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Genetic analysis of measles viruses isolated in the united states between 1989 and 2001: absence of an endemic genotype since 1994.

This report describes measles virus surveillance in the United States for 1989-2001. During the resurgence of measles in the United States between 1989 and 1992, only viruses of genotype D3 were isolated. In contrast, virological surveillance conducted after the resurgence period showed that at least 12 different genotypes were associated with the greatly reduced number of measles cases. Eight different genotypes were identified for 27 chains of transmission in which the source of infection was unknown. The diversity of measles virus genotypes observed in the United States between 1994 and 2001 reflected multiple imported sources of virus and indicated that no genotype of measles is endemic in the United States. Therefore, the data obtained from virological surveillance are consistent with the conclusions made by disease surveillance and epidemiological investigations that measles is no longer an endemic disease in the United States.

Endemic Diseases↗

Low risk of measles transmission after exposure on an international airline flight.

In May 2000, a passenger with measles traveled aboard a 7-hour flight from Japan to Hawaii. A follow-up survey was sent to 307 (91%) of the 336 exposed passengers to identify susceptible passengers and subsequent occurrences of measles. The median age of the 276 respondents (90%) was 34 years; 268 (97%) were residents of Japan. Self-reports determined that 173 (63%) were immune through prior measles or vaccination; 6 (2%) denied a history of prior measles or immunization, and 97 (35%) were unaware of their status. Only 1 nonimmune respondent received immunoprophylaxis. None of the respondents developed a febrile rash illness 7-21 days after exposure. The risk of in-flight measles transmission among passenger populations with similar susceptibility profiles appears to be low. An aggressive response by health departments may not be warranted after airborne exposure to measles. Each health department should make such determinations on the basis of specific circumstances and availability of resources.

Adolescent↗

Evaluation of the measles clinical case definition.

An accurate system of identifying and classifying suspected measles cases is critical for the measles surveillance system in the United States. To examine the performance of the clinical case definition in predicting laboratory confirmation of suspected cases of measles, we reviewed 4 studies conducted between 1981 and 1994. A clinical case definition was examined that included a generalized maculopapular rash, fever (>or=38.3 degrees C, if measured), and either a cough, coryza, or conjunctivitis. Serological confirmation of measles was done either by hemagglutination inhibition assay, complement fixation assay, or enzyme immunoassays. The positive predictive value of the clinical case definition decreased from 74% to 1% as incidence decreased from 171 cases/100000 population to 1.3 cases/100000 population. Sensitivity was high, and for the larger studies with the most precise estimates, sensitivity was 76%-88%. The low positive predictive value of the clinical case definition in settings of low incidence demonstrates that serological confirmation is essential to ensure an accurate diagnosis of measles when measles is rare.

Adolescent↗

Lessons learned from establishing and evaluating indicators of the quality of measles surveillance in the United States, 1996-1998.

As part of a strategy to eliminate measles, 7 indicators were adopted in the United States in 1996 to ensure the quality of measles surveillance. This report summarizes the US experience with these indicators during 1996-1998. The indicators are compiled from data reported to the Centers for Disease Control and Prevention (CDC) during routine surveillance supplemented with information collected directly from states. Measles case investigations are generally thorough, and sufficient information is collected to control and monitor disease. A high proportion of measles cases are imported from other countries, suggesting that investigations are complete. For some states, the lag from disease onset to reporting is long, and the number of health department investigations of measleslike illnesses is low. Most of these investigations include laboratory testing of clinical specimens. Collection of measles virus specimens from cases for genetic analysis needs improvement. The CDC and health departments need to continue efforts directed at health care professionals to ensure the recognition, proper diagnostic workup, and reporting of measles.

Centers for Disease Control and Prevention, U.S.↗

Human leukocyte antigen haplotypes in the genetic control of immune response to measles-mumps-rubella vaccine.

To elucidate the contribution of human leukocyte antigen (HLA) haplotypes and their genotypic combinations to immune status after measles-mumps-rubella (MMR) vaccination, 346 children 12-18 years of age were studied. The class I A*29-Cw*16-B*44 haplotype was associated with lower levels of immunoglobulin G (IgG) antibody to both measles (P=.08) and mumps (P=.03) viral antigens. The A*26-Cw*12-B*38 haplotype was associated with higher cellular immune responses to measles (P=.02) and mumps (P=.01) vaccine viruses. Subjects with the class II DRB1*03-DQB1*02-DPB1*04 haplotype had higher lymphoproliferative responses to measles virus (P=.01) and mumps virus (P=.006). The DRB1*15/16-DQB1*06-DPB1*03 haplotype was associated with high levels of IgG antibody to measles virus (P=.09) but low levels of IgG antibody to rubella virus (P=.02), whereas DRB1*04-DQB1*03-DPB1*03 was associated with high lymphoproliferative responses to both measles (P=.01) and rubella (P=.002) vaccine viruses. A*26-Cw*12-B*38 was associated with both mumps virus-specific humoral (P=.007) and cell-mediated (P=.01) immune responses after 2 doses of MMR vaccine. Haplotype DRB1*04-DQB1*03-DPB1*03 was associated with both lower rubella virus IgG antibody levels (P=.02) and higher rubella virus-specific lymphoproliferation (P=.002). Better characterization of such HLA profiles could inform and improve the design of novel epitope-rich vaccines and help to predict protective immune responses at the individual and population level.

Adolescent↗

Current impact of measles in the United Kingdom.

Annual measles notifications in the United Kingdom continue to exceed 100,000 despite the introduction in 1968 of routine measles vaccination for children aged one to two years. One in 5,000 children with notified cases of measles die; complications of the disease remain similar in incidence and severity to those observed in 1963. The overall vaccine acceptance of 50% has reduced notifications of disease primarily among children aged one to four and five to nine years. In areas where vaccination acceptance is higher than the national average, there has been a reduction in notifications for all age groups. Schwarz strain vaccine, which has been in use since 1968, has been shown to give protection lasting up to 16 years. Despite the reduction in the incidence of measles and the low acceptance of vaccine, no apparent increase has been found in the number of 11-year-old children susceptible to measles, a finding demonstrated by an unchanging percentage of children with measles antibody from 1974-1981.

Adolescent↗

Current measles control in Tanzania.

Measles is one of the major public health problems in Tanzania and is recognized as such by the population. Since 1975 measles vaccination has been given as part of the national expanded immunization program. On the basis of the findings of measles surveys and a vaccination trial, the policy of vaccination at six months of age has been changed to that of vaccination at nine months of age, and malnourished children are now vaccinated. Vaccination coverage is unsatisfactory because many villages are too far from health units and because measles vaccination has low credibility. The epidemiology of measles appears to be changing as a result of vaccination, and the age of vaccination may have to be modified in the future. A policy of vaccinating each child twice is being considered as well as one of vaccinating sick children who are attending maternal and child health clinics. At present eradication of measles is not a realistic target for countries such as Tanzania.

Age Factors↗

International measles importations United States, 1980-1985.

Between 1980 and 1985, 89-121 international measles importations were reported annually in the US, accounting for 0.7-6.9% of the annual number of reported measles cases. These measles cases were acquired in more than 70 different countries. Three countries accounted for over one third of all imported cases: Mexico, the UK and the Philippines. Thirty-six states reported importations. However, over half of all importations were reported from only six states: California, New York, Maryland, Florida, Texas and Hawaii. Most measles importations did not cause transmission in the US. In 1982 and 1985 only 16% and 29% of importations resulted in any spread cases. Until there is better control of measles worldwide, high immunization levels are crucial for continued measles control in the US.

Adolescent↗

Measles transmission in health facilities during outbreaks.

BACKGROUND: Consultation waiting rooms and similar medical settings, either public or private, are places where children have higher probability of acquiring some infectious diseases, especially during outbreaks. METHODS: During a measles outbreak which occurred in Lisbon in 1989 a case-control study was carried out in a major paediatric hospital to estimate the risk of measles infection associated with the exposure in medical settings. The statistical analysis was performed with data matched on age, using conditional logistic regression, to reach a multivariate model which explains the risk in the presence of the main variables of interest. RESULTS: The crude odds ratio (OR), based upon 72 cases and 216 controls, in children younger than 12 years, was 4.1 (P < 0.001). Hospital emergency settings had an OR of 4.9 (P < 0.001) and private physicians' offices an OR of 1.4 (P = 0.689). Non-whites showed a 2.4-fold increase in the crude probability of getting measles, although this was not statistically significant (P = 0.118). Children who had a recent contact with cases of measles had an OR of 14.7 (P = 0.005). Immunization against measles was an important protective factor (OR = 0.1; P < 0.001), as was attendance at kindergartens or wet nurses, although less significant (OR = 0.4; P = 0.051). CONCLUSIONS: This study supports the need for children to avoid unnecessary exposure in medical settings during measles outbreaks, especially if those settings are crowded and result in long waiting periods before a consultation.

Case-Control Studies↗

Immunization of 6 and 9 month old infants with AIK-C, Edmonston-Zagreb, Leningrad-16 and Schwarz strains of measles vaccine.

BACKGROUND: Measles kills more than 1 million infants per year and is particularly lethal in infants < 1 year old in developing countries. Recent reports have suggested that measles vaccines of different strains and titre differ in their immunogenicity in young infants. We sought to identify strains and titres of measles vaccines which would be effective in 6 and 9 month old infants. METHODS: We conducted a randomized trial of AIK-C, Edmonston-Zagreb (EZ), Leningrad-16 and Schwarz strains of measles vaccine at different titres in 1202 6 month old and 1250 9 month old infants. Antibody levels were measured by haemagglutination inhibition assay. Seroconversion was defined as a change from seronegative to seropositive or a fourfold rise in titre above the expected level after antibody decay (assumed antibody half-life = 6 weeks). Chi-square tests were used to compare seroconversion rates and rates of adverse reactions among the groups. Comparison of geometric mean titres (GMT) was done by the Student's t-test. RESULTS: No severe or unusual adverse reactions occurred during the 6 weeks after vaccination. All strains induced high seroconversion rates in 9 month old infants. In 6 month olds, medium- and standard-titre AIK-C induced the highest rates of seroconversion. Antibody titres at 6 weeks after vaccination were highest in recipients of Schwartz vaccine and lowest for EZ vaccine recipients. CONCLUSIONS: Standard-titre AIK-C may be more effective than other measles vaccine strains for early measles immunization and should be evaluated further for efficacy, long-term immunogenicity, and long-term safety.

Antibodies, Viral↗

Measles antibody: reevaluation of protective titers.

A school blood drive before a measles outbreak permitted correlation of preexposure measles antibody titers with clinical protection using the plaque reduction neutralization (PRN) test and an EIA. Of 9 donors with detectable preexposure PRN titer less than or equal to 120, 8 met the clinical criteria for measles (7 seroconfirmed) compared with none of 71 with preexposure PRN titers greater than 120 (P less than .0001). Seven of 11 donors with preexposure PRN titers of 216-874 had a greater than or equal to 4-fold rise in antibody titer (mean, 43-fold) compared with none of 7 with a preexposure PRN titer greater than or equal to 1052 (P less than .02). Of 37 noncases with preexposure PRN titer less than 1052, 26 (70%) reported one or more symptoms compared with 11 (31%) of 35 donors with preexposure PRN titers greater than or equal to 1052 (P less than .002). By EIA, no case had detectable preexposure antibody; the preexposure geometric mean titer of asymptomatic donors (220) was not significantly higher than that of symptomatic donors who did not meet the clinical criteria for measles (153) (P = .10). The study suggests that PRN titers less than or equal to 120 were not protective against measles disease and illness without rash due to measles may occur in persons with PRN titers above this level.

Adult↗

Successes and failures in measles control.

The Expanded Programme on Immunization (EPI) of the World Health Organization has a global target of reducing measles incidence by 90% and mortality by 95% from pre-EPI levels by 1995. Both developed and developing countries that have given priority to measles control have substantially reduced measles morbidity and mortality, and some have come close to eliminating measles. A variety of vaccination schedules and strategies have been used, which reflect the differing program goals, health services infrastructure, and availability of resources in different countries. Failure to control measles has usually been due to a failure to implement planned strategies adequately. The highest priority in measles control is to assist countries, especially the lowest-income countries, to implement vaccination programs more effectively.

Developing Countries↗

Vitamin A administered with measles vaccine to nine-month-old infants does not reduce vaccine immunogenicity.

After a report of reduced seroconversion to measles in infants, aged 6 mo, given vitamin A with their measles vaccination, serious concerns were raised regarding the safety of the WHO's recommendation that infants be supplemented with vitamin A at the time of measles immunization. To determine the impact of coadministered vitamin A on the antibody response to measles vaccine given to infants aged 9 mo, the more common age for immunization in developing countries, we conducted a randomized, double-blind, placebo-controlled trial in an urban slum community in Delhi. Infants (618) were randomly allocated to receive 30 mg vitamin A or a placebo with the measles immunization. Antibodies to measles were measured by ELISA in serum samples obtained at before (baseline) and 12 wk after immunization. Overall, the seroconversion rates did not differ between vitamin A (89.5%) and placebo (87.6%) groups. There were no significant differences in the geometric mean titers in the two groups (ratio of geometric means, 1.19; 95% confidence interval, 0.97-1.46). Among malnourished infants, the geometric mean titer was significantly greater in the vitamin A group compared to the placebo group (ratio of geometric means, 1.57; 95% confidence interval, 1. 18-2.0), but seroconversion rates did not differ. There were no differences in seroconversion rates and geometric mean titers in the two study groups among the well-nourished children. These results indicate that 30 mg vitamin A does not reduce the immune response to the coadministered vaccine and, therefore, can be continued to be given safely in public health programs.

Antibody Formation↗

Measles (rubeola) susceptibility among elementary schoolchildren.

Measles (rubeola) immunity among 479 elementary schoolchildren from suburban Minneapolis was serologically surveyed in December 1971. Of the 479 children, 25 (5.2%) had hemagglutination-inhibition (HI) titers less than 2. These children were considered susceptible to measles. For the 233 immunized children with no measles history, 13 (5.6%) had rubeola HI titers less than 2 while 5 (5.1%) of the 98 youngsters with a history of clinical measles had rubeola HI titers less than 2. Of the 454 immune children, 73 (16%) had measles HI titers between 2 and 8. These findings confirm durable immunity and a low rate of vaccine failure following live attenuated measles vaccination but demonstrate the importance of testing sera beginning at a dilution of 2 in order to detect children with low antibody levels. This survey also suggests that maternal antibody interferes with the active immune response in youngsters immunized when less than 1 year of age because this group of children had significantly lower geometric mean titers and significantly more susceptibles than the children immunized when greater than or minus 2 years.

Age Factors↗

Measles in rural Ohio county.

Between December 23, 1975, and March 31, 1976, 169 cases of measles were reported from Defiance County, Ohio, a small rural county in the northwest corner of the State. The outbreak spread from a single junior high school basketball player to eventually involve 19 of the 28 county schools. Among the affected schools, measles attack rates varied from 0.3-7.2% with a mean of 2.0%. A likely source of illness was determined for 160 of the 169 cases (95%). Intraschool transmission was most common, accounting for 97 of the 169 cases (57%) followed by sibling contact for 23 cases (14%). The pattern of measles spread was complex and would have been difficult to predict in advance even if surveillance systems reported each case the day it occurred. A control program held between February 2 and February 20, 1976, vaccinated 5145 of the 11,114 (46.3%) county schoolchildren. Forty-four cases of measles occurred 4 or more days following school clinics, 22 (50%) in children who requested measles vaccine at school clinics, 17 of whom were actually vaccinated. Most of the other cases occurred in students whose parents thought their children to be protected. Measles is a disease which spreads rapidly in a complex pattern over wide geographic areas. A control program vaccinating a large proportion of the children without definitive history of adequate vaccination or disease was apprently effective in curtailing the outbreak.

Adolescent↗

Measles vaccination and childhood mortality in rural Bangladesh.

To ascertain whether measles vaccination was associated with reduced mortality rates in rural Bangladeshi children, the authors conducted a case-control study in four contiguous areas, two of which had participated in an intensive measles vaccination program which began in the spring of 1982. Cases were 536 children who had died in the four-area region at the age of 10-60 months between April 1982 and December 1984. Two age- and sex-matched controls were selected from the four-area region for each case; each control had survived at least through the date of death of the matched case. Measles vaccination was associated with a 36% (95% confidence interval 21%-48%) proportionate reduction in the overall rate of death and a 57% (95% confidence interval 43%-67%) reduction in the rate of deaths directly attributed to measles or ascribed to diarrhea, respiratory illness, or malnutrition. The association of measles vaccination and reduced mortality remained unchanged after the authors restricted controls to children who had survived at least one year after the deaths of their matched cases. Moreover, children vaccinated in 1982 exhibited a sustained reduction in the rate of death in 1983 and 1984. The authors concluded that measles vaccination was associated with a pronounced and sustained reduction in the rate of death among children in this study.

Bangladesh↗

Assessment and possible control of endemic measles in urban Nigeria.

BACKGROUND: Measles remains as a serious problem of infancy and childhood in the developing world, despite the availability of a vaccine. Increasing urbanization is changing patterns of endemicity. METHODS: A survey of measles in an urban area of Nigeria, using a rapid assessment approach, was carried out to characterize measles in this community. RESULTS: An annual incidence rate of 11.8% among under-fives was found, associated with an acute case fatality rate of 3.3%. This level of endemicity was two orders of magnitude greater than that suggested by official case reports. An endemic, rather than epidemic, pattern was found over the six-month period of the study. Vaccine efficacy was estimated at 26%. Risk factor analyses showed the major risks for measles to be clinic attendance in the month preceding disease, households with more than one mother, and having under-five siblings. Measles itself was the principal risk factor for malnutrition and against survival. CONCLUSIONS: Improved understanding of measles epidemiology and risk factors are prerequisites for effective control. Possible strategies should include vertical vaccination efforts in addition to routine programmes.

Child, Preschool↗

The duration of maternal measles antibodies in children.

The most important factor affecting the success of measles immunization is the disappearance of maternal anti-measles antibodies. In order to determine the optimum age for measles vaccination and to contribute towards the Expanded Programme on Immunization as currently applied in Turkey, we investigated the rate of disappearance of anti-measles antibodies. The study population consisted of 124 healthy infants aged 1-15 months from Erzurum, Erzincan, and Kars. The overall proportion of seropositivity, which is the result of the presence of maternal anti-measles antibodies, was 67/124 (54 per cent). The proportion of infants with detectable antibodies declined progressively with increasing age. The distribution of maternal antibody levels with respect to age showed a progressive reduction with increasing age from 7 months to 15 months. Thus the proportion of antibody-positive infants declined from 50 per cent at 7-9 months to 10 per cent at 13-15 months. While an evident decrease occurred during these months, no important decline was observed up to 9 months of age. The results of this study show that the minimum proportion of antibody-positive infants (10 per cent at 13-15 months of age) is still higher than the optimum proportion (5 per cent). The Schwarz vaccine, which is used mostly in measles immunization, seems not to be effective to obtain a high seroconversion rate in our infants. Edmonston-Zagreb vaccine strain should be given to children under the age of 15 months in eastern Turkey. In addition, serological studies should be performed periodically, and vaccination programmes appropriate for our country should be determined according to these data.

Aging↗