January 01, 2008

Killer Fungus Expanding Its Range: Cryptococcus gattii in Oregon

Back in October, I wrote about a pathogenic fungus called Cryptococcus neoformans that has been documented as having evolved same-sex mating that allows less virulent strains to combine with more virulent ones and produce extra-virulent, asexually-reproducing hybrids. This is a devious mechanism in the genus that hasn't been seen in any other to date, as far as I'm aware.

C. neoformans has a close relative, C. gattii, that was known only from Oceania — primarily Australia — until 1999 when it suddenly popped up on Vancouver Island in British Columbia, having switched host from eucalyptus to a variety of conifers. Nobody knows how the microscopic, highly toxic fungus got half way around the planet and showed up on one island without any known intermediate hops, but it's definitely there. C. gattii is even more pathogenic than C. neoformans and also engages in same-sex mating that produces highly toxic asexual hybrids. We know this because it's genome encodes a non-functional mating site that, while different from it's relative's mating site truncation, yields a non-functional product. In other words, both species have hit on the same trick, they've just taken different genetic pathways to achieve it. From a purely scientific standpoint, it's fascinating stuff. We get to see a whole new kind of mating that's developed and can easily demonstrate the evolutionary pathway by which it occurred.

Unfortunately, this is a very bad thing on the practical level. Cryptococcus gattii has expanded its range out of British Columbia and has now progressed all the way to Oregon. As the article quoted below mentions, infection by this fungus is easily treatable if its caught before the pathogen makes its way to the nervous system, but the trick there is to know what you're dealing with before this occurs. Once in the nervous system, the fungus causes a potentially lethal form of meningitis and/or encephalitis. It's a particular problem for immunocompromised individuals and the elderly, but there's a very real potential for anyone to become infected by C. gattii, even moreso than with C. neoformans. This may be because we humans evolved with the latter fungus in the environment; various strains of the fungus originated in Europe, Africa and Asia and it's very likely that our remotest ancestors already had its company. C. gattii, on the other hand, likely evolved apart from humans, so our immune systems haven't had a few million years to get used to it.

Toxic fungus moving into Oregon

EUGENE, Ore. (AP) — It sounds like a bad B movie, a toxic fungus in the woods of the Pacific Northwest drifting into peoples' lungs, causing illness and death.

But Cryptococcus gattii is out there and has affected a handful of Oregonians, most recently a Junction City woman hospitalized for more than four months this fall.

In the Northwest it was first detected on Vancouver island in 1999, where it has sickened about 180 residents and killed eight, said Karen Bartlett, associate professor of environmental health at the University of British Columbia. The disease is still rare...

Once the fungus is established in soil or in trees, it can float in the air in dry weather, she said, causing an infection in the lungs, or more seriously, in the central nervous system, causing fungal meningitis.

Symptoms include severe cough and shortness of breath, often accompanied by chills, night sweats and anorexia.

Until 2004, the only human cases in Canada were found among people who lived on or had traveled to Vancouver Island.

In 2004, when the first case was found in someone who had never been to the island, researchers began looking elsewhere and found other cases including two in Oregon...

"We don't know how long it's been here. The researchers said they don't know whether the samples found outside Vancouver Island means the fungus has colonized other areas, or whether they just represented transient dispersal of the fungus," Bartlett said...

Initial symptoms resemble flu and a general malaise. Only after symptoms continue for several weeks or worsen with a cough that doesn't go away, unexplained weight loss and night sweats do physicians realize they're dealing with something else, she said.

Illness occurs six to nine months after exposure. Once diagnosed, it is very treatable unless it gets to the central nervous system, as happened to the Junction City woman.

She was treated for bacterial meningitis, but wasn't getting better. It wasn't until lab tests came back that Eugene Dr. Robert Barnes figured out she had fungal meningitis...

All told, she spent about four months in the hospital, including stints in the intensive care unit at Sacred Heart Medical Center in Eugene and the Oregon Health & Science University. She went home Dec. 10 and appears to be doing well, her husband said...

From a public health perspective, it is more a curiosity than a real threat at this point, said Cieslak, but said he wants to learn where it is in the state and how it works.

"You've got bigger things to worry about," he said. "If we start to get more reports and it's increasing, I'll sit up and take note.
I'm not an epidemiologist, but I do have my concerns about this "curiosity," as does Dr. Cieslak, apparently. C. neoformans is spread by birds; it gets into their droppings and so gets distributed into new locales. If C. gattii is spread the same way, it might well be just a matter of time before it finds its way to some pigeon poop deposited in a large city like Portland, for instance, where one would expect a higher proportion of vulnerable people. Right now, it sounds like one would have to go for a hike in the woods to inhale spores or resting bodies, but obviously if it made it into a city that wouldn't be the case. Luckily, it doesn't appear that Cryptococcus of either species can be communicated from person to person, and due to the nature of its lifecycle that doesn't seem a likely development. However, a simple mutation or two combined with an unfortunate avian vector could wind up constituting a much bigger problem. It only took one mutation, after all, to give rise to a whole new mating mechanism in these fungi. A mutation that affects capsular lipoprotein (Cryptococci are encapsulated yeasts, sensu latu) could yield a new strain that gives our immunity the slip, and we already know that this can occur, and has occurred, to a limited extent (Jain et al., 2006). The potential exists for C. gattii to make the leap from curiosity to real menace in very short order, particularly since it has been isolated from its Australian ancestral population.

Genetic drift can be a real bitch, you know.

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