Call for Open Data on All Influenza, Human & Animal, from Around the World

[Laidback Al]

Call for open data on human avian influenza cases from around the world

An important research paper on the epidemiology of avian influenza A(H5N1) has just been published by Eurosurveillance (Avian influenza A(H5N1) in humans: new insights from a line list of World Health Organization confirmed cases, September 2006 to August 2010 FluTracker?s link to full article).

Since 2005, researchers from Robert Koch Institute (RKI) in Germany have been compiling a ?line list? of confirmed, probable, and suspected human cases of avian influenza (AI) from around the world. They performed several statistical analyses on the data set which consisted of a total 294 cases of which 234 were confirmed by WHO between 2006 and 2010. The RKI authors make several observations about the results of their analyses that are worth pointing out.

But first a couple of corrections and comments about the article.

With this study, we summarised the current global AI situation in humans. It is, to our knowledge, the first study that not only analysed human AI cases worldwide on the basis of a line list collected over several years but in addition made these case-based data available online.

The first part of this sentence is correct, the second part is not. The first on-line case-based data for avian influenza that I am aware of was posted on February 2, 2006, as an Microsoft Access database as an adjunct to the ?Influenza Report? and online textbook. (Link). The database included 116 WHO confirmed cases. The database was updated for several months in 2006 with the final downloadable database including 176 cases as of May 5, 2006. After May 2006 the online database was no longer updated and by March 28, 2007 it was no longer available on line.

Between November, 2003 and July 31, 2010, a total of 483 human cases of A(H5N1) were confirmed by WHO. The analysis of the RKI researchers only includes 234 of these cases, less than half. Care should be taken in interpreting the epidemiological results in this article.

Important Conclusions and Discussions in the Article

In our study all patients hospitalised eight or more days after symptom onset died. This suggests a rather narrow time window for antiviral drug administration.

This observation indicates that in most cases, especially severe, virulent cases of AI, early hospitalization and treatment with antivirals is critical for survival when infected with H5N1.

Our study was solely based on data from publicly available case reports and is subject to several limitations. Our monitoring instrument was only entirely implemented in August 2006 and thus trend analyses were not exploited to its full extent. Within the used reports, negative values, e.g. ?case not hospitalised?, were not systematically mentioned, which may lead to biases. Time specifications, e.g. on dates of exposure or hospitalisation, needed for time-to-event analyses, were often incomplete. Case reports did not systematically contain details on medical care and specific antiviral treatment. Therefore, analyses were restricted to ?hospitalisation? as general indicator for access to medical care. Given the sparse information on possible contact with infected individuals and clusters of human AI cases available from the serial reports within the investigated period, clusters could not be evaluated as initially planned. Other studies reporting on clustered cases had mostly accessed additional case-investigation reports and patient interviews [23,30]. We based our analyses on WHO confirmed cases, although unconfirmed cases had been recorded in our line list, due to lacking information for probable and suspected cases. Including probable cases in our analyses did, however, not change the cases? sex ratio or CFR substantially when compared to confirmed cases only.

The gist of this observation is simple. The RKI researchers were hampered by lack of publicly available data. As I have previously discussed, there is little publicly available detail on human H5N1 cases. Several years ago, media reports on human cases could be used to supplement details from WHO reports on these human cases. Information on age, sex, specific location, family contacts and relationships, etc. could often be obtained from media reports. Now these media reports no longer have critical details, and often times media outlets no longer even report details of suspected or confirmed cases of AI.

A line list needs to be flexible in view of potential new information to be entered. . . . Presenting cases in the format of a line list is not a goal in itself, but a prerequisite for targeting surveillance and identifying risk factors, as well as a starting point for prospective studies, e.g. investigating potential human-to-human transmission, the transmissibility of avian influenza viruses, and host-related factors including age-dependent immunity in humans.

All of us at FluTrackers supports the development and maintenance of open databases to track emerging infectious diseases. In 2009, FluTrackers members compiled a database of some of the earliest media reported cases of pandemic H1N1 and made it publicly available. (Link)

We would like to encourage that an anonymised case-based database for AI in humans is directly placed publicly and continuously updated, e.g. by an internationally renowned organisation such as WHO. Open access to analysable data might accelerate the identification and implementation of research questions and surveillance priorities and thus enhance our understanding of ? still mostly fatal ? AI in humans and permit the rapid detection of epidemiological changes with implications for human health.

FluTrackers.com agrees that a publicly available database of all human A(H5N1) cases be maintained and updated by WHO. The data should be consistent across all fields and provided in a timely manner by all WHO members as required by International Health Regulations.

Avian Influenza is an emerging infectious disease that has affected less than 600 people worldwide since 1997. So far it has been unable to easily transmit between humans. But with an overall death rate of more than 50% among confirmed cases, an avian influenza pandemic could wipe out large portions of the world?s population if it becomes easily transmissible between humans. That is why all countries throughout the world need to comply with IHR and report human outbreaks of A(H5N1) immediately. And that is also why WHO needs to maintain and update, on a daily basis, a publicly accessible database of human cases of A(H5N1).

[sharon sanders]

Call for Open Data on Human Avian & Swine Influenza Cases from Around the World

Swine-Origin Influenza A (H3N2) Virus Infection in Two Children --- Indiana and Pennsylvania, July--August 2011
Early Release
September 2, 2011 / 60(Early Release);1-4

Influenza A viruses are endemic in many animal species, including humans, swine, and wild birds, and sporadic cases of transmission of influenza A viruses between humans and animals do occur, including human infections with avian-origin influenza A viruses (i.e., H5N1 and H7N7) and swine-origin influenza A viruses (i.e., H1N1, H1N2, and H3N2) (1). Genetic analysis can distinguish animal origin influenza viruses from the seasonal human influenza viruses that circulate widely and cause annual epidemics. This report describes two cases of febrile respiratory illness caused by swine-origin influenza A (H3N2) viruses identified on August 19 and August 26, 2011, and the current investigations. No epidemiologic link between the two cases has been identified, and although investigations are ongoing, no additional confirmed human infections with this virus have been detected. These viruses are similar to eight other swine-origin influenza A (H3N2) viruses identified from previous human infections over the past 2 years, but are unique in that one of the eight gene segments (matrix [M] gene) is from the 2009 influenza A (H1N1) virus. The acquisition of the M gene in these two swine-origin influenza A (H3N2) viruses indicates that they are "reassortants" because they contain genes of the swine-origin influenza A (H3N2) virus circulating in North American pigs since 1998 (2) and the 2009 influenza A (H1N1) virus that might have been transmitted to pigs from humans during the 2009 H1N1 pandemic. However, reassortments of the 2009 influenza A (H1N1) virus with other swine influenza A viruses have been reported previously in swine (3). Clinicians who suspect influenza virus infection in humans with recent exposure to swine should obtain a nasopharyngeal swab from the patient for timely diagnosis at a state public health laboratory and consider empiric neuraminidase inhibitor antiviral treatment to quickly limit potential human transmission (4).

Case Reports

Patient A. On August 17, 2011, CDC was notified by the Indiana State Department of Health Laboratories of a suspected case of swine-origin influenza A (H3N2) infection in a boy aged <5 years. The boy, who had received influenza vaccine in September 2010, experienced onset of fever, cough, shortness of breath, diarrhea, and sore throat on July 23, 2011. He was brought to a local emergency department (ED) where a respiratory specimen later tested positive for influenza A (H3). The boy was discharged home, but was not treated with influenza antiviral medications. He has multiple chronic health conditions, returned to the ED on July 24, 2011, and was hospitalized for treatment of those health problems, which had worsened. The boy was discharged home on July 27, 2011, and has since recovered from this illness. As part of routine CDC-supported influenza surveillance, the respiratory specimen collected on July 24, 2011, was forwarded to the Indiana State Department of Health Laboratories, where polymerase chain reaction (PCR) testing identified a suspect swine-origin influenza A (H3N2) virus on August 17, 2011. The specimen was forwarded to CDC where the findings were confirmed through genome sequencing on August 19, 2011.

No direct exposure to swine was identified for this child; however, a caretaker reported direct contact with asymptomatic swine in the weeks before the boy's illness onset and provided care to the child 2 days before illness onset. No respiratory illness was identified in any of the child's family or close contacts, the boy's caretaker, or in the family or contacts of the caretaker.

Patient B. On August 24, 2011, CDC was notified by the Pennsylvania Department of Health of a suspected case of swine-origin influenza A (H3N2) virus infection in a girl aged <5 years. The girl, who had received influenza vaccine in September 2010, experienced acute onset of fever, nonproductive cough, and lethargy on August 20, 2011. She was brought to a local hospital ED where a nasopharyngeal swab tested positive for influenza A by rapid influenza diagnostic test. She was not treated with influenza antiviral medications and was discharged home the same day. The girl has completely recovered from this illness.

A nasopharyngeal swab and nasal wash specimen were obtained at the ED and forwarded to the Pennsylvania State Department of Health Bureau of Laboratories for additional testing as part of routine CDC-supported influenza surveillance. On August 23, 2011, the state public health laboratory identified a suspected swine-origin influenza A (H3N2) virus by PCR testing, and both specimens were forwarded to CDC. On August 26, 2011, genome sequencing confirmed the virus as swine-origin influenza A (H3N2). On August 16, 2011, the girl was reported to have visited an agricultural fair where she had direct exposure to swine and other animals. No additional illness in the girl's family or close contacts has been identified, but illness in other fair attendees continues to be investigated. No additional confirmed swine-origin influenza virus infections have been identified thus far.

Epidemiologic and Laboratory Investigations
As of September 2, 2011, no epidemiologic link between patients A and B had been identified, and no additional cases of confirmed infection with the identified strain of swine-origin influenza A (H3N2) virus had been identified. Surveillance data from both states showed low levels of influenza activity at the time of both patients' illnesses. Case and contact investigations by the county and state human and animal health agencies in Indiana and Pennsylvania are ongoing, and enhanced surveillance for additional human cases is being implemented in both states.

Preliminary genetic characterization of these two influenza viruses has identified them as swine-origin influenza A (H3N2) viruses. Full genome sequences have been posted to publicly available web sites. The viruses are similar, but not identical to each other. Seven of the eight gene segments, including the hemagglutinin (HA) and neuraminidase (NA) genes, are similar to those of swine H3N2 influenza viruses circulating among U.S. pigs since 1998 (2) and previously identified in the eight other sporadic cases of human infection with swine-origin influenza A (H3N2) viruses in the United States since 2009.* The one notable difference from the viruses previously identified in human infections with swine-origin influenza A (H3N2) virus is that these two viruses have a matrix (M) gene acquired from the 2009 influenza A (H1N1) virus, replacing the classical swine M gene present in the prior eight swine-origin influenza A (H3N2) virus infections in humans.

Although reassortment between swine influenza and 2009 influenza A (H1N1) viruses has been reported in pigs in the United States (3), this particular genetic combination of swine influenza virus segments is unique and has not been reported previously in either swine or humans, based on a review of influenza genomic sequences publicly available in GenBank.† Analysis of data submitted to GenBank via the U.S. Department of Agriculture (USDA) Swine Influenza Virus Surveillance Program subsequent to this case identified two additional influenza A (H3N2) isolates from swine containing the M gene from the 2009 influenza A (H1N1) virus. Genome sequencing is underway to completely characterize the genetic composition of these two swine influenza isolates. (USDA Agricultural Research Service and USDA Animal and Plant Health Inspection Service, unpublished data, 2011).

The viruses in these two patients are resistant to amantadine and rimantadine, but are susceptible to the neuraminidase inhibitor drugs oseltamivir and zanamivir. Because these viruses carry a unique combination of genes, no information currently is available regarding the capacity of this virus to transmit efficiently in swine, humans, or between swine and humans.

Reported by
Kumar Nalluswami, MD, Atmaram Nambiar, MD, Perrianne Lurie, MD, Maria Moll, MD, James Lute, PhD, Owen Simwale, MPH, Erica Smith, MPH, Larry Sundberg, MPH, Brian Seiler, Stephen Swanson, Pennsylvania Dept of Health; Nanette Hanshaw, DVM, Craig Shultz, DVM, Erin Moore, DVM, Pennsylvania Dept of Agriculture. Shawn Richards, Mark Glazier, Katie Masterson, Lyndsey Hensler, MS, Indiana State Dept of Health; Cheryl Miller, DVM, Melissa Justice, DVM, Indiana Board of Animal Health. Swine Influenza Virus Team, US Dept of Agriculture. Scott Epperson, MPH, Lynnette Brammer, MPH, Lyn Finelli, DrPH, Susan Trock, DVM, Michael Jhung, MD, Joseph Bresee, MD, Stephen Lindstrom, PhD, Alexander Klimov, PhD, Daniel Jernigan, MD, Nancy Cox, PhD, Influenza Div, National Center for Immunization and Respiratory Diseases; Jeffrey Miller, MD, Div of Applied Sciences, Office of Surveillance, Epidemiology, and Laboratory Services, CDC. Corresponding Contributor: Scott Epperson, sepperson@cdc.gov, 404-639-3747.

Editorial Note
To detect human infections with animal influenza viruses more effectively, CDC and state and local health departments have strengthened laboratory and epidemiologic procedures to promptly detect sporadic cases such as these. Since 2005, state public health laboratories have had the capability to detect non-human origin--influenza A viruses by PCR testing. From 2005 to 2007, CDC received reports of approximately one human infection with a swine-origin influenza virus each year. In 2007, human infection with a novel influenza A virus, including swine-origin influenza virus infections, became a nationally notifiable condition. Since that time, CDC has received approximately three to five reports a year of human infections with swine-origin influenza viruses. The recent increase in reporting might be, in part, a result of increased influenza testing capabilities in public health laboratories that allows for identification of human and swine-origin influenza viruses, but genetic changes in swine influenza viruses and other factors also might be contributing to this increase (5--7). During December 2005--November 2010, before the two cases described in this report, 21 cases of human infection with swine-origin influenza were reported (12 cases with swine-origin influenza A (H1N1) virus infection, eight cases with swine-origin influenza A (H3N2) virus infection, and one case with swine-origin influenza A (H1N2) virus infection). Six of these 21 cases occurred in patients who reported direct exposure to pigs; 12 patients reported being near pigs; human-to-human transmission was suspected in two cases after epidemiologic investigations revealed no reported contact with swine in either case, but contact with ill persons who reported swine exposure was the suspected source of infection; the exposure in one case was unknown (8) (CDC, unpublished data; 2011). Although the vast majority of human infections with animal influenza viruses do not result in human-to-human transmission (9,10), each case should be investigated fully to ascertain whether these viruses are transmitted among humans and to limit further exposure of humans to infected animals, if infected animals are identified. Such investigations require close collaboration between CDC, state and local public health officials, and animal health officials.

The lack of known direct exposure to pigs in one of the two cases described in this report suggests the possibility that limited human-to-human transmission of this influenza virus occurred. Likely transmission of swine-origin influenza A (H3N2) virus from close contact with an infected person has been observed in past investigations of human infections with swine-origin influenza A virus, but has not resulted in sustained human-to-human transmission. Preliminary evidence from the investigation of the Indiana case shows no ongoing transmission. No influenza illness has been identified, but if additional chains of transmission are identified rapid intervention is warranted try to prevent further spread of the virus. Clinicians should consider swine-origin influenza A virus infection as well as seasonal influenza virus infections in the differential diagnosis of patients with febrile respiratory illness who have been near pigs. Clinicians who suspect influenza virus infection in humans with recent exposure to swine, should obtain a nasopharyngeal swab from the patient, place the swab in a viral transport medium, contact their state or local health department to facilitate transport and timely diagnosis at a state public health laboratory, and consider empiric neuraminidase inhibitor antiviral treatment (4). CDC requests that state public health laboratories send all suspected swine-origin influenza A specimens to the CDC, Influenza Division, Virus Surveillance and Diagnostics Branch Laboratory.

References
Wright PF, Neumann G, Kawaoka Y. Orthomyxoviruses. In: Knipe DM, Howley PM, eds. Fields virology. Vol. 2. 5th ed. Philadelphia, PA: Lippincott, Williams, and Wilkins; 2007:1692--740.
Vincent AL, Ma W, Lager KM, Janke BH, Richt JA. Swine influenza viruses: a North American perspective. Adv Virus Res 2008;72:127--54.
Duchatez MF, Hause B, Stigger-Rosser E, et al. Multiple reassortment between pandemic (H1N1) 2009 and endemic influenza viruses in pigs, United States. Emerg Infect Dis 2011;17:1624--9.
CDC. Antiviral agents for the treatment and chemoprophylaxis of influenza: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR 2011;60(No. RR-1).
Vincent AL, Ma W, Lager KM, Janke BH, Richt JA. Swine influenza viruses: a North American perspective. Adv Virus Res 2008;72:127--54.
Vincent AL, Swenson SL, Lager KM, Gauger PC, Loiacono C, Zhang Y. Characterization of an influenza A virus isolated from pigs during an outbreak of respiratory disease in swine and people during a county fair in the United States. Vet Microbiol 2009;137:51--9.
Newman AP, Reisdorf E, Beinemann J, et al. Human case of swine influenza A (H1N1) triple reassortant virus infection, Wisconsin. Emerg Infect Dis 2008;14:1470--2.
Shinde V, Bridges CB, Uyeki TM, et al. Triple reassortant swine influenza A (H1) in humans in the United States, 2005--2009. N Engl J Med 2009;25:2616--25.
Myers KP, Olsen CW, Gray GC. Cases of swine influenza in humans: a review of the literature. Clin Infect Dis 2007;44:1084--8.
Wells DL, Hopfensperger DJ, Arden NH, et al. Swine influenza virus infections. Transmission from ill pigs to humans at a Wisconsin agricultural fair and subsequent probable person-to-person transmission. JAMA 1991;265:478--81.

* Additional information is available at http://www.cdc.gov/flu/weekly/pastreports.htm.

† Available at http://www.ncbi.nlm.nih.gov/Genbank.


What is already known on this topic?

During December 2005--November 2010, 21 cases of human infection with swine-origin influenza were reported, including 12 cases with swine-origin influenza A (H1N1) virus infection, eight cases with swine-origin influenza A (H3N2) virus infection, and one case with swine-origin influenza A (H1N2) virus infection.

What is added by this report?

This report describes two cases of febrile respiratory illness caused by swine-origin influenza A (H3N2) viruses identified on August 19 and August 26, 2011. The viruses identified in these cases are unique in that one of the eight gene segments (matrix [M] gene) is from the 2009 influenza A (H1N1) virus.

What are the implications for public health practice?

Non-human influenza virus infections rarely result in human-to-human transmission, but the implications of sustained ongoing transmission between humans is potentially severe; therefore, prompt and thorough identification and investigation of these sporadic human infections with non-human influenza viruses are needed to reduce the risk for sustained transmission.

http://www.cdc.gov/mmwr/preview/mmwrhtml/mm60e0902a1.htm?s_cid=mm60e0902a1_w

[Giuseppe]

Re: Call for Open Data on Human Avian &amp; Swine Influenza Cases from Around the World

The reason behind the presumptive seasonal vaccine failure in the above two paediatric cases is presumably the fact that H3N2 - although human/animal reassortant - reacts poorly with current seasonal H3N2 trivalent vaccine component, and that matrix protein is not one of the main antigenic sites for influenza, as hemagglutinin and neuramminidase are (HA and NA).

Further, since swoH3N2 contains several human influenza virus genes - it is possible that people born before a certain year have a partial immunity, so a major outbreak could be less likely than the incident in 2009 when the swoH1N1 was much more able to evade our immune response.

This could also explain the likelihood of asymptomatic carriers for swoH3N2, already in the past suspected by the US CDC to have had a limited but unsustained human-to-human transmission. (IOH)

[Giuseppe]

Re: Call for Open Data on Human Avian &amp; Swine Influenza Cases from Around the World

See Emerg Infect Dis. Journal for an antigenic overview of swoH3N2: http://www.cdc.gov/ncidod/eid/vol12no07/06-0268.htm


Dispatch
Triple Reassortant H3N2 Influenza A Viruses, Canada, 2005

Christopher W. Olsen,*<SUP></SUP> Alexander I. Karasin,* Suzanne Carman,? Yan Li,? Nathalie Bastien,? Davor Ojkic,? David Alves,? George Charbonneau,? Beth M. Henning,# Donald E. Low,** Laura Burton,** and George Broukhanski**

*University of Wisconsin-Madison, Madison, Wisconsin, USA; ?Animal Health Laboratory, Guelph, Ontario, Canada; ?Canadian Science Centre for Human and Animal Health, Winnipeg, Manitoba, Canada; ?Ontario Ministry of Agriculture, Food, and Rural Affairs, Guelph, Ontario, Canada; ?Swine Services Group, Stratford, Ontario, Canada; #Ontario Ministry of Health and Long Term Care, Clinton, Ontario, Canada; and **Ontario Ministry of Health and Long Term Care, Toronto, Ontario, Canada

Suggested citation for this article
<HR>

Since January 2005, H3N2 influenza viruses have been isolated from pigs and turkeys throughout Canada and from a swine farmer and pigs on the same farm in Ontario. These are human/classical swine/avian reassortants similar to viruses that emerged in US pigs in 1998 but with a distinct human-lineage neuraminidase gene.

Influenza viruses of the classical H1N1 lineage were the dominant cause of influenza among North American pigs for >60 years (1). However, in 1998, H3N2 viruses emerged and rapidly spread throughout the US swine population (2?4). These were unique triple reassortant genotype viruses, with hemagglutinin (HA), neuraminidase (NA), and RNA polymerase (PB1) genes of human influenza virus lineage; nucleoprotein (NP), matrix (M), and nonstructural (NS) genes of classical swine virus lineage; and RNA polymerase (PA and PB2) genes of North American avian virus lineage. Further reassortment between these viruses and classical H1N1 swine viruses led to the emergence of reassortant H1N2 and H1N1 viruses among pigs in the United States (1). The reassortant H3N2 and H1N2 viruses have also been isolated from turkeys and ducks in the United States (5?8). Despite geographic proximity and cross-boundary trade in pigs and turkeys between the United States and Canada (9, D. Harvey, pers. comm.), these reassortant viruses did not initially infect animals in Canada. However, beginning in approximately January 2005, H3N2 influenza viruses swept rapidly across Canada. We describe the genetic characterization of reassortant H3N2 viruses from pigs, turkeys, and a swine farm worker in contact with sick pigs during this outbreak.

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[tetano]

Call for Open Data on Human Avian &amp; Swine Influenza Cases from Around the World

We want open data so that we can better understand what viral "brew" is circulating.....

Journal of Virology

First published November 2011, doi: 10.1128/JVI.06203-11 JVI.06203-11


Reassortment and mutation of the avian influenza polymerase PA subunit overcomes species barriers

Andrew Mehle1,*,
Vivien G. Dugan2,
Jeffery K. Taubenberger2 and
Jennifer A. Doudna1,3,4

+ Author Affiliations

1Department of Molecular and Cell Biology
3Department of Chemistry University of California, Berkeley, CA 94720, USA
2Viral Pathogenesis and Evolution Section, Laboratory of Infectious Diseases, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
4Physical Biosciences Division, Lawrence Berkeley National Laboratory Berkeley, CA 94720, USA

ABSTRACT

Emergence of new pandemic influenza A viruses requires overcoming barriers to cross-species transmission as viruses move from animal reservoirs into humans. This complicated process is driven by both individual gene mutations and genome reassortment. The viral polymerase complex, composed of the proteins PB1, PB2 and PA, is a major viral factor controlling host-adaptation, and reassortment events involving polymerase gene segments occurred in past pandemic viruses. Here we investigate the ability of polymerase reassortment to restore the activity of an avian influenza polymerase that is normally impaired in human cells. Our data show that substitution of human-origin PA subunits into an avian influenza polymerase alleviates restriction in human cells and increases polymerase activity in vitro. Reassortants with 2009 pandemic H1N1 PA proteins were the most active. Mutational analyses demonstrate that the majority of the enhancing activity in human PA results from a threonine to serine change at residue 552. [

Reassortant viruses with avian polymerases and human PA subunits, or simply the T552S mutation, displayed faster replication kinetics in culture and increased pathogenicity in mice compared to those containing a wholly avian polymerase complex. Thus, acquisition of a human PA subunit, or the signature T552S mutation, is a potential mechanism to overcome the species-specific restriction of avian polymerases and increase virus replication.

Our data suggest that the human, avian, swine and 2009 H1N1-like viruses that are currently co-circulating in pig populations set the stage for PA reassortments with the potential to generate novel viruses that could possess expanded tropism and enhanced pathogenicity.

http://jvi.asm.org/content/early/2011/11/09/JVI.06203-11.abstract