Re: China - H5N1 death in Alberta, Canada upon return from China trip - died from meningoencephalitis
Canadian who died from H5N1 flu may have caught it in illegal bird market
Helen Branswell, The Canadian Press
Published Tuesday, February 11, 2014 1:05PM EST
Last Updated Tuesday, February 11, 2014 1:07PM EST .
...
In a letter to the Journal of Infection, they say that even though Beijing banned live poultry markets in 2005, an illegal trade in live poultry continues in the city. They say it is possible the woman was infected while passing market stalls that surreptitiously sell live poultry.
It is the custom in China to eat chicken when it has been freshly killed, and the sale of live poultry remains common in many parts of the country.
The scientists point to a previous H5N1 case in Beijing, a woman who died in early January 2009. She had bought a live duck at a market in Hebei province, near Beijing, and prepared it for cooking by defeathering it and gutting it.
...
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Re: China - H5N1 death in Alberta, Canada upon return from China trip - died from meningoencephalitis
It seems that a similar H5N1 virus was isolated from a tiger died from infection in a China's zoo last year (see the paper for details).
This strain seems also to belong to a sub-lineage little known so far, but with avian-like signatures and little evidence of mammalian host adaptation.
It is sensitive to neuraminidase inhibitors oseltamivir and zanamivir and to the older adamantanes, since it has not showed the mutations in the NA & M gene segments known to confer resistance to these drugs.
The H5N1 isolated has a polybasic cleavage site in HA and a NS1 aminoacids residues known to increase pathogenicity in humans.
Neurologic complications seen in the infected patient suggested that this virus may behave different and needs further characterization and analysis, concluded the authors.
gm
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Re: Full-Genome Analysis of Avian Influenza A(H5N1) Virus from a Human, North America, 2013 - ex-China
Originally posted by sharon sanders View PostAgain condolences to the Canadian who traveled to China and then died as a result of this illness. Thank you to her family and the governments of Alberta and Canada for sharing this information with the world.
"analysis of each gene of A/Alberta/01/2014 showed that 7 of 8 genes shared ≥99% identity at the nucleotide and protein levels with HPAI A(H5N1) viruses of avian origin. However, the PB2 gene showed 98% nt similarity and 99% aa identity to avian influenza A(H9N2) viruses collected in China."
"No mutations conferring resistance to adamantanes or neuraminidase inhibitors were found."
"Other mutations of interest in A/Alberta/01/2014 were D94N, S133A, S155N, and T156A.....T156A is consistently found in ferret-adapted mutants capable of airborne transmission (5). The collective effects of all these mutations and their phenotypic manifestations are unclear."
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Re: Full-Genome Analysis of Avian Influenza A(H5N1) Virus from a Human, North America, 2013 - ex-China
Again, condolences to the Canadian who traveled to China and then died as a result of this illness. Thank you to her family and the governments of Alberta and Canada for sharing this information with the world. It was widely reported that she had no contact with poultry.
"analysis of each gene of A/Alberta/01/2014 showed that 7 of 8 genes shared ≥99% identity at the nucleotide and protein levels with HPAI A(H5N1) viruses of avian origin. However, the PB2 gene showed 98% nt similarity and 99% aa identity to avian influenza A(H9N2) viruses collected in China."
"No mutations conferring resistance to adamantanes or neuraminidase inhibitors were found."
"Other mutations of interest in A/Alberta/01/2014 were D94N, S133A, S155N, and T156A.....T156A is consistently found in ferret-adapted mutants capable of airborne transmission (5). The collective effects of all these mutations and their phenotypic manifestations are unclear."
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China - H5N1 death in Alberta, Canada upon return from China trip - died from meningoencephalitis
Volume 20, Number 5?May 2014
Dispatch
Full-Genome Analysis of Avian Influenza A(H5N1) Virus from a Human, North America, 2013
Article Contents
- Case Report and Laboratory Investigations
- Conclusion
- Acknowledgment
- References
- Figure 1
- Figure 2
- Technical Appendix 1 - 57 KB
- Technical Appendix 2 - 974 KB
- Suggested Citation
Kanti Pabbaraju, Raymond Tellier, Sallene Wong, Yan Li, Nathalie Bastien, Julian W. Tang, Steven J. Drews, Yunho Jang, C. Todd Davis, Kevin Fonseca , and Graham A. Tipples
Author affiliations: Provincial Laboratory for Public Health, Calgary, Alberta, Canada (K. Pabbaraju, R. Tellier, S. Wong, J.W. Tang, S.J. Drews, K. Fonseca, G.A. Tipples); Public Health Agency of Canada, Winnipeg, Manitoba, Canada (Y. Li, N. Bastien); Centers for Disease Control and Prevention, Atlanta, Georgia, USA (Y. Jang, C.T. Davis); University of Calgary, Calgary (R. Tellier, K. Fonseca, S.J. Drews); University of Manitoba, Winnipeg (Y. Li); and University of Alberta, Edmonton, Alberta, Canada (J.W. Tang, G.A. Tipples)
Suggested citation for this article
Abstract
Full-genome analysis was conducted on the first isolate of highly pathogenic avian influenza A(H5N1) virus from a human in North America. The virus has a hemagglutinin gene of clade 2.3.2.1c and is a reassortant with an H9N2 subtype lineage polymerase basic 2 gene. No mutations conferring resistance to adamantanes or neuraminidase inhibitors were found.
Since the 1997 emergence of highly pathogenic avian influenza (HPAI) A(H5N1) virus in Hong Kong, China, 648 HPAI A(H5N1) infections and 384 associated deaths in humans have been reported. During 2013, Cambodia reported the most human infections, followed by Egypt, Indonesia, China, and Vietnam (www.who.int/influenza/human_animal_interface/H5N1_cumulative_table_archives/en/, December 10, 2013, report). In December 2013, an HPAI A(H5N1) infection was reported in a Canadian resident who recently returned from China. No human or poultry HPAI A(H5N1) infections had been previously reported in North America.
Case Report and Laboratory Investigations
Preliminary details of this case have been reported (1) (Technical Appendix 1 [PDF - 57 KB - 4 pages]). The patient initially sought care for respiratory symptoms; however, the probable cause of death was listed as meningoencephalitis, an unusual outcome for HPAI A(H5N1) infections in humans. Detailed interviews with close contacts have not identified exposure to infected avian sources or environmental contamination, although these investigations are continuing. Because symptom onset occurred during a return flight from China, it is probable that the patient was exposed to the virus while in China.
Nasopharyngeal swab (NP) samples, bronchoalveolar lavage (BAL), and cerebrospinal fluid (CSF) samples tested positive for influenza A(H5N1) virus by various molecular testing methods, including sequencing, at the Provincial Laboratory for Public Health and the National Microbiology Laboratory, Public Health Agency of Canada (1). An isolate cultured from BAL (A/Alberta/01/2014) underwent full-genome sequencing (methods available in online Technical Appendix 1); analysis results are presented here.
Partial sequences of virus from the primary specimens (shown in parentheses) included 1,378 bp of the hemagglutinin (HA) gene (CSF, BAL, NP), 1,350 bp of the neuraminidase gene (BAL), 810 bp of the matrix gene (NP), and 687 bp of the polymerase basic 2 (PB2) gene (NP). These sequences were identical to corresponding sequences obtained from the isolate, suggesting the absence of cell culture?induced changes.
Figure 1
Figure 1. . Neighbor-joining phylogenetic tree of the polymerase basic 2 (PB2) genes of H9N2 subtype lineage avian influenza A viruses with A/Alberta/01/2014 (GISAID accession no. EPI500778). The avian influenza A(H5N1) virus detected...
Figure 2
Figure 2. . Neighbor-joining phylogenetic tree of the hemagglutinin (HA) genes of clade 2.3.2.1 highly pathogenic avian influenza A(H5N1) viruses with A/Alberta/01/2014 (GISAID accession no. EPI500771). The avian influenza A(H5N1) virus detected in...
BLAST (http://blast.ncbi.nlm.nih.gov/Blast.cgi) analysis of each gene of A/Alberta/01/2014 showed that 7 of 8 genes shared ≥99% identity at the nucleotide and protein levels with HPAI A(H5N1) viruses of avian origin. However, the PB2 gene showed 98% nt similarity and 99% aa identity to avian influenza A(H9N2) viruses collected in China. Phylogenetic analysis of each gene (Technical Appendix 2 [PDF - 57 KB - 4 pages]) with sequences from related viruses confirmed that only the PB2 gene resulted from reassortment with an avian influenza A virus containing an H9N2 subtype lineage PB2 gene (Figure 1). Phylogenetic analysis of the HA gene demonstrated that the virus belongs to clade 2.3.2.1c (2) (Figure 2), which has been detected in many countries and has recently been reported in China, Vietnam, and Indonesia (2). The HA gene of A/Alberta/01/2014 (H5N1) was most closely related to the sequence for an HPAI A(H5N1) virus from a tiger that died in 2013 at a zoo in Jiangsu, China. This combination of clade 2.3.2.1c lineage HA, neuraminidase, and internal gene segments derived from other influenza A(H5N1) viruses and an H9N2 subtype lineage PB2 gene indicated that this virus is a previously undescribed genotype of HPAI A(H5N1).
To assess the virus for molecular markers of pandemic risk, we reviewed all protein sequences for mutations listed in the H5N1 Genetic Changes Inventory (3).The HA protein possessed a multibasic amino acid cleavage site motif (PQRERRRKR*G) similar to other clade 2.3.2.1 viruses (4). The sequence of the 220-loop receptor binding site (RBS) contained the typical avian amino acids, Q222/G224, predictive of a preference for the avian α2,3 rather than the human α2,6 sialic acid (SA) host cell receptor (5); all HA gene numbering is based on H5 viruses unless otherwise indicated. The RBS sequence was identical in the NP and BAL samples, suggesting the absence of adaptive changes in the cultured isolate. The G221R substitution, uncommon in HPAI A(H5N1) virus, was detected in the RBS. Previously reported in a clade 2 HPAI A(H5N1) virus (GenBank accession no. ABR13964), R221 has been shown in influenza A/H3 (R225 by H3 numbering) to slightly increase binding to human erythrocytes (6). Other mutations of interest in A/Alberta/01/2014 were D94N, S133A, S155N, and T156A. D94N decreased binding to α2,3 SA and increased it to α2,6 SA in a pseudotyping assay (7). S133A, together with T188I (not present in A/Alberta/01/2014), increased binding to α2,6 SA by pseudotyping and glycan array assays (8). When together, S155N and T156A also increased binding to α2,6 SA (assayed with resialated erythrocytes). T156A abrogates a N-glycosylation site and, when together with S223N (not found in A/Alberta/01/2014), may improve virus replication in the upper respiratory tract of ferrets (9); T156A is consistently found in ferret-adapted mutants capable of airborne transmission (5). The collective effects of all these mutations and their phenotypic manifestations are unclear.
Comparison of the HA amino acid sequence of A/Alberta/01/2014 with that of the nearest H5N1 clade 2.3.2.1c World Health Organization candidate vaccine virus (A/duck/Vietnam/NCVD-1584/2012) identified only 2 aa substitutions in the HA1 region, R189K and G221R. Although position 189 was within the putative antigenic site B, the overall conservation of sequence suggests that A/Alberta/01/2014 is a close antigenic match to the candidate vaccine virus.
In agreement with Xu et al. (4), no mutations conferring reduced susceptibility to neuraminidase inhibitors were identified for another clade 2.3.2.1 virus. The predicted amino acid sequence of the M2 protein did not reveal any changes associated with reduced susceptibility to adamantanes (10). Mutation V27I was found, but its significance is uncertain. Mutations N30D and T215A found in the M1 gene of A/Alberta/01/2014 were associated with increased virulence in mice. The cumulative effect of these changes may result in increased lethality (11).
The PB2 sequence showed the presence of E627 in both the primary specimen and isolate, establishing the lack of a well-known mammalian adaptation motif (5,12). Amino acid changes L89V, G309D, T339K, R477G, I495V, and K627E and a change to Met at the predicted position A676T (13) were noted in the A/Alberta/01/2014 isolate. These PB2 substitutions in conjunction with changes in the M1 and HA proteins (only some of which were identified) have been described to enhance polymerase activity and virulence in mice. Experiments in mice also demonstrated that compensatory amino acid substitutions in PB2 can rescue polymerase activity in K627E mutants (13). Lethal HPAI A(H5N1) isolates, such as A/quail/Vietnam/36/04, show the presence of E627, suggesting that compensatory mutations are possible in PB2 and other genes (14). The PB1 protein showed the P598L mutation reported to enhance polymerase activity in mammalian cells and mice (3). This change has been reported to enhance the polymerase activity of an attenuated human virus carrying the PB2 K627E mutation (15). Of the polymerase mutations hypothesized to increase the RNA polymerase activity of HPAI A(H5N1) viruses, namely P149S, R226H, K357I, and T515S, only two, 149S and 357T, were present in the A/Alberta/01/2014 isolate (3).
Mutations in the nucleoprotein gene reported to enhance replication efficiency, virulence, and transmission (3) were absent in the isolate. Several NS1 mutations reported to increase virulence in mice were present in A/Alberta/01/2014: P42S, D87E, L98F, and I101M; a 4-bp deletion from nt 80?84, along with the D92E shift; and the PDZ ligand domain (ESEV) at the C terminus (3). The multifunctional NS1 protein is a recognized virulence determinant that counters the cellular innate immune response, and the P42S change has been shown to antagonize interferon induction and prevent activation of the nuclear factor?κB and interferon regulatory factor?3 pathways (16).
Conclusion
Analysis of the whole genome of HPAI A(H5N1) virus provides valuable insight into the presence of mutations that may reflect adaptive changes, altered virulence, and/or transmission phenotype. Because of the unique manifestation of neurologic symptoms and encephalitis reported in this patient, additional studies are needed to understand the broader aspects of virus heterogeneity and its role in this fatal case.
Ms Pabbaraju is a senior laboratory scientist at the Provincial Laboratory for Public Health. Her research focuses on the development of diagnostic tests for viral and bacterial pathogens as well as studies on the epidemiology of viruses.
Acknowledgment
We gratefully acknowledge the tremendous work of the clinical and public health teams in Alberta involved in the management and follow-up of this case and deeply appreciate the cooperation of the family during the investigation of this tragic event. We thank the technical laboratory staff for their work and contributions to the confirmation and analysis of this influenza strain. We greatly appreciate and acknowledge the generous discussions and expert input of Nancy Cox and her team at the US Centers for Disease Control and Prevention.
References
- ProMED-mail. Fatal avian influenza A(H5N1) infection in a Canadian traveler. 2014 Jan 12 [cited 2014 Jan 24]. http://www.promedmail.org, archive no. 20140112.2167282
- World Health Organization/World Organization for Animal Health/Food and Agriculture Organization (WHO/OIE/FAO) H5N1 Evolution Working Group, 2013. Revised and updated nomenclature for highly pathogenic avian influenza A (H5N1) viruses. Influenza Other Respir Viruses. 2014. Epub 2014 Jan 31. PubMed
- Centers for Disease Control and Prevention. H5N1 Genetic Changes Inventory: a tool for influenza surveillance and preparedness [cited 2014 Jan 24]. http://www.cdc.gov/flu/avianflu/h5n1...ic-changes.htm
- Xu L, Bao L, Yuan J, Li F, Lv Q, Deng W, Antigenicity and transmissibility of a novel clade 2.3.2.1 avian influenza H5N1 virus. J Gen Virol. 2013;94:2616?26. DOIPubMed
- Herfst S, Schrauwen EJ, Linster M, Chutinimitkul S, de Wit E, Munster VJ, Airborne transmission of influenza A/H5N1 virus between ferrets. Science. 2012;336:1534?41. DOIPubMed
- Mart?n J, Wharton SA, Lin YP, Takemoto DK, Skehel JJ, Wiley DC, Studies of the binding properties of influenza hemagglutinin receptor-site mutants. Virology. 1998;241:101?11. DOIPubMed
- Su Y, Yang HY, Zhang BJ, Jia HL, Tien P. Analysis of a point mutation in H5N1 avian influenza virus hemagglutinin in relation to virus entry into live mammalian cells. Arch Virol. 2008;153:2253?61. DOIPubMed
- Yang ZY, Wei CJ, Kong WP, Wu L, Xu L, Smith DF, Immunization by avian H5 influenza hemagglutinin mutants with altered receptor binding specificity. Science. 2007;317:825?8. DOIPubMed
- Wang W, Lu B, Zhou H, Suguitan AL Jr, Cheng X, Subbarao K, Glycosylation at 158N of the hemagglutinin protein and receptor binding specificity synergistically affect the antigenicity and immunogenicity of a live attenuated H5N1 A/Vietnam/1203/2004 vaccine virus in ferrets. J Virol. 2010;84:6570?7. DOIPubMed
- Govorkova EA, Baranovich T, Seiler P, Armstrong J, Burnham A, Guan Y, Antiviral resistance among highly pathogenic influenza A (H5N1) viruses isolated worldwide in 2002?2012 shows need for continued monitoring. Antiviral Res. 2013;98:297?304. DOIPubMed
- Fan S, Deng G, Song J, Tian G, Suo Y, Jiang Y, Two amino acid residues in the matrix protein M1 contribute to the virulence difference of H5N1 avian influenza viruses in mice. Virology. 2009;384:28?32. DOIPubMed
- Long JS, Howard WA, N??ez A, Moncorg? O, Lycett S, Banks J, The effect of the PB2 mutation 627K on highly pathogenic H5N1 avian influenza virus is dependent on the virus lineage. J Virol. 2013;87:9983?96. DOIPubMed
- Li J, Ishaq M, Prudence M, Xi X, Hu T, Liu Q, Single mutation at the amino acid position 627 of PB2 that leads to increased virulence of an H5N1 avian influenza virus during adaptation in mice can be compensated by multiple mutations at other sites of PB2. Virus Res. 2009;144:123?9. DOIPubMed
- Salomon R, Franks J, Govorkova EA, Ilyushina NA, Yen HL, Hulse-Post DJ, The polymerase complex genes contribute to the high virulence of the human H5N1 influenza virus isolate A/Vietnam/1203/04. J Exp Med. 2006;203:689?97. DOIPubMed
- Xu C, Hu WB, Xu K, He YX, Wang TY, Chen Z, Amino acids 473V and 598P of PB1 from an avian-origin influenza A virus contribute to polymerase activity, especially in mammalian cells. J Gen Virol. 2012;93:531?40. DOIPubMed
- Jiao P, Tian G, Li Y, Deng G, Jiang Y, Liu C, A single-amino-acid substitution in the NS1 protein changes the pathogenicity of H5N1 avian influenza viruses in mice. J Virol. 2008;82:1146?54. DOIPubMed
Figures
- Figure 1. . Neighbor-joining phylogenetic tree of the polymerase basic 2 (PB2) genes of H9N2 subtype lineage avian influenza A viruses with A/Alberta/01/2014 (GISAID accession no. EPI500778). The avian influenza A(H5N1)...
- Figure 2. . Neighbor-joining phylogenetic tree of the hemagglutinin (HA) genes of clade 2.3.2.1 highly pathogenic avian influenza A(H5N1) viruses with A/Alberta/01/2014 (GISAID accession no. EPI500771). The avian influenza A(H5N1) virus...
Technical Appendices
- Technical Appendix 1. . Case details and methods for a full-genome analysis of highly pathogenic avian influenza A(H5N1) virus isolated from clinical samples of an infected human, North America, 2013. 57 KB
- Technical Appendix 2. . Neighbor-joining phylogenetic trees of the polymerase basic 1, polymerase, nucleoprotein, neuraminidase, matrix, and nonstructural protein genes of highly pathogenic avian influenza A(H5N1) viruses with A/Alberta/01/2014. 974 KB
Suggested citation for this article: Pabbaraju K, Tellier R, Wong S, Li Y, Bastien N, Tang JW, et al. Full-genome analysis of avian influenza A(H5N1) virus from human, North America, 2013. Emerg Infect Dis. 2014 May [date cited]. http://dx.doi.org/10.3201/eid2005.140164
DOI: 10.3201/eid2005.140164
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Re: China - H5N1 death in Alberta, Canada upon return from China trip - died from meningoencephalitis
Source: http://www.cbc.ca/news/health/h5n1-s...rain-1.2498128
H5N1 strain from Alberta nurse resembles Chinese strain
Complete genome sequence of H5N1 virus a research priority for national lab
CBC News Posted: Jan 15, 2014 6:24 PM ET Last Updated: Jan 15, 2014 6:24 PM ET
..."Based on the genome sequence data collected to date, researchers at the [National Microbiology Laboratory] have found it to be consistent with a previously circulating H5N1 strain from China," a spokesperson said in an email Wednesday."
"The first research priority for the NML is to complete the whole genome sequence of the virus, and then analyze the data to learn more about the specific traits and characteristics of the virus. The genome analysis will help inform and guide all future research priorities..."
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Re: China - H5N1 death in Alberta, Canada upon return from China trip - died from meningoencephalitis
Source: http://metronews.ca/news/canada/9091...rom-h5n1-case/
Updated: January 14, 2014 | 4:50 pm
National lab to study virus from H5N1 case
By Helen Branswell The Canadian Press
TORONTO ? Canada?s National Microbiology Laboratory has isolated live H5N1 virus from respiratory specimens taken from an Alberta woman who died recently from infection with that bird flu virus.
The Winnipeg-based lab is working in collaboration with Alberta?s provincial laboratory to sequence the entire genome of the virus, which the woman is believed to have contracted during a three-week trip to China in December...
...In an emailed response to questions, officials at the Winnipeg lab say copies of the virus will be shared with the U.S. Centers for Disease Control, which is part of the World Health Organization?s network of influenza reference laboratories.
They also say the full genetic blueprint of the virus will be entered into GISAID, an online influenza database accessible to flu researchers from around the globe...
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Re: China - H5N1 death in Alberta, Canada upon return from China trip - died from meningoencephalitis
[Source: European Centre for Disease Prevention and Control (ECDC), full PDF document: (LINK). Extract.]
COMMUNICABLE DISEASE THREATS REPORT
Week 2, 5-11 January 2014
(...)
Influenza A(H5N1) - Multistate (world) - Monitoring human cases
Opening date: 15 June 2005 Latest update: 9 January 2014
Epidemiological summary
A fatal case of A(H5N1) was reported on 8 January 2014 in Canada.
The case had onset of symptoms on 27 December 2013 during a return flight from Beijing to Edmonton via Vancouver. The patient developed symptoms while flying that worsened during travel.
The patient was admitted to hospital on arrival in Edmonton and passed away on 3 January 2014.
The clinical presentation, fever, malaise and headache, was consistent with meningo-encephalitis and did not involve the respiratory system which is unusual for A(H5N1) infection.
Tests at a reference laboratory confirmed influenza A(H5N1) infection on 7 January.
The case had not been outside of Beijing during the trip to China and had not visited live bird markets or farms.
Thirty-nine human cases with influenza A(H5N1) virus infection have been laboratory-confirmed worldwide since the beginning of 2013 and as of 9 January 2014. The countries affected during this period are Cambodia (26), Egypt (4), Indonesia (3), China (2), Vietnam (2), Bangladesh (1) Canada ex China (1). Among these cases, 25 were fatal, most of them in Cambodia (14). The last case of A(H5N1) in China was reported in February 2013.
From 2003 through to 9 January 2014, 649 laboratory-confirmed human cases with avian influenza A(H5N1) virus infection have been officially reported from 15 countries. Of these cases, 385 have died.
In Cambodia, the reported incidence of human cases has increased in 2013 compared to previous years (26 cases in 2013 compared with 21 cases from 2005 through to December 2012). However, the case-fatality ratio among reported cases has decreased (54% in 2013 compared with 90% over all previous years).
(?)
ECDC assessment
The risk of secondary cases and co-primary cases among the close contacts of the Canadian case is considered to be very low since more than 10 days have passed since the onset of disease, transmission of A(H5N1) on board aircraft has never been documented, and there is no evidence of sustained human-to-human transmission of A(H5N1) ever occurring.
The risk of healthcare-associated transmission in Canada is considered to be very low.
The evidence points to an isolated case who was infected following exposure in China, although the source and mode of transmission has not yet been established. A(H5N1) is a strain of avian influenza that occasionally crosses the species barrier and infects humans.
Sporadic cases originating in areas where A(H5N1) transmission has been documented in the recent past are therefore not unexpected.
Although the case reported from Canada had an atypical clinical presentation and exposure to potentially infected birds has not been established, these circumstances do not change the conclusions in the latest ECDC Risk Assessment of 12 January 2012.
ECDC concurs with the recommendations made by the Canadian Public Health Agency which are in line with the ECDC recommendations that:
- Europeans travelling to China and South-East Asia should avoid live poultry markets and any contact with chickens, ducks, wild birds, and their droppings. This reduces the risk of exposure not only to A(H5N1) but also to A(H7N9).
- Poultry meat and eggs should be well cooked.
Hong Kong reported the world's first outbreak of bird flu among humans in 1997, when six people died. Most human infections are the result of direct contact with infected birds, and countries with large poultry populations in close contact with humans are considered to be most at risk of bird flu outbreaks. There are currently no indications of a significant change in the epidemiology associated with any clade or strain of the A(H5N1) virus from a human health perspective.
This assessment is based on the absence of sustained human-to-human transmission, and on the observation that there is no apparent change in the size of clusters or reports of chains of infection. However, vigilance for avian influenza in domestic poultry and wild birds in Europe remains important.
Actions
ECDC follows the worldwide A(H5N1) situation through epidemic intelligence activities in order to identify significant changes in the epidemiology of the virus. ECDC re-assesses the potential of a changing risk for A(H5N1) to humans on a regular basis. WHO is now reporting H5N1 cases on a monthly basis. ECDC will continue monthly reporting in the CDTR to coincide with WHO reporting.
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Re: China - H5N1 death in Alberta, Canada upon return from China trip - died from meningoencephalitis
WHO is confident bird flu won't spread in Canada
CTVNews.ca Staff
Published Monday, January 13, 2014 7:51AM EST
The World Health Organization says it is confident that the bird flu virus will not spread in Canada after an Alberta nurse who had recently travelled to China died of the virus earlier this month.
Bernhard Schwartlander, a WHO representative in China, said that it?s very rare for the H5N1 virus to be transmitted from one infected person to another.
"That's what makes us confident right now, based on the current evidence, that people do not need to worry in Canada that the virus will spread any further," Schwartlander told CTV News.
...
Schwartlander says while Chinese authorities will attempt to track every possible source of the infection, it will be very difficult considering the woman had likely visited several heavily populated areas during her stay.
"Chinese authorities work very closely with the WHO and the Canadian authorities to see whether we can actually track the likely cause, which is not only important to clarify what happened to this person, but also to see whether we can take action to make sure these cases are not happening in the future," he said.
...
"The Chinese authorities recognize that one, it's an obligation that they have entered into in terms of international health regulations, and second, that it's in their very own interest to protect their own society."
...
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Re: China - H5N1 death in Alberta, Canada upon return from China trip - died from meningoencephalitis
These two siblings from Dong Thap described by Menno D. de Jong the clinical presentation appears to be similar but with Diarrhoea
Fatal Avian Influenza A (H5N1) in a Child Presenting with Diarrhea Followed by Coma — NEJM
Case Summary:
Patient 1: Probable (9F)
1-Feb-04 admitted to Dong Thap Hospital ,4 day Hx fever 38.5°C, watery diarrhoea, increasing drowsiness, GCS 9 No respiratory symptoms, CXR clear; within a few hrs GCS-5, Int/M/V pt died on 2-Feb-04- septicaemia from encephalitis of unknown origin
Exposure:
Pt-1 Dx- encephalitis of unknown origin parents apparently owned healthy fighting cocks, swam in canal
Patient 2 Retrospectively confirmed Nov 2004: (4M)
12-Feb-04 also presented Dong Thap Hospital two day history of fever, headache, vomiting, and severe diarrhoea, 1st. CXR normal GCS 12, After 12hrs, convulsions, comatose, GCS 7, CXR on 16-Feb-04 bilateral infiltrates and interstitial shadowing died on February 17, 2004. Acute encephalitis of unknown origin was reported as the cause of death.
No autopsy was performed.
Exposure:
Pt-2 ? Faeces/Ducks? Inconclusive HTH; parents apparently owned healthy fighting cocks
See article for F/U lab diagnostics!
Encephalitis study samples
Fatal Avian Influenza A (H5N1) in a Child Presenting with Diarrhea Followed by Coma — NEJM
Retrospectively confirmed in 2005
This article is most likely on FT's but no need to search!
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Re: Canada - H5N1 death in Alberta after travel from China - died from meningoencephalitis
Originally posted by Giuseppe Michieli View Post[Source: ProMedMail.org, full page: (LINK). Edited.]
Published Date: 2014-01-12 10:23:15 / Subject: PRO/AH/EDR> Avian influenza, human (13): Canada ex China (BJ) H5N1, fatal, case report / Archive Number: 20140112.2167282
AVIAN INFLUENZA, HUMAN (13): CANADA ex CHINA (BEIJING), H5N1, FATAL, CASE REPORT
A ProMED-mail post http://www.promedmail.org / ProMED-mail is a program of the International Society for Infectious Diseases http://www.isid.org
Date: Sat 11 Jan 2014 / From: Kevin Fonseca <kevin.fonseca@albertahealthservices.ca> [edited]
_____
Avian influenza A(H5N1) was detected in the respiratory samples and CSF [cerebrospinal fluid] of a young adult, who died from the infection 7 days after returning from a vacation in Beijing, China accompanied by a family member.
[excerpt]
3 Jan 2014
A lumbar puncture was performed after brain death determination and prior to removal of ventilatory and inotropic support.
[excerpt]
Nasopharyngeal swabs and BAL were sent to the Provincial Laboratory for complementary viral investigations for influenza and other respiratory viral agents, and CSF for the herpesvirus group, enterovirus and parechoviruses.
Screening for influenza A and B and other respiratory viruses was performed on the respiratory samples (2 nasopharyngeal swabs and a BAL) through a combination of a direct fluorescent antigen (DFA) test (D3 Ultra DFA Influenza A/B reagent, Diagnostic Hybrids, Ohio), real time singleplex Taqman assays to influenza A and B assays targeting the matrix (M) gene of influenza A and NS1 gene of influenza B (1), and Luminex Respiratory Viral panel (Luminex, Ontario).
The swabs were negative by the DFA, however all these samples were positive for influenza A, with good Ct values in the Taqman assay, and were immediately subtyped, using real time assays to A(H1N1) pdm09 and seasonal H3 (2,3). Negative subtyping results were obtained on 2 independent runs, and when viewed in conjunction with recent travel history, strongly pointed to the possibility that this strain could be one of the avian subtypes known to occasionally infect humans. To investigate this possibility, a combination of real time and gel-based assays were performed to target the following genes H5, H7 and N9, on the viral RNA from the BAL, which had the highest titre of virus. Additionally, the M (matrix), NA (neuraminidase) and HA (haemagglutinin) genes were amplified and sequenced.
A compilation of the results from all these assays indicated that this strain was an influenza A(H5N1) subtype. Supplementary testing performed at the National Microbiology Reference Laboratory, Winnipeg, confirmed our findings that this was an avian influenza A (H5N1) virus.
[excerpt]
Of interest is that the respiratory samples tested negative for influenza A in the Luminex Respiratory Viral panel but identified a human coronavirus 229E in the nasopharyngeal swabs, but not from the BAL. The negative influenza A results from this commercial assay were in contrast to the positive results obtained from the in-house Taqman assays.
The CSF collected also tested positive for influenza A and subtyped as H5.
An autopsy was not done due to concerns regarding the risk of virus transmission.
[excerpt]
From a laboratory diagnosis aspect, this case shows the value of having screening assays, in-house or commercial, known to be capable of identifying all influenza subtypes. Often, the proprietary information of the target and detection sites of commercial assays makes it difficult to know if non-seasonal subtypes can be detected (6). In this case, the discrepant results between our in-house screening Taqman assays and the Luminex Respiratory Viral Panel were very helpful in indicating this strain was not a seasonal subtype.
[excerpt]
References
- Swine Influenza CDC Realtime RTPCR (rRTPCR) Protocol for Detection and Characterization of Swine Influenza (version 2009). CDC REF. #I-007-05 Page 1 of 8 Version 2009.
- CDC Realtime RTPCR (rRTPCR) Protocol for Detection and Characterization of Influenza (version 2007).
- Pabbaraju K, S Wong, AW Wong, GD Appleyard, et al. Design and Validation of Real-Time Reverse Transcription-PCR Assays for Detection of Pandemic (H1N1) 2009 Virus. J Clin Microbiol 2009;47(11):3454-60.
- Gambatto A, SM Barratt-Boyes, MD de Jong and Y Kawaoka. Human infections with highly pathogenic H5N1 influenza virus. Lancet 2007;371:1464-75.
- Lipatov AS, A Krauss, Y Guan, M Peiris et al. Neurovirulence in mice of H5N1 influenza virus genotypes isolated from Hong Kong poultry in 2001. J. Virol 2003;77(6):3816-3823.
- Hatchette TF, SJ Drews, N Bastien, Y. Li et al. Detection of Influenza H7N9 virus: all molecular tests are not equal. J Clin Microbiol 2013;51(11):3835-38.
Lead and corresponding authors
- Kevin Fonseca, Clinical Virologist, Provincial Laboratory, Alberta Health Services, Canada
- Martin Lavoie, Deputy Medical Officer of Health, Alberta Health, Canada
Additional authors in alphabetical order by organization and last name:
- Alberta Health:
- James Talbot, Chief Medical Officer of Health, Alberta Health, Canada
- Alberta Health Services:
- Jeff Fuller, Clinical Microbiologist, Provincial Laboratory, Alberta Health Services, Canada
- Robyn Harrison, Communicable Disease Consultant Workplace Health & Safety, Alberta Health Services
- Mark Joffe, Senior Medical Director, Infection Prevention and Control, Alberta Health Services
- Kanti Pabbaraju, Senior Scientist, Provincial Laboratory, Alberta Health Services, Canada
- Raymond Tellier, Medical Microbiologist, Provincial Laboratory, Alberta Health Services, Canada
- Graham Tipples, Medical Director, Provincial Laboratory, Alberta Health Services, Canada
- Stephen Tsekrekos, Medical Director, Workplace Health & Safety, Alberta Health Services
- Sallene Wong, Scientist, Provincial Laboratory, Alberta Health Services, Canada
- National Microbiology Laboratory:
- Natalie Bastien, Research Scientist, Influenza and Respiratory Virus Section, National Microbiology Laboratory, Winnipeg, Canada
- Yan Li, Chief, Influenza and Respiratory Virus Section, National Microbiology Laboratory, Winnipeg, Canada
Acknowledgments
The named authors would like to acknowledge the timely, thorough and expert contributions made by local medical, nursing, public health, infection control, and health care professionals to this work and this publication. At the request of the family, to preserve confidentiality, additional contributing authors have agreed not to be named. We would also like to express particular thanks to the family for their kind cooperation in this difficult time for them.
(…)
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-------H5N1
Clade 2.3.2.1
Detection
by
Testing Method and Location
- NasoPharyngeal Swabs (NP)
- Influenza A
- Negative_ - D3 Ultra DFA Influenza A/B reagent
- Negative_ - Luminex Respiratory Viral panel
- Positive_ - RT singleplex Taqman assay Influenza A
- SubType pH1 and sH3
- Negative_ - RT SubType pH1 and sH3 (2 Runs)
- HCoV 229E
- Positive_ - Luminex Respiratory Viral panel
- Influenza A
- BronchoAlveolar Lavage (BAL)
- Influenza A
- Positive_ - RT singleplex Taqman assay Influenza A
- SubType H5
- Positive_ - Combo RT & Gel SubType H5, H7 and N9
- H5N1
- Amplified_ - M, HA, NA Segments
- HCoV 229E
- Negative - Luminex Respiratory Viral panel
- Influenza A
- CerebroSpinal Fluid (CSF)
- Influenza A
- Positive_ - Test Not Specified
- SubType H5
- Positive_ - Test Not Specified
- Influenza A
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Re: Canada - H5N1 death in Alberta after travel from China - died from meningoencephalitis
Originally posted by sharon sanders View PostThis is we are listing this for now:
1) Canada* - Person tested positive after trip to China, died January 3 Death
* The country designation may change to China pending investigation.
http://www.flutrackers.com/forum/sho...d.php?t=216111
Therefore, I have re-titled this thread and moved it into the China H5N1 tracking forum.
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Re: Canada - H5N1 death in Alberta after travel from China - died from meningoencephalitis
[Source: ProMedMail.org, full page: (LINK). Edited.]
Published Date: 2014-01-12 10:23:15 / Subject: PRO/AH/EDR> Avian influenza, human (13): Canada ex China (BJ) H5N1, fatal, case report / Archive Number: 20140112.2167282
AVIAN INFLUENZA, HUMAN (13): CANADA ex CHINA (BEIJING), H5N1, FATAL, CASE REPORT
A ProMED-mail post http://www.promedmail.org / ProMED-mail is a program of the International Society for Infectious Diseases http://www.isid.org
Date: Sat 11 Jan 2014 / From: Kevin Fonseca <kevin.fonseca@albertahealthservices.ca> [edited]
_____
Avian influenza A(H5N1) was detected in the respiratory samples and CSF [cerebrospinal fluid] of a young adult, who died from the infection 7 days after returning from a vacation in Beijing, China accompanied by a family member.
The individual left Canada for China on 6 Dec 2013 and was exclusively in Beijing, in urban locations. There was no contact reported with live poultry, no visits to wet markets, or handling of fresh poultry. Work is ongoing to obtain a detailed account of activities during the trip.
During the return flight on 27 Dec 2013, the individual experienced symptoms of malaise, chest pain, and fever and presented to the local Emergency Department on 28 Dec 2013. The complete blood count (CBC) showed a total white blood count (WBC) of 12.6 x 10 to the power of 9/L (reference range 4.0 - 10.0 x10 to the power of 9/L) with raised neutrophils (11.1 x 10 to the power of 9/L) and low lymphocytes (0.8 x 10 to the power of 9/L). A chest X-ray and CT scan revealed a right apical infiltrate. A diagnosis of pneumonia was made; the patient was prescribed levofloxacin and discharged home.
The individual returned to the same Emergency Department on 1 Jan 2014, now with worsening pleuritic [inflammation of the membrane surrounding the lung] chest pains and shortness of breath, a mild headache, exacerbated by head movement, right upper quadrant and epigastric pain, nausea and vomiting with no diarrhea. A chest X-ray showed a multi-lobar pneumonia, with moderate effusion, reflecting significant progression when compared with the X-ray from the 1st ED visit. A thoracentesis [a procedure to remove excess fluid in the space between the lungs and the chest wall], performed while in the ED, revealed a dark amber cloudy fluid that was sterile in bacterial culture. The CBC again showed a WBC count of 10.2 x 10 to the power of 9/L, neutrophil count of 9.5 x 10 to the power of 9/L, platelet count within the normal range, normal ALT, slightly elevated AST at 46 U/L (reference range 7 - 40 U/L) and LDH at 288 U/L (reference range 100 - 225 U/L).
Admission to a general medicine ward for investigation was facilitated, and treatment was initiated with intravenous piperacillin-tazobactam. On 2 Jan 2014, the individual reported visual changes and ongoing headache, and, coupled with increasing oxygen requirements, was admitted to the ICU for intubation and ventilation. In the early morning of 3 Jan 2014, the individual developed a sudden episode of tachycardia and severe hypertension followed by hypotension requiring inotropic support. At this point, pupils were dilated, and there was no response to pain.
A CT brain scan suggested diffuse encephalitis and intracranial hypertension. The neurological examination was consistent with brain death. An MRI/MRA showed significant generalized edema, evidence of meningitis and ventriculitis [inflammation of the ventricles in the brain] and significant reduction in cerebral blood flow.
A lumbar puncture was performed after brain death determination and prior to removal of ventilatory and inotropic support. The attending physician felt that, while unlikely, avian influenza was possible given the travel history and neurological symptoms, and contacted the local Medical Officer of Health on 3 Jan 2014 to report to public health. Contact tracing of family and hospital contacts was initiated as a precaution, given the severity of the illness and its rapid progression.
Laboratory investigations:
Blood cultures were negative as were cultures of the broncho-alveolar lavage (BAL) fluids for a range of bacterial pathogens. Nasopharyngeal swabs and BAL were sent to the Provincial Laboratory for complementary viral investigations for influenza and other respiratory viral agents, and CSF for the herpesvirus group, enterovirus and parechoviruses.
Screening for influenza A and B and other respiratory viruses was performed on the respiratory samples (2 nasopharyngeal swabs and a BAL) through a combination of a direct fluorescent antigen (DFA) test (D3 Ultra DFA Influenza A/B reagent, Diagnostic Hybrids, Ohio), real time singleplex Taqman assays to influenza A and B assays targeting the matrix (M) gene of influenza A and NS1 gene of influenza B (1), and Luminex Respiratory Viral panel (Luminex, Ontario).
The swabs were negative by the DFA, however all these samples were positive for influenza A, with good Ct values in the Taqman assay, and were immediately subtyped, using real time assays to A(H1N1) pdm09 and seasonal H3 (2,3). Negative subtyping results were obtained on 2 independent runs, and when viewed in conjunction with recent travel history, strongly pointed to the possibility that this strain could be one of the avian subtypes known to occasionally infect humans. To investigate this possibility, a combination of real time and gel-based assays were performed to target the following genes H5, H7 and N9, on the viral RNA from the BAL, which had the highest titre of virus. Additionally, the M (matrix), NA (neuraminidase) and HA (haemagglutinin) genes were amplified and sequenced.
A compilation of the results from all these assays indicated that this strain was an influenza A(H5N1) subtype. Supplementary testing performed at the National Microbiology Reference Laboratory, Winnipeg, confirmed our findings that this was an avian influenza A (H5N1) virus.
Sequence data of the HA and NA genes from both laboratories showed the following.
From the HA sequence this virus;
- (a) belongs to clade 2.3.2.1,
- (b) is a highly pathogenic influenza A(H5), based upon the presence of multiple basic amino-acid residues occurring at the cleavage site,
- (c) has a wild-type receptor binding site, consistent with preferential affinity for the avian alpha-2-3 sialic-acid receptor.
The NA sequence shows genotypic sensitivity to oseltamivir (Tamiflu) based upon the histidine residue at position 275. This genotypic susceptibility result was considered to be helpful information as chemoprophylaxis with oseltamivir had been prescribed for close contacts of the individual.
Of interest is that the respiratory samples tested negative for influenza A in the Luminex Respiratory Viral panel but identified a human coronavirus 229E in the nasopharyngeal swabs, but not from the BAL. The negative influenza A results from this commercial assay were in contrast to the positive results obtained from the in-house Taqman assays.
The CSF collected also tested positive for influenza A and subtyped as H5.
An autopsy was not done due to concerns regarding the risk of virus transmission.
This case identifies a number of key issues, the 1st being the rapid onset and tragic death of a young, healthy traveler due to an avian influenza A(H5N1) infection. The index of suspicion was low as travel was to an area in China where there have been no recent reports of the circulation of this virus, and coupled with no obvious exposure to poultry, the diagnostic work-up and consideration for A(H5N1) infection was very low.
The clinical course, detection of the virus in the CSF, and results of imaging studies are consistent with an infection of the brain. A review of the literature indicates that such events are uncommon in humans, although animal models show that this virus is neurotropic and neuroinvasive (4,5).
From a laboratory diagnosis aspect, this case shows the value of having screening assays, in-house or commercial, known to be capable of identifying all influenza subtypes. Often, the proprietary information of the target and detection sites of commercial assays makes it difficult to know if non-seasonal subtypes can be detected (6). In this case, the discrepant results between our in-house screening Taqman assays and the Luminex Respiratory Viral Panel were very helpful in indicating this strain was not a seasonal subtype.
The availability of advanced molecular tools at the Alberta Provincial Laboratory allowed us to suspect, within 24 hours of testing these samples, that this was an unusual strain. Such information was valuable in implementing appropriate communication processes to healthcare workers who cared for this patient and to regularly update the appropriate authorities.
Finally, this infection of a Canadian resident is the 1st case of influenza A(H5N1) occurring in North America.
With the rapidity of travel between countries and continents and the globalization of many cultures, this will likely not be the last case to occur in North America.
- Swine Influenza CDC Realtime RTPCR (rRTPCR) Protocol for Detection and Characterization of Swine Influenza (version 2009). CDC REF. #I-007-05 Page 1 of 8 Version 2009.
- CDC Realtime RTPCR (rRTPCR) Protocol for Detection and Characterization of Influenza (version 2007).
- Pabbaraju K, S Wong, AW Wong, GD Appleyard, et al. Design and Validation of Real-Time Reverse Transcription-PCR Assays for Detection of Pandemic (H1N1) 2009 Virus. J Clin Microbiol 2009;47(11):3454-60.
- Gambatto A, SM Barratt-Boyes, MD de Jong and Y Kawaoka. Human infections with highly pathogenic H5N1 influenza virus. Lancet 2007;371:1464-75.
- Lipatov AS, A Krauss, Y Guan, M Peiris et al. Neurovirulence in mice of H5N1 influenza virus genotypes isolated from Hong Kong poultry in 2001. J. Virol 2003;77(6):3816-3823.
- Hatchette TF, SJ Drews, N Bastien, Y. Li et al. Detection of Influenza H7N9 virus: all molecular tests are not equal. J Clin Microbiol 2013;51(11):3835-38.
Lead and corresponding authors
- Kevin Fonseca, Clinical Virologist, Provincial Laboratory, Alberta Health Services, Canada
- Martin Lavoie, Deputy Medical Officer of Health, Alberta Health, Canada
Additional authors in alphabetical order by organization and last name:
- Alberta Health:
- James Talbot, Chief Medical Officer of Health, Alberta Health, Canada
- Alberta Health Services:
- Jeff Fuller, Clinical Microbiologist, Provincial Laboratory, Alberta Health Services, Canada
- Robyn Harrison, Communicable Disease Consultant Workplace Health & Safety, Alberta Health Services
- Mark Joffe, Senior Medical Director, Infection Prevention and Control, Alberta Health Services
- Kanti Pabbaraju, Senior Scientist, Provincial Laboratory, Alberta Health Services, Canada
- Raymond Tellier, Medical Microbiologist, Provincial Laboratory, Alberta Health Services, Canada
- Graham Tipples, Medical Director, Provincial Laboratory, Alberta Health Services, Canada
- Stephen Tsekrekos, Medical Director, Workplace Health & Safety, Alberta Health Services
- Sallene Wong, Scientist, Provincial Laboratory, Alberta Health Services, Canada
- National Microbiology Laboratory:
- Natalie Bastien, Research Scientist, Influenza and Respiratory Virus Section, National Microbiology Laboratory, Winnipeg, Canada
- Yan Li, Chief, Influenza and Respiratory Virus Section, National Microbiology Laboratory, Winnipeg, Canada
Acknowledgments
The named authors would like to acknowledge the timely, thorough and expert contributions made by local medical, nursing, public health, infection control, and health care professionals to this work and this publication. At the request of the family, to preserve confidentiality, additional contributing authors have agreed not to be named. We would also like to express particular thanks to the family for their kind cooperation in this difficult time for them.
--
Kevin Fonseca, PhD, D(ABMM) / Clinical Virologist, Provincial Laboratory of Public Health / Alberta Health Services / Canada kevin.fonseca@albertahealthservices.ca
[ProMED is grateful to Kevin Fonseca and colleagues for providing this authoritative information. This report provides many additional historical, clinical and laboratory details of the recent fatal case of H5N1 influenza in a Canadian traveler returned from Beijing. (Media reports have stated that the patient was a female healthcare worker originally from China, in her 20s.) Notable features include the absence of apparent contact with poultry (though investigation is ongoing), the presence of pneumonia progressing from the right apex to multiple lobes and pleural effusion, the presence of intracranial edema, and radiographic evidence of inflammation of the meninges. It does not appear that influenza was suspected early enough to institute timely antiviral therapy.
H5N1 influenza A virus was detected from respiratory samples and from cerebrospinal fluid by nucleic acid amplification methods. Sequence analysis confirmed the identity of the virus and is indicative of viral features including high-pathogenicity, absence of oseltamivir resistance mutations at position 275, and wild-type affinity for the avian sialic acid receptor. - Mod.LM
A HealthMap/ProMED-mail map can be accessed at: http://healthmap.org/r/1zaU.]
(?)
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Re: Canada - H5N1 death in Alberta after travel from China - died from meningoencephalitis
We must also bear in mind that Influenza Group 1 SubTypes, especially those along the "H1.a" lineage<sup>1</sup> such as H1N1 and H5N1, tend toward neurotropism in passage experiments on murine model. Wilson Smith's UK NIMR lab established that cornerstone research in 1933.
Ergo, wider foundation for discussion of human neurological H5N1 pathology may be required beyond mouse studies.
1. Influenza A viruses: new research developments
Rafael A. Medina & Adolfo García-Sastre
Nature Reviews Microbiology 9, 590-603 (August 2011)
doi:10.1038/nrmicro2613
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Re: Canada - H5N1 death in Alberta after travel from China - died from meningoencephalitis
Originally posted by Giuseppe Michieli View PostAs for the encephalitis presentation (and the presence in the liquor of viral particles), it may be useful to remind that H5N1 has a polybasic cleavage site in the hemagglutinin (when H7N9 doesn't) and thus its tissue tropism is enhanced (especially if present the E627K amino-acid substitution in the PB2 gene).
Encephalitis is known to occur when pure avian influenza viruses jumps to human: see for example the accounts of first waves of 1918 H1N1 virus and earlier those from 1889-90 Northern Italy 'Nona' H3Nx outbreak.
Encephalopathy is also a feature - although seldomly - of the seasonal influenza viruses, such as H1, H3 & B.
Definitely, the HA polybasic cleavage site of H5N1 viruses enhances its penetration in extra pulmonary tissues. gm
____
See for example this paper: Source: Journal of Virology, full document (and abstract): http://jvi.asm.org/content/77/6/3816.full
J. Virol., March 2003, vol. 77 no. 6, 3816-3823 - doi: 10.1128/JVI.77.6.3816-3823.2003
Neurovirulence in Mice of H5N1 Influenza Virus Genotypes Isolated from Hong Kong Poultry in 2001
Aleksandr S. Lipatov 1, Scott Krauss 1, Yi Guan 2, Malik Peiris 2, Jerold E. Rehg 3, Daniel R. Perez 1, and Robert G. Webster 1,4,*
Author Affiliations: 1Division of Virology, Department of Infectious Diseases - 3Department of Pathology, St. Jude Children's Research Hospital - 4Department of Pathology, University of Tennessee, Memphis, Tennessee 38105 - 2Department of Microbiology, University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, People's Republic of China
ABSTRACT
We studied the pathogenicity of five different genotypes (A to E) of highly pathogenic avian H5N1 viruses, which contained HA genes similar to those of the H5N1 virus A/goose/Guangdong/1/96 and five different combinations of “internal” genes, in a mouse model. Highly pathogenic, neurotropic variants of genotypes A, C, D, and E were isolated from the brain after a single intranasal passage in mice. Genotype B virus was isolated from lungs only. The mouse brain variants had amino acid changes in all gene products except PB1, NP, and NS1 proteins but no common sets of mutations. We conclude that the original H5N1/01 isolates of genotypes A, C, D, and E were heterogeneous and that highly pathogenic neurotropic variants can be rapidly selected in mice.
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You are right on track, Guiseppe. Thank you for reminding our readers and adding the Virology 2003 paper.
This genetic fact may be found as an important aspect of the case if the evidence basis is made more comprehensive.
At the beginning of this investigation, we discussed the matter of PolyBasic Cleavage in combination with high-volume, under-reported Emergent H7N9 exposure in Post #47 earlier on this thread, alongside our Case Summary and the "thermocline" aspect of host switching:
Originally posted by NS1 2 Days Ago View Post
[excerpt]
. . .
If the Case Summary is accurate to this point, we may consider a virus with aberrant genetics or a host with deranged immune response.
Deranged Immune Response- Host Genetic Immune Variance
- Multiple Pathogens
- Emergent H7N9
- H5N1
- Multiplicity of Exposure
Exposure to high-volume, under-reported Emergent H7N9 may have deranged the young woman's immune system prior to or during an H5N1 infection. Recall the normalcy of false negative testing results in eH7N9 and the lack of cough in cases, early and recent. A suppressed immune response stultified by asymptomatic eH7N9 infection is an opportunity for variant tropism with a PolyBasic-cleaved virus like H5N1.
A negative test is not a measure of absence or an exclusion, but only a lack of detection at a point in time and at a sample location using a certain method. Testing fails to detect at a rate above 50% under certain conditions. This young woman with variant tissue tropism may be one of those cases.
Neurological symptoms in avian hosts are common during host switching.
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