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  • Ocular syphilis, which affects the eye and can lead to blindness, is on the rise
  • Like syphilis in general, most cases are reported among men who have sex with men
  • Nearly half of the people diagnosed with ocular syphilis were HIV positive

Syphilis is a common sexually transmitted condition. For the past two decades, rates of syphilis have been on the rise in Canada and other high-income countries. Gay, bisexual and other men who have sex with men (MSM) have been disproportionally affected by syphilis. What’s more, HIV-positive men seem particularly susceptible to syphilis. The germ T. pallidum causes syphilis and can lead to complex and multi-stage disease that affects nearly every organ-system in the body. If caught early, syphilis is easily treated. People may not be aware that they have syphilis, so regular blood tests can be useful in uncovering this condition.

In the United States

In 2015 the U.S. Centers for Disease Control and Prevention (CDC) published a report about several hundred cases of syphilis that affected the eye(s); this is called ocular syphilis. Affected people were overwhelmingly MSM. If left undiagnosed and untreated, ocular syphilis can lead to blindness. After the CDC’s report, other reports of ocular syphilis in the U.S. and in other countries appear to have increased.

In British Columbia

As in other parts of Canada, cases of syphilis have been on the rise in B.C. since 2000. Scientists at the BC Centre for Disease Control (BCCDC) who have been monitoring syphilis in the province have noted the following trends:

  • cases of syphilis rose by 40% between 2014 and 2015
  • males accounted for 97% of infectious syphilis cases in 2016

Spurred by reports of ocular syphilis in the U.S. and elsewhere, a team of scientists at the BCCDC and the University of British Columbia conducted a study. They reviewed cases of syphilis and ocular syphilis diagnosed in B.C. between January 2010 and December 2018. The scientists also compared health-related information between people with ocular syphilis and people with syphilis who did not have eye complications. 

They found that cases of ocular syphilis increased over the course of the study period. Other findings and recommendations from the B.C. scientists appear later in this CATIE News bulletin.

Study details

The BCCDC scientists reviewed data collected on people who had been diagnosed with syphilis in the province. They also compared information between 66 people with ocular syphilis and 264 people with syphilis who did not have eye complications. Therefore, all of the people in this study had syphilis.

Results—Overall

The scientists found the following:

  • 6,716 people were diagnosed with syphilis between January 2010 and December 2018
  • 74% of all syphilis cases were considered infectious (occurring in the primary, secondary or early latent stages of this disease)
  • 66 people were diagnosed with ocular syphilis
  • ocular syphilis represented about 1% of syphilis cases

Trends

  • In 2010, ocular syphilis represented 0.48% of syphilis cases. By 2018, ocular syphilis cases represented 0.83% of total syphilis cases (almost 1%).
  • The majority of people with syphilis in general and ocular syphilis in particular were MSM.

Focus on HIV

Nearly half of the people with ocular syphilis were HIV positive. In contrast, among people without ocular syphilis (but who also had a diagnosis of syphilis), 26% were HIV positive.

In this study, among HIV-positive people with ocular syphilis, slightly more than half (52%) had a viral load test result greater than 1,000 copies/mL. By contrast, among HIV-positive people without ocular syphilis, scientists found that 78% had an undetectable viral load (less than 50 copies/mL).

Ocular syphilis treatment and outcomes

According to the scientists, “the vast majority (89%) of ocular syphilis cases were treated with intravenous penicillin—the treatment of choice for ocular syphilis.” Furthermore, the scientists stated that at the end of a course of intravenous treatment, “most” patients with ocular syphilis were given an injection of benzathine penicillin into muscle. Subsequently, muscle tissue slowly releases this penicillin into circulation. Intramuscular injection of penicillin is a way to provide extended exposure to penicillin to kill any residual germs that cause syphilis. The scientists stated that such injections at the end of intravenous therapy are part of the standard of care in B.C. for ocular syphilis. 

The scientists reported that 91% of patients had an improvement in their vision at the end of their treatment for ocular syphilis.

Why are cases of ocular syphilis increasing?

In high-income countries there appears to be increased reporting of ocular syphilis. It is not clear why this is occurring, but below are some reasons:

  • It is plausible that there may be a strain of syphilis in circulation that more easily infects the eye. For instance, previous research has found that there are strains of T. pallidum (the germ that causes syphilis) that are more commonly found in people with neurosyphilis. However, preliminary research has not so far confirmed that there is a particular strain of syphilis associated with eye complications. 
  • It is possible that since the release of the 2015 CDC report about ocular syphilis, more doctors and nurses are conducting assessment and screening for ocular syphilis. In turn, this increase in assessment and screening for ocular syphilis has led to increased diagnoses of this condition.

Bear in mind

The B.C. study was retrospective in design. Such studies look back on data collected for one purpose and analyse the data for another purpose. Retrospective study designs are imperfect, but the B.C. scientists took care to minimize the possibility of errors when analysing the data and drawing conclusions. Furthermore, the findings from B.C. are similar to those from other high-income countries where ocular syphilis has been reported.

The B.C. study is important and will hopefully encourage other provinces and territories to consider assessing their own outbreaks of ocular syphilis. 

The scientists made several important points arising from their research, as follows:

  • “It is vital to comprehensively explore the symptoms of syphilis complications with patients, paying special attention to those with infectious syphilis and high [levels of antibodies in the blood associated with syphilis].”
  • “Prompt identification of ocular syphilis and urgent ophthalmological evaluation is critical as most patients achieve excellent visual recovery after treatment.”
  • “Our findings also underlie the importance of determining HIV status in ocular syphilis patients given the high proportion of co-infection. Therefore, we recommend testing all ocular syphilis cases of syphilis for HIV, as a diagnosis of ocular syphilis may also reveal a new HIV diagnosis.”

Notes on the eye

The eyeball consists of three layers of tissue called the uvea. Inflammation of the different parts of the uvea has the following names:

  • anterior uveitis – inflammation of the front layer of the uvea
  • intermediate uveitis – inflammation of the intermediate layer of the uvea
  • posterior uveitis – inflammation of the back layer of the uvea

Panuveitis is the term used when all the layers of the uvea are inflamed. 

Symptoms of uveitis, including panuveitis, can include the following:

  • the white part of the eye becomes red (this may or may not be painful)
  • increased sensitivity to bright light
  • blurry vision 
  • seeing tiny dark dots (commonly called “floaters”)
  • cloudy vision

In addition, the germs that cause syphilis can affect other parts of the eye, such as the following:

  • the retina – the light-sensitive portion of tissue at the back of the eye
  • the optic nerve – this sends images from the retina to the brain

When syphilis affects these parts of the eye, one or more of the following can occur:

  • floaters can appear
  • small flashing spots appear
  • vision can become blurry
  • blind spots develop

Note that symptoms of uveitis and injury to the retina and/or optic nerve can occur with other conditions. Whatever the underlying cause, new or sudden onset of visual problems should prompt immediate medical consultation. 

Resources

Canadian guidelines on STIs – Management and treatment of syphilis

BC Centre for Disease Control – Syphilis

Guide québécois de dépistage des infections transmissibles sexuellement et par le sang

Syphilis - BMJ

SyphilisCATIE Factsheet

American doctors focus on cases of ocular syphilisCATIE News

Syphilis cases on the rise among HIV-positive people in CalgaryCATIE news

Sean R. Hosein

REFERENCES:

  1. Hamze H, Ryan V, Cumming E, et al. HIV seropositivity and early syphilis stage associated with ocular syphilis diagnosis: A case-control study in British Columbia, Canada, 2010-2018. Clinical Infectious Diseases. 2019; in press.
  2. Woolston S, Cohen SE, Fanfair RN, et al. A cluster of ocular syphilis cases—Seattle, Washington, and San Francisco, California, 2014-2015. MMWR. Morbidity and Mortality Weekly Report. 2015 Oct 16;64(40):1150-1.
  3. O’Byrne P, MacPherson P. Syphilis. BMJ. 2019 Jun 28;365:l4159.
  4. Marra CM, Ghanem KG. et al. Centers for Disease Control and Prevention Syphilis Summit: Difficult clinical and patient management issues. Sexually Transmitted Diseases. 2018 Sep;45(9S Suppl 1):S10-S12.
  5. Oliver S, Sahi SK, Tantalo LC, et al. Molecular typing of Treponema pallidum in ocular syphilis. Sexually Transmitted Diseases. 2016 Aug;43(8):524-7.
  6. Hook EW 3rd. Syphilis. Lancet. 2017 Apr 15;389(10078):1550-1557.
  7. Lang R, Read R, Krentz HB, et al. A retrospective study of the clinical features of new syphilis infections in an HIV-positive cohort in Alberta, Canada. BMJ Open. 2018 Jul 10;8(7):e021544.
  8. Refugio ON, Klausner JD. Syphilis incidence in men who have sex with men with human immunodeficiency virus comorbidity and the importance of integrating sexually transmitted infection prevention into HIV care. Expert Review of Anti-Infective Therapy. 2018 Apr;16(4):321-331.
  9. Rekart ML, Ndifon W, Brunham RC, et al. A double-edged sword: does highly active antiretroviral therapy contribute to syphilis incidence by impairing immunity to Treponema pallidum? Sexually Transmitted Infections. 2017 Aug;93(5):374-378.
  10. Marra C, Baker-Zander SA, Hook EW 3rd, et al. An experimental model of early central nervous system syphilis. Journal of Infectious Diseases. 1991 Apr;163(4):825-9.
  11. Lukehart SA, Hook EW 3rd, Baker-Zander SA, et al. Invasion of the central nervous system by Treponema pallidum: implications for diagnosis and treatment. Annals of Internal Medicine. 1988 Dec 1;109(11):855–62.
  12. Radolf JD, Tramont EC, Salazar JC. Syphilis (Treponema pallidum). In: Bennett JE, Dolin R and Blaser MJ, editors. Mandell, Douglas, and Bennett's principles and practice of infectious diseases. 8th ed. Vol. 2. Philadelphia (PA): Elsevier; 2015. p. 2584-2709.
  13. Leber A, MacPherson P, Lee BC. Epidemiology of infectious syphilis in Ottawa. Recurring themes revisited. Canadian Journal of Public Health. 2008 Sep-Oct;99(5):401-5.
  14. Costiniuk CT, MacPherson PA. Neurocognitive and psychiatric changes as the initial presentation of neurosyphilis. CMAJ. 2013 Apr 2;185(6):499-503.
  15. Marra CM, Tantalo LC, Sahi SK, et al. Reduced Treponema pallidum-specific opsonic antibody activity in HIV-infected patients with Syphilis. Journal of Infectious Diseases. 2016 Apr 15;213(8):1348-54.
  16. Marra C, Sahi S, Tantalo L, et al. Enhanced molecular typing of treponema pallidum: geographical distribution of strain types and association with neurosyphilis. Journal of Infectious Diseases. 2010 Nov 1;202(9):1380-8.