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Measles--United States, 2005.

Measles is a highly infectious, acute viral illness that can be complicated by severe pneumonia, diarrhea, and encephalitis and can result in death. In the prevaccine era, approximately 500,000 cases of measles occurred annually in the United States. During 2005, local and state health departments reported to CDC 66 confirmed cases of measles (incidence rate: less than one case per 1 million population), 34 of which were from a single outbreak in Indiana associated with infection in a traveler returning to the United States. This report describes the epidemiology of U.S. measles cases in 2005 and documents the absence of endemic measles and the continued risk for imported measles infections that can result in transmission within the United States. The findings underscore the need to maintain the highest possible measles vaccination coverage in the United States and to adhere to recommendations regarding measles vaccination.

Adolescent↗

A review of measles admissions and deaths in the paediatric ward of Goroka Base Hospital during 1989.

We reviewed all measles cases admitted to the paediatric ward of Goroka Base Hospital in 1989, and also interviewed a sample of measles patients attending the paediatric outpatient department. Measles accounted for 11% of all paediatric admissions and 32% of deaths. The case fatality rate for measles was 17%. Children with nosocomial infections and children with low birthweight were more likely to die. The most common complications of measles were pneumonia and diarrhoea, pneumonia being the most common cause of death. Twelve cases of subacute sclerosing panencephalitis were admitted during the year (0.5% of paediatric admissions). Measles was underreported because it was frequently omitted from the discharge diagnosis, the emphasis being placed on the complications. The majority of children with measles admitted to the ward and seen in outpatients had not been vaccinated. Nosocomial infections could have been reduced if all paediatric admissions aged 6-35 months had been vaccinated on admission. We strongly endorse the policy of vaccinating children in Papua New Guinea against measles from the age of 6 months.

Age Factors↗

[A measles epidemic in an adequately vaccinated middle school population].

OBJECTIVE: To assess the extent of a measles epidemic in a secondary school. DESIGN: Retrospective and questionnaire investigation. SETTING: Secondary school, Bilthoven. METHOD: Questionnaire followed by laboratory testing for measles and other infectious diseases with exanthema. RESULTS: The response rate was 99% (935/949 pupils, aged 12-21 years, vaccination rate 92%). Seventy-seven students underwent laboratory investigations. Measles virus was isolated in 2 suspected patients. Thirty-three of 37 patients with clinical or laboratory criteria of measles had been vaccinated. Complications of measles were not detected. Infection was also detected in patients with relatively few or atypical symptoms. The protective efficacy of measles vaccine could be determined because the attack rate of the school population was less than 5%. CONCLUSION: Primary failure of the measles vaccine might be the cause of the minor epidemic but the results do not cast doubt on the efficacy of the current measles vaccination programme.

Adolescent↗

Influence of the specific T cell response on seroconversion after measles vaccination in autologous bone marrow transplant patients.

Six patients who were seronegative to measles after autologous bone marrow transplantation (ABMT) were vaccinated with a live attenuated measles vaccine. The specific T helper cell response was studied by measuring lymphocyte proliferation induced by measles antigen and B cell response by measles specific IgG by ELISA. Blood samples were drawn before, at 1-3 months, and at 1 year after vaccination. It was found that a pre-existing T cell response correlated with an impaired B cell response 1 year after vaccination (r = 0.83, P = 0.04), whereas no correlation was found between IgG titers before vaccination and IgG titer increase, or T cell response after vaccination. Furthermore, there was a transient negative correlation between the T cell response at 1-3 months after vaccination and the T cell response before vaccination (r = -0.90, P = 0.04) that became positive at 1 year after vaccination (r = 0.90, P = 0.02). In conclusion, in patients seronegative to measles who were revaccinated with measles vaccine after ABMT, a pre-existing T cell response correlated with an impaired B cell response, while pre-existing low-level IgG antibodies had no significant influence on the IgG titer rise. A sustained T cell response to measles antigen before vaccination may thus be one possible explanation for measles vaccine failure in ABMT patients.

Adolescent↗

Effect of vitamin A supplementation on measles vaccination in nine-month-old infants.

OBJECTIVE: Childhood immunization programs have been suggested as an infrastructure to deliver vitamin A supplements to children in developing countries. The effects of giving vitamin A, a potent immune enhancer, with measles immunization to nine-month-old infants is unknown. METHODS: A randomized, double-masked, placebo-controlled clinical trial of vitamin A, 100,000 IU at the time of standard titer Schwarz measles immunization was conducted with nine-month-old infants in Bogor District, West Java, Indonesia. Antibody titers to measles were measured at baseline and one and six months following immunization. RESULTS: 394 infants received measles immunization, and 37 infants (9.4%) had baseline antibody titers > 1:120, which is consistent with previous natural measles infection. Of the remaining infants, 98.8% seroconverted to measles, and 99.3% had titers consistent with protection against measles six months postimmunization. Seroconversion rates were similar in vitamin A and placebo treatment groups. CONCLUSION: High dose vitamin A supplementation can be given without reducing seroconversion to standard titer Schwatz measles immunization in nine-month-old infants.

Antibodies, Viral↗

Do vaccinated cases transmit measles? A systematic review and meta-analysis.

INTRODUCTION: We reviewed evidence on whether vaccinated individuals can transmit measles and conducted a meta-analysis to understand transmission characteristics. METHODS: We searched and extracted data from peer-reviewed and gray literature and included studies reporting measles transmission events from vaccinated individuals. We meta-analyzed the data to calculate the median number of transmissions from vaccinated cases by measles burden, number of doses, and time since first and last dose. RESULTS: We identified 11,911 peer-reviewed and 22 gray literature records and included 33 articles in our review. Seventy individuals who had received 1 or more doses of measles-containing vaccine transmitted measles virus, resulting in 237 secondary cases. Vaccinated transmitters in eliminated areas were older (median age of 19 years (IQR: 3, 21)) than those in non-eliminated areas (median age 16 years; IQR 13, 18) (p = 0.12). Additionally, 91% (30/33) of studies provided data on subsequent transmission generations, leading to 812 measles cases traced back to vaccinated individuals, with a median of 4 (IQR: 1, 10) cases per vaccinated transmitter. CONCLUSION: Measles transmissions from vaccinated cases, although relatively uncommon, must be considered in public health investigations, as such transmissions can contribute to outbreaks.

Adolescent↗

IgM antibodies in sera from patients with chronic active hepatitis reacting with the measles virus matrix protein and nucleoprotein.

The antigenic specificity of measles virus IgM antibodies in sera from patients with chronic active hepatitis not caused by hepatitis B virus has been examined. An immunosorbent column containing antihuman IgM covalently bound to Sepharose was used to pick up IgM from the sera. Radiolabelled measles virus antigens were then allowed to react with the IgM antibodies. The immune complexes were eluted and analysed by sodium dodecyl sulfate [SDS]-polyacrylamide gel electrophoresis. Four sera from patients with hepatitis B surface antigen [HBsAg]-negative chronic active hepatitis with high measles virus haemagglutination inhibition [HI] and complement fixation [CF] antibody titres and positive enzyme-linked immunosorbent assay [ELISA] for measles-virus-specific IgM were examined. The results were compared with those obtained using sera from patients with an acute measles virus infection and from healthy controls. In both patient groups, IgM antibodies with specificity against the matrix protein represented the major portion of the measles virus IgM. IgM antibodies against the measles virus nucleoprotein and probably against host-cell-derived actin were also present. The patient sera contained only traces of IgM antibodies with specificity against the measles virus haemagglutinin or fusion protein. No specific IgM antibodies were found in sera from healthy controls.

Actins↗

Surveillance of measles in the Sudan using filter paper blood samples.

Dried blood spots collected on filter paper are considered potential clinical specimens for measles surveillance because of their ease of collection, storage, and transport. The usefulness of these samples for surveillance of measles was evaluated in a field setting. Blood spots were collected by finger-prick from 316 clinically diagnosed measles patients in suburban Khartoum, mostly within a week after onset of the rash. Samples were collected between October, 2000 and April, 2003, and stored at 4 degrees C. Measles virus-specific IgM antibodies were detected in 200 (63%) of the samples using an "in-house" IgM capture ELISA. For 201 samples reconstitution and IgM measurement was repeated 1 year after initial testing with essentially the same results, showing the stability of IgM in the filter paper under these conditions. In a limited number of samples (n = 38) measles virus-specific IgM was also tested with a commercial indirect IgM ELISA. Although the results of the two assays correlated well, the "in-house" IgM capture ELISA proved slightly more sensitive. Measles virus-specific reverse transcriptase polymerase chain reaction (RT-PCR) amplicons were obtained from 16 of 57 (28%) samples tested. Sequencing of the 3' 456 nucleotides of the nucleoprotein gene showed the continued endemic circulation of genotype B3 viruses identified previously in this region. Although problems related to limited sample quantities were encountered, the present study confirms the usefulness of dried blood spots for measles surveillance. The results also demonstrate that measles continues to be endemic in the Sudan.

Antibodies, Viral↗

Investigation of measles and rubella outbreaks in Tamil Nadu, India-2003.

The aims of the present study were to confirm measles outbreaks by detection of measles-specific IgM antibodies, isolation of measles virus, and genetic characterization to document the circulating genotypes in Tamil Nadu. Eight outbreaks were reported from six districts of Tamil Nadu, India during the period Jan-Dec 2003. Blood samples were collected for serology, urine, and throat swabs for virus isolation. Genotypic characterization of measles isolates was based on the sequence of the N gene. All the clinically suspected outbreaks (n = 8) were confirmed by serology; six out of the eight as measles and two as combination of measles and rubella highlighting the need to carry out rubella serology on measles-negative samples. Genetic characterization of three isolates obtained revealed one as genotype D4 and two as D8. Measles genotypes D4 and D8 were found to circulate in three districts of Tamil Nadu. It is necessary to be aware of the circulating genotypes within the geographical area. The information would be valuable to evaluate control measures and identify viral transmission and importation.

Adolescent↗

Study of combined vaccination against yellow fever and measles in infants from six to nine months.

A study has been carried out in the Ivory Coast to assess the efficacy of a combined vaccine against yellow fever and measles relative to that of each vaccine administered separately. Healthy children aged six to nine months were recruited and divided into two age groups: less than seven months (group I) and more than eight months (group II). In each group, they were randomly assigned to receive either yellow fever vaccine only (A), measles vaccine only (B), or the combined vaccine (C). The serological responses to measles and yellow fever were assessed in 219 initially seronegative children 45 days after immunization. More than 90% of the children developed yellow fever haemagglutination inhibiting antibodies. Neither age nor combination with measles vaccine influenced the responses to yellow fever vaccine. Measles haemagglutinational inhibiting antibodies were found in 97% of the children and the seroconversion rate was influenced neither by age nor by combination with yellow fever vaccine. Younger infants had lower titres of measles antibody. No particular adverse reactions were notified during the follow up. This study shows that combined yellow fever and measles vaccines are immunogenic in infants from the age of six months. Controlling yellow fever in endemic areas and the prevention of measles in young infants may greatly benefit by this combination.

Antibodies, Viral↗

Re-exposure to wild-type virus stabilizes measles-specific antibody levels in late convalescent patients.

BACKGROUND: Infection with wild-type (wt) measles virus strains induces high antibody levels believed to provide life-long protection against disease. OBJECTIVES: Humoral immunity was followed up in convalescent measles patients to assess the persistence of specific antibodies after measles disease in individuals without and with documented re-exposure to wt virus. STUDY DESIGN: Paired sera were collected from 43 late convalescents (LC) before re-exposure and 3.7-4.8 years after re-exposure to at least one measles patient (LC+ group). Antibody persistence in this group was compared to paired sera from 43 age- and sex-matched controls without documented exposure to wt virus (LC- group). Paired sera were also obtained from 26 measles patients 1.3-1.7 and 3.8-4.1 years after they had recovered from measles to observe the waning of antibodies in early convalescents (EC group). RESULTS: Antibody levels decreased by 12.1% (CI: 3.2-20.3%, p=0.01) within 6.3 years in the LC- group of late convalescent measles patients. In contrast, in the LC+ group GMT of first and second sera were virtually identical, indicating that exposure to wt virus stabilizes antibody levels even in absence of a detectable secondary immune response. In a subset of late convalescents of group LC+ with a secondary immune response, antibody waning after re-exposure was as high as 15.6%/year (CI: 13.0-17.7%/year), corresponding to a half-life of 4.1 years (CI: 3.5-5.0 years), but antibodies were still higher than before re-exposure. In the EC group GMT decreased by 6.5% (95% CI: -13.3% to +0.1%) during 2.5 years but significance was low (p=0.08). CONCLUSION: The maintenance of antibody levels in convalescent measles patients is at least partially dependant on recurrent exposure to circulating wt virus.

Adolescent↗

Crohn's disease after in-utero measles virus exposure.

BACKGROUND: An epidemiological association between Crohn's disease and measles virus exposure in early life has been suggested in case-control studies. METHODS: To determine absolute risk estimates for in-utero measles virus exposure and Crohn's disease, maternity charts for all 25000 deliveries at University Hospital, Uppsala, between 1940-49 were reviewed: four cases of measles infection in the mother during pregnancy were identified. The children and two of their mothers were interviewed and case records reviewed. Three offspring had undergone multiple intestinal resections; tissue from these cases were examined by routine histology, and for measles-virus nucleoprotein antigen by immunohistochemistry and immunogold electronmicroscopy. FINDINGS: Three of the four children had Crohn's disease. In each the disease was preceded by recurrent, antibiotic-resistant pneumonia. They had extensive ileal and colonic disease; two patients required intravenous feeding. The only offspring to have had measles as a child did not develop Crohn's disease. Measles virus antigen was detected in foci of granulomatous and lymphocytic inflammation in all children with Crohn's disease. INTERPRETATION: The data indicate that exposure of mothers to measles virus in utero is a risk factor for Crohn's disease in their children. Exposure at this time may lead to persistent infection, or modify the response to infection in later life, leading to persistence of measles virus.

Adult↗

Vaccination against acute respiratory virus infections and measles in man.

Several viruses may cause more or less severe acute respiratory infections in man, some of which are followed by systemic infection. Only for influenza and measles are licensed vaccines available at present. The protection induced by influenza vaccines, which are based on inactivated whole virus or viral subunits, depends largely on the matching of vaccine strain and circulating virus. Measles vaccines, which are based on attenuated live virus, have been quite effective in controlling the disease in vaccinated populations in the industrialized world. In developing countries, severe measles infections occur in infants from six to nine months of age, which necessitates the vaccination of children of less than six months. At that time maternal antibodies, that may interfere with the induction of protection, may still be present. Therefore, instead of using the parenteral route, the possibility to use the mucosal route of primary immunization is also investigated for vaccination with attenuated live measles vaccines. The use of inactivated measles vaccines has resulted in a state of immunity which upon exposure to the virus may induce an atypical measles syndrome including a severe pneumonia. Measles virus proteins presented in an iscom matrix have recently been shown to induce functional B and T cell responses to both the surface glycoproteins of the virus. These responses could also be induced in the presence of virus neutralizing antibodies and they proved to be protective in several animal model systems. Many of the problems that have been encountered in the development of measles vaccines, proved to be similar in the development of vaccines against other paramyxoviruses causing acute respiratory infections in man, including respiratory syncytial virus. Parenteral application of inactivated and attenuated live vaccines against these paramyxoviruses has generally had little success. Topical application of attenuated live vaccines has been more successful, and also the use of vaccinia recombinant viruses expressing foreign paramyxoviral glycoproteins has shown promising results in laboratory animals. Live vaccines based on adenovirus types 4 and 7 in oral enteric-coated vaccines, which lead to virus replication in the intestines but not in the respiratory tract have been included in military vaccination programs. The possibility to replace e.g. the E3 region with foreign DNA makes adenoviruses also suitable as cloning vectors for proteins of other respiratory viruses. Although live attenuated vaccines against some of the serotypes of rhinoviruses have shown promising results, the generation of a multivalent vaccine against this epidemiologically most significant cause of acute respiratory infections will be almost impossible, due to the multiplicity of serotypes involved.(ABSTRACT TRUNCATED AT 400 WORDS)

Humans↗

Plant-derived measles virus hemagglutinin protein induces neutralizing antibodies in mice.

Measles remains a significant problem in both the developed and developing world, and new measles vaccination strategies need to be developed. This paper examines the strategy of utilizing transgenic plants expressing a measles antigen for the development of an oral sub-unit measles vaccine. A 1.8 kb fragment encompassing the coding region of the measles virus hemagglutinin (H) protein was cloned into a plant expression cassette. Three different expression constructs were tested: pBinH (H gene alone), pBinH/KDEL (addition of a C-terminal endoplasmic reticulum-retention sequence SEKDEL) and pBinSP/H/KDEL (further addition of an authentic N-terminal plant signal peptide). The highest levels of recombinant H protein production were observed in plants transformed with pBinH/KDEL. Mice inoculated intraperitoneally with transgenic plant derived recombinant H protein produced serum anti-H protein antibodies that neutralized the measles virus (MV) in vitro. Mice gavaged with transgenic tobacco leaf extracts also developed serum H protein-specific antibodies with neutralizing activity against MV in vitro. These results indicate that the plant-derived measles H protein is immunogenic when administered orally and that, with further development, oral vaccination utilizing transgenic plants may become a viable approach to measles vaccine development.

Administration, Oral↗

Introducing a novel model to estimate national and global measles disease burden.

OBJECTIVES: In discussions of expanded measles control, elimination, and possible eradication, better estimates of disease burden are increasingly important to target vaccination control measures. Because global surveillance for measles is inadequate, a model to quantify country-specific estimates of measles disease burden was formulated to help policy-makers consider control options. METHODS: Country-specific demographics, developmental status, historic vaccine coverage rates, and age-specific vaccine efficacy and attack rates were used to determine the number of measles cases and deaths for 5-year periods. RESULTS: The model estimates an annual global incidence of 32 million measles-susceptible persons ( approximately 25% of the global birth cohort), resulting in 28 million cases and 691 thousand deaths. Eighty-four percent (578,000) of the global deaths occur in the World Health Organization African and Southeast Asian regions. Twenty countries account for 82% of deaths attributable to measles. In nine countries, over 2% of the birth-cohort are estimated to die from measles. CONCLUSIONS: This methodology quantifies country- and age-specific measles disease burden and establishes regional and global disease patterns, allowing aggregations by income groups and regions, which aids policy formulation. The data may be continuously updated, based on dynamic changes in vaccine coverage rates and the incorporation of national vaccination campaigns.

Adolescent↗

Rubella and measles seroprevalence among women of childbearing age, Argentina, 2002.

To assess rubella and measles susceptibility among women of childbearing age we conducted a cross-sectional seroprevalence study in four cities and one rural area in Argentina. A convenience sample of women aged 15-49 years seeking care in public health-care institutions was selected (n=2804). Serum specimens were tested for rubella and measles IgG antibody titres. The overall susceptibility to rubella and measles was 8.8 and 12.5% respectively. Seroprevalence differences were found for both rubella (P<0.001) and measles (P=0.002) across sites. Rubella seroprevalence was higher in women aged >or=40 years than in younger women (P=0.04). Measles seroprevalence tended to increase with age (P<0.001). Approximately 15% of women aged 15-29 years were not immune to measles. No risk factors were associated with rubella seronegativity; however, age (P<0.001) and having less than four pregnancies (P<0.001) were factors associated with measles seronegativity. Our findings support the introduction of supplemental immunization activities targeting adolescents and young adults to prevent congenital rubella syndrome and measles outbreaks over time.

Adolescent↗

Molecular epidemiology of measles virus in Japan.

BACKGROUND: Measles virus has been classified into 22 genotypes. The present report examines the molecular epidemiology of measles virus in Japan from 1984 to 2002, and the epidemiological link between imported cases in several foreign countries and Japanese strains was elucidated from the literature. METHODS: B95a or Vero cells was used to isolate the measles virus. The measles virus genome was amplified in the N and H genes by reverse transcriptase-polymerase chain reaction and were partially sequenced. Phylogenetic analysis of a partial sequence of the N gene, from position 1230 to 1685, of the recent measles strains was performed in comparison with the World Health Organization reference strains. RESULTS: There were large outbreaks of measles in Japan in 1984, 1987-1988, 1991-1993, and 2001-2002 and each outbreak was caused by a different genotype. Genotype C1 was an indigenous strain for a long period before 1985, while D3 was isolated in 1987-1988 and D5 in 1991-1993 outbreaks. In addition, the Chicago-type D3 caused sporadic regional outbreaks from 1998 to 1999. After 2000, H1 became the dominant circulating strain. It should be noted that the Japanese strains were detected as imported cases by epidemiological linkage in several countries. CONCLUSIONS: Among the recent circulating strain of measles virus in Japan the genotype H1 was dominant after 2000 and the Japanese strains D3, D5, and H1 were exported to several countries. It is recommended that Japan should adopt a more extensive and active vaccination strategy for measles elimination in line with other countries in the world.

Humans↗

Acute and long-term changes in T-lymphocyte subsets in response to clinical and subclinical measles. A community study from rural Senegal.

To investigate the possibility of long-term suppression of T-lymphocyte subsets, we examined children exposed to measles at home during an epidemic in rural Senegal, at time of exposure and 1 and 6 months later. The measles case fatality ratio was 1%. Subclinical measles was common among vaccinated children exposed to measles (45%). Both clinical and subclinical cases of measles showed a significant rise in absolute CD4 count in the incubation period. In the prodromal phase and the first week after the rash, the lymphocyte percentage, the white blood cell count and the absolute CD4 cell numbers were significantly reduced. There was no persistent decrease of absolute CD4 or CD8 numbers at 1 or 6 months after exposure. Measles infection was followed by significant changes in the subset composition, both CD4 and CD8 percentages being significantly higher in the second month after measles than among non-seroresponders. These changes were more marked among girls, since they had significantly higher CD4 percentages and CD4/CD8 ratios than boys in the convalescence phase. In conclusion, measles infection is not associated with a long-term suppression of CD4+ or CD8+ T-lymphocytes.

Adolescent↗