Infectious Disease Compendium




Treponema pallidum is the cause of syphilis.  Use both non-specific tests (RPR/VDRL) and specific test (FTA) to diagnose.

Now days use the "reverse screening": Treponemal chemiluminescent immunoassay (CIA) is the initial syphilis screen and if postive a non-Treponemal test (Rapid Plasma Reagin, RPR), followed by another Treponemal test (Treponema pallidum Particle Agglutination, TP-PA), if indicated.

Still follow the RPR for response to therapy.

Syphilis Testing Algorithms

 The FTA is for life, the RPR should decline after treatment.  Mostly. "Although the decline in RPR titers was ≥ 4­fold among 88.0% (293/333) of participants at 3 months and ≥ 8 ­fold among 77.8% at 6 months, only 9.6% achieved complete RPR seroreversion at 6 months and 17.1% at 12 months after therapy." (PubMed).

Serological non­response is 12.1 % overall and the serofast state can occur in perhaps a third (PubMed).  The prozone effect ("Prozone phenomenon is a false negative response resulting from high antibody titer which interferes with formation of antigen- antibody lattice, necessary to visualize a positive flocculation test") can also lead to a negative VDRL but a positive FTA (PubMed).

T. pallidum subsp. endemicum causes Bejel.

Treponema carateum causes Pinta. Named after the ship that brought lues back to Spain. Not really (PubMed). But it should have been.

Treponema pallidum, subsp. pertenue causes Yaws. True story: In NE Portland growing up there was a great burger joint called Yaws, sadly now gone, but I now wonder what went into the meat.

Epidemiologic Risks

Spread by human contact, primarily sexual, occasionally from in utero. Huge increases in incidence are occurring in China, the old USSR and to a lessor extent, the US.

Rates of syphilis in men who have sex with men is 160 times that of men who have sex with women. See how your state rates as you plan the weekend (PubMed).

And planning on a trip to Japan for the 2020 Olympics (assuming N. Korea doesn't nuke the country)? The disease is skyrocketing in females who have sex with men (PubMed).

Routine screening should occur in men who have sex with men; you will find disease and prevent progression and spread from asymptomatic patients (PubMed).

In men who have sex with men, a diagnosis of syphilis has an huge association of new HIV infection in the next year (PubMed).

Treponema pallidum, subsp. pertenue can be found in Free-Range and captive Macaques, so a potential zoonotic reservoir (PubMed) as well as olive and yellow baboons, vervet monkeys, and blue monkeys making eradication problematic (PubMed). Free range macaques taste so much better.


Divided into

Primary: usually a painless, single ulcer on the body part in question.

Early Secondary: a relapsing illness fevers, rash involving palms and soles, hepatitis, adenopathy, constitutional symptoms. Hepatitis is common in HIV patients (76%), with 20% being the presenting syndrome.

Late Secondary: no symptoms while it slowly eats you from the inside.

Aortitis, which may occur earlier in the disease that we suspected (PubMed).

Tertiary: CNS disease.

General paresis: Argyll Robertson pupils, changes in personality, affect, sensorium, intellect, insight, and judgment, hyperactive reflexes, slurred speech, tremors.

Tabes dorsalis: Argyll Robertson pupils, uveitis, ataxia, bladder dysfunction, Cranial nerve involvement (II-VII), fecal incontinence, impotence, peripheral neuropathy, Rhomberg sign, shooting or lightning pains.

When to LP an HIV patient? When neurologic symptoms (duh), CD4 < 350 or serum RPR >= 1:32 (PubMed, PubMed). "The estimated prevalence of neurosyphilis among non-HIV patients with untreated latent syphilis and serum VDRL < 1:16, was below 6.2% (PubMed)."

CSF CXCL13 levels, a cytokine, may be helpful in diagnosing CNS disease (PubMed).

There may be a genetic predisposition to getting neurosyphilis (PubMed); I look forward to the day when I can test for Toll-like polymorphisms,

Meningovascular: Aphasia, hemiplegia or hemiparesis, seizures.

Uveitis, and other eye involvement (PubMed)(PubMed), is a common and increasing manifestation, they may be VDRL negative but FTA positive. Discordant serologies are a pain (PubMed) and I usually end up treating for CNS syphilis:

"Persons with serodiscordant serologies (i.e. confirmed positive treponemal and persistently negative non treponemal tests) and no history of syphilis treatment present several important clinical and public health questions, particularly since they would likely be missed by the traditional algorithm: What is their risk of transmitting syphilis sexually? What is their risk of transmitting syphilis vertically? What is their risk of progression to tertiary syphilis? … A recent retrospective review suggests that it is low. The risk of progression to tertiary syphilis in serodiscordant patients in the modern antibiotic era is unknown and ethical and logistical challenges make it unlikely that a study to address this issue will be forthcoming. Two retrospective studies (Wohrl and Tuddenham) suggest that the risk of neurosyphilis at the time of discordant test results is low. The risk of ophthalmic syphilis may be higher, but the lack of objective measures for this diagnosis makes drawing conclusions difficult."


From CDC 2002 Guidelines

(IDSA Update)

Primary: Benzathine penicillin G 2.4 million units IM in a single dose. If allergic to PCN then doxycycline 100 mg po bid x 14 d (PubMed), (PubMed).

Early Secondary: Benzathine penicillin G 2.4 million units IM in a single dose. If allergic to PCN then doxycycline 100 mg po bid x 14 d.

Late Secondary: Benzathine penicillin G 2.4 million units IM q week x 3; if allergic to PCN then doxycycline 100 mg po bid x 28 d.

Tertiary: Aqueous crystalline penicillin G 18 - 24 million units per day, administered as 3 - 4 million units IV every 4 hours or continuous infusion, for 10 - 14 days.

Probably the only time you would do penicillin desensitization is to treat tertiary syphilis and pregnancy.

What data there is suggests ceftriaxone is no worse the penicillin for primary and early latent but not secondary (PubMed), perhaps for tertiary disease (PubMed).

And doxycycline? "Among the 118 patients, the serological response rate at 12 months was 100.0% (7/7) in patients with primary syphilis, 96.9% (62/64) in patients with secondary syphilis, 91.3% (21/23) in patients with early latent syphilis, and 79.2% (19/24) in patients with late latent syphilis." (PubMed). Not bad, but still use penicillin if you can.

DO NOT EVEN THINK of using azithromycin: resistance is increasing and fails to prevent transmission to the baby.

Yaws: However, a single dose of azithromycin 30mg/kg will cure acute and latent Yaws in children but mass eradication efforts have led to azithromycin resistance.


Beware the Jarisch-Herxheimer reaction.

There is conflicting data as to whether repeat syphilis is more likely to be asymptomatic than initial syphilis, in HIV patients it appears to be the case (PubMed).

Pregnant women have to be treated with penicillin G and if allergic they have to be desensitized. Maybe. There are case reports of success with amoxicillin and ceftriaxone (PubMed). It is still the rule in pregnancy to NOT give macrolides.

As a rule of thumb, the serum RPR will fall to normal in one year with primary, 2 years with secondary and 3 years with tertiary. Usually you prove cure of CNS disease with a repeat LP, but who wants and LP. If the serum RPR falls, it is a reliable marker that the CNS disease is cured as well (PubMed).

HIV patients appear to need standard treatment. No extra penicillin needed (PubMed). The titer in HIV patients will fall slower and more likely end up seropositive after treatment, but it does not mean treatment failure (PubMed).

In some normal people, despite appropriate therapy and a fall in the serum titer, they went on to develop symptomatic neurosyphilis (PubMed).

There is "cross-reactivity of Lyme screening among syphilis-positive sera but not false-positive syphilis screening tests from previous Borrelia burgdorferi infection (PubMed).

Not related to the (classic song).

I used to worry about being reincarnated as a rabbit in a syphilis lab (why). Now I worry about being reincarnated as macaque (why).

They have reconstructed of T. pallidum genomes from archaeological material from 16th century Mexico (PubMed).

Curious Cases

Relevant links to my Medscape blog

Louie Louie, oh no Me gotta go

Lue Lue

Forgotten but not gone.

Trying to Classify an LBB

Great Pox Never Goes Away

Regrets and Records

Other Explanations Are Needed

Look. But Do Not Touch.

What's Going On?



Rich Little is Second

Alternative Facts

Last Update: 08/12/18.