Syphilis Testing and Management

Hosts: Jake Lancaster MD, Chief Medical Information Officer and Amanda Comer DNP, System Director, Advanced Practice Providers

Guest: Alex Yoby, Pharmacist

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CDC’s Sexually Transmitted Infections (STI) Treatment

Guidelines, 2021

Notable updates:

These guidelines discuss 1) updated recommendations for

treatment of Neisseria gonorrhoeae, Chlamydia trachomatis, and

Trichomonas vaginalis; 2) addition of metronidazole to the recommended

treatment regimen for pelvic inflammatory disease; 3) alternative treatment

options for bacterial vaginosis; 4) management of Mycoplasma genitalium;

5) human papillomavirus vaccine recommendations and counseling messages; 6) expanded risk factors for syphilis testing

among pregnant women; 7) one-time testing for hepatitis C infection; 8)

evaluation of men who have sex with men after sexual assault; and 9) two-step

testing for serologic diagnosis of genital herpes simplex virus

Syphilis

Lore

It is postulated that syphilis came to Europe in the 1490s when Columbus

arrived in Italy from America. After Italy surrendered to the invading French

in 1495, this new disease rapidly spread across Europe. The name

"syphilis" comes from the work of Girolamo Fracastoro, a noted poet

and physician in Verona, Italy. In 1530, he wrote about a shepherd named

Syphilus who angered Apollo, causing the god to curse the entire population

with the affliction that we now know as syphilis

T. pallidum

Syphilis is a systemic, bacterial infection caused by

Treponema pallidum.  Treponema are thin,

Gram-negative, slowly metabolizing spirochetal bacterium, requiring an average

of 30 hours to multiply. It is microaerophilic and cannot grow on standard

culture media. Treponema pallidum’s outer membrane lacks lipopolysaccharides

and has few surface-exposed unique proteins, making it difficult for the immune

system to fight the infection. Because of this characteristic, T

pallidum is labeled as a stealth pathogen. T. pallidum is the

only Treponema species that causes sexually transmitted disease.

Syphilis is characterized by a wide range of variable

clinical symptoms that can resemble other diseases, which make it difficult to

diagnose without a test, therefore, it is often referred to as “The Great

Imitator”. The infection progresses through multiple stages (primary,

secondary, latent, and tertiary) and can affect virtually every organ system in

the body, even many years or even decades after the original infection.

Infected people are contagious during the primary and secondary stages of

syphilis.

Stages of syphilis

Primary syphilis: Primary syphilis classically

presents as a single painless ulcer or chancre at the site of infection but can

also present with multiple, atypical, or painful lesions. A chancre is defined

as a firm, round, painless ulcer at the site of entry of an infecting organism.

Chancres appear 10 to 90 days (median of 21 to 25 days) after exposure to the

infecting organism. While the chancre represents the initial local reaction to

the infection, the bacteria quickly become widely disseminated in the body,

including the cerebrospinal fluid, even without any additional immediate

symptoms. Up to 70% of early syphilis patients will demonstrate cerebrospinal

fluid (CSF) changes consistent with neurosyphilis, and 30% will have direct

evidence of T pallidum.  Despite this occurrence, very few will develop

clinical neurosyphilis.

Secondary syphilis: A diffuse and extensive

maculopapular rash that includes the palms of the hands and the soles of the

feet, as well as oral lesions in the mouth, are the characteristic cutaneous

manifestations of secondary syphilis. Symptoms typically appear 2 to 8 weeks

after the disappearance of the primary chancre and have multiple systemic

manifestations that can involve any system or body part. The T pallidum multiply

and spread rapidly, causing fevers, myalgias, headaches, anorexia, sore throat,

weight loss, joint pain, malaise, and particularly, the cutaneous

manifestations characteristic of secondary syphilis. Enlarged lymph nodes

are common in this stage and are usually described as firm, rubbery, and with

only minimal tenderness. The lesions of secondary syphilis generally resolve

within a few weeks, even without treatment, but will relapse in 25% of

untreated patients, usually within 12 months. After that, without treatment,

the disease enters the latent stage, and about 33% of patients will eventually

develop tertiary syphilis.

Tertiary syphilis: Late symptomatic disease that can

manifest months, years, or even decades after the initial infection as

cardiovascular syphilis (aortic aneurysm, aortic valvulopathy), neurosyphilis

(meningitis, hemiplegia, stroke, aphasia, seizures, spinal neuroarthropathy,

tabes dorsalis, syphilitic paresis), or gummatous syphilis (infiltration of any

organ and its subsequent destruction).

Latent syphilis: Latent syphilis is defined as

syphilis characterized by seroreactivity without other evidence of primary,

secondary, or tertiary disease. Latent infections (i.e., those lacking clinical

manifestations) are detected by serologic testing. Latent syphilis acquired

within the preceding year is referred to as early latent syphilis; all other

cases of latent syphilis are classified as late latent syphilis or latent

syphilis of unknown duration. Latent syphilis is not transmitted sexually

Neurosyphilis: T. pallidum can infect the CNS, which

can occur at any stage of syphilis and result in neurosyphilis. Early

neurologic clinical manifestations or syphilitic meningitis (e.g., cranial

nerve dysfunction, meningitis, meningovascular syphilis, stroke, and acute

altered mental status) are usually present within the first few months or years

of infection. Late neurologic manifestations (e.g., tabes dorsalis and general

paresis) occur 10 to >30 years after infection.

Congenital syphilis: Congenital syphilis results from

transplacental transmission or contact with infectious lesions during birth and

can be acquired at any stage, often causing stillbirth or neonatal

congenital infections. Without treatment, up to 40% of women with syphilis will

have stillborn births, and many more will have premature labor or

low-birth-weight babies.

Effective prevention and detection of congenital syphilis

depends on identifying syphilis among pregnant women and, therefore, on the

routine serologic screening of pregnant women during the first prenatal visit

and at 28 weeks’ gestation and at delivery for women who live in communities

with high rates of syphilis, women with HIV infection, or those who are at

increased risk for syphilis acquisition. Certain states have recommended

screening three times during pregnancy for all women; clinicians should screen

according to their state’s guidelines.

Epidemiology

Per the CDC, a syphilis

epidemic is occurring in the United States, with sustained increases in primary

and secondary syphilis from 5,979 cases reported in 2000 to 133,945 cases

reported in 2020, a 2,140% increase

The rate of reported congenital syphilis in the United

States has increased dramatically since 2012.

About 53 percent of congenital syphilis is reported from

southern states, according to data from the U.S. Centers for Disease Control

and Prevention.

3,761 cases of

congenital syphilis in the United States were reported to CDC in 2022.

including 231(6%) stillbirths and 51(1%) infant deaths. 88% of cases of

congenital syphilis in 2022 were directly impacted by the lack of timely

testing and adequate treatment during pregnancy.

·        

MISSISSIPPI: In 2022, Mississippi ranked 5th in

reported rates of primary and secondary syphilis with a rate of 31.1 per

100,000 individuals (the rate was 28.1 per 100,000 individuals in 2021).

Mississippi also ranked 6th in reported rates of congenital syphilis with a

rate of 207.6 per 100,000 live births (the rate was 182.0 per 100,000 live

births in 2021).

·        

ARKANSAS: In 2017, only 27 pregnant women with

reported...