(Circulation. 1998;97:2481.)
© 1998 American Heart Association, Inc.
Chronic Disease: Infectious Cause?
Ruth SoRelle, Circulation Newswriter
Nothing is more
excoriated in medicine than the notion of the "magic bullet." Yet
that is, in part, the allure that draws the public and researchers to
seek an infectious cause for chronic disease. Who would not like to
eliminate cancer or heart disease with a pill or a vaccine?
When the federal Centers for Disease Control and other public health
and infectious disease organizations held the First Annual Conference
on Emerging Infectious Diseases in Atlanta, Ga, earlier this year, it
was that search for a magic bullet that made the issue of chronic
disease and infections was one of the plenary topics.
Gail Cassell, PhD, formerly of the University of Alabama School of
Medicine and now a vice president with Eli Lilly & Co in Indianapolis,
Ind, gave that lecture. She said that perhaps it all began with
acquired immune deficiency syndrome. "AIDS was an eye opener," she
said. "It was something unimaginable: an infectious agent that could
lie dormant for so long and then cause such a devastating infection."
Now, she said, a growing body of knowledge indicates that a variety of
infectious agents may be associated with chronic diseases. The best
known of these is the Helicobacter pylori story, in which
Australian physician Barry J. Marshall, MD, fought an uphill battle to
have the association between the bacterium and ulcers recognized. As
recently as the mid-1980s, peptic ulcers were blamed on stress and
other environmental factors. Drugs to reduce the flow of stomach acid
were among the most prescribed drugs in the United States and many
areas of the developed world. But Dr Marshall and his colleagues found
that treatment with antibiotics and some bismuth-containing compounds
cured the acute ulcer and even seemed to prevent it from returning. At
the time, most medical experts scoffed. Dr Marshall, failing to find an
animal model for the infection, drank a pure culture of H
pylori in 1984, which resulted in the type of severe acute
gastritis associated with the finding of many H pylori in
the digestive tract. This finding netted Marshall a Lasker Award in
1995 and eventual vindication in the medical community.
Although the ulcer–infectious disease connection was largely
unsuspected, other chronic diseases had long been thought to have an
infectious component, said Dr Cassell. For example, she said,
rheumatoid arthritis has long been thought to have an infectious
origin. The same sorts of suspicions have long lingered about
cardiovascular disease. Most recently, Chlamydia
pneumoniae has been closely linked with the development of
atherosclerosis. Recent data indicate that mycoplasmas
may cause chronic arthritis, chronic asthma, and chronic lung diseases
in adults, as well as meningitis in newborns, Dr Cassell said.
According to Dr Cassell, increasing numbers of chronic infections have
been linked with cancer in recent years. H pylori is
itself associated with gastric cancer as well as mucosa-associated
lymphoid tissue lymphoma. Schistosoma haematobium is
associated with bladder cancer and Opisthorchis viverrini
with cholangiocarcinoma. Hepatitis B and C have been shown to be causal
factors in hepatocellular cancer, she said. Human
Papillomavirus is strongly associated with cervical cancer;
human herpes virus 8 and Kaposi sarcoma are similarly associated.
All these findings have major implications for treatment, prevention,
and research, said Dr Cassell. Research to pinpoint the exact risks
posed by these infectious agents and to determine who is at risk will
not be inexpensive, she warned. "It will require long-term, sustained
studies," she said.
One agent will not be found to be the single cause of all cancer or
arthritis, said Dr Cassell. Many agents could contribute to the
development of heart diseases. "You could culture 50 patients and
find nothing," she stated. "We would need something on the order of
a Framingham study to sort it all out."
Simply treating patients with antibiotics willy-nilly is unlikely to
work and raises a whole new specter of creating resistant
infectious agents. "Lots of antibiotics will not kill the organisms
that are implicated," Dr Cassell said. "Patients [with chronic
infections] would have to be treated over a long period of time."
The treatment might be something like that currently prescribed for
tuberculosis, she said.
Dr Cassell argues that the best course will be to look for multiple
agents to be involved in chronic diseases. On the basis of current
knowledge, she said, thousands of patients would have to be followed up
for many years by both clinical epidemiologists and laboratory
personnel with the ability and willingness to look for a host of
virtually undetectable organisms. Information about the genetic
backgrounds and immune systems of the patients will also play a crucial
role in this task of molecular epidemiology,
she said.
Such studies will require inordinate cooperation among a host of
groups. "But I think it will happen," said Dr Cassell. "There are
compelling preliminary data."
The promises of such findings are great. It is unlikely that the
discovery of a link between chronic disease and a variety of infectious
agents will lead to elimination of the long-term disorders in question;
however, such a discovery could lead to treatments that would, in part,
prevent primary disease and recurrence. In some instances,
treatment might even prevent the infection in the first place. That,
said Dr Cassell, could decrease the long-term burden of chronic disease
on the population.
