New 2013 incidence peak in childhood narcolepsy: more than vaccination?

SLEEP ◽  
2020 ◽  
Author(s):  
Zhongxing Zhang ◽  
Jari K Gool ◽  
Rolf Fronczek ◽  
Yves Dauvilliers ◽  
Claudio L A Bassetti ◽  
...  
Keyword(s):  
De Novo ◽  
Influenza Pandemic ◽  
Disease Onset ◽  
Fold Increase ◽  
H1n1 Influenza ◽  
Incidence Rates ◽  
Influenza Viruses ◽  
Smoothing Methods ◽  
Immune Mediated ◽  
Data Driven Modeling

Abstract Increased incidence rates of narcolepsy type-1 (NT1) have been reported worldwide after the 2009–2010 H1N1 influenza pandemic (pH1N1). While some European countries found an association between the NT1 incidence increase and the H1N1 vaccination Pandemrix, reports from Asian countries suggested the H1N1 virus itself to be linked to the increased NT1 incidence. Using robust data-driven modeling approaches, that is, locally estimated scatterplot smoothing methods, we analyzed the number of de novo NT1 cases (n = 508) in the last two decades using the European Narcolepsy Network database. We confirmed the peak of NT1 incidence in 2010, that is, 2.54-fold (95% confidence interval [CI]: [2.11, 3.19]) increase in NT1 onset following 2009–2010 pH1N1. This peak in 2010 was found in both childhood NT1 (2.75-fold increase, 95% CI: [1.95, 4.69]) and adulthood NT1 (2.43-fold increase, 95% CI: [2.05, 2.97]). In addition, we identified a new peak in 2013 that is age-specific for children/adolescents (i.e. 2.09-fold increase, 95% CI: [1.52, 3.32]). Most of these children/adolescents were HLA DQB1*06:02 positive and showed a subacute disease onset consistent with an immune-mediated type of narcolepsy. The new 2013 incidence peak is likely not related to Pandemrix as it was not used after 2010. Our results suggest that the increased NT1 incidence after 2009–2010 pH1N1 is not unique and our study provides an opportunity to develop new hypotheses, for example, considering other (influenza) viruses or epidemiological events to further investigate the pathophysiology of immune-mediated narcolepsy.

scholarly journals A new incidence peak of childhood narcolepsy type 1 in 2013: a new perspective on the role of influenza virus?

2020 ◽  
Author(s):  
Zhongxing Zhang ◽  
Jari Gool ◽  
Rolf Fronczek ◽  
Claudio L. Bassetti ◽  
Yves Dauvilliers ◽  
...  
Keyword(s):  
De Novo ◽  
Influenza Pandemic ◽  
Disease Onset ◽  
H1n1 Influenza ◽  
Incidence Rates ◽  
Influenza Viruses ◽  
Immune Mediated ◽  
New Perspective

AbstractIncreased incidence rates of narcolepsy type 1 (NT1) after the 2009-2010 H1N1 influenza pandemic (pH1N1) have been reported world-wide. While some European countries found an association between the NT1 increase and H1N1 vaccination Pandemrix, reports from Asian countries suggested the H1N1 virus rather than Pandemrix to be linked with the increase of new NT1 cases. We analyzed the number of de-novo NT1 cases in the last two decades until 2016 using the European Narcolepsy Network (EU-NN) database. Using robust data-driven modelling approaches we confirmed the peak of NT1 incidence in 2009-2010 pH1N1 and identified a new peak in 2013 that is age-specific for children/adolescents. Most of these de-novo cases showed a subacute disease onset consistent with an immune-mediated type of narcolepsy, which is most likely not related to Pandemrix vaccination that was used in 2009-2010, but may have been triggered by some new epidemiological event in Europe. Our finding of an unexpected peak in de-novo children narcolepsy in 2013 provides a unique opportunity to develop new hypotheses, such as considering other (influenza) viruses to further investigate the pathophysiology of immune-mediated narcolepsy.

scholarly journals Natural Variation Can Significantly Alter the Sensitivity of Influenza A (H5N1) Viruses to Oseltamivir

2006 ◽  
Vol 50 (11) ◽  
pp. 3809-3815 ◽  
Author(s):  
M. A. Rameix-Welti ◽  
F. Agou ◽  
P. Buchy ◽  
S. Mardy ◽  
J. T. Aubin ◽  
...  
Keyword(s):  
Influenza A ◽  
Influenza Pandemic ◽  
Fold Increase ◽  
Influenza Viruses ◽  
Control Measures ◽  
Inhibition Assay ◽  
Highly Pathogenic ◽  
H5n1 Influenza ◽  
The Impact

ABSTRACT Geographic spread of highly pathogenic avian H5N1 influenza viruses may give rise to an influenza pandemic. During the first months of a pandemic, control measures would rely mainly on antiviral drugs, such as the neuraminidase (NA) inhibitors oseltamivir and zanamivir. In this study, we compare the sensitivities to oseltamivir of the NAs of several highly pathogenic H5N1 viruses isolated in Asia from 1997 to 2005. The corresponding 50% inhibitory concentrations were determined using a standard in vitro NA inhibition assay. The Km for the substrate and the affinity for the inhibitor (Ki ) of NA were determined for a 1997 and a 2005 virus, using an NA inhibition assay on cells transiently expressing the viral enzyme. Our data show that the sensitivities of the NAs of H5N1 viruses isolated in 2004 and 2005 to oseltamivir are about 10-fold higher than those of earlier H5N1 viruses or currently circulating H1N1 viruses. Three-dimensional modeling of the N1 protein predicted that Glu248Gly and Tyr252His changes could account for increased sensitivity. Our data indicate that genetic variation in the absence of any drug-selective pressure may result in significant variations in sensitivity to anti-NA drugs. Although the clinical relevance of a 10-fold increase in the sensitivity of NA to oseltamivir needs to be investigated further, the possibility that sensitivity to anti-NA drugs could increase (or possibly decrease) significantly, even in the absence of treatment, underscores the need for continuous evaluation of the impact of genetic drift on this parameter, especially for influenza viruses with pandemic potential.

scholarly journals H1N1 INFLUENZA VERSUS SEASONAL INFLUENZA MORBIDITY AND MORTALITY: A PROSPECTIVE STUDY IN AL-KINDY TEACHING HOSPITAL/ IRAQ-BAGHDAD

2016 ◽  
Vol 12 (2) ◽  
pp. 18-21
Author(s):  
Ismail A. Hussain AL-Ameri ◽  
Baker Fadel ◽  
Ali Sajid ◽  
Imad Kareem
Keyword(s):  
Teaching Hospital ◽  
Seasonal Influenza ◽  
Influenza Pandemic ◽  
Age Groups ◽  
H1n1 Influenza ◽  
Influenza Viruses ◽  
Morbidity And Mortality ◽  
Severe Illness ◽  
Wide Range ◽  
Symptoms And Signs

Background: H1N1 influenza pandemic or swine flu was an influenza pandemic first described in Iraq in October 2009 .The virus appeared to be anew strain of H1N1 causes wide range of morbidity and mortality among different genders and age groups as part of worldwide pandemics.Seasonal flu is a contagious respiratory illness caused by influenza viruses that infect the nose, throat, and lungs. It can cause mild to severe illness, and at times can lead to death. The best way to prevent the flu is by getting a flu vaccine each year. Objectives: Is to determine the morbidity and mortality in different age groups in patients with H1N1 influenza versus those patients with seasonal influenza who were admitted at the same time to AL-kindy teaching hospital during pandemic 2009. Type of the study: A retrospective observational study. Methods: A total number of 210 cases with influenza symptoms and signs were included in this study which was conducted at AL-kindy teaching hospital , Baghdad, Iraq at inpatient medical wards over a period from October to December 2009. All cases were tested by real time PCR for H1N1 influenza virus by taking nasal and throat swab in addition to monitoring symptoms and signs of influenza and chest radiographs. Results: Out of 210 cases, 90 (42.85%) cases were positive for H1N1 influenza and 120 (57.14%) cases had negative test are considered having seasonal influenza. Of the positive cases(64.44%) were males and (35.55%) were females. Of negative cases(seasonal flu)male gender were (61.66%) , while female gender were (38.33%). 57.77% of positive cases developed flue like illness compared with 54.16% of negative while 25.55% of positive developed pneumonia compared with 22.5% of negative.5.55% of positive cases developed ARDS compared with 5% only in negative cases.11.11% had different presentation in positive cases (bronchitis ,gastroenteritis) while 18.33%of negative. Mortality in positive cases are 14.4% compared with only 10% in negative cases. Conclusions: Influenza A/H1N1had same symptoms and signs of epidemic seasonal influenza but run aggressive and short course of morbidity in 3-5 days with high percentage of complication and high mortality compared with seasonal epidemic influenza with rare affection above 65 years old, both groups had same incidence of complication with pneumonia and ARDS

scholarly journals The PB2-E627K Mutation Attenuates Viruses Containing the 2009 H1N1 Influenza Pandemic Polymerase

mBio ◽  
2010 ◽  
Vol 1 (1) ◽  
Author(s):  
Brett W. Jagger ◽  
Matthew J. Memoli ◽  
Zong-Mei Sheng ◽  
Li Qi ◽  
Rachel J. Hrabal ◽  
...  
Keyword(s):  
Influenza A Virus ◽  
Influenza A ◽  
H1n1 Virus ◽  
Influenza Pandemic ◽  
Influenza Infection ◽  
H1n1 Influenza ◽  
Influenza Viruses ◽  
Pandemic Virus ◽  
2009 H1n1 ◽  
Animal Reservoirs

ABSTRACTThe swine-origin H1N1 influenza A virus emerged in early 2009 and caused the first influenza pandemic in 41 years. The virus has spread efficiently to both the Northern and the Southern Hemispheres and has been associated with over 16,000 deaths. Given the virus’s recent zoonotic origin, there is concern that the virus could acquire signature mutations associated with the enhanced pathogenicity of previous pandemic viruses or H5N1 viruses with pandemic potential. We tested the hypothesis that mutations in the polymerase PB2 gene at residues 627 and 701 would enhance virulence but found that influenza viruses containing these mutations in the context of the pandemic virus polymerase complex are attenuated in cell culture and mice.IMPORTANCEInfluenza A virus (IAV) evolution is characterized by host-specific lineages, and IAVs derived in whole or in part from animal reservoirs have caused pandemics in humans. Because IAVs are known to acquire host-adaptive genome mutations, and since the PB2 gene of the 2009 H1N1 virus is of recent avian derivation, there exists concern that the pathogenicity of the 2009 H1N1 influenza A pandemic virus could be potentiated by acquisition of the host-adaptive PB2-E627K or -D701N mutations, which have been shown to enhance the virulence of other influenza viruses. We present data from a mouse model of influenza infection showing that such mutations do not increase the virulence of viruses containing the 2009 H1N1 viral polymerase.

scholarly journals Adaptive Mutations That Occurred during Circulation in Humans of H1N1 Influenza Virus in the 2009 Pandemic Enhance Virulence in Mice

2015 ◽  
Vol 89 (14) ◽  
pp. 7329-7337 ◽  
Author(s):  
A. Otte ◽  
M. Sauter ◽  
M. A. Daxer ◽  
A. C. McHardy ◽  
K. Klingel ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Avian Influenza ◽  
Molecular Mechanisms ◽  
Influenza Pandemic ◽  
H1n1 Influenza ◽  
Influenza Viruses ◽  
Pandemic H1n1 ◽  
Adaptive Mutations ◽  
Pandemic H1n1 Influenza ◽  
Viral Hemagglutinin

ABSTRACTDuring the 2009 H1N1 influenza pandemic, infection attack rates were particularly high among young individuals who suffered from pneumonia with occasional death. Moreover, previously reported determinants of mammalian adaptation and pathogenicity were not present in 2009 pandemic H1N1 influenza A viruses. Thus, it was proposed that unknown viral factors might have contributed to disease severity in humans. In this study, we performed a comparative analysis of two clinical 2009 pandemic H1N1 strains that belong to the very early and later phases of the pandemic. We identified mutations in the viral hemagglutinin (HA) and the nucleoprotein (NP) that occurred during pandemic progression and mediate increased virulence in mice. Lethal disease outcome correlated with elevated viral replication in the alveolar epithelium, increased proinflammatory cytokine and chemokine responses, pneumonia, and lymphopenia in mice. These findings show that viral mutations that have occurred during pandemic circulation among humans are associated with severe disease in mice.IMPORTANCEIn this study, novel determinants of 2009 pandemic H1N1 influenza pathogenicity were identified in the viral hemagglutinin (HA) and the nucleoprotein (NP) genes. In contrast to highly pathogenic avian influenza viruses, increased virulence in mice did not correlate with enhanced polymerase activity but with reduced activity. Lethal 2009 pandemic H1N1 infection in mice correlated with lymphopenia and severe pneumonia. These studies suggest that molecular mechanisms that mediate 2009 pandemic H1N1 influenza pathogenicity are distinct from those that mediate avian influenza virus pathogenicity in mice.

scholarly journals Assessing the impact of the 2009 H1N1 influenza pandemic on reporting of other threats through the Early Warning and Response System

2009 ◽  
Vol 14 (45) ◽  
Author(s):  
A Cox ◽  
P Guglielmetti ◽  
D Coulombier
Keyword(s):  
Early Warning ◽  
Influenza Pandemic ◽  
Health Resources ◽  
Fold Increase ◽  
H1n1 Influenza ◽  
The European Union ◽  
Response System ◽  
2009 H1n1 ◽  
The Impact ◽  
H1n1 Influenza Pandemic

Since the start of 2009 H1N1 influenza pandemic, a notable surge in messages communicated through the Early Warning and Response System (EWRS) for the prevention and control of communicable diseases in the European Union has been recorded. In order to measure the impact of this increase on the reporting of other events, we compared the messages posted in the EWRS since April 2009 with those posted in the previous years (2004-2008). The analysis revealed that a ten-fold increase in messages was recorded during the pandemic period, from April to September 2009, and that the reporting of other threats dropped to a significantly low rate. These results suggest an important impact on the notification process of events in case of a situation requiring extensive mobilisation of public health resources. It emphasises the importance keeping an appropriate balancing of resources during sustained emergencies, in particular in view of a possible second wave of pandemic influenza cases, to ensure prompt detection and reporting of potential concomitant emerging threats.

scholarly journals Identification and Characterization of Swine Influenza Virus H1N1 Variants Generated in Vaccinated and Nonvaccinated, Challenged Pigs

Viruses ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 2087
Author(s):  
Álvaro López-Valiñas ◽  
Marta Sisteré-Oró ◽  
Sergi López-Serrano ◽  
Laura Baioni ◽  
Ayub Darji ◽  
...  
Keyword(s):  
Influenza A ◽  
Influenza Pandemic ◽  
Viral Evolution ◽  
Swine Influenza Virus ◽  
Swine Influenza ◽  
H1n1 Influenza ◽  
Influenza Viruses ◽  
Viral Fitness ◽  
Ns1 Protein ◽  
Trivalent Vaccine

Influenza viruses represent a continuous threat to both animal and human health. The 2009 H1N1 A influenza pandemic highlighted the importance of a swine host in the adaptation of influenza viruses to humans. Nowadays, one of the most extended strategies used to control swine influenza viruses (SIVs) is the trivalent vaccine application, whose formulation contains the most frequently circulating SIV subtypes H1N1, H1N2, and H3N2. These vaccines do not provide full protection against the virus, allowing its replication, evolution, and adaptation. To better understand the main mechanisms that shape viral evolution, here, the SIV intra-host diversity was analyzed in samples collected from both vaccinated and nonvaccinated animals challenged with the H1N1 influenza A virus. Twenty-eight whole SIV genomes were obtained by next-generation sequencing, and differences in nucleotide variants between groups were established. Substitutions were allocated along all influenza genetic segments, while the most relevant nonsynonymous substitutions were allocated in the NS1 protein on samples collected from vaccinated animals, suggesting that SIV is continuously evolving despite vaccine application. Moreover, new viral variants were found in both vaccinated and nonvaccinated pigs, showing relevant substitutions in the HA, NA, and NP proteins, which may increase viral fitness under field conditions.

Pandemic influenza A (H1N1) virus infection and avian influenza A (H5N1) virus infection: a comparative analysisThis paper is one of a selection of papers published in this special issue entitled “Second International Symposium on Recent Advances in Basic, Clinical, and Social Medicine” and has undergone the Journal's usual peer review process.

2010 ◽  
Vol 88 (4) ◽  
pp. 575-587 ◽  
Author(s):  
Christine Korteweg ◽  
Jiang Gu
Keyword(s):  
Virus Infection ◽  
Influenza A ◽  
Peer Review Process ◽  
Influenza Pandemic ◽  
H1n1 Influenza ◽  
Influenza Viruses ◽  
Influenza A Viruses ◽  
H5n1 Influenza ◽  
Influenza A H1n1 ◽  
2009 H1n1

The 2009 H1N1 and H5N1 influenza viruses are newly (re-) emerged influenza A viruses (2009 A(H1N1) and A(H5N1), respectively) that have recently posed tremendous health threats in many regions worldwide. With the 2009 outbreak of H1N1 influenza A, the world witnessed the first influenza pandemic of the 21st century. The disease has rapidly spread across the entire globe, and has resulted in hundreds of thousands of cases with confirmed infection. Although characterized by high transmissibility, the virulence and fatality of the 2009 A(H1N1) influenza virus have thus far remained relatively low. The reverse holds true for A(H5N1) influenza; at a fatality rate that exceeds 60%, it is known to cause severe damage to the human respiratory system, but is not presently capable of efficient transmission from human to human. Apart from the clear differences between the two types of influenza, there are some significant similarities that warrant attention. In particular, the more severe and fatal 2009 A(H1N1) influenza cases have shown symptoms similar to those reported in cases of A(H5N1) influenza. Histopathological findings for these cases, to the extent available, also appear to have similarities for both diseases in terms of damage and severity. Here we review important recent publications in this area, and we discuss some of the key commonalities and contrasts between the two influenza A types in terms of their biology, origins, clinical features, pathology and pathogenesis, and receptors and transmissibility.

scholarly journals Transmission of Pandemic H1N1 Influenza Virus and Impact of Prior Exposure to Seasonal Strains or Interferon Treatment

2009 ◽  
Vol 84 (1) ◽  
pp. 21-26 ◽  
Author(s):  
John Steel ◽  
Peter Staeheli ◽  
Samira Mubareka ◽  
Adolfo García-Sastre ◽  
Peter Palese ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Guinea Pigs ◽  
Influenza Pandemic ◽  
H1n1 Influenza ◽  
Influenza Viruses ◽  
Prior Exposure ◽  
Pandemic H1n1 ◽  
H1n1 Strain ◽  
H3n2 Influenza ◽  
The Impact

ABSTRACT Novel swine-origin influenza viruses of the H1N1 subtype were first detected in humans in April 2009. As of 12 August 2009, 180,000 cases had been reported globally. Despite the fact that they are of the same antigenic subtype as seasonal influenza viruses circulating in humans since 1977, these viruses continue to spread and have caused the first influenza pandemic since 1968. Here we show that a pandemic H1N1 strain replicates in and transmits among guinea pigs with similar efficiency to that of a seasonal H3N2 influenza virus. This transmission was, however, partially disrupted when guinea pigs had preexisting immunity to recent human isolates of either the H1N1 or H3N2 subtype and was fully blocked through daily intranasal administration of interferon to either inoculated or exposed animals. Our results suggest that partial immunity resulting from prior exposure to conventional human strains may blunt the impact of pandemic H1N1 viruses in the human population. In addition, the use of interferon as an antiviral prophylaxis may be an effective way to limit spread in at-risk populations.

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