokes a local immune response within the inner ear.

Adult↗

Serological and clinical characteristics of measles vaccine failure in Japan.

In 1991, in Fukuoka, Japan, a measles outbreak occurred in which we observed 15 cases of measles vaccine failure (MVF). We examined these patients both clinically and serologically. Seven of them, with a response pattern of an early rise in and attainment of a high hemagglutination inhibition (HI) antibody titre, were considered to be secondary vaccine failures (EH group). Eight others showed a normal (relatively late rise and low titre) HI antibody response pattern and were considered to be primary vaccine failures (LL group). In both MVF groups, measles-specific IgM antibody was detected by enzyme immunoassay. The EH group had a milder rash than did the LL group and unvaccinated controls. We believe they had an immunological memory that modified the clinical manifestations of measles. Two cases of encephalitis were observed in the EH group; both patients recovered without sequelae. These data suggest that the mere presence or absence of IgM antibody is not sufficient to differentiate primary from secondary MVFs. A two-dose measles vaccination scheme should be recommended to secure a booster effect, because immunity is waning in the population in which the measles vaccination rate is not high enough and in which natural measles still exists.

Antibodies, Viral↗

What is the cause of a rash after measles-mumps-rubella vaccination?

Surveillance and laboratory confirmation of measles will increase in importance as Australia implements enhanced measles control. We describe a 17-month-old child with fever and rash after measles-mumps-rubella vaccination. Detection of vaccine-strain measles virus in his urine by polymerase chain reaction confirmed the diagnosis of a vaccine reaction rather than wild-type measles. We propose that measles virus should be sought and identified as vaccine or wild-type virus when the relationship between vaccination and measles-like illness is uncertain.

Diagnosis, Differential↗

[Classification of measles control situation in different areas of China].

Based on initial description of measles epidemiology, principal component analysis and cluster analysis were applied to analyze the epidemiological pattern of measles in China. Several indicators of socioeconomic status, epidemiological characteristics of measles, as well as status of EPI performance were selected as creteria for classification. It was demonstrated that four groups could be identified as undercontrol, moderate, less advanced and poor areas in terms of the status of measles controlled program. Different strategies were recommanded for different groups. For the undercontrol areas, establishment of measles surveillance system should be prioritized. For the moderate epidemic areas, supplemental immunization should be considered while measles surveillance system is initiated. In the less advanced areas, supplemental immunization and strengthening outbreak response activities should be considered. For poor areas, routine measles immunization needs further improvement to reduce outbreaks.

Adolescent↗

[Measles in 1997].

Since 1990, the decrease of measles morbidity rates and the increase of the areas with limited measles transmission are observed in Poland. In 1997, 338 measles cases was reported, the lowest number of measles cases ever reported. This represents 47% decrease from the number of measles cases (639) reported in 1996. The increase of the number of measles incidence during last two month of 1997 may forecast epidemic 1998 year. The laboratory confirmation of suspected measles, especially sporadic cases should be implemented in all voivodeships in Poland.

Adolescent↗