How is Syphilis Tested & Diagnosed?

Syphilis Testing

There are many initiatives nowadays that are trying to prevent the stigma on sexual health from ever happening again, but it is apparent that the issue is still prevalent due to the steady, albeit slow, increase of STD cases.

Sure, the numbers are positively going in the right direction, but there is still some drag preventing the numbers from ultimately going down—and this is widely associated with the existing fear of many to consult their doctors or talk about the sexual problems that they are having.

We have determined that the best way to resolve such problems once and for all is to provide the public with the necessary information as to how they would be able to be appropriately diagnosed while still maintaining a more distant approach to avoid overwhelming those who are admittedly still uncomfortable to deal with such topics directly. While this outline does not cover all the options that you might have to provide some answers to the questions that you might have regarding your possible condition, it does have the necessary points that will direct you to the right option—from where you could then begin to unravel the answers to the questions that you have had for quite some time. Again, the answer is always in the early diagnosis of the condition, and this outline will undoubtedly provide you with the necessary information that you will need moving forward.

For this particular outline, perhaps it might be more efficient to first look at a rather complicated disease that many people are already slightly familiar with on some level.

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Defining Syphilis Infections

Before anything else, perhaps it might be more efficient to define and describe the characteristics of the disease that this outline will be focusing on. For this one, we will be dealing with one of the most well-known sexually transmitted conditions as this has been present for several years already—ranging back from the time of monarchial rule, even: syphilis. Syphilis is a rather complex disease as several things might occur from your initial infection to the development of certain complications, but there are some things that you can initially do to rule out another possible differential diagnosis from the determination of your symptoms and manifestations alone.

Presentations and Manifestations

Syphilis infections are caused by the microorganism known as Treponema pallidum. This particular condition can be divided into four different stages: primary syphilis, secondary syphilis, latent syphilis, and tertiary syphilis. The following are its respective manifestations in each stage:

  • Primary Syphilis: This serves as the initial manifestation point of a syphilis infection. The first sign of syphilis infection is the appearance of chancre sores, and this would appear mainly in the area where you came into contact with another infected tissue (often in the genitalia). The number of chancres might range from one to several, depending on your body's reaction to the ongoing infection. The chancres are supposed to be painless, and they would typically resolve on their own within three to six weeks, albeit the disease would still be present.
  • Secondary Syphilis: Secondary syphilis occurs when your primary infection is not immediately resolved. Following the healing of the original chancres, you may then observe the presence of a rash that would cover your trunk and then your entire body. It is not usually itchy, and at this point, you may also experience systemic symptoms such as a fever, muscle aches, and sore or swollen lymph nodes.
  • Latent Syphilis: If the infection is still not resolved by this point, the condition will regress into a latent stage where you are still infectious but are not showing any evident signs and symptoms. This stage may last for years—returning only if your immune system becomes compromised or if the condition is not resolved at all.
  • Tertiary Syphilis: This stage is considered the most severe phase as this only occurs when no management strategy has been given. You may experience multiple organ issues that are primarily extra-genital in this stage.

Syphilis Complications

Syphilis complications are more prominent when the patient reaches the tertiary stage of syphilis as this would then involve several other organs in the body, such as the liver, brain, nerves, eyes, bones, and joints.

Some commonly known complications are neurosyphilis, where the infection reaches the nervous system to cause issues within the eye and brain, or congenital syphilis, where the disease is passed through vertical transmission from an infected mother to their baby.

Common Treatment Methods

There are several treatment approaches for syphilis infections. This would mainly rely on the proper diagnosis of the condition and determining what stage the patient is currently in. For most cases, the recommended treatment regimen is a single dose Penicillin injection as this could generally resolve T. pallidum infections with ease, depending, of course, on the progression of the condition. However, other options can be taken if the patient could not tolerate Penicillin well or if the regimen is not adequate for their case. Penicillin injections are the only safe option for infected pregnant patients, though.

Please do note, however, that although we did provide some information on the standard treatment methods, this outline does not encourage self-medication as the use of antibiotics without proper instruction from the physician may cause antibiotic resistance that will make your options more limited when you are infected again in the future with probably the same or another condition entirely. Furthermore, treating the disease without a proper diagnosis may render the treatment moot—causing financial and health drawbacks in the long run. Consult your doctor first if you are experiencing similar symptoms and are worried about your sexual health.

Preventive Measures to Be Done

As with any other condition or disease, the best way to avoid any untoward health issues is to apply the proper preventive measures necessary to avoid being infected in the first place. Some of the things that may do to prevent contracting the infection are:

  • Abstinence: avoiding sexual encounters altogether, especially with people who are not aware of their sexual health status, will prevent exposure to the causative microorganism entirely.
  • Monogamy: being with only one sexual partner ensures that you are consistently informed and aware of your partner’s sexual health status, and this guarantees that you will not be contracting any infection that you or your partner may be unaware of.
  • Condoms: while condoms do not precisely prevent infection completely, they do somehow provide a barrier against direct contact with infected tissue, which will go a long way in minimizing the risk of contracting a disease. Remember that it is a must to use a properly-sized condom to ensure that there will be minimal to no issues with the use of the contraceptive.

Understanding Syphilis Diagnosis: A Rough Overview

When it comes to diagnosing a syphilis infection, there are several things to consider since the condition is relatively complex. However, there are some critical points that you can try to take note of to ensure that you will be informed about the essential things that you should know about syphilis diagnosis.

Please do note, however, that while this outline does not cover all the things that there is to know about syphilis diagnosis, it will provide you with necessary points that you can use to be diagnosed immediately and adequately.

Why Is a Syphilis Diagnosis Necessary?

As previously mentioned, syphilis is a rather complicated disease that integrates several stages and manifestations into its repertoire—all of which would have to be considered when deciding what the best management approach is for the patient and their partner. Syphilis is divided into four stages in total. The exact timeline of each is a blur for many professionals due to the slight inconsistency of its progression—making it hard to provide a sole timeline that would give people an idea of what to expect from the current condition. In addition to this, the latent phase of the disease could even go on for years, leading people to believe that they are already cured when in reality, the microorganism is just steadily replicating to cause a full-blown condition once the patient becomes immunocompromised or if the factors align just right for the infection to proceed to its tertiary stage.

All of this defines the necessity for a proper syphilis diagnosis, and most importantly, an early and timely one, considering that the condition could progress indefinitely if the disease is left alone with any appropriate management strategy to keep its complications at bay. Sure, the effects of syphilis infection are somewhat minor at first, but the complications may be life-threatening and irreversible unless the condition is addressed before it even reaches that point of no return.

When Should Someone Be Tested for Syphilis Infections?

As discussed initially, the timeliness of syphilis diagnosis is critical in ensuring that the condition does not progress into its more severe stages and cause complications that might affect several organs within your body, including your brain and liver. As such, it is crucial that people who are presenting sure signs and symptoms of a syphilis infection, whether it is a single chancre or a rash covering the entire trunk of the patient, be tested right away for a potential syphilis case for the physician to be able to administer the medication right away and prevent its progression to its later stages. Do note that self-medication is highly discouraged to ensure that your treatment will be specific to the condition and that it will be sufficiently dosed to address the disease without causing side effects or even resistance, for that matter.

What to Expect from a Syphilis Test?

Several tests can be done to diagnose a syphilis infection, and the type of expectations you have to set would largely depend on the test that will be administered to you. In most cases, the test would require a blood sample, so be sure to expect that a blood sample will be collected from you. However, there may be cases wherein fluid from the sore will be collected, or a lumbar puncture will be done to ensure that the infection is not yet invading other parts of your body. You may experience some discomfort and pain during this collection process, but the range will again depend on the test that has been administered to you.

Who Is at Greatest Risk of Contracting the Infection?

It is recommended for individuals who are under this group of people who are at risk of contracting the infection to be tested routinely for syphilis infections:

  • Males under the age of 29
  • Those with a history of incarceration
  • Sex workers
  • Those living in an area with high syphilis infection cases
  • African Americans

The following age groups/populations are also advised to be tested for syphilis infections at their respective recommended instances:

  • Pregnant
  • Tested at the first prenatal visit, after 28 weeks, and again if the patient’s delivery is considered high risk
  • If the patient is sexually active, it is recommended to be tested annually. Those with additional risk factors mentioned above may be tested more regularly
  • Annual screening with an increase in rate depending on the risk of exposure and sexual behaviors
  • Screened during first HIV testing, then tested regularly depending on behaviors, local infection rates, and habits

Who Should be Immediately Tested for Syphilis Infections?

Apart from those who are at risk for the infection that has been mentioned above, it is highly recommended for people to be tested for syphilis if they have several risk factors and if they are already experiencing extra-genital syphilis symptoms, as this may indicate that the condition has already progressed to its most severe stage.

What Type of Tests Are Available in the Field for Syphilis Diagnosis?

Five tests can be administered for a patient with a suspected syphilis infection, and the use of each would vary depending on your history, the sample that will be collected, and the current stage of the disease:






Sample Required

Blood sample or spinal fluid

Blood/serum sample

Blood sample

Blood/serum sample

Blood/serum sample

Waiting Time

24 to 36 hours

7 to 10 days


1-7 days

2-3 days

Tool Used

Laboratory performed

Laboratory performed

Laboratory performed

Laboratory performed

Laboratory performed


Syphilis screening; more sensitive during the middle stages

Supplementary test for syphilis screening

Detection of T. pallidum antibodies

Confirmatory test for stand-alone RPR results

Confirmatory test procedure

Syphilis Diagnosis: Tests Available to Request For

Let us then look at the specific details of the tests that you can either avail of or your doctor may prescribe to you to confirm whether a T. pallidum infection causes your condition. The following section contains information regarding the general mechanism of action of the tests, the waiting time necessary before results are released, the cost of each test, the sensitivity and specificity of the procedure, and whether several insurance companies and plans cover the test itself.

Non-Treponemal Antigen Tests

Non-treponemal tests are procedures used to detect specific biomarkers such as antibodies directed toward the damages that have been caused or are being caused by an ongoing infection. Unlike treponemal tests, the test's sensitivity wanes over time and is most effective for determining a current disease alone.

Venereal Disease Research Laboratory (VDRL)

Proposed Procedure

VDRL, or a Venereal Disease Research Laboratory Test, is a procedure that is primarily used for the diagnosis of bacterial infections such as syphilis. When a particular microorganism or antigen infects a person, the average body response is that the immune system will start producing antibodies to counter the foreign bodies and maintain your system's health. Sure, in most cases, these antibodies are insufficient to ward off the infection completely, but it does serve a purpose in diagnosing the condition as these would typically remain within the system for quite some time as long as the infection persists. The antibody that will be present in the blood sample that has been collected from you will first be exposed to the antigen that it typically reacts to – which, in this case, is the antigen of T. pallidum. This antigen will be composed of beef cardiolipin, cholesterol, and lecithin that will collectively produce a qualitative signal when the antigen binds with the antibodies in the serum.

If the test returns negative, no antibody in your sample reacted with the antigen. The test is likely to produce a false-negative result in the early primary stages of the infection, but it does provide a better determination around the secondary or latent stage of the disease, wherein your body is already producing the antibodies at decent rates.

Waiting Time for Results

It may take around 24 to 36 hours before your VDRL test results are released.

Cost and Expenses

The test may only range from around $3 to $5, but this price may vary depending on your selected testing laboratory.

Insurance Coverage

Insurance plans do not cover the test itself widely, but this coverage may vary depending on your premium.

Specificity and Sensitivity

Approximately 100% sensitivity for late-stage/tertiary syphilis, but varied specificity due to the use of antibodies as a determinant.

Rapid Plasma Reagin (RPR)

Proposed Procedure

The rapid plasma reagin or RPR test follows almost the same principle as a VDRL test, albeit it provides specific tweaks to the antigen that will be used in the test so that the entire procedure will not be as complex as the test previous one. In an RPR test, the antigen is combined with a substance known as choline chloride to eliminate the need for heating the serum thoroughly and EDTA to ensure the stability of the suspension once it starts binding with the lipid particles. An RPR test utilizes IgM and IgG antibodies to lipoidal material, allowing it to attach to the lipid particles included in the formulation of the RPR antigen, which is then co-agglutinated with charcoal particles producing black clumps if the serum contains anti-lipid antibodies.

Waiting Time for Results

It takes time for RPR test results to come back compared to a VDRL test, as it typically takes around 7 to 10 days for your results to return.

Costing and Expenses

The price range for an RPR test would be approximately $3.60, depending on the laboratory where you did your test in.

Insurance Coverage

The coverage for the test varies, but there are specific insurance programs and premiums that cover syphilis tests, such as an RPR test.

Specificity and Sensitivity

According to some studies, an RPR test for syphilis is 77.5% sensitive and 94.1% specific. This is primarily impacted by the mechanism of the procedure, which still utilizes antibodies as the target molecule.

Treponemal Antigen Tests

While they still detect antibodies, Treponemal tests utilize antibodies specific to the T. pallidum protein, making them more efficient at specifically targeting T. pallidum infections. The only downside to such a procedure is that it can also detect previous diseases due to the presence of antibodies.

T. pallidum Hemagglutination Test

Proposed Procedure

A T. pallidum Hemagglutination Test utilizes the presence of antibodies within the patient’s serum following an infection. The procedure generally entails that the substances added to the serum will then sensitize the red blood cells of the sample using T. pallidum fragments to mimic its interaction within the body. When this occurs, the cells will then aggregate towards the surface, producing an agglutinated structure or clumps/mats that will then be used to determine whether there is a presence of syphilis antibodies in the sample or not.

Waiting Time for Results

Due to the longitudinal observation of when the clumping occurs, the time it takes to release results varies widely for each facility and test.

Costing and Expenses

According to a detailed cost-utility analysis, the price of a TPHA test came out at around $5, albeit this may still vary depending on the laboratory.

Insurance Coverage

A TPHA test is usually not covered in most insurance policies, but this may change depending on your premium.

Specificity and Sensitivity

TPHA tests have a very high sensitivity and specificity rate at >95% and >99%, respectively.

T. pallidum Particle Agglutination Test

Proposed Procedure

The TPPA Test or T. pallidum Particle Agglutination Test utilizes the same principle as a TPHA, but in this case, it uses sensitized gelatin particles when performing the test. The serum will be diluted in microplate wells, and the gelatin particles will then be added to each respective well and then incubated for around 2 hours. When there are serum-specific antibodies present within the sample, there will be a formation of a smooth mat of agglutinated particles in the wells, which will then be interpreted as a positive result following a qualitative assessment. This test, however, is not utilized for the general screening of syphilis, nor is it used to evaluate response to therapy as the test is mainly qualitative.

Waiting Time for Results

Based on the estimate of specific studies, it takes around 1 to 7 days for TPPA test results to be released—varying depending on the facility that performed the test.

Costing and Expenses

Since the procedure is highly technical, the test prices are not freely accessible and subject to variation depending on the facility that performed the test.

Insurance Coverage

Unfortunately, TPPA tests are not widely covered by typical insurance policies, but they can be included depending on the plan that you have availed.

Specificity and Sensitivity

TPPA tests have a specificity and sensitivity rate of 96% and 88%, respectively.

Fluorescent Treponemal Antibody Absorption Test

Proposed Procedure

A Fluorescent Treponemal Antibody Absorption Test or FTA Test utilizes the inclusion of a fluorescent substance to provide a visual cue as to whether syphilis antibodies are present within the patient sample. Initially, the patient serum is first exposed to substrate cells. If there are antibodies present, an antibody-antigen interaction will occur. Following this, we will then add anti human immunoglobulin labeled with fluorescein isothiocyanate to the substrate cells, wherein the cells will take up the immunoglobulin if it has formed an interaction with the antibody. The entire solution will then be examined using a fluorescence microscope. The fluorescence intensity will then be determined to identify whether there were antibodies in the serum sample.

Waiting Time for Results

It typically takes 2 to 3 days for FTA test results to be released.

Costing and Expenses

Depending on the laboratory, an FTA-ABS test may cost as high as $79 to perform.

Insurance Coverage

Unfortunately, similar to other tests, insurance policies do not typically cover FTA-ABS procedures.

Specificity and Sensitivity

FTA-ABS procedures are relatively accurate procedures with a sensitivity rate of 84% and a specificity rate of 97%.

Syphilis: Summary of Diagnosis Expenses

The following section outlines the costs incurred when performing Syphilis diagnostic tests, as well as whether the test is covered by standard insurance policies in the United States:






Average Price

Around $3.00 to $5.00

Approximately $3.60

Around $5.00


Approximately $79.00

Covered by Insurance?






Frequently Asked Questions (FAQs)

Are follow-up tests necessary for syphilis?

Not necessarily, but negative tests may sometimes prompt doctors to order a test every six weeks to rule out an ongoing infection that cannot be detected.

What other factors may affect the reliability of non-treponemal tests?

Since non-treponemal tests detect antibodies directed towards cellular damage, other conditions such as HIV, IV drug use, Lyme disease, and certain types of pneumonia may skew the results.

Are reactive treponemal tests indicative of a current infection?

Since treponemal tests may also indicate that the patient has been infected before, not necessarily. However, to ensure that the diagnosis is as accurate as possible, confirmatory tests are necessary to finalize the diagnosis.

Are there any special preparations necessary before testing?

There are no specific activities that you should do to prepare for your appointment with the laboratory in most cases. However, if you are indicated for a lumbar puncture, your doctor may instruct you to empty your bowels and bladder beforehand.

Are there any particular tasks necessary after testing?

None. However, in cases where a lumbar puncture is done, you may be instructed to lie down for a few hours to avoid a headache.


Centers for Disease Control and Prevention

World Health Organization


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Written by Mark Riegel, MD

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