Mounting evidence may link viruses and bacteria to everything from gallstones to Alzheimer's

From: JWissmille (jwissmille_at_aol.com)
Date: 01/02/05 

Date: 02 Jan 2005 00:49:41 GMT

http://www.altcorp.com/AffinityLaboratory/newdiseaseidea.htm

Spreading a New Idea on Disease

Mounting evidence may link viruses and bacteria to everything from
gallstones to Alzheimer's.

By THOMAS H. MAUGH II
L. A. Times Medical Writer

Ignaz Semmelweis was ahead of his time. Working at Vienna General Hospital
in the 1850s, the Hungarian physician was one of the first to adopt the
idea that germs cause disease. Semmelweiss noted that doctors would perform
autopsies in the hospital's basement, then care for healthy pregnant women
without cleaning their hands.

Many of the women developed fatal fevers, and Semmelweis reasoned that the
doctors were transferring some kind of infectious agent from the corpses to
the women. Contagion was a radical idea at a time when illness was thought
to be caused by bad blood or other mysterious forces, and Semmelweis was
ridiculed for his ideas.

Today, we know that most acute diseases are caused by bacteria, viruses and
other agents. Now, a growing number of latter-day Semmelweises are
advocating an even more radical notion--that viruses and bacteria play a
major role in many chronic diseases where infection has never been
suspected.

At a time when much research focuses on the genetic underpinnings of
disease, researchers say, it is time to take a fresh look at how an old
foe--infections--can interact with genes to produce chronic disease.

If they are right, physicians might soon have new antibiotic and antiviral
weapons to add to their arsenal for treating heart disease, Alzheimer's,
kidney stones, gallstones and a variety of other chronic conditions. It
might even be possible to develop vaccines to prevent some of these
conditions.

Already, bacteria and viruses have been firmly linked to ulcers, liver
cancer, cervical cancer, leukemia and Kaposi's sarcoma.

Strong evidence is also unfolding for other diseases:
Epidemiologists have found that a majority of heart disease patients have
been infected with a common bacterium, and Canadian researchers recently
reported a mechanism by which it could trigger heart disease. Some
researchers suspect that as many as 80% of all cases of heart disease are
linked to infections.

Pennsylvania scientists have found the same bacterium in the brains of
patients with Alzheimer's disease.

Finnish biologists have strong evidence that a previously unrecognized
bacterium can produce kidney stones.

More tentatively, other researchers have linked infections to a broad
spectrum of diseases, ranging from Crohn's disease and irritable bowel
syndrome to obsessive-compulsive disorder, schizophrenia, multiple
sclerosis and arthritis (see box).

Studies Focusing on Antibiotics

The links to infection raise "the prospects for treating and preventing
these chronic diseases," said biologist Paul Ewald of Amherst University.
"If it's a bacterium that is susceptible to a wide range of antibiotics,
that is incredibly encouraging."

Already, some small studies have suggested that antibiotics might prevent
heart attacks, and three large clinical trials enrolling nearly 8,000
people have begun or are beginning. Neurologists are also preparing a trial
using antibiotics to treat Alzheimer's disease, and it is likely that
trials for other chronic diseases are on the horizon.

That doesn't mean you are going to be able to throw away your
blood-pressure medicine or eat more fatty foods. Infections are just one
more risk factor to add to the complex equations determining risk. Some
researchers believe, for example, that controlling infections might have
the same benefit for heart disease patients as lowering cholesterol.

"This is an idea whose time has come," said Dr. W. Ian Lipkin of the UC
Irvine School of Medicine. "We have been tracking [this] for many years,
and it is finally achieving some respectability."

The new discoveries are occurring in part because some researchers are
choosing to look for links to infectious agents. But more important,
perhaps, has been the development of sophisticated DNA-based techniques for
identifying the presence of trace quantities of bacteria or viruses.

Polymerase chain reaction (PCR) technology, widely heralded for its use in
providing genetic fingerprints of humans, can be used to fish out the
genetic fingerprints of viruses or bacteria in human tissue, even though
the organisms are present only in minute quantities.

"If the viruses or bacteria] were causing disease in an obvious way," Ewald
adds, "we would have seen it long ago. It shouldn't surprise us . . . that
every new one we find tends to be a little more cryptic."

The godfather of the new movement is Dr. Barry J. Marshall, who was at the
Royal Perth Hospital in Australia in 1981 when he and Dr. J. Robin Warren
began studying an unidentified spiral bacterium that they observed in
stomach linings.

After several years of study, they concluded that the bacterium, named
Helicobacter pylori, is the cause of most ulcers not associated with
over-ingestion of painkillers--an idea that the vast majority of physicians
considered laughable at the time. They also found that eradicating the
bacteria, which is found in the stomachs of a third of Americans, cured the
ulcers.

But it was not until Marshall himself, now at the University of Virginia,
swallowed a vial of H. pylori and developed a painful case of gastritis
that other physicians began to be convinced. "That surprised people," Ewald
said. "At least two generations of doctors were trained to think of ulcers
as being caused by too much stomach acid," said Dr. Monty Bodenheimer of
the Long Island Jewish Medical Center in New Hyde Park, N.Y. "But now we
know differently and don't treat ulcers as too much acid. We treat the
infection."

Current guidelines, in fact, call for the use of two antibiotics plus an
anti-acid drug, but many doctors have not yet gotten the message. A recent
Colorado study showed that 46% of patients seeking treatment for ulcers are
never tested for H. pylori by their physicians.

Subsequent studies have also shown a strong link between the bacterium and
stomach cancer. Some researchers have also found tentative links between H.
pylori and heart disease, the No. 1 killer in the United States. Others
think the villain might be either cytomegalovirus, a herpes virus, or even
the bacteria in dental plaque.

But the strongest evidence implicates another bug, called Chlamydia
pneumoniae, in heart disease. Discovered in the 1980s, C. pneumoniae is now
known to be widespread in the environment, causing, for example, at least
10% of all cases of pneumonia. It is also a close relative of Chlamydia
trachomatis, the most common cause of sexually transmitted disease in this
country.

The idea that bacteria and viruses can damage the heart is not farfetched.
The streptococcal bacteria that cause rheumatic fever also attack the
heart, causing lingering damage. Several viruses attack the heart directly,
causing myocarditis, which is often fatal.

Staphylococcal and streptococcal bacteria have also recently been shown to
cause Kawasaki syndrome, a childhood disease that is marked by severe heart
problems. If infectious agents can cause acute heart disease, some
researchers reason, it is not a big leap to the idea that they can cause
chronic disease as well.

Beginning in the late 1980s, researchers such as Dr. J. Thomas Grayston of
the University of Washington began finding high levels of antibodies
against C. pneumoniae in the blood of patients with heart disease. Few paid
much attention to such findings until 1995, when Dr. James Summersgill and
his colleagues at the University of Louisville found the same bacterium in
the atherosclerotic plaques that blocked blood vessels taken from a patient
undergoing bypass surgery.

Researchers have since found the bacterium in the blood vessels of
virtually every heart disease patient studied, but never in vessels from
healthy patients. But just because the bacterium is at the scene of a crime
doesn't mean it is necessarily a criminal. It may simply find plaque an
ideal environment in which to grow. "Chlamydia pneumoniae may just be an
innocent bystander in diseased blood vessels," said Dr. John Danesh of
Oxford University.

Nevertheless, proponents like Grayston think there are good reasons to
suspect it. Scientists have long known that atherosclerosis is an
inflammatory disease that affects vessels throughout the body, but
particularly those supporting the heart and brain.

Heart disease develops when our immune systems mobilize to remove fat,
cholesterol and other irritants from vessel walls. As immune cells called
macrophages burrow into the arterial walls to gobble up foreign material,
they can set off a vicious cycle of irritation and scarring.

Germ Warfare

Grayston and others suspect that C. pneumoniae exacerbates that
inflammatory process, or may even provoke it in the first place.

Recently, Dr. Josef Penninger and his colleagues at the Ontario Cancer
Institute in Toronto showed how that could occur. They reported that the
surfaces of three strains of chlamydia carry a protein very similar to a
protein found only in heart tissue.

When they injected the chlamydia proteins into mice, the mice developed
heart disease. The question then is: If the bacterium contributes to the
development of heart disease, will eradicating it reduce risk?

In February, Dr. Hershel Jick and his colleagues at Boston University
Medical Center reported that patients who took tetracycline or
quinolones--antibiotics known to kill C. pneumoniae--were less likely to
have heart attacks than people who took other antibiotics or no
antibiotics. Other small studies have found similar results.

To test this idea on a larger scale, Grayston and Dr. P.K. Shah at
Cedars-Sinai Medical Center in Los Angeles have independently begun testing
the anti-chlamydia antibiotic Zithromax against a placebo to determine if
the drug reduces heart attack risk. Zithromax manufacturer Pfizer Inc. is
also conducting a large trial.

Perhaps even more surprising than C. pneumoniae's link to heart disease is
a potential link to Alzheimer's, a devastating neurological disease that
afflicts more than 4 million Americans.

Dr. Brian J. Balin of the Philadelphia College of Osteopathic Medicine and
Dr. Alan P. Hudson of the Wayne State School of Medicine in Detroit
reported at a November meeting of the Society for Neuroscience that they
found traces of C. pneumoniae in the brains of 17 of 19 people who died of
Alzheimer's disease, but in only one of 18 people who died from other
causes.

They have since found it in 10 more Alzheimer's victims, Balin said in a
telephone interview. "We wanted to be clear about what we found, so we used
seven different techniques to identify it," he said.

The presence of inflammation in the brain triggered by an immune attack of
the bacterium might explain studies suggesting that aspirin and other
anti-inflammatory drugs delay the progression of Alzheimer's, he said.

Balin also noted that some Alzheimer's patients have told him that their
cognitive ability improved while they were taking antibiotics for other
conditions.

"That might be giving us a clue," he said. He plans to conduct a clinical
trial to see if antibiotics can slow the progression of Alzheimer's in its
early stages.

Triggering an immune attack may not be the only way that bacteria cause
chronic disease. Other recent studies suggest that certain bacteria can act
like the proverbial grain of sand that triggers the formation of a pearl in
an oyster. But in these studies, the bacteria produce kidney stones and
gallstones.

Biochemist E. Olavi Kajander of the University of Kuopio in Finland has
spent the last decade studying new strains of bacteria that he calls
nanobacteria because they are extremely small, some as small as a virus.

The nanobacteria have been unknown in the past, he said, because they are
so small and because they are extremely difficult to grow in the
laboratory. But he has found that 5% of the Finnish population has
antibodies against nanobacteria, indicating that those people have been
infected at some time.

Last July, Kajander reported that every one of 30 kidney stones he and his
colleagues took from various patients had nanobacteria in their centers.
His lab had previously shown that the bacteria cloak themselves in a shell
of crystalline minerals. He speculates that such bacteria, which live in
urine, act like a seed around which calcium and other minerals can grow to
form a large stone.

"I think it is the first real theory as to what" is the seed in kidney
stones, said Dr. Leroy M. Nyberg of the National Institute of Diabetes and
Digestive and Kidney Diseases.

Dr. Phillip B. Hylemon of the Medical College of Virginia suspects that
more common bacteria, clostridia and eubacteria, may play a similar role in
gallstones. He found that gallstone patients have 100 to 1,000 times as
many of these bacteria in their intestines as do healthy people. He also
reported last year that giving such patients antibiotics reduced their
levels of bile--a bitter fluid produced by the liver to aid
digestion--below the threshold necessary to make gallstones.

Many experts believe that researchers have just barely begun to scratch the
surface in looking for dangerous infectious agents. "My gut feeling is
that, the more we look, the more we are going to find microorganisms that
have taken up residence in the human body," said biologist Hal B. Nash of
Western Wyoming College. "Some may not be doing any harm, but others may be
doing quite a bit."

Spread by Germs
Several chronic diseases once thought to be caused solely by genes and
lifestyle have now been shown to be caused, at least in part, by infectious
agents. Others have been tentatively linked to such agents as well.

FIRMLY LINKED
Disease Organism

Liver cancer Hepatitis B virus
                        Hepatitis C virus

Cervical cancer Papilloma virus

Leukemia HTLV-1 virus

Ulcers Heliobacter pylori

B-cell lymphoma Epstein-Barr virus

Nasopharyngeal cancer Epstein-Barr virus

Burkitt's lymphoma Epstein-Barr virus

Kidney stones Nanobacteria

Kawasaki syndrome Staphyloccus bacteria
                        Streptococcus bacteria

SUSPECTED LINKS
Disease Organism

Heart disease Chlamydia pneumoniae

Juvenile diabetes Coxsackie B virus

Obsessive-compulsive Streptococcal bacteria
disorder

Alzheimer's disease Chlamydia pneumoniae

Schizophrenia Brona virus
                        Influenza virus

Gallstones Clostridia and eubacteria

Breast cancer Human version of mouse mammary tumor virus

Crohn's disease Mycobacterium paratuberculosis

Juvenile rheumatoid Mycoplasma pneumoniae
arthritis

Scleroderma Mycoplasma

Copyright 1999 Los Angeles Times. All Rights Reserved. Non commercial use
only research and discussion only

Maugh, Thomas II. 1999. Spreading a New Idea on Disease: Mounting evidence
may link viruses and bacteria to everything from gallstones to Alzheimer's.
Los Angeles Times

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