Spreading a New Idea on Disease . Mounting evidence may link viruses and bacteria to everything from gallstones to Alzheimer's.
Magic2626
http://www.latimes.com/CNS_DAYS/990422/t000036141.html
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, 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 andn
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 Helicobacter 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
Disease Organism
Heart disease Chlamydia pneumoniae
Juvenile diabetes Coxsackie B virus
Obsessive-compulsive disorder Streptococcal bacteria
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 arthritis Mycoplasma pneumoniae
Scleroderma Mycoplasma
Copyright 1999 Los Angeles Times. All Rights Reserved
.....................................
non commercial use only research and discussion only
MrsMeister
>swallowed a vial of H. pylori and developed a painful case of gastritis
First of all, God bless this doctor!
Two... I think it would be a great idea for Allan Steere to step up to plate
and ingest a handful of ticks and then all those experts at Yale can study all
the variouses diseases he develops and tell him it's coincidental!!
Sinaj101
>and ingest a handful of ticks and then all those experts at Yale can study
>all
>the variouses diseases he develops and tell him it's coincidental!!
>
>
Great Idea!!!! I go for that.