December 3, 2008
Until 1997, it seemed that syphilis rates were declining in Canada. However, since then, outbreaks of syphilis have been reported in every major Canadian urban centre. These outbreaks are not occurring in isolation -- parallel outbreaks of syphilis, particularly among men who have sex with men (MSM), are also occurring in major urban centres in North America, Western Europe and Australia. Before we delve into a recent Canadian report about syphilis, here is some background information.
Syphilis is the name given to a chronic infection caused by the germ T. pallidum. This disease can be spread in the following ways:
The germs that cause syphilis (called treponemes) can cause sores on the genitals, rectum and mouth. These sores can be an entry point for HIV and other sexually transmitted infections (STIs) to get inside the body. Once inside the body, treponemes, like HIV, can enter the lymphatic system or the blood stream. From there, in a matter of hours or a few days, treponemes can quickly spread throughout the body and reach the brain.
In early stages of syphilis a sore can appear on the penis or in the rectum or, in women, on the cervix. In people co-infected with HIV, multiple sores can appear. Because the sores appear in hidden locations, early-stage syphilis might go unnoticed in both men and women.
Lymph nodes in the groin may become swollen, usually within a week of the appearance of the syphilitic sore. Although the sore, sometimes called a chancre, can heal within four to six weeks, lymph nodes may remain swollen for several months.
Still, early-stage syphilis can have minimal symptoms and may go unnoticed by affected people. Troublingly, treponemes have been found in the spinal fluid of people with primary syphilis, regardless of HIV infection.
In this stage, generally two to 12 weeks after the appearance of the chancre, symptoms of a widespread T. pallidum infection occur. Symptoms can vary considerably but the following can be common:
The skin rash can begin on the trunk but may also appear anywhere else, including on the palms of the hands and soles of the feet. If the rash affects a hairy area, temporary patchy hair loss can occur. For instance, thinning of the eyebrows, beard or parts of the head can be a feature of syphilitic rash.
Painless lesions called mucous patches can appear on the wet tissues of the genitals, mouth, throat and tonsils. These lesions are teeming with treponemes and are highly infectious.
In up to 40% of people with secondary syphilis, the brain and spinal cord (CNS -- central nervous system) can become infected, with or without symptoms. In some cases, symptoms such as the following may appear:
If left untreated, neurosyphilis can develop, leading to severe complications.
The germs that cause syphilis can also infect the liver, causing liver damage or hepatitis, detected by increasing levels of liver enzymes in the blood.
Secondary syphilis can also turn into latent syphilis. In this case, no symptoms are present and the infection is only detectable with blood tests. However, despite the lack of symptoms, the disease is still eating away at the body.
In this stage of illness, any organ of the body may become slowly inflamed and affected by T. pallidum. Generally, late syphilis can affect the nervous system (neurosyphilis), the heart and blood vessels (cardiovascular syphilis) and just about any organ/system where a syphilitic lesion can appear. Such solitary lesions are called gummas.
If left untreated, late-stage syphilis can eventually lead to unpleasant and dreadful complications, including the following:
Given all of these, regular blood tests for syphilis (and other STIs) are important for sexually active people who wish to remain healthy.
Different tests are available for assessing syphilis. For further information about which tests are available in your region, contact your local laboratory.
Blood tests commonly used to help diagnose syphilis include the following:
These two tests are indirect tests in that they detect antibodies produced against proteins unrelated to T. pallidum but that still occur in cases of syphilis. In people with primary syphilis or latent syphilis, these indirect tests may not always work. In such cases, where syphilis is suspected, the Public Health Agency of Canada (PHAC) recommends that doctors repeat the indirect test several weeks later and also consider the use of tests that specifically assess the presence of antibodies to T. pallidum. These tests include the treponemal enzyme immunoassay (EIA). Other tests that may be useful include FTA-ABS, MHA-TP.
PCR tests are not routinely used to detect T. pallidum and they cannot distinguish between live and dead treponemes. Moreover, PCR tests are only available at specialized laboratories, including Canada's National Microbiology Laboratory.
Recently, researchers in the Netherlands have suggested that routine assessment of blood for syphilis may be useful in HIV positive MSM because this disease can, at least initially, be symptom-free. This Dutch study will be the focus of an upcoming CATIE News story.
Unlike the case with many other diseases, one syphilis expert writing in an infectious disease textbook noted that "there have not been many well-controlled, carefully planned, prospective studies to determine [the best dose or length] of therapy." Current recommendations for treatment of syphilis are based on extrapolations of older data. Despite these drawbacks, an antibiotic called benzathine penicillin G is considered the gold standard of anti-syphilis therapy.
Ideally, maintaining high levels of penicillin in the blood should keep T. pallidum from reproducing and still higher levels can help kill these germs. So, for treating early syphilis, high levels of penicillin G are needed for at least seven days. The most convenient way to achieve this while avoiding the issue of patient adherence is an injection of benzathine G penicillin into muscle. However, it is important to note that this dose is inadequate for neurosyphilis; indeed, levels of penicillin that can kill treponemes in the CNS are not reliably achieved with a single injection of benzathine penicillin G 2.4 million units. Yet, in cases of early diagnosis, where, in theory, there are fewer treponemes, the evidence shows that treatment with a single injection of penicillin is sufficient therapy for the average person with primary syphilis.
Antibiotics such as doxycycline impair the growth of treponemes and are sometimes used in patients who are allergic to penicillin. Bear in mind that unlike penicillin, doxycycline does not kill treponemes and may be less effective in people with severely weakened immune systems. In cases of penicillin allergy, some experts prefer to desensitize their patients to penicillin -- a course of action suggested by PHAC. Penicillin desensitization is also recommended for cases of syphilis in pregnant women.
Another potential treatment is the antibiotic azithromycin (Zithromax). However, reports have emerged of cases of syphilis resistant to azithromycin in the United States, Ireland and recently in the province of British Columbia. All of the B.C. cases of azithromycin-resistant syphilis were in MSM. PHAC does not recommend the use of this antibiotic for the routine treatment of syphilis.
Also, the antibiotic ceftriaxone is not recommended for routine treatment of syphilis in Canada.
The treatment of syphilis in people co-infected with HIV is controversial. Some physicians are in favour of the same therapy that would be used in HIV negative people -- a single intramuscular injection of benzathine penicillin G 2.4 million units. However, because of a number of factors, some doctors may opt for more rigourous therapy in HIV positive people. These factors can include the following:
Such considerations have prompted some physicians to use benzathine penicillin G 2.4 million units, injected intramuscularly, once weekly for three consecutive weeks as treatment in HIV positive people for primary or secondary syphilis.
Alternatively, other physicians may opt for the antibiotic doxycycline 100 mg taken orally twice daily for two to four consecutive weeks. Although effective in early-stage syphilis, doxycyline has not been tested for late-stage syphilis, so syphilis experts recommend desensitization to penicillin in patients with penicillin allergy, followed by penicillin therapy. Moreover, unlike penicillin, doxycycline does not kill treponemes.
For neurosyphilis, regardless of HIV infection status, PHAC recommends therapy with penicillin G 3 to 4 million units given intravenously every four hours each day (for a total of between 16 and 24 million units daily) for 10 to 14 days.
PHAC has excellent guidelines (updated in 2008) for the management of patients with syphilis, including a penicillin desensitization plan, available at:
For further information about syphilis and HIV, see "The Story of Syphilis" in The Positive Side magazine (spring/summer 2004), available at:
Recently, doctors in the Ottawa region have been studying an outbreak of syphilis to try to better understand it. Our report on this appears in the next CATIE News bulletin.