Canadian Public Health Laboratory Network guidelines for the use of point-of-care tests for Treponema pallidum in Canada

Abstract

Over the past few years, the increase in infectious syphilis outbreaks in major urban centres and remote or rural locations in Canada, often affecting hard-to-reach patient populations, has renewed an interest and urgency in studying the use of point-of-care tests (POCTs) that can provide test results at the time and place of primary health care delivery, obviating the repeat visit necessary with traditional syphilis serology or molecular diagnostic tests. In 2015, the Canadian Public Health Laboratory Network released its first laboratory guideline for the use of POCTs in the diagnosis of syphilis in Canada. Although Canada has no licensed POCT, two POCTs (Syphilis Health Check and the DPP® HIV Syphilis System) have received US Food and Drug Administration (FDA) approval under premarket approval applications. Most syphilis POCTs detect antibodies to treponemal antigens, so their results cannot be used to differentiate between active and past infection. The only POCT that detects antibodies to both treponemal and non-treponemal antigens does not yet have Health Canada or FDA approval. In this updated guideline, the current landscape of POCTs for syphilis, with an emphasis on data from low-prevalence countries, is described. Individual operators should consider the questions of where, when, how, and why a POCT is used before its actual implementation. Training in the operation and interpretation, quality control, proficiency program, safety, and careful documentation of the process and results are especially important for the successful implementation of POCTs.

Key Summary Points: Point-of-Care Tests for Syphilis

• No point-of-care test (POCT) for syphilis has been licensed by Health Canada.

• Performance of POCTs for syphilis may vary depending on the prevalence of disease in each setting.

• Each investigator should define how the POCT is to be used; that is, they should consider what answers the POCT results will provide.

• A comprehensive quality control program is recommended, including documentation on training, lot numbers of test kits, quality control sample performance to reflect integrity of test kits and competency of operators, and trends in quality control results and patient samples.

Introduction

Laboratory diagnostic tests are often an essential component of patient care, with most laboratory tests carried out in licensed facilities incorporating various degrees of regulated and accredited infrastructures and with validated tests performed by trained and licensed technologists. As such, the results of laboratory tests are often not available to the clinician or the patient at the time of the doctor–patient consultation. Therefore, conventional laboratory tests often do not have an immediate impact on treatment decisions or public health responses, such as contact tracing. To improve the turn-around time for test results and the accessibility of tests to patients living in resource-poor or remote communities, rapid tests such as point-of-care tests (POCTs) have been developed and marketed to provide this essential service to such patient populations. In addition to individual patient management, the role of POCTs for public health use may also be considered.

The use of POCTs in resource-limited countries is well recognized and accepted because conventional laboratory tests are nearly non-existent as a result of the lack of laboratory infrastructure, equipment, and trained personnel. For example, POCTs for HIV screening were introduced in African countries more than a decade ago (1). Rapid diagnostic tests for neurologic infections that can be used at the point of care have also been introduced and evaluated in Central Africa (2). An integrated panel of POCTs for both infectious and non-infectious conditions has been studied in western Kenya (3).

However, the use of POCTs, especially those for detection of infectious conditions, in resource-rich countries is less defined. In resource-rich countries, the questions of why, where, when, and how POCTs for infectious conditions can or should be used, require thorough evaluation of and consultation with all parties (primary care providers, laboratory personnel, public health officials, and government policy developers) involved. In this article, we examine the questions of why, where, when, and how POCTs can or should be used in a resource-rich country such as Canada with regard to the detection of syphilis infections.

Definitions of Point-of-Care Tests

There are many definitions of POCTs in the public domain, including those of the College of American Pathologists (4,5); the Australian Government Department of Health (6); provincial governments, such as the Ontario Ministry of Health and Long-Term Care (7); and non-governmental organizations, such as the Canadian Agency for Drugs and Technologies in Health (8). An international definition of POCT has also been published and is based on consensus reached by an international expert panel representing health care professionals, such as family physicians, policy-makers, manufacturers, and laboratory personnel (9). Instead of choosing one definition that would be suitable, it is more useful to consider the characteristics common to most of the definitions of POCTs. The common themes usually involve the following parameters:

• Performed near the patient or where care is provided; usually carried out during or just before the clinical consultation; not performed in a traditional clinical laboratory

• Performed by individuals without laboratory experience, that is, by any member of the health care team

• Rapid turnaround time for test results; results are available during the clinic visit, thereby immediately affecting patient care, including initiation of treatment

• Ease of use with non-invasive specimens, such as blood (without venipuncture but possibly by finger prick), urine, saliva, sputum, feces, or other body secretions

Rationale for Considering the Use of Point-of-Care Tests to Control Syphilis in Canada

Infectious syphilis has been on the rise in Canada in the past decade, with rates increasing by 85.6% between 2010 and 2015 (10). In 2018, 6,311 cases of infectious syphilis were reported in Canada, a 151% increase in disease from 2014, with three provinces and one territory reporting rate increases of 393% to 831% (11). During this period, eight provinces and territories reported outbreaks, with major cities such as Edmonton and Winnipeg reporting very high incidence rates not seen in recent history (11,12,13). Syphilis outbreaks have also been reported in less dense populations in Northwest Territories (14), northwest Saskatchewan (15,16), and Northwestern Ontario (17). The mobility of some of the affected population groups (sex trade workers, illicit drug users, homeless or transient persons) makes testing and treatment of those who are infected very difficult. Even for patients visiting sexually transmitted infection (STI) clinics in major urban centres, the traditional laboratory diagnostic algorithm for syphilis does not allow them to be seen, tested, and treated during the same visit, thereby leading to the loss of opportunity to initiate immediate treatment for patients and begin contact tracing to minimize further spread of the disease. Moreover, the infection has shifted from mainly affecting the communities of gay and bisexual men who have sex with men to affecting women via heterosexual contact, with a consequential increase in congenital syphilis cases (17 confirmed cases in 2018) (11). This adds another layer of urgency to controlling syphilis outbreaks in Canada. The current epidemiology of infectious syphilis in Canada has renewed health care providers’ and public health policy advisors’ interest in using POCTs to reach communities in remote locations or marginalized communities (because of homelessness, transient residency, or mistrust in the health care system) in an attempt to break the cycle of infection through diagnosis and treatment offered at the point of care of the infected subjects (18).

Types of Point-of-Care Tests

Although commercial syphilis POCTs have been available since the early 2000s, research and evaluations have focused on their use in resource-poor countries with a high prevalence of syphilis. Only in the past 5–6 years has the use of these assays in developed countries with a low prevalence of syphilis been studied, and data on when and how to use POCTs in Canada are scarce.

Treponemal tests

Although no treponemal (TP) antigen-based POCT has Health Canada approval, numerous commercial kits (Table 1) are available on the international market. These are immunochromatographic tests onto which TP antigens have been immobilized. When a patient’s whole blood, plasma, or serum containing TP antibodies is added to the test kit (with or without the addition of a test reagent), the antigen–antibody reaction produces a visible colour change.

Table 1:

POCTs for the detection of syphilis

Type and test name	Manufacturer	Specimen	Antigens	Antibodies detected	Time to results (min)
Syphilis only
Onsite™ Syphilis Ab Rapid Test	CTK Biotech, Inc. (United States)	Whole blood (venous or finger prick)	Not disclosed*	IgG, IgM, IgA	15
Determine™ Syphilis TP†	Abbott (Alere)	Serum, plasma, whole blood	Not disclosed	Not disclosed	15
SD Bioline Syphilis 3.0†	Abbott (Alere)	Serum, whole blood	Not disclosed	IgG, IgM, IgA	5–20
Syphicheck® WB	QualPro Diagnostics (India)	Serum, plasma, whole blood	47 kDa, 17 kDa	IgG, IgM	15
Visitect® Syphilis	Omega Diagnostics (United Kingdom)	Serum, plasma, whole blood	Not disclosed	IgG, IgM	30
Syphilis Health Check™‡	Trinity Biotech (Ireland); Diagnostics Direct (United States)	Serum, plasma, or whole blood (finger prick)	Not disclosed	IgG, IgM	10
Syphilis Rapid Test	Cypress Diagnostics (Belgium)	Serum, plasma, or whole blood	Not disclosed	IgG, IgM, IgA	5–20
Uni-Gold™ Syphilis Treponemal	Trinity Biotech (Ireland)	Whole blood (venous or finger prick), plasma, or serum	Not disclosed	Not disclosed	±15
DPP® Syphilis Screen and Confirm	Chembio (United States)	Whole blood (venous or finger prick), plasma, serum	Treponemal antigens (17 kDa, 47 kDa) and non-treponemal	IgG, IgM	±20
Syphilis Antibody Test	Ulti med (Germany)	Serum, plasma, or whole blood	Not disclosed	IgG, IgM	NA
Reveal Rapid TP Antibody test	MedMira Laboratories, Inc. (Canada)	Serum, plasma, or whole blood	Synthetic peptides of treponemal antigens	IgG	5–10
Dual HIV–syphilis
DPP HIV-Syphilis‡	Chembio (United States)	Serum, plasma, or whole blood (venous or finger prick)	Syphilis: 17 kDa	IgG	15–30
SD Bioline HIV / Syphilis Duo†	Abbott (Alere)	Serum, plasma, or whole blood	Not disclosed	IgG, IgM, IgA	15–20
Multiplo TP / HIV	MedMira Inc. (Canada)	Serum, plasma, or whole blood (venous or finger prick)	Syphilis: TP recombinant antigens (15 kDa, 47 kDa, 17 kDa) HIV: synthetic HIV peptides to gp36, gp41, gp120, and HIV-1 group O	IgG, IgM	Once all fluid is absorbed (±3)
INSTI™ HIV-1 / HIV-2 / Syphilis	bioLytical (Canada)	Serum, plasma, or whole blood (venous or finger prick)	Syphilis: TP recombinant antigens (15 kDa, 47 kDa, 17 kDa) HIV: recombinant antigens (gp41, gp36)	IgM, IgG	Immediately after adding clarifying solution (±2)

*Not disclosed by the manufacturer

† The SD Bioline assays are made for low- and middle-income countries and the Determine™ assays, made by the same manufacturer, are made for the developed countries

‡These two POCTs are approved by the US Food and Drug Administration

POCTs = point-of-care tests; IgG = Immunoglobulin G; IgM = Immunoglobulin M; IgA = Immunoglobulin A; NA = Not available

Non-treponemal tests

Positive results for TP POCTs may indicate a new or an old infection, but the presence of a positive non-treponemal (NT) test may indicate active infection and hence may be helpful. However, there are currently no commercial POCTs that detect only NT antibodies.

Dual treponemal and non-treponemal tests

The DPP® Syphilis Screen and Confirm test (Chembio Diagnostics System Inc., Medford, New York) has become available in North America, and some evaluations of this assay have been published. Another dual POCT described in the literature is manufactured by Span Diagnostics (Gujarat, India), but no published data on its performance are available (19).

Commercial Syphilis Point-of-Care Test Performance

A 2018 review for the World Health Organization (WHO) by Murtagh reports that syphilis POCTs perform comparably to standard laboratory tests in resource-limited settings with a high prevalence of syphilis (5%) (20).

Studies conducted in middle- to high-income countries with a low prevalence of syphilis reported sensitivities of 51.0%–98.8% and specificities of 66.2%–100% in the field when compared with results obtained by traditional laboratory serological tests (Table 2). As expected, evaluations performed in the laboratory produced better results than those performed in the field. This emphasizes the need for appropriate training of personnel performing these tests, in addition to strict adherence to operating protocols, quality control measures, and proficiency testing to produce high-quality accurate results when any assay is used in the field.

Table 2:

Summary of studies evaluating syphilis POCTs in countries with a low prevalence of syphilis

Assay and country	Study	Sens	Spec	Lab	Field	Serum	Whole blood
Determine™ Syphilis TP
United Kingdom	Perry et al (21)	91.3	100		X		X
Australia	Causer et al (22)	97.3	96.4	X		X
SD Bioline
Italy	Zorzi et al (23)	51.0–80.0	100	X	X		X
Australia	Causer et al (22)	87.8	98.5	X	X		X
Canada	Morshed (unpublished personal communication)			Sens 85.0 Spec 100	Sens 95.0 Spec 100	Sens 85.0 Spec 100	Sens 95.0 Spec 100
DPP® Syphilis Screen and Confirm
Italy	Zorzi et al (23)	57.7–65.4	99.5	X		X	X
France	Guinard et al (24)	>90%	>90%	X		X
Australia	Causer et al (22)	89.8	98.3	X		X
Australia	Skinner et al (25)	95.6	66.2	X		X
Canada	Caya et al (26)	91.0	100	X		X
Portugal	Castro et al (27)	98.8	94.7	X		X
Syphilis Health Check™
United States	Obafemi et al (28)	90.0	98.5		X		X
United States	Matthias et al (29)	71.4	91.5		X		X
Onsite™ Syphilis Ab Rapid Test
Australia	Causer et al (22)	92.5	97.0	X		X

POCTs = Point-of-care tests; Sens = Sensitivity; Spec = Specificity; Lab = Laboratory

Castro et al (27) performed one of the earliest evaluations of the DPP Syphilis Screen and Confirm POCT for the simultaneous detection of NT and TP antibodies in sera of 1,601 patients. Results from the dual test were compared with those from the Rapid Plasma Reagin (RPR) and Treponema pallidum particle agglutination (TPPA) tests. Compared with the RPR, the reactive concordance of the NT result was 98.4%, with RPRs greater than 1:2. However, when the RPR was 1:2 or less, the sensitivity declined to 88%. Compared with the TPPA, the reactive and non-reactive concordances of the TP line were 96.5% and 95.5%, respectively. This dual TP–NT POCT is designed for use with serum, plasma, and whole blood. In a Canadian laboratory study (26), Caya et al reported a sensitivity of 91% and a specificity of 100% for this same assay.

Causer et al (30) performed a study to specifically investigate the use of the dual TP–NT POCT (DPP Syphilis Screen and Confirm) in distinguishing active from past treated infection. These authors found that although this assay improves the identification of past infections (and reduces over-treatment), it has a reduced sensitivity for the detection of early primary syphilis (defined by the presence of a primary chancre and reactive syphilis serology, a positive polymerase chain reaction test, a dark field microscopy test, or all of these).

In a meta-analysis of the dual HIV–syphilis (TP antigen only) POCTs, Gliddon et al (31) evaluated the performance characteristics of three assays, the Chembio DPP HIV–Syphilis, the SD Bioline HIV/Syphilis Duo, and the INSTI™ HIV-1/HIV-2/Syphilis in 18 studies conducted among pregnant women. The sensitivities and specificities of these assays for syphilis diagnosis ranged from 93% to 100% and 91% to 100%, respectively, in the laboratory, with sensitivities falling to 47%–96% in the field. Diagnostic performance for syphilis was better when the specimen was serum (sensitivity of 93%–100%, specificity of 97%–100%) than when it was whole blood (sensitivity of 47%–100%, specificity of 91%–100%).

In 2019, Van Den Heuvel et al performed a laboratory evaluation in Belgium of four HIV–syphilis (TP antigen only) POCTs as part of the WHO prequalification of in vitro diagnostic assessments (32). They used the WHO panel of stored sera and plasma from specimens of African, European, Asian, South American, and Australian origins. See Table 3 for the results. When the results were read by highly trained laboratory technologists, Van Den Huevel et al observed higher inter-reader variability on the syphilis TP component of the assays than on the HIV component.

Table 3:

Summary of studies evaluating dual HIV–syphilis POCTs in countries with a low prevalence of syphilis

Assay and country	Study	Site (lab or field)	HIV		Syphilis		Specimen (serum / WB)
			Sens	Spec	Sens	Spec
Chembio DPP HIV / Syphilis
United States	Hess et al (33)	Field	95.7	99.7	47.4	99.5	WB
United States	Humphries et al (34)	lab	97.9	98.1	95.3	100	Serum
United States	Kalou et al (35)	Lab	99.8	98.4	98.8	99.4	Serum
International	Van Den Heuvel et al (32)	lab	100	97.5	86.5	100	Serum / plasma
SD Bioline HIV / Syphilis Duo
United States	Humphries et al (34)	lab	97.9	100	93.0	100	Serum
International	Van Den Heuvel et al (32)	lab	100	97.5	86.5	100	Serum / plasma
United States	Holden et al (36)	lab	85.7	96.8	91.7	99.5	Serum / plasma
Multiplo TP / HIV
United States	Humphries et al (34)	lab	97.9	94.2	94.1	96.9	Serum
International	Van Den Heuvel et al (32)	lab	99.5	99.5	73.5	99.5	Serum / plasma
INSTI™ HIV-1 / HIV-2 / Syphilis
International	Van Den Heuvel et al (32)	lab	99.5	93.5	81.0	99.0	Serum / plasma

Notes: These were studies performed in high-income, countries with a low prevalence of syphilis (except [ ³² ], which used stored specimens from low-, middle-, and high-income countries) and are included on the basis of our literature search results

POCTs = Point-of-care tests; lab = Laboratory; Sens = Sensitivity; Spec = Specificity; WB = Whole blood

In summary, these and other studies in high-prevalence countries found

• better performance with serum than with whole blood;

• better performance in the laboratory than in the field; and

• poor performance of all tests among patients with low RPRs (<1:4–1:8) (21, 23, 25, 31, 32).

Point-of-Care Test Interpretation and Follow-Up

To enable accurate and valid results, POCTs require verification of their performance characteristics in the population in which they are to be used, according to established criteria. The Clinical and Laboratory Standards Institute has published guidelines for such assessments of these tests’ performance (37). Provinces, local health authorities, and provincial Colleges of Physicians and Surgeons may also have guidelines on the performance requirements of POCT.

The absence or presence of clear test lines in the presence of clear control lines on the assays are easily interpretable as negative or positive test results. Some studies cite high user variability in interpreting the POCT results. This variability is due to faint lines on the assays that some interpret as positive and others as negative. Some POCT kits may come with small portable readers that may reduce operator subjectivity and hence enhance reproducibility in test interpretation (38). Such readers may also have the potential to be connected to a computer for automatic recording of results, thus minimizing the potential of transcription errors. However, evaluations of such readers would be required before they are routinely deployed for use. A clear operating and interpretation protocol will further assist in decreasing the interpretation variability in such instances.

Use of Point-of-Care Tests in the Diagnosis of Syphilis

The POCTs that detect antibodies to only TP cannot distinguish between previously treated and active disease. When setting up a program for the use of syphilis POCTs, users need to establish whether or not to treat a patient with a positive test and whether over-treatment is acceptable and necessary in that setting to interrupt transmission in an ongoing outbreak or, for example, in pregnancy when transmission has serious consequences.

Depending on the prevalence of syphilis, access to laboratory services, acceptability of Western medical facilities in the community, risk of significant sequelae (as in mother-to-child transmission), and performance characteristics of the assay in the verification study, syphilis POCTs can be a valuable tool in the diagnosis of syphilis.

However, the WHO and others have concluded that when using a POCT (21, 28, 32, 39, 40), a positive TP antibody result on its own cannot be used to diagnose infectious syphilis. It is recommended that all positive syphilis POCTs be confirmed with standard laboratory tests.

Challenges in Implementing Point- of-Care Tests for Syphilis in Canada

Currently, no POCTs are licensed by Health Canada for detection or diagnosis of syphilis infections in Canada. Preferably, for any POCT to be deployed for clinical diagnostic purposes, it should, for the most part, meet the ASSURED criteria (41): Affordable, Sensitive, Specific, User-friendly, Rapid and robust, Equipment free, and Deliverable to end users. This is not an easy task to fulfil, even though steps to accomplish this are clearly outlined (42).

Presently, there are not enough publicly available data in Canada to make recommendations on how, where, and when POCTs can or should be used for the detection and diagnosis of infectious syphilis. In November 2017, the US Centers for Disease Control and Prevention’s Division of Sexually Transmitted Disease Prevention and the American Association of Public Health Laboratories held a 2-day consultation on best practices for the laboratory diagnosis of syphilis and concluded that the data are insufficient to make a recommendation on the use of rapid or point-of-care syphilis tests (43).

As with any other diagnostic test, the first step to consider before choosing a test is to define the test’s objective—that is, the questions of who, what, why, when, and where. The population for whom the test is intended is critically important because the prevalence of disease in that population affects the test’s performance. The next factor to be considered is the test’s purpose. Is it for diagnosis of active or past syphilis? Another factor to be considered is the setting in which the POCT is to be performed. Will it be used in a resource-scarce setting, such as remote and hard-to-access regions in Canada—for example, the Canadian North? Or in a busy STI clinic in a major urban centre where the prevalence of the disease will be higher relative to the general population? The questions of who, where, when, and why are interconnected; therefore, any study to gather data needs to be carefully planned and clearly defined as to which questions will be addressed by the research data obtained. Besides these considerations, the research plan has to incorporate details of requirements for the implementation step. These details will include

1. training of the POCT operator because the test will be carried out by non-laboratory personnel who (unlike laboratory technologists) would not be experienced with laboratory or instrument-mediated testing;

2. maintenance of competency of the POCT operator;

3. a quality assurance program that covers quality of the specimen, quality control of test kits (lot variations, expiry date), and strict adherence to standard operating procedures, including the manufacturer’s instructions on how to use, interpret, and record results of the POCT;

4. having a biosafety training and procedure manual in place with procedures on how to deal with blood and body fluid exposure as well as needle stick injury;

5. data monitoring of quality indicators that provides alerts to any deviations in the POCT performance or operator variations;

6. data management to capture the POCT results in the traditional or mainstream laboratory test result database for notification of public health officials; and

7. gathering data to address how to interpret POCT results under the study’s conditions.

Although there are no federal guidelines or policy on the use of POCTs, some provinces have their own policy and guidelines, which include adherence to ISO15189 and ISO22870 (44, 45).

For any POCT to be widely adopted for use in Canada, the manufacturer of the assay may be expected to apply for licensure with Health Canada, which in itself requires documentation of the necessary data to satisfy the regulatory requirements (46). The issue of licensure of laboratory diagnostic tests is beyond the scope of this guideline; however, the challenge of the lack of licensed rapid diagnostic tests during a serious outbreak situation may warrant special attention with novel solutions. Therefore, studies designed to gather data to inform policy would require careful attention to the details discussed here for a seamless transition from research to implementation.

Despite the fact that POCTs have many advantages over conventional laboratory tests, there may be difficulties and limitations, which may include the following:

• Cost–benefit analysis: this type of analysis has to be done according to the conditions of who, where, when, what, or why the syphilis POCT will be applied. This is especially relevant if additional laboratory confirmatory tests are required.

• Most current POCTs offer a rather narrow range of analyte measurement that provides a qualitative result of positive or negative and do not offer quantitative results that may be required for diagnostic and treatment monitoring of syphilis infections.

• The accuracy and precision of syphilis POCTs may not offer the same level of diagnostic performance in the field as do current laboratory-based conventional testing methods.

• Readings of results for most current POCTs are subjective and are thus operator dependent for interpretation and recording of results. Lighting in the area in which the assay will be read and testing of the operator’s visual acuity and colour discrimination to detect colour blindness are other considerations.

• To be practical, most POCTs for syphilis rely on whole blood obtained by finger prick as the specimen source, whereas evaluations of POCTs have been done on whole blood, serum, or plasma samples. Other specimen types, such as cerebrospinal fluid for diagnosis of neurosyphilis, have not been evaluated.

• Most syphilis POCT results are not captured electronically but rely on manual reading and recording of results on paper or entry into a computer, leading to the potential for transcription errors in the data recording step. Data captured in a decentralized non-laboratory setting may not be easily linked to current laboratory databases, which are accessible for public health use.

• Because the use of POCTs is decentralized, the roles and responsibilities of the operator and the laboratory personnel may not be as clearly defined as for traditional laboratory tests, which can lead to confusion regarding compliance with quality assurance and proficiency programs.

• A rigorous quality assurance program has to be in place for continuous monitoring of quality control, proficiency testing, assay functioning, training, and updating of the standard operating procedures.

Summary

Depending on the prevalence of syphilis, the access to laboratory services, the acceptability of Western medical facilities, the risk of significant sequelae (as in mother-to-child transmission), and the performance characteristics of the assay in the verification study, syphilis POCTs can be an asset in the control of this disease. Selection of a syphilis POCT should include ease of use and readability in addition to the usual required performance characteristics. An essential aspect in implementation of such assays is a rigorous quality assurance program that will ensure reliable, reproducible, and accurate results. As currently recommended, all positive syphilis POCT results should be confirmed with a standard laboratory test. However, POCTs can be used to complement existing syphilis serology tests to fill the gap where testing is lacking, as in remote regions of the country, and as a rapid tool to tackle outbreaks in high-risk groups. In these situations, a decrease in sensitivity would be more tolerable than low specificity, because the latter would be associated with a false diagnosis of a stigmatizing disease.

Syphilis POCTs add to the armamentarium of tests used in the syphilis diagnostic algorithm. Their use promises great benefit in remote locations with poor access to medical facilities and among marginalized populations. Here, these assays could assist public health in halting uncontrolled transmission at the expense of over-treatment while awaiting the results of conventional tests. The role these assays play in infectious syphilis diagnosis must be determined by the medical director of each program that uses them. If adopted, integration of results from POCTs into the routine surveillance program will require prudent consideration and attention. Future research should address the development of newer POCTs for antigen and nucleic acid detection as well as carry out rigorous field trials to inform the interpretation of POCT results in the different settings in which they may be deployed for patient management or for overall public health considerations. Field trials can also compare the results of POCTs with those of conventional syphilis serology in addition to comparing POCT results when using whole blood versus serum.

Declarations:

Opinions expressed in this document are those of the authors and do not necessarily represent the official position of the Public Health Agency of Canada.

Ethics Approval:

N/A

Informed Consent:

N/A

Registry and the Registration No. of the Study/Trial:

N/A

Funding:

No funding was received for this work.

Disclosures:

P Naidu received an honorarium from Seegene for speaking at their workshop on urogenital mycoplasma detection. RSW Tsang has nothing to disclose.

Peer Review:

This manuscript has been peer reviewed.

Animal Studies:

N/A