1. Abnormal Measles-Mumps-Rubella Antibodies and CNS Autoimmunity in Children with Autism
Abstract
“Autoimmunity to the central nervous system (CNS), especially to myelin basic protein (MBP), may play a causal role in autism, a neurodevelopmental disorder. Because many autistic children harbor elevated levels of measles antibodies, we conducted a serological study of measlesmumps-rubella (MMR) and MBP autoantibodies. Using serum samples of 125 autistic children and 92 control children, antibodies were assayed by ELISA or immunoblotting methods. ELISA analysis showed a significant increase in the level of MMR antibodies in autistic children. Immunoblotting analysis revealed the presence of an unusual MMR antibody in 75 of 125 (60%) autistic sera but not in control sera. This antibody specifically detected a protein of 73–75 kD of MMR. This protein band, as analyzed with monoclonal antibodies, was immunopositive for measles hemagglutinin (HA) protein but not for measles nucleoprotein and rubella or mumps viral proteins. Thus the MMR antibody in autistic sera detected measles HA protein, which is unique to the measles subunit of the vaccine. Furthermore, over 90% of MMR antibody-positive autistic sera were also positive for MBP autoantibodies, suggesting a strong association between MMR and CNS autoimmunity in autism. Stemming from this evidence, we suggest that an inappropriate antibody response to MMR, specifically the measles component thereof, might be related to pathogenesis of autism”
Link
https://www.ncbi.nlm.nih.gov/pubmed/12145534
Citation
Singh, Vijendra K., Sheren X. Lin, Elizabeth Newell, and Courtney Nelson. "Abnormal Measles-Mumps-Rubella Antibodies and CNS Autoimmunity in Children with Autism." Journal of Biomedical Science 9.4 (2002): 359-64.
“Autoimmunity to the central nervous system (CNS), especially to myelin basic protein (MBP), may play a causal role in autism, a neurodevelopmental disorder. Because many autistic children harbor elevated levels of measles antibodies, we conducted a serological study of measlesmumps-rubella (MMR) and MBP autoantibodies. Using serum samples of 125 autistic children and 92 control children, antibodies were assayed by ELISA or immunoblotting methods. ELISA analysis showed a significant increase in the level of MMR antibodies in autistic children. Immunoblotting analysis revealed the presence of an unusual MMR antibody in 75 of 125 (60%) autistic sera but not in control sera. This antibody specifically detected a protein of 73–75 kD of MMR. This protein band, as analyzed with monoclonal antibodies, was immunopositive for measles hemagglutinin (HA) protein but not for measles nucleoprotein and rubella or mumps viral proteins. Thus the MMR antibody in autistic sera detected measles HA protein, which is unique to the measles subunit of the vaccine. Furthermore, over 90% of MMR antibody-positive autistic sera were also positive for MBP autoantibodies, suggesting a strong association between MMR and CNS autoimmunity in autism. Stemming from this evidence, we suggest that an inappropriate antibody response to MMR, specifically the measles component thereof, might be related to pathogenesis of autism”
Link
https://www.ncbi.nlm.nih.gov/pubmed/12145534
Citation
Singh, Vijendra K., Sheren X. Lin, Elizabeth Newell, and Courtney Nelson. "Abnormal Measles-Mumps-Rubella Antibodies and CNS Autoimmunity in Children with Autism." Journal of Biomedical Science 9.4 (2002): 359-64.
2. Adverse Events following 12 and 18 Month Vaccinations: a Population-Based, Self-Controlled Case Series Analysis
Abstract
“Background:
Live vaccines have distinct safety profiles, potentially causing systemic reactions one to 2 weeks after administration. In the province of Ontario, Canada, live MMR vaccine is currently recommended at age 12 months and 18 months.
Methods:
Using the self-controlled case series design we examined 271,495 12 month vaccinations and 184,312 18 month vaccinations to examine the relative incidence of the composite endpoint of emergency room visits or hospital admissions in consecutive one day intervals following vaccination. These were compared to a control period 20 to 28 days later. In a post-hoc analysis we examined the reasons for emergency room visits and the average acuity score at presentation for children during the at-risk period following the 12 month vaccine.
Results:
Four to 12 days post 12 month vaccination, children had a 1.33 (1.29–1.38) increased relative incidence of the combined endpoint compared to the control period, or at least one event during the risk interval for every 168 children vaccinated. Ten to 12 days post 18 month vaccination, the relative incidence was 1.25 (95%, 1.17–1.33) which represented at least one excess event for every 730 children vaccinated. The primary reason for increased events was statistically significant elevations in emergency room visits following all vaccinations. There were non-significant increases in hospital admissions. There were an additional 20 febrile seizures for every 100,000 vaccinated at 12 months.
Conclusions:
There are significantly elevated risks of primarily emergency room visits approximately one to two weeks following 12 and 18 month vaccination. Future studies should examine whether these events could be predicted or prevented.”
Link
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0027897
Citation
Wilson, Kumanan, Steven Hawken, Jeffrey C. Kwong, Shelley Deeks, Natasha S. Crowcroft, Carl Van Walraven, Beth K. Potter, Pranesh Chakraborty, Jennifer Keelan, Michael Pluscauskas, and Doug Manuel. "Adverse Events following 12 and 18 Month Vaccinations: A Population-Based, Self-Controlled Case Series Analysis." PLoS ONE 6.12 (2011)
“Background:
Live vaccines have distinct safety profiles, potentially causing systemic reactions one to 2 weeks after administration. In the province of Ontario, Canada, live MMR vaccine is currently recommended at age 12 months and 18 months.
Methods:
Using the self-controlled case series design we examined 271,495 12 month vaccinations and 184,312 18 month vaccinations to examine the relative incidence of the composite endpoint of emergency room visits or hospital admissions in consecutive one day intervals following vaccination. These were compared to a control period 20 to 28 days later. In a post-hoc analysis we examined the reasons for emergency room visits and the average acuity score at presentation for children during the at-risk period following the 12 month vaccine.
Results:
Four to 12 days post 12 month vaccination, children had a 1.33 (1.29–1.38) increased relative incidence of the combined endpoint compared to the control period, or at least one event during the risk interval for every 168 children vaccinated. Ten to 12 days post 18 month vaccination, the relative incidence was 1.25 (95%, 1.17–1.33) which represented at least one excess event for every 730 children vaccinated. The primary reason for increased events was statistically significant elevations in emergency room visits following all vaccinations. There were non-significant increases in hospital admissions. There were an additional 20 febrile seizures for every 100,000 vaccinated at 12 months.
Conclusions:
There are significantly elevated risks of primarily emergency room visits approximately one to two weeks following 12 and 18 month vaccination. Future studies should examine whether these events could be predicted or prevented.”
Link
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0027897
Citation
Wilson, Kumanan, Steven Hawken, Jeffrey C. Kwong, Shelley Deeks, Natasha S. Crowcroft, Carl Van Walraven, Beth K. Potter, Pranesh Chakraborty, Jennifer Keelan, Michael Pluscauskas, and Doug Manuel. "Adverse Events following 12 and 18 Month Vaccinations: A Population-Based, Self-Controlled Case Series Analysis." PLoS ONE 6.12 (2011)
3. Epidemiologic and Molecular Relationship Between Vaccine Manufacture and Autism Spectrum Disorder Prevalence
Abstract
“OBJECTIVES:
To assess the public health consequences of fetal cell line manufactured vaccines that contain residual human fetal DNA fragments utilizing laboratory and ecological approaches including statistics, molecular biology and genomics.
METHOD:
MMR coverage and autism disorder or autism spectrum disorder prevalence data for Norway, Sweden and the UK were obtained from public and government websites as well as peer reviewed published articles. Biologically, the size and quantity of the contaminating fetal DNA in Meruvax II and Havrix as well as the propensity of various cell lines for cellular and nuclear uptake of primitive human DNA fragments were measured and quantified using gel electrophoresis, fluorescence microscopy and fluorometry. Lastly, genomic analysis identified the specific sites where fetal DNA fragment integration into a child's genome is most likely to occur.
RESULTS:
The average MMR coverage for the three countries fell below 90% after Dr. Wakefield's infamous 1998 publication but started to recover slowly after 2001 until reaching over 90% coverage again by 2004. During the same time period, the average autism spectrum disorder prevalence in the United Kingdom, Norway and Sweden dropped substantially after birth year 1998 and gradually increased again after birth year 2000. Average single stranded DNA and double stranded DNA in Meruvax II were 142.05 ng/vial and 35.00 ng/vial, respectively, and 276.00 ng/vial and 35.74 ng/vial in Havrix respectively. The size of the fetal DNA fragments in Meruvax II was approximately 215 base pairs. There was spontaneous cellular and nuclear DNA uptake in HFF1 and NCCIT cells. Genes that have been linked to autism (autism associated genes; AAGs) have a more concentrated susceptibility for insults to genomic stability in comparison to the group of all genes contained within the human genome. Of the X chromosome AAGs, 15 of 19 have double strand break motifs less than 100 kilobases away from the center of a meiotic recombination hotspot located within an exon.
CONCLUSION:
Vaccines manufactured in human fetal cell lines contain unacceptably high levels of fetal DNA fragment contaminants. The human genome naturally contains regions that are susceptible to double strand break formation and DNA insertional mutagenesis. The "Wakefield Scare" created a natural experiment that may demonstrate a causal relationship between fetal cell-line manufactured vaccines and ASD prevalence”
Link
https://www.ncbi.nlm.nih.gov/pubmed/26103708
Citation
Reed, P., J. Howse, B. Ho, and L. A. Osborne. "Relationship between Perceived Limit-setting Abilities, Autism Spectrum Disorder Severity, Behaviour Problems and Parenting Stress in Mothers of Children with Autism Spectrum Disorder." Autism (2016)
“OBJECTIVES:
To assess the public health consequences of fetal cell line manufactured vaccines that contain residual human fetal DNA fragments utilizing laboratory and ecological approaches including statistics, molecular biology and genomics.
METHOD:
MMR coverage and autism disorder or autism spectrum disorder prevalence data for Norway, Sweden and the UK were obtained from public and government websites as well as peer reviewed published articles. Biologically, the size and quantity of the contaminating fetal DNA in Meruvax II and Havrix as well as the propensity of various cell lines for cellular and nuclear uptake of primitive human DNA fragments were measured and quantified using gel electrophoresis, fluorescence microscopy and fluorometry. Lastly, genomic analysis identified the specific sites where fetal DNA fragment integration into a child's genome is most likely to occur.
RESULTS:
The average MMR coverage for the three countries fell below 90% after Dr. Wakefield's infamous 1998 publication but started to recover slowly after 2001 until reaching over 90% coverage again by 2004. During the same time period, the average autism spectrum disorder prevalence in the United Kingdom, Norway and Sweden dropped substantially after birth year 1998 and gradually increased again after birth year 2000. Average single stranded DNA and double stranded DNA in Meruvax II were 142.05 ng/vial and 35.00 ng/vial, respectively, and 276.00 ng/vial and 35.74 ng/vial in Havrix respectively. The size of the fetal DNA fragments in Meruvax II was approximately 215 base pairs. There was spontaneous cellular and nuclear DNA uptake in HFF1 and NCCIT cells. Genes that have been linked to autism (autism associated genes; AAGs) have a more concentrated susceptibility for insults to genomic stability in comparison to the group of all genes contained within the human genome. Of the X chromosome AAGs, 15 of 19 have double strand break motifs less than 100 kilobases away from the center of a meiotic recombination hotspot located within an exon.
CONCLUSION:
Vaccines manufactured in human fetal cell lines contain unacceptably high levels of fetal DNA fragment contaminants. The human genome naturally contains regions that are susceptible to double strand break formation and DNA insertional mutagenesis. The "Wakefield Scare" created a natural experiment that may demonstrate a causal relationship between fetal cell-line manufactured vaccines and ASD prevalence”
Link
https://www.ncbi.nlm.nih.gov/pubmed/26103708
Citation
Reed, P., J. Howse, B. Ho, and L. A. Osborne. "Relationship between Perceived Limit-setting Abilities, Autism Spectrum Disorder Severity, Behaviour Problems and Parenting Stress in Mothers of Children with Autism Spectrum Disorder." Autism (2016)
4. Increased emergency room visits or hospital admissions in females after 12-month MMR vaccination, but no difference after vaccinations given at a younger age
Abstract
“Background:
Previous studies have suggested that a child’s sex may be a predictor of vaccine reactions.
Methods:
We used a self-controlled case series design, an extension of retrospective cohort methodology which controls for fixed confounders using a conditional Poisson modeling approach. We compared a risk period immediately following vaccination to a control period farther removed from vaccination in each child and estimated the relative incidence of emergency room visits and/or hospital admissions following the 2-, 4-, 6-, and 12-month vaccinations to investigate the effect of sex on relative incidence. All infants born in Ontario, Canada between April 1, 2002 and March 31, 2009 were eligible for study inclusion.
Results:
In analyses combining immunizations at 2, 4 and 6 months and examining these vaccinations separately, there was no significant relationship between the relative incidence of an event and sex of the child. At 12 months, we observed a significant effect of sex, with female sex being associated with a significantly higher relative incidence of events (P = 0.0027). The relative incidence ratio (95% CI) comparing females to males following the 12-month vaccination was 1.08 (1.03 to 1.14), which translates to 192 excess events per 100,000 females vaccinated compared to the number of events that would have occurred in 100,000 males vaccinated.
Conclusions:
As theMMRvaccine is givenat 12months of age in Ontario, ourfindings suggestthat girlsmay have an increased reactogenicity to the MMR vaccine which may be indicative of general sex differences in the responses to the measles virus”
Link
https://www.ncbi.nlm.nih.gov/pubmed/24440113
Citation
Wilson, Kumanan, Robin Ducharme, Brian Ward, and Steven Hawken. "Increased Emergency Room Visits or Hospital Admissions in Females after 12-month MMR Vaccination, but No Difference after Vaccinations given at a Younger Age." Vaccine 32.10 (2014): 1153-159
“Background:
Previous studies have suggested that a child’s sex may be a predictor of vaccine reactions.
Methods:
We used a self-controlled case series design, an extension of retrospective cohort methodology which controls for fixed confounders using a conditional Poisson modeling approach. We compared a risk period immediately following vaccination to a control period farther removed from vaccination in each child and estimated the relative incidence of emergency room visits and/or hospital admissions following the 2-, 4-, 6-, and 12-month vaccinations to investigate the effect of sex on relative incidence. All infants born in Ontario, Canada between April 1, 2002 and March 31, 2009 were eligible for study inclusion.
Results:
In analyses combining immunizations at 2, 4 and 6 months and examining these vaccinations separately, there was no significant relationship between the relative incidence of an event and sex of the child. At 12 months, we observed a significant effect of sex, with female sex being associated with a significantly higher relative incidence of events (P = 0.0027). The relative incidence ratio (95% CI) comparing females to males following the 12-month vaccination was 1.08 (1.03 to 1.14), which translates to 192 excess events per 100,000 females vaccinated compared to the number of events that would have occurred in 100,000 males vaccinated.
Conclusions:
As theMMRvaccine is givenat 12months of age in Ontario, ourfindings suggestthat girlsmay have an increased reactogenicity to the MMR vaccine which may be indicative of general sex differences in the responses to the measles virus”
Link
https://www.ncbi.nlm.nih.gov/pubmed/24440113
Citation
Wilson, Kumanan, Robin Ducharme, Brian Ward, and Steven Hawken. "Increased Emergency Room Visits or Hospital Admissions in Females after 12-month MMR Vaccination, but No Difference after Vaccinations given at a Younger Age." Vaccine 32.10 (2014): 1153-159
5. Largest Measles Epidemic in North America in a Decade—Quebec, Canada, 2011: Contribution of Susceptibility, Serendipity, and Superspreading Events
Abstract
“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.”
Link
https://www.ncbi.nlm.nih.gov/pubmed/23264672
Citation
Serres, G. De, F. Markowski, E. Toth, M. Landry, D. Auger, M. Mercier, P. Belanger, B. Turmel, H. Arruda, N. Boulianne, B. J. Ward, and D. M. Skowronski. "Largest Measles Epidemic in North America in a Decade--Quebec, Canada, 2011: Contribution of Susceptibility, Serendipity, and Superspreading Events." Journal of Infectious Diseases 207.6 (2012): 990-98.
“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.”
Link
https://www.ncbi.nlm.nih.gov/pubmed/23264672
Citation
Serres, G. De, F. Markowski, E. Toth, M. Landry, D. Auger, M. Mercier, P. Belanger, B. Turmel, H. Arruda, N. Boulianne, B. J. Ward, and D. M. Skowronski. "Largest Measles Epidemic in North America in a Decade--Quebec, Canada, 2011: Contribution of Susceptibility, Serendipity, and Superspreading Events." Journal of Infectious Diseases 207.6 (2012): 990-98.