Diagnosis of Syphilis: Tests and Techniques Used to Detect the Infection

Introduction

Syphilis belongs to a group of infections known as sexually transmitted infections (STI). As the name implies, STIs are transmitted through sexual intercourse. The number of cases of syphilis has seen a significant rise in recent times and has drawn the attention of the medical world. If left untreated, syphilis presents with adverse consequences which are severely detrimental to health and will be discussed below.

Overview

How common is syphilis?

About 8692 people were diagnosed with syphilis in 2022 in the United Kingdom which is 15.2% higher than the previous year.^1,2 It is becoming more common, particularly among men who have sex with men.^3,4 

What is syphilis?

Syphilis is a sexually transmitted Infection caused by a bacterium, Treponema pallidum, with a variety of clinical manifestations.^5,6 

How is syphilis spread?

It is most commonly spread through unprotected penetrative sex with an infected person. Other ways include: 

• Oral sex 
• Mother-to-child transmission during pregnancy, known as congenital syphilis 
• Sharing of needles used by an infected person
• Blood transfusion and organ transplant^7,8,9

It takes about 21 days after contracting the infection for symptoms to develop. Sometimes, the symptoms may disappear spontaneously but the infection will still remain if it has not been treated. In the period where signs and symptoms are absent, known as latent syphilis, the blood tests are usually positive, it can be divided into early and late latent syphilis based on duration.¹⁰ 

The stages of syphilis

The symptoms of syphilis manifest in four stages. The first and second stages are when the chances of spreading infection are higher:

Primary syphilis: Is characterised by a painless single ulcer on the genitals, anus or mouth known as a ‘chancre’. It may also present with enlargement of surrounding lymph nodes. The ulcer usually disappears on its own over weeks or months. Without treatment, this stage progresses to the next.

Secondary syphilis: This occurs some weeks or months after contracting the infection and mostly in individuals who have not received treatment. Usually, it appears as a rough and raised rash on the trunk, limbs, palms and soles of the hands and feet, which is not itchy. 

At this stage, the infection is systemic, meaning it affects the whole body and the associated symptoms may include fever, sore throat, headaches, body pains and weight loss. Without treatment, the symptoms can come and go and the individual remains infectious to others. Secondary syphilis will also transform into the next latent stage if not treated. 

Latent syphilis: This stage occurs mainly in people who are not treated in the earlier stages and can last for years. The person remains asymptomatic but may sometimes experience periodic flares. Conversely, the infection may resolve on its own in some people. At this stage, the infection can damage your heart, bones, nerves and organs such as the liver and kidneys. The infection is not easily spread in this stage. 

Late (tertiary) syphilis: About 30% to 40% of people with untreated syphilis experience complications known as tertiary or late syphilis. It is usually more severe as it causes a range of serious health problems. These conditions progress slowly and include:

• Brain and nerve damage, dementia and cognitive health problems
• Cardiovascular disease
• Movement disorders, muscle and joint problems
• Seizures
• Eye and vision problems, including blindness^10,11,12,13 

Congenital Syphilis 

In congenital syphilis, a mother passes the infection to her baby during pregnancy through the placenta which may be severely detrimental to the baby. The consequences of the infection for the baby may include hearing loss, blindness and death. This is why mothers are screened for STIs during pregnancy and treated if they are infected. Syphilis can also complicate a pregnancy by causing: 

• Miscarriage 
• Stillbirth 
• Low birth weight 
• Premature birth^14,15

The importance of early diagnosis 

Syphilis causes more damage to your body the longer the infection persists which is why you need to get tested and treated immediately. Syphilis can affect various organs in the body such as your heart, eyes, brain, and muscles causing irreparable damage to them. 

Infection with each type of STI increases the risk of acquiring another type, which is why a range of STI tests called an STI panel are requested. Syphilis can also be asymptomatic, especially in the latent stage, and cause irreparable damage without being noticed.^8,16

Diagnosis 

Symptoms and signs 

Primary syphilis: the most visible symptom is the chancre - a painless sore/ulcer on the genitals, mouth or anus present during primary syphilis. It typically disappears on its own within a few weeks.

Secondary syphilis: a non-itchy but bumpy rash appears on the body. Other symptoms such as fatigue and swollen lymph nodes may also occur. 

Latent syphilis: the symptoms are generally absent in the later stages, but this does not mean you are not infected. 

If you think you have syphilis, you can access confidential services by attending a sexual health clinic (some do not even require an appointment) or visiting your GP. They will have to ask you questions related to your sexual history as part of the diagnostic procedure. Therefore, it is important that you answer accurately as this may affect how you are managed.⁵

Samples required for tests

Blood: Blood may be taken from your vein. This is the most common method used to detect antibodies (a type of protein produced by the body) specific for fighting off the syphilis infection.

Swab: This is taken from the sore or ulcer and viewed under the microscope to look for the bacteria. Alternatively, it can be tested by other modern methods like Polymerase Chain Reaction (PCR)

Cerebrospinal fluid (CSF): The CSF is a fluid produced in the brain that circulates around the brain and spinal cord removing metabolic waste, providing nutrients, and keeping the brain afloat in the skull and cushioned from crashing into it during mechanical shocks. 

If it is suspected a person has neurosyphilis (a complication involving a syphilitic infection affecting the brain), a cerebrospinal fluid sample may be taken by a procedure called lumbar puncture whereby a hollow needle is inserted in your lower back between 2 vertebral bones and fluid is drawn off from between the spinal cord and its outer protective coating (meninges). 

This fluid is then tested to find out whether there is an infection in the central nervous system (CNS). A positive result usually indicates that the syphilis infection is in the late stage.^5,17 

Diagnostic tests

Direct detection 

• Dark-field microscopy: This test is not widely used because it requires a person who is highly experienced at detecting Treponema pallidum under the microscope. Also, this test is not usually used for swabs taken from the mouth because there are organisms in the same family as Treponema pallidum that reside in the body normally, which can be confused with it
• PCR: This test can be used using swabs taken from the mouth. It is used to monitor the impact of treatment and is only available in laboratories¹⁹
• Direct fluorescent antibody testing: This is the most specific test for people who still have ulcers present. It uses swabs taken from the mouth and anus

Serologic testing

• Treponemal tests: Examples commonly used in the UK are treponemal enzyme immunoassay (EIA) or chemiluminescent assay (CIA). These tests detect proteins produced by your body called antibodies. The antibodies fight against the proteins produced specifically by the Treponemal pallidum organism. The antibodies remain in your body even after successful treatment. The test is used to detect if you have had syphilis previously or have it currently. There are rapid test kits available to detect the infection but you should seek medical help for a confirmatory test if the rapid test is positive
• Non-treponemal tests: It is known as the Venereal Disease Research Laboratory (VDRL) carbon antigen test/RPR test. This test is commonly used for people who have had syphilis before. It detects antibodies produced in response to proteins that are released from the destruction of the organism. These tests are rapid, easy and cheap to conduct. However, confirmation with a second specific test, or with examination of a tissue sample for infectious organisms is required^5,18,20,21

FAQs

What are the symptoms of syphilis?

Syphilis may go unnoticed as it does not present with the common symptoms associated with other STIs like discharge or burning sensation. It may however present with a painless single ulcer/sore in the genitals or mouth after about three weeks of acquiring the infection.

How can I get the infection?

It is obtained through sexual contact with an infected person. If you are pregnant and have syphilis, you can infect your baby during pregnancy and birth. Other routes include the sharing of needles. 

Does my partner need to be tested?

Yes, even if your partner does not have symptoms, they may still have the infection and still need to be treated.

What samples will be needed for the tests?

Your doctor may collect your blood sample or take a swab from the sore. It depends on the type of diagnostic test available in the clinic.

Can I test myself at home?

Yes, but if your test is positive, you will still need to go to the clinic for a confirmatory test and treatment.

How do I protect myself?

It is important to use protection, especially with new sexual partners. It is also recommended to do regular STI checks to know your status.

Can I be treated?

Yes, most cases can be treated with antibiotics which is why it needs to be detected early to prevent further complications. If you think you have an STI, there are sexual health services available within the United Kingdom. They can provide free tests, contraception and treatment, and also counselling on safe sex.

Summary

Syphilis is a sexually transmitted infection transmitted by direct contact with an infectious ulcer or sore during sex. It can persist for years and progress to a more serious infection, affecting various organs in your body. Early diagnosis and treatment are needed to stop the progression and transmission to other sexual partners. If someone is aware that they have syphilis and refuses treatment or testing, they may be prosecuted if they are found to have spread the infection to other people.