Fw: [Health_and_Healing] Microbiologists catch the chronic disease bug

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[Health_and_Healing] Microbiologists catch the chronic disease bug

Microbiologists catch the chronic disease bug by Bea Perks, BioMedNet News

http://news.bmn.com/news/story?day=020621 & story=1

BioMedNet News and Comment bug

Is migraine infectious? Can you catch arthritis or Alzheimer's disease? A

growing body of research suggests that these and other chronic diseases do have

an infectious component, but it's a notoriously tricky area to study. Thus -

despite landmark discoveries such as the association between Helicobacter pylori

infection and stomach ulcers - those trying to link microbes with chronic

disease continue to wage an uphill battle.

It's much easier to study cause and effect with acute infection, which is the

traditional focus of microbiology, says Ruth Itzhaki, professor of molecular

neurobiology at the University of Manchester Institute of Science and

Technology, who is in the process of writing up her latest findings on the

association between herpes simplex 1 (HSV1) infection and Alzheimer's disease

(AD).

" People are getting more and more interested " in links between bacteria or

viruses and chronic conditions, said Itzhaki. " The only thing is, there are

still some die-hards who don't believe a word of it. "

Itzhaki has detected, for the first time, antibodies against the virus in

samples of cerebrospinal fluid from patients with AD. Importantly, she has ruled

out the possibility that they have simply leaked across the blood-brain barrier.

" We're very excited about that, because it really very strongly supports our

findings by the polymerase chain reaction of the viral [HSV1] DNA in the brain, "

she said.

Itzhaki surprised AD researchers when she provided the first evidence, in

1991, for a link between herpes simplex virus 1 (HSV1) infection in the brain

and Alzheimer's disease (AD).

Most people are infected with HSV1 at some point, but the virus lurks in the

peripheral nervous system, not in the brain. Itzhaki used PCR to show that the

virus can find its way into the brains of older people, including people with

AD. Crucially, she found that people who have the infection and carry the Apoe4

allele, which was identified by a separate research group as a risk factor in

AD, are at high risk of developing the disease - higher than if they had either

Apoe4 or HSV1 alone.

The situation bears similarities with cold-sore pathology, says Itzhaki. Cold

sores are the result of HSV1 infection in the peripheral nervous system, but not

all infected individuals have cold sores. She looked for the Apoe4 allele in

people with cold sores, and discovered that, as with AD, people who carry the

Apoe4 allele are much more likely to develop cold sores. The discovery has

important implications for her work with AD, suggesting an interaction between

the Apoe4 protein product and HSV1.

Itzhaki wants to find out whether people who have cold sores are more likely to

develop AD. In the absence of relevant medical records, this would be a

Herculean task. Even her approaches to the British Medical Association and the

UK General Medical Council have failed to provide a workable solution. " It

seemed to be almost impossible to set it up and I haven't got the time, " she

sighed.

The next question on Itzhaki's agenda is HSV1's whereabouts in the brain. Is the

virus associated with abnormal features of the Alzheimer's brain, or more evenly

distributed? She is also looking to see whether other viruses play roles in

different types of dementia.

" There's so much to look at and so little money to do it, " she said. " The

trouble is the more original and unexpected the work, the harder it is to get

funding. "

Itzhaki applauds researchers who investigate the contribution of microbial

infection to chronic disease in the face of opposition. She cites the example of

research into the link between H. pylori infection and stomach ulcers, which

took ten years to gain acceptance. " People just didn't want to know, " she

recalled.

Even Itzhaki is surprised, though intrigued, to hear of a recently proposed link

between H. pylori infection and migraine.

Rita Gismondo at the Ospedale Luigi Sacco in Milan has found that H.

pylori infection is common among people with migraine without aura. The number

of CagA-positive bacterial strains significantly outweighs the number of

VacA-positive strains in these patients, she reports - an observation previously

associated with stomach ulcers and active gastritis.

In a follow-up clinical study, Gismondo showed that treatment with the harmless

bacteria Lactobacillus, which reportedly wards off stomach ulcers by

outcompeting H. pylori in the gut, significantly reduced migraine symptoms. The

results are unpublished.

Bacterial infection is implicated in numerous chronic-disease processes, from

heart disease to cancer. But with a few notable exceptions, such as tuberculosis

and leprosy, the infectious component of those processes is poorly understood,

says Alan Hudson, professor of microbiology at Wayne State University in

Detroit.

" We've been absolutely fabulously successful over the last 300 years at fishing

out microbial causes of diseases, " said Hudson. " But essentially

99.9% of everything that's been sorted out is acute diseases, and those are

easy. "

Microbiologists need to focus on all the diseases with no known cause, he says.

Hudson and his team are investigating the role of Chlamydia infection in

reactive arthritis. Half of all patients with reactive arthritis subsequently

develop chronic arthritis, which particularly interests him.

Reactive arthritis had been correlated with Chlamydia infection for ages, says

Hudson, but how this led to chronic disease, which can last for 30 years, was a

mystery. It was assumed that bacteria that migrated to patients' joints and

triggered the acute disease were dead once chronic symptoms set in.

Looking for Chlamydia in synovial fluid from patients' joints supported this:

The samples were culture-negative. But examining joint tissue by electron

microscopy revealed round objects that resembled bacteria.

Hudson's research over the past ten years has shown that Chlamydia is living

there, although in tissue rather than fluid.

" It's perfectly alive, " he said. " It's viable, it's metabolically active, but

there's something funny about its biochemistry in this long-term infection

state. "

Hudson's research is now focused on the molecular genetics and biochemistry of

Chlamydia that distinguishes long-term from acute infection. The cytokine

profiles in patients with either acute or chronic arthritis are completely

different, he adds.

Based on his unpublished findings and earlier data, Hudson anticipates that an

altered host-pathogen relationship distinguishes the transition from acute to

chronic infection. " We think that this organism overtly manipulates its

long-term host cell to maintain itself, " he said.

Hudson has also reported a controversial association between C. pneumoniae

infection and AD (though even he is not convinced that this relationship is

causal). Others have reported associations between the bacterium and multiple

sclerosis, atherosclerosis, and meningoencephalitis. The findings join data on a

range of other viral and bacterial pathogens and chronic disease.

How many of these connections will turn out to have been ephemeral? " We're at

the beginning, " he said. " I think some of this stuff is going to turn out to be,

if not wrong, not exactly right. "