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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 syphilis, and 13 congential syphilis cases per the State Health
Department Data Hub. Rates have steadily increased since, now in 2023, 104
pregnant women, with 64 reported congenital syphilis cases. 1,426 syphilis
cases were reported in 2023.
·
TENNESSEE: In Tennessee, Syphilis has increased 162%
from 2017 to 2022 (950 to 3813 cases). Syphilis among women has increased 311%
from 2017 to 2022 (290 to 1191 cases). Congenital syphilis has increased >400%
from 2017 to 2022 (11 to 61 cases). Per TN Dept of Health
Diagnosis
Who and when do we test?
Syphilis testing should be performed on patients with signs
or symptoms of infection, as well as asymptomatic patients at high risk for
infection or for transmitting to others. In TN, AR, and MS, testing during
pregnancy is REQUIRED by law. Any woman who has a fetal death after 20 weeks’ gestation should be
tested for syphilis. No mother or neonate should leave the hospital without
maternal serologic status having been Recommendations and Reports 50 MMWR /
July 23, 2021 / Vol. 70 / No. 4 US Department of Health and Human
Services/Centers for Disease Control and Prevention documented at least once
during pregnancy. Any woman who at the time of delivery has no prenatal care
history or has been at risk for syphilis acquisition during pregnancy (e.g.,
misuses drugs; has had another STI during pregnancy; or has had multiple sex
partners, a new partner, or a partner with an STI) should have the results of a
syphilis serologic test documented before discharge.
REQUIRED IN MS: In April of 2023, syphilis testing during
pregnancy was made a requirement for pregnant people in their first trimester,
third trimester, and at delivery as a part of Mississippi’s efforts to prevent
congenital syphilis in infants. Per MS Dept of Health
REQUIRED IN AR: Arkansas law requires syphilis testing during the first prenatal visit
and during the 3rd trimester (between 28-32 weeks of pregnancy).
Testing at delivery is required if not done during the pregnancy. Per AR Dept
of Health
REQUIRED IN TN:
Currently, state law requires all pregnancies be tested for syphilis in the 1st
trimester or at the 1st prenatal care visit. Rescreening for
syphilis at 28-32 weeks gestation and at delivery is highly encouraged by TDH
for ALL patients, regardless of first trimester test results. Per TN Dept of
Health
Do we test for cure?
Yes, at six and 12 months after treatment, patients with
primary syphilis should be reexamined and undergo repeat serologic testing.
Testing
Consists of dark-field microscopy and serum, tissue, or CSF
serological testing. Darkfield microscopy and polymerase chain reaction (PCR)
assays for T pallidum are not generally available in the US, and
silver-staining techniques are considered unreliable.[19] Nucleic acid
amplification tests (NAATs) can be clinically helpful but have not been
approved by the FDA for use in the US.[139][144] Therefore,
serological testing is the preferred primary diagnostic modality for syphilis. Serological
testing for syphilis is classified as either nontreponemal or
treponemal. The tradition algorithm for diagnosing syphilis is to screen with a
non-treponemal test and then if the non-treponemal test is reactive, verify
with a specific tests such as the FTA-abs, TPHA, MHATP, or ELISA. Use of only
one type of serologic test (non-treponemal or treponemal) is insufficient for
diagnosis and can result in false-negative results among persons tested during
primary syphilis and false-positive results among persons without syphilis or
previously treated syphilis
New guidelines for testing in February 2024 -> CDC
Laboratory Recommendations for Syphilis Testing, United States, 2024
Laboratories have a critical role in the public health
response to the syphilis epidemic. The responsibility of the laboratory is to
test specimens and report results in a timely manner, allowing clinicians to
efficiently make clinical diagnoses for patient management. Public health
reporting by laboratories also allows local health departments and CDC to
conduct surveillance and monitor disease trends. This report details CDC’s new
recommendations for syphilis testing, including laboratory-based tests, point-of-care
(POC) tests, processing of samples, and reporting of test results to aid
laboratorians and clinicians in the diagnosis of syphilis. Future revisions to
these recommendations will be based on new research or technologic advancements
for syphilis clinical laboratory science.
Traditional algorithm: The traditional algorithm for syphilis serologic screening begins with a
nontreponemal (lipoidal antigen) test, and any reactive specimens are tested
for confirmation by a treponemal test. This sequence has been widely used for
decades because nontreponemal (lipoidal antigen) tests were relatively
inexpensive and treponemal tests were manual, labor intensive, more costly, and
limited in number.
Reverse sequence algorithm: However, automated treponemal immunoassays, which were originally
cleared by FDA for blood bank screening, are now cleared by FDA for clinical
screening, leading to the reverse sequence algorithm. Initial screening with an
automated treponemal test of a sample with a positive result must be followed
by a quantitative nontreponemal (lipoidal antigen) test. When the reverse
sequence algorithm is used, any discordant results should be adjudicated by a
second treponemal assay (e.g., TPPA) that has a different format and includes
different antigens (85).
Each algorithm
has advantages and disadvantages and both are acceptable. The traditional
algorithm might be less sensitive in detecting early or late latent syphilis,
although an increase in false positives might occur when applying the reverse
algorithm in low-prevalence populations
The way that Baptist has chosen is to do antibody testing
first, then if positive reflex to RPR-> If discordant, do another test
Nontreponemal Tests
Nontreponemal tests for syphilis (venereal
disease research laboratory [VDRL] and rapid plasma reagin [RPR]) are screening
examinations that detect IgG and IgM antibodies to the patient's cardiolipin
that have become integrated with the T pallidum bacteria in
the blood or CSF and are therefore not specific for syphilis. The VDRL and RPR
tests are only positive after the development of the primary chancre. By the
tertiary (late) stages of syphilis, VDRL titers are usually low or
undetectable. These tests are relatively inexpensive and simple but somewhat
time-consuming to perform as they require a trained laboratory technician. Patients
with a reactive nontreponemal test should always receive a treponemal test to
confirm the syphilis diagnosis.
RPR and VDRL tests are still the primary screening methods
used in public health laboratories in the United States
Can’t interchange RPR and VDRL, example if mom gets RPR,
baby needs to get RPR. Why?
Regardless of which
test method is applied, serum antibody titers from RPR, VDRL, and other
nontreponemal (lipoidal antigen) tests should not be used interchangeably to
manage patients because they are different test methods and the subjective
titer results can vary by laboratory. Therefore, patient specimens should be
tested using the same nontreponemal (lipoidal antigen) test method and specimen
type.
Treponemal Tests
Treponemal antibody tests (fluorescent treponemal antibody
absorption assay [FTA-ABS], T pallidum particle agglutination assay [TPPA], T
pallidum hemagglutination assay [TPHA], chemiluminescent immunoassay [CIA],
enzyme immunoassay [EIA], and rapid chromatographic immunoassays) that detect
specific serum antibodies to T pallidum are considered necessary and required
for a confirmed diagnosis of syphilis when the VDRL or RPR tests are initially
positive. Of these, the most sensitive and preferred confirmatory treponemal
antibody tests would be the FTA-ABS or the TPPA for all syphilis stages, where
available, although the TPPA is considered more specific. The majority of
patients who have reactive treponemal tests will have reactive tests for the
remainder of their lives, regardless of adequate treatment or disease activity.
Reason why need both
tests?
Combination of both tests can give us ability to accurately
stage. To diagnose syphilis accurately, you must utilize both treponemal and
nontreponemal tests since they detect different aspects of the infection,
providing...
