The bug first came under suspicion in 1988, when doctors Pekka Saikku and Maija Leinonen of Helsinki Center Hospital published a pair of intriguing studies. The first showed that people with coronary-artery disease were more likely than healthy control subjects to have antibodies to C. pneumoniae circulating in their blood. The second study turned up unusually high antibody levels in the blood of heart-attack victims. Most experts dismissed the Finnish findings as a statistical oddity. But Dr. Thomas Grayston, an epidemiologist at the University of Washington, was intrigued enough to launch a study of his own. Grayston documented the same pattern in Seattle that Saikku had seen in Helsinki, and eight research teams from five countries have since confirmed it.
Searching for evidence: But does the association mean anything? The presence of antibodies tells you only that a person has encountered a pathogen and mounted an immune response. It doesn’t reveal whether the bug is still present or, if so, how it’s affecting the body. With those questions in mind, researchers set out in the early ’90s to look for direct evidence of C. pneumoniae in clogged, brittle blood vessels. The first break came in 1993, when a South African researcher spotted what looked like tiny, pear-shaped bacterial cells in tissue cut from diseased arteries during autopsies. Grayston’s team analyzed snippets of the same tissue and detected C. pneumoniae’s proteins and genetic material in 20 out of 36 samples.
Other labs followed, and most of them managed to find bacterial fingerprints by one method or another. But few experts paid much attention until 1995, when a team led by Dr. James Summersgill of the University of Louisville recovered the bug itself, alive and kicking, from a patient’s blood vessels. The patient, a 56-year-old man undergoing a heart transplant, hadn’t suffered any recent respiratory illness. Yet when researchers placed tissue from his coronary arteries in a culture dish, they got colonies of C. pneumoniae. Today, says Grayston, no one familiar with the literature denies that the microbe is associated with vascular disease. Whatever their age, sex or nationality, people with sclerotic arteries tend to show signs of infection. And unlike the other microbes sometimes found in damaged vessels, this one never shows up in truly healthy tissue.
Yet, as the germ hunters readily admit, finding the bug at the crime scene doesn’t prove it’s a criminal. No one has shown conclusively that C. pneumoniae causes the damage that leads to heart attacks and strokes, but there are good reasons to suspect that it plays a role. Scientists have long known that atherosclerosis is an inflammatory disease. It affects vessels throughout the body, but those supporting the heart and brain are particularly vulnerable. The trouble starts when our immune systems mobilize to remove fat, cholesterol and other irritants from vessel walls (chart). As immune cells called macrophages burrow into the arterial tissue to gobble up foreign material, they can set off a vicious cycle of irritation and scarring. The result is a scabby lesion, or plaque, that can foster blood clots and impede circulation. Some experts now suspect that C. pneumoniae fuels that inflammatory process. It’s only a hunch, but the preliminary evidence supports it nicely.
Immune-cell magnet: According to the hypothesis, macrophages that have helped clear C. pneumoniae from the respiratory system may sometimes become active carriers of the bug. And when an infected macrophage hunkers down on a vessel wall, it may infect the cells lining the arterial surface. The artery would then attract more immune cells, which would deliver more bacteria, causing still more inflammation. Researchers at Johns Hopkins have shown in test-tube experiments that C. pneumoniae can indeed survive within macrophages and arterial cells. And the University of Louisville team has found that infected arterial cells do in fact serve as a magnet to immune cells. “I was leery a few years ago,” says Charlotte Gaydos, director of the Johns Hopkins group. “But this evidence has made me more of a believer.”
The evidence isn’t all confined to test tubes. During the past few months three teams have shown that C. pneumoniae spontaneously invades arterial tissue in animals. Researchers at St. Michael’s Hospital in Toronto infected a dozen rabbits through the nose and found that two developed lesions in their aortas within two weeks. Saikku and Leinonen, now with the National Public Health Institute in Oulu, Finland, infected five rabbits by the same route. Rabbits don’t normally get atherosclerosis, even when they’re fed high-fat diets. But within seven weeks of contracting C. pneumoniae, three of the Finns’ five animals had developed arterial plaques. If a second round of studies shows that antibiotics can stall the growth of those plaques, there won’t be much doubt about what triggered them.
There will still be plenty of questions about how all of this applies to people. Even if scientists can prove that C. pneumoniae causes heart disease, they’ll be left to wonder how great a role it plays and why some people are more susceptible than others. Do fat and cholesterol make us sick by themselves, or only in the company of this bug? And if all these risk factors reinforce each other, how do they interact? Maybe C. pneumoniae aggravates wounds caused by fat and cholesterol–or maybe it causes wounds that later become dump sites for those substances. And then there’s the matter of treatment. Could antibiotics quickly rid the body of infected cells? And would clearing the infection stop the disease process?
The hope, of course, is that antibiotic therapy will prove as useful for clearing arteries as it is for healing ulcers. And optimists see some encouraging signs. Heart-attack mortality has dropped by half since the mid-1960s. The decline is due partly to changes in lifestyle and improvements in medical care, but it coincides nicely with the rise of drugs like tetracycline and erythromycin. Researchers are now gearing up to test such remedies in controlled settings. In a preliminary study, researchers at St. George’s Hospital in London recently treated 46 heart-attack survivors with two brief courses of placebos or the antibiotic azithromycin. After six months, blood tests showed that the patients who got the drug were producing fewer inflammatory proteins. Several teams are now planning studies to see if that effect will translate into improved survival. If it does, cardiology is in for a revolution.
Scientists have long known that atherosclerosis is an inflammatory disease. Some experts now suspect that a mircrobe called Chlamydia pneumoniae is at least partly to blame for inflaming the arterial wall. Here is how the precess might work:
l. Immune cells known as macrophages become infected with C. pneumoniae and carry it from the respiratory system–its primart target–into the blood stream.
When a macrophage burrows into the wall of a blood vessel to gobble up irritants such as fat or cholesterol, it transfers C. pneumoniae into neighboring arterial cells.
Infected arterial cells than attract more macrophages, which rush to the vessel wall, gorge themselves on diseased tissue and die, setting off a vicious cycle of inflamation.
The result is a large fibrous lesion, or plaque, that narrows the blood vessel. When pieces of the plaque break loose, they can start blood clots and cause heart attacks.
