National Advisory Committee on Sexually Transmitted and Blood-Borne Infections statement: Syphilis screening recommendations for non-pregnant adults and adolescents

On this page

• Preamble
• Executive summary
• Introduction
  • Public health importance in Canada
  • Screening and diagnostic testing
  • Syphilis treatment
  • Purpose/Rationale for new recommendations and approach to the updates of existing syphilis screening guidelines for adults and adolescents
  • Objectives
  • Target audience
• Methods
  • Working group
  • Questions and outcomes
  • Reviews and evidence
  • Making recommendations
  • Management of conflicts of interest
• Recommendations
  • Syphilis screening for sexually active, non-pregnant adults and adolescents
  • Syphilis screening for high prevalence groups and communities
    • Factors associated with Syphilis infections
  • Summary of evidence
• Dissemination, implementation, monitoring and evaluation
  • Dissemination
  • Implementation
    • Congenital Syphilis
  • Monitoring and evaluation
  • Limitations
• Research priorities and implications
• List of abbreviations
• Acknowledgements
• Appendices
  • Appendix 1: Flow diagram of study selection on syphilis screening since 2019
  • Appendix 2: Summary of evidence-to-decision framework judgements
  • Appendix 3: Characteristics of included studies and summary of findings
    • Table 3.1. Relevant systematic reviews on syphilis screening
    • Table 3.2. Major studies on syphilis screening
    • Table 3.3. Characteristics of patient values and preferences, cost-effectiveness studies on syphilis screening
    • Table 3.4. Evidence profiles
  • Appendix 4: Environmental scan of guidelines
• References

Preamble

The National Advisory Committee on Sexually Transmitted and Blood-Borne Infections (NAC-STBBI) is an External Advisory Body that provides the Public Health Agency of Canada (PHAC) with ongoing scientific and public health advice and recommendations for the development of sexually transmitted and blood-borne infections (STBBI) guidance, in support of its mandate to prevent and control infectious diseases in Canada.

PHAC acknowledges that the advice and recommendations in this statement are based upon the best available scientific knowledge at the time of writing and is disseminating this document for information purposes to primary care providers and public health professionals. The NAC-STBBI statement may also assist policy makers or serve as the basis for adaptation by other guideline developers. NAC-STBBI members and liaison members conduct themselves within the context of PHAC's Policy on Conflict of Interest, including yearly declaration of interests and affiliations.

The recommendations in this statement do not supersede any provincial or territorial legislative, regulatory, policy and practice requirements or professional guidelines that govern the practice of health professionals in their respective jurisdictions, whose recommendations may differ due to local epidemiology or context. The recommendations in this statement may not reflect all the situations that may arise in professional practice and are not intended as a substitute for clinical judgment in consideration of individual circumstances and available resources.

Executive summary

Background

Syphilis is caused by the bacterium Treponema pallidum, and can cause serious health problems if left untreated, and in extreme cases, can result in severe complications like dementia or death. Syphilis progresses through stages with varying symptoms, including primary, secondary, latent, and tertiary stages. The World Health Organization (WHO) estimated 7.1 million new syphilis infections globally in 2020. Infectious (primary, secondary, and early latent stages) and congenital syphilis are also on the rise in Canada; all jurisdictions have declared increased rates of infection. The national rate of infectious syphilis increased from 5.1 per 100,000 population in 2011 to 24.7 per 100,000 in 2020.

Rationale for the guidelines

Sustained and significant increases in Canadian rates of syphilis prompted the National Advisory Committee on Sexually Transmitted and Blood-Borne Infections (NAC-STBBI) to prioritize the review and update of the Public Health Agency of Canada's (PHAC) existing screening recommendation for non-pregnant adults and adolescents.

Objectives

The objectives of this work are:

• to assess the evidence for syphilis screening in non-pregnant adults and adolescents to inform the development of evidence-based guidance; and
• to update, as required, the existing syphilis screening recommendation.

Methods

A working group composed of NAC-STBBI members was formed at the beginning of the project to undertake this work. These guidelines were developed following the methods outlined in the 2014 WHO handbook^{Footnote 1} for STI experts, clinicians, researchers, and program managers. The research question was "what is the clinical utility of syphilis screening using risk-based approaches versus population-wide approaches for adolescents and adults"? A methodologist and a team of systematic reviewers from the STBBI Guidance for Health Professionals team at the PHAC independently conducted a systematic review, an environmental scan of previously published syphilis screening guidelines and commissioned a rapid review in 2022 by the Canadian Agency for Drugs and Technologies in Health (CADTH)^{Footnote 2}. The evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE)^{Footnote 3Footnote 4} approach and presented to the working group to inform development of the recommendations. Conflicts of interest were managed according to PHAC guidelines, and no conflicts were declared before the recommendations were discussed and finalized. Research implications were also developed by the working group. This statement has been endorsed by PHAC.

Summary recommendations

This statement provides two screening recommendations for adults and adolescents. Recommendation 1 includes syphilis screening for sexually active adults and adolescents and recommendation 2 includes syphilis screening for high prevalence groups/communities (such as gay, bisexual and other men who have sex with men; people living with HIV; people who are incarcerated; people who access addiction services; certain Indigenous or First Nation communities). Table 1 shows the summarized recommendations.

Introduction

This statement focuses on syphilis screening for sexually active non-pregnant adults and adolescents. For the purpose of these recommendations, screening is defined as testing asymptomatic individuals. Sustained and significant increases in Canadian rates of syphilis prompted the National Advisory Committee on Sexually Transmitted and Blood-Borne Infections (NAC-STBBI) to prioritize the review and update, or validation, of the Public Health Agency of Canada's (PHAC) existing screening recommendation.

Public health importance in Canada

Syphilis is a sexually transmitted infection (STI) caused by the organism Treponema pallidum subspecies pallidum and can have significant morbidity if left untreated. In 2020, the World Health Organization (WHO) estimated that 7.1 million new syphilis infections occurred globally.^{Footnote 5} Infectious (primary, secondary, and early latent stages) and congenital syphilis are on the rise in Canada.^{Footnote 6} Other high-income countries, such as the United States of America (USA), Australia and the United Kingdom (UK) have reported similar trends.^{Footnote 7}

Syphilis is a notifiable infection in Canada and cases are reported to the Canadian Notifiable Disease Surveillance System (CNDSS). It is the third most commonly reported STI in Canada, but over the past decade, rates have increased by 393.1%; compared to 33.1% and 181.7% increase in rates for chlamydia and gonorrhea respectively. The national rate of infectious syphilis increased from 5.1 per 100,000 population in 2011 to 24.7 per 100,000 in 2020. While rates have historically been higher in males than in females, reported rates of infectious syphilis have been increasing faster among females. Between 2010 and 2019, the female rate increased by 1,446.8% compared to a 287.9% increase in males. During this time, the male to female ratio has gone from 10.3:1.0 to 2.6:1.0; however, in 2019 males still accounted for 71.7% of all infectious syphilis cases.^{Footnote 7}

As of January 2020, all jurisdictions have declared increased rates of infection. The majority of cases continue to be among gay, bisexual and other men who have sex with men (gbMSM), but an increase has been reported in the heterosexual population with the most significant increase being in women of childbearing age leading to increases in rates of congenital syphilis.^{Footnote 6Footnote 8} The outbreaks have been reported to be associated with behavioural risks such as anonymous or multiple partners, condomless sex and substance use (e.g., methamphetamine),^{Footnote 9} and also linked to social determinants of health (race, poverty, access to health services, and housing instability).

Screening and diagnostic testing

Syphilis is diagnosed using serology: some tests detect non-treponemal antibodies (non-treponemal tests, or NTT), and others detect treponemal antibodies (treponemal tests, or TT). Screening relies on a testing algorithm (with a combination of both types of serologic tests) for the diagnosis of syphilis. The "traditional algorithm" uses an initial NTT, followed by confirmatory treponemal testing. The "reverse algorithm" uses an initial TT, followed by confirmatory NTT. In the reverse algorithm, an additional TT may be done in some cases. Most provinces and territories in Canada use the reverse algorithm.

NTTs licensed for use in Canada include the rapid plasma reagin (RPR) and Venereal Disease Research Laboratory (VDRL). The VDRL is used primarily for the testing of cerebral spinal fluid (CSF).^{Footnote 10} All NTTs have similar performance and their sensitivity in primary syphilis is approximately 75%.^{Footnote 11} Acute false-positive results may be attributed to febrile illness, immunization, and pregnancy; chronic false-positives may be attributed to hepatitis C infection, connective tissue disease, intravenous drug use, malignancy, malaria, Chagas disease, tuberculosis, and leprosy.^{Footnote 1Footnote 12Footnote 13} False-positive results can occur in a small portion of the population and may be caused by other spirochetal infections as well as the infections/conditions that can cause false-positive NTT results.^{Footnote 14} The positive predictive value (PPV) of a syphilis test result is dependent on the prevalence of the infection in the population being tested.^{Footnote 15} A quantitative RPR is used to help stage syphilis infection, monitor response to treatment or detect re-infection.^{Footnote 10Footnote 16} An analysis of traditional and reverse algorithms found that outcomes such as the number of cases detected, adverse events prevented, and overtreatment rates would be similar.^{Footnote 17} A cross-sectional study found that the traditional algorithm had the highest negative likelihood ratio (0.24), a missed diagnosis rate of 24.2%, and only 75.8% sensitivity. However, the reverse algorithm had a higher diagnostic efficacy compared to the traditional algorithm with reported sensitivity, specificity, and accuracy all superior to 99%.^{Footnote 18}

Syphilis treatment

The efficacy of treatment for syphilis has been well established and therefore, was not included in this recommendation report. The preferred treatment for infectious syphilis (primary, secondary or early latent) in non-pregnant adults is long-acting benzathine penicillin G (2.4 million units IM as a single dose).^{Footnote 19} This treatment has been shown to have a success rate of 90% to 100%.^{Footnote 20}

Purpose/Rationale for new recommendations and approach to the updates of existing syphilis screening guidelines for adults and adolescents

An update to the syphilis screening recommendation for adults and adolescents was prioritized at the October 2019 National Advisory Committee on Sexually Transmitted and Blood-Borne Infections (NAC-STBBI) face-to-face meeting and work started on the project immediately with the formation of a working group and completion of a scoping exercise. The research question was "what is the clinical utility of syphilis screening using risk-based approaches versus population-wide approaches for adolescents and adults"? Based on the results of the 2019 scoping exercise and a review completed by the Canadian Agency for Drugs and Technologies in Health (CADTH, July 2022)^{Footnote 2} the working group determined that the existing syphilis screening recommendation remains valid (i.e., screening is recommended for anyone presenting with risk factors for syphilis to prevent complications, transmission and reinfection). This was further confirmed by the US Preventive Services Task Force's (USPSTF) review and validation of their 2016 syphilis screening recommendation.^{Footnote 21} The systematic review (SR) conducted by the USPSTF identified one relevant study examining the effectiveness of syphilis screening in reducing complications of the disease (Chow et al, 2017)^{Footnote 22}; this study had been identified in the 2019 scoping exercise. Due to project delays resulting from the COVID pandemic and competing priorities, the working group decided to repeat the search performed as part of the 2019 scoping exercise with the goal of identifying new evidence that may have been published in the interim. This search was completed in January 2023 and used the same research question and criteria identified in 2019.

This document outlines the evidence collected and assessed by the working group to inform the NAC-STBBI's validation of the existing syphilis screening recommendation. The statement also acknowledges the ongoing outbreaks of infectious and congenital syphilis in jurisdictions across Canada and highlights the importance of making regular screening of sexually active adults and adolescents an essential part of routine medical care.

Objectives

The objectives of these guidelines are:

• to update the syphilis screening evidence on non-pregnant adults and adolescents, and to provide evidence-based guidance on syphilis screening for non-pregnant adults and adolescents; and
• to determine whether the existing syphilis screening recommendation remains valid.

Target audience

This document is intended to be used by primary care providers (i.e., nurses, physicians), provincial/territorial sexual health programs, local public health agencies, sexual health clinics, professionals' association, and researchers.

Methods

Working group

These syphilis screening recommendations were developed following the methods outlined in the 2014 edition^{Footnote 1} of the WHO handbook for guideline development. The NAC-STBBI established a working group (WG) for guideline development comprising four (4) members of the NAC-STBBI and supported by the secretariat. The WG included STI experts, clinicians, researchers, and programme managers (see Acknowledgements for member lists). The WG identified and agreed on the key population, intervention, comparator, outcome (PICO) questions that formed the basis for the SR and the recommendations. Following this meeting, the WG members prioritized outcomes according to clinical relevance and importance. The WG participated in meetings and teleconferences to prioritize the questions to be addressed, discuss the evidence reviews and finalize the recommendations for presentation to the NAC-STBBI for final approval.

A methodologist and a team of systematic reviewers from the PHAC STBBI Guidance for Health Professionals Section (PHAC SR team) independently conducted a SR update of major studies on syphilis screening and scanned previously published syphilis screening guidelines using Google, the websites of international organizations, provincial/territorial organizations, and a SR in 2022 by CADTH^{Footnote 2}. PHAC SR team included studies published between January 2010 and January 2023 on syphilis screening, patient values and preferences, equity, feasibility, acceptability, economic analyses, and health technology assessments. The evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE)^{Footnote 3} approach and presented to the WG. Conflicts of interest were managed according to PHAC guidelines and declared before the recommendations were discussed and finalized (see section 2.5 Management of conflict of interests). Research implications were also developed by the WG.

Questions and outcomes

In October 2019 the NAC-STBBI formulated the research question "what is the clinical utility of syphilis screening using risk-based approaches versus population-wide approaches for adolescents and adults"? The WG identified the key PICO question that formed the basis for the SR and the recommendations as follows:

• Population: Non-pregnant adolescents and adults
• Intervention: Risk-based screening (based on clinician assessment and opinion) for syphilis with serologic testing using traditional or reverse sequence algorithms
• Comparator: Population-wide screening, at any time interval (e.g., 3 months, 6 months, 12 months), for syphilis with serologic testing using traditional or reverse sequence algorithms
• Outcomes: Clinical utility (e.g., incidence of infectious/non-infectious syphilis, neurosyphilis, or congenital syphilis), proportion of participants who receive unnecessary or inadequate treatment (e.g., due to false-positive or false-negative test results), participant acceptability, safety (e.g., adverse events, psychosocial harms)
• Study designs: Health technology assessments, systematic reviews, randomized controlled trials, non-randomized studies

Reviews of the evidence

A hierarchical approach was used to search for evidence to update the recommendations. The environmental scan on existing syphilis screening recommendations of different organizations was conducted by PHAC SR team. The PHAC SR team also searched for SR, then primary studies when no SR were available. Evidence for outcomes, patient values and preferences, resources, acceptability, equity and feasibility were reviewed from published and unpublished literature. Comprehensive searches for previously conducted SR, randomized controlled trials and non-randomized studies were performed from September 2019 to January 2023 (Appendix 1). Additional searches were conducted to identify studies on patient values and preferences (e.g., qualitative research designs) and resources (e.g., cost of intervention, cost-benefits and cost-effectiveness studies). Two members (HB, SG) of the Systematic Review Team screened studies, extracted and analysed the data, and assessed the quality/certainty of the evidence using the GRADE approach.^{Footnote 3}

The certainty of the evidence was assessed at four levels:^{Footnote 3Footnote 4}

• High: We are very confident that the true effect lies close to that of the estimate of the effect.
• Moderate: We are moderately confident in the effect estimate; the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different.
• Low: Our confidence in the effect estimate is limited; the true effect may be substantially different from the estimate of the effect.
• Very low: We have very little confidence in the effect estimate; the true effect is likely to be substantially different from the estimate of effect.

Details of evidence from different sources/types and evidence to decision (EtD) judgements are available in Appendix 2 and Appendix 3. A total of 11 guidelines on syphilis screening were published between 2014 and January 2023 (Appendix 4).^{Footnote 23Footnote 24Footnote 25Footnote 26Footnote 27Footnote 28Footnote 29Footnote 30Footnote 31Footnote 32Footnote 33} The most common screening intervals were every three to six months. The Appraisal of Guidelines Research and Evaluation (AGREE) II instrument^{Footnote 34} was used to evaluate the methodological quality of the identified guidelines.

From the literature search with the Health Canada Librarian in 2019, two systematic reviews^{Footnote 35Footnote 36} were identified and included. The updated literature search since November 6, 2019 to January 17, 2023, with the Health Canada librarian resulted in 220 records. After removal of duplicates, there was a total of 176 articles. WG members shared 4 articles and 1 article was found in an article reference list. After title and abstract screening, 31 records were included for full text screening. All 31 full text records were retrieved and a final total of 9 records were included (Appendix 3). There were no published SR on the effectiveness of risk-based screening or the comparison of risk-based screening with interval screening. However, one recent randomized control trial (RCT) was published.^{Footnote 37}

There were two more updated SR findings included here. Updated SRs were from CADTH^{Footnote 2} and USPSTF.^{Footnote 21} Of the 1,032 search records found by CADTH, 31 potentially relevant articles were included for full text screening. Only one overview of reviews by Fernane & Fowler^{Footnote 38} met the pre-specified inclusion criteria. It was written by Canadian authors, based on a research question focusing on screening adult patients (16 years of age and older) at low risk for syphilis.^{Footnote 38} The updated search by the USPSTF included one study by Chow et al.^{Footnote 22} on screening effectiveness from 2,780 abstracts and 40 full-text articles. In addition, 10 studies were included from the librarian's search, hand search, and suggested citations from the WG members on "Risk-based screening vs. interval screening", "Comparison of annual, three month, and six month screening intervals", "Syphilis screening as part of HIV viral load testing", and "Opt-in vs. Opt-out approach".

Making recommendations

Between March 2023 to May 2023, the WG developed the recommendations in three meetings. The four members were present and reviewed the evidence to decision table presented by PHAC SR team. They also reviewed the evidence and additional references from their experiences and practice. During formulation of the recommendations, the WG considered and discussed both the desirable and undesirable outcomes of screening interventions, the values and preferences, feasibility, equity, resources, cost and cost effectiveness of the interventions. They also discussed the implementation of the recommendations and research gaps. The discussion was facilitated by a methodologist with the goal of reaching consensus across the WG.

The recommendations having been finalized by the WG were presented to the NAC-STBBI on June 29, 2023. The Committee reviewed the evidence and the working group's rationale for the recommendation. Consensus was obtained to approve the recommendations and send them to PHAC for endorsement. PHAC approval was provided by the Vice-President of the Infectious Diseases and Vaccination Programs Branch on August 24, 2023. The recommendations were subsequently added to PHAC's Syphilis Guide within the STBBI Guides for Health Professionals.

According to the GRADE approach, the strength of both recommendations were rated as moderate. Moderate recommendations are worded as "the NAC-STBBI guideline recommends....". The implication of moderate recommendation are:

• For patients: "most individuals in this situation would want the recommended course of action, and only a small proportion would not. Formal decision aids are not likely to be needed to help individuals make decisions consistent with their values and preferences".
• For clinicians: "most individuals should receive the recommended course of action. Adherence to this recommendation, according to the guidelines, could be used as a quality criterion or performance indicator"
• For policy makers: "the recommendation can be adopted as policy in most situations".

Management of conflicts of interest

Members of the NAC-STBBI are required to identify affiliations and conflicts of interest on an annual basis. The Secretariat reviews member affiliations to ensure there are no conflict of interests. Committee members are also asked to identify any new affiliations at the start of every meeting and teleconference. No conflicts were identified by the working group and NAC-STBBI members that would prevent them from participating in the discussion and voting on the committee recommendation.

Recommendations

Recommendations developed by the NAC-STBBI are made at the population level. It is important to note that they may not apply to specific individuals within those groups, particularly as it relates to groups and communities who may have higher rates of syphilis when compared to the general public. It is always essential to consider each case on an individual basis in the context of the risk behaviours and epidemiological factors outlined in the recommendation.

Syphilis screening for sexually active, non-pregnant adults and adolescents

The NAC-STBBI recommends syphilis screening in all sexually active persons with a new or multiple partners, and/or upon request of the individual. The NAC-STBBI recommends screening every three (3) to six (6) months in individuals with multiple partners.

(strong recommendation, moderate certainty of evidence)

Syphilis screening for high prevalence groups and communities

The NAC-STBBI recommends that targeted "opt-out" screening programs should be considered as frequently as every three (3) months* when serving population groups and/or communities** experiencing high prevalence of syphilis (and other STBBI), such as:

• Gay, bisexual and other men who have sex with men;
• People living with HIV;
• Person who is or has been incarcerated;
• People who use substances and/or access addiction services; and/or
• Some Indigenous communities

(strong recommendation, moderate certainty of evidence)

Note:

* Consider aligning screening with other health services ("opportunistic screening") for individuals living with HIV and other individuals at increased risk accessing care services. Opportunistic screening is defined as offering screening when an individual is accessing non-emergency health services and has not undergone recent STBBI testing.

** Consider local epidemiology when determining which groups/communities to target, and for a specific individual, travel history and patient risk factors need to be considered.

Factors associated with Syphilis infections^{Footnote 39Footnote 40Footnote 41Footnote 42}

Behaviours/Activities

• Barrierless sexual activity involving contact with oral, genital or anal mucosa
• Multiple sexual partners
• Sexual contact with a known case of syphilis or other STBBI
• Substance use, including chemsex

Epidemiological

• Previous syphilis infection or other STBBI
• HIV infection
• High prevalence area/groups
• Housing instability/street involvement

Summary of the evidence

The certainty of the evidence for the screening for syphilis is moderate. The evidence review included three SR^{Footnote 35Footnote 36Footnote 38}, and 11 studies: one 1 randomised^{Footnote 37} and 10 non-randomized studies (including three cohort studies^{Footnote 43Footnote 44Footnote 45}, seven retrospective chart review, and cross-sectional studies)^{Footnote 22Footnote 46Footnote 47Footnote 48Footnote 49Footnote 50Footnote 51} on syphilis screening. In addition, there was an environmental scan of 11 guidelines on syphilis screening published between 2014 and January 2023.^{Footnote 23Footnote 24Footnote 25Footnote 26Footnote 27Footnote 28Footnote 29Footnote 30Footnote 31Footnote 32Footnote 33} All organizations recommend risk-based screening. Of the included guidelines, four organizations recommend screening for those at increased risk of infection at varying intervals – from annual screening to up to four times a year depending on risk behaviours. The most common intervals were every three to six months.

From the PHAC search results, one RCT^{Footnote 37} reported that in risk-based screening versus interval screening, the average annual number of syphilis tests per individual increased from 0.53 to 2.02 tests and the time-adjusted rate ratio, 2.03 (1.85–2.22).^{Footnote 37} With intervention, the annualized proportion of newly identified early syphilis increased from 0.009 to 0.032 and the odds of annual screening increased nearly 4-fold and the mean number of tests per year increased 2-fold.^{Footnote 37} Comparison of annual, 3-month, and 6-month screening intervals during routine serology taken as part of HIV monitoring resulted in a marked increase in the proportion of HIV-positive MSM diagnosed with asymptomatic syphilis.^{Footnote 22Footnote 43Footnote 46Footnote 47Footnote 51} Additional studies using modeling projected similar results.^{Footnote 52Footnote 53} These studies showed that increasing the frequency of syphilis screening to every 3 months was the most effective strategy for reducing infectious syphilis cases. Targeted screening was more effective than universal screening.

Enhanced screening of MSM with prior syphilis may efficiently reduce transmission, especially when identification of high-risk men via self-reported partner numbers or high-frequency screening is difficult to achieve. A 2010 study examining syphilis screening as part of HIV viral load testing found same day tests were highest in clinics with the opt-out strategy (87%; range: 84% - 91%), compared with opt-in (74%, p=0.121), and risk-based (22%; range: 20% - 24%, p<0.01).^{Footnote 44} Over 50.8% of incident syphilis cases were asymptomatic and were only identified through routine screening.^{Footnote 44} One observational study compared three strategies: risk-based screening, opt-in, and opt-out approach for HIV-positive gbMSM.^{Footnote 45} The opt-in approach was defined as offering syphilis testing to HIV-positive gbMSM during HIV viral load testing (which was recommended every three to six months) and testing those who agree; with opt-out screening, syphilis testing was done automatically unless the patient declined. Risk-based screening involved assessing risk and then offering a syphilis test accordingly. The authors found that the opt-in and opt-out approaches led to increased uptake of syphilis testing. Risk-based testing resulted in lower testing frequencies and potentially missed opportunities.^{Footnote 45} Reekie and others^{Footnote 48} also examined the uptakes of opt-out vs opt-in screenings using a cross-sectional retrospective review in a remand (pretrial, presentence, or detention) facility in Alberta, Canada, between March 1, 2018, and February 28, 2020 among individuals ≤ 35 years. The same definitions for opt-in and opt-out were used in both instances. They found that opt-out screened more admissions among ≤ 25 years, even though total opt-out uptake was low (n=902/2906; 31.2%). Opt-out screening resulted in high levels of treatment completion (93.7%) while also capturing a high proportion (52.6%) of asymptomatic cases. Opt-in achieved significantly high positivity rates for syphilis. Opt-out screening resulted in higher STI positivity rates compare to other STIs (CT, GN) (29.5%), however, lower than opt-in screening (35.8%). However, opt-out screening diagnosed higher new syphilis cases (case-finding rate). Opt-out: 7.3% (150/2053 tests); opt-in 7.1% (150/1995 tests). Both found similar HIV positivity rates. There were no differences in the proportion of positive test results between testing programs across gender, age categories, or over time (p = 0.120).^{Footnote 48}

Another study in USA, examined the prevalence of syphilis in the population to evaluate the routine, opt-out syphilis screening model.^{Footnote 49} They found a large number of missing cases while targeting screening to only those deemed "high-risk" by behavior or symptoms. Little more than 50% (7 of 13) of those testing positive did not present with complaints. Venegas et al^{Footnote 50} also found Opt-out screening using technology and risk factor identified 27 of the 59 patients with reactive syphilis tests considered newly diagnosed syphilis infection (no history of syphilis infection reported in the system) and require follow-up treatment.

A qualitative study reported on patient values and preferences, feasibility, and equity for syphilis screening in males (n=21) accessing HIV care.^{Footnote 54} A majority of males were in favour of routinely testing for syphilis as part of conventional HIV care. The routine method was thought to have a de-stigmatizing effect on syphilis testing. From the patient's point of view, HIV care clinics are easy locations to be tested for syphilis. Reekie et al reported^{Footnote 48} the feasibility of opt-out screening in a short-term correctional facility for individuals ≤35 years in Alberta, Canada. They reported that opt-out screening at admission is feasible and can improve STI testing in high-risk individuals experiencing incarceration in Canada.^{Footnote 48}

There was no other study on patient values and preferences, feasibility, and equity for syphilis screening in non-pregnant adults and adolescents in Canadian settings. Most studies focused on the acceptability and feasibility of treatment and point-of-care testing, which are not within the scope of the review. The WG also recognizes that some population groups face higher rates of stigma and discrimination, creating barriers to accessing care and unequal access to care services across jurisdictions and public health agencies (e.g., rural versus urban), as resource levels vary across provinces and territories. They considered and agreed that certain population groups have higher rates of mistrust in health care services making them less likely to seek care and previous negative experience with the health care system may result in individuals avoiding care.

Four cost-effectiveness modelling studies examining either risk-based screening or interval screening were included.^{Footnote 55Footnote 56Footnote 57Footnote 58} The modeling studies were based in Canada, the US, Germany, and Australia. The studies did not directly compare the cost-effectiveness of risk-based screening to interval screening for syphilis. Studies also focused primarily on high risk population groups, such as gbMSM, people living with HIV and sex workers. Generally, targeted screening at 3 or 6 month intervals were considered more cost-effective compared to universal annual screening in these populations.^{Footnote 55Footnote 56Footnote 57Footnote 58}

Overall, the WG therefore agreed that syphilis screening should be offered to all sexually active persons with a new or multiple partners, and/or upon request of the individual. They agreed that screening should be offered every three (3) to six (6) months in individuals with multiple partners. They also agreed that targeted "opt-out" screening programs should be considered as frequently as every three (3) months for health services serving population groups and/or communities experiencing a high prevalence of syphilis (and other STBBI).

See Appendix 2 for the evidence to decision judgements, and Appendix 3 for the characteristics of included studies and summary of findings, including evidence profiles.

Dissemination, implementation, monitoring and evaluation

Dissemination

These recommendations have been incorporated within the Screening and Diagnostic Testing section of PHAC's Syphilis Guide. An advance copy of the statement will be provided to the provinces and territories via the Communicable and Infectious Diseases Steering Committee and the Council of Chief Medical Officers of Health.

Implementation

Canada is experiencing tremendous strain on the health care system due to a lack of trained professionals and extremely limited primary care capacity.^{Footnote 59} These challenges have been exacerbated by the COVID-19 pandemic. Syphilis and other STBBI screening are often considered based on individual risk factors for the person seeking care. Nurses and physicians must discuss these factors with the individual to determine their sexual health history and to identify the appropriate screening tests required. Due to stigma and prior negative experience with the healthcare system, individuals may not be fully transparent when discussing their sexual health, and often underestimate their own personal risk. Health care providers should consider implementing an "opt-out" approach to screening, removing the need for an in-depth discussion on the person's sexual history. These programs have experienced greater success compared to "opt-in" programs in certain settings. Applying opt-out programs normalize STBBI screening and can help reduce stigma related to sexual health.

Health care providers should consider offering screening when patients are accessing other non-emergency health care services. In some circumstances, such as with individuals living with HIV, STBBI screening is considered part of routine care. These patients will often undergo regular blood testing to ensure they are responding to treatment and maintaining a suppressed viral load. This provides an opportunity for screening for other STBBI. For individuals with limited or infrequent access to health services, health care providers should practice opportunistic screening for STBBI. Regardless of whether the individual is there for STBBI related care, health care providers should take the opportunity to determine when they last underwent STBBI screening and offer it if appropriate. For individuals who engage in behaviours that increase their risk level (such as multiple partners) or are part of a high prevalence population (for example people who use substances), screening can occur as frequently as every three months.

Many individuals are apprehensive when discussing factors associated with STBBI due to fears of potential or past stigma and/or discrimination. When individuals experience stigma and discrimination with the health care system, it can make them hesitant to seek care and share information related to factors associated with STBBI. Further normalizing and standardizing the offering of STBBI screening can help mitigate the perception of stigma.

Congenital Syphilis

This statement does not address prenatal screening, though a recommendation is available in the Syphilis Guide. It is important to be aware of the increasing rates of congenital syphilis across Canada. There were 96 cases of confirmed congenital syphilis in 2021, compared to only 7 cases in 2017, representing an increase of 1271%. Additionally, cases of infectious syphilis among females increased by 720% over that span.^{Footnote 60} Healthcare providers should be mindful of these trends when providing care to females of childbearing age (approximately ages 15 to 45). Care providers are reminded that universal screening is recommended in all pregnant people.

Monitoring and evaluation

PHAC and the NAC-STBBI continue to monitor syphilis activity in Canada for changes in the epidemiology of high prevalence populations and behaviours. Likewise, the publication of new evidence is monitored to respond to the latest developments. This screening recommendation will be revised if new evidence becomes available in the coming years, or the epidemiological situation changes to justify subsequent updates to the recommendation.

Limitations

Much of the evidence used to inform the development of these recommendations are based on an assessment of key populations or groups, such as gbMSM and people living with HIV. Considering that gbMSM populations continue to have higher rates of STBBI infections compared to the general public and individuals living with HIV are at increased risk of acquiring other STBBI, the recommendations may overestimate the frequency of screening needed in the public.

Research priorities and implications

Rapidly changing epidemiology has resulted in significant change to the incidence and prevalence of syphilis. This can cause certain studies to become quickly outdated when the population being assessed no longer reflects the population being impacted by the infection. Ongoing review and monitoring of the most recent surveillance data is integral to ensure individuals and populations with high infection prevalence are identified quickly.

STBBI research is primarily focused on specific key populations, such as people living with HIV and gbMSM. While the evidence for these groups is thorough, studies focused on the general population are lacking and can present a gap in the evidence. Extrapolating evidence from these groups to apply to the general population is not always feasible given significant differences in population groups. Prioritizing STBBI research on the general public should be considered.

List of abbreviations

CADTH

Canadian Agency for Drugs and Technologies in Health

CIA

Chemiluminescence immunoassay

CSF

Cerebral spinal fluid

CUA

Cost-utility analysis

EIA

Enzyme immunoassay

EtD

Evidence to decision

FNIM

First Nations, Inuit and Métis Peoples

FTA-ABS

Fluorescent treponemal antibody absorption assay

gbMSM

Gay, bisexual and other men who have sex with men

GRADE

Grading of Recommendations Assessment, Development and Evaluation

ICER

Incremental cost-effectiveness ratio

NAC-STBBI

National Advisory Committee on Sexually Transmitted and Blood-Borne Infections

NTT

Non-treponemal tests

PHAC

Public Health Agency of Canada

PPV

Positive predictive value

QALY

Quality adjusted life years

RCT

Randomized control trial

RPR

Rapid plasma reagin

SR

Systematic review

STBBI

Sexually transmitted and blood-borne infections

STI

Sexually transmitted infections

TPHA

T. pallidum hemaglutination assay

TPPA

T. pallidum particle agglutination assay

TT

Treponemal tests

VDRL

Venereal Disease Research Laboratory

WG

Working group

WHO

World Health Organization

Acknowledgements

Contributors to PHAC Syphilis screening guidelines for non-pregnant adults and adolescents:

NAC-STBBI Syphilis screening working group: J Bullard, J Gratrix, T Grennan, T Hatchette

NAC-STBBI members: I Gemmill (chair), T Grennan (vice-chair), J Bullard, W Fisher, J Gratrix, T Hatchette, AC Labbé, T Lau, G Ogilvie, M Steben, P Smyzcek, M. Yudin

NAC-STBBI Ex-Officio: I Martin

NAC-STBBI Secretariat (PHAC): H Begum, A Fleurant, S Gadient, S Ha, S Sabourin

Appendices

Appendix 1: Flow diagram of study selection on syphilis screening since 2019

Appendix 2: Summary of evidence-to-decision framework judgements

Interpretation of strong and conditional recommendations

The recommendations are labeled as "strong" or "conditional" according to the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. The words "the guideline panel recommends" are used for strong recommendations, and "the guideline panel suggests" for conditional recommendations. The table below provides GRADE's interpretation of strong and conditional recommendations by patients, clinicians, health care policy makers, and researchers.

Appendix 3: Characteristics of included studies and summary of findings

Table 3.1. Relevant systematic reviews on syphilis screening

Table 3.2. Major studies on syphilis screening

Table 3.3. Characteristics of patient values and preferences, cost-effectiveness studies on syphilis screening

Table 3.4. Evidence profiles

Q1: Should [risk-based approaches] vs. [population wide/interval screening approaches] be used for [syphilis screening among sexually active adolescents and adults]?

Appendix 4: Environmental scan of guidelines