Wednesday, March 01, 2006

More on house cats, bird flu and Indonesia

European mammals, like its birds, are now on the chopping block. Not all mammals. Yet. but at least domestic cats. A laboratory has confirmed H5N1 infection in a cat found dead on the same island in northern Germany where 100 birds were found infected last week. German officials have ordered cats found within 200 yards of the area where the dead cat was discovered to be killed. Wild birds in southern Germany (Bavaria) have now also tested positive for the virus, the fifth of 16 German states to have infected birds (Bloomberg).

This is not the first time cats have been found to host the virus, although it is the first non-bird species infected in Europe. Big cats in a Thai zoo fed infected chicken were sickened and some died and three housecats in Bangkok died from the disease in 2004. In the Netherlands Thijs Kuiken and his collaborators have published two papers on experimental cat infections with H5N1 (earlier post here). The first appeared in the journal Science in September of 2004. The investigators infected three laboratory cats with an isolate from a Vietnamese patient. The cats became very sick and were able to pass the disease on to other cats housed with them. Cats are not usually made ill by influenza virus, and Kuiken's attempts to make them sick with the H3N2 virus currently circulating in human populations (seasonal influenza) did not succeed. Thus the H5N1 isolated from humans was uniquely dangerous for the housecats (Deborah McKenzie by-line, New Scientist).

In January 2006 Kuiken published another paper, this time in the American Journal of Pathology (v. 168, p. 176, January 1, 2006). He was able to infect eight cats (4 to 6 month old pathogen free European shorthair cats from a commercial breeder), again with a 2004 Vietnam isolate from a fatal human case. Three cats were infected via direct inoculation of virus into the cat windpipe (trachea), three were fed virus-infected chicks and two cats were put into the same enclosure as the first group to see if they would catch the virus.

All eight cats became infected. Especially troubling about this study was the cats became systemically infected with the virus, with viral replication both in and outside the respiratory tract. There wassevere tissue damage and all animals excreted virus from both the respiratory and digestive tracts. The study broached serious questions about how this virus spreads both within the animal and between animals. In particular, the question of intestinal infection and spread through food was left open by these findings. In addition the wide tissue tropism (ability to affect many tissue types) suggested that the human isolates are especially dangerous to mammals.

The discovery of the dead German cat again raises the question of spread from other mammalian reservoirs or dead-end hosts like the house cat. In many western nations the cat, like birds in southeast asia, lives in close proximity to humans.
[Thomas Mettenleiter, head of Germany's Friedrich Loeffler Institute] insisted, however, there was no danger to humans as there have been no documented cases of a cat transmitting the virus to people.

However, Maria Cheng of the World Health Organization in Geneva said there was not enough information on how the disease is transmitted to be sure. She noted that tigers and snow leopards in a zoo in Thailand became infected after being fed chicken carcasses, dying from H5N1 in 2003 and 2004.

"But we don't know what this means for humans. We don't know if they would play a role in transmitting the disease. We don't know how much virus the cats would excrete, how much people would need to be exposed to before they would fall ill," Cheng said. (AP)
We note that in an earlier version of the AP story Mettenleiter was quoted this way:
Mettenleiter said there are no known cases of the virus moving from cats to humans, but he still cautioned pet owners on Ruegen to keep their cats inside for now.

"An infection of humans, which theoretically cannot be ruled out, could probably only occur with very intimate contact to infected animals," Mettenleiter said. (AP)
Unfortunately, intimate contact with house cats is more the rule than the exception in Europe and the US. WHO has the message exactly right this time. We don't know.

On a different but related note, a few days ago we posted on an interview given by Dr. Andrew Jeremijenko in Australia. There he said the Indonesian virus isolated from birds differed from that isolated from humans and the closest match to the human version came from a kitten he swabbed. I have since had some communication with Dr. Jeremijenko and he clarified the difference in the bird and human viruses lay in a single amino acid in the polybasic cleavage site. This kind of difference would not be expected to affect pathogenicity or host specificity, but it is striking that almost all the human isolates have one version and almost all the avian isolates the other. The cat has the human version, suggesting it is related to, or a marker for, mammalian host adaptation. Dr. Jeremijenko repeated to me his interview assertion that Indonesia authorities are struggling to cope with an ongoing outbreak and needs immediate high level international expertise. The US NAMRU2 lab is still operating but has no significant input to the Indonesians. [NB: See Dr. Jeremijenko's clarification of the NAMRU2 situation in the Comments to this post].

The short version is that the Indonesian bird flu pot is threatening to boil over and there is no one in the kitchen.