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PANDEMIC ALERT LEVEL
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Tracking the next pandemic: Avian Flu Talk

B2H v. H2H

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kparcell View Drop Down
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    Posted: March 27 2007 at 4:39pm
Alert levels are keyed to rate of human infection, but to bird-to-human efficient transmission would likely soon be followed by human pandemic as it would create many opportunities for a foothold.

And what's far more likely to happen first - efficient B2H or efficient H2H?

So...
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RE efficent B2H all the way back to 2004....

Although in all 10 cases the infection appears to have been acquired directly from infected poultry, the potential exists for genetic reassortment with human influenzaviruses and the evolution of human-to-human transmission.

Previous Volume 350:1179-1188 March 18, 2004 Number 12
Avian Influenza A (H5N1) in 10 Patients in Vietnam

Tran Tinh Hien, M.D., Nguyen Thanh Liem, M.D., Nguyen Thi Dung, M.D., Luong Thi San, M.D., Pham Phuong Mai, M.D., Nguyen van Vinh Chau, M.D., Pham Thi Suu, M.D., Vo Cong Dong, M.D., Le Thi Quynh Mai, M.D., Ph.D., Ngo Thi Thi, M.D., Dao Bach Khoa, M.D., Le Phuc Phat, M.D., Nguyen Thanh Truong, M.D., Hoang Thuy Long, M.D., Ph.D., Cao Viet Tung, M.D., Le Truong Giang, M.D., Ph.D., Nguyen Dac Tho, M.D., Le Hong Nga, M.D., Nguyen Thi Kim Tien, M.D., Ph.D., Le Hoang San, M.D., Le Van Tuan, M.P.H., Christiane Dolecek, M.D., Tran Tan Thanh, B.Sc., Menno de Jong, M.D., Ph.D., Constance Schultsz, M.D., Ph.D., Peter Cheng, M.Sc., Wilina Lim, M.B., B.S., Peter Horby, M.B., B.S., the World Health Organization International Avian Influenza Investigative Team, and Jeremy Farrar, F.R.C.P., D.Phil.



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Perspective
by Klempner, M. S.


ABSTRACT

Background Recent outbreaks of avian influenza A (H5N1) in poultry throughout Asia have had major economic and health repercussions. Human infections with this virus were identified in Vietnam in January 2004.

Methods We report the clinical features and preliminary epidemiologic findings among 10 patients with confirmed cases of avian influenza A (H5N1) who presented to hospitals in Ho Chi Minh City and Hanoi, Vietnam, in December 2003 and January 2004.

Results In all 10 cases, the diagnosis of influenza A (H5N1) was confirmed by means of viral culture or reverse transcriptase–polymerase chain reaction with primers specific for H5 and N1. None of the 10 patients (mean age, 13.7 years) had preexisting medical conditions. Nine of them had a clear history of direct contact with poultry (median time before onset of illness, three days). All patients presented with fever (temperature, 38.5 to 40.0°C), respiratory symptoms, and clinically significant lymphopenia (median lymphocyte count, 700 per cubic millimeter). The median platelet count was 75,500 per cubic millimeter. Seven patients had diarrhea. In all patients, there were marked abnormalities on chest radiography. There was no definitive evidence of human-to-human transmission. Eight patients died, one patient has recovered, and one is recovering.

Conclusions Influenza A (H5N1) infection, characterized by fever, respiratory symptoms, and lymphopenia, carries a high risk of death. Although in all 10 cases the infection appears to have been acquired directly from infected poultry, the potential exists for genetic reassortment with human influenzaviruses and the evolution of human-to-human transmission. Containment of influenza A (H5N1) in poultry throughout Asia is therefore urgently required.



Source Information

From the Hospital for Tropical Diseases (T.T.H., N.T.D., P.P.M., N.V.C., D.B.K., N.T. Truong) and the Oxford University Clinical Research Unit at the Hospital for Tropical Diseases (C.D., T.T.T., M.J., C.S., J.F.); Pediatric Hospital Number Two (V.C.D.); Health Service of Ho Chi Minh City (L.T.G.); the Pasteur Institute (N.T.K.T., L.H.S., L.V.T.); and the Preventive Medicine Center (N.D.T., L.H.N.) — all in Ho Chi Minh City, Vietnam; the National Pediatric Hospital (N.T.L., L.T.S., P.T.S., N.T. Thi, L.P.P., C.V.T.); and the National Institute of Hygiene and Epidemiology (H.T.L., L.T.Q.M.) — both in Hanoi, Vietnam; the Government Virus Unit, Department of Health, Hong Kong, China (P.C., W.L.); and the Vietnam Office, World Health Organization, Hanoi, Vietnam (P.H.).

This article was published at www.nejm.org on February 25, 2004.

Address reprint requests to Dr. Farrar at the Hospital for Tropical Diseases, 190 Ben Ham Tu, Quan 5, Ho Chi Minh City, Vietnam, or at jeremyjf@hcm.vnn.vn.



Full Text of this Article



This article has been cited by other articles:
http://content.nejm.org/cgi/content/abstract/350/12/1179
    
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Their thoughts ....
Published online before print December 7, 2006, 10.1073/pnas.0609227103
PNAS | December 19, 2006 | vol. 103 | no. 51 | 19368-19373 Articles by Kilpatrick, A. M.
Articles by Daszak, P.

PubMed

PubMed Citation
Articles by Kilpatrick, A. M.
Articles by Daszak, P.
Pubmed/NCBI databasesMedline Plus Health Information
Bird Flu
International Health


From the Cover
BIOLOGICAL SCIENCES / ECOLOGY
Predicting the global spread of H5N1 avian influenza

A. Marm Kilpatrick*,, Aleksei A. Chmura*, David W. Gibbons, Robert C. Fleischer, Peter P. Marra¶, and Peter Daszak*

*Consortium for Conservation Medicine, New York, NY 10001; Royal Society for the Protection of Birds, Sandy, Bedfordshire SG19 2DL, United Kingdom; and National Museum of Natural History, and ¶Smithsonian Migratory Bird Center, National Zoological Park, Smithsonian Institution, Washington, DC 20008

Communicated by Hans R. Herren, Millennium Institute, Arlington, VA, October 19, 2006 (received for review April 26, 2006)


The spread of highly pathogenic H5N1 avian influenza into Asia, Europe, and Africa has resulted in enormous impacts on the poultry industry and presents an important threat to human health. The pathways by which the virus has and will spread between countries have been debated extensively, but have yet to be analyzed comprehensively and quantitatively. We integrated data on phylogenetic relationships of virus isolates, migratory bird movements, and trade in poultry and wild birds to determine the pathway for 52 individual introduction events into countries and predict future spread. We show that 9 of 21 of H5N1 introductions to countries in Asia were most likely through poultry, and 3 of 21 were most likely through migrating birds. In contrast, spread to most (20/23) countries in Europe was most likely through migratory birds. Spread in Africa was likely partly by poultry (2/8 introductions) and partly by migrating birds (3/8). Our analyses predict that H5N1 is more likely to be introduced into the Western Hemisphere through infected poultry and into the mainland United States by subsequent movement of migrating birds from neighboring countries, rather than from eastern Siberia. These results highlight the potential synergism between trade and wild animal movement in the emergence and pandemic spread of pathogens and demonstrate the value of predictive models for disease control.


emerging | introduced species | model | trade | zoonotic disease



--------------------------------------------------------------------------------
Author contributions: A.M.K., D.W.G., P.P.M., and P.D. designed research; A.M.K., A.A.C., D.W.G., and R.C.F. performed research; A.M.K. and R.C.F. contributed new reagents/analytic tools; A.M.K., A.A.C., D.W.G., and R.C.F. analyzed data; and A.M.K., A.A.C., D.W.G., R.C.F., P.P.M., and P.D. wrote the paper.
The authors declare no conflict of interest.

This article contains supporting information online at www.pnas.org/cgi/content/full/0609227103/DC1.

To whom correspondence should be addressed. E-mail: kilpatrick@conservationmedicine.org

© 2006 by The National Academy of Sciences of the USA

http://www.pnas.org/cgi/content/abstract/103/51/19368

   
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I have a question that sort of pertains to this thread. My DD just called from Tenn, w/ a very sick cat. Her vet says all of the test have come back negative and they do not know what he is dying of, within 48 hrs the cat has become paralized, blood in urine, and today in respiratory distress, he is also running a very high fever for a cat. I ask her to ask her doc if they tested for avian flu, she called back and said that it was one of the many tests that they did and it was negative. Did I read somewhere or is it just my imagination that the H5N1 test took several days to process and in fact could not be a true test in just a short time. They have put her cat on antibiotics today and stated that the next 24 hrs he will either recover or he will die. She lives in a wooded area and all of her cats (4) are outside cats. We were in fact planning on going there this weekend as it is spring break next week for our grandchildren. Could someone please let me know if the initial test does rule out H5N1 for cats or does it take longer to get the true results. Thank you in advance.
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Originally posted by frankiew frankiew wrote:

I have a question that sort of pertains to this thread. My DD just called from Tenn, w/ a very sick cat. Her vet says all of the test have come back negative and they do not know what he is dying of, within 48 hrs the cat has become paralized, blood in urine, and today in respiratory distress, he is also running a very high fever for a cat. I ask her to ask her doc if they tested for avian flu, she called back and said that it was one of the many tests that they did and it was negative. Did I read somewhere or is it just my imagination that the H5N1 test took several days to process and in fact could not be a true test in just a short time. They have put her cat on antibiotics today and stated that the next 24 hrs he will either recover or he will die. She lives in a wooded area and all of her cats (4) are outside cats. We were in fact planning on going there this weekend as it is spring break next week for our grandchildren. Could someone please let me know if the initial test does rule out H5N1 for cats or does it take longer to get the true results. Thank you in advance.
Hi so far the only thing that has stood out is this statement .....
It is not recommended to perform an in-house influenza detection test.

The following report is for vets ...This time last year .. This is what the vet would ask if suspect to flu .. Still looking ..... They are to send suspect samples to the lab ..


24 March 2006
Infection of cats with H5N1 Avian Influenza Virus


Compiled by Etienne Thiry (Liege/B), with the assistance of Diane Addie (Glasgow/UK), Herman Egberink (Utrecht/NL), Katrin Hartmann (Munich/D), Hans Lutz (Zurich/CH) and Hervé Poulet (Lyon/F).

Introduction
The H5N1 subtype of Avian Influenza Virus type A, a member of the Orthomyxoviridae family, occurs primarily in birds. Transmission to mammals happens sporadically, and the infection then may cause disease with a high morbidity and a high number of deaths among ill animals. Humans, primates, rodents, lagomorphs, mustelids and felids, including the domestic cat may be infected and may succumb to the disease. A listing of susceptible species is given at http://www.nwhc.usgs.gov/disease_information/avian_influenza/affected_species_chart.jsp.

Infection of cats
Felids can be naturally and experimentally infected with H5N1 virus. In February 2004, infection of household cats was reported from Thailand (WHO, 2004); also from that country, two outbreaks of fatal disease in tigers and leopards have been published (Keawcharoen et al., 2004; Thanawongnuwech et al., 2005). In February/March 2006, three cats were found dead on the island of Rügen, Germany and infection with H5N1 virus was established by laboratory tests. Also in March 2006, three cats were found infected but alive in an animal shelter in Graz, Austria. - First experimental evidence for the pathogenicity of H5N1 avian influenza virus for the domestic cat was obtained by Kuiken et al. (2004).

A statement from the WHO (28th February 2006) reads: “There is no present evidence that domestic cats play a role in the transmission cycle of H5N1 viruses. To date, no human case has been linked to exposure to a diseased cat. No outbreaks in domestic cats have been reported. Unlike the case in domestic and wild birds, there is no evidence that domestic cats are a reservoir of the virus. All available evidence indicates that cat infections occur in association with H5N1 outbreaks in domestic or wild birds.”

The following data have been obtained from experimental infections (Kuiken et al., 2004; Rimmelzwaan et al., 2006); they reflect the current state of knowledge and will have to be revised and expanded, as additional information becomes available:

cats can be infected via the intratracheal and oral routes, and by feeding them infected chickens;
infection can occur through contact with infected birds;
infected cats can transmit the virus to in-contact cats;
moderate amounts of virus are sufficient to infect a cat;
the virus is shed with nasal secretions and in faeces; nasal excretion starts 3 days after infection and continues for 4 days or longer;
the incubation period in experimental infections is about 2 days;
clinical signs are fever, lethargy/depression, dyspnoea, conjunctivitis; when clinical signs occur, the outcome of the disease is mostly fatal within one week. Also icterus has been observed.
at necropsy, multifocal lung lesions and petechial haemorrhages in the tonsils, mandibular and retropharyngeal lymph nodes, and the liver are seen;
histologically, inflammatory and necrotic lesions are seen in the lungs, heart, brain, kidneys, liver and adrenal glands. Lesions in the small intestine are observed in cats that had been fed infected chickens.
Risk considerations – questions and answers
1. How may a cat become infected after contacts with birds or poultry products?
Precondition is that the cat lives in a region where one or more H5N1 virus infected birds have been identified by laboratory tests; if this condition applies, the following risk factors must be considered:
the cat lives in an environment where aquatic birds are present;
the cat has access to outdoors;
the cat has contact with free ranging or indoor poultry;
the cat has been fed uncooked poultry meat.
2. How may a cat be infected by another cat?
close contact with an H5N1 infected, sick cat is required at least during the first seven days of infection; although inapparent infection might occur for a limited period, persistent H5N1 virus infections have not been reported.
3. How may a cat transmit the infection to a person?
To date (March 2006), virus transmission from a cat to a person has not been reported.

However,

a H5N1 virus which had infected a cat is already adapted to a mammalian species; viruses isolated from humans exhibited increased virulence for mammals (Maines et al., 2005);
this virus is excreted by the respiratory route and in the faeces;
the level of excretion is high enough to allow in-contact cats to become infected;
in view of the habitual close contacts between cats and their owners, an infected cat can probably infect a human;
the risk of infection and disease for humans can presently not be estimated.
4. When should a veterinary practitioner suspect an ill cat to be infected with H5N1 virus?
Before expressing a suspicion, the potential risk must be evaluated according to the answers to the anamnestic questions above;
if a risk is assumed, a clinical assessment must be performed and clinical signs as given above should be observed: fever, lethargy/depression, dyspnoea, conjunctivitis, rapid death; also neuroligical signs have been reported;
the differential diagnosis should exclude other infections leading to similar systemic and respiratory signs, as caused by feline herpesvirus and calicivirus and by bacteria (Bordetella bronchiseptica, Chlamydophila felis, also mycoplasma);
clinical signs can only result in a probability diagnosis, which must be confirmed by laboratory testing.
5. How should samples for laboratory diagnosis be taken and handled?
The authorities must be notified as specified by the national regulations and the diagnostic laboratory is contacted for detailed instructions. There are some general rules:

To take oropharyngeal, nasal, and rectal swabs or faecal samples:

plastic tubes should be labelled using an alcohol-proof ink marker;
the samples are transferred to the tubes, which are tightly closed;
the outside of the tubes is swabbed with ethyl alcohol to reduce the risk of infection for the receiving personal;
the material safely enclosed in plastic bags is shipped to the national reference laboratory according to procedures defined by the authorities;
Post mortem samples of lung and mediastinal lymph nodes should be kept and shipped in 10% formol saline.

It is not recommended to perform an in-house influenza detection test.

6. Which measures must be taken by the veterinary practitioner when a case of H5N1 virus infection in a cat is suspected?
For own protection:

physical contact with the cat must be minimized, scratching and biting avoided;
gloves, mask and goggles (protective eyewear) should be worn when the cat is manipulated;
sedation of the cat is recommended before taking samples;
for surface decontamination, a standard medical disinfectant is used.
For protection of attending personnel and other animals:

in the veterinary clinic, the suspected cat is kept in isolation in a cage.
For protection of owners and relatives:

in the owner’s house, the cat has to be kept in a separate room;
physical contact with the cat must be minimized, scratching and biting avoided;
litter trays, bowls, baskets and other potentially contaminated objects must be disinfected using a hypochloride solution (bleech);
rooms where the cat had access before the visit to the veterinarian should be thoroughly cleaned using a household detergent (which is expected to inactivate influenza virus).
7. What can owners do to minimize the risk of an H5N1 avian influenza virus infection?
the development of the epidemic must be followed in the national and local media;
feeding of uncooked poultry meat to cats must be avoided;
if many deaths occur amongst wild birds, cats should be kept indoors until further information about the cause is available.
References
Keawcharoen et al., Avian influenza H5N1 in tigers and leopards. Emerg. Infect. Dis., 2004, 10, 2189-2191.

Kuiken et al. Avian H5N1 influenza in cats. Science, 2004, 306, 241.

Maines et al. Avian influenza (H5N1) viruses isolated from humans in Asia in 2004 exhibit increased virulence in mammals. J. Virol., 2005, 79, 11788-11800.

Rimmelzwaan et al. Influenza A virus (H5N1) infection in cats causes systemic disease with potential novel routes of virus spread within and between hosts. Am. J. Pathol., 2006, 168, 176-183.

Thanawongnuwech et al., Probable tiger-to-tiger transmission of avian influenza H5N1. Emerg. Infect. Dis., 2005, 11, 699-701.

WHO, Avian influenza A (H5N1) – update 28: reports of infection in domestic cats, 20 February 2004.

Relevant web sites
World Health Organisation

World Organisation for Animal Health

European Commission, Animal Health and Welfare
http://www.vetscite.org/publish/items/002817/index.html


    
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CANDLES, thank you so much for this infor. My DD vet has done none of this as far as I can tell. I am going to email this to her, thank you again, as I could not find the infor, but had a vague recollection of this or a similar article.  Talklking to her last night one of my grandchildren has come down with a fever of 101 day before yesterday she is 7. Mom kept her home for 1 day and stated she was feeling better yesterday.
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Post Options Post Options   Thanks (0) Thanks(0)   Quote kparcell Quote  Post ReplyReply Direct Link To This Post Posted: March 29 2007 at 5:04am
So...

efficient transmission from birds to other species is perhaps the underlying threat that isn't being adequately addressed because we focus on H2H. For example, focus on H2H results in focus on human vaccine, which may provide a solution years down the road; but focus on B2H would aim at reducing opportunities for mutation among birds, something that isn't being adequately addressed now.
    
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