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Measles eradication: experience in the Americas.

In 1994, the Ministers of Health from the Region of the Americas targeted measles for eradication from the Western Hemisphere by the year 2000. To achieve this goal, the Pan American Health Organization (PAHO) developed an enhanced measles eradication strategy. First, a one-time-only "catch-up" measles vaccination campaign is conducted among children aged 9 months to 14 years. Efforts are then made to vaccinate through routine health services ("keep-up") at least 95% of each newborn cohort at 12 months of age. Finally, to assure high population immunity among preschool-aged children, indiscriminate "follow-up" measles vaccination campaigns are conducted approximately every 4 years. These vaccination activities are accompanied by improvements in measles surveillance, including the laboratory testing of suspected measles cases. The implementation of the PAHO strategy has resulted in a marked reduction in measles incidence in all countries of the Americas. Indeed, in 1996 the all-time regional record low of 2109 measles cases was reported. There was a relative resurgence of measles in 1997 with over 20,000 cases, due to a large measles outbreak among infants, preschool-aged children and young adults in São Paulo, Brazil. Contributing factors for this outbreak included: low routine infant vaccination coverage, failure to conduct a "follow-up" campaign, presence of susceptible young adults, and the importation of measles virus, apparently from Europe. PAHO's strategy has been effective in interrupting measles virus circulation. This experience demonstrates that global measles eradication is an achievable goal using currently available measles vaccines.

Adolescent↗

Measles antibody in vaccinated human immunodeficiency virus type 1-infected children.

OBJECTIVES: The goals of this study were to evaluate the proportion of previously vaccinated human immunodeficiency virus (HIV) type 1-infected children with detectable postvaccination measles antibody; to assess risk factors for vaccine failure; and to evaluate the response to reimmunization. METHODS: A total of 81 perinatally HIV-infected children receiving medical care in the Bronx, New York who had previously received measles vaccine were enrolled. The Centers for Disease Control and Prevention (CDC) HIV class, lymphocyte subsets, and measles antibody were determined upon enrollment. Additional data abstracted from medical records included dates and number of prior measles vaccinations and CDC HIV class at the time of vaccination. Measles antibody was determined by microneutralization enzyme-linked immunosorbent assay (ELISA). RESULTS: The median age at time of study was 42 months (range, 9 to 168 months). Overall, 58 (72%) subjects had detectable measles antibody (microneutralization ELISA titer > 1:5). Children studied within 1 year of vaccination were more likely to have detectable measles antibody than children evaluated more than 1 year after vaccination (83% vs 52%, P < .01). The proportion of children with detectable measles antibody was higher among children with no or moderate immunosuppression compared to those with severe immunosuppression when immune status was based on CD4%. Children vaccinated at 6 to 11 months of age appeared to have a higher proportion of detectable measles antibody than those who received a first measles vaccination after age 1. Only 1 (14%) of 7 previously vaccinated children who were seronegative or had very low titers experienced a four-fold rise in measles antibody when reimmunized. CONCLUSION: These results support current recommendations to vaccinate HIV-infected children against measles. The proportion of children with detectable measles antibody among vaccinated HIV-infected children is considerably lower than in vaccinated healthy children. HIV-infected children may respond better to measles vaccine when it is administered before the first birthday. From our limited data it appears that reimmunization of previously vaccinated HIV-infected children with moderate to severe immunosuppression does not result in an antibody recall response.

Adolescent↗

Measles & malnutrition.

Measles is an important acute childhood viral infection having severe consequences on the nutritional status. The adverse nutritional effects of measles are experienced by both the well-nourished and the malnourished children. However, the severe nutritional deficiencies like kwashiorkor/marasmus are precipitated only in children who are already malnourished. As high as 3-4 per cent of children with measles suffered from these clinical nutritional syndromes in their post-measles period. Though malnutrition is widespread among Asian children also, measles appears to run a milder course with low mortality rates in developing Asian countries, as compared to African children. The associated secondary infections which apparently complicate the primary illness in malnourished children might be responsible for higher mortality and could be due to socioeconomic and environmental causes that are associated with poverty and malnutrition rather than due to malnutrition or measles per se. Measles related blindness is of multifactorial aetiology. While acute measles triggers corneal ulceration through viral proliferation in the cornea, nutritional keratomalacia is often the cause of blindness in the post-measles period. Measles vaccination is the major preventive measure. However, timely use of local antibiotic therapy to the eyes and administration of vitamin A supplements offer protection to the child who already has measles. Response of malnourished children to live attenuated measles vaccine has been found to be safe and effective. Neither malnutrition nor tuberculosis which are widespread among malnourished children of developing countries appear to be contraindications for measles vaccination. Thus, the beneficial effects of the measles vaccination should be fully exploited by adequate supply of potent vaccine and coverage of all susceptible children.

Africa↗

Evaluation of potentially common adverse events associated with the first and second doses of measles-mumps-rubella vaccine.

BACKGROUND/OBJECTIVES: In 1989, the American Academy of Pediatrics and the Advisory Committee on Immunization Practices recommended that school children receive 2 doses of measles-mumps-rubella vaccine. With measles and rubella eliminated from the United States, measles-mumps-rubella vaccine adverse events have come under scrutiny, but no study has compared the reactogenicity of the first (measles-mumps-rubella vaccine dose 1) and second (measles-mumps-rubella vaccine dose 2) doses at the most common ages of administration in the United States. METHODS: From a health maintenance organization, 3 groups of children were recruited: (1) toddlers aged 12 to 24 months receiving measles-mumps-rubella vaccine dose 1; (2) kindergartners aged 4 to 6 years receiving measles-mumps-rubella vaccine dose 2; and (3) middle schoolers aged 10 to 12 years receiving measles-mumps-rubella vaccine dose 2. From 2 weeks before measles-mumps-rubella vaccine administration until 4 weeks afterward, families recorded in diaries the occurrence of potentially common symptoms. Postvaccination symptom rates were compared with the prevaccination baseline, with significance assessed by testing incidence rate ratios estimated by Poisson regression. RESULTS: Of 2173 children enrolled, 373 (17%) were lost to attrition, producing a study population of 1800. Compared with the prevaccination baseline, rates of fever, diarrhea, and rash were significantly elevated postvaccination among 535 toddlers receiving measles-mumps-rubella vaccine dose 1. An estimated net 95 (18%) experienced measles-mumps-rubella vaccine-associated events (median onset 5-10 days postvaccination, duration 2-5 days), with high fever (temperature > or = 39.5 degrees C) occurring in 33 (6%). None required medical attention. For 633 kindergartners and 632 middle schoolers, symptom rates were not significantly elevated after measles-mumps-rubella vaccine dose 2 compared with baseline. CONCLUSIONS: Vaccination-associated adverse events occur in approximately 1 of every 6 toddlers receiving measles-mumps-rubella vaccine dose 1, with high fever occurring in 1 of 20. Adverse events are infrequent for measles-mumps-rubella vaccine dose 2 administered to school-aged children.

Age Factors↗

Severity of measles: a study at the Queen Sirikit National Institute of Child Health.

INTRODUCTION: Thousands of measles cases are reported annually in Thailand even though measles vaccine has been introduced in the expanded program of immunization for every 9-month-old infant for nearly 20 years. Severe cases are admitted to the hospital, usually with complications, some cases lead to death. OBJECTIVES: To study the clinical presentations of severe cases of measles and its complications and find the correlations of severity of pneumonia with age, nutritional status and history of vaccination. MATERIAL AND METHOD: The hospital charts of measles patients admitted to the Queen Sirikit National Institute of Child Health (QSNICH) during 1998-2002 were retrospectively reviewed. Demographic data, history including history of measles vaccination, physical examinations, laboratory investigations, treatment and hospital course which were relevant were recorded. Paired t-test and Pearson's correlation were used for data analysis. RESULTS: There were 156 cases of measles admitted to the QSNICH. There were 95 boys and 61 girls and the male to female ratio was 1.56:1. The age range was 2 months to 14.8 years, median = 1.5 years, mode 8 months. Fifty-nine percent of the cases were under 2 years of age; 40% under one year and 23.9% were under 9 months. About 44% of the cases had one dose of previous measles vaccination, no history of measles vaccination in 91.4% of cases whose age was under 1 year in contrast to 80% of cases over 5 years that had a history of measles vaccination. Sixty-six percent of the cases had normal nutritional status while 12.4%, 4.8% and 2.1% had mild, moderate and severe protein calorie malnutrition. Fourteen cases (9%) had underlying diseases. At least 3 of the classical signs and symptoms of measles (rash, cough and coryza) were found in 92.3% of the cases. The mean duration of fever at the time of admission was 5.3 days. The common complications in admitted measles cases were pneumonia (62.2%) and diarrhea (38.1%). The likely causes of pneumonitis were measles viruses (52.6%) and bacteria (47.4%). There was one dead case with severe pneumonia, with ARDS and respiratory failure. Young infants had a higher incidence of diarrhea with dehydration (p = 0.000) but severity of pneumonia was not different from older children (p = 0.512). The severity of pneumonia was not correlated with the age (r = 0.087), nutritional status (r = 0122) or the history of receiving measles vaccine (r = 0.116). CONCLUSION: Measles is one of the important diseases of in-patients admitted to the QSNICH, because of the severity of the diseases due to pneumonia and diarrhea. One severe case died because of severe pneumonia that lead to ARDS and respiratory failure. Young infants had a higher incidence of diarrhea and dehydration, while there was no correlation between severe pneumonia with age, nutritional status and history of vaccination.

Adolescent↗

The geographic distribution of measles in the United States, 1980 through 1989.

OBJECTIVE: To describe the geographic distribution of measles cases in the United States by county for the 10-year period from 1980 through 1989. DESIGN: Ecological analysis of national measles surveillance data. METHODS: Measles cases reported to the Morbidity and Mortality Weekly Report from 1980 through 1989 were analyzed. Data from the 1980 and 1990 US censuses were used to produce demographic profiles for each of the 3137 countries. Outcome variables examined included mean annual incidence and number of years reporting measles, with use of Spearman's rank correlation coefficients to examine the association between the demographic and the two outcome variables. RESULTS: A total of 56,775 measles cases were reported during the decade. Of the nation's 3137 counties, 1690 (53.9%) did not report any cases; only 17 (0.5%) reported measles in all 10 years. Counties reporting measles more frequently during the decade had higher median populations, population densities, and percentage of black and Hispanic populations than those counties reporting less frequently. Population size, population density, and percentage of Hispanic population were associated with number of years reporting measles and mean annual measles incidence rate. Measles cases in counties reporting measles every year predominantly occurred in unvaccinated preschoolers; cases in counties reporting less frequently predominantly occurred in vaccinated school-aged children. CONCLUSIONS: This analysis illustrates the focal nature of measles in the United States during the past decade. Most counties have not reported a single case of measles during the entire decade, and only 17 counties reported measles every year. Targeted strategies are needed to improve age-appropriate immunization levels among preschool-aged children living in large inner-city areas.

Adolescent↗

Deficiency of the humoral immune response to measles vaccine in infants immunized at age 6 months.

CONTEXT: Measles causes serious morbidity in infants, with the highest risk among those who are 6 to 12 months of age. In the United States, measles vaccine has been given at age 12 to 15 months to minimize interference by passive antibodies and to achieve the high seroprevalence required for herd immunity. Infants of mothers with vaccine-induced immunity may lose passively acquired antibodies before 12 months, leaving them susceptible to measles infection. OBJECTIVE: To assess the immunogenicity of measles vaccine in infants younger than 12 months. DESIGN: Cohort study conducted before and after measles immunization. SETTING: Pediatric clinic in Palo Alto, Calif. PARTICIPANTS: Infants 6 (n = 27), 9 (n = 26), and 12 (n = 34) months of age were enrolled; 72 provided both initial and follow-up samples. MAIN OUTCOME MEASURES: Evaluation of immunogenicity before and 12 weeks after measles vaccination, including measles neutralizing antibody titers, measles-specific T-cell proliferation, and cytokine profiles. RESULTS: Measles neutralizing antibodies were present before vaccination in 52% (12/23), 35% (7/20), and 0% (0/22) of 6-, 9-, and 12-month-old infants, respectively. In the absence of detectable passive antibodies, geometric mean titers after vaccination were significantly lower in 6-month-old infants compared with 9-month-old infants (27 vs 578, P = .01) and 12-month-old infants (27 vs 972, P=.001). The seroconversion rate, defined as a 4-fold rise in antibody titer, in these 6-month-old infants was only 67%, and only 36% of these infants achieved seroprotective neutralizing antibody titers of 120 or higher after vaccination compared with 100% of 9- and 12-month-old infants lacking detectable passive antibody prior to vaccination. T-cell proliferation and cytokine responses to measles did not differ with age. CONCLUSIONS: Humoral immunity was deficient in 6-month-old infants given measles vaccine, even in the absence of detectable passively acquired neutralizing antibodies. Comparison of their responses with those of 9- and 12-month-old infants indicates that a developmental maturation of the immune response to measles may occur during the first year of life, which affects the immunogenicity of measles vaccine.

Age Factors↗

Detection of measles virus genome in lymphocytes from asymptomatic healthy children.

A total of 342 samples of peripheral blood mononuclear cells (PBMC) were obtained from 145 healthy individuals, which we examined for the presence of measles virus genome RNA by reverse transcription-polymerase chain reaction (RT-PCR), to identify whether asymptomatic infection of measles virus has occurred in healthy children. Measles virus genome was detected in 11 (23.4%) of 47 nonimmunized individuals; all positives for RT-PCR were infants who experienced measles exposure. No genome was detected in those without measles exposure. In 83 individuals immunized with measles vaccine, the vaccine strain genome was detected in 10 (71.4%) of 14 recipients whose PBMC were obtained within 2 months of vaccination. Measles wild-type genome was detected in 36 (46.2%) of 78 individuals, 40 (25.2%) of 159 samples, who had been immunized more than 2 months before. The wild-type measles genome was also detected in 6 (46.2%) of 13 individuals who had been infected with measles in the distant past. The measles PCR-positive rate was not related to the period since immunization or natural infection. Sequence analysis of PCR products demonstrated they were all in the same cluster of D5 lineage, which was the circulating strain during the study period. We obtained 13 samples of nasopharyngeal secretion (NPS) simultaneously from individuals whose PBMC were positive for measles PCR but did not detect virus genome. Measles genome was, however, detected from NPS in cases of acute infection. We conclude that asymptomatic measles infection is common but would rarely become a source of transmission because of negative PCR in NPS.

Adolescent↗

Prevalence of measles antibody among children under 15 years of age in Santa Cruz, Bolivia: implications for vaccination strategies.

We conducted a community-based survey in Santa Cruz city, Bolivia, to determine the age-specific prevalence of measles antibodies, determine factors associated with absence of detectable measles antibodies, and to compare results of salivary and serum measles immunoglobulin G (IgG) antibody assays. Serum samples from 1654 children were assayed for measles IgG antibody using the haemagglutination inhibition (HI) assay, and salivary samples were also obtained from 187 children and tested for measles IgG antibody using an antibody capture radioimmunoassay. Reported measles vaccine coverage in children aged 12-35 months was 77% (95% confidence interval [CI], 72-81%). Eighty-seven percent (95% CI 85-89%) had detectable HI antibody, but a high proportion had antibody levels below 200 miu (30-40% of 2-14 years old children). Measles seronegativity was associated with not being vaccinated against measles, a negative history of measles disease, living in the inner city, being a lifetime resident of Santa Cruz, and young age. Of 212 children without detectable measles antibody, 58% had a positive history of vaccination or measles disease, so that historical information was not sufficiently reliable to identify susceptibles. The salivary measles antibody assay was not sufficiently sensitive to be used for population screening; only 54% of 171 salivary samples from children who had detectable serum HI antibody were positive. A mass measles vaccination campaign of all children under 15 years of age is planned in Bolivia in 1994. Although only 7% of school-age children in Santa Cruz were seronegative, the effectiveness of a mass campaign in this age group depends in part on the response to revaccination of children with low, but detectable, antibody levels.

Adolescent↗

Effect of subclinical infection on maintaining immunity against measles in vaccinated children in West Africa.

BACKGROUND: Despite a high coverage with measles vaccines in parts of west Africa, epidemics of measles occur with reduced severity in an increasing proportion of older children who have been vaccinated. We examined the effect of exposure to natural measles on immunity in vaccinated children. METHODS: Our study was carried out in 1992 during an epidemic of measles in Niakhar, a rural area of Senegal with about 27,000 inhabitants who mostly live in compounds that include several households; within each household people live in different huts. Vaccine coverage in Niakhar was 81% at the time of our study. We measured haemagglutinin-inhibiting antibody at exposure and twice thereafter (after 4-5 weeks and at 6 months) in 36 vaccinated and 87 unvaccinated children. The frequency of measles and subclinical measles--defined as a four-fold or greater rise in antibody titre without clinical signs or symptoms--was related to intensity of exposure according to whether the index case was in the same hut, household, or compound. FINDINGS: Clinical measles occurred in 20 (56%) of 36 unvaccinated children and in one (1%) of 87 vaccinated children. Subclinical measles occurred in 39 (45%) of 86 vaccinated children who were exposed to measles and in four (25%) of 16 unvaccinated children. The frequency was inversely related to pre-exposure antibody concentration (p<0.001 for trend) and directly related to intensity of exposure (p=0.002 for trend). Antibody concentrations in subclinical cases increased on average by 45-fold and remained raised for at least 6 months. INTERPRETATION: Increased antibody titre after subclinical measles may be common in vaccinated children in West Africa where the intensity of exposure is high. As measles vaccination coverage increases, the circulation of wild measles will decrease, and vaccine-induced antibody is less likely to be boosted. Thus, new epidemics, albeit milder in form, may occur in vaccinated areas which should be recognised in campaigns to eradicate measles.

Adolescent↗

Construction of vaccinia virus recombinants expressing several measles virus proteins and analysis of their efficacy in vaccination of mice.

Measles virus genes encoding the haemagglutinin (HA), fusion protein (F) or nucleoprotein (NP) have been inserted into the vaccinia virus genome either alone or in various combinations. In each case the measles virus genes were expressed from the 7.5K promoter and were incorporated into the thymidine kinase (tk) or K1L loci of the Copenhagen strain of vaccinia virus. Cells infected by the recombinants synthesized measles virus proteins indistinguishable from those induced in measles virus-infected cells. However, in some instances the level of expression in cells infected by recombinants expressing more than one measles virus gene was reduced when compared to those encoding a single gene. The sera from mice immunized with recombinants containing either HA, HA.F, HA.NP or HA.F.NP had similar levels of measles virus neutralizing antibodies which remained constant throughout a 7 month period. Analysis of these sera by immunoprecipitation of radiolabelled measles virus confirmed the presence of specific antibody to each of the antigens where appropriate. The introduction of the measles virus genes into the K1L and the tk sites despite attenuating the virus for mice by 10-fold and 1000-fold respectively did not affect the vaccination efficiency, i.e. ability to induce measles virus antibody and protect mice. Vaccination of BALB/c (H2d) mice with HA and F, but not NP, recombinants completely protected the animals against a lethal measles virus challenge. In contrast, although the HA recombinant protected CBA (H2k) mice, the F recombinant did so poorly. However, by immunizing CBA mice with a recombinant expressing both F and NP, protection was increased to more than 75%. Our findings demonstrate the ability of three measles virus antigens expressed from the vaccinia virus genome alone or in combination to contribute to protective immunity against measles virus infection of mice. They also suggest that the association of measles virus antigens in a single recombinant DNA vaccine could be beneficial to overcome host-related restriction of the immune response to particular antigens.

Animals↗

Humoral and cellular immune response after measles vaccination in Taiwan.

Measles immunoglobulin G (IgG) seroepidemiologic studies have been widely used to monitor the effectiveness of measles immunization programs in Taiwan. However, studies about cellular immunity against the measles virus have been lacking. This study surveyed cellular immunity after measles, mumps and rubella combined vaccine (MMR) immunization in Taiwan. Seventy six people between 1 and 80 years of age were enrolled. All patients lived in northern Taiwan, and none of them had immunodeficient disease. Every enrolled patient donated a tube of heparinized blood between January 2004 and June 2004 for cross-sectional studies of IgG seroepidemiologic and MMR-specific lymphoproliferative response. The results showed that the current 3-dose (measles x 1 + MMR x 2) measles immunization program induced slightly higher IgG seroprevalence (100% vs 85%, p=0.244) and a higher frequency of significant (stimulation indices > or = 3) MMR-specific lymphoproliferative response (50% vs 15%, p=0.044) than a 2-dose (measles x 1 + MMR x 1) immunization program, although there was no difference in IgG titers and stimulation indices. Furthermore, the population aged older than 36 years (pre-immunization era) had higher IgG titers and seroprevalence, and similar MMR-specific lymphoproliferative responses to that of the population aged younger than 36 years (post-immunization era). In summary, with the limited data, the current 3-dose (measles x 1 + MMR x 2) measles immunization policy probably more effectively induces humoral and cellular immunity than the 2-dose (measles x 1 + MMR x 1) policy. Measles IgG seroprevalence in populations of different age groups exceeds nearly 90%. Measles has been eliminated temporarily in Taiwan. For a better understanding of the durability of vaccine-induced immunity and in order to establish the most appropriate immunization schedule, long-term and large-scale prospective studies of measles-specific seroepidemiology and cellular immunity will be needed.

Adolescent↗

Effectiveness of vaccination at 6 to 11 months of age during an outbreak of measles.

HYPOTHESIS: Monovalent measles vaccine can be administered to children 6 to 11 months of age during an outbreak. Efficacy and effectiveness of this control measure still have to be assessed. METHODS: During and outbreak of measles, monovalent measles vaccine was administered as part of outbreak control to children aged 6 to 11 months. Active surveillance was used to detect cases of measles occurring during the following month. Children who did not develop measles were tested for measles antibody before their revaccination at 15 months of age. RESULTS: Of 81 children 6 to 11 months of age, 56 were vaccinated and two received immunoglobulins; the latter were excluded from the analysis. Measles occurred in 15 of the 79 children during and after the vaccination campaign, for an overall attack rate of 19%. The attack rate among unvaccinated children was 39% (9 of 23), compared with 11% (6 of 56) among those vaccinated (relative risk = 3.6, 95% confidence interval [CI] = 1.5 to 9.1). All of those who sustained measles in the vaccinated group developed the disease within 10 days after vaccination. The overall vaccine effectiveness was 73% (95% CI = 32% to 89%) when children were classified as vaccinated as soon as they were given measles vaccine. It rose to 96% (95% CI = 72% to 99%) when children were considered vaccinated 1 week postimmunization. Nineteen infants who were vaccinated and who did not develop measles during the outbreak were tested for measles antibody status at 15 months of age before revaccination. All had plaque reduction neutralizing antibody titers greater than 120. CONCLUSION: This study confirms that measles vaccination of infants aged 6 to 11 months is an effective intervention measure during measles outbreaks.

Antibodies, Viral↗

Following in the footsteps of smallpox: can we achieve the global eradication of measles?

BACKGROUND: Although an effective measles vaccine has been available for almost 40 years, in 2000 there were about 30 million measles infections worldwide and 777,000 measles-related deaths. The history of smallpox suggests that achieving measles eradication depends on several factors; the biological characteristics of the organism; vaccine technology; surveillance and laboratory identification; effective delivery of vaccination programmes and international commitment to eradication. DISCUSSION: Like smallpox, measles virus has several biological characteristics that favour eradication. Humans are the only reservoir for the virus, which causes a visible illness and infection leading to life-long immunity. As the measles virus has only one genetic serotype which is relatively stable over time, the same basic vaccine can be used world-wide. Vaccination provides protection against measles infection for at least 15 years, although efficacy may be reduced due to host factors such as nutritional status. Measles vaccination may also confer other non-specific health benefits leading to reduced mortality. Accurate laboratory identification of measles cases enables enhanced surveillance to support elimination programmes. The "catch-up, keep-up, follow-up" vaccination programme implemented in the Americas has shown that measles elimination is possible using existing technologies. On 17th October 2003 the "Cape Town Measles Declaration" by the World Health Organisation and the United Nations Childrens Fund called on governments to intensify efforts to reduce measles mortality by supporting universal vaccination coverage and the development of more effective vaccination. SUMMARY: Although more difficult than for smallpox, recent experience in the Americas suggests that measles eradication is technically feasible. Growing international support to deliver these programmes means that measles, like smallpox, may very well become a curiosity of history.

Journal Article↗

Detection of measles virus genome directly from clinical samples by reverse transcriptase-polymerase chain reaction and genetic variability.

A simple and sensitive method for the detection of measles virus genome was developed, amplifying the regions encoding the nucleocapsid (N) protein and hemagglutinin (H) protein of measles virus by reverse transcriptase-polymerase chain reaction (RT-PCR). We examined a variety of measles patients: 28 patients with natural infection, 4 with measles encephalitis and 1 with subacute sclerosing panencephalitis (SSPE). In 28 patients with natural measles infection a single step PCR amplifying the N region resulted in a high detection rate for all plasma samples (28/28) within 3 days of the onset of rash and 80% (20/25) even on day 7 of the onset of rash and later. Within 3 days of the onset of rash, 24/25 (96.0%) of nasopharyngeal secretions (NPS) and 27/28 (96.4%) of peripheral blood mononuclear cells (PBMC) were positive for the N region PCR and the positivity rate of PCR decreased in NPS and PBMC after 7 days of the rash. In acute measles infection, measles genome was detected in all cell fractions, CD4, CD8, B cells, and monocytes/macrophages by the H gene nested PCR. Measles genome was also detected from cerebrospinal fluids (CSF) in patients with measles encephalitis, SSPE, and acute measles by the H gene nested PCR. PCR products of the N and H regions were sequenced and we confirmed the presence of measles genome. Based on the sequence data, chronological sequence differences were observed over the past 10 years. The sequences obtained from the SSPE patient were closely related to those of the wild viruses that were circulating at the time when the patient initially acquired measles. RT-PCR for NPS, PBMC, CSF, and plasma provides a useful method for the diagnosis of measles and molecular epidemiological study in addition to virus isolation.

Adolescent↗

A 'post-honeymoon period' measles outbreak in Muyinga sector, Burundi.

In Muyinga sector, Burundi, an area with good vaccination levels against measles and recent low incidence of measles, a major outbreak of measles in 1988 raised questions about the efficacy of the immunization programme. To help answer these questions, we 1) reviewed programme data on doses of measles vaccine administered, vaccine coverage, and measles incidence, and 2) conducted a census of the affected area to examine vaccine efficacy and measles mortality. We found that between 1980 and 1988 in Burundi, 1) measles vaccine coverage by age 1 had increased from 0% to 55%, 2) the incidence of reported measles cases declined from 12.1/1000 to 6.2/1000, 3) reported measles mortality dropped from 0.18/1000 to 0.08/1000, and 4) the interepidemic period had increased from 25 to 35 months. In the census, the best estimate of measles vaccine efficacy administered at 9 months of age was 73%. Measles increased the risk of death by 2.5-fold with the effect limited to the first month after measles. This outbreak demonstrated the 'post-honeymoon period' epidemic predicted by mathematical models in which outbreaks occur among accumulated susceptibles in a partially immunized population. Understanding this phenomenon is important in providing a basis for improved strategies of measles control. Such outbreaks present new challenges to newly maturing immunization programmes in improving skills in surveillance, outbreak investigation, and public relations.

Burundi↗

Measles outbreak in the Republic of the Marshall Islands, 2003.

BACKGROUND: Measles is a highly contagious viral infection. Measles transmission can be prevented through high population immunity (>or=95%) achieved by measles vaccination. In the Republic of the Marshall Islands (RMI), no measles cases were reported during 1989-2002; however, a large measles outbreak occurred in 2003. Reported 1-dose measles vaccine coverage among children aged 12-23 months varied widely (52-94%) between 1990 and 2000. METHODS: RMI is a Pacific island nation (1999 population: 50,840). A measles case was defined as fever, rash, and cough, or coryza, or conjunctivitis, in an RMI resident between July 13 and November 7, 2003. A vaccination campaign was used for outbreak control. RESULTS: Of the 826 reported measles cases, 766 (92%) occurred in the capital (Majuro). There were 186 (23%) cases in infants aged <1 year and 309 (37%) of cases in persons aged >or=15 years. The attack rate was highest among infants (Majuro atoll: 213 cases/1,000 infants). Among cases aged 1-14 years, 281 (59%) reported no measles vaccination before July 2003. There were 100 hospitalizations and 3 deaths. The measles H1 genotype was identified. The vaccination campaign resulted in 93% coverage among persons aged 6 months to 40 years. Interpretation Populations without endemic measles transmission can accumulate substantial susceptibility and be at risk for large outbreaks when measles virus is imported. 'Islands' of measles susceptibility may develop in infants, adults, and any groups with low vaccine coverage. To prevent outbreaks, high population immunity must be sustained by maintaining and documenting high vaccine coverage.

Adolescent↗

Increased susceptibility to measles in infants in the United States.

BACKGROUND: Women born in the United States after measles vaccine licensure in 1963 transfer less measles antibody to their infants than do older women. This may result in increased susceptibility to measles among infants. OBJECTIVE: To determine the effect of maternal year of birth on the risk for measles in infants. METHODS: We enrolled 128 unvaccinated infants </=15 months of age who had documented exposure to measles from 1990 through 1992 in a retrospective cohort study. We interviewed their mothers by telephone to obtain demographic data, medical and vaccination history, and details of measles exposure and outcome. We used logistic regression analysis to estimate the effect of maternal year of birth. RESULTS: Infants whose mothers were born after 1963 had a measles attack rate of 33%, compared with 12% for infants of older mothers. In logistic regression analysis, the adjusted odds ratio for maternal year of birth (born after 1963) was 7.5 (95% confidence interval 1.8, 30.6). Other significant risk factors were older infant age, mothers who developed measles after delivery, and exposure within 2 days of the rash onset of the exposing case. CONCLUSIONS: Infants whose mothers were born after 1963 are more susceptible to measles than are infants of older mothers. An increasing proportion of infants born in the United States may be susceptible to measles. Infants at high risk of exposure to measles should be vaccinated at 12 months of age. Vaccination programs that reduce transmission of the measles virus in the general population reduce the risk of infant exposure to measles.

Age Distribution↗