What is Syphilis Rapid Test Strip Supplier and Why Do We Use Them?

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Key Messages

• This Horizon Scan summarizes available information regarding rapid point-of-care testing for the detection of Treponema pallidum, the bacteria that causes syphilis.

• Rapid point-of-care testing to screen people for a possible case of syphilis allows health care providers to screen people where they are, rather than relying on people&#;s access to traditional health care settings. The rapid provision of test results can also help to guide treatment in the moment, rather than requiring additional appointments that could increase the number of people with active syphilis infections lost to follow-up.

• There are currently no point-of-care syphilis tests licensed for use by Health Canada; however, at least 1 multiplex syphilis and HIV-1/HIV-2 detection test could be licensed for use in Canada by the end of .

• Based on the evidence reviewed, rapid tests for the detection of syphilis appear to be adequately sensitive and specific for screening. The use of point-of-care testing, at-home self-testing, at-home sample collection methods, and telemedicine and virtual care options may be interventions to consider as health care systems move forward and work to catch up on the screening backlog and missed tests related to the COVID-19 pandemic, and also find ways to connect with people who have previously been harder to reach.

Point-of-Care Tests Can Facilitate a Faster Syphilis Diagnosis Than Standard Lab Tests

Traditional lab tests used to diagnose syphilis can take weeks to provide a result. Point-of-care tests can provide the user with a result in less than 20 minutes, and may help to improve uptake because they can be administered in locations outside of traditional health care settings.

How It Works

Syphilis infection is confirmed by the detection of antibodies. The presence of treponemal antigens can indicate a current or past infection, so tests for treponemal antigens alone cannot confirm a current infection.1 A positive treponemal test is usually confirmed with a non-treponemal test.

Point-of-care tests for syphilis are visually interpreted, rapid vertical flow immunoassays that can be performed by health care providers using a fingerstick or IV blood sample.2 They can test for syphilis alone, or may include multiplex testing for both syphilis and HIV-1 and HIV-2 antibodies. Some rapid tests can return results in as little as 1 minute.3 Recently, in Canadian trials, rapid multiplex tests have been used to help curb the spread of outbreaks and provide immediate access to treatment.4 Currently available point-of-care tests for syphilis are only able to test for the presence of treponemal antigens and do not have the ability to detect non-treponemal antigens. Therefore, these tests are designed to be used to screen a person for a potential current syphilis infection, but additional non-treponemal testing is required to confirm the diagnosis. In harder to reach populations, the initial screening test may be the only time a health care provider gets to see the person being tested and, in some cases, treatment may be initiated before the diagnosis is confirmed if there are concerns that a person might not return to receive the results of the confirmatory diagnostic test.

Who Might Benefit?

Syphilis is a curable sexually transmitted infection (STI) caused by the bacteria Treponema pallidum. Syphilis is the third most reported notifiable STI in Canada, following chlamydia and gonorrhea.5 In , the rate of infectious syphilis in Canada was 24.7 per 100,000 population, up from 5.1 per 100,000 in .5 Infection rates increased in almost all provinces, but the relative increase in the Prairie provinces was particularly large, increasing by more than 400%.5 Infection rates are consistently higher for those who are male, but the female infection rate in Canada increased by 773% between and .5 Some have attributed the rise to changes in behaviour, such as increased substance use and the increasing use of dating apps, and the corresponding increased accessibility to multiple sexual partners.4

Persistent syphilis infection can cause long-term issues like heart, brain, and nerve damage in adults. Syphilis can be passed from a pregnant parent to their unborn child and cause complications like stillbirth, premature delivery, and disability in infants.6 Early syphilis infection can be treated with antibiotics. Syphilis can also increase a person&#;s risk of becoming infected with HIV.6 Syphilis has a long latent phase of infection before symptoms begin to show, which makes it difficult to screen for and inhibits efforts to prevent transmission and reduce infection rates.6 People who tend to be the most likely to become infected with syphilis are also more likely to face barriers to seeking preventive health care and attending regular health screenings.6 National and international efforts are under way to reduce the global incidence of syphilis by up to 90% by .6

People face many barriers to accessing STI screening, including syphilis testing. These barriers may include access to reliable transportation, access to a or the internet to make an appointment, access to a primary care provider or sexual health clinic, or other pre-existing health issues like substance use disorders.4 Traditional lab-based diagnostic testing for syphilis can take a week or longer to provide results to guide patient care. This delay can lead to further spread of syphilis by those with unknown infection and can also result in loss to follow-up for people who do not return to receive their test results or obtain treatment.4 Point-of-care tests allow providers to test people where they are, whether that is at a usual medical appointment, sexual health clinic, emergency department, or outreach site, and provide a preliminary test result and treatment plan immediately.4

Availability in Canada

The tests used in recent Canadian clinical studies, the Medmira Multiplo TP/HIV and bioLytical INSTI multiplex tests (refer to ), have not received Health Canada regulatory approval. bioLytical anticipates the INSTI® Multiplex HIV-1/2 Syphilis Antibody Test will receive a class IV medical device licence from Health Canada before the end of .7 The Medmira Multiplo TP/HIV test and the Medmira Multiplo complete syphilis (TP/nTP) antibody test tests have received a CE mark in Europe, but are not FDA approved.2 The bioLytical INSTI multiplex test has received the CE mark for the HIV component (CE mark for syphilis by self-declaration), but is not currently FDA approved.3

Figure 1

bioLytical INSTI Multiplex HIV-1/2 Syphilis Antibody Test.

There is 1 standalone point-of-care syphilis test available in the US, the Syphilis Health Check assay, and 1 multiplex assay, the DPP HIV Syphilis System, authorized for use by the FDA; however, these are not available for use in Canada.8

What Does It Cost?

The cost of the bioLytical INSTI Multiplex HIV-1/2 Syphilis Antibody Test is anticipated to be C$24.99.7 There is potential for these point-of-care tests to reduce costs within the Canadian health care system by removing the need for lab-based tests for screening purposes. Lab tests could be reserved for confirmation of a positive point-of-care screening test, thereby reducing the costs of lab materials and human resources required for syphilis testing.

In an economic analysis, dual screening for HIV and syphilis was shown to be more cost-effective than single rapid tests for each when examining the costs of prevention and care related to pregnancy.9

Current Practice

In Canada, there are 2 blood test screening algorithms used to diagnose syphilis. Most provinces use the reverse algorithm, which uses a treponemal test to screen for infection by detecting treponemal antibodies in the blood sample; and a quantitative non-treponemal test, typically a rapid plasma reagin (RPR) test, to detect non- treponemal antibodies and confirm positive treponemal test results.10,11 Treponemal tests will typically show a positive result for life once a person has had syphilis, regardless of treatment, which can lead to false-positive test results and means a positive treponemal test result should be confirmed with a non-treponemal test to accurately diagnose an active, untreated case of syphilis.11 These tests require time to complete and a patient will be tested, diagnosed, and treated across a number of appointments.1

Although there may be circumstances in which the benefit of treponemal tests alone for diagnosis (instead of screening) may outweigh the risk of overtreatment, WHO recommends that all positive point-of-care tests for syphilis be confirmed using a standard laboratory test.1

What Is the Evidence?

As demonstrated in a variety of controlled lab evaluation studies12-14 field evaluations,15,16 and systematic reviews and meta-analyses,9,17,18 rapid tests for the detection of syphilis appear to be adequately sensitive and specific for screening. A summary of diagnostic accuracy for a variety of point-of-care syphilis and syphilis/HIV multiplex tests is provided in . The current commercially available tests are only able to detect treponemal antibodies and cannot distinguish between an active and a prior treated syphilis infection. Positive results therefore require confirmation with a non-treponemal lab test to diagnose a current case of syphilis.

Table 1

Evaluation of Point-of-Care Diagnostic Test Accuracy for the Detection of Syphilis.

Safety

No information was identified regarding safety issues related to the use of rapid, point-of-care syphilis testing.

Issues to Consider

People with a suspected case of syphilis through point-of-care testing will still require follow-up with a health care provider to receive their confirmatory diagnostic tests results and complete treatment. The implementation of point-of-care testing for syphilis can help to reduce the time to diagnosis and also reduce the number of patients lost to follow-up by allowing health care providers to initiate treatment based on the person&#;s screening test result rather than waiting weeks to receive the confirmation of diagnosis to begin treatment.

User Perspectives

Qualitative evaluations of the use of rapid tests for the detection of syphilis, and particularly dual tests with HIV detection, found that users were generally positive about their experience with the tests.9 The short time to receive the results and the need for a single finger prick sample to run both tests were important characteristics that users liked.9 Rapid tests used in settings outside of traditional medical care settings, like mobile outreach programs, provided a discrete, easy to access, and effective way for people to be screened.20 Users in 1 study indicated that they would be more likely to be tested regularly if a mobile clinic continued to be offered.20

Related Developments

Following the most recent Canadian trials of the combined syphilis and HIV-1/HIV-2 tests, further trials are ongoing in Saskatchewan.4 The trial will start at clinics and pharmacies in Regina, and will potentially expand to include Indigenous communities.4 bioLytical is working toward introducing a self-test version of the INSTI Multiplex HIV-1/2 Syphilis Antibody Test in the first quarter of .7The Stopping Syphilis Transmission in Arctic Communities Through Rapid Diagnostic Testing (STAR) study began in January and will continue through the end of .21 Its aim is to evaluate the clinical and epidemiological impact of using the Chembio DPP Syphilis Screen and Confirm Test, a rapid test that can detect both treponemal and non-treponemal antibodies and provide a confirmed diagnosis at the point of care, in the context of ongoing transmission in Nunavut and Nunavik.21 The test is not currently available for use in Canada and was obtained for use in the study through Health Canada&#;s Special Access Program.

In the US, individuals can purchase kits for syphilis testing with at-home sample collection.22 The tests do not provide the user with rapid results, but facilitate the user to collect their own fingerprint blood sample that is then sent by mail to a lab for processing.22 The results are usually returned within 7 business days. Some, but not all, of these at-home test kits include follow-up advice from a medical professional upon receipt of the results.22 The use of these sorts of tests may increase access for some, but their use requires the ability to pay out of pocket for the point-of-care kits, and internet access to be able to order them. Despite the availability of these tests to the individual, none of these tests have FDA authorization for at-home use.22 These tests cost between US$29 and US$78.22

Clinical trials are ongoing in China evaluating the use of a rapid saliva-based molecular detection test for syphilis.23 Researchers have identified high levels of T. pallidum DNA in saliva samples of people diagnosed with laboratory-confirmed syphilis.24 Saliva samples are collected in convenient and non-invasive ways and their use in testing could help to increase acceptability and ease of use.24

Looking Ahead

The service restrictions related to the COVID-19 pandemic resulted in a decrease in routine screening procedures and uptake of voluntary STI testing and screening.25 This decreased uptake has highlighted the potential for increasing testing and screening outside of traditional clinical settings and using alternative testing and sample collection methods.25 The use of point-of-care testing, at-home self-testing, at-home sample collection methods, and telemedicine and virtual care options may be interventions to consider as health care systems move forward and work to catch up on the screening backlog and missed tests, and also find ways to connect with people who have previously been harder to reach.25

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Sexually Transmitted Infections (STIs) are a pressing public health concern worldwide, affecting millions of people each year. Among the many STIs, one that often hides in the shadows, yet can have severe and long-lasting consequences if left untreated, is syphilis. In this blog, we will dive deep into the world of syphilis, exploring its causes, symptoms, diagnosis, treatment, and the importance of prevention.

Understanding Syphilis

Syphilis is a bacterial infection caused by the spirochete bacterium Treponema pallidum [1]. It primarily spreads through sexual contact, but it can also be transmitted from an infected mother to her unborn child during pregnancy [1]. The infection progresses in stages, each characterized by distinct symptoms and potential complications. There are four stages of syphilis: primary, secondary, latent, and tertiary syphilis [1-2].

Stages of Syphilis and Symptoms

1. Primary Syphilis
   • This stage begins with the appearance of a painless sore or ulcer known as a chancre at the site where the bacterium entered the body. Chancres are typically found on or around the genitals, anus, or mouth.
   • The chancre usually heals on its own within a few weeks, even if left untreated.
2. Secondary Syphilis
   • If the infection is not treated during the primary stage, it progresses to the secondary stage. This stage is marked by a wide range of symptoms, including skin rashes, fever, sore throat, muscle aches, and swollen lymph nodes.
   • These symptoms may come and go, but they can persist for weeks or even months.

1. Latent Syphilis
   • If the infection goes untreated even after the secondary stage, it enters the latent stage, where no symptoms are present. Latent syphilis can last for years, and the bacterium can still be present in the body.
   • During this stage, the infection may remain asymptomatic or progress to the most severe form of syphilis, tertiary syphilis.

1. Tertiary Syphilis
   • Tertiary syphilis is the most serious and potentially life-threatening stage. It can damage various organs, including the heart, brain, nerves, eyes, and blood vessels.
   • The complications from tertiary syphilis can be severe and irreversible, leading to disability and, in some cases, death.

Transmission of Syphilis

Syphilis is primarily transmitted through sexual contact, but it can also be transmitted from an infected mother to her unborn child during pregnancy. Here are the main modes of transmission for syphilis:

1. Sexual Contact: Syphilis is most commonly spread through direct sexual contact with an infected person. This includes vaginal, anal, or oral sex [2]. The bacterium Treponema pallidum, which causes syphilis, can enter the body through mucous membranes and skin lesions, including chancres (sores) that are characteristic of primary syphilis [2].
2. Mother-to-Child Transmission: Pregnant women with syphilis can transmit the infection to their unborn child through the placenta. This is known as congenital syphilis [3]. If not detected and treated early, congenital syphilis can result in serious health problems or even stillbirth [3].

1. Bloodborne Transmission: While syphilis is not as commonly transmitted through blood as some other STIs, it is theoretically possible. This may occur if a person with syphilis has an open sore or cut that comes into direct contact with the blood of another person, such as through sharing needles or syringes [2].
2. Rare Non-Sexual Transmission: Although rare, syphilis can also be transmitted through non-sexual contact with an infected person, such as through close personal contact. This can occur when an individual comes into contact with a syphilis sore (chancre) or an open syphilis rash. However, this mode of transmission is not common.

It&#;s important to note that syphilis is highly contagious during the primary and secondary stages when chancres and other symptoms are present [3]. In later stages, when the infection becomes latent or progresses to tertiary syphilis, the risk of transmission to others decreases, but the potential for severe health complications remains.

To reduce the risk of syphilis transmission, it&#;s essential to practice safe sex by using latex or polyurethane condoms consistently and correctly, get regular STI screenings, and seek prompt medical treatment if you suspect you have syphilis or have been in close contact with an infected person. Early diagnosis and treatment are key to preventing the spread of syphilis and its associated health problems.

Epidemology of Syphilis

Syphilis is a global concern, with its impact varying by region and influenced by factors such as healthcare infrastructure, education access, and sexual behavior. Although it can affect individuals of all ages and genders, certain areas experience higher prevalence rates. Notably, young adults in their 20s and 30s are often at higher risk due to increased sexual activity and inconsistent protection use [4]. Men who have sex with men (MSM) face a heightened risk, witnessing significant increases in syphilis rates. However, the infection can affect people of any gender.

Annual infection rates fluctuate, with the United States reporting a notable increase in recent years. Meanwhile, Europe has seen an upward trend in syphilis incidence [4]. This regional variation underscores the importance of national and international monitoring and response [4]. Syphilis outbreaks can occur in specific communities linked to high-risk sexual behaviors and limited healthcare access, resulting in a sudden surge in cases.

Public health agencies respond by increasing education, testing, and treatment services in affected areas, aiming to reduce transmission and raise awareness. Understanding syphilis epidemiology is vital for developing effective prevention and control strategies, targeting high-risk groups, promoting education, and ensuring accessible testing and treatment, ultimately reducing its impact in various communities.

Prevention

Preventing syphilis is essential for protecting your sexual health and reducing the risk of this sexually transmitted infection (STI). Here are some key prevention measures [5]:

1. Safe Sex Practices:
   • Practice safe sex with consistent condom use, whether latex or polyurethane, to reduce the risk of syphilis and other STIs. Engage in sexual activities with a trusted partner, and both should undergo syphilis and STI testing before any sexual activity.
   • Reducing the number of sexual partners can lower your risk of syphilis and other STIs. Limiting your sexual activity to a monogamous relationship with a partner who has also been tested for syphilis and other STIs can be an effective prevention strategy.
2. Regular STI Testing:
   • Get tested for syphilis and other STIs regularly, especially if you are sexually active or engage in high-risk sexual behaviors. Early diagnosis and treatment of syphilis are crucial to prevent its progression and complications.
3. Avoid Sharing Needles:
   • If you use drugs, do not share needles or syringes. Sharing injection equipment can lead to the transmission of syphilis and other bloodborne infections.

1. Prenatal Care:
   • If you are pregnant, seek early prenatal care and testing for syphilis. This is important to prevent the transmission of syphilis to your baby (congenital syphilis).
2. Vaccination:
   • While there is no vaccine for syphilis, getting vaccinated against other preventable STIs, such as hepatitis B and human papillomavirus (HPV), can reduce your overall risk of STIs.
3. Seek Treatment Early:
   • If you are diagnosed with syphilis, it&#;s important to follow your healthcare provider&#;s treatment recommendations. Early treatment with antibiotics, typically penicillin, is highly effective in curing syphilis.

Treatment of Syphilis

The treatment for syphilis differs depending on its stage. In the early stages, such as primary and secondary syphilis, a single injection of a long-acting penicillin is the preferred course of action [2]. For those with a penicillin allergy, alternative antibiotics like doxycycline or tetracycline are available, although penicillin remains the top choice [6].

When it comes to latent syphilis, the treatment approach depends on whether it&#;s in its early or late stage. If it&#;s early latent syphilis (less than a year in duration), a single dose of benzathine penicillin G typically does the trick [6]. Late latent syphilis, lasting more than a year, may necessitate three weekly doses of benzathine penicillin G to ensure complete eradication of the infection.

For tertiary syphilis, which involves severe complications, a more extensive treatment plan is required, often including intravenous penicillin G [6].

When syphilis affects the nervous system, a condition known as neurosyphilis, the treatment typically involves a more intensive regimen, with intravenous penicillin G administered daily for 10 to 14 days [6].

If you suspect you have syphilis or have been exposed to the infection, seeking prompt medical attention is essential. Early diagnosis and treatment are paramount in halting the progression of syphilis and averting the development of severe complications.

Diagnosis Methods

Certainly, in addition to the traditional laboratory-based blood tests, rapid test kits have become increasingly available for the diagnosis of syphilis. Here&#;s an updated overview of the diagnostic methods for syphilis, including the use of rapid test kits:

1. Clinical Evaluation:
   • A healthcare provider begins the diagnostic process by taking a comprehensive medical history and conducting a physical examination. They inquire about any signs and symptoms and assess potential risk factors.
2. Blood Tests:
   • Blood tests are the most common and reliable way to diagnose syphilis. There are two types of blood tests used:
     • Non-Treponemal Tests: These tests, like the Rapid Plasma Reagin (RPR) and Venereal Disease Research Laboratory (VDRL) tests, detect antibodies in response to the infection and may be used as initial screening tests [7].
     • Treponemal Tests: Treponemal tests, such as the Fluorescent Treponemal Antibody Absorption (FTA-ABS) and Treponema Pallidum Particle Agglutination (TP-PA) tests, confirm syphilis diagnosis after a positive non-Treponemal test result [7]. These tests detect antibodies specific to the syphilis bacterium and remain positive even after successful treatment.
3. Cerebrospinal Fluid Analysis:
   • If neurosyphilis is suspected, a lumbar puncture (spinal tap) may be performed to analyze cerebrospinal fluid for signs of infection.

1. Direct Visualization:
   • In cases where syphilis sores (chancres) are present, a healthcare provider may perform a dark-field microscopy examination of material from the sore to identify the spirochete bacterium Treponema pallidum.
2. Swab Tests:
   • For oral or genital lesions, swab samples may be collected for polymerase chain reaction (PCR) testing, which detects the presence of the bacterium&#;s genetic material.
3. Rapid Test Kits:
   • Rapid test kits are becoming more accessible for syphilis diagnosis. These kits are point-of-care tests that provide quick results, often within minutes. They are particularly useful in settings where timely diagnosis and treatment are crucial, such as in resource-limited areas or during outreach programs.
4. Screening During Pregnancy:
   • Pregnant women are often screened for syphilis as part of their prenatal care. Screening is essential to prevent the transmission of syphilis to the unborn child (congenital syphilis).

The choice of diagnostic method may depend on factors such as the availability of resources and the specific healthcare setting. Regardless of the method used, accurate and timely diagnosis of syphilis is essential for initiating appropriate treatment and preventing the progression of the infection and its complications. If you suspect you have syphilis or have been exposed to the infection, it&#;s important to seek medical attention promptly for testing and diagnosis.

How to Use Syphilis (Treponema Pallidum) Rapid Test Kit?

Using a syphilis (Treponema pallidum) rapid test kit typically involves a few simple steps. These rapid test kits are designed for quick, point-of-care syphilis testing and can be used by healthcare professionals or trained individuals. It&#;s important to follow the manufacturer&#;s instructions provided with the specific kit you are using, as the exact steps may vary slightly. However, here is a general guide on how to use a syphilis rapid test kit:

Materials Needed:

• Syphilis rapid test kit (provided by the manufacturer)
• Safety gloves (recommended)
• A clean and flat surface for performing the test
• Timer or stopwatch (for timing the test)

Steps to Use a Syphilis Rapid Test Kit:

1. Read the Instructions: Start by carefully reading the instructions provided with the kit. The instructions will include important information on the correct procedure, required materials, and interpretation of results. Follow the instructions precisely.
2. Gather Supplies: Ensure that you have all the necessary materials ready, including the test kit, safety gloves, and a clean, flat surface to work on.
3. Prepare the Test Kit: Remove the test kit from its packaging and check for any visible damage. Ensure that it is within the expiration date. The kit typically consists of a test device, a sample collection swab or lancet, reagents, and a buffer solution.
4. Prepare the Sample: Depending on the specific kit, you may need to collect a blood sample, serum, or plasma. Follow the instructions to collect the sample using the provided swab or lancet. Be sure to follow all safety precautions and proper hygiene during sample collection.
5. Apply the Sample to the Test Device: Apply the collected sample to the designated area on the test device, following the instructions carefully. This may involve placing a drop of the sample onto the test device.

6. Add Buffer Solution: Add the buffer solution provided in the kit to the test device. This solution helps the test react and provides accurate results.
7. Wait for Results: Follow the recommended waiting time (specified in the instructions) for the test results to develop. Typically, you will need to wait for a specific duration, such as 10-15 minutes.
8. Read and Interpret Results: After the designated waiting time, check the test device for the appearance of lines or other indicators, as per the manufacturer&#;s instructions. A positive or negative result will be indicated by the presence or absence of specific lines or symbols on the test device. It&#;s important to follow the interpretation guidelines provided in the instructions.
9. Dispose of Materials: Safely dispose of any used materials, including the sample collection swab or lancet, according to proper biohazard disposal procedures.
10. Document the Results: Record the results of the test as either positive or negative. Accurate record-keeping is essential for healthcare documentation.

Remember that the interpretation of rapid test results should be done by a trained healthcare professional. If a syphilis test is positive, it is essential to seek further evaluation and confirmatory testing by a healthcare provider for diagnosis and treatment. False-positive or false-negative results can occur, so confirmatory tests are typically necessary to ensure accuracy.

The Most Effective and Commonly Used Syphilis Rapid Test Kit

The Anti-Syphilis Rapid Test Kit is a user-friendly, point-of-care tool designed for qualitative syphilis screening in human serum, plasma, and whole blood samples. Its advantages include early detection and immediate treatment initiation, which is vital for preventing transmission and reducing the overall prevalence of syphilis. The test also helps prevent long-term complications associated with the disease and unfavorable pregnancy outcomes. Its easy sampling and simple procedure make it accessible, and the results are easily interpretable, making it a valuable tool for both healthcare professionals and individuals seeking self-testing options, ultimately contributing to improved syphilis control and public health.

REFERENCES

[1] Syphilis &#; CDC detailed fact sheet. Centers for Disease Control and Prevention. https://www.cdc.gov/std/syphilis/stdfact-syphilis-detailed.htm. Accessed November 9, .

[2] Sexually transmitted infections treatment guidelines, : Syphilis. Centers for Disease Control and Prevention. https://www.cdc.gov/std/treatment-guidelines/syphilis.htm. Accessed November 9,

[3] Garnett, G. P., Aral, S. O., Hoyle, D. V., WILLARD CATES, J., & Anderson, R. M. (). The natural history of syphilis: implications for the transmission dynamics and control of infection. Sexually transmitted diseases, 24(4), 185-200.

[4] Syphilis &#; Annual Epidemiological Report . European Centre for Disease Prevention and Control. (b, October 23). https://www.ecdc.europa.eu/en/publications-data/syphilis-annual-epidemiological-report-

[5] Saloojee, H., Velaphi, S., Goga, Y., Afadapa, N., Steen, R., & Lincetto, O. (). The prevention and management of congenital syphilis: an overview and recommendations. Bulletin of the World Health Organization, 82(6), 424-430.

[6] Clement, M. E., Okeke, N. L., & Hicks, C. B. (). Treatment of syphilis: a systematic review. Jama, 312(18), -.

[7] Larsen, S. A., Steiner, B. M., & Rudolph, A. H. (). Laboratory diagnosis and interpretation of tests for syphilis. Clinical microbiology reviews, 8(1), 1-21.

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