H1N1 Associated with Narcolepsy among Children and Adolescents - Research Paper Example

Is H1N1 Associated with Narcolepsy among Children and Adolescents? Executive Summary Due to the upsurge of the cases of narcolepsy among children and adolescents during the outbreak of the pandemic H1N1 across European and Asian nations around 2009-2010, investigations regarding the possible connection between the vaccine Pandemrix and the increase of narcolepsy cases among countries that issued vaccination sessions among patients 19 years of age and below. Countries in the European Union (EU) such as Finland, France, Germany, Sweden, Denmark, the Netherlands, Ireland, the United Kingdom, Norway, Denmark and Italy were able to conduct their own studies regarding the relationship between the increase in the cases of narcolepsy cases within the country and the vaccinations against H1N1 done within the last ten years. China, an Asian country that also had the pandemic conducted similar studies, and acquired similar results, with most of the narcolepsy cases connected to numerous vaccinations done to young patients as well. All of the studies in the report were able to generate data that shows at least five to fifteen-fold increases in the narcolepsy cases around the year 2009 as compared to previous cases recorded in the last 10-15 years. Narcolepsy is a sleeping disorder that causes a person to suddenly and unexpectedly fall asleep. The disease is characterized by the sudden and unexpected onset of uncontrollable and excessive daytime sleepiness (EDS), drowsiness and grogginess in an individual, episode of muscle weakness (cataplexy), sleep paralyses and hallucinations resulting from rapid-eye movements (REM) and being unable to sleep during the night. It can be triggered either singly by genetic or environmental factors, or the combination of both. Problems may arise when a narcoleptic person suddenly falls asleep in the middle of doing daytime activities such as work or travel, and may cause fatalities if the disease is not taken care of immediately. Because narcolepsy itself is a very rare disease, occurring in roughly 1 out of every 100,000 persons within the world’s population, the sudden increase in the affected people and the recorded narcolepsy cases by up to 8.1 out of every 100,000 persons, as well as observing the occurrence of the phenomenon during the outbreak of the H1N1 pandemic around 2009-2010 caused panic and alarm regarding the use of the H1N1 vaccine Pandemrix, especially among younger children and adolescents. While the split, inactivated virion component of the vaccine was not directly involved in the increase of narcolepsy cases, the studies included in this report create a connection between the use of an oil-based adjuvant, AS03 in the manufacturing of the vaccine, and this may well have been the environmental trigger for the rise in narcolepsy cases among ages 19 years old and below. However, the studies also recommended further investigations regarding the use of AS03 in the medication, as well as the controlled use of Pandemrix among young individuals. Thus, the studies mentioned in this report all agreed in the suggested revising of the guidelines and the administration of the Pandemrix vaccine among adolescents and young children so as to prevent further additional cases of narcolepsy among the younger generation. Introduction The onset of the H1N1 pandemic during 2009 to 2010 has caused widespread panic among many individuals, especially among the developed and densely-populated countries. In order to protect all members of each country’s population against the fatal flu virus, H1N1 vaccines such as Pandemrix adjuvanted with AS03 was developed from inactivated H1N1 virion particles, and was later administered in order to prevent the progression of the disease and deaths, especially among young and elderly members of the population, as well as the severely immune-compromised (Nohynek 1). The vaccine became available to most countries around the globe around the last quarter of 2009, and was administered to nearly 39 million individuals within the European Union, and in the year after another 46 million people became vaccinated. Other vaccine brands such as Celvapan and Focetria became available as seasonal flu shots in order to sparingly use Pandemrix due to initial side-effects such as drowsiness or narcolepsy, but it eventually became a substitute vaccine when Celvapan and Focetria were unavailable during flu season (European Centre for Disease Prevention and Control, ECDC 1). Narcolepsy is considered to be a rare sleep disorder that occurs roughly at a rate of 1 person per 100,000 worldwide (Narcolepsy Study Steering Committee, NSSC 9). Its causes are mostly unknown, but are narrowed down to genetic and environmental factors. For the genetic basis of narcolepsy, the gene that is commonly associated with the sleep order is the human leukocyte antigen (HLA) gene, mainly the sequences are HLA-DQA1*0102 or HLA-DAB1*0602 allele, both of which decrease the production of hypothalamic hypocretin (orexin) as well as the low levels of CSF-hypocretin-1, causing some of the typical symptoms of narcolepsy (Han 410; Partinen 2). Other possible genetic bases of the development of narcolepsy is the formation of anti-tribbles 2 antibodies and the genetic associations with T-cell receptor alpha and the P2RY11 receptor loci, wherein the detection of such antibodies among narcolepsy sufferers suggests that autoimmune diseases may also play a role in the development of the disease by targeting and affecting hypocretin neurons (Han 410; Partinen 2). With regards to the environmental aspect of the disease, the presence of certain Streptococcus pyogenes – specific antibodies like antistreptolysin O (ASO) that might have occurred either before or after the vaccination of anti-flu shots suggest that narcolepsy might be triggered with the formation of such antibodies (ECDC 13; Han 411). The most recently looked-into reason for the development of narcolepsy among the younger members of the population is the use of Pandemrix as anti-flu shots, and while the active ingredient itself, the inactivated H1N1 virion particles may not be the main reason for the disease development, the oil-based adjuvant AS03 is seen as a possible cause for the development of narcolepsy, although it may also be a multi-factorial event that needs to be studied and proved even further (Nohynek 8). It can be inferred that based on the studies used in this report, the hypothesis that aside from the genetic bases of narcolepsy the adjuvant AS03 also poses as a possible trigger in the onset of narcolepsy among patients 19 years old and below, which strengthens the need to limit the administration of the Pandemrix vaccines to the said age group, as well as to investigate the molecular and biological effects of the adjuvant to the leukocyte and hypocretin receptors in the body. The increase in the number of individuals that have been vaccinated by Pandemrix also saw the increase in the incidences of some becoming narcoleptic, especially during the initial release of the drug (Committee for Medicinal Products for Human Use, CHMP 2). In Sweden, 71 cases of narcolepsy that occurred among individuals aged 4-19 years were recorded in 2009-2010, and of these 67 were confirmed to have been suffering from narcolepsy (Nohynek 4). A media scare succeeding the increase in cases of narcolepsy among adolescents and children after being administered with Pandemrix came out even before the final results of the study were published, which caused alarm with the use of the vaccine among younger children. However, this also alerted other nearby countries such as Finland in reviewing the effects of Pandemrix among the young members of the population, as well as drafting some suggested changes in the target population of the medicine (CHMP 2). Other countries that made surveillances in the increase of reported cases of narcolepsy were France, Germany, Ireland, Norway, and the United Kingdom (UK), and the results that were obtained also generated an age-specific range of patients that developed narcolepsy around the time when Pandemrix was made public, as well as noticing that the cases were not related to batch date releases but more on the total effects of the drug as a whole (2-3). China followed suit, after 182 patients developed narcolepsy after the October 2009 vaccinations of Pandemrix in Beijing, China (Han 410). After the release of the results of the studies that were conducted between the 2009-2010 vaccination sessions in some key countries were assimilated, further plans of continuing the research regarding the effects of the adjuvant AS03 on the development of narcolepsy among the adolescent and school-aged children who previously received Pandemrix shots were to be set (415). This was done in order to strengthen or disprove the hypothesis that the adjuvant AS03 increases the disruption of the receptors of patients with HLA-DQA1*0102 or HLA-DAB1*0602 alleles, which further increases the chances of said patients in developing narcolepsy under the premise of being vaccinated by Pandemrix. Probing into the molecular basis of how the adjuvant could affect the hypocretin receptors and in turn cause narcolepsy, additional advisories regarding careful administration of Pandemrix among adolescents and children would be implemented properly and promptly among numerous medical personnel that give the vaccine to many people, especially during flu season. Thus, this report aims to provide the evidences by various studies from the European Union (EU) and China with regards to the connection between the administration of Pandemrix vaccines to young people 19 years old and below, as well as to devise a standard set of procedures that aim to minimize of limit the control of giving vaccines to susceptible individuals in the population, thereby decreasing further the cases of narcolepsy among adolescents and children. Presentation of the Evidences This report utilizes seven observational studies that aim to clarify the connections between the administration of Pandemrix to adolescents and children and the increase of narcolepsy cases in countries that had vaccination sessions during the years 2009-2010, with one study coming from China and the six studies coming from key countries in the EU. Due to the increase in the cases of narcolepsy, people from the medical field started to become alarmed to the possible effects of H1N1 vaccine administration to all individuals, and studies were able to show that the age range that had increased cases of narcolepsy were from ages 19 years old and below. Each study conducted were able to generate nearly similar results, thus the studies concluded that there were indeed some connections between the rise in the narcolepsy cases among young children and adolescents, as well as the increase in the number of people from this age group that get vaccinated by Pandemrix. The MPA or Medical Products Agency in Sweden was one of the first to observe the possible connections between the Pandemrix vaccinations and the occurrence of narcolepsy in young children and adolescents. As of mid-October 2009 to March 2010, there were around 6 million people that received the H1N1 vaccine Pandemrix (Medical Products Agency, MPA 1). While the vaccinations occurred around October 2009 to March 2010, the increase in the cases of adolescents and children only became more apparent around the spring of 2010, which caused widespread alarm not just within Sweden but also in other countries that use Pandemrix for seasonal flu shots. Roughly 1.25 million people younger than 20 years of age were recorded to have been given the H1N1 vaccine, and this number was used in order to provide estimates for the percent increase in the narcolepsy cases in Sweden (MPA 4). The study discovered that the median age for vaccine recipients was around 3-19 years, and that symptoms were noticed to have occurred during the first month after receiving the vaccination (MPA 6). Also, the hypocretin levels of the patients that received the vaccine and developed narcolepsy were mostly below the minimum detection limit of 10pg/ml, and that the genotype HLA-DQB1*0602, which has a strong tendency to develop the disease was present in roughly 96% of the sample size. The increase in the risk for increased narcolepsy levels were apparent after the October 2009 vaccinations, and that during the first three months after the vaccination took place, the risk of developing narcolepsy increased by up to 22 per 100,000, while the incidences after the first three months were around 14.1 per 100,000, suggesting that the vaccine increases the risks for vaccinated individuals to develop symptoms for narcolepsy (7). Lastly, the study found out that while within the study cohort, all narcoleptics had EDS, all of the patients that also had the vaccine developed cataplexy, while those which were narcoleptic but not vaccinated by Pandemrix did not have it, which further implicates the effects of the vaccine in the development of the narcolepsy symptoms. Most of the information that were initially generated by the MPA study were also present in the other studies, as the MPA handled one of the first few researches that found a possible connection between the rise in the vaccination sessions of Pandemrix and the increase in the cases of narcolepsy among ages 19 and below. This gives them credit for initiating further studies in order to find the link between the increases of narcolepsy in the general population, as well as creating measures to prevent misuse of frequent vaccinations of the H1N1 vaccine to younger patients. While the whole study did accept that it had weaknesses due to the bias in terms of the selection of the cohort for the study, a pending statistic on the narcolepsy cases in Sweden, as well as the lack of completeness in the case inventories of most vaccinated individuals, the study also mentioned its strengths, such as the meticulous scrutiny of the medical records by independent clinical experts, and that the possible cases were extracted from previous registries, which were very helpful in tracing which individuals were possible subjects for the study (MPA 8). However, the study would have benefited greatly by having a larger sample size, as well as including other areas in Sweden that also have recorded cases of narcolepsy occurring after vaccinations of Pandemrix. The Committee for Medicinal Products for Human Use, or CHMP also conducted studies regarding the possible links between the increases in the reported cases of narcolepsy among the ages below 20 years old and the large number of people that were vaccinated against the H1N1 flu strain. Key countries that generated the information for data assimilation in the study were the UK, Norway, Ireland, Germany and France (CHMP 3-4). Similar to the MPA study it also mentioned the genetic and the environmental factors that could trigger narcolepsy symptoms among susceptible patients. However, the study also mentioned the possible method by which the adjuvant AS03 is able to cause narcolepsy to people with the HLA-DQB1*0602 and HLA-DQ11*0102 alleles. The squalene component of AS03 combined with polysorbate 80 during the emulsification process could help in eliciting immune responses, and the added ?-tocopherol increases the immunostimulatory action of the adjuvant, which could possibly explain why patients could develop narcolepsy after getting immunization via Pandemrix (CHMP 11). However, the study did not clearly discuss further upon this mechanism, and the proponents concluded that other observational studies of vaccinated populations be conducted outside the EU, as well as performing in vivo tests on transgenic animals, mainly those which express the HLA-DQB1*0602 and HLA-DQ11*0102 alleles (12). The study also prepared a risk management plan for medical practitioners in the administration of Pandemrix, as well as some of the recorded and needed-to-be-proved side effects of the drug (13-17). This initiated the Vaccine Adverse Event Surveillance and Communication (VAECO) to conduct consortium studies in some countries of the EU, and some of them also generated nearly similar results. The study concluded that the revised indication of the use of Pandemrix as an alternative vaccine should seasonal vaccines for influenza ran out in hospitals was added to the guidelines, as well as in its regulated use among individuals aged 19 and below be indicated in the guidelines for Pandemrix use, and also suggested that further studies with regards to the connection between narcolepsy and Pandemrix in the future (21-22). The CHMP study was able to generate sufficient data that would allow medical personnel to check their records and see if it was indeed the H1N1 vaccine that may have caused the increase in the narcolepsy cases in some areas. However, because the final paper did mostly a summarization of the similarities of results in only a few countries in the EU, it would have been better if the paper discussed the results of the cohort studies in these countries further, such as mentioning the discrepancies of the results or the time frame when the studies were conducted. Still, the paper had plus points for showing the consistencies of the age groups that were most affected by the vaccine, thereby increasing the proof of Pandemrix having increased effects among the young age groups. In relation to the EU studies of CHMP, other researches such as the Finland cohort studies conducted nearly at the same time with the Sweden cohort studies was also included in this report and generated some results that showed some data with the highest preliminary peaks regarding the connection of numerous narcolepsy cases and vaccinations, which also initiated the immediate campaign to regulate Pandemrix among younger individuals (CHMP 18-19), in which the results of those studies shall be discussed. Two related researches in Finland that conducted sleep studies as well as kept records to assess the effects of Pandemrix in younger individuals were conducted in the beginning of 2010, after an upsurge of narcolepsy cases among children were observed (Nohynek 2; Partinen 2). The studies were able find an increase of 12.7-fold risk of narcolepsy in 4-19-year-olds (Nohynek 6) after performing multiple sleep latency tests (MSLT) and analyzing the cerebrospinal fluid hypocretin-1 of the identified HLA children which had the Pandemrix vaccine (Partinen 2-4). It was also found out that the subjects did not have previous histories of narcolepsy, and became affected by it at an average of 38 days after vaccination, which nearly coincides with the studies conducted in Sweden (7). The cause for alarm heightened when the cases for narcolepsy among adults did not significantly change, indicating that the age group of 19 years and below were rather susceptible to the effects of the vaccine (8). Also, it was observed that because the HLA alleles were much more common in northern EU countries compared to the south, the number of narcolepsy cases recorded in Sweden and Finland were much more profound than others, including studies from outside the EU (Nohynek 8; Partinen 8). However, the relation between the AS03 adjuvant and the triggering of narcoleptic symptoms were still not fully established at this point, other than the possibility that Pandemrix could trigger immunological responses that could result in the patients developing narcoleptic symptoms without any possibilities of molecular mimicry, and further studies were warranted to support the possible roles of AS03 in the introduction of the disorder among young patients, especially since such adjuvants are necessary to increase the immune responses among the vaccinated populations (Nohynek 8). The two studies were fairly reliable, especially due to the ease in finding hospital records of individuals in Finland, as well as the members of the research team capable of scrutinizing each record for its inclusion in the study. While the study may have inadvertently included some narcolepsy cases that were already present despite the vaccination, the researchers were able to increase possibilities of autoimmune responses that could increase due to the presence of potent adjuvants in the vaccine, thus increasing awareness and initiating restrictions in the use of Pandemrix among individuals 19 years of age and below, further strengthening the need for the vaccine’s restriction in other countries. While the previous four studies had a rough estimate of the occurrences of narcolepsy in the populations, a study conducted by the Narcolepsy Study Steering Committee (NSSC) in Ireland only recently noticed the changes in the number of afflicted individuals after the issuance of the Pandemrix vaccine in the height of the H1N1 pandemic. The study was able to tackle other information that were previously discussed in the other four reports, but is was also able to add information with regards to the percentage of the HLA alleles in the populations within the EU countries, with the northern regions having 25%-28% of the population having the allele, and the genetic risk decreasing to 4-13% of the population at the southern parts of EU (NSSC 10). While the incidence of adult narcolepsy did not change much for the age group of adolescents and children the incidences reached up to 88% in the sample population, and half of these were detected positive for the HLA alleles, which suggest that their narcolepsy was triggered by the vaccine (25). The Ireland study of Pandemrix and narcolepsy was able to correlate their results with the previously published studies regarding the effects of the H1N1 vaccine and the onset of the sleep disorder among young individuals, however the very small sample size (n=25) may not be sufficient enough to back up the results, thus further studies are needed to establish the validity of the results. After the release of the initial data that pertains to the possible effects of Pandemrix in the increase of the narcolepsy cases among children and adolescents, the European Center for Disease Prevention and Control (ECDC) conducted a larger multi-country study and released their results in September 2012. With the support of VAECO, results showed that despite the rise in the incidences in the cases for narcolepsy in some EU countries, Finland and Sweden generated higher rates due to the high percentage of the population having the HLA alleles, designating them as the signaling countries, while the UK, Denmark, Italy, France, the Netherlands and Norway had lower, though increased rates of narcolepsy in the susceptible populace, thus labeling them as non-signaling countries (ECDC 146). It was further mentioned in the study that due to the larger populace in the study, it was much harder to track the individuals and the onset of the narcolepsy in accordance with the beginning of the vaccination periods in the six countries, as well as the possibilities of miscalculations and incorrect designations of the patients, in addition to media pressure and censorship of the issue (144-145). While the study was able to show that some countries were much more susceptible to the effects of Pandemrix, due to its inability to access patient records promptly and completely, it could only provide a rough image of which countries would either show high or susceptibility to the vaccine, as well as further investigations in other countries that were not included in the cohort studies. The last study in this report is a case of an increase of narcoleptic patients in a public hospital in Beijing. It produced results which may be comparable to the previous studies, such as the seasonal onset of narcolepsy after the October 2009 vaccinations started, as well as the possibility that the adjuvants used in the Pandemrix vaccines could have triggered the onset of symptoms among young children and adolescents (Han 416). However the fact that it only focused on one hospital alone indicates that the sample population was highly-biased in comparison with the EU studies, even though it has roughly 600 patients for subjects (n=629). Also, it was harder to track as to whether the narcolepsy was indeed caused by the vaccine or by other factors themselves, due to the 5-7month delays in the onset of the disease (410). Thus the study still needs to be reviewed, as well as providing a wider range of sample populations to make the results even more conclusive. Discussion The findings in the seven studies are mostly similar, which makes it easy to summarize all of the findings into a few points: Vaccinations of Pandemrix started from October 2009 up to March of 2010 in the key countries, and the increase in the narcolepsy cases started out as early as the end of 2009 and were still noticeable until the middle of 2010, long after the flu season has subsided Most of the narcolepsy cases involved children and adolescents, thus encompassing the age group of 19 years of age and below. Sweden and Finland had the most cases attributed to the increase in the vaccinations of Pandemrix among younger individuals, giving the two countries a designation of signaling countries. Other countries also had an increase, but not as profound, marking the rest as non-signaling countries. One possible cause of narcolepsy may be traced to the presence of the HLA-DAB1*0602 allele in some members of the susceptible population, which decreases the production of hypocretin, further allowing the symptoms of narcolepsy to develop. Another possible cause for the increase would be the adjuvant added to increase immunoresponse within the body, in this case the AS03 in Pandemrix that triggers the decrease in the production of hypocretin, further increasing the narcolepsy symptoms among vaccinated patients. Restrictions or limitations in the administration of Pandemrix must be done to observe whether the cases of narcolepsy would indeed decrease or remain the same, as well as finding out exactly how AS03 could possibly trigger the disorder using molecular and transgenic studies. The six points were mostly present in the seven observational studies used for this report, which makes the generated data much more reliable. Despite the various geographical locations of the studies and the high variability of the gene pools for each sampled population did not affect the results much, except for the Finnish and Swedish studies, due to the high percentage of people having the HLA alleles. Also, because the various results from various countries have some degree of similarities imply that the possible effect of the Pandemrix vaccine, or theAS03 adjuvant added to it must be the potent ingredient, it is thus needed to be looked upon further to strengthen the claims that the vaccine or the adjuvant indeed causes the narcolepsy. While the main hypothesis of the studies that the adjuvant is able to trigger the onset of the disease, because most of the studies did not focus on the molecular aspects of this possible disorder trigger, and it would be hard to simply rely on the statistics presented by the seven studies. Still, the correlation is fairly enough to warrant further research on the effects of AS03. Another strong point in the connection of the vaccine and the rise in narcolepsy cases is that the increase in the sleep disorder cases only happened after the release of the Pandemrix vaccine, and that because narcolepsy in itself is a fairly rare disease that occurs at a low rate, a strong correlation between the upsurge of the narcolepsy and the large number of immunizations that happened beginning from October of 2009 can easily be made through the results. Conclusion and Recommendations Based on the collected information in the seven studies used in this report, it can be concluded that children and adolescents are susceptible in developing narcolepsy after getting a Pandemrix vaccine. This may further be increased due to inherent factors like HLA alleles that become triggered by the AS03 adjuvant. However, some countries such as Finland and Sweden have higher rates of narcolepsy due to a large percentage of the population, up to 28% having the HLA alleles, and the increase in the narcolepsy cases may be attributed to this while in other countries the populace may not have such tendencies in developing the disorder due to the low penetrance of the HLA genotype. Still, the studies concluded that aside from establishing the possible effects of AS03 in the development of narcolepsy, vaccine restrictions and risk management and assessments must also be made to prevent the increase of the disorder among young individuals in the future. It is possible that the vaccine may have strong effects to the individuals aged 19 years and below, especially to those that tested positive for the HLA allele, thus further restrictions or limitations in the vaccinations of Pandemrix to this age group must be made, only responding to the need should an outbreak occurred in the area. Also, the use of Pandemrix as a substitute for trivalent seasonal anti-influenza vaccines must be avoided to further increase possible narcolepsy cases in the future. Lastly, if the cases of narcolepsy did increase in certain areas, aside from attributing the causes from the vaccines, the patients could also get genetic tests to find out if they are already susceptible in developing the disorder by having the HLA alleles. Thus, aside from making risk management and assessments in the administration of Pandemrix vaccines among the target age group, before giving the H1N1 vaccine to young patients all possible narcolepsy factors must first be taken into account, so as to avoid the unnecessary increases in the cases of child and adolescent-onset narcolepsy in later years. Works Cited Committee for Medicinal Products for Human Use. Pandemrix. Assessment Report. London: European Medicines Agency, 2011. Print. European Centre for Disease Prevention and Control. Narcolepsy in association with pandemic influenza vaccination (a multi-country European epidemiological investigation). Technical Report. Stockholm: European Centre for Disease Prevention and Control, 2012. Print. Han, Fang; Lin, Ling; Warby, Simon C.; Faraco, Juliette; Li, Jing; Dong, Song X.; An, Pei; Zhao, Long; Wang, Ling H.; Li, Qian Y.; Yan, Han; Gao, Zhan C.; Yuan, Yuan; Strohl, Kingman P.; Mignot, Emmanuel. "Narcolepsy is Seasonal and Increased following the 2009 H1N1 Pandemic in China." Annals of Neurology (2011): 70(3): 410-417. Print. Medical Products Agency. "Narcolepsy - Case Inventory Study in Sweden 2009-2010." Case Inventory Study. 2011. Print. Narcolepsy Study Steering Committee. "Investigation of an increase in the incidence of narcolepsy in children and adolescents in 2009 and 2010." Final Report. 2011. Print. Nohynek, Hanna; Jukka, Jokinen; Partinen, Markku; Vaarala, Outi; Kirjavainen, Turkka; Sundman, Jonas; Himanen, Sari-Leenen; Hublin, Christer; Julkunen, Ilkka; Olsen, Paivi; Saarenpaa-Heikkila, Outi; Kilpi, Terhi. "AS03 Adjuvanted AH1N1 Vaccine Associated with an Abrupt Increase in the Incidence of Childhood Narcolepsy in Finland." PLoS One (2012): 7(3): e33536 1-9. Print. Partinen, Markku; Saarenpaa-Heikkila, Outi; Ilveskosky, Ismo; Hublin, Christer; Linna, Miika; Paivi, Olsen; Nokelainen, Pekka; Alen, Reija; Wallden, Tiina; Espo, Merimaaria; Rusanen, Harri. "Increased Incidence and Clinical Picture of Childhood Narcolepsy Following the 2009 H1N1 Pandemic Vaccination Campaign in Finland." PLoS One (2012): 7(3): e33723 1-9. Print. Read More