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Deaths from syphilis were at their highest in 1995 with 102,505 deaths, with 99,248 of children under 5 making up most of those deaths.

Notice a steep decline in deaths between 2005 and 2010.

Deaths from syphilis were at their lowest in 82,212 in 2018, with 79,973 of children under 5 making up most of those deaths.

Children under 5 have consistently made up the bulk of the deaths from syphilis each year.

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Looking at the graph, you can see that American Indian/ Alaska Native men and women, and Black or African American men have the highest syphilis rates.

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Looking at the graph, you can see males between 25-29 and 30-34 have the highest rates of syphilis.

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This graph shows a trend of syphilis starting from 1941 to 2022 in the United States.

There has been a major decline in syphilis cases since 1941, however there was a spike in 1991, which cases falling back down and remaining fairly steading until 2011.

From 2011 onward, there seems to be a slow increase of cases.

It will be interesting to see how this data continues to change as time goes on.

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Having unprotected sex

Having sex with more than one partner

Live with HIV

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Use condoms.

when used correctly they can reduce the risk of contracting syphilis

They offer protection when they cover the infected area

Can still get syphilis if they do not cover the lesions

Get tested regularly!

Pregnant women should be tested for syphilis at the first prenatal care visit and treated right away if result is positive

Partner notification

Notify partners if you test positive. This will help to prevent the spread of syphilis to others

No US FDA approved vaccines

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Syphilis increases the risk of acquiring HIV as well as other STIs such as gonorrhea, chlamydia, genital herpes, and others.

If not treated, it can cause:

heart problems like angina, aortic aneurysm, and heart failure

brain problems like seizures, memory problems, personality changes, and dementia

nerve and joint problems such as shooting pains, joint pain, and gradual damage to the joints

Problems with the skin, bones, testicles, liver, and any other organ

Neurosyphilis can manifest as meningitis, stroke, cranial nerve palsies, dementia, or general paresis

Cranial nerve palsies: May cause a partial weakness or complete paralysis of the areas served by the nerves

General paresis: decline in mental functioning due to damage of the brain

Can cause HIV infection to have higher virus replication rates and lower CD4 counts

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Penicillin acts on Treponema pallidum by interfering with cell wall synthesis. By inhibiting cell wall synthesis, this would inhibit both growth and multiplication

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Antibiotic therapy

Penicillin, which is an antibiotic used to manage and treat a wide range of infections

Primary, secondary, or early latent syphilis is treated with a single dose of intramuscular (IM) benzathine penicillin G

Neurosyphilis is treated with IV penicillin G aqueous

Alternative regimen is procaine penicillin intramuscularly AND probenecid 500mg orally 4x a day for 10-14 days

Tertiary and latent syphilis and HIV-infected patients should be treated with weekly benzathine penicillin intramuscularly for 3 weeks

Congenital syphilis treated with aqueous crystallin penicillin G given by IV every 12 hours during the first seven days after birth, then every 8 hours for 10 days.

Alternative regimen is procaine penicillin intramuscularly in a single daily dose for 10 days

Pediatric syphilis treatment is aqueous crystalline penicillin G by IV every 4-6 hours for 10 days followed by a single dose of benzathine penicillin G

Penicillin of choice: Benzathine penicillin intramuscularly

Procaine penicillin is the 2nd choice

Alternative therapies :

doxycycline 100mg orally 2x a day for 14 days

ceftriaxone intramuscularly or intravenously daily for 10 to 14 days

tetracycline by mouth 4x daily for 14 days

azithromycin is no longer recommended due to reports of resistance

Doxycycline not recommended for children or pregnant women

Patients must be followed post-treatment 6, 12, and 24 months after treatment with a clinical evaluation and nontreponemal (RPR and VDRL) testing.

Re-examination at 3 and 9 months are suggested for high-risk individuals

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I will only be discussing the most common tests below.

Non-treponemal (recall that this type of test is typically done first)

RPR and VDRL detects cardiolipin antibodies produced in response to syphilis infection. These non-specific antibodies can be present in other conditions, such as lupus, which is why they are considered screening tests.

RPR: Rapid Plasma Reagin

How it is performed:

Blood is taken from the patient from the back of the hand or inside of the elbow. Fresh serum of plasma should be used.

In the lab:

Pipette 1 drop of 50 microliters of test specimen, positive control, and negative control on separate reaction circles on RPR card.

Add 1 drop of RPR antigen reagent to the positive control, negative control, and test specimen.

Mix with a mixing stick and spread uniformly over the entire reaction circle. Rotate continuously and check after 8 minutes.

Results:

Reactive: large and medium black floccules against white background

Weakly reactive: small black floccules against a white background

Non reactive: no floccules, even grey background

VDRL: Venereal Disease Research Laboratory

How it is performed:

Most often performed by taking a blood sample, but can be done using a sample of spinal fluid.

In the lab:

heated serum or unheated cerebrospinal fluid is mixed with reagin (a purified mixture of lipids such as cardiolipin, lecithin, and cholesterol) on a glass slide. Clumping of the mixture is read microscopically

Results:

Reactive: clumping occurs

Non-reactive: no clumping

Treponemal tests:

FTA-ABS: Fluorescent treponemal antibody absorption

detects the presence of antibodies specifically against T.pallidum

usually performed if pt has a positive VDRL and RPR test

How it is performed:

Blood is drawn.

Serum is diluted in 1:5 sorbent. The absorbed serum is layered on a microscope slide which contains fixed T.pallidum

If the patient's serum contains antibodies, the antibodies will coat the treponema.

Later, fluorescein isothiocyanate (FTIC) is added which combines with the patient's antibodies that are adhering to T.pallidum and results in a visible test reaction when examined by fluorescent microscopy.

Results:

Negative result: no presence of antibodies to T.pallidum

Positive result: presence of antibodies to T. pallidum

results will be positive even if the pt has been previously diagnosed and successfully treated

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Requires 2 different serologic test be positive

healthcare professionals also need to consider presence or absence of clinical disease and any prior hx of syphilis

Two types of tests: Serologic and non-serologic tests

Serologic tests: Non-treponemal and treponemal:

Non-treponemal

start with this test and if it is positive then move to treponemal tests

usually react with IgM and IgG antibodies

non-specific

Include tests called: Rapid Plasma Reagin, Venereal Disease Research Laboratory, Toluidine Red Unheated Serum Test

results usually reported as a titer of the antibody reflecting the number of dilutions where activity is still detected

Treponemal

Detects antibodies to specific treponemal antigens

specific

once positive, remains positive for life

Includes tests called: Fluorescent treponemal antibody absorption, microhemaglutination test for antibodies to T.pallidum, T.pallidum agglutination assay, T.pallidum enzyme immunoassay, and chemiluminescence immunoassay

Results of these tests are reported as reactive or non-reactive

Non-serologic tests:

Done on biopsies of active lesons

Darkfield microscopy used to see spirochete on dark field illumination

Direct fluorescent antibody: fluorescent antibody binds to treponemal antigen given them a bright green appearance

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T.pallidum remains poorly understood due to the difficulties of working with this pathogen, including the inability to grow T.pallidum in a pure culture

Progress in the understanding of pathogenesis of syphilis is hindered by several limitations

inability to grow T.pallidum continuously in vitro in pure culture

its envelope is fragile compared to more conventional gram-negatives organisms due to a very thin peptidoglycan layer that is only loosely associated to the outer membrane

Displays a very low density (small concentration) of proteins on its surface

not much is known about the membrane proteins, but they have the potential to be virulence factors

Tp0954 was predicted to be a surface lipoprotein of T.pallidum. It was seen on a physiologically related derivative strain, Borrelia burgdorferi which causes Lyme disease

protein was shown to help promote its binding to epithelial and non-epithelial cells

suggests that the lipoprotein may initiate infection by colonizing skin epithelium and may also contribute to disseminated (spread of) infection and colonization of distal tissues

also found to facilitate binding to cells derived from placenta as well as placental tissues

suggests this protein may be responsible for infecting fetus in pregnant women

Genome sequence does not reveal any obvious classical virulence factors that could account for syphilis signs and symptoms

it lacks a lipopolysaccharide, which is an endotoxin found in the outer membrane of many gram-negative bacteria that causes fever and inflammation.

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Congenital Syphilis

Can cause spontaneous abortion, stillbirth, death of the neonate, premature delivery, and disease in the infant

Affected infants typically have low weight at birth

Pulmonary hemorrhage, secondary bacterial infections, and severe hepatitis cause death of approximately 4% of infected neonates soon after delivery.

Divided into stages: early manifestations appearing in the first 2 years of life, late manifestations appearing after 2 years, and residual stigmata

Early manifestations: severe symptoms of adult secondary syphilis

becomes apparent in 2-10 weeks after delivery

Late manifestations: may cause damage to cornea and iris, 8th nerve deafness, neurosyphilis, bilateral effusions (collection of fluid) of knees and elbows, and Hutchinson's teeth

becomes apparent between 5-25 years old

Primary syphilis

Initiated when T.pallidum penetrates dermal microabrasions (skin injuries) or intact mucous membranes, typically resulting in a single chancre sore at the site of inoculation.

chancre sores commonly appear on penis, labia, cervix, rectum, anal canal, and oral cavity

diagnosis can be delayed if chancre sore is in an inconspicuous anatomical site and because they are usually painless

development of sore is on average of 3 weeks after being exposed and heals within 4-6 weeks

Secondary Syphilis

Usually takes 3 months for symptoms to manifest

sore throat, malaise, weight loss, body rash, swollen lymph nodes, infection of hair follicles results in alopecia of the scalp

body rash usually found on palms of hands and soles of the feet

Latent syphilis

No visible symptoms

Manifestations of secondary syphilis usually resolves spontaneously within 3 months and symptoms are absent for a variable amount of time

Two stages:

Early latent syphilis for the first year after infection.

25% may have recurrent secondary manifestations

Late latent syphilis for those who are asymptomatic for longer than one year or for unknown duration

ends when antibiotic therapy is administered or when manifestations of tertiary disease develops

Tertiary syphilis

Without treatment, syphilis can spread to the brain, nervous system, the eyes, or the ears.

can also happen during any of the above stages

can develop 10-30 years after infection

Symptoms

Inflammation causing gumma, which is a

a localized form of tissue and bone destruction and may also occur in the liver, heart, brain, stomach, and upper respiratory tract

Cardiovascular syphilis which can result in aortic insufficiency or aneurysm

Neurosyphilis which can lead to severe headache, muscle weakness, and/or trouble with muscle movements, changes in your mental state, and/or dementia

Ocular syphilis which can cause eye pain and/or redness, changes in your vision, and even blindness

Otosyphilis can lead to hearing loss, tinnitus, dizziness, or vertigo

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Organism enters the body through direct contact, usually sexual, with active primary or secondary lesions.

Organism can also cross the placenta and infect the fetus

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Gram-negative bacteria

Shape: thin, tightly coiled spirochetes

Structure: thin layer of peptidoglycan

Motility: endoflagella allow for corkscrew motility and are located in perisplasmic space

Able to carry out glycolysis but not Kreb's cycle or electron transport chain

Cannot survive outside of the host

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Treponema pallidum, which is T.pallidum for short

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Syphilis