NEW YORK, Friday, April 9, 1999 - The recent isolation of the spiral-shaped bacterium that causes Lyme disease from apparently cured patients with persistent chronic symptoms may make it difficult to rule out a role for syphilis in causing a variety of health problems - including AIDS - two Canadian researchers maintain.

In a controversial, ground-breaking paper presented at the 12th International Conference on Lyme Disease and Other Spirochetal and Tick-Borne Disorders, taking place April 9 & 10 at the Equitable Conference Center in New York City, John Scythes, director of Toronto's Community Initiative for AIDS Research (CIFAR), explains how the culture technique recently developed for Lyme disease may potentially offer new insights into the diagnosis of syphilis, a potentially deadly disease caused by a closely-related member of the spirochete family of bacteria. This issue is especially important for HIV-infected people, who have always been at high risk for (re-)exposure to syphilis, which may damage their immune system, present itself in atypical fashion, and turn up negative on standard blood tests.

These very same arguments have been advanced for years by some Lyme specialists and patient advocates, who maintain there is a chronic form of the disease that can persist after conventional antibiotic treatment, often despite negative results on standard blood tests. This small but increasingly vocal group has been agitating for the medical establishment to take them seriously and support research into chronic Lyme symptoms.

Like other spirochetes, the Lyme microbe, Borrelia burgdorferi, is difficult -- often impossible -- to isolate in patients, and some researchers have long suspected the bacteria mutate in the body, losing their cell wall and becoming drug-resistant.

Now a new laboratory technique, published last November, can demonstrate the presence of the altered forms of the bacteria in the blood of late-stage patients with long-time infections. These included patients who have been on a regular, month-long course of oral antibiotics and several weeks of intravenous antibiotics. The new procedure for culturing the bacteria proves that many people can still harbour the B. burgdorferi spirochetes in their bodies despite supposedly adequate treatment and negative blood tests, suggesting the disease is, in the authors' view, "vastly underdiagnosed."

In the current paper, Scythes, along with his co-author, science writer and broadcaster Colman Jones, point out the Lyme finding also raises questions about the closely-related, perhaps more dangerous spirochete of syphilis, Treponema pallidum. Most STD specialists in Eastern Europe have always believed that T. pallidum maintains latency by surviving in this altered part of the life cycle.

The ability to culture the Lyme bacteria from patients presumably cured of the infection represents an exciting development that holds promise for the detection of syphilis, especially in HIV-infected persons. Scythes and Jones suggest it may now be incumbent on the syphilis research community to adapt this technique for the syphilis spirochete and establish a new gold standard in the diagnosis of this deadly sexually-transmitted disease. This is especially important given the problems with syphilis serologic blood tests that, as with those for Lyme disease, don't detect the organism itself, but rather detect only one part of the body's immune response to it.

The finding by Phillips and colleagues - i.e., that altered, cell-wall deficient forms of B. burgdorferi can be made to revert back into fully-formed spirochetes capable of causing disease - may help explain how syphilis can remain latent in the body for years, the spirochetes remaining undetectable by the most sensitive techniques.

For decades, theories have been advanced postulating a life-cycle survival mechanism for T. pallidum. Observers in several American centers in the 1940s and 1950s found evidence suggesting atypical forms of treponemes, as did investigators in Russia and Hungary. At a 1962 symposium on syphilis sponsored by the World Health Organization, leading expert Herman Beerman stressed the question of a life cycle remains unresolved.

With the overwhelming success of penicillin in the treatment of early syphilis, these unanswered questions were largely pushed aside, and are no longer referred to in current textbooks dedicated to syphilis research - a field which has long been starved of funds. Most STD budget allocations have been diverted into research on AIDS, which scientists have traditionally viewed as a "new" disease caused by a "new" virus - HIV. But others, including a growing body of so-called "AIDS dissidents" aren't convinced that the virus is sufficient to explain this complex syndrome.

"HIV isolation is shoddy science", Scythes insists. "Finding genetic sequences of the virus is one thing, and finding whole, infectious virus is quite another." He notes that despite billions of dollars and 15 years, HIV-based research is essentially going around in circles, with no sight of a vaccine on the horizon. While anecdotal accounts claim a benefit from the new combination therapies which include protease inhibitors, alarming reports suggest side effects and toxicities prevent many patients from adhering to the rigorous regimen. Furthermore, the hugely expensive medications are completely unaffordable to the vast majority of the world's HIV-infected populations.

Scythes, Jones and others wonder whether syphilis has made a deadly comeback and is responsible for much of the sexually-transmitted epidemic of AIDS. Historically, long-standing syphilitics often succumbed to early death from strange pneumonias, rare cancers, and especially re-activated TB - all AIDS-defining conditions today. The authors suggest that this the well-documented excess mortality associated with a history of syphilis is enough to explain the susceptibility to HIV and opportunistic infections in gay men since 1980, in light of the millions of latent syphilis cases known to have gone untreated or inadequately in this population worldwide. They are also concerned about the dangers re-infection with syphilis may pose to the immune system, and note the well-documented association between past syphilis and becoming HIV-positive and/or developing AIDS.

CIFAR was founded in 1988 to encourage research into possible co-factors in AIDS. Scythes has worked in conjunction with specialists at Toronto Hospital, HIV primary care physicians, and the Ontario Ministry of Health's Laboratory Services Branch, documenting unusual behaviour in the syphilis blood tests among people with HIV, and publishing findings at AIDS and STD conferences for over a decade. These findings include the discovery that some patients with a past history of syphilis appear to lose their specific antibodies directed against the infection - normally life-long markers of past exposure, often shortly prior to death from AIDS. Scythes and colleagues are worried that the mysterious disappearance of this antibody (which is highly selective, i.e. antibodies against other infections remain) may signal a loss of immunity against this deadly disease.

Jones' 2-hour radio documentary on this topic, produced for the Canadian Broadcasting Corporation radio program Ideas ("Déja Vu: AIDS in Historical Perspective"), garnered the Canadian Science Writers Association 1996 Science in Society Journalism Award. He notes that if syphilis researchers are able to apply the B. burgdorferi culture technique to T. pallidum, they may well uncover what may represent a vast mountain of previously undiagnosed syphilis among AIDS patients.

Such a finding would pose a severe threat to the new-virus/new-disease paradigm, which has governed virtually all AIDS research. In fact, a large body of historical data suggests the syndrome is an age-old condition that eluded medical understanding. It was not until an explosion of syphilis in gay communities worldwide throughout the 1960s and 1970s, coupled with the development of tools to measure immune markers such as T-cells, that modern medicine identified what initially appeared to be a "new" syndrome, AIDS.

Syphilis shocker
Is there AIDS clue in "negative" tests that come back positive?
Colman Jones, NOW Toronto, 2000, Vol 19, No. 48

Ontario health officials have made a shocking discovery that threatens to blow the roof off conventional thinking about a dangerous sexually-transmitted infection -- syphilis -- and how to test for it among people at risk for AIDS.

In a presentation at this year's meeting of the American Society of Microbiology, Neal denHollander, who directs research at the Public Health Laboratory of Ontario, showed how a new type of syphilis test found otherwise undetected cases in nearly five per cent of samples from STP clinics including the Hassle Free Clinic on Church.

These were positive results in samples that showed up negative in the regular screening test.

The significance of this might well be that there are many people walking around today who are carrying the STD and don't know it. But more than that, the finding may inch us much closer to answering the question that has preoccupied me for several years now -- does syphilis play an important and possibly necessary role in the development of AIDS itself?

The new technology that allows us to find the formerly unfindable STD is called the Trep-Chek. To see how well the new test performed against the regular ones, denHollander and colleagues took 557 recent blood specimens mostly from Hassle Free's routine syphilis submissions -- all had come back negative in the standard screening test (called the VDRL).

To their surprise, they found 27 registered positive.

The study, which has taken the local AIDS community by surprise, revives concerns first sounded over 10 years ago by then-chief provincial serologist Bob Notenboom. With the help of Douglas MacFadden, director of the HIV Clinic at Toronto Hospital's Western Division, and local bookstore owner and AIDS expert John Scythes, Notenboom and his officials documented unexplainable irregularities in syphilis testing among people with HIV.

Thorny question
With the aid of this more sophisticated biotechnology, denHollander now has taken up the issue again. He stresses that the standard methods used to screen for syphilis are "clearly under-sensitive."

How much of a concern is this diagnostic gap? That all depends on how dangerous one considers untreated syphilis to be.

AIDS experts readily acknowledge the high correlation between being HIV-positive and having had syphilis, but only insofar as the sores produced by syphilis allow HIV to enter the body more easily. However, some theorists argue that untreated or inadequately treated syphilis may be a factor in the development of AIDS -- especially as new evidence suggests bacterial infections can "wake up" an otherwise latent, inactive HIV infection.

Indeed, emerging research into the immune response in the later stages of syphilis suggests there may be much more going on between syphilis and HIV than was previously thought. Recent findings from veteran Polish syphilis researcher Jadwiga Podwinska point to pronounced immune irregularities once the disease has reached the latent (hidden) stage.

Among HIV primary-care physicians, the surprising new findings only confirm their own doubts about syphilis tests. "Compared to other tests, they tend to be less reliable," says John Goodhew. "I compensate for that by doing syphilis tests on everybody every year."

But no one knows how well the syphilis tests Goodhew is using really work. Indeed, Notenboom found AIDS patients with a past history of syphilis who seemed to lose their normally lifelong specific antibodies against syphilis, while antibodies against other infections remain. "It is possible," he says, "to have syphilis, and yet all the tests are negative."

Could untreated chronic syphilis be making a lot of people sick, especially those with HIV? It's a concern I voice to Bill Cameron from the University of Ottawa, one of Canada's leading AIDS authorities.

"I agree with you," he admits from Oxford University in England where he is a visiting research scientist. "I would be happy to see a large-scale evaluation of these newer and better tests.