An 11-year-old female patient, whose systemic type juvenile idiopathic arthritis (JIA) had maintained in remission for the previous 4 years while taking only a small amounts of ibuprofen, showed an abrupt 2nd relapse with congestive heart failure five days after receiving a live-attenuated rubella vaccine, which was a primary immunization. Her serum levels of anti-rubella IgM and IgG antibodies increased, and her laboratory findings such as a leukocytosis, elevated serum levels of CRP, IL-6 and other inflammatory cytokine profiles were similar to the findings observed during her previous JIA active stage. After being administration of co-therapy with steroid pulse, ibuprofen, methotrexate and phosphodiesterase inhibitor gradually improved her clinical symptoms such as spiky fever, heart failure and arthralgia. Her intermittent fever and increased serum levels of CRP and IL-6, however, have been sustained for more than 2 years, and this prolonged active clinical course therefore differed from her previous JIA active stage.This abrupt relapse only five days after vaccination was suggested not to be directly related with rubella infection, but instead to be related with the molecular mimicry between rubella and JIA.

We report here a case involving a 14-year-old boy who developed acute disseminated encephalomyelitis following live rubella vaccination. The patient became febrile and began to experience nuchal pain 16 days after the immunization. By 22 days after immunization, he experienced difficulty in walking. By 24 days, he had developed tetraparesis with retention of urine, and total sensory loss below the Th1 dermatomal level. He was febrile at this point and showed nuchal rigidity and Lhermitte's sign. Cerebrospinal fluid examination revealed elevated cell counts, protein level, and myelin basic protein. T2-weighted magnetic resonance imaging detected high intensity lesions in the bilateral cerebral white matter and cervical spinal cord. Following the administration of intravenous corticosteroids, the patient's clinical symptoms improved rapidly.

OBJECTIVE:To determine if there is evidence for a causal relationship between acute encephalopathy followed by permanent brain injury or death associated with the administration of further attenuated measles vaccines (Attenuvax or Lirugen, Hoechst Marion Roussel, Kansas City, MO), mumps vaccine (Mumpsvax, Merck and Co, Inc, West Point, PA), or rubella vaccines (Meruvax or Meruvax II, Merck and Co, Inc, West Point, PA), combined measles and rubella vaccine (M-R-Vax or M-R-Vax II, Merck and Co, Inc, West Point, PA), or combined measles, mumps, and rubella vaccine (M-M-R or M-M-R II, Merck and Co, Inc, West Point, PA), the lead author reviewed claims submitted to the National Vaccine Injury Compensation Program.

METHODS:The medical records of children who met the inclusion criteria of receiving the first dose of these vaccines between 1970 and 1993 and who developed such an encephalopathy with no determined cause within 15 days were identified and analyzed.

RESULTS:A total of 48 children, ages 10 to 49 months, met the inclusion criteria after receiving measles vaccine, alone or in combination. Eight children died, and the remainder had mental regression and retardation, chronic seizures, motor and sensory deficits, and movement disorders. The onset of neurologic signs or symptoms occurred with a nonrandom, statistically significant distribution of cases on days 8 and 9. No cases were identified after the administration of monovalent mumps or rubella vaccine.

CONCLUSIONS:This clustering suggests that a causal relationship between measles vaccine and encephalopathy may exist as a rare complication of measles immunization.

BACKGROUND: According to studies from Guinea-Bissau and Senegal, live vaccines may reduce the female-male mortality ratio (MR) whereas inactivated vaccines increase this ratio. We used data from The Gambia to examine whether similar tendencies could be found in a different setting.

SETTING: Forty villages in the Farafenni area in rural Gambia. SUBJECTS: A population of 17,000 was followed with demographic surveillance between 1998 and 2002; 537 children less than 5 years of age died in this period.

METHODS: We used two vaccination surveys and community mortality data to examine, first, the female-male mortality ratio (MR) in the age groups in which DTP and MV are recommended and have a high coverage. Second, using vaccination cards seen post-mortem, we examined the distribution of live or inactivated vaccines as last vaccination in different age groups. Third, we examined the effect of DTP and MV administered simultaneously.

MAIN OUTCOME MEASURES: The female-male MR in different age groups and for different vaccines.

RESULTS: Vaccination coverage was high for BCG, third dose of DTP (DTP3) and MV, reaching a level of 80-90% within a few months of the recommended age of vaccination. First, the female-male MR was 0.93 (0.63-1.38) in the first 2 months of life when children had received no vaccination or the combination of BCG, HBV and OPV. From 2 to 8 months of age, with DTP and HBV being the main vaccinations, the female-male MR was 1.28 (0.86-1.89). Between 9 and 17 months of age, with MV as the main vaccination, this ratio dropped to 0.73 (0.50-1.07), a significant inversion of the female-male MR (p=0.045). Second, using information from vaccination cards of dead children, boys who died at 2-4 months of age were more likely to have received live BCG and girls to have received inactivated DTP and HBV as last vaccination (p<0.001). At 5-8 months of age, essentially all dead children had received DTP as last vaccination and the female-male MR was 1.68 (0.96-2.93), whereas the MR was 0.70 (0.43-1.15) at 12-17 months of age when nearly all dead children had received MV (p=0.022). Third, compared with the general population of children who had received MV, dead children who had received MV were more likely to have received DTP3 simultaneously with MV (relative risk (RR)=5.59 (2.10-14.8)) or after MV (RR=2.61 (1.13-6.05)).

CONCLUSION: Most children dying at a specific age had received the recommended vaccines. BCG and MV as last vaccination was associated with a low female-male MR, whereas DTP as last vaccination was associated with a high female-male MR. These trends are consistent with observations from other African countries.

BACKGROUND:In Korea, measles occurs mainly in infants<12months of age, who are unvaccinated. In addition, vaccine populations, including adolescents and young adults, can become infected though importation. Thus, the question arises whether the current level of herd immunity in Korea is now insufficient for protecting against measles infection.

METHODS:Age-specific measles seroprevalence was evaluated by performing enzyme immunoassays and plaque reduction-neutralization tests on 3050 subjects aged 0-50years (birth cohort 1964-2014) and 480 subjects aged 2-30years (birth cohort 1984-2012).

RESULTS:The overall seropositivity and measles antibody concentrations were 71.5% and 1366mIU/mL, respectively. Progressive decline in antibody levels and seropositivity were observed over time after vaccination in infants, adolescents, and young adults. The accumulation of potentially susceptible individuals in the population was confirmed by comparing data from 2010 and 2014 seroprevalence surveys. The statistical correlation between measles incidence and measles seronegativity was determined.

CONCLUSIONS:Waning levels of measles antibodies with increasing time post-vaccination suggests that measles susceptibility is potentially increasing in Korea. This trend may be related to limitations of vaccine-induced immunity in the absence of natural boosting by the wild virus, compared to naturally acquired immunity triggered by measles infection. This study provides an important view into the current measles herd immunity in Korea.

AIM:Allergies to hen's egg and cow's milk are the most frequent food allergies in infancy and childhood. Current guidelines recommend safe administration of measles-mumps-rubella (MMR) vaccine in egg allergic patients.

METHODS:We present three cases of anaphylaxis that we encountered after MMR vaccination in children sensitized to hen's egg and cow's milk.

RESULTS:Even though MMR vaccine is generally known to be safe in children with egg allergy, there may still be isolated cases of anaphylaxis.

CONCLUSION:Therefore, we recommend that all children not only those who were sensitized to foods should receive the MMR vaccination in a setting that is equipped to deal with anaphylactic reactions. As stated by WHO in immunization safety surveillance, 'Each vaccinator must have an emergency kit with adrenaline, and be familiar with its dosage and administration'.

Many reports associating uveitis after vaccination have been reported, including 2 cases after measles, mumps, and rubella (MMR) vaccine. We report the case of a 12-month-old girl who developed a unilateral anterior uveitis with rubeosis and cataract 3 months after an MMR vaccination at 9 months of age. Aqueous humor analysis showed the presence of more rubella-specific immunoglobulin G in the affected eye than in the unaffected one. This is the second report showing an association between MMR vaccine and anterior uveitis and the first supported by the presence of intraocular rubella antibodies.

To link the presence of intrathecal virus-specific oligoclonal immunoglobulin G (IgG) in multiple sclerosis patients to a demyelinating activity, aggregating rat brain cell cultures were treated with antibodies directed against two viruses, namely, rubella (RV) and hepatitis B (HB). Anti-RV antibodies in the presence of complement decreased myelin basic protein concentrations in a dose-dependent manner, whereas anti-HB antibodies had no effect. A similar but less pronounced effect was observed on the enzymatic activity of 2',3'-cyclic nucleotide 3'-phosphohydrolase, which is enriched in noncompact membranes of oligodendrocytes. These effects were comparable to those in cultures treated with antibodies directed against myelin oligodendrocyte glycoprotein (MOG), previously found to be myelinotoxic both in vitro and in vivo. Sequence homologies were found between structural glycoprotein E(2) of RV and MOG, suggesting that demyelination was due to molecular mimicry. To support the hypothesis that demyelination was caused by anti-RV IgG that recognized an MOG epitope, we found that anti-RV antibodies depleted MOG in a dose-dependent manner. Further evidence came from the demonstration that anti-RV and anti-MOG IgG colocalized on oligodendrocyte processes and that both revealed by Western blot a 28 kDa protein in CNS myelin, a molecular weight corresponding to MOG. These findings suggest that a virus such as RV exhibiting molecular mimicry with MOG can trigger an autoimmune demyelination.

The vaccination has much profit for an infectious disease. On the other hand, there is little frequency, side effects may appear. It includes severe complication. We reported the case that resulted in bilateral acute profound hearing loss after mumps alone and measles and rubella (MR) vaccination. The case was a 5 years old girl. She inoculated mumps alone and MR vaccine. After 18days later, both sides profound hearing loss occurred in her. The hearing loss was not improved by the intravenous feeding of the steroid. Three months later, cochlea implantation was carried out to her right ear. She got hearing again. As for the hearing loss, mumps vaccine was considered as a cause from a latency period until the onset. The bilateral profound hearing loss that was a very rare complication was occurred by vaccination. The care of the hearing is important, but the mental care of an affected child and the parent is important, too.

We describe a case of vaccine-associated measles in a two-year-old patient from British Columbia, Canada, in October 2013, who received her first dose of measles-containing vaccine 37 days prior to onset of prodromal symptoms. Identification of this delayed vaccine-associated case occurred in the context of an outbreak investigation of a measles cluster.

Complex regional pain syndrome type I (CRPS I) is a disorder of one or more extremities characterized by pain, abnormal sensitivity (allodynia), swelling, limited range of motion, vasomotor instability, fatigue and emotional distress. The symptoms may be aggravated by even minor activity or weather change. It is usually provoked by injury, surgery or injection but in a small proportion of patients CRPS I develops without a clear causative event. There are several literature reports on CRPS after rubella and hepatitis B vaccination. We present a case of CRPS I affecting the left arm after diphtheria and tetanus (Di-Te) vaccination in the left deltoid muscle in a young girl having experienced profound emotional stress before the vaccination procedure. History data on previous minor trauma at the site of vaccination or emotional stress may necessitate temporary vaccination delay due to their proneness to impaired local or systemic immune response and CRPS as a complication of vaccination. If a child or an adult has prominent swelling and severe pain after vaccination, the diagnosis of CRPS I should be considered and if confirmed, the multidisciplinary treatment should start as soon as possible.

Routine childhood vaccination against measles, mumps and rubella has virtually abolished virus-related morbidity and mortality. Notwithstanding this, we describe here devastating neurological complications associated with the detection of live-attenuated mumps virus Jeryl Lynn (MuV) in the brain of a child who had undergone successful allogeneic transplantation for severe combined immunodeficiency (SCID). This is the first confirmed report of MuVassociated with chronic encephalitis and highlights the need to exclude immunodeficient individuals from immunisation with live-attenuated vaccines. The diagnosis was only possible by deep sequencing of the brain biopsy. Sequence comparison of the vaccine batch to the MuVisolated from brain identified biased hypermutation, particularly in the matrix gene, similar to those found in measles from cases of SSPE. The findings provide unique insights into the pathogenesis of paramyxovirus brain infections.

PURPOSE:To report two cases of optic neuritis with onset less than 24 hours following measles-rubella (MR) vaccination.

CASE REPORT:Two teenage patients developed acute optic neuritis 6 to 7 hours after MR booster vaccination. The first patient demonstrated bilateral papillitis and severe visual loss but improved significantly with pulse intravenous steroid therapy with methylprednisolone 500 mg/day. The second patient had unilateral retrobulbar optic neuritis and demonstrated excellent visual recovery without intervention.

CONCLUSION:Acute optic neuritis is a rare complication of MR vaccination and may occur early after immunization.

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.

Involvement of the central nervous system is common in measles, but rare in rubella. However, rubella virus (RV) can cause a variety of central nervous system syndromes, including meningitis, encephalitis, Guillain-Barré syndrome and sub acute sclerosing panencephalitis. We report the occurrence of one fatal case of the encephalitis associated with measles-rubella (MR) vaccine during an immunization campaign in São Paulo, Brazil. A 31 year-old-man, previously in good health, was admitted at emergency room, withconfusion, agitation, inability to stand and hold his head up. Ten days prior to admission, he was vaccinated with combined MR vaccine (Serum Institute of India) and three days later he developed 'flu-like' illness with fever, myalgia and headache. Results of clinical and laboratory exams were consistent with a pattern of viral encephalitis. During hospitalization, his condition deteriorated rapidly with tetraplegia and progression to coma. On the 3rd day of hospitalization he died. Histopathology confirmed encephalitis and immunohistochemistry was positive for RV on brain tissue. RV was alsodetected by qPCR and virus isolation in cerebrospinal fluid, brain and other clinical samples. The sequence obtained from the isolated virus was identical to that of the RA 27/3 vaccine strain.

A CAUSAL ASSOCIATION BETWEEN MEASLES: mumps-rubella (MMR) vaccine and idiopathic thrombocytopenic purpura (ITP) was confirmed using immunisation/hospital admission record linkage. The absolute risk within six weeks of immunisation was 1 in 22 300 doses, with two of every three cases occurring in the six week post-immunisation period being caused by MMR. Children with ITP before MMR had no vaccine associated recurrences.

We quantified measles transmissibility during a measles outbreak in Ohio in 2014 to evaluate the impact of public health responses. Case incidence and the serial interval (time between symptom onset in primary cases and secondary cases) were used to assess trends in the effective reproduction number R (the average number of secondary cases generated per case). A mathematical model was parameterized using early R values to determine the size and duration of the outbreak that would have occurred if containment measures had not been initiated, as well as the impact of vaccination. As containment started, we found a 4-fold decline in R (from approximately 4 to 1) over the course of 2 weeks and maintenance of R<1 as control measures continued. Under a conservative scenario, the model estimated 8,472 cases (90% confidence interval (CI): 8,447, 8,489) over 195 days (90% CI: 179, 223) without control efforts and 715 cases (90% CI: 103, 1,338) over 128 days (90% CI: 117, 139) when vaccination was included; 7,757 fewer cases (90% CI: 7,130, 8,365) and 67 fewer outbreak days (90% CI: 48, 98) were attributed to vaccination. Vaccination may not account entirely for transmission reductions, suggesting that changes in community behavior (social distancing) and other control efforts (isolation, quarantining) are important. Our findings highlight the benefits of measles outbreak response and of understanding behavior change dynamics.

Circulating immunoglobulin E (IgE) is one of the characteristics of human allergic diseases including allergic asthma. We recently showed that infection of human B cells with rhinovirus or measles virus could lead to the initial steps of IgE class switching. Since many viral vaccines are live viruses, we speculated that live virus vaccines may also induce IgE class switching in human B cells. To examine this possibility, we selected the commonly used live attenuated measles mumps rubella (MMR) vaccine. Here, we show that infection of a human IgM(+) B cell line with MMR resulted in the expression of germline epsilon transcript. In addition, infection of freshly prepared human PBLs with this vaccine resulted in the expression of mature IgE mRNA transcript. Our data suggest that a potential side effect of vaccination with live attenuated viruses may be an increase in the expression of IgE.

BACKGROUND:The largest measles epidemic in North America in the last decade, occurred in 2011 in Quebec, Canada, where rates of 1- and 2-dose vaccine coverage among children 3 years of age were 95%-97% and 90%, respectively, with 3%-5% unvaccinated.

METHODS:Case patients identified through passive surveillance and outbreak investigation were contacted to determine clinical course, vaccination status, and possible source of infection.

RESULTS:There were 21 measles importations and 725 cases. A superspreading event triggered by 1 importation resulted in sustained transmission and 678 cases. The overall incidence was 9.1 per 100,000; the highest incidence was in adolescents 12-17 years old (75.6 per 100,000), who comprised 56% of case patients. Among adolescents, 22% had received 2 vaccine doses. Outbreak investigation showed this proportion to have been an underestimate; active case finding identified 130% more cases among 2-dose recipients. Two-dose recipients had milder illness and a significantly lower risk of hospitalization than those who were unvaccinated or single-dose recipients.

CONCLUSIONS:A chance superspreading event revealed an overall level of immunity barely above the elimination threshold when unexpected vulnerability in 2-dose recipients was taken into account. Unvaccinated individuals remain the immunization priority, but a better understanding of susceptibility in 2-dose recipients is needed to define effective interventions if elimination is to be achieved.

No Abstract Available