More cats found with bird flu -Declan Butler-Nature

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News

Published online: 25 July 2006; | doi:10.1038/news060724-4
More cats found with bird flu
Researchers suggest feline 'sentinels' could identify dangerous outbreaks.Declan Butler

Could cats help help us keep watch on bird flu?

© AP Photo/Amy Sancetta

Domestic cats may be widely susceptible to infection with the avian flu H5N1 virus, according to scientists who this week reported the virus in two dead cats in northern Iraq. The latest reports, following recent cat cases in Austria, Germany, Thailand and Indonesia, reinforce the hypothesis that cats may play a role in the spread of the virus, although none of the human victims thus far is thought to have caught the virus from a cat.

The findings also suggest that cats might help provide an early-warning system for avian flu by acting as 'sentinels', say the scientists, who work at a US Naval Medical Research Unit in Cairo, Egypt. Many remote areas lack the veterinary infrastructure to test quickly for H5N1. So as a proxy, they argue, H5N1 should be immediately suspected and guarded against whenever unusual bird and cat die-offs happen together.

Bird flu continues to hit Asia. Thailand has just seen a resurgence in chicken cases this week, after being apparently free of the virus for a year.

Cat curiosity

H5N1 was first reported in domestic cats in Thailand in 2004, and a later survey showed that some Thai cats carry antibodies to the virus. Further lab work showed that cats can carry the virus in their guts and faeces, and so could contaminate the environment to spread the virus. "In nature we saw exactly what they saw in the lab," says Samuel Yingst, the lead author of the new work, speaking from Bishkek, Kyrgyzstan.

The researchers tested the cats out of curiosity during a two-week field trip last February near Erbil City, in Kurdish northern Iraq, after hearing anecdotal reports of cat deaths associated with H5N1 outbreaks in Turkey and Iraq the month before. Their findings are published in the August issue of Emerging Infectious Diseases1.

"It's conceivable that cats could spread the virus," says Yingst, although he suspects that they may be 'dead-end' hosts that die after receiving the disease without passing it on.

Baffling virus

Dick Thompson, a spokesman for the World Health Organization (WHO), says the latest paper does not change the WHO's current position: "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."

That said, some cases of H5N1 continue to baffle scientists. There have been reports of cat die-offs in Indonesia in areas where no bird outbreaks have been reported, for example. And one cat virus has been shown to share gene sequences with human cases; gene sequences that have not been reported in poultry samples.

Some human cases from Java "have no obvious avian counterparts", concluded a dozen international experts in animal and human health at the Avian Influenza Expert Consultation meeting in Jakarta from 20-23 June. They said there is an "urgent need" to compare human, cat and bird sequences, but that such efforts are being hindered by a lack of data.

On the alert

In the meantime, the study could help spark an idea for early-alert systems. "Where cats show respiratory infections in areas where avian flu is endemic, H5N1 will probably be one of the causes," says Magdi Saad, a co-author on the work. Cats could therefore serve "as sentinels in areas which don't have access to good diagnostics", adds Yingst.

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"I'd completely agree that cats can serve as sentinels, they seem very susceptible," says Albert Osterhaus, whose team at Erasmus University in Rotterdam, the Netherlands, has shown that experimentally infected cats can transmit the virus. Other carnivores are also likely to fall foul of flu, he says, adding that his group is now also looking at ferrets, foxes and seals.

Sentinels are important as a first alert, the experts agree, but they are no substitute for detailed investigation.

Visit our newsblog to read and post comments about this story.

References
Yingst S. L., Saad M. D.& Felt S. A. . Emerg. Infect. Dis., http://www.cdc.gov/ncidod/EID/vol12no08/06-0264.htm (2006).

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Declan Butler, European Correspondent, Paris

Declan's interests include science in France, global health, science and development, computing, electronic publishing and space science. Before joining Nature in 1993, Declan wrote freelance, and worked for the French biotechnology magazine Biofutur. He graduated in biology from Queen's University, Belfast, and has a PhD in marine biology from the University of Leeds. He was made a Chevalier of France's National Order of Merit in 2003 for for service to science and society.

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The related science article ahead of print from CDC.
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Volume 12, Number 8–August 2006
Letter
Qinghai-like H5N1 from Domestic Cats, Northern Iraq
Samuel L. Yingst,* Magdi D. Saad,* and Stephen A. Felt*
*US Naval Medical Research Unit No. 3, Cairo, Egypt

Suggested citation for this article

To the Editor: Natural infection of several cat species with highly pathogenic avian influenza (HPAI) H5N1 viruses in Thailand (1–4) and experimental infection of domestic cats with similar viruses have been reported (5,6). Thus, literature describing HPAI H5N1 infection of cats is limited to descriptions of infections with a subset of clade I viruses. HPAI H5N1 viruses, highly similar to viruses isolated from Qinghai Lake in western People's Republic of China in spring 2005, are now rapidly disseminating throughout Eurasia and Africa. To our knowledge, this is the first report of a Qinghai-like virus detected in domestic cats. This finding is noteworthy because the host range of influenza viruses is determined by the antigenic characteristics of the hemagglutinin and neuraminidase molecules; clade II viruses are antigenically distinct from clade I viruses, and Qinghai-like viruses are genetically distinct from other clade II viruses.

Personal communications in January 2006 from field veterinarians noted deaths of domestic cats that were associated with suspected (eventually confirmed) H5N1 outbreaks in eastern Turkey (2 villages) and Kurdish northern Iraq (Sarcapcarn in Sulymaniyah Governorate and Grd Jotyar in Erbil Governorate). The clinical conditions of the birds did not suggest HPAI to villagers or consulting veterinarians. In both scenarios in Iraq, results of rapid antigen detection tests with the Anigen kit (Suwon, Republic of Korea), while positive for influenza A, were negative for H5, so the outbreaks were not thought to be caused by HPAI, but concern about the unusual deaths in cats remained. Because the regions are remote and veterinary services limited, such anecdotal reports have rarely been followed up.

After H5N1 influenza was diagnosed in a person in Sarcapcarn, Kurdish northern Iraq, the government of Iraq requested a World Health Organization investigation, which was supported in part by Naval Medical Research Unit No. 3 veterinarians. While investigating the situation in Erbil Governorate, the team was informed of suspicious deaths in cats associated with the death of all 51 chickens in a household in Grd Jotyar (≈10 km north of Erbil City) From February 3 to February 5, 2006, five cats reportedly died; 2 of these were available for examination on February 8. A sick goose from an adjacent household was killed and underwent necropsy with the cats. Gross pathologic changes in cats were similar to those previously reported, except that severe hemorrhagic pancreatitis was observed (5,6). Tissues from these animals and archived tissues from 1 of the 51 chickens were conveyed to Cairo for virologic examination.

An influenza A H5 virus was present in multiple organs in all species from the outbreak site in Grd Jotyar (Table). cDNA for sequencing was amplified directly from RNA extracts from pathologic materials without virus isolation. On the basis of sequence analysis of the full HA1 gene and 219 amino acids of the HA2 gene, the viruses from the goose and 1 cat from Grd Jotyar and from the person who died from Sarcapcarn (sequence derived from PCR amplification from first-passage egg material) are >99% identical at the nucleotide and amino acid levels (GenBank nos. DQ435200–02). Thus, no indication of virus adaptation to cats was found. The viruses from Iraq are most closely related to currently circulating Qinghai-like viruses, but when compared with A/bar-headed goose/Qinghai/65/2005 (H5N1) (GenBank no. DQ095622), they share only 97.4% identity at the nucleic acid level with 3 amino acid substitutions of unknown significance. On the other hand, the virus from the cat is only 93.4% identical to A/tiger/Thailand/CU-T4/2004(H5N1) (GenBank no. AY972539). These results are not surprising, given that these strains are representative of different clades (8,9). Sequencing of 1,349 bp of the N gene from cat 1 and the goose (to be submitted to GenBank) show identity at the amino acid level, and that the N genes of viruses infecting the cat and goose are >99% identical to that of A/bar-headed goose/Qinghai/65/2005(H5N1). These findings support the notion that cats may be broadly susceptible to circulating H5N1 viruses and thus may play a role in reassortment, antigenic drift, and transmission.

The route of infection in these cats cannot be determined definitively. How cats behave when eating birds makes both oral and respiratory infection possible. However, the source of infection seems clear in that an identical H5N1 virus was detected in samples from a goose from the same dwelling, and an H5 virus was detected from archived samples from 1 of 51 chickens that died over the course of a few days. The potential for horizontal spread cannot be ruled out since we detected viral RNA in gut, stool, and trachea; clinical signs developed in all cats, and all died from the acute illness 2–4 days after the chicken deaths began; therefore, simultaneous exposure seems likely. Death in cats, spatially and temporally associated with unusual deaths in poultry, especially when the cats show positive results of a rapid antigen detection test for influenza A, should be considered to indicate a presumptive diagnosis of HPAI, and appropriate response should ensue.

Acknowledgments
We thank Elham Botrus Shabo, Saman Najeeb, Faisal Polus, Sura Jabar, Saidawan Omer Yussif, and Burhan Sulaiman for facilitation and technical assistance in sampling and performing necropsies, and Bradford Camp, Odis Kendrick, and Kosar Shaheer for communications and security.

This work was supported by funding through the Naval Medical Research Center work unit GEIS E0018.

References
Keawcharoen J, Oraveerakul K, Kuiken T, Fouchier RA, Amonsin A, Payungporn S, et al. Avian influenza H5N1 in tigers and leopards. Emerg Infect Dis. 2004;10:2189–91.
Thanawongnuwech R, Amonsin A, Tantilertcharoen R, Damrongwatanapokin S, Theamboonlers A, Payungporn S, et al. Probable tiger-to-tiger transmission of avian influenza H5N1. Emerg Infect Dis. 2005;5:699–701. Erratum in Emerg Infect Dis. 2005;11:976.
Songserm T, Amonsin A, Jam-on R, Sae-Heng N, Meemak N, Pariyothorn N, et al. Avian influenza H5N1 in naturally infected domestic cat. Emerg Infect Dis. 2006;12:681–3.
Amonsin A, Payungporn S, Theamboonlers A, Thanawongnuwech R, Suradhat S, Pariyothorn N, et al. Genetic characterization of H5N1 influenza A viruses isolated from zoo tigers in Thailand. Virology. 2006;344:480–91.
Rimmelzwaan GF, van Riel D, Baars M, Bestebroer TM, van Amerongen G, Fouchier RA, 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;168:176–83.
Kuiken T, Rimmelzwaan G, van Riel D, van Amerongen G, Baars M, Fouchier R, et al. Avian H5N1 influenza in cats. Science. 2004;306:241.
Spackman E, Senne DA, Myers TJ, Bulaga LL, Garber LP, Prdue ML, et al. Development of a real-time reverse transcriptase PCR assay for type A influenza virus and the avian H5 and H7 hemagglutinin subtypes. J Clin Microbiol. 2002;40:3256–60.
World Health Organization Global Influenza Program Surveillance Network. Evolution of H5N1 avian influenza viruses in Asia. Emerg Infect Dis. 2005;11:1515–21.
Chen H, Smith GJD. LI KS, Wang J, Fan XH, Rayner JM, et al. Establishment of multiple sublineages of H5N1 influenza virus in Asia: implications for pandemic control. Proc Natl Acad Sci U S A. 2006;103:2845–50.
Table
Table. Detection of influenza A H5 by real-time PCR

Suggested Citation for this Article
Yingst SL, Saad MD, Felt SA. Qinghai-like H5N1 from domestic cats, northern Iraq [letter]. Emerg Infect Dis [serial on the Internet]. 2006 Aug [date cited]. Available from http://www.cdc.gov/ncidod/EID/vol12no08/06-0264.htm

[HenryN]

Comments on sequences published in March

http://www.recombinomics.com/News/03...Sequences.html

[Mellie]

Human H5N1 Iraq Sequence Includes N186S

Recombinomics Commentary
March 15, 2006

HA sequences from Iraq have been released (A/human/Iraq/207-NAMRU3/2006(H5N1), A/domestic goose/Iraq/812/2006(H5N1), A/domestic cat/Iraq/820/2006(H5N1) by the US Naval Medical Research Unit in Cairo. As expected, all three have the HA cleavage site GERRRKKR, which is the signature sequence of the Qinghai strain of H5N1 bird flu. All three sequences are wild type at position 227 (serine).

The sequences are most closely related to the Kurgan isolate, A/chicken/Kurgan/3/2005(H5N1), which shares some polymorphisms with the Nigerian sequence, A/chicken/Nigeria/641/2006(H5N1). There are some polymorphisms that are specific to Iraq, including R565K.

The most intriguing change however is the change that is only in the human sequence, A609G, which creates N186S. This change could alter the affinity of receptor binding domain, which includes position 190, for human receptors. Donor sequences for this change were not identified in a search of the Los Alamos flu database, highlighting the need for a more complete database and release of the sequestered sequences.

The human sequence from Iraq is the first Qinghai related human sequence made public, and the cat sequence is the second mammalian Qinghai related sequence to be made public. Kudos goes to the Cairo research group for timely and transparent release of critical sequence information.

The above data provides more compelling reasons for the release of the H5N1 sequences sequestered by WHO, including human sequences from Turkey and Indonesia. The sequences each have unique features that are critical in mapping the paths of H5N1 spread as well as changes that will impact vaccine development. Release of the sequestered sequences is long overdue.

[AlaskaDenise]

...This change could alter the affinity of receptor binding domain, which includes position 190, for human receptors.....

can we assume a mutation at 190 would be identical to 1918 NY1 H1N1, whose single 190 mutation completed the RBS requirement for successful binding?

.

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Related to this from Declan Butler's blog

http://declanbutler.info/blog/

More ‘Aaargh plop;’ cat flu in Iraq
0 comments Published July 25th, 2006 in avian influenza.

Back in March I reported on what we know, and don’t know, about the avian flu virus H5N1 in cats. The issue has new resurfaced with a paper in Emerging Infectious Diseases reporting avian flu in cats in northern Iraq — see my story today; “More cats found with bird flu“.

The earlier post commented on the fact that cat infections were more common than recognized:

“But scientists may just be learning what is already common knowledge among Indonesian villagers. Peter Roeder, a consultant for the UN Food and Agriculture Organization, says locals have an onomatopoeic name for bird flu “that sounds like ‘plop’, the sound of a chicken hitting the ground when it falls out of a tree. They also have a name for the cat form of avian flu — ‘aaargh plop’ — because cats make a screaming noise before they fall out of the tree.””

Today’s story looks at the significance of the new cases in Iraq, and in particular that they provide further field support for earlier lab findings that cats likely spread virus in the environment through contaminated faeces.

The researchers at the US Naval Medical Research Unit in Cairo, Egypt (NAMRU-3), who uncovered the cases, also suggest that cats could serve as sentinels:

“The findings also suggest that cats might help provide an early-warning system for avian flu by acting as ’sentinels’, say the scientists, who work at a US Naval Medical Research Unit in Cairo, Egypt. Many remote areas lack the veterinary infrastructure to test quickly for H5N1. So as a proxy, they argue, H5N1 should be immediately suspected and guarded against whenever unusual bird and cat die-offs happen together.”

[AlaskaDenise]

History better not name this the ‘Aaargh plop flu'.

.