Can syphilis be undetected in tests?

Syphilis is a sexually transmitted infection caused by the bacterium Treponema pallidum. It is spread through direct contact with a syphilis sore, which mainly occurs during vaginal, oral, or anal sex. Syphilis can cause serious health complications if not treated properly, so getting tested and treated is crucial.

Can syphilis go undetected on tests?

Yes, it is possible for syphilis to go undetected on initial screening tests. Here are some key points:

• Screening tests like the nontreponemal antibody tests (RPR or VDRL) do not directly detect the syphilis bacteria. Rather, they detect antibodies that the body produces in response to a syphilis infection.
• It can take 3-4 weeks for the body to produce enough antibodies to be detectable on these screening tests after initial syphilis infection.
• If a person is tested during this early window period before sufficient antibodies have developed, the screening test may miss the infection.
• The screening tests also cannot distinguish between a new active syphilis infection versus an old treated infection.

For these reasons, there is a chance syphilis will not be detected on an initial screening test. However, the infection can then be detected on follow-up tests once antibody levels rise.

When is syphilis most likely to be undetected?

There are two main time periods when syphilis is most likely to be missed on testing:

1. Early syphilis: Syphilis is most likely to be undetected during the first 1-4 weeks after infection. This is due to the window period before antibodies reach detectable levels.
2. Late/latent syphilis: If syphilis remains untreated, the infection can exist in a latent form where antibody levels fluctuate and drop to low levels. This can cause false negative test results later on.

So the beginning and late stages of syphilis infection carry the highest risk of undetected results on screening tests.

Who is at highest risk for having undetected syphilis?

The following groups have the highest likelihood of having syphilis go undetected:

• People who have been recently exposed to syphilis through unprotected sex, especially men who have sex with men (MSM).
• People with new or multiple sex partners.
• People with HIV infection.
• Pregnant women – syphilis can cause complications in pregnancy if undetected.

Those who suspect they may have been exposed to syphilis should get tested, and be re-tested after the window period if initial results are negative.

How can syphilis be accurately detected?

To maximize the detection of syphilis, health providers can:

• Use both a treponemal test and nontreponemal test together. Combining these two types of tests increases diagnostic accuracy.
• Retest after 1-4 weeks if syphilis exposure is suspected but initial results are negative. This allows more time for antibodies to develop.
• Screen high-risk groups, such as sexually active MSM, more frequently to detect any new infections.
• Use direct detection methods such as darkfield microscopy or PCR tests. However, these are not widely available.

Pregnant women should be screened for syphilis early in pregnancy and again in the third trimester to detect any new infections. Prompt treatment can prevent transmission to the fetus.

What are the stages of syphilis infection?

Syphilis progresses through the following stages if not treated:

1. Primary syphilis: The first signs are a single or multiple chancres (sores) at the site of infection. This lasts 2-6 weeks.
2. Secondary syphilis: Rash, fever, sore throat, fatigue, and other flu-like symptoms occur. The rash commonly occurs on the palms and soles. This stage lasts 2-10 weeks.
3. Latent syphilis: Symptoms resolve but the infection remains in the body. Early latent syphilis is still contagious. Late latent syphilis is unlikely to be contagious but can progress to late stage complications.
4. Tertiary syphilis: Severe late stage complications like neurosyphilis and cardiovascular syphilis can occur 10-30 years after infection, leading to organ damage and death.

The latent period where symptoms disappear can lead to undetected syphilis if testing is not done. Syphilis remains in the body if not treated.

What are the complications of untreated syphilis?

If syphilis goes undetected and untreated, it can lead to severe complications over time such as:

• Neurosyphilis: Syphilis bacteria spread to the brain and spinal cord leading to headache, dementia, numbness, blindness, and stroke.
• Cardiovascular syphilis: Inflammation of the heart and blood vessels causing heart disease.
• Gummas: Soft growths that form on organs like the skin, bones, liver.
• Congenital syphilis: Syphilis passes from a mother to her fetus leading to birth defects and infant death.

In addition, having syphilis increases the risk of acquiring and transmitting HIV.

What are the syphilis screening tests?

There are two main types of syphilis screening tests:

1. Nontreponemal antibody tests: RPR (rapid plasma reagin) and VDRL (Venereal Disease Research Laboratory). Detects antibodies to cardiolipin released during infection.
2. Treponemal antibody tests: TP-PA (T. pallidum particle agglutination), FTA-ABS (fluorescent treponemal antibody absorption), EIAs (enzyme immunoassays). Detects antibodies to T. pallidum proteins.

Both types of tests are done initially for screening and supplemental testing. The nontreponemal test may need to be repeated to monitor response to treatment.

Key differences between syphilis screening tests:

Test	Nontreponemal (RPR/VDRL)	Treponemal (TP-PA/FTA-ABS/EIA)
Antibodies detected	Against cardiolipin released by host cells	Against Treponema pallidum antigens
When positive	Active or treated syphilis infections	Past and present syphilis infections
Possibility of false positives	Yes – with some other conditions	Rare

How long before syphilis antibodies are detectable?

On average, it takes:

• 1-4 weeks for nontreponemal antibodies (RPR/VDRL) to become detectable after syphilis infection.
• 1-4 weeks for treponemal antibodies (TP-PA/FTA-ABS/EIA) to become detectable.

However, up to 25% of people may take longer to develop detectable antibodies. Treponemal antibodies tend to appear slightly sooner but both can take 3-4 weeks. This window period around the time of initial infection carries the highest risk of having undetected syphilis.

Can syphilis reinfections go undetected?

Yes, it is possible to get reinfected with syphilis, including in people who were previously treated and cured. Reinfections can sometimes go undetected for the following reasons:

• A previous syphilis infection may give a lifelong positive result on treponemal antibody tests even after treatment and cure. So a positive test may be falsely attributed to past infection instead of new infection if not careful.
• People may assume they cannot be reinfected and may not get regularly retested after initial treatment.
• If the reinfection occurs soon after treatment, antibodies may still be circulating and mask new infection.

To detect possible syphilis reinfections, clinicians should closely monitor groups at high risk with both treponemal and nontreponemal tests to detect increasing antibody titers.

How is neurosyphilis detected?

Neurosyphilis, one of the most severe complications of untreated syphilis, occurs when the infection spreads to the brain and spinal cord. To help detect neurosyphilis, additional lab tests may be done such as:

• Cerebrospinal fluid (CSF) VDRL: Looks for antibodies against syphilis in the CSF. A reactive CSF VDRL is highly specific for neurosyphilis.
• CSF cell count: Elevated white blood cells in CSF can indicate inflammation due to neurosyphilis.
• CSF protein: Increased CSF protein levels can indicate neurosyphilis.

These CSF tests allow detection of neurosyphilis that may not be identified on standard syphilis blood tests. Symptoms like vision changes, headaches, and neurological deficits also provide clues to possible neurosyphilis.

Conclusion

In summary, syphilis can sometimes go undetected, especially during the early window period before antibodies develop and in latent stages. Using both treponemal and nontreponemal antibody tests, repeating testing at intervals, and evaluating high-risk groups can improve detection. If syphilis is missed and progresses to late stage disease, it can have severe complications like neurosyphilis and congenital syphilis. That’s why ongoing public health efforts focused on better screening, treatment, and preventing ongoing transmission remain vital for syphilis control.