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What causes syphilis

Syphilis is a sexually transmitted infection (STI) caused by the bacterium Treponema pallidum. It can also be transmitted vertically, from mother to child, and via contact with blood. In many high-income countries, it is most prevalent in men who have sex with men (MSM), but it can also occur in other demographic groups. Early pregnancy screening in most countries includes testing for syphilis. It is entirely treatable and preventable, but unfortunately, there are only a few countries in which mother-to-child transmission has been eradicated, such as Cuba and Thailand.

Although unlikely, it is still possible to encounter sexually active teenagers who have syphilis. More commonly, congenital syphilis is a problem many paediatricians face. It is the third most prevalent bacterial STI internationally, after chlamydia and gonorrhoea. Its worldwide prevalence is around 0.5-0.7%, and six million people get syphilis each year. It is estimated that around 100,000 to 200,000 people per year die from syphilis; most of these are young children, due to congenital syphilis. Syphilis has been around for centuries and has been a subject for many great artists.

Edvard Munch, “Inheritance” (1897), Munch Museum, Oslo, Norway

The stages of syphilis

A list of symptoms will never be exhaustive; the disease is known as “The Great Imitator” for a reason. Classically, there are three disease stages:

First stage: a chancre also known as ulcus durum. This is a hard, usually single, ulcer found in the genital area or elsewhere.

Second stage: skin and mucosa lesions such as condylomata lata, hepatitis, nephrotic syndrome, cranial nerve damage.

Third stage: neurosyphilis, such as tabes dorsalis, demyelination of sensory pathways in the dorsal root ganglia, and dementia paralytica or heart problems, such as aneurysms or coronary arteritis. The third stage can often occur decades after infection.

The natural history of STIs in many patients, both adults or children, is often initially asymptomatic. The first presenting symptoms or signs in syphilis may be in its later stages. Around 60-90% of neonates with congenital syphilis are asymptomatic at birth. Most only develop symptoms after three months of age.

Congenital syphilis

Early: includes skin defects (maculae, condylomata lata, roseolae), persistent rhinitis, failure to thrive, hepatomegaly, splenomegaly, neurological problems, lymphadenopathy, fever, and skeletal problems (osteochondritis, periostitis).

Late (after two years of age): deafness, keratitis, more pronounced skeletal issues (such as dental problems – known as Hutchinson’s teeth – and saddle nose).        

Syphilis can have the following consequences in pregnant women:

  • Spontaneous abortion
  • Intra-uterine death
  • Premature birth or babies with very low birthweight
  • Congenital syphilis; mother-to-child transmission is very likely if the mother is in the first or second stage of syphilis and not treated. Around 40% of affected cases result in foetal or perinatal death.

Diagnosing syphilis

It is not useful nor possible to diagnose syphilis, or any STI, based on reported symptoms or observed signs during clinical examination. If you suspect that a child has syphilis, you should test for it.

There is no gold standard testing of syphilis. Refer to your local or national guidelines, as testing algorithms may vary a little and can be complicated. Most algorithms use non-treponemal blood tests such as venereal disease research laboratory (VDRL) and rapid plasma reagin (RPR) to screen for the disease. VDRL and RPR however can be false-positive – if the test is positive, they are followed by a treponemal test to confirm the patient has syphilis. Several point-of-care tests have become available in the past decades, some of which have excellent performance. These tests can be incorporated in testing algorithms, by performing a point-of-care test first and, if positive, using an RPR test for confirmation. In the case of neurosyphilis, testing of liquor may be needed. The diagnosis of neurosyphilis in newborns is notoriously difficult. Treponemal bacteria can also be detected using dark field microscopy or PCR performed on ulcer swabs.

When syphilis is proven in sexually active teenagers, it is important to also test for other STIs , the “big five”: HIV, hepatitis B, chlamydia, gonorrhoea, and trichomoniasis. In babies with congenital syphilis, test for HIV and hepatitis B. Do not forget to refer the parents of a child with congenital syphilis for testing and treatment. In children beyond the infant years diagnosed with syphilis, always consider the possibility of sexual abuse.


  • There is no vaccine against syphilis.
  • Prevention of mother-to-child transmission by screening pregnant women and treating them (and testing their sexual partners) yields excellent results.
  • Condom use decreases transmission risk but doesn’t entirely eliminate it as skin-to-skin contact with ulcers may still be possible.

How do we treat syphilis?

Treatment is best done in cooperation with an infectious disease expert. Primary and secondary syphilis is treated with antibiotics, usually a single shot of intramuscular benzathine benzylpenicillin. Congenital syphilis is treated intravenously with aqueous crystalline penicillin G for 10 days, increased to 10-14 days in neurosyphilis. Pregnant women are treated weekly for three weeks with benzathine benzylpenicillin. Ceftriaxone, erythromycin, and doxycycline can be alternatives, but are less suitable for pregnant women. After treatment, careful serological follow-up is necessary to assess the effectiveness of treatment.

A well-known side-effect of syphilis treatment is the Jarisch–Herxheimer reaction in which endotoxins released from dying Treponema pallidum bacteria trigger a strong inflammatory response leading to fever, rash, tachycardia, and hypotension. 

The bottom line

Syphilis is fortunately rare in many places nowadays but it still causes great morbidity and mortality worldwide, especially in children.

Symptoms vary greatly, so testing should be performed if you suspect syphilis.

Literature list

Arrieta AC & Singh J. Congenital syphilis. NEJM 2019;381:2157.

Galvis AE & Arrieta A. Congenital Syphilis: A U.S. Perspective. Children 2020;7:203.

Golden MR et al. Update on syphilis – resurgence of an old problem. JAMA 2003;290:1510-14.

Keuning MW et al. Congenital syphilis, the great imitator-case report and review. Lancet ID 2020;20:e173-e179.

Kliegman R (editor). Nelson textbook of pediatrics. Edition 21. Philadelphia, PA: Elsevier, 2020.

Ortiz DA et al. The traditional or reverse algorithm for diagnosis of syphilis: pros and cons. CID 2020;71:S43-S51.

Verwijs MC et al. Targeted point-of-care testing compared with syndromic management of urogenital infections in women (WISH): a cross-sectional screening and diagnostic accuracy study. Lancet ID 2019;19:658-79.

World Health Organization. WHO guidelines for the treatment of Treponema pallidum (syphilis). Available at:


  • Marijn is a resident in paediatrics at the Sophia Children's Hospital in Rotterdam, the Netherlands. He is interested in infectious diseases, neonatology, and acute medicine. In his free time he likes to play tennis, read books, and worship his two cats.



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