November 2013 – What’s been an obscure disease until recently is gaining more attention, and seasonal influenza vaccine as well as the 2009 pandemic influenza vaccine with adjuvant may be partly to blame. A CTV W5 ‘Fact File’ discusses the sleep disorder: “Narcolepsy is an under-recognized and underdiagnosed condition. Many patients say it takes years to get a proper diagnosis. Some cases are mistakenly labelled as ADHD or depression. Children struggle in school and can be placed in classes for the learning disabled. Yet what many teachers, parents, even doctors may not realize is that the symptoms are due to narcolepsy.” An in-depth W5 broadcast has investigated possible reasons for a recent worldwide upsurge in narcolepsy cases, especially focusing on those in children after the 2009/2010 pandemic.
The CTV website describes 8 year old Makenna, a Canadian child who’s developed the condition. Her symptoms began in 2011, shortly after she’d been hospitalized with a severe influenza-like infection which had arisen over a year after she’d been vaccinated with the 2009 H1N1 pandemic influenza vaccine. Before the infection, she’d been alert and active. A video shows her after her medication had been temporarily withdrawn; during a board game, her head bobs then drops, and her face hits the table where she’s seated. Makenna also suffers from multiple daily bouts of cataplexy, a condition found in about two thirds of narcoleptics; their muscles suddenly weaken when they experience intense emotions including laughter, love, anger and pride.
The disease complicates and restricts Makenna’s life in ways which those of us who are healthy would normally never imagine. Even walking down a flight of stairs puts her at risk of serious injury. Makenna’s parents withdrew her from swimming for fear that she would drown and, in order to attend school and partake in gymnastics, she must take several medications to stay alert. As well as daytime sleeping spells, narcoleptics can also have difficulty sleeping at night, suffer hallucinations, and be unable to move when they awaken.
Dr Emmanuel Mignot, director of the Stanford Center for Sleep Sciences and Medicine is a leading expert on the disease. He theorizes that the influenza H1N1 virus can trigger the brain to destroy hypocretin cells which operate the sleep/wake cycle. He notes that for several years following the 1918 H1N1 pandemic a disorder labelled ‘encephalitis lethargica’ was identified. That disease involved excessive daytime sleepiness. Dr Mignot’s recent research has shown that China experienced a three-fold rise in narcolepsy following the 2009 H1N1 pandemic, the majority occurring in children.
During the 2009-2010 pandemic influenza season many Canadians were injected with Arepanrix™ H1N1 vaccine with AS03 adjuvant, manufactured by GlaxoSmithKline; another GSK vaccine, Pandemrix™, a slightly different version of Arepanrix, was used in Europe; it also contained the very potent AS03 adjuvant. By 2013, 800 European paediatric narcolepsy cases had been linked to Pandemrix™. As well, Finland and France have reported a 3-5 times increase of narcolepsy in adults aged 20-64 who’d been injected with Pandemrix™.
At the behest of the European Medicine’s Agency (EMA) which continues to allow the use of Pandemrix™ in those older than 19 years, GSK is now sponsoring a Quebec study which is not examining the effects of Pandemrix™ but those of the Arepanrix™ which was used in that province. Their stated purpose is to conduct “a more robust assessment…limiting the impact of biases” compared to studies conducted in Sweden, Finland, Ireland, Norway and Britain. Those studies all showed a 7-12 times increased risk of narcolepsy in children who’d received Pandemrix™ compared to those who had not. But Outi Vaarala of the Immune Response Unit at Finland’s National Institute for Health and Welfare has found differences in the way antibodies elicited by Pandemrix™ bind to the H1N1 pandemic virus compared to those elicited by Arepanrix™. Also, since questions had arisen about the advisability of using both seasonal and pandemic vaccine, Quebec chose to not offer the seasonal influenza vaccine during the 2009-2010 influenza season. Considering these points, it’s an enigma just how GSK’s study will be “more robust” than those conducted in Europe using Pandemrix™!
The US FDA has recently endorsed another GSK pandemic vaccine which contains the same adjuvant as Pandemrix™, ie AS03. Dr Mignot suspects that this adjuvant resulted in an excessively strong immune response and, combined with the potent pandemic H1N1 virus (AH1N1pdm09) in the vaccine, could have caused narcolepsy in children who were genetically susceptible to it. Reuters reports that Dr Vaarala agrees; she thinks the fact that both narcolepsy and vaccines are associated with the immune system provides biological plausibility of a link between that disorder and a vaccine with a potent adjuvant.
The Public Health Agency of Canada acknowledges only five reported vaccine-related cases of narcolepsy in children and three in adults. One study examining all narcolepsy and cataplexy cases diagnosed between January 2009 and December 2010 in the province of Quebec, the only Canadian jurisdiction which keeps records on narcolepsy, concluded: “Results are compatible with an excess risk of approximately one case per million vaccine doses but a confounding effect of the pandemic virus infection cannot be ruled out.” Edmonton paediatric sleep specialist, Dr Manisha Witmans usually treats only two narcoleptics per year. But within the last year and a half, she’s diagnosed ten cases and arranged tests for a few more. Not only that, but the cases are also more severe and more likely to suffer cataplexy as well. She knows of similar surges in Toronto and some US cities.
Another interesting point is that receipt of seasonal influenza vaccine prior to vaccination with the H1N1 pandemic vaccine appears to have increased the incidence of pandemic influenza. Dr Danuta Skowronski was the first to discover this trend when she examined records on British Columbians who’d been vaccinated with seasonal influenza vaccine in the autumn of 2008. Although other countries initially reported no similar effects, many later admitted to increases of the disease. We note that FluWatch records show that the AH1N1pdm09 virus was detected in 8.7% of all surveillance test samples found positive for influenza virus during Canada’s 2011-2012 influenza season and 4.0% during the 2012-2013 season. Since some cases of narcolepsy appear to have occurred as a result of infection with pandemic H1N1 influenza, seasonal influenza vaccines as well as 2009 pandemic vaccine with adjuvant might be driving the current rise in narcolepsy cases.
If future pandemic vaccines contain potent adjuvants like AS03, can we expect a continuing rise in cases of narcolepsy? And, if so, will it be allowed to become like the pandemic, autism?
2011-2012 influenza season: See Table 2 at http://www.phac-aspc.gc.ca/bid-bmi/dsd-dsm/rvdi-divr/2011-2012/34/ld/rvdi_divr34ld_t2-eng.php; 1063/(5680+6514) X 100 = 8.7%.
2012-2013 influenza season: See Table 2 at http://www.phac-aspc.gc.ca/bid-bmi/dsd-dsm/rvdi-divr/2012-2013/34/ld/ld-te_t2-eng.php; 1274/(27020+4717) X 100 = 4.0%.