Infection eyed as culprit in chronic disease

Washington -- Imagine prescribing antibiotics for patients with atherosclerosis, or administering vaccines to prevent schizophrenia. Many researchers are thinking outside the box and are pursuing the infectious agents they believe might play a large role in causing chronic diseases.

"It is becoming increasingly acceptable and recognized that infections are probably an underappreciated cause of chronic disease," said Siobhan O'Connor, MD, MPH, assistant to the director of the National Center for Infectious Diseases at the Centers for Disease Control and Prevention.

The list of chronic diseases known to be caused by infectious agents is growing. AIDS, cervical cancer, liver cancer and peptic ulcers all result from these bugs, and researchers are exploring links to heart disease, additional cancers and psychiatric disorders. About 70% of all deaths in the United States are caused by chronic diseases, making them a prime target for research attention.

There was a time when the very idea of an infectious agent causing a chronic disease brought heaps of scorn upon the scientists who proposed it. That's what happened in the 1980s when it was suggested that ulcers were caused by Helicobacter pylori rather than stress and spicy food. Since then, H. pylori has been linked to duodenal ulcers, gastric cancer and certain types of lymphomas.

The ulcer story caused a shift in thinking that went well beyond that one disease, said E. Fuller Torrey, MD, associate director of laboratory research at the Stanley Medical Research Institute. He has been examining the role of infectious agents in schizophrenia and bipolar disorder "for more years than I care to remember." As for the current status of his research: "I wouldn't say we were respectable, but we are no longer not respectable, either."

His work with Robert H. Yolken, MD, professor of pediatrics at Johns Hopkins University in Baltimore, has recently centered on the roles of the herpes viruses and a parasite, Toxoplasma gondii, as possible triggers for the psychiatric disorders.

But in general, even if an infection plays some role in chronic disease, it is hardly the sole cause, experts agree. Drs. Torrey and Yolken devised a working hypothesis, for instance, stating that most cases of schizophrenia are generated by infections and other environmental events occurring in genetically susceptible individuals.

The role of genes in many disorders has been recognized for about a century, Dr. Torrey noted, and the hope was that sequencing of the human genome would solve the riddle of chronic diseases and present a cure.

"If you asked someone in the mid to late 1980s where we were going researchwise, they would say these are genetic diseases, and as soon as we get the human genome sorted out, we will identify the genes involved and we can all go home and play golf," Dr. Torrey said. "That clearly has not been the case." What is clear to him is that multiple genes are involved in many diseases, and evidence points to a link between predisposing genes and infectious agents. "That made our research of greater interest."

The role of infection in cardiovascular disease is another area that, while not yet accepted, is attracting notice, particularly since heart disease is the No. 1 killer in the United States.

For example, recent studies have linked several common infections with a person's risk of developing atherosclerosis. It is possible that a bug causes the disease, said Michael Dunne, MD, vice president of clinical development in infectious disease at Pfizer Inc. Chlamydia pneumoniae is his prime suspect at the moment. "If you look at the arteries at autopsy of people with atherosclerosis you find evidence of Chlamydia in 50% or 60% of patients."

"The next step is: Can you do anything about it?" Dr. Dunne asked. That's where a series of antibiotic trials enter the picture. Although early results have not been positive, the findings from large trials scheduled for release later this summer could show whether a course of antibiotics is beneficial to heart patients.

Continuing search for MS trigger

The search for an infectious trigger for multiple sclerosis also has been under way for decades, said Richard T. Johnson, MD, distinguished professor of neurology, microbiology and neuroscience at Johns Hopkins School of Medicine.

When he first began researching the causes of MS in the 1960s, there was a firm conviction that the disease was due to an external agent, most likely a virus. But the early suspects turned out to result from mistakes, either misidentifications or lab contamination. That caused the idea to fall out of fashion.

Recently, however, interest peaked again. The targets are four rather ubiquitous agents: Chlamydia pneumoniae, herpes virus 6, Epstein-Barr virus and endogenous retroviruses. Since all are common, research is focusing on the quantity of the microbes and their location in the body. "That's a very interesting but complicated argument," Dr. Johnson said.

New technologies should help with the recognition of novel agents or already established agents in chronic disease, Dr. O'Connor said. "We also need to design epidemiologic studies in a more rigorous fashion so they are reproducible," she added.

Meanwhile, some of the confirmed relationships between infections and chronic diseases aren't receiving sufficient consideration in the clinical world, she said. Even the well-established link between H. pylori and peptic ulcers may be missed.

And other established links, such as that between Lyme disease and neurologic symptoms, also could go unrecognized, Dr. O'Connor said.

There are also prevention opportunities to be seized, she said. For example, physicians can tell patients that they have the power to prevent some liver cancers by avoiding exposure to the hepatitis B and C viruses.