November 07, 2019

A Generation Asleep? Narcolepsy in Teens and Young Adults

By the Children’s Health Defense Team

Narcolepsy, a severe sleep disorder that typically emerges in adolescence, appears to be on the rise in the U.S. A new analysis of U.S. health care claims reports prevalence roughly 50% higher (1.6 per 2,000) than the upper limit cited in most prior studies (1 per 2,000), with the highest incidence in late adolescence and the early 20s. Pharmaceutical company ads that encourage readers to wonder why
they are “tired all the time” and to take a “Narcolepsy Symptom Screener” test are an indication of the growing problem—and the growing market.
An uptick in narcolepsy in young people is concerning, given the lifelong social, academic, workplace and daily life challenges that the condition’s unwelcome symptoms impose. These include excessive daytime sleepiness, abnormal rapid eye movement (REM) sleep, hallucinations and—in many narcoleptics—sudden muscle weakness or paralysis triggered by strong emotions (a state called cataplexy). In adults, those with narcolepsy are more likely to suffer from anxiety and depression than individuals without the disorder.
As with many of the chronic conditions that plague today’s youth, narcolepsy researchers suspect that environmental exposures in genetically susceptible individuals are a key trigger. This perspective is compatible with recent studies proposing that narcolepsy is an autoimmune disease. Like type 1 diabetes, narcolepsy is the result of selective cell loss (beta cells in the case of diabetes and hypothalamus neurons in the case of narcolepsy)—and in both instances, autoimmune processes are key drivers of the cell loss. And among the environmental exposures capable of setting autoimmunity in motion, recent medical history provides one clearly established culprit: an H1N1 influenza vaccine widely used in Europe in 2009–2010 during the so-called swine flu “pandemic.”

In countries that experienced the spike in narcolepsy, Pandemrix coverage was widespread (roughly 60% of the population).

A surge in sleepiness

In 2010, an unusually high number of young people began presenting with narcolepsy after receiving an H1N1 influenza vaccine manufactured by GlaxoSmithKline (GSK). The vaccine—named Pandemrix—received fast-tracked approval from the European Medicines Agency (EMA) under special rules for declared pandemics but was never licensed in the United States. In countries that experienced the spike in narcolepsy, Pandemrix coverage was widespread (roughly 60% of the population).
Around 2013, researchers began publishing highly consistent studies describing elevated narcolepsy risks in Pandemrix-vaccinated youth. These studies—from England, Finland, France, Ireland, Norway, Sweden and elsewhere—often showed as much as a 14-fold increased risk in children and adolescents as well as lesser but significant risks in adults (such as a 2- to 7-fold increased risk in Finnish adults). In all, an estimated 1300 European youth and adults developed narcolepsy as a result of Pandemrix.

In 2011, the EMA quietly recommended limiting Pandemrix use in persons under 20 years of age due to ‘very rare cases of narcolepsy in young people,’ but publicly, both GSK and the European Centre for Disease Prevention and Control maintained that there was ‘no clear link’ with vaccination.

Safety signal prevarication

Early on, a Swedish neurologist asserted that “The strong temporal relationship made it natural to suspect a link” between Pandemrix vaccination and narcolepsy, and many other in-the-trenches clinicians agreed. For vaccine officials and manufacturers, however, conceding the possibility of a Pandemrix safety signal did not seem to come easily. In 2011, the EMA quietly recommended limiting Pandemrix use in persons under 20 years of age due to “very rare cases of narcolepsy in young people,” but publicly, both GSK and the European Centre for Disease Prevention and Control maintained that there was “no clear link with vaccination.” In 2015, when Pandemrix’s marketing authorization was up for renewal, GSK let it lapse due to “lack of demand for the vaccine.”
Observing the Pandemrix fiasco, an individual submitting a letter to The BMJ commented, “If vaccine regulators were serious about safety, the entire vaccine fleet would have been grounded following the Pandemrix narcolepsy disaster, to check for the same mechanism of failure in other vaccines. But nothing of that sort happened.” Instead, as late as 2018, the prevarication continued. In July of that year, long after European countries had published their compelling research, a CDC-funded investigator told STAT News about a large study that had failed to find evidence of a vaccine-narcolepsy link. Perplexingly, the same researcher (also a consultant for GSK and other vaccine manufacturers) had just participated in a March 2018 meeting that grudgingly reached the opposite conclusion. Following the Brussels-based meeting—attended by top-tier representatives from CDC, FDA, the World Health Organization, European public health agencies, GSK and others—the group published its “consensus that an increased risk of narcolepsy was consistently observed after Pandemrix.”
In September 2018, The BMJ Associate Editor Peter Doshi wrote a scathing critique of regulatory agency and GSK behavior with regard to Pandemrix. Doshi noted that, very early on, GSK possessed evidence of “warning signs” showing “a striking difference in the number and frequency of adverse events” associated with Pandemrix in comparison with two other H1N1 vaccines manufactured by GSK. Yet, despite GSK’s assertions that it had passed along all relevant safety data to regulatory agencies, the sequestered safety signal information did not come to light for eight years—and then, only in response to concerted independent research and lawsuits.

In the United Kingdom, health providers never informed Pandemrix recipients that the not-fully-tested vaccine had been fast-tracked or that the government had given GSK indemnity from any liability.

The attorney of an Irish victim of Pandemrix-induced narcolepsy (who is suing both GSK and Ireland’s regulatory agency) has scolded GSK for keeping the important safety signal information to itself, writing in an affidavit that the disparity between Pandemrix and GSK’s two other vaccines was “of such striking difference that any person contemplating taking the Pandemrix vaccine would be likely, if in receipt of this information, not to choose to have the Pandemrix vaccination.” Likewise, an Irish member of Parliament has called out the Irish vaccine-purchasing agency for “choosing GlaxoSmithKline’s Pandemrix for its swine flu programme when it knew it had a higher risk of side effects than other vaccines.”
In the United Kingdom, health providers never informed Pandemrix recipients that the not-fully-tested vaccine had been fast-tracked or that the government had given GSK indemnity from any liability. To add insult to injury, when approximately 100 families filed compensation claims for Pandemrix-induced narcolepsy under the UK’s Vaccine Damage Payment Act, the government’s Department of Work & Pensions (DWP) strenuously disputed its obligation to pay compensation. Deploying the hair-splitting argument that it need “only recognise the impact of the disability at the precise time the claim was assessed, and not take into account any impact it would have in future,” the DWP succeeded in dragging the process out for years “with unsuccessful appeal after unsuccessful appeal.” In 2017, however, the UK Court of Appeal disagreed and paved the way for payouts to proceed, stating that the DWP must “take into account the impact that disability has on a person’s entire life.”

Reports of narcolepsy to the CDC- and FDA-maintained Vaccine Adverse Event Reporting System (VAERS) raise a number of questions not answered by the CDC’s circumscribed study.

What about the U.S.?

Could other influenza vaccines—or vaccines against other infections—also be contributing to narcolepsy? In light of the evidence linking vaccines to other autoimmune outcomes, the question is a reasonable one. Researchers who have delved into the Pandemrix-narcolepsy association agree, noting that “Further studies on vaccinations (other than Pandemrix) and their relationship with narcolepsy will be conducive to expanding our knowledge on the crucial link between H1N1 infection or vaccination and narcolepsy.”
The CDC appeared to take a step in this direction in 2014 when it looked at the H1N1 and seasonal vaccines used in the United States in 2009–2010 and 2010–2011 and assessed narcolepsy risks for those two years. The agency concluded that the two vaccines “were not associated with an increased risk of narcolepsy.” However, the CDC does not appear to have assessed potential narcolepsy risks for any influenza vaccines since that time nor for other types of vaccines before or since. A CDC webpage on narcolepsy cites a single U.S. study—its own 2014 study—and just five European studies, even though a National Library of Medicine search using the terms “narcolepsy” and “vaccination” brings up 169 hits.
Reports of narcolepsy to the CDC- and FDA-maintained Vaccine Adverse Event Reporting System (VAERS) raise a number of questions not answered by the CDC’s circumscribed study. Among the 84 reports—all but one from 2010 or later—it is possible to note the following:

Eleven reported cases of narcolepsy (13%) were from 2010 or 2011—the years in which the CDC denied any increased risk of narcolepsy.
The 2010 and 2011 reports were associated with both H1N1 (n=4) and seasonal influenza (n=7) vaccines.
In all, 47 narcolepsy reports (56%) followed vaccination with influenza vaccines that included monovalent, trivalent and quadrivalent; seasonal, H1N1 and H5N1; and influenza vaccines administered both via injection and intranasally.
The remaining 37 narcolepsy reports followed vaccination with 14 other types of vaccines—notably Gardasil and Gardasil 9—which is to say, a good many of the vaccines on the child, adult or military vaccine schedules. (Anthrax, DTaP, DtaP/IPV, Hepatitis B, Gardasil, Gardasil 9, other HPV, MMR [ProQuad], meningococcal, rabies, Tdap, tetanus, typhoid, and varicella [Varivax])

Over the past two decades especially, there have been thousands of reports of potential narcolepsy symptoms following vaccination with influenza and other vaccines.

If one broadens the VAERS search to include terms such as “hypersomnia” (excessive daytime sleepiness) that describe narcolepsy symptoms more specifically, the CDC’s complacency about vaccination’s potential contribution to narcolepsy is even more surprising. Over the past two decades especially, there have been thousands of reports of potential narcolepsy symptoms following vaccination with influenza and other vaccines. Symptoms include:

“Sleep disorders” (3400 reports)
“Hypersomnia” (1807 reports)
“Poor quality sleep” (905 reports)
“Abnormal sleep-related events” (89 reports)
“Sudden onset of sleep” (36 reports)
“Sleep paralysis” (11 reports)
“Rapid eye movement sleep abnormal” (10 reports)

Building on the Pandemrix vaccine’s clues

In addition to the vaccine antigen—an inactivated “split influenza virus” described as “A/California/7/2009 (H1N1)v-like strain (X-179A)”—the Pandemrix vaccine contained a novel “adjuvant system” called AS03 made up of alpha-tocopherol (vitamin E), squalene and polysorbate 80 in an oil-in-water emulsion. Other Pandemrix ingredients included the mercury-based preservative thimerosal; more polysorbate 80; and octoxynol 10 (an emulsifier often used in hair dyes).
Discussing the Pandemrix experience, some researchers have pointed fingers at the vaccine’s viral antigen alone, suggesting that it could have triggered “a more exuberant inflammatory response” and “skew[ed] the immune response in such a manner that is harmful, rather than helpful.” Other researchers—who have confirmed Pandemrix’s ability to provoke autoimmune narcolepsy via molecular mimicry—suggest that the cross-reactivity seen in narcolepsy sufferers might result from a synergistic interplay between Pandemrix’s problematic viral component helped along by ingredients such as its adjuvant.
In fact, more scientists are calling attention to the need for focused research on the “immunological mechanisms of action” of vaccine adjuvants, particularly since the very function of adjuvants is to elicit an immune response that otherwise would be unlikely to occur. GSK likes to brag about AS03’s ability to kickstart a strong immune response but, as Children’s Health Defense recently noted, when a vaccine pairs a powerful adjuvant with foreign viral peptides that are similar to human peptides, a “reasonable outcome may be the development of crossreactivity and autoimmunity.” Considering all of these facts together, it seems likely that the Pandemrix-narcolepsy story is a cautionary tale with far broader relevance than has, until now, been admitted.

Templeton Times

Thursday, November 7, 2019