Finland - National Health Dept. Suspends A/H1N1 Vaccine Due to Possible Narcolepsy Connection + other countries investigate

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Re: Finland - National Health Dept. Suspends A/H1N1 Vaccine Due to Possible Narcolepsy Connection

Europe probes swine flu shot, narcolepsy link

LONDON ? The European Medicines Agency is investigating whether there is a link between narcolepsy and a swine flu vaccine.

Narcolepsy is a rare disorder that causes people to suddenly fall asleep.

In a statement issued Friday, the agency said there have been a "limited" number of narcolepsy cases in people mainly in Sweden and Finland who got the Pandemrix shot, made by GlaxoSmithKline PLC.

Officials in France have also reported six cases of narcolepsy in three children and three adults.

The European agency doesn't know if the vaccine caused narcolepsy or if people just coincidentally got the disorder after getting vaccinated.

The agency approved Pandemrix in September and about 30 million Europeans have received the injection.

GlaxoSmithKline said it is conducting its own investigation into the possible link and said it was aware of the reported narcolepsy cases in a small number of countries.

In a statement, the drug maker said "the currently available information is insufficient to assess the likelihood of a causal relationship between Pandemrix and narcolepsy."

http://www.google.com/hostednews/ap/article/ALeqM5jE0ktgt3xK4VVgFFZnL1FmDpqHQwD9HRRR180

[tetano]

Re: Finland - National Health Dept. Suspends A/H1N1 Vaccine Due to Possible Narcolepsy Connection


New cases of sleeping sickness in Finland

In Finland, the growing number of cases of sleeping sickness among children and adolescents suspected of having links to the swine flu vaccine Pandemrix.

- Now we have received 19 complaints from doctors and health professionals, "says Hanna Nohynek, medical professor at the Finnish Institute of Welfare and Health, THL.

Most affected are children and young people under 19 years.

THL stopped vaccination with Pandemrix on 24 August. This is then received 14 notifications of sleeping sickness can be a serious side effect.

The Authority has now also asked the medical staff to notify any case of disease and symptoms similar to sleeping sickness, or narcolepsy.

-Now that we have highlighted the care of the problem, I think we can expect additional reports of suspected cases, "says Dr Nohynek.

Finland has so far only found a temporal link between vaccination against swine flu and narcolepsy.

-All have fallen ill with narcolepsy 2-10 weeks after they receive the vaccine against swine flu, "says Hanna Nohynek.

Unusually, however, many children have been diagnosed.

"We usually have 1-7 cases of narcolepsy per year among children up to 16 years - while about 50 adults get the disease each year.

"But we still do not know if there is a causal link between the vaccine and illnesses, stresses Hanna Nohynek.

There may be one other cause, typm infections and other viral diseases, "she says.

Those who become ill are likely to also have a genetic predisposition to narcolepsy, she said.

-There are now several studies.

THL vaccination stopped in the expectation that these tests should be completed.

It has, so far no plans to cancel the upcoming autumn general vaccination with influenza vaccine, which also includes porcine influenza vaccine.

-According to immunologists, it is unlikely that you can get an autoimmune reaction of an inactivated virus, says Hanna Nohynek.

-If there is a causal link between the vaccine and narcolepsy, I say if, it is more likely that it is adjuvansen (ed note: a strengthening substance) that gives the incident.

Adjuvansen was added to dilute the concentration of ?ggodlat viruses and to trigger the immune reaction.

In the case of seasonal vaccine is working right now with THL to develop recommendations on which risk groups should be vaccinated.

In New Zealand during their winter season, had 300 cases of swine flu a week and several deaths, according to Hanna Nohynek.

A seasonal influenza vaccine to swine influenza virus (without adjuvant) were given in winter to 29 million children in the U.S., but noted that more cases of narcolepsy, according to THL.

http://www.nyteknik.se/nyheter/bioteknik_lakemedel/lakemedel/article2465447.ece

[tetano]

Re: Finland - National Health Dept. Suspends A/H1N1 Vaccine Due to Possible Narcolepsy Connection

GSK investigates Pandermix link to chronic sleep disorder news


The UK's largest drugmaker, GlaxoSmithKline, is investigating whether its H1N1 pandemic vaccine Pandemrix is responsible for inducing the sleep disorder narcolepsy.

GSK initially became aware of possible cases of narcolepsy following vaccination with Pandemrix through adverse event reports received by the Swedish Medical Products Agency, subsequently reported in the media reports in Finland.

So far, information on the individual cases is limited, but GSK says it is conducting its own investigation to gather as much additional data regarding the reported cases, and working with key regulatory authorities, including the European Medicines Agency (EMA).

GSK says it has also contacted the regulatory authorities in other countries where Pandemrix was used extensively.

"The cases reported as of 1500h GMT on 2 September 2010 have been primarily, but not exclusively, in Finland and Sweden, with a small number of additional cases reported in France," GSK said in a statement.

Media coverage has suggested small numbers of cases in Norway and Germany, but GSK says it has, so far, not received any reports from these countries.

http://www.domain-b.com/companies/companies_g/GlaxoSmithKline/20100904_pandemrix.html

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Re: Finland - National Health Dept. Suspends A/H1N1 Vaccine Due to Possible Narcolepsy Connection

Several Swedish children have narcolepsy


The number of children who have been sleeping disease narcolepsy, has increased since the Swedish authorities started mass vaccination against influenza A (H1N1). It notes L?kemedelsverket in connection with an investigation of suspicions that influenza vaccine Pandemrix may increase the risk of having narcolepsy.


Health authorities in Sweden have received reports of 20 children under 18 who have been diagnosed with narcolepsy in the period from October 2009 to August 2010. If disease prevalence was the same for previous years, would in ten children have been sleeping disease in that period.

L?kemedelsverket estimates that 65 per cent. of children under 18 years in Sweden have been vaccinated with Pandemrix.


The authorities have also analyzed data from the Stockholm area. In the years 2005 to 2009 registered health care no or only a few cases of narcolepsy among children per year, while in the first seven months of 2010 recorded six cases.


Among these six cases there were two children who were not vaccinated with Pandemrix. The same trend was seen among adults, where only half of those who had been diagnosed with narcolepsy had been vaccinated.


L?kemedelsverket points out however that the total number of cases of narcolepsy in the Stockholm area is low and the figures should be interpreted with caution.


Unlike in Sweden and Norway, the Danish authorities have not offered influenza vaccine to all children, and so far has not found an increased number of cases of narcolepsy in Denmark.


The European pharmaceutical authorities (EMA) has initiated an investigation into a possible. link between narcolepsy and Pandemrix. CHMP, the European registration boards for medicines for humans want in a meeting tomorrow to discuss the investigation.

http://www.dagensmedicin.dk/nyheder/2010/09/07/flere-svenske-born-har-fae/index.xml

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Re: Finland - National Health Dept. Suspends A/H1N1 Vaccine Due to Possible Narcolepsy Connection

Swedish Narcolepsy Cases Not Linked to H1N1 Vaccine

Sweden?s Medical Products Agency (MPA) on Wednesday reported that that no apparent link exists between recent narcolepsy cases and the H1N1 swine flu vaccine Pandemrix.

The results of a preliminary study by the Swedish agency suggest that while narcolepsy cases increased in the aftermath of the vaccinations, the condition had also developed among people who were not inoculated.

In the greater Stockholm area, six cases of child narcolepsy were reported in connection with the swine flu epidemic. Two of these children were not vaccinated. Among the adult population, the ten latest narcolepsy cases are divided equally among those who received the vaccine and those that did not get the jab.

Finnish experts consider the results of the Swedish study to be reliable.

?We know that a respiratory infection coupled with a high fever, such as swine flu, can trigger narcolepsy,? says Ville Valtonen, head physician responsible for infectious diseases at the Helsinki and Uusimaa Hospital District (HUS).

http://yle.fi/uutiset/news/2010/09/swedish_narcolepsy_cases_not_linked_to_h1n1_vaccine_1965524.html

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Re: Finland - National Health Dept. Suspends A/H1N1 Vaccine Due to Possible Narcolepsy Connection

Already in August the Swedish medicament agency (MPA) had reported about Narkolepsief?llen in the temporal connection with the pork influenza-vaccination. A causal connection seems not plausible up to now. The MPA has published topically further information in addition.


UPPSALA. Till the beginning of September a total of 22 cases of a Narkolepsie have been announced by employees of the health service after a vaccination with Pandemrix ?. 20 these cases concern children and youngsters, thus among 18-year-old. Now in her topical statement the MPA compares the Narkolepsie-Inzidenzen: On the one hand, them of the population group inoculated against pork influenza with the Inzidenz more uninoculated, to the other with the Inzidenz in the time before the beginning of the Pandemie vaccinations.
Per year a Narkolepsie is anew diagnosed in Sweden, therefore, with about 100 people. The prevailing interest comes from the age group of 20-to 40 year-old. During the past six years 7 to 17 Narkolepsie-new illnesses per year were announced to people less than 20 years, writes the MPA on her homepage. Because possibly two-thirds of the children and youngster in Sweden were inoculated against pork influenza, a number is to be expected computationally from ten Narkolepsiediagnosen. The number of the Narkolepsiemeldungen in connection with the pandemischen vaccination (20) is higher than the expected number (10), sums up the MPA.
Increase of the Narkolepsief?lle similarly high the MPA has undertaken, in addition, a comparison of the Narkolepsie-Inzidenzen from the district Stockholm. Here everything were grasped with Pandemrix ? inoculated in own register.
Also here had received possibly two-thirds of the children and youngster a pork influenza-vaccination. From in the district Stockholm announced six Narkolepsief?llen with among 18-year-old four fall in the group of the Pandemie-inoculated and two in the uninoculated one. Five were inoculated by ten patients with a Narkolepsie diagnosis at the age of 18 years or higher, against pork influenza and five not. The statistical calculation has proved here no differences, according to the MPA. The increase of the Narkolepsie-Inzidenz has in the inoculated ones as well as the uninoculated group a similar magnitude, concludes the MPA.
The Swedish agency offers several possible explanations of the increase of the Narkolepsie-Inzidenz in the time of the pork influenza-vaccination in Sweden: On the one hand, the attention could be raised by the new Pandemie vaccine for undesirable medicament effects all together. Then here a so-called capture Bias would be. Hence, it is important that about the Narkolepsie illnesses is reported very exactly and in detail. This counts above all concerning the appearance of the first symptoms of the illness, according to the MPA further.
Autoimmunological reaction as a Narkolepsieursache?
To the other vaccines are associated against a row by illnesses with autoimmunological reactions, even if only seldom.
Such a mechanism the MPA can also fancy concerning the Narkolepsie. Moreover responsible Paul honestly institute (PEI) writes in Germany for vaccines in a statement: " Isolated suspicion cases of a Narkolepsie have been reported during the past years the PEI after other vaccines. Two cases from 2004 and 2006 concerned children at the age of eight and 13 years who had received FSME vaccinations. With the third case it concerned a 48 year-old woman after great fury vaccination. Is to be noted that from the temporal association cannot be closed by suspicion cases of undesirable medicament effects automatically on a causal connection. "
As a result the MPA shows on her homepage expressly that the knowledge about the possible causes of a Narkolepsie is still widely incomplete. Life style factors like stress and very incriminating situations are connected also with the appearance of Narkolepsie, like environmental factors, possibly infections with flu viruses or Streptokokken as well as fever illnesses. Also innate factors played a role. Moreover the PEI on his homepage explains that 98 percent of the Caucasian Narkolepsie patients show a certain HLA type. In few cases Narkolepsie also appears after damages of certain brain regions (brain trunk and Dienzephalon).
In addition, multifaktorielle causes would be accepted with disturbances in cholinergen and noradrenergen system as well as a decrease of Hypocretin containing neurons in dorsolateralen Hypothalamus, according to the PEI further.
The responsible health institutes within the EU are, in any case, in narrow vote in relation on Narkolepsie and Pandemie vaccination. The MPA would like to receive above all data to people inoculated against pork influenza who have received not the Pandemrix inoculated in Sweden ?, but another Pandemie vaccine.

http://www.aerztezeitung.de/medizin/krankheiten/infektionskrankheiten/schweinegrippe/article/619632/eher-entwarnung-narkolepsie-durch-schweinegrippe-impfung.html

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Re: Finland - National Health Dept. Suspends A/H1N1 Vaccine Due to Possible Narcolepsy Connection

UPDATE 1-EU drug body finds no narcolepsy link to Pandemrix


* Most cases of sleep disorder reported in Sweden, Finland

(Adds EMA quote, GSK Biologicals quote, background)

LONDON, Sept 23 (Reuters) - There is no evidence to link GlaxoSmithKline's (GSK.L) H1N1 swine flu vaccine Pandemrix to cases of narcolepsy, European drugs regulators said on Thursday, but a full review is needed and will take three to six months.

The European Medicines Agency (EMA) said its Committee for Medicinal Products for Human Use had reviewed all available data on the suspected link between narcolepsy and Pandemrix.

"The committee concluded that the available evidence was insufficient to determine whether there is any link between Pandemrix and reports of narcolepsy, and that further studies were necessary to fully understand this issue," it said in a statement.

Narcolepsy is a rare sleep disorder that causes a person to fall asleep suddenly and unexpectedly. Its precise cause is unknown, but it is generally considered to be triggered by a combination of genetic and environmental factors.

Glaxo said in a statement that the total number of cases of narcolepsy following immunisation with Pandemrix reported to it as of Sept. 17, 2010, was 80, the majority of which were from Sweden and Finland.

Pandemrix has been used since September 2009 for vaccination against H1N1 pandemic flu, also known as swine flu, and has been given to at least 30.8 million Europeans,

"We will also continue our own investigation in an effort to gather additional data and information regarding the reported cases," Norman Begg, chief medical officer at GSK Biologicals, said in a statement. (Reporting by Kate Kelland; Editing by Will Waterman)

http://www.reuters.com/article/idUSLDE68M1R420100923

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Re: Finland - National Health Dept. Suspends A/H1N1 Vaccine Due to Possible Narcolepsy Connection

Investigations into possible links between a vaccine against the H1N1 or swine flu virus and an increase in narcolepsy among children this past year might stretch into next year, and could prove inconclusive.
Results of the first registry study by the National Institute for Health and Welfare (THL) are expected before the new year. Information is now being gathered on the cases of the neurological disease that have been diagnosed this year.
However, Hanna Nohynek, special researcher at THL, says that the study may not establish a clear indication one way or another as to whether or not there is a link between the Pandemrix vaccine and narcolepsy.

The aim of the study is to ascertain if children vaccinated for the virus are more likely to come down with the disease than those who were not.

The fact that more than 80 per cent of children in Finland were given the vaccine makes it difficult to compare the two groups statistically.
Furthermore, the vaccines were administered at the time that the pandemic was raging, which makes it difficult to determine if the rise in cases of narcolepsy was caused by the vaccine, or the virus.
“It could be that the truth will not be found. It may be that there is some third factor at work in combination with the virus and the vaccine, that we have not even though of”, Nohynek says.

A study covering the whole Nordic region could bring a more definitive result. However, the study is only in its early stages, and it could take a long time to complete.
The European Centre for Disease Prevention and Control (ECDC) has informed Helsingin Sanomat that a European study will take at least six months.

...

http://www.hs.fi/english/article/Narcolepsy+studies+could+prove+inconclusive/1135261034920

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Re: Finland - National Health Dept. Suspends A/H1N1 Vaccine Due to Possible Narcolepsy Connection

The National Institute for Health and Welfare (THL) has set up a special team of researchers to investigate a spate of narcolepsy cases suspected to have been triggered by swine flu vaccinations.

Minister of Health and Social Services Paula Risikko told YLE that the team has been working for some time already and is well advanced in its study. Researchers are focusing on examining cases of children who began showing signs of narcolepsy after receiving vaccinations against swine flu. The team includes experts from THL and other research institutes. Their work may be completed by the end of the year.

The parents of several of the children with narcolepsy interviewed by YLE said that they were unaware of the research project. Risikko expressed surprise and said that she would take the issue up immediately with the National Institute for Health and Welfare.

Parents say that according to the information they have received, 37 children in Finland came down with narcolepsy soon after being injected with the vaccine.

Some of the children have sustained serious brain damage that has made it impossible for them to attend school. They suffer from symptoms including hallucinations, personality changes and cataplexy, which is a severe muscle weakness that can lead to a complete collapse up to 20 -30 times a day.

http://www.yle.fi/uutiset/news/2010/11/special_team_investigating_narcolepsy_cases_2128496.html

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Re: Finland - National Health Dept. Suspends A/H1N1 Vaccine Due to Possible Narcolepsy Connection

The Chancellor of Justice has received 14 complaints regarding ties between GlaxoSmithKline (GSK), the manufacturer of the swine flu vaccine, and the National Institute for Health and Welfare (THL).

The Chancellor has been asked to assess if the THL was biased when it recommended that Finland purchase the H1N1 vaccine from GSK, according to YLE current affairs TV programme Ajankohtainen kakkonen. The institute had received significant research grants from the pharma giant.

Complainants also requested the Chancellor assess whether a special team assigned by the THL to investigate a possible link between the H1N1 vaccine and narcolepsy is biased for the same reason. They want a clear answer on whether Finland?s highest health authority, the THL, may work in close cooperation with pharmaceutical companies.

Children develop narcolepsy

Thirty-seven children in Finland came down with narcolepsy soon after being injected with the vaccine against swine flu.

Some of the children have sustained serious brain damage that has made it impossible for them to attend school. They suffer from symptoms including hallucinations, personality changes and cataplexy, which is a severe muscle weakness that can lead to a complete collapse up to 20 -30 times a day.

The THL maintains that cooperation with pharmaceutical companies is standard practice for professional organisations.

http://www.yle.fi/uutiset/news/2010/11/ties_between_big_pharma_and_thl_draw_complaints_2147563.html

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Re: Finland - National Health Dept. Suspends A/H1N1 Vaccine Due to Possible Narcolepsy Connection

Narcolepsy diagnosed in 41 children vaccinated for H1N1 last year
Surge seen only in Sweden and Finland

Narcolepsy diagnosed in 41 children vaccinated for H1N1 last year
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Forty one children and young people in Finland who were vaccinated for the H1N1, or swine flu virus last winter have been diagnosed with narcolepsy. In addition, there have been a few cases of the disease in which there was no record of a swine flu vaccination.
Sweden and Finland are the only two countries to report a surge in narcolepsy the same vaccine was used in Canada, where there were only a few cases of the disease.

Narcolepsy has been on the increase in Finland in the past ten years, but not among such young patients. The symptoms of the young victims have been more severe than usual.
?Kataplexy, the sudden loss of muscle tone in connection with a strong emotional state, has not been this common before?, says child neurologist Outi Saarenp??-Heikkil? of the Tampere University Hospital.
?The symptoms are complicated and they are more severe than before. We have to learn how to treat it, because the medicines have not been intended for children, and they should not be used too easily. Older patients suffer most from personality changes - irritability and fits of rage. Going to school becomes impossible for some, and social life becomes more narrow.?

Although the increase in cases of narcolepsy coincides with the vaccines, there is still some question as to whether or not it was actually the cause.
The question was analysed on Monday when families affected by the disease and public health officials met at the Ministry of Social Affairs and Health. The families had little doubt about the connection, and blasted last winter?s vaccinations as a complete failure, which only benefited the manufacturers.
In their appeals to both the Ministry of Social Affairs and health, and to Minister of the Interior Anne Holmlund (Nat. Coalition Party) the parents called for an independent investigation which would not involve those experts who took part in deciding on the vaccination programme.

Several studies have already started. One of them involves ten European Union countries, and there are two others concentrating on Finland. One of the studies is looking into the prevalence of narcolepsy, and the other concentrates on immunology. Previous studies indicate that heredity and immune defence have an impact on the likelihood of getting the disease.
There are other possible factors as well. ?Vaccines were given at the same time that children were exposed to the swine flu virus. The cause may be the virus and the vaccine together?, pondered Professor Timo Vesikari, the head of the Vaccine Research Center of the University of Tampere.

One possible cause of the increase in narcolepsy could be the H1N1 virus itself. ?Last year?s conference of sleep researchers was concerned about the arrival of swine flu. It was similar to the Spanish flu virus, and the Spanish flu caused people to fall asleep suddenly?, says necrologist Markku Partinen of the Skogby Sleep Clinic.
?We were pleased that vaccines were introduced in reaction to the swine flu. This could help avert an increase in narcolepsy.?
?Getting the disease requires a hereditary susceptibility - a certain type of tissue?, Partinen said, adding that all of those who were diagnosed in Finland had it.
?The tissue type increases the danger of getting the disease as much as 140-fold. There can also be a lack of genes that protect against the illness, and such genes have so far been missing from the ones who have been classified by type. Coming down with the disease can be a factor of many simultaneous factors.?

It is possible that a clear causal relationship is never established.
This would be bad news for those who have come down with the disease, as it would make it more difficult to get compensation.
The vaccine was insured for possible damage that it might cause. However, for any payout, the connection with the suspected disease should be firmly established. Compensations are applied for on a case-by-case basis.
Families of affected by narcolepsy could also get special compensation from the Social Insurance Institution KELA.

http://www.hs.fi/english/article/Narcolepsy+diagnosed+in+41+children+vaccinated+for+H1N1+last+year/1135262379639

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Re: Finland - National Health Dept. Suspends A/H1N1 Vaccine Due to Possible Narcolepsy Connection

Clear link between narcolepsy and vaccines

There is a link between swine influenza vaccinations and the increasing cases of the disorder narcolepsy. It is enshrined in the interim report by the Institute for Health and Welfare published today. According to THL, it is likely that Pandemrix-vaccination was a contributing factor in cases of narcolepsy increased among 4-19 year olds in our country in 2009 and 2010.

This must in THL still be some other factor which, together with Pandemrix led to the increasing narcolepsy cases, but what is known remains incomplete. In addition to Finland increased narcolepsy cases, also in Sweden and Iceland.

THL exclude that it would have been something wrong with the lots of Pandemrix Finland received.

http://svenska.yle.fi/nyheter/artikel.php?id=207327

[sharon sanders]

Re: Finland - National Health Dept. Suspends A/H1N1 Vaccine Due to Possible Narcolepsy Connection

Vaccines and immunization

Pandemrix? vaccine and increased risk of narcolepsy

01-02-2011
The National Institute of Health and Welfare of Finland today issued a statement indicating an increased risk of narcolepsy (a rare sleep disorder that causes a person to fall asleep suddenly and unexpectedly) observed among children and adolescents vaccinated with Pandemrix?, an adjuvanted pandemic H1N1 vaccine manufactured by GlaxoSmithKline.
The National Institute (on the advice of the Finnish National Narcolepsy Task Force) concludes that the risk of falling ill with narcolepsy among those vaccinated in the 4-19 year age group is 9 times greater than those unvaccinated in the same age group. The National Institute considers it probable that the Pandemrix? vaccine was a contributing factor to this observed increase, but states that further investigation is required of other significant co-factors associated with the increased risk of narcolepsy. The final report from the Finnish National Narcolepsy Task Force is expected to be issued by 31 August 2011.
Pandemrix? vaccine has been used in 38 countries worldwide during the 2009/2010 season. An increase in cases of narcolepsy has been observed only in Finland, Sweden and Iceland.
The issue of an increased rate of narcolepsy has not been raised in association with the use of other influenza A(H1N1) pandemic vaccines, seasonal influenza vaccines or any other adjuvanted vaccines used in childhood immunization programmes.
WHO's Global Advisory Committee on Vaccine Safety (GACVS) is considering all available data relating to reports of increased rates of narcolepsy and is expected to issue a statement on its web site within the coming days.
WHO agrees that further investigation is required concerning narcolepsy and Pandemrix? vaccine. In collaboration with a number of European Union Member States, the European Centre for Disease Prevention and Control (ECDC) is currently conducting a joint epidemiological study of narcolepsy and pandemic vaccines.
Recommendations for the use of seasonal 2010/2011 influenza vaccines in children and adolescents remain unchanged.
WHO's attention was first drawn to reports of narcolepsy following vaccination with Pandemrix? in Finland and Sweden in August 2010 and committed, through GACVS, to monitor the situation as new data became available.
Updates will be provided as further information becomes available and is assessed.

http://www.euro.who.int/en/what-we-do/health-topics/disease-prevention/vaccines-and-immunization/news/news/2012/02/pandemrix-vaccine-and-increased-risk-of-narcolepsy

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Re: Finland - National Health Dept. Suspends A/H1N1 Vaccine Due to Possible Narcolepsy Connection

http://www.washingtonpost.com/wp-dyn/content/article/2011/02/14/AR2011021404944.html

Scientists may have found a clue to explain a possible increased risk for narcolepsy among some people who got the H1N1 flu vaccine. According to the World Health Organization, excess cases of narcolepsy appear to have occurred among people with a gene that increases the risk for the rare disorder, which causes people to suddenly fall asleep.

Cases of narcolepsy have been reported in 12 countries among children and adolescents who received the swine flu vaccine in 2009. Sweden and Finland reported the most cases, with 60 of them in the latter country.

..

http://www.washingtonpost.com/wp-dyn/content/article/2011/02/14/AR2011021404944.html

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Re: Finland - National Health Dept. Suspends A/H1N1 Vaccine Due to Possible Narcolepsy Connection

ECDC: Reports of cases of narcolepsy and cataplexy in children and adolescents in Finland, Iceland, and Sweden


02 Mar 2011
In February 2011, ECDC published a report concerning a rise in narcolepsy in children and adolescents in some northern countries. This update provides initial findings on this topic and describes relevant developments for Europe.

Background
Increased numbers of narcolepsy-cataplexy in children and adolescents became apparent in Finland in mid-2010. An increase in cases was also reported in Sweden and, to a lesser degree, in Iceland. Initial reports associated the rise with the 2009 pandemic and the use of pandemic vaccines. In late August 2010, Finnish authorities stopped using the adjuvanted pandemic vaccine (GlaxoSmithKline?s Pandemrix).

The European Commission initiated a formal procedure, and the European Medicines Agency?s Committee on Human Medical Products (EMA CHMP) reviewed the available data. The CHMP noted that no similar aggregation of cases was reported from other countries (Pandemrix was used extensively in at least 19 EU/EEA countries) and hence no clear link with vaccination [1]. In September 2010, EMA stated that further studies were needed, but did not recommend suspending Pandemrix or withdrawing its marketing authorisation.

Analytic studies were initiated in Finland and Sweden. ECDC commissioned a large-scale study through its VAESCO project (Vaccine Adverse Events Surveillance and Communication), attempting to estimate background rates of narcolepsy while simultaneously investigating a possible association between pandemic vaccination, wild-type influenza infection, and other vaccines. Results are expected for June 2011.

Narcolepsy
Narcolepsy is a disabling chronic neurological disorder characterised by recurrent episodes of excessive daytime sleepiness. Cataplexy (episodic muscle weakness), sleep paralysis, and hypnagogic hallucinations often accompany narcolepsy. Symptoms usually develop gradually [2]. A multi-factorial aetiology has been suggested for narcolepsy, involving a genetic predisposition in combination with environmental risk factors. A majority of genetically susceptible individuals have one or more alleles of HLA DQB1*0602 across all ethnic groups [3]. Possible environmental risk factors include streptococcal infections, passive smoking, withdrawal from antidepressants, and obesity [4-6]. Researchers have proposed an autoimmune mechanism as a trigger for the selective loss of hypothalamic orexin/hypocretin-producing neurons involved in REM-sleep regulation [7-9].

The incidence rate has been estimated at around 0.74 to 1.37 cases per 100 000 person-years, depending on the way the condition is defined. Because narcolepsy is an enduring condition, prevalence rates are much higher [5] and since early presentations can be subtle, diagnoses may be brought forward through increased awareness.

Working case definitions for narcolepsy with and without cataplexy, with levels of diagnostic certainty from 1 (lowest) to 3 (highest), were developed by the ECDC-VAESCO consortium in collaboration with the European Narcolepsy Network (Annex). This built upon the prior experience of the Brighton Collaboration.

Finland ? interim THL report
As of 10 February 2011, the Finnish National Institute for Health and Welfare (THL) had received 62 notifications of suspicion of narcolepsy or narcolepsy/cataplexy following vaccination with Pandemrix [10]. Of these, 59 occurred in children and adolescents (4?19 years of age). The majority showed narcoleptic/cataplectic symptoms compatible with ICD-10 code G47.4. Vaccination coverage in this age group was around 65%. The average time from vaccination to the onset of excessive day time sleepiness or cataplexy was 52 days. An interim report of a nationwide, register-based retrospective cohort study by a National Narcolepsy Task Force suggested that the risk of developing narcolepsy/cataplexy in the 4?19 age group was increased by 9.2% if vaccinated with Pandemrix (95% CI: 4.5?21.4). The Task Force concluded that it is probable that the vaccination contributed to the observed increase in narcolepsy/cataplexy, but most likely in association with a still unknown genetic and/or environmental factor. However, the strength of the observed association is of such magnitude that it is unlikely to be explained by confounding factors. A final report is expected for August 2011 [10].

Sweden
As of 27 January 2011, 61 cases of narcolepsy following vaccination with Pandemrix have been received by the Swedish Medical Product Agency and forwarded to the EMA EudraVigilance database for spontaneous adverse drug reports [11]. Fifty-three cases were in people younger than 20. Most of the cases reported the onset of disease before the end of February 2010, the remainder before the summer of 2010. An earlier ECDC-VENICE survey* reported vaccination coverage for Sweden at 59% [12]. Sweden is currently involved in three activities:

* Registry studies of narcolepsy/cataplexy cases in vaccinated versus unvaccinated people.
* Case ascertainment of cases appearing in healthcare information systems during 2009?2010.
* Identifying and investigating cases being included in the ECDC-VAESCO case-control study.

Iceland
Iceland reported increased narcolepsy diagnoses in the age group 0?18 years for 2010. No cases of narcolepsy have been diagnosed in those 19 years or older. Of the five cases diagnosed in 2010, three were vaccinated. 40,875 individuals were vaccinated with Pandemrix in the 0?18 years age group (total age group: 85,318). 109,414 individuals received Pandemrix in the age group above 19 years of age (total age group: 232,312). All cases have been confirmed by neurologists.

Reports to EudraVigilance
As of 27 January 2011, 162 reports suggestive of narcolepsy and mentioning Pandemrix have been recorded in the EU EudraVigilance database of suspected adverse reactions to medicinal products maintained by the European Medicines Agency. Of these, 55 reports had been received from Finland, 20 from France, 8 from Germany, 2 from Ireland, 1 from the Netherlands, 10 from Norway, 1 from Portugal, 61 from Sweden, and 4 from Switzerland. There were no reports from other EU/EEA countries.

Canada
Canada uses large amounts of Arepanrix, a product very similar to Pandemrix, which is produced locally by GlaxoSmithKline in Canada. As of 26 January 2011, two cases of narcolepsy have been reported per around 2 million vaccinated among those 0?17 years of age (0.1 cases/100,000 vaccinated).

2010/2011 influenza season and use of Pandemrix in the European Union
The vaccine used in Finland and Sweden (Pandemrix) was used in 2009/10 by at least 30.8 million Europeans in 19 EU/EEA countries. In February 2010, WHO recommended that the 2010/2011 seasonal influenza vaccines for the northern hemisphere be based on influenza antigens for A(H1N1)2009, A(H3N2), and B viruses [13], and most manufacturers produced these vaccines as unadjuvanted products. ECDC supported the WHO guidance that seasonal vaccines should be used to prevent seasonal influenza. Vaccines reached EU countries in the summer/autumn of 2010 [14]. At the same time, Pandemrix remained authorised for use preventing A(H1N1)2009. Those viruses predominated the season and accounted for most of the severe cases [15]. However, B viruses have been detected throughout the season in steadily increasing proportions. They have caused deaths and latterly have predominated over A(H1N1)2009 in some countries (see ECDC?s Weekly Influenza Surveillance Overviews). In early February 2011, the European Commission?s DG SANCO undertook a rapid survey of the current use of Pandemrix in EU/EEA Member States, when only a few EU countries were still using Pandemrix: in Sweden, Pandemrix was used for a small number of immunodeficient individuals who benefited from an adjuvanted preparation. Ireland reported using the vaccine but not in children and adolescents (under the age of 20). Portugal was using the vaccine in children and adolescents, although numbers were diminishing. The same was the case for the UK. Six countries known to have used Pandemrix during the 2009/10 season did not respond to the enquiry.

Authorisation and effectiveness of pandemic and seasonal vaccines in Europe
Assessing the benefit-risk profile of centrally-authorised vaccines is the responsibility of EMA?s Committee for Human Medicinal Products, and granting a marketing authorisation for these vaccines in the European Union is the responsibility of the European Commission. Both the 2009 pandemic vaccines and the new seasonal vaccines have been shown to be effective in the field in 2009 and 2010 [16-18].

ECDC -VAESCO study ? initial report on background rates
As of 15 February 2011, the VAESCO network has estimated preliminary background incidence rates of narcolepsy in six European countries (Denmark, Finland, Netherlands, Italy, Sweden, UK). The data were gathered from population-based healthcare databases (GPs and hospitals). Background incidence rates of narcolepsy were presented to EMA, WHO, and the ECDC Advisory Forum in mid-February. Updated background rates for a total of over 40 million persons are now available.

Observed narcolepsy incidence rates were around 1 per 100,000 person years and varied only slightly over time. In Finland, a statistically significant increase in the incidence rate has been observed after September 2009 only in the age group of 5?19 years of age (as in the THL study). The rates in the age groups 20?59 and 60+ years of age have been unchanged since 2006. In the Netherlands, an increase in the incidence rate of narcolepsy based on yet unvalidated diagnoses was observed in the 20?59 years age group, an age group that generally was not offered pandemic vaccine. No age-specific increases could be observed in other countries.

The VAESCO network is conducting its case-control study in nine European countries, estimating the relative risk of narcolepsy in vaccinated-versus-unvaccinated individuals. Other possible risk factors that will be assessed include natural influenza infection, other vaccines administered before/after pandemic vaccination, and, sufficient funds provided, genetic predisposition. Results from the ongoing case-control study are expected in June 2011.

Assessment of EMA/CHMP
On 18 February 2011, EMA?s Committee on Human Medical Products published a review of data on narcolepsy and possible association with Pandemrix. The Committee concluded that the new evidence added to the concern arising from the case reports in Finland and Sweden, but data were insufficient to establish a causal relationship between Pandemrix and narcolepsy and no change to the product information was warranted. The Committee indicated that it is important to gather more data from other studies, including the ECDC-VAESCO network, and the manufacturer has now also announced details of their own investigations.

WHO position on related influenza immunisation policy
WHO?s Global Advisory Committee on Vaccine Safety reviewed the data in early February without changing its position on pandemic or seasonal influenza vaccines [13]. WHO specifically stated that countries could continue using monovalent vaccines, including Pandemrix, in order to immunise persons at risk of severe disease from A(H1N1)2009 if trivalent seasonal vaccine was unavailable.

ECDC comment (2 March 2011)
The Finnish Task Force concluded that it was probable that Pandemrix contributed to the observed increase in narcolepsy/cataplexy, but most likely in association with a still unknown genetic and/or environmental factor, and Finland suspended the use of Pandemrix in August 2010. Sweden reports contemporaneous increases in diagnoses of narcolepsy-cataplexy, and awaits the results of a detailed national investigation. Numbers of cases are small in Iceland, and no such signals have been noted elsewhere in Europe despite large-scale use of the same vaccine. All in all, the signal is concerning but lacks the consistency needed to come to a conclusion on a causative relationship [1].

EMA?s Committee on Medical Products for Humans concluded that the results from Finland added to the concern arising from earlier case reports in Finland and Sweden while at the same time the data remained insufficient to establish a causal relationship between Pandemrix and narcolepsy.

WHO?s northern hemisphere influenza vaccination guidance (February 2010) recommended the usual trivalent seasonal vaccines for the 2010/11 season, and ECDC supported this in its guidance for Member States [13,14]. WHO has stated that the triple seasonal vaccine would be preferred over Pandemrix. At the time of writing, Pandemrix is limited in use throughout Europe. Exceptions following local or individual risk-benefit analysis are made for small special groups (e.g. immunodeficient individuals) and in situations that carry a risk of A(H1N1)2009 infection but no seasonal vaccine is available. Such risk-benefit analyses would take into account the Finnish and subsequent findings.

In ECDC?s view it is essential to pursue independent scientific investigations in order to test various hypotheses [1,10,11]. This is happening through the independent national and ECDC-VAESCO studies, which will deliver results in June/July 2011. There is no need for policy decisions ahead of these findings since Pandemrix is essentially no longer in use in any EU/EEA country.

ECDC?s position remains unchanged from that in December 2010 and January 2011, namely that immunisation against seasonal influenza is important and prevents many severe influenza cases and fatalities. Of course personal hygiene measures and medical treatments are also important. When it comes to the choice of vaccines, seasonal vaccines are what should be used to prevent seasonal influenza as they will cover the different viruses involved. [13,14].

Assuring the highest standards of vaccine safety requires constant monitoring and systematic epidemiological assessments. This is an essential component of safe and effective vaccination programmes. It is also important in retaining the confidence of the public and professionals in the safety and effectiveness of vaccines [1]. ECDC?s role as an EU scientific agency is to support EMA and national regulatory and public health authorities. This includes designing, financing, and coordinating rigorous and independent scientific studies on vaccines and vaccine-preventable diseases. The ECDC-VASECO studies will elucidate the epidemiology of narcolepsy/cataplexy after the detection of a signal for vaccine side effects in three countries This is to evaluate the potential risk factors for the observation which may include infections and other factors not just vaccination [1]. Results of such studies will facilitate policy decisions by EU and national authorities.

Further information will be made available by ECDC through its website.

Contact: influenza@ecdc.europa.eu

Annex. Narcolepsy-cataplexy working ECDC-VAESCO case definition criteria

General note
In rare cases, a suspected narcolepsy case may not be classifiable according to the levels below (e.g. when there is cataplexy, no sleepiness, and hypocretin-1 levels are unavailable). In these instances, the case definition committee will examine the clinical data and decide whether or not the patient can be classified as having narcolepsy, and if yes, at which level.

Level 1

In the presence of:

criterion 1: Excessive daytime sleepinessa and/or suspected cataplexy AND
criterion 2: CSF hypocretin-1 deficiency

Level 2

In the presence of:

criterion 1: Excessive daytime sleepinessa AND
criterion 2: Definite cataplexy AND
criterion 3: Level 1 or 2 MSLT abnormalities

Note: criterion 3 has only been added to add some form of ?objectivity? (without sacrificing sensitivity)

Level 3

In the presence of:

criterion 1: Excessive daytime sleepinessa AND
criterion 2: Level 1 MSLT abnormalities

aExcessive daytime sleepiness

Definition in adults (>= 16 years): An acquired condition, characterised by:

* involuntary sleep episodes during the day
* present almost daily for at least one month

Definition in children (< 16 years):

An acquired condition, characterised by:

* clear increase in daytime sleep episodes
* usually in combination with feelings of subjective sleepiness and impaired concentration
* present almost daily for at least one month

References

1. WHO Global Advisory Committee on Vaccine Safety. Causality assessment following immunisation WER 2001; 76: 85-89 http://www.who.int/docstore/wer/pdf/2001/wer7612.pdf

2. Westchester I. The International Classification of Sleep Disorders: Diagnostic and Coding Manual. 2005, American Academy of Sleep Medicine.

3. Pelin Z, Guilleminault C. HLA-DQB1*0602 homozygosity increases relative risk for narcolepsy but not disease severity in two ethnic groups. US Modafinil in Narcolepsy Multicenter Study Group. Tissue Antigens, 1998. 51(1): p. 96-100.

4. Ton TG, Longstreth WT Jr, Koepsell TD. Environmental toxins and risk of narcolepsy among people with HLA DQB1*0602. Environ Res, 2010. 1160(565-570).

5. Koepsell TD, Longstreth WT, Ton TG. Medical exposure in youth and the frequency of narcolepsy with cataplexy: a population-based case-control study in genetically pre-disposed people. J Sleep Res, 2010. 19 (1 Pt 1): p. 80-86.

6. Longstreth WT, Ton TG. Narcolepsy and streptococcal infections. Sleep, 2009. 32(12): p. 1548.

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9. Aran A, Lin L, Nevsimalova S, Plazzi G, Hong SC, Weiner K, et al. Elevated anti-streptococcal antibodies in patients with recent narcolepsy onset. Sleep, 2009. 32(8): 979-983.

10. National Narcolepsy Task Force Interim Report. 31 January, 2011 http://www.thl.fi/thl-client/pdfs/dc...8-3f774d6d1875

11. EMAs utredning av narkolepsi och Pandemrix fortsatter http://www.lakemedelsverket.se/Alla-...ix-fortsatter/

12. Merecekiene J, on behalf of the VENICE Consortium. Overview of pandemic A(H1N1) 2009 influenza vaccination in Europe. Preliminary results of survey conducted by VENICE, 2010. Presentation ESCAIDE Conference Lisbon November 13th 2010 http://ecdc.europa.eu/en/ESCAIDE/ESC...Mereckiene.pdf

13. Recommended viruses for influenza vaccines for use in the 2010-2011 northern hemisphere influenza season. Wkly Epidemiol Rec. 2010;85(10):81-92. Available from: http://www.who.int/wer/2010/wer8510.pdf

14. Nokleby H, Nicoll A. Risk groups and other target groups ? preliminary ECDC guidance for developing influenza vaccination recommendations for the season 2010-11. Euro Surveill. 2010;15(12):pii=19525. Available from: http://www.eurosurveillance.org/View...rticleId=19525

15. European Medicines Agency Product Pandemrix product characteristics (Updated October 2010) http://www.ema.europa.eu/docs/en_GB/...C500038121.pdf

16. Pebody R, Hardelid P, Fleming DM, McMenamin J, Andrews N, Robertson C, et al. Effectiveness of seasonal 2010/11 and pandemic influenza A(H1N1)2009 vaccines in preventing influenza infection in the United Kingdom: mid-season analysis 2010/11 . Euro Surveill. 2011;16(6):pii=19791. Available online: http://www.eurosurveillance.org/View...rticleId=19791

17. Castilla J, Mor?n J, Mart?nez-Artola V, Reina G, Mart?nez-Baz I, Garc?a Cenoz M, et al. Effectiveness of trivalent seasonal and monovalent influenza A(H1N1)2009 vaccines in population with major chronic conditions of Navarre, Spain: 2010/11 mid-season analysis. Euro Surveill. 2011;16(7):pii=19799. Available online: http://www.eurosurveillance.org/View...rticleId=19799

18. Valenciano M, Kissling E, Cohen J-M, Oroszi B, Barret AS, Rizzo C, et al. Estimates of Pandemic Influenza Vaccine Effectiveness in Europe, 2009?2010: Results of Influenza Monitoring Vaccine Effectiveness in Europe (I-MOVE) Multicentre Case-Control Study. Plos Medicine PLoS Med 8(1): e1000388. doi:10.1371/ journal.pmed.1000388

* ECDC and the national collaborators of the VENICE-II Programme (Vaccine European New Integrated Collaboration Effort) produce annual surveys of vaccination policies and performance in EU/EEA countries.

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