MMR - Measles/Mumps/Rubella
SYNOPSIS
This study explores the D-4 escape measles mutant, a strain that has emerged in countries that have intense vaccination.
TITLE
Antigenic Drift Defines a New D4 Subgenotype of Measles Virus
CITATION
SUMMARY
Measles virus is a paradigmatic RNA virus, as the antigenic composition of the vaccination has not needed to be updated since its discovery. The vaccine confers protection by inducing neutralizing antibodies that interfere with the function of the hemagglutinin protein. Viral strains are indistinguishable serologically, although characteristic nucleotide sequences differentiate 24 genotypes. In this work, we describe a distant evolutionary branch within genotype D4. Designated subgenotype D4.2, this virus is distinguishable by neutralization with vaccine-induced monoclonal antibodies that target the neutralizing epitope (NE). The subgenotype D4.2 viruses have a higher predominance in countries with intermediary levels of vaccine coverage. Our studies demonstrate that subgenotype D4.2 lacks epitopes associated with half of the known antigenic sites, which significantly impacts our understanding of measles virus evolution.
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Out-of-sequence vaccinations may increase child mortality.
TITLE
Out-of-sequence DTP and measles vaccinations and child mortality in Guinea-Bissau: a reanalysis.
CITATION
Thysen SM, Rodrigues A, Aaby P, et al. British Medical Journal Open 2019;9:e024893; doi:10.1136/bmjopen-2018-024893.
SUMMARY
This study’s objective was to assess whether the sequence of diphtheria-tetanus-pertussis vaccine (DTP) and measles vaccine (MV) was associated with child survival. Using a data set previously used to assess non-specific effects of vaccines with no consideration of vaccination sequence researchers found that out-of-sequence vaccinations in children were associated with higher mortality compared with children vaccinated in-sequence.
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These data suggest that specific immune outcomes may wane at different rates and highlight our currently incomplete understanding of protective immune responses to mumps and measles.
TITLE
Differential durability of immune responses to measles and mumps following MMR vaccination.
CITATION
Richard B. Kennedy Inna G. Ovsyannikova, Antonia Thomas, Beth R. Larrabee, Steven Rubin, Gregory A. Poland, Vaccine, Volume 37, Issue 13, 22 March 2019, Pages 1775-1784
SUMMARY
The development and wide-spread use of mumps vaccine resulted in a dramatic and sustained decrease in the incidence of mumps disease; however, since 2000, an increase in the size and number of mumps outbreaks in the United States and other countries has sparked renewed interest in the durability of mumps-specific immunity elicited by mumps vaccination. The most likely explanation for mumps cases in previously immunized persons may be secondary vaccine failure, or waning immunity. Researchers examined changes in markers of measles and mumps immunity at two timepoints, approximately 7 and 17 years after two-dose MMR-II® vaccination, and found that the mumps IgG titers exhibited a large and significant decline during this time period. There was a similar discrepancy with measles-specific immune responses.
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Waning levels of measles antibodies with increasing time post-vaccination suggests that measles susceptibility is potentially increasing in Korea.
TITLE
An increasing, potentially measles-susceptible population over time after vaccination in Korea
CITATION
Kang, H. J., et al. Vaccine, 35 (2017) 4126–4132.
SUMMARY
In Korea, measles occurs mainly in infants <12 months of age, who are unvaccinated. In
addition, vaccine populations, including adolescents and young adults, can become infected through importation. Thus, the question arises whether the current level of herd immunity in Korea is now insufficient for protecting against measles infection.
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More than one in ten vaccine-related adverse events in Zimbabwe are serious (11%), and measles-containing vaccines are one of the vaccines most frequently responsible for serious and systemic reactions.
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Adverse events following immunisation (AEFI) reports from the Zimbabwe expanded programme on immunisation (ZEPI): an analysis of spontaneous reports in Vigibase from 1997 to 2017
CITATION
SUMMARY
The authors examined passively collected reports of adverse events following immunization (AEFI) in Zimbabwe from 1997 to 2017. Given widespread underreporting to the country’s still-developing vaccine surveillance system, just 272 Individual Case Safety Reports (ICSRs) were available, of which 11% represented “serious events.” Of these, 6% were deaths and 5% were life-threatening or involved prolonged hospitalization. Measles-containing vaccines had the highest AEFI reporting rate and were also strongly associated with serious events, as was a six-component vaccine containing antigens for oral poliovirus, diphtheria, tetanus, pertussis, Haemophilus influenzae type b and hepatitis B (OPV/DTP-Hib-HepB). The majority of AEFI were systemic (versus vaccine site reactions)—and systemic events, again, were associated with measles-containing vaccines.
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In Israel in 2017, nine measles cases were identified in a population with high measles vaccination coverage.
TITLE
Measles Outbreak in a Highly Vaccinated Population – Israel, July-August 2017
Citation
Avramovich E, Indenbaum V, Haber M, Amitai Z, Tsifanski E, Farjun S, Sarig A, Bracha A, Castillo K, Markovich MP, Galor I. MMWR Morbidity and Mortality Weekly Report. 2018 Oct 26;67(42):1186-1188.
Summary
On August 6, 2017, the Israeli Defense Force Public Heath Branch (IDFPHB) was notified of two suspected measles cases. IDFPHB conducted an epidemiologic investigation, which identified nine measles cases in a population with high measles vaccination coverage. All measles patients had signs and symptoms consistent with modified measles (i.e., less severe disease with milder rash, fever, or both, with or without other mild typical measles symptoms). A total of 1,392 contacts were identified, and 162 received postexposure prophylaxis (PEP) with measles-mumps-rubella (MMR) vaccine; the remaining contacts were followed for 21 days (one incubation period). No tertiary cases were identified.
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Researchers found that febrile seizures occurred in roughly one in every 1,000 children who were given the MMR vaccine and two genetic variants came to light that pointed to a higher risk of a febrile seizure in the second week following MMR vaccination.
TITLE
Common variants associated with general and MMR vaccine–related febrile seizures
CITATION
Bjarke Feenstra, Bjorn Pasternak, Frank Geller, Lisbeth Carstensen, et. al. Nature Genetics 46, 1274-1282; 26 October, 2014.
SUMMARY
Febrile seizures represent a serious adverse event following measles, mumps and rubella (MMR) vaccination. We conducted a series of genome-wide association scans comparing children with MMR-related febrile seizures, children with febrile seizures unrelated to vaccination and controls with no history of febrile seizures. Two loci were distinctly associated with MMR-related febrile seizures. Furthermore, four loci were associated with febrile seizures in general, implicating the sodium channel genes and a region associated with magnesium levels.
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Israeli and Italian researchers demonstrate that exposure to aluminum in vaccines can lead to autoimmune and brain dysfunction.
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Autoimmune/inflammatory syndrome induced by adjuvants (ASIA) 2013: Unveiling the pathogenic, clinical and diagnostic aspects
CITATION
Perricone C, Colafrancesco S, Mazor RD, Soriano A, Agmon-Levin N, Shoenfeld Y. Journal of Autoimmunity. 2013;47:1-16.
SUMMARY
Environmental factors play a critical role in the induction of autoimmunity, with an interplay between genetic susceptibility and environment. Several neurologic demyelinating diseases have been reported following vaccination, notably Guillain-Barre syndrome (GBS) and acute disseminated encephalomyelitis (ADEM) (an inflammatory disease of the central nervous system). A number of the most common vaccines appear to have some involvement with autoimmunity.
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Swedish researchers found that children who had natural measles infection had much lower rates of allergy than children vaccinated against measles.
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Allergic disease and atopic sensitization in children in relation to measles vaccination and measles infection
CITATION
Rosenlund H, Bergstrom A, Alm JS, … PARSIFAL Study Group. Pediatrics. 2009;123(3):771-778.
SUMMARY
In these analyses, measles infection [natural measles] was inversely associated with any allergic symptom or physician’s diagnosis of allergy, suggesting that natural measles infection may protect against allergies in children.
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A high percentage of autistic children with positive antibodies to the measles and/or human herpesvirus-6 (HHV-6) also have autoantibodies to brain components. Might the MMR vaccine be an early event in brain autoimmunity?
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Serological association of measles virus and human herpesvirus-6 with brain autoantibodies in autism.
CITATION
SUMMARY
Environmental exposures to toxins as well as viral infections are known to be triggers for autoimmunity. Individuals with autism suffer from a variety of immunological abnormalities with 55-70% having autoantibodies to brain antigens that include myelin basic protein (MBP), neuron-axon filament proteins (NAFP), and serotonin receptor. Many parents have reported the onset of autism soon after receiving a vaccine for the measles-mumps-rubella (MMR) and/or diptheria-pertussis-tetanus (DPT). The authors point out that both measles virus and human herpesvirus-6 (HHV-6) can manifest neurologic sequelae, show molecular mimicry with MBP and NAFP, and are associated with demyelination. To understand a possible association of viruses to brain autoimmunity, these researchers investigated virus serology of the measles virus and HHV-6. Children diagnosed with autism using the DSM-IIIR criteria were compared to normal controls. Both the controls and the children with autism had a high percentage of positive titers to measles as well as HHV-6 antibodies. According to the authors this was to be expected given that, “A high proportion (78%) of general populations is known to have positive titers of HHV-6 antibody.” The high percentage of measles antibody titers (85%) in children with autism was also expected. There is a high rate of seroconversion post MMR vaccination and none of the children had a history of exposure to the wild-type measles infection. An interesting finding was revealed when comparing the virus serology to brain autoantibodies. Among the control group, there were no brain autoantibodies found in any participant. However, among autistic subjects:
“approximately 90% of measles-IgG-positive sera also had anti-MBP”
“73% of measles-IgG- positive sera also had anti-NAFP”
“84% of HHV-6-IgG-positive sera also had anti-MBP”
“72% of HHV-6-IgG-positive sera also had anti-NAFP.”
“the higher the virus antibody titer the greater the chance of brain autoantibody”
The report closing by stating, “In conclusion, we suggest that while the etiology is not known, it is quite instructive to consider environmental factors, for example measles virus and HHV-6, as etiological agents linked to autoimmunity in autism.”
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Measles transmission can be sustained in a highly vaccinated population
TITLE
Investigation of a measles outbreak in a fully vaccinated school population including serum studies before and after revaccination.
CITATION
Matson DO, Byington C, Canfield M, Albrecht P, Feigin RD. Investigation of a measles outbreak in a fully vaccinated school population including serum studies before and after revaccination. Pediatric Infectious Disease Journal. 1993 Apr;12(4):292-9. PubMed PMID: 8483623.
SUMMARY
A measles outbreak in early 1989 among approximately 4200 students at a high school and two intermediate schools in suburban Houston, TX, was investigated to evaluate reasons for vaccine failure and to predict the efficacy of a booster dose of measles vaccine. Seventy-seven cases occurred (71 at the high school, 6 at intermediate schools; attack rate, 3.2 and 0.3%, respectively). Vaccination in the first year of life an 13 to 14 years since last vaccination were independent risk factors for being a case. Forty-three (18%) of 239 sera collected from students just before revaccination during the outbreak were negative by enzyme immunoassay; a neutralization assay confirmed these 43 lacked antibody predicting protection against measles infection. Of 43 enzyme immunoassay-negative students 24 gave another blood sample 9 to 10 months after revaccination. Revaccination appeared to reduce the portion of all students with neutralization titers predicting susceptibility to measles illness with rash from 7.9% to 3.0% and left the portion predicted to be susceptible to illness without rash unchanged (45%).
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A computer model was created to study the effect of the measles elimination program in the United States on the number of susceptibles in the population. The simulation reveals that in the prevaccine era, approximately 10.6% of the population was susceptible to measles, most of whom were children less than 10 years of age.
TITLE
The future of measles in highly immunized populations. A modeling approach.
CITATION
Levy DL. American Journal of Epidemiology. 1984 Jul;120(1):39-48.
SUMMARY
Little is known about how an intensive measles elimination program changes the overall immune status of the population. A computer model was created to study the effect of the measles elimination program in the United States on the number of susceptibles in the population. The simulation reveals that in the prevaccine era, approximately 10.6% of the population was susceptible to measles, most of whom were children less than 10 years of age. With the institution of the measles immunization program, the proportion of susceptibles in the population fell to 3.1% from 1978 through 1981, but then began to rise by approximately 0.1% per year to reach about 10.9% in the year 2050. The susceptibles at this time were distributed evenly throughout all age groups. The model did not consider the potential effect of waning immunity. The results of this study suggest that measles elimination in the United States has been achieved by an effective immunization program aimed at young susceptibles combined with a highly, naturally immunized adult population. However, despite short-term success in eliminating the disease, long-range projections demonstrate that the proportion of susceptibles in the year 2050 may be greater than in the prevaccine era. Present vaccine technology and public health policy must be altered to deal with this eventuality.
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The 1989 measles outbreak in the province of Quebec has been largely attributed to an incomplete vaccination coverage, despite a 99% vaccination rate.
TITLE
Major measles epidemic in the region of Quebec despite a 99% vaccine coverage
Citation
Boulianne N, De Serres G, Duval B, Joly JR, Meyer F, Déry P, Alary M, Le Hénaff D, Thériault N. Canadian Journal of Public Health. 1991 May-Jun;82(3):189-90.
Summary
The 1989 measles outbreak in the province of Quebec has been largely attributed to an incomplete vaccination coverage. In the Quebec City area (pop. 600,000) 1,363 confirmed cases of measles did occur. A case-control study conducted to evaluate risk factors for measles allowed us to estimate vaccination coverage. The vaccination coverage among cases was at least 84.5%. Vaccination coverage for the total population was 99.0%. Incomplete vaccination coverage is not a valid explanation for the Quebec City measles outbreak.
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The report makes useful recommendations for future investigations, for the problem has yet to be solved of finding a vaccine which causes only slight reactions and provides long-lasting immunity.
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More Work on Measles Vaccine
CITATION
SUMMARY
Discussing the indications for the large-scale use of measles vaccines, the report stresses the need to consider the importance of the disease in different countries individually. It shows that there is an urgent need for effective protection against measles in developing countries where the disease generally has a high death rate. Against this must be weighed the characteristics and properties of the available vaccines-for example, safety, efficacy, acceptability, availability, cost, and ease of administration. Unfortunately none of the vaccines at present available is completely satisfactory. The further-attenuated vaccines are effective and relatively easy to administer, though great care is necessary to avoid contamination of the syringe with preservatives, detergents, alcohols, or other lipid solvents, since these rapidly inactivate the virus. These vaccines are expensive and not yet available in large quantities, though these objections may be overcome in the future, but the main drawback to their mass use remains-namely, the severity of the reaction in a few of the children vaccinated. The report makes useful recommendations for future investigations, for the problem has yet to be solved of finding a vaccine which causes only slight reactions and provides long-lasting immunity. Meanwhile further trials of the Beckenham 20 vaccine are proceeding, this time in Great Britain.