PROCESS STATEMENT
The development of these recommendations arose in the spring of 2009 under the support
and recommendation of the Canadian Public Health Laboratory Network (CPHLN). The initial
group was formed of a federal co-chair (RT), a provincial co-chair (MM) and a CPHLN
secretariat lead (SR). An initial environmental scan was performed in 2009, which
was published in August 2011 (R Tsang, SM Radons, M Morshed. Laboratory diagnosis
of syphilis: A survey to examine the range of tests used in Canada. Can J Infect Dis
Med Microbiol 2011;22[3]:83–87). National representation was added to the working
group in 2010, including laboratory scientists from the provincial public health laboratories,
STI clinicians, epidemiologists and researchers. The group divided into smaller groups
for the drafting of each chapter, which was written and presented back to the larger
group. Once the document was finalized by the Syphilis Working Group, it was reviewed
and approved by the CPHLN Laboratory Directors Council (comprised of federal/provincial/territorial
PHL directors or their representatives), before submission to the Journal.
TREPONEMA PALLIDUM AND RELATED AGENTS
Syphilis is caused by the spirochaete, Treponema pallidum subsp. pallidum. The spiral-shaped
bacteria is related to other species causing non-venereal diseases including Treponema
pertenue, which causes yaws; Treponema endemicum, which causes endemic syphilis (bejel);
and Treponema carateum, which causes pinta (1). There is a high degree of antigenic
relatedness among the pathogenic treponemes (2,3). Available serological tests for
syphilis are reactive in persons infected with any of the treponematoses, but none
of these tests can distinguish endemic treponemal infections from venereal syphilis
(2,3). Currently, therefore, they are indistinguishable by morphological, immunological
or serological methods (2,3). Although several minor genetic differences have been
identified among the subspecies, the means to distinguish between these species remain
limited (2,3). It is noteworthy, however, that a recent case report from Canada described
the use of genomic techniques to demonstrate transmission of endemic syphilis in Canada
(4).
TRANSMISSION, PATHOGENESIS AND CLINICAL MANIFESTATIONS OF SYPHILIS
T. pallidum is an obligate human parasite with no known reservoirs in animals or in
the environment. Most cases of venereal syphilis occur due to direct sexual contact
with lesions containing the bacteria. Studies of sexual partners of patients with
syphilis report a risk of infection to approximately one-third (10% to 60%) of patients
exposed to early syphilis (1). Transmission by sexual contact does not occur during
the late latent and tertiary stages of infection. Untreated syphilis in pregnant women
can lead to complications during pregnancy and delivery including neonatal death,
still birth, blindness, deafness, abnormal bone growth and/or mental retardation.
T. pallidum is usually transmitted sexually through microabrasions in mucosal membranes
or skin, and rapidly enters the bloodstream to disseminate to other tissues (5,6).
To establish infection, T. pallidum adheres to epithelial cells and extracellular
matrix components of the skin and mucosa (6). T. pallidum replicates at the site of
initial inoculation, inducing a local inflammatory response that results in a painless
chancre approximately three to six weeks after initial infection. Within three to
eight weeks, the chancre heals, indicating clearance of T. pallidum locally. Once
the organism breaches the epidermal layer, multiplication occurs locally, followed
by dissemination through the blood vessels and lymphatics. Secondary syphilis results
from the multiplication and dissemination of the spirochaetes and can occur up to
six months after healing of the primary lesion. This stage can last from several weeks
to months and may reoccur in approximately 25% of untreated patients. It is characterized
by a range of clinical symptoms including malaise, headache, low-grade fever, rash
(including on the palms and soles of the feet), and mucous patches in the oral cavity
or genital tract. The symptoms of secondary syphilis will resolve with or without
treatment. Without treatment, however, the infection will progress to the latent and
tertiary stages of syphilis. The latent stage is divided into early (within one year
of infection) and late phases. Latency can last for many years and approximately 70%
of untreated patients will remain in this stage for the rest of their lives. The last
stage of syphilis, the tertiary stage, is rarely seen today given effective antibiotic
therapy. It usually occurs in 15% to 40% of untreated individuals, and can occur between
five and 40 years after infection (5). In this stage of syphilis, the bacteria invade
the central nervous system, eyes, skin, cardiovascular system and other organs.
EPIDEMIOLOGY OF SYPHILIS
Despite the existence of simple and validated screening tests, effective prevention
measures, such as condoms, and effective and relatively cheap treatment options, syphilis
remains a global problem, with an estimated 12 million people infected annually (7).
The World Health Organization (WHO) estimates that two million pregnant women each
year are infected with syphilis globally and that approximately 25% end in stillbirth
or spontaneous abortion (7).
In Canada, infectious syphilis (comprising of the primary, secondary and early latent
stages) is notifiable. Based on nationally reported case reports, during the early
and mid-1990s, Canada, like other high-income countries, was approaching or achieving
its goal to eliminate of endemic transmission of syphilis (8). Since 2000, however,
there has been a re-emergence of syphilis in the country, driven, in part, by reported
outbreaks among men who have sex with men, although recent reports suggest increased
incidence among the heterosexual population. Between 2000 and 2012, the overall reported
rate of infectious syphilis has increased by 481%, from 1.84 per 100,000 population
to 8.85 per 100,000 population (Figure 1) (9).
PUBLIC HEALTH IMPLICATIONS OF INCREASES IN INFECTIOUS SYPHILIS
The global increases in the reported prevalence of infectious syphilis is cause for
public health concern (10). Syphilis is, in principle, entirely preventable and potentially
eradicable because humans are the sole reservoir for this infection. Therefore, investment
in syphilis prevention and treatment should result in reduced disease burden and associated
costs in the future. In addition, HIV transmission is believed to be facilitated by
ulcerative sexually transmitted infections. While the relationship between syphilis
and HIV in the context of coinfection is complex, syphilis has been estimated to increase
HIV transmission two- to ninefold and HIV acquisition two- to fourfold (11–13). Hence,
treatment and prevention of syphilis will likely also reduce HIV transmission in that
population. Finally, syphilis is an important public health marker for behavioural
risk factors. In the United States, for example, the resurgence of syphilis among
men who have sex with men was associated with increases in the number of anonymous
sex partners, use of the Internet for meeting sex partners, decreases in condom use
and more widespread use of methamphetamine (14,15). Similarly, in the downtown east
side of Vancouver (British Columbia), a syphilis outbreak was associated with crack
cocaine use and the sex trade (16). Any sustained decline in syphilis will, therefore,
need to be accompanied by behavioural changes.
While prevention and treatment are essential for the control of syphilis, diagnosis
forms the third critical component in public health programming. In Canada, testing
for syphilis has traditionally consisted of initial screening with an inexpensive
nontreponemal test and confirmatory testing of the reactive specimen with a more expensive
treponemal test. However, since the advent of immunoassays and recombinant T. pallidum
antigens as screening tools, there have been rapid changes to laboratory testing algorithms
for syphilis across Canada. These approaches have introduced complexities in the interpretation
of test results and how patients with such results should be managed. In addition,
newer tests have become available that allow for rapid, point-of-care testing, and
new molecular tests have emerged. Special situations, such as neurosyphilis and congenital
syphilis, remain diagnostic challenges. The purpose of the chapters contained in this
supplement is to provide guidance on testing for syphilis in Canada.