Measles Revaccination Research Articles

THE CHARACTERISTICS OF HOSPITALIZED MEASLES AFFECTED CHILDREN DURING THE 2017-2018 EPIDEMIC IN THE JABLANICA DISTRICT

Despite the availability of safe, effective and inexpensive vaccine since the 1960s, in 2018, more than 140.000 people worldwide died from measles. The aim of this study was to determine socio-epidemiological and clinical characteristics among hospitalized, measles-infected children during the epidemic from December 2017 to July 2018 in the Jablanica District and to estimate the influence of socio-epidemiological factors on the severity of disease. This cross-sectional study involved 55 measles-infected, hospitalized children at the Pediatric Department of the General Hospital of Leskovac. Data were collected with an original questionnaire and analyzed using descriptive statistics methods. The influence of factors on the severity of disease among infected children with and without complications was examined using ch² and t-test. P < 0.05 was considered statistically significant. During the measles epidemic in the Jablanica District in 2017-2018, 110 children were affected, aged 0-19 years. Out of a total measles affected children in the Jablanica District only 9 (8.18%) were vaccinated, of which 5 (4.54%) were hospitalized. A total of 55 measles-infected, hospitalized children aged 22.85 ± 23.94 months were analyzed. The most infected children, 25 (45.45%), were aged 0-12 months. The infected children were mostly living in poor conditions, 34 (61.81%). Pneumonia was the most common complication, 24 (51.88%). There were no lethal outcomes. Severe complications were more frequent in younger children (p < 0.05), in children who lived in poor conditions (p < 0.05) and in those who had infection during the winter (p < 0.05). The development and implementation of strategies to achieve high coverage for measles vaccination and revaccination are necessary for measles elimination.

Sustained Responses to Measles Revaccination at 24 Months in HIV-infected Children on Antiretroviral Therapy in Kenya.

There are limited data on whether HIV-infected children in resource-limited countries who are receiving antiretroviral therapy (ART) are able to produce sustained, protective levels of measles antibody after multiple measles vaccinations. We administered an additional measles vaccine to HIV-infected children 15 months to 12 years of age receiving ART in Nairobi, Kenya. Measles antibody concentrations were determined by enzyme-linked immunosorbent assay at enrollment, 1 month, 12 months and 24 months post revaccination. At enrollment, 125 (54%) of 232 study participants had protective concentrations of measles antibody. Measles seropositivity increased to 98% of all children at 1 month post revaccination but decreased to 71% at 12 months and 60% at 24 months post revaccination. Measles seroconversion and sustained measles seropositivity among those who were measles seronegative at enrollment was 25% at 24 months post revaccination. In this group, 39% of children with <50 copies/mL plasma HIV RNA measles seroconverted compared to 4% of children with plasma HIV RNA ≥1000 copies/mL (P = 0.018). Measles revaccination can result in a sustained antibody response in a subset of HIV-infected children receiving ART, especially among those with HIV suppression.

T cell anergy and activation are associated with suboptimal humoral responses to measles revaccination in HIV-infected children on anti-retroviral therapy in Nairobi, Kenya.

HIV-infected children are less capable of mounting and maintaining protective humoral responses to vaccination against measles compared to HIV-uninfected children. This poses a public health challenge in countries with high HIV burdens. Administration of anti-retroviral therapy (ART) and revaccinating children against measles is one approach to increase measles immunity in HIV-infected children, yet it is not effective in all cases. Immune anergy and activation during HIV infection are factors that could influence responses to measles revaccination. We utilized a flow cytometry-based approach to examine whether T cell anergy and activation were associated with the maintenance of measles-specific immunoglobulin (Ig)G antibodies generated in response to measles revaccination in a cohort of HIV-infected children on ART in Nairobi, Kenya. Children who sustained measles-specific IgG for at least 1year after revaccination displayed significantly lower programmed cell death 1 (PD-1) surface expression on CD8(+) T cells on a per-cell basis and exhibited less activated CD4(+) T cells compared to those unable to maintain detectable measles-specific antibodies. Children in both groups were similar in age and sex, CD4(+) T cell frequency, duration of ART treatment and HIV viral load at enrolment. These data suggest that aberrant T cell anergy and activation are associated with the impaired ability to sustain an antibody response to measles revaccination in HIV-infected children on ART.

Measles seroprevalence and revaccination efficacy among healthcare workers in southern Taiwan

Measles seroprevalence and revaccination efficacy among healthcare workers in southern Taiwan

Serological Response to Measles Revaccination in a Small Population After a Mass Measles Revaccination Program

Background: In spite of vaccination, outbreaks of measles occur in many countries, and measles remains the most frequent cause of death among vaccine preventable diseases. Objectives: To compare anti-measles antibody titer between revaccinated and non-revaccinated medical students 2 years after the National MR (Measles, Rubella) Vaccination Program, which was implemented in 2002-2003 for individuals aged 5 to 25 years in Iran. Patients and Methods: This stratified cross-sectional study was conducted on 78 revaccinated and unvaccinated for national MMR vaccination (2002) medical students aged 22-25 years, who attended our Markaz Tebi Children Hospital in Tehran for their pediatric rotation from summer to winter in 2005. The revaccinated group was selected by simple random sampling from a list of names of the students and the non-revaccinated group included all the non-revaccinated students. Serum IgG and IgM anti-measles antibody titers of the subjects were measured using indirect enzyme-linked immunosorbent assay (ELISA), and the levels were compared between the 2 groups of students. Data were analyzed using chi square test and independent samples t test. Statistical significance was defined as P values of < 0.05 by SPSS ver.13 Software. Results: Overall, we recruited 45 subjects with a mean age of 23.7 ± 0.12 years in the revaccinated group and 33 subjects with a mean age of 24 ± 0.25 years in the non-revaccinated group (P = 0.2). The mean anti-measles IgG antibody titer was 31.8 ± 21.2 IU/mL (range, 1-190 IU/mL) in the revaccinated group and 6.12 ± 8.8 IU/mL (range, 1-45 IU/mL) in the non-revaccinated group (P < 0.001). The mean anti-measles IgM antibody titers were 2.6 ± 6.7 IU/mL (range, 1-45 IU/mL) and 1 ± 0 IU/mL (range, 0-1 IU/mL) in the revaccinated and non-revaccinated groups, respectively (P = 0.1). Anti-measles IgG was present (serum titer ≥ 13 IU/mL) in 46.7% of the individuals of the revaccinated group and 6% of the individuals of the non-revaccinated group (P < 0.001). Conclusions: The results of this study indicate that although the percentage of individuals with protective levels of anti-measles antibody increased to 46.7% after revaccination, the protection was inadequate in more than 50% of vaccine recipients, thereby, emphasizing the need for checking antibody levels after revaccination.

Serological Response to Measles Revaccination in a Small Population After a Mass Measles Revaccination Program

Background: In spite of vaccination, outbreaks of measles occur in many countries, and measles remains the most frequent cause of death among vaccine preventable diseases. Objectives: To compare anti-measles antibody titer between revaccinated and non-revaccinated medical students 2 years after the National MR (Measles, Rubella) Vaccination Program, which was implemented in 2002-2003 for individuals aged 5 to 25 years in Iran. Patients and Methods: This stratified cross-sectional study was conducted on 78 revaccinated and unvaccinated for national MMR vaccination (2002) medical students aged 22-25 years, who attended our Markaz Tebi Children Hospital in Tehran for their pediatric rotation from summer to winter in 2005. The revaccinated group was selected by simple random sampling from a list of names of the students and the non-revaccinated group included all the non-revaccinated students. Serum IgG and IgM anti-measles antibody titers of the subjects were measured using indirect enzyme-linked immunosorbent assay (ELISA), and the levels were compared between the 2 groups of students. Data were analyzed using chi square test and independent samples t test. Statistical significance was defined as P values of < 0.05 by SPSS ver.13 Software. Results: Overall, we recruited 45 subjects with a mean age of 23.7 ± 0.12 years in the revaccinated group and 33 subjects with a mean age of 24 ± 0.25 years in the non-revaccinated group (P = 0.2). The mean anti-measles IgG antibody titer was 31.8 ± 21.2 IU/mL (range, 1-190 IU/mL) in the revaccinated group and 6.12 ± 8.8 IU/mL (range, 1-45 IU/mL) in the non-revaccinated group (P < 0.001). The mean anti-measles IgM antibody titers were 2.6 ± 6.7 IU/mL (range, 1-45 IU/mL) and 1 ± 0 IU/mL (range, 0-1 IU/mL) in the revaccinated and non-revaccinated groups, respectively (P = 0.1). Anti-measles IgG was present (serum titer ≥ 13 IU/mL) in 46.7% of the individuals of the revaccinated group and 6% of the individuals of the non-revaccinated group (P < 0.001). Conclusions: The results of this study indicate that although the percentage of individuals with protective levels of anti-measles antibody increased to 46.7% after revaccination, the protection was inadequate in more than 50% of vaccine recipients, thereby, emphasizing the need for checking antibody levels after revaccination.

Immunogenicity, Immunologic Memory, and Safety Following Measles Revaccination in HIV-Infected Children Receiving Highly Active Antiretroviral Therapy

Response rates and immunologic memory following measles vaccination are reduced in human immunodeficiency virus (HIV)-infected children in the absence of highly active antiretroviral therapy (HAART). HIV-infected children 2 to <19 years old receiving HAART and with HIV loads <30,000 copies/mL, CD4% ≥15, and ≥1 prior measles-mumps-rubella vaccination (MMR) were given another MMR. Measles antibody concentrations before and 8, 32, and 80 weeks postvaccination were determined by plaque reduction neutralization (PRN). A subset was given another MMR 4-5 years later, and PRN antibody was measured before and 7 and 28 days later. At entry, 52% of 193 subjects were seroprotected (PRN ≥120 mIU/mL). Seroprotection increased to 89% 8 weeks postvaccination, and remained at 80% 80 weeks postvaccination. Of 65 subjects revaccinated 4-5 years later, 85% demonstrated memory based on seroprotection before or 7 days after vaccination. HIV load ≤400 copies/mL at initial study vaccination was associated with higher seroprotection rates, greater antibody concentrations, and memory. Grade 3 fever or fatigue occurred in 2% of subjects. Measles revaccination induced high rates of seroprotection and memory in children receiving HAART. Both endpoints were associated with HIV viral load suppression. NCT00013871 (www.clinicaltrials.gov).

Measles, mumps and rubella (MMR) revaccination induces a protective antibody response in most children with HIV and immune recovery after HAART,

Measles, mumps and rubella (MMR) revaccination induces a protective antibody response in most children with HIV and immune recovery after HAART,

Measurement of measles virus-specific neutralizing antibodies: evaluation of the syncytium inhibition assay in comparison with the plaque reduction neutralization test

Plaque reduction neutralization (PRN) is the "gold-standard" for the measurement of measles-specific neutralizing antibodies. However, it is a complicated assay and tends to be operator-dependent. It has been suggested that the simpler syncytium inhibition assay (SIA) can give results comparable to the PRN test. We compared these two assays using 594 serum or plasma samples obtained from children at various times after natural infection, primary measles immunization, and measles revaccination. The results of the two assays correlated well overall (r = .86; p < 0.0001). The strain of challenge virus (wild-type versus vaccine strain) did not significantly influence SIA titers and the assay performed equally well with serum and plasma. PRN titers > or = 120 and > 800 are thought to indicate protection against clinical illness and infection respectively. The equivalent SIA cut-off values using 125 plaque-forming units as the challenge inoculum were > or = 16 and > 128 respectively. At low PRN titers (< 200), the correlation between PRN and SIA values was reasonable (r = 0.60; p < 0.001) when a challenge inoculum of 12.5 plaque-forming units was used. At the lowest PRN titers (< 100), 15% of the samples gave divergent results. These data confirm the utility of the SIA in the determination of measles-specific neutralizing antibodies when antibody titers are high. However, the PRN assay remains the test of choice when maximum sensitivity at low titers is required.

Response to measles revaccination among toddlers in Saudi Arabia by the use of two different trivalent measles-mumps-rubella vaccines

This trial confirmed the immunogenicity of a standard dose of measles vaccine Edmonston-Zagreb strain administered at the age of 6 months as evaluated serologically at 12 months of age in 94 healthy children in Saudi Arabia. The residual seropositivity rate for measles was 53.4 and 80.6% as measured by enzyme immunoassay (EIA) and plaque neutralization, respectively, and could be increased to virtually 100% seroprotection after immunization with 1 of 2 measles-mumps-rubella (MMR) vaccines (Triviraten Berna or MMR II MSD) at 12 months of age. In both groups, more than 90% of infants showed an immune response to the mumps and rubella vaccine strains at 14 months of age. There was a difference in the geometric mean titres of mumps antibodies in favour of MMR II (P < 0.001). The seroconversion rates for mumps antibodies differed between the 2 vaccines because of the different test systems and/or the different cut-off levels used. The study reconfirmed that for the assessment of Rubini mumps vaccine-induced antibodies the indirect immunofluorescence test is superior to the EIA. The systemic tolerability of both vaccines was excellent. Triviraten Berna is exclusively propagated on human diploid cell cultures and hence free of avian proteins.

Response to measles revaccination among Bolivian school-aged children

The response to measles revaccination was evaluated in 1994 among 202 Bolivian school-aged children whose antibody levels were below 200 miu (milli-international units) by haemagglutination inhibition (HI) in a large-scale serosurvey conducted in Santa Cruz one year earlier. Of the 202 revaccinated children, 164 (82%) had seroconverted between the 1993 serosurvey and the pre-revaccination blood sample. A measles outbreak occurred in Santa Cruz 6 months before the revaccination. Among the seroconvertors, only 6% gave a history of measles, and 15% a history of contact with a case of measles. All 20 children with undetectable HI antibody pre-revaccination, and all 6 children with levels below 100 miu, seroconverted after revaccination. The geometric mean titres by HI at 4 weeks after revaccination were 2018 miu (95% confidence limits [95% CL] 1143, 3564) and 398 miu (95% CL 254, 625) in the 2 groups, respectively. Six of 9 children with pre-revaccination antibody titres of 100-199 miu also seroconverted. No child demonstrated a measles-specific immunoglobulin M response. Among the 29 children who seroconverted and were followed up at one year after revaccination, 15(52%) showed a fourfold or greater decline in antibody levels, which in 8 fell to levels below 200 miu. This study confirmed the observation that revaccination is successful in producing an antibody response in children with low or undetectable pre-revaccination titres, but it also confirmed that vaccine-induced immunity wanes rapidly.

An Evaluation of Measles Revaccination Among School-entry-aged Children

A two dose measles vaccination schedule is recommended routinely for all school-entry-aged children. We evaluated this recommendation by determining both measles antibody seroprevalence and the response to revaccination in seronegative children in this age group. Children 4 to 6 years of age who had received a single dose of measles vaccine between the ages of 15 to 17 months were tested for measles antibody by using enzyme-linked immunosorbent assay (ELISA) microneutralization technique. Seronegative children were revaccinated and again tested for measles antibody (immunoglobulin M [IgM] and neutralizing). Of 679 children tested, 37 (5.4%) were seronegative. Seronegativity was not significantly associated with age, sex, race, age at initial vaccination, time since vaccination, or maternal year of birth. However, children mothers with a college degree were 12 times more likely to be seronegative than children of mothers who never attended college (P < .01). Of the 37 seronegative children, 36 seroconverted after revaccination--33 producing IgM measles antibody, suggestive of a primary immune response. The cost per seroconversion would have been an estimated $415 if all 679 children had been revaccinated. Revaccination reduces the pool of children who are susceptible to measles. Although the cost per seroconversion is high, a two-dose schedule should reduce the substantial costs of controlling measles out breaks by reducing the number of outbreaks.

Should All Children Receive Two Measles Vaccinations?

Because of the rising incidence of rubeola, we tested all our patients who were vaccinated prior to 15 months of age and those vaccinated after 15 months, if requested, for susceptibility to measles (IgG, ELISA). Those found to be susceptible were revaccinated. Of 1,228 tested, 264 (21.5%) were susceptible. In the group vaccinated before 1980, 237 of 901 (26.3%) were susceptible, whereas only 27 of 327 (8.3%) vaccinated after 1980 were not immune. Susceptibility was sharply divided by month of age at vaccination at the 14-month mark. Less than 5% of those vaccinated after age 15 months in the 1980s (one of 22, or 4.5%) were susceptible. Waning immunity (secondary vaccine failure) was not found to be a factor in our patients. Despite outbreaks of measles in surrounding communities and in our area, none of our patients developed measles. Identification of high-risk groups and selective measles revaccination should be considered as an alternative to universal revaccination in populations such as ours, since ...

Should All Children Receive Two Measles Vaccinations?

Because of the rising incidence of rubeola, we tested all our patients who were vaccinated prior to 15 months of age and those vaccinated after 15 months, if requested, for susceptibility to measles (IgG, ELISA). Those found to be susceptible were revaccinated. Of 1,228 tested, 264 (21.5%) were susceptible. In the group vaccinated before 1980, 237 of 901 (26.3%) were susceptible, whereas only 27 of 327 (8.3%) vaccinated after 1980 were not immune. Susceptibility was sharply divided by month of age at vaccination at the 14-month mark. Less than 5% of those vaccinated after age 15 months in the 1980s (one of 22, or 4.5%) were susceptible. Waning immunity (secondary vaccine failure) was not found to be a factor in our patients. Despite outbreaks of measles in surrounding communities and in our area, none of our patients developed measles. Identification of high-risk groups and selective measles revaccination should be considered as an alternative to universal revaccination in populations such as ours, since it is more cost-effective and may prove equally successful.

Measles Revaccination Response in a School-Age Population

Due to the dramatic upsurge in the incidence of measles, the American Academy of Pediatrics and the Immunization Practices Advisory Committee of the Centers for Disease Control revised their measles immunization policies in 1989 to include a routine two-dose schedule. The objectives of this study were the following: (1) determine the prevalence of immunologically measles-susceptible subjects in a previously vaccinated, school-age, military dependent population; and (2) assess risk factors to identify immunologically measles-susceptible subjects. Serum was collected just prior to measles revaccination and again 2 weeks later. Measles-specific IgG and IgM titers were determined by enzyme-linked immunosorbent assay. Immunologically measles-susceptible subjects constituted 9.8% of the population. The interval since previous measles vaccination was significantly related to pre- and postrevaccination IgG titers in a repeated-measures analysis of variance model. The magnitude of increase in IgG titer following revaccination and analysis of trend for proportions of measles-susceptible subjects were significantly related to the age of initial vaccination. This study supports continued measles revaccination; in addition, revaccination appears to be of greater value at 11 to 12 years of age than at 4 to 6 years of age.

Serological response to measles revaccination in a highly immunized military dependent adolescent population

In the spring of 1986, there was a measles outbreak in the city of El Paso, Texas, with 92 cases reported to the City-County Health Department. Of those 92 cases, 31 (32%) occurred within a public high school's student population of 2524. A mass measles vaccination program was undertaken at that high school in order to limit the outbreak. The student enrollment included a military dependent population of 368 students. Despite documented histories of prior measles immunizations in this military dependent subgroup, three individuals contracted the disease. Since this subgroup of students represented a highly immunized adolescent population, it was of interest to serologically determine their immune status prior to and following reimmunization with the expectation that such a study would provide information relating to the level of "protective" immunity. Prevaccination and postvaccination sera were obtained from 95 students. Results of measuring anti-measles antibody activity by ELISA indicate that 13 (14%) students responded to revaccination and experienced a fourfold or greater rise in IgG antibody levels. There were no detectable IgM responses. All of the students who responded to revaccination produced an anamnestic response (IgG boost only). Since most of these individuals had received first immunizations at 15 months of age or older, these findings suggest that secondary vaccine failure (waning immunity) was responsible for the putative "lowered" immunity in these individuals, instead of primary vaccine failure (maternal antibody suppression). These findings support current recommendations for measles booster revaccination of school-age children and adolescents.

The costs of measles revaccination

The costs of measles revaccination

Need for measles revaccination in adolescents: Correlation with birth data prior to 1972

Measles hemagglutination inhibition (HI) antibody titers of less than 1:4 were significantly (P less than 0.05) more prevalent among subjects born from 1962 through 1971 and vaccinated with a single dose of live measles virus vaccine at 12 months of age (14.5%) than among subjects born during the same years but vaccinated at 13 months or older (2.3%). For subjects born in 1972 through 1976, however, this difference was not statistically significant; titers of less than 1:4 occurred in 6.2% of those vaccinated at 12 months, compared to 0% in those vaccinated at 13 months or older. A decline in maternally derived measles HI antibody may be related to the increased rate of HI antibody titers of 1:4 or greater following vaccination of more recently born subjects. Following revaccination of subjects whose measles HI antibody titers were less than 1:4, measles HI titers were lower than would be expected after successful primary vaccination. Nevertheless, measles HI antibody persisted at a level of 1:4 or more until the latest titer measurement of this study (one to two years after revaccination) in 87.5% of those whose initial vaccination had been at 11 or 12 months of age. No adverse reactions to revaccination occurred. Revaccination programs should be considered for adolescents and young adults born before 1972 who received live measles virus vaccine at or before 12 months. Children born from 1972 through 1976 who were vaccinated at 12 months or later are not in need of revaccination.

Measles revaccination. Persistence and degree of antibody titer by type of immune response.

During a measles immunization campaign 203 children were enrolled in an antibody response study. Of this group, follow-up clinical data and sera samples were available from 125 children three weeks after immunization and from 90 children ten months later. Seventy-six of the children had been previously vaccinated, ten had a history of measles and 39 denied vaccination or illness. Twenty-six of the children had prevaccination hemagglutination inhibiting antibody titers of less than 5. Of this group 12 had a primary immune response (IgM measles antibody) with geometric mean titers (GMT) of 90 and 40 three weeks and ten months respectively after vaccination. In contrast, the other 14 children with initial titers of less than 5 had secondary immune responses (only IgG measles antibody) with GMTs of 28 and 9 three weeks and ten months after vaccination. Since the antibody responses in these children who had previously been stimulated by measles antigen were modest and transient, it is suggested that booster immunization may not be effective in preventing future secondary vaccine failures. Also noted in this study was a poor correlation between historical data and actual measles antibody.

Measles Immunity and Revaccination

To the Editor.— The starting serum dilution for measles hemmaglutination-inhibition (HI) antibody titers in many laboratories has been 1:10. The article on booster measles vaccination by Bass et al (235:31, 1976) provides data confirming our observation that when assessing measles-immune status by the HI method, it is important to test sera beginning at a dilution of 1:2. 1 Of 368 persons studied by Bass et al, 89 (24%) had HI titers of 1:2 or 1:4. In our study, 73 (15%) of 479 children had measles HI titers between 1:2 and 1:8. Most, if not all, persons with these low antibody titers are resistant to clinical measles. Therefore, using a 1:10 starting dilution would cause one to seriously overestimate the number of persons susceptible to measles and vaccinate many children who already are immune. As Linnemann points out in his editorial (235:63, 1976), there are cogent reasons not to revaccinate immune