SyphilisLesson 3. SyphilisLearning Objective Performance Indicators
Last Updated: October 21st, 2022 Authors: David H. Spach, MD David H. Spach, MD Disclosures: None , Meena S. Ramchandani, MD Meena S. Ramchandani, MD, MPH Disclosures: Shareholder: Gilead Sciences Reviewer: Khalil G. Ghanem, MD, PhD Khalil G. Ghanem, MD, PhD Disclosures: None Introduction
Syphilis is a systemic infection caused by Treponema pallidum, a spirochete bacterium that is transmitted primarily through sexual activity or with vertical transmission during pregnancy. Cases of syphilis, including congenital syphilis, have risen substantially in recent years in the United States. In the absence of treatment, persons who acquire T. pallidum remain chronically infected and can develop an array of clinical manifestations. Syphilis characteristically progresses in stages (primary, secondary, latent, and tertiary), with episodes of active clinical disease interrupted by periods of latent infection; neurologic manifestations can occur at any of these stages (Figure 1).[1,2] Chronic disease can result in significant morbidity, potentially affecting nearly every organ system, and rarely, can result in death. In addition, untreated syphilis in pregnant women can lead to fetal demise and devastating congenital infection for the neonate. Epidemiology in the United States
2020 Syphilis Surveillance DataAlthough surveillance reporting of syphilis cases includes data for multiple syphilis stages, the reported cases for primary and secondary syphilis most accurately represent new infections. During the past 80 years in the United States, the incidence of syphilis has fluctuated (Figure 2).[3] Since the year 2000, the reported number of syphilis cases in the United States has dramatically increased, peaking at 133,945 reported cases (of all stages) in 2020 (Figure 3).[3] In 2020, a total of 41,655 cases of primary and secondary syphilis were reported, which represents a 75% increase from 2015 and the highest reported number of cases since 1992.[3] In recent years, there reported cases of syphilis in women have increased, in conjunction with a sharp increase in the number of cases of congenital syphilis.[3] The following summarizes several key epidemiologic features for syphilis as reported in the United States for the year 2020.[3] Note: the Centers for Disease Control and Prevention (CDC) surveillance report provides data on gender that is based on sex assigned at birth (male and female) and therefore the terms male and female are used below.[3]
Factors Associated with Syphilis DiagnosisPersons with the highest rates of syphilis include MSM and individuals with HIV (men or women).[3,5] Additional factors associated with an increased rate of syphilis include age younger than 29 years, a history of incarceration, methamphetamine use, injection drug use, and exchanging sex for money or drugs.[5,6,7] Among MSM, the use of methamphetamine has been associated with a substantially increased risk of acquiring syphilis.[7] ImpactUntreated syphilis can result in major morbidity and rarely in death. In the United States, the estimated lifetime cost for syphilis infections acquired in 2018 was $173.7 million.[8] This estimate correlated with an approximate lifetime cost per syphilis infection of $1,190. The overall lifetime medical cost for syphilis represented about 1% of the $15.9 billion lifetime cost for all sexually transmitted infections acquired in the United States in 2018; notably, HIV accounted for approximately $13.7 billion of those total lifetime medical costs.[8] Microbiology, Pathogenesis, and Transmission
Organism and ClassificationThe etiologic agent in syphilis is Treponema pallidum—from the Greek terms trepo (“to turn”) and nema (“thread”) and the Latin term pallida (“pale”).[9] Treponema pallidum belongs to the spirochete class and is a corkscrew-shaped, motile microaerophilic bacterium that cannot be viewed by normal light microscopy (Figure 10). Until recently, isolation of T. pallidum required a live rabbit-model system, but new methods have led to successful long-term in vitro cultivation and propagation of T. pallium.[10,11,12] This spirochete bacterium is thin (0.1 to 0.18 micrometers in diameter) and 6 to 20 micrometers in length (Figure 11).[13] Treponema pallidum has been erroneously described as a gram-negative bacterium, but this organism lacks lipopolysaccharide (LPS), a hallmark of gram-negative organisms.[14] Which one of the following statements is TRUE regarding the biology of Treponema pallidum?Check Which one of the following statements is TRUE regarding the biology of Treponema pallidum?Treponema pallidum can be cultured in most microbiology labs if special culture media is used Treponema pallidum can be visualized via standard light microscopy with a modified Gram's stain Treponema pallidum is a motile spirochete bacterium that is approximately 6 to 20 micrometers in length Treponema pallidum is an atypical gram-negative bacterium that lacks lipopolysaccharide and is approximately 0.1 to 0.3 micrometers in length TransmissionThe major routes of transmission for T. pallidum are sexual (during the primary and secondary stages of syphilis) and hematogenous (in utero via transplacental spread to a fetus).[15] During sexual transmission, T. pallidum enters the body via skin and mucous membranes through macroscopic and microscopic abrasions during sexual contact.[14] Persons who acquire T. pallidum are contagious to their sex partners throughout the primary and secondary stages of infection—when lesions or rash are present.[14,16] Although sexual transmission of T. pallidum usually results from contact at genital mucous membranes, it can also occur at other body areas, including the mouth, anorectal areas, and cutaneous lesions. Maternal transmission predominantly occurs via transplacental passage of T. pallidum during maternal spirochetemia; less often, transmission can occur if the newborn has contact with maternal genital lesions at the time of delivery.[14,17] In contrast to sexual transmission of syphilis, which nearly always occurs in early stages of syphilis, vertical transmission can occur during any stage of syphilis. Other forms of hematogenous transmission of T. pallidum are rare: transfusion-associated syphilis has been virtually eliminated in the United States, and transmission through needle-sharing with injection drug use is infrequent.[15] Which one of the following statements is TRUE regarding transmission of
Treponema pallidum?Check Which one of the following statements is TRUE regarding transmission of Treponema pallidum?Transmission most often occurs via airborne respiratory droplets during the secondary stage Transmission is frequently transmitted through fomites (contaminated objects) and with gastrointestinal secretions Transmission most often occurs during the early stages of syphilis through contact with infected mucosal surfaces or skin lesions Transmission can occur with about the same risk at any stage of syphilis Clinical Manifestations
Syphilis has often been called “the great imitator” because so many of the signs and symptoms may be difficult to differentiate from those of other diseases.[15,18,19,20] Early after infection, before clinical signs or symptoms appear, T. pallidum can spread to the circulatory system, the lymphatic system, regional lymph nodes, and the central nervous system. Early clinical manifestations (primary and secondary stages) predominantly involve the skin and mucosal surfaces, although secondary syphilis may be accompanied by systemic manifestations.[15,21] Latent disease has no clinical signs or symptoms, but late manifestations (seen after years of infection) may affect virtually any organ system. Neurosyphilis, ocular syphilis, and otosyphilis can occur at any stage of infection. Obtaining a detailed history is critical for determining the duration of infection and assessing for the possibility of reinfection. Assessment should include the following:
Primary SyphilisFollowing the inoculation of T. pallidum at the entry site, organisms proliferate, sensitize lymphocytes, and activate macrophages, causing the formation of a primary lesion or “chancre” at the site of inoculation.[16] If clinically evident, the chancre appears about 2 to 3 weeks (range 10 to 90 days) after the acquisition of T. pallidum.[2,15] Chancres progress from a papule to an ulcer, which is typically painless, round to oval, indurated, well-circumscribed, with a clean base and heaped up margins.[1] Less often, individuals with primary syphilis may develop multiple, painful anogenital lesions.[22] The most common sites where chancres develop include the penis (Figure 12), labia, perianal region, or mouth (Figure 13).[1,15] Regional firm lymphadenopathy often develops in proximity to primary syphilitic lesions.[23,24] Syphilitic chancres are highly infectious and heal spontaneously (without treatment) in approximately 3 to 8 weeks.[2,15] If untreated, persons with primary syphilis may subsequently develop other manifestations of syphilis. Evaluation of any sexually active persons with a genital or perianal ulcer should include testing for syphilis and genital herpes.[25] Secondary SyphilisSecondary lesions reflect hematogenous dissemination of T. pallidum and generally appear 4 to 10 weeks after the onset of the primary chancre.[2] In fewer than 10% of cases, primary and secondary stages may overlap.[15] Signs and symptoms of secondary syphilis are often the first observed clinical manifestation of syphilis, as primary lesions are often overlooked or not recognized.[15] Relapses of secondary symptoms occur in up to 25% of untreated persons.[2] A wide array of manifestations can occur with secondary syphilis:[1,20]
Latent SyphilisLatent syphilis is a stage of syphilis characterized by the persistence of T. pallidum organisms in the body without causing signs or symptoms. Periods of clinical latency may occur between the primary and secondary stages, between secondary relapses, and after the secondary stage. The diagnosis of latent syphilis is made when an individual has (1) seroreactivity indicating infection with T. pallidum, (2) no past diagnosis of syphilis, and (3) no active manifestations of syphilis.[26] Latent syphilis is classified into early latent and late latent.[26,27] When evaluating an individual with latent syphilis, the health care provider should inquire about prior symptoms of primary or secondary syphilis, determine whether sexual contact occurred with a partner with primary or secondary syphilis within the past year, perform an examination to look for syphilis-related manifestations, and review all prior syphilis serologic test results.
Tertiary SyphilisTertiary syphilis is rare because of the widespread availability of antibiotics, enhanced screening for syphilis, and treatment for early syphilis. Without treatment, however, approximately 30% will progress to the tertiary stage at 2 to 50 years after the original infection.[1] Tertiary syphilis most often manifests as gummatous lesions and cardiovascular syphilis; late neurosyphilis, such as general paresis, tabes dorsalis, and psychiatric manifestations, are also often categorized as tertiary syphilis.[1] Otic and ocular syphilis are less common manifestations of tertiary syphilis.[1] Gummatous lesions are formed by a proliferative granulomatous process and can form in almost any tissue or organ.[1,15] The destructive lesions can clinically mimic carcinoma. Cardiovascular syphilis is indicated by pathologic lesions of the aortic vasa vasorum, can manifest as an ascending aortic aneurysm, aortic valve insufficiency, or coronary artery disease.[15] NeurosyphilisNeurosyphilis occurs when T. pallidum invades the central nervous system, and this may occur at any stage of syphilis; neurosyphilis is categorized as early neurosyphilis and late neurosyphilis.[2,28] Ocular and otic involvement can occur with early or late infection.[1]
Which one of the following statements is TRUE regarding
neurosyphilis?Check Which one of the following statements is TRUE regarding neurosyphilis?Neurosyphilis occurs only in persons with late latent syphilis Neurosyphilis occurs only in persons with early latent syphilis Neurosyphilis can occur in persons with early or late latent syphilis, but not with secondary syphilis Neurosyphilis can occur in persons with secondary, early latent, or late latent syphilis Ocular SyphilisSince T. pallidum can potentially infect any part of the eye, a broad range of symptoms and manifestations associated with ocular syphilis may occur with or without neurosyphilis.[32,33,34] Ocular syphilis can develop at any stage of syphilis and can cause acute or chronic symptoms.[33] Although ocular syphilis can involve virtually any region of the eye, the most common clinical presentation is uveitis—anterior, posterior, or panuveitis (Figure 17).[33,34] Other described manifestations include lid involvement, episcleritis, vitritis, papillitis, interstitial keratitis, retinitis, and optic neuritis.[33] The clinical presentation of ocular syphilis can have significant overlap with other infectious and noninfectious eye diseases. Persons with syphilis who have ocular complaints should have a complete cranial nerve evaluation and receive a referral to an ophthalmologist for an immediate evaluation.[26] In addition, if any cranial nerve abnormalities are present, a lumbar puncture should be performed with cerebrospinal fluid analysis to determine if concomitant neurosyphilis is present.[26] OtosyphilisOtic involvement from T. pallidum infection can occur at any stage of syphilis, and persons with otosyphilis usually present with hearing loss, tinnitus, or vertigo, or a combination of these manifestations.[35,36] The hearing loss with otosyphilis is typically sensorineural and can involve one or both ears.[35,36] Otosyphilis can develop with other syphilis manifestations, including neurosyphilis or ocular syphilis. Thus, individuals with suspected or diagnosed otosyphilis should undergo an initial screening evaluation for neurosyphilis and ocular syphilis.[36] Persons with a suspected diagnosis of otosyphilis should receive a referral for an immediate evaluation by an otolaryngologist.[26] Individuals with a positive serologic test for syphilis who have isolated auditory symptoms and a normal neurologic examination do not require lumbar puncture with cerebrospinal fluid examination.[26] Congenital SyphilisCongenital syphilis occurs when T. pallidum is transmitted from a pregnant woman with syphilis to her fetus.[14,17] Less often, perinatal transmission of T. pallidum can occur at the time of the delivery if the newborn has contact with maternal genital lesions.[14,17] Untreated syphilis during pregnancy may result in a wide range of outcomes, including infant death, stillbirth, birth of an infant with clinical signs or symptoms, and birth of infant with no documented signs or symptoms (Figure 18).[3,37,38] Transmission to the fetus in pregnancy can occur during any stage of syphilis, but the risk is much higher with primary or secondary syphilis, especially if the mother acquires T. pallidum in the third trimester of pregnancy.[3] Fetal infection can occur during any trimester of pregnancy. Congenital syphilis is traditionally classified as either early or late disease.[16] Early manifestations occur within the first two years of life, and late manifestations occur after two years of age. Although infants with congenital syphilis most often display some early manifestations, some do not have clinical manifestations of active disease at the time of birth or early in life. Accordingly, regardless of symptoms, all neonates with a reactive serologic test for syphilis or who are at risk for congenital should undergo a thorough examination for signs or symptoms of congenital syphilis, as well as testing for HIV.[26]
Laboratory Diagnosis
The laboratory diagnosis of syphilis is challenging and requires using a combination of clinical and laboratory criteria to differentiate active infection, prior infection, and absence of infection.[41,42] Serologic testing remains the primary tool for diagnosis in most patients with syphilis, and these tests include nontreponemal and treponemal tests.[41,43,44] Treponema pallidum cannot be cultivated in artificial media, but the organism can be grown using special techniques that involve inoculation in rabbits. The following summarizes the different test types used for diagnosing syphilis. All persons diagnosed with syphilis should also have HIV testing. Direct Detection of Treponema pallidumDark-Field MicroscopyDark-field microscopy of lesion exudate or tissue is a definitive method for making an immediate diagnosis of primary or secondary syphilis.[26,41] Treponema pallidum cannot be viewed by normal light microscopy. Dark-field microscopy can identify T. pallidum with its spiral shape, a total length of 6 to 20 micrometers, and corkscrew motion (Figure 21).[45] Dark-field microscopy is infrequently used in clinical practice because most facilities do not have dark-field microscopy, and most clinicians do not know how to appropriately obtain specimens. The specificity of dark-field on oral specimens is extremely poor due to the abundant non-syphilitic oral Treponema species. Polymerase Chain ReactionAlthough polymerase chain reaction (PCR) testing is sometimes used for research purposes, there is no FDA-approved PCR test for syphilis at present. Direct Fluorescent Antibody TestThe direct fluorescent antibody test can detect T. pallidum antigens in tissue samples. The test uses antibodies specific to pathogenic treponemes and can generally identify T. pallidum in samples—such as oral or rectal lesions—that may have background nonpathogenic spirochetes.[42] Tissue StainingSilver staining and immunohistochemical staining of tissue samples can demonstrate characteristic spirochetes on clinical biopsy specimens.[41] Serologic Testing for SyphilisSerologic testing for syphilis involves the use of two types of serologic tests—treponemal and nontreponemal.[43] Use of only one type of serologic test is insufficient for diagnosis since each test used alone has major limitations, including false-positive results in persons without syphilis and the inability for treponemal tests to distinguish between recent and distant infection. Treponemal Serologic TestsThe treponemal serologic tests include various enzyme immunoassays (EIAs) and chemiluminescence immunoassays (CIAs), as well as the T. pallidum particle agglutination (TP-PA) and fluorescent treponemal antibody absorption (FTA-ABS) tests.[41] These tests measure antibodies directed against T. pallidum antigens by enzyme immunoassay immunofluorescence (Figure 22) or particle agglutination; most detect IgG only, whereas some detect both IgM and IgG. These qualitative tests most often remain reactive for life, even after adequate treatment, but 15 to 25% of persons treated during the primary stage of syphilis eventually revert to being serologically nonreactive with a treponemal serologic test.[46] Nontreponemal Serologic TestsThe commonly used nontreponemal tests are the Venereal Disease Research Laboratory (VDRL) and the Rapid Plasma Reagin (RPR) tests.[41] The nontreponemal tests, which measure antibodies directed against lipoidal antigens, such as cardiolipin and lecithin, are not specific for T. pallidum.[47] Positive test results are then reported as a quantitative titer, which typically correlates with disease activity.[26] A fourfold change in titer, equivalent to a change of two dilutions (e.g. from 1:16 to 1:4 or from 1:8 to 1:32), is considered necessary to demonstrate a clinically significant difference.[43] The nontreponemal tests are labor-intensive to perform, and biologic false-positive tests can occur from multiple causes, including pregnancy, autoimmune diseases, HIV, hepatitis C virus, other treponemal infections, and immunizations.[47] For monitoring persons with syphilis, sequential serologic tests should use the same testing method (VDRL or RPR) and preferably in the same laboratory. Further, when evaluating congenital syphilis, the neonate and mother should have the same type of nontreponemal test used for comparison. Several years after effective syphilis treatment, the nontreponemal tests usually become nonreactive (or persist at a very low titer).[43] In addition, some individuals with syphilis will have seroreversion to a negative syphilis test even without syphilis treatment. Performance of Serologic Tests for SyphilisThe common patterns for serologic reactivity with syphilis tests depend on the specific test used, the stage of syphilis, and whether the person has received treatment for syphilis.[43,44,48] The sensitivity of serologic testing also varies based on the test used and the stage of syphilis (Table 1).[42,44] Serologic testing for syphilis has the highest yield for secondary syphilis. Serologic tests for syphilis may be negative during very early primary syphilis, especially with nontreponemal tests.[43,48] Thus, when serologic tests do not correspond with clinical findings suggestive of primary syphilis, presumptive treatment is recommended if the person has known risk factors for syphilis; in this setting, use of other tests, such as dark-field microscopy, biopsy, or PCR, should be considered.
Prior Serologic Testing for SyphilisThe health care professional should determine the date and results of the most recent serologic test for syphilis, even if the person under evaluation reports no history of the disease. Prior results, if available, are particularly helpful when evaluating an individual who has a low titer for a nontreponemal serologic test for syphilis, no signs or symptoms that suggest a clinical diagnosis of syphilis, and no known contact with an early case of syphilis. Local health departments can usually provide information on whether the person has been reported as having had syphilis in the past, including reported serologic test results and treatment history. Serologic Testing AlgorithmsGiven that treponemal and nontreponemal tests each have significant advantages and disadvantages, these lab tests are used together as part of a screening algorithm in order to maximize sensitivity and specificity for the detection of syphilis infection. Clinicians should be aware of their institution’s chosen method for syphilis serologic testing. The two main serologic testing algorithms used by laboratories are traditional sequence screening and reverse sequence screening. The major advantages of using the reverse sequence algorithm, when compared with the traditional screening method, include improved detection of early primary and treated infection, lower cost of the initial screening test, and reduced laboratory time and effort with the initial screening test. The CDC, however, does not recommend one screening method over the other. Traditional Screening AlgorithmThe traditional syphilis screening algorithm uses initial screening with a nontreponemal test (VDRL or RPR), with further testing on a positive initial test using a treponemal test (TP-PA or EIA) (Figure 23).[14,26] Persons who have an initial negative nontreponemal test are considered unlikely to have syphilis, unless they have early syphilis from a recent exposure. Persons with a positive initial nontreponemal result require a treponemal test (usually TP-PA); if this treponemal test is positive, then a diagnosis is confirmed.[26] If the treponemal test is negative, then a diagnosis of syphilis is unlikely, and the positive nontreponemal test may represent a biologic false-positive test result. Reverse Sequence Screening AlgorithmThe reverse sequence screening algorithm uses a treponemal test (EIAs or CIAs) as the initial screening test (Figure 24).[54] A negative initial treponemal result essentially rules out the diagnosis of syphilis, except for persons with a very recent exposure to T. pallidum. A positive initial EIA or CIA test requires further testing with a quantitative nontreponemal test (e.g. RPR or VDRL).[26,54] If this nontreponemal test is positive and there is no history of prior treatment for syphilis, then a diagnosis of syphilis is confirmed, and treatment is indicated. With a positive initial treponemal test (EIA or CIA) and a negative nontreponemal test (RPR or VDRL), a second different treponemal test (TP-PA) should be performed.[26,54] If this second treponemal test is negative, then syphilis is unlikely. If, however, the sequence of tests is a positive treponemal test, a negative nontreponemal test, and a positive second treponemal test, then several possible scenarios exist: prior treated syphilis, early syphilis, untreated latent syphilis, or a false-positive test. In this situation, those with a prior history of syphilis treatment do not require further management unless there has been a known reexposure to syphilis after completing prior treatment. Those without a prior history of treatment should be offered treatment, typically for late latent syphilis, unless their history or examination indicates a recent exposure or other syphilis-related complications, such as neurologic involvement.[54] Positive Titers in Persons Previously Treated for SyphilisAlthough persons with early syphilis who are treated usually have a fourfold or greater decline in nontreponemal titers within 12 months after treatment, some fail to achieve seroreversion at month 12.[55] Persons previously treated for syphilis who had a documented adequate reduction in nontreponemal titer after treatment may have a persistent low-positive nontreponemal titer that does not significantly change; this is referred to as “lack of seroreversion” or “serofast state”, and does not require additional therapy. Persons with prior treatment who have nontreponemal titers that are higher or unchanged (the titer did not decline 4-fold) from the pretreatment values are either treatment failures or have been reinfected with T. pallidum. Laboratory Evaluation for NeurosyphilisAll persons with a positive serologic test for syphilis and any new neurologic signs or symptoms should have a lumbar puncture with cerebrospinal fluid (CSF) analysis.[26] Persons with ocular syphilis or otosyphilis do not require CSF examination, unless they have concomitant neurologic symptoms or signs.[26] In this situation, the laboratory diagnosis of neurosyphilis should take into account the CSF white blood cell count, CSF protein (in persons without HIV), and CSF VDRL.[26] An elevated CSF white blood cell count and elevated CSF protein can support the diagnosis of neurosyphilis, but are not diagnostic, since these findings are common in persons with untreated primary and secondary syphilis, even without any neurologic abnormalities.[56] The CSF VDRL has high specificity, but the sensitivity is low; the CSF RPR is not recommended for evaluation of neurosyphilis.[26,28,57] The diagnosis of neurosyphilis is considered highly likely if a person has the following three findings: a positive serologic test, neurologic clinical manifestations, and a positive CSF VDRL (in the absence of blood contamination of the CSF). Because of the low sensitivity of CSF VDRL, when this test is negative and a person has suspected neurosyphilis, additional testing should occur with a CSF treponemal test (FTA-ABS).[56,58] Persons who have a negative CSF FTA-ABS (or TP-PA) are highly unlikely to have neurosyphilis.[26] In addition, CSF protein is not used for diagnosing neurosyphilis in persons with HIV. Diagnosis of Syphilis in Persons with HIVIn general, the clinical course and diagnostic evaluation of syphilis in persons with HIV is similar to that in persons without HIV.[26] Although not common, unusual serologic responses among persons with HIV can occur. If the clinical suspicion of syphilis is high and the serologic tests for syphilis are negative, then use of other tests (e.g. biopsy of the lesion or rash) should be considered. Conventional therapy is usually effective. Several studies have shown that CSF abnormalities (mononuclear pleocytosis and elevated protein) are more common in persons with HIV who have a CD4 count of 350 cells/mm3 or less and/or a nontreponemal serologic test titer of greater than or equal to 1:32.[26] For persons with HIV, a lumbar puncture with CSF examination should be reserved for those with neurologic manifestations.[26] Since persons with HIV may have slight elevations in CSF white blood cell counts at baseline, some experts suggest using a higher cutoff (white blood cell count greater than 20 cells/mm3) to improve the specificity of this test as a component of the neurosyphilis diagnosis.[56] Diagnosis of Syphilis in Infants and ChildrenThe diagnosis of congenital syphilis is often difficult since maternal nontreponemal and treponemal IgG antibodies can be transferred through the placenta to the fetus; the treponemal antibodies can persist for 15 months or longer.[26] Evaluation and treatment of congenital syphilis is complex and should ideally include expert consultation. The decision to treat a neonate (aged fewer than 30 days) is based on (1) identification of syphilis in the mother; (2) adequacy of maternal treatment; (3) clinical, laboratory, and radiographic evidence of disease in the neonate; and (4) comparison of maternal and neonatal nontreponemal serologic titers.[26] Based on the evaluation and test results, neonates are classified as:[26]
Reporting RequirementsLaws and regulations in all states require clinicians, laboratories, or both to report persons diagnosed with syphilis (including congenital syphilis) to local public health authorities. Reporting can be done by medical providers, laboratories, or both. Screening for Syphilis
In the United States, the main recommendations for syphilis screening are from the 2021 STI Treatment Guidelines and the 2016 US Preventive Services Task Force (USPSTF) Recommendation Statement on Screening for Syphilis Infection in Nonpregnant Adults and Adolescents.[5,26] These recommendations both identify MSM and persons with HIV as high priority groups for routine syphilis screening.[5,59,60] The following summarizes the most recent syphilis screening recommendations in the 2021 STI Treatment Guidelines.[26,60] Men and Nonpregnant Women [60]
Men Who Have Sex with Men [60,61]
Pregnant Women [60,62]
Persons with HIV [60]
Transgender and Gender Diverse People [60,63]
Correctional Facilities [64]
Treatment
General ConsiderationsPenicillin G, administered parenterally, is the preferred drug for treating all stages of syphilis.[26] The preparation(s) of penicillin used (e.g. benzathine, aqueous procaine, or aqueous crystalline), the dosage, and the length of treatment depend on the stage and clinical manifestations of the disease. Benzathine penicillin G is slowly released from the intramuscular site due to extremely low solubility and is also hydrolyzed to penicillin G; the combination of slow absorption and hydrolysis results in prolonged low serum levels of penicillin with this preparation. Benzathine-procaine penicillin coformulations and oral penicillin preparations are not appropriate for the treatment of syphilis.[26] Reports have identified the inappropriate use of benzathine-procaine penicillin (Bicillin C-R) instead of the standard benzathine penicillin G (Bicillin L-A) product.[65] Treatment of Primary and Secondary Syphilis in AdultsParenteral penicillin G is effective in resolving clinical symptoms associated with primary and secondary syphilis and prevents late sequelae in those who receive appropriate treatment. The recommended regimen for adults with primary and secondary syphilis is benzathine penicillin G given as 2.4 million units once as a single intramuscular dose (Table 2).[26] Treatment of Primary or Secondary Syphilis with Penicillin AllergyFor persons who report a penicillin allergy, it is important to determine the severity of the reaction, if the reaction was consistent with an IgE-mediated reaction, and whether the reaction occurred within the prior 10 years. Among all persons who self-report a history of an allergic reaction to penicillin or another beta-lactam antibiotic, only 7.1% had a positive objective test that confirmed the penicillin allergy.[66] In addition, approximately 80% of persons with a true IgE-mediated allergic reaction to penicillin will lose sensitivity to penicillin after 10 years.[67] The optimal treatment of primary and secondary syphilis in persons with a true documented allergy to penicillin is unknown due to limited available data. The following summarizes alternative regimens to consider for persons allergic to penicillin; individuals receiving one of these alternative regimens should have close follow-up after treatment.[26]
Treatment of Latent Syphilis in AdultsThe treatment of individuals with latent syphilis requires appropriate classification into early latent syphilis (acquired less than 1 year ago as detailed above) or late latent syphilis (acquired longer than 1 year ago). The main goal of treating persons with latent syphilis is to prevent the development of late syphilis manifestations. Early latent syphilis is treated with intramuscular benzathine penicillin G 2.4 million units given as a single dose; late latent syphilis is treated with intramuscular benzathine penicillin G 7.2 million units total, which is split into three weekly doses, each with 2.4 million units (Table 3).[26] Alternative therapies for treatment of latent syphilis have not been well studied. Treatment of Latent Syphilis in Persons Allergic to PenicillinFor penicillin-allergic, nonpregnant persons with early latent syphilis, the treatment approach should be the same as penicillin-allergic persons with primary or secondary syphilis. For penicillin-allergic individuals with late latent syphilis, the only acceptable treatment alternatives are a 28-day course of oral therapy with either doxycycline (100 mg orally twice daily) or tetracycline (500 mg orally four times daily).[26] Ceftriaxone may be a reasonable option in this setting, but the optimal number of doses or schedule has not been determined, and use of ceftriaxone to treat latent syphilis should involve consultation with a specialist.[26] All persons treated with an alternative regimen should have close serologic and clinical follow-up, especially individuals with HIV. Persons for whom adherence and follow-up are a concern should ideally undergo penicillin desensitization and receive treatment with benzathine penicillin G.[26] Treatment of Tertiary Syphilis in AdultsThe recommended regimen for tertiary syphilis (without evidence of neurosyphilis) is benzathine penicillin G 7.2 million units total divided into three weekly intramuscular injections of 2.4 million units with each dose (Table 4).[26] All persons diagnosed with tertiary syphilis should undergo a CSF examination prior to starting therapy due to the high rates of neurosyphilis that is not clinically apparent.[26] Some experts treat tertiary cardiovascular syphilis with a neurosyphilis regimen, regardless of the CSF results.[26] Treatment of Tertiary Syphilis in Persons Allergic to PenicillinPersons diagnosed with tertiary syphilis who have a documented penicillin allergy also should be treated in consultation with an expert; for these individuals, there is inadequate data for any alternative regimens.[26] Treatment of Neurosyphilis, Ocular Syphilis, and Otosyphilis in adultsThe recommended treatment regimen for neurosyphilis, ocular syphilis, and otosyphilis is aqueous crystalline penicillin G 18-24 million units per day, given as 3-4 million units intravenously every 4 hours (or as continuous infusion), for a total of 10 to 14 days (Table 5).[26] If adherence to therapy can be ensured, an acceptable alternative is a 10- to 14-day course of intramuscular procaine penicillin G 2.4 million units once daily plus probenecid 500 mg orally four times a day.[26] Some experts recommend giving additional therapy with intramuscular benzathine penicillin G 2.4 million units once per week for up to 3 weeks—starting after the completion of the 10- to 14-day regimen—to provide a total duration of therapy comparable to the treatment for late latent syphilis; although this approach is often used, data are lacking to support this enhanced treatment regimen.[26] In addition, there is insufficient data to support the use of systemic corticosteroids as adjunctive therapy for neurosyphilis, ocular syphilis, or otosyphilis. Treatment of Neurosyphilis in Persons Allergic to PenicillinLimited data suggest that intramuscular or intravenous ceftriaxone 1-2 grams daily for 10 to 14 days can be used as an alternative treatment for persons with neurosyphilis who are allergic to penicillin.[26,74] Other regimens have not been adequately studied for use in persons with neurosyphilis. Which one of the following regimens would
you recommend for treatment?Check A 32-year-old man is diagnosed with secondary syphilis and neurosyphilis. He does not have any antibiotic allergies, and he recently had a negative HIV-1/2 antigen-antibody test. Which one of the following regimens would you recommend for treatment?Benzathine penicillin G 4.8 million units total, administered as 2 doses of 2.4 million units IM each at 1-week intervals Benzathine penicillin G 7.2 million units total, administered as 3 doses of 2.4 million units IM each at 1-week intervals 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 Ceftriaxone 1 g IV daily for 3 days Treatment of Syphilis in Adults with HIVThe recommended treatment of all stages of syphilis (primary, secondary, latent, or tertiary) and neurosyphilis in persons with HIV is the same as for persons without HIV (Table 6).[26] Available data suggest that persons with HIV may have an increased risk of developing neurologic complications and may have higher rates of treatment failure (based on inadequate serologic response).[26,75] All persons with HIV who are diagnosed with syphilis should undergo careful neurologic, ocular, and otic examination, and those with abnormal findings should promptly undergo lumbar puncture for CSF examination.[26] Initiation of antiretroviral therapy for HIV concurrently with syphilis treatment may improve clinical response to syphilis treatment.[76] Delays in Treatment DosesFor persons scheduled to receive a weekly 3-dose benzathine penicillin G treatment regimen, unplanned delays can occur between the scheduled weekly doses. When these delays occur, the optimal management is not clear. Although the pharmacokinetic profile of benzathine penicillin G suggests an interval of 7 to 9 days between doses is optimal and preferred, clinical experience suggests that an interval of 10 to 14 days between doses for the treatment of late latent syphilis (or latent syphilis with unknown duration) might be acceptable.[21] For nonpregnant persons, an interval greater than 10 to 14 days warrants restarting therapy. For pregnant women, if an interval between penicillin doses exceeds 9 days, the 3-dose benzathine penicillin G treatment regimen should start over.[26,77] Treatment of Syphilis in PregnancyAll pregnant persons diagnosed with syphilis should receive treatment according to stage of infection and whether there is any evidence of neurologic disease. Treatment of pregnant women is a very high priority to minimize the risk of maternal transplacental transmission of T. pallidum. All pregnant persons with a diagnosis of syphilis should receive treatment with penicillin, with the exact regimen based on the state of disease and whether neurologic involvement is present. There are no recommended alternative regimens for the treatment of pregnant women with syphilis.[26] Accordingly, pregnant women with syphilis who have an allergy to penicillin should undergo desensitization and receive treatment with penicillin.[26] Some experts recommend giving a second dose of intramuscular benzathine penicillin G 2.4 million units 1 week after the initial dose for pregnant women who have primary, secondary, or early latent infection. Treatment of the mother during the last month of pregnancy or with a drug other than penicillin is not considered adequate treatment for the fetus. Pregnant women should be informed that treatment for syphilis may precipitate early labor and that they should notify an obstetrician if problems develop. Treatment of Neonates and Infants and Children with SyphilisThe approach to treating congenital syphilis depends on whether the child is younger than 1 month of age (neonate) or ≥1 month of age (infants and children).[26] The evaluation and treatment of congenital syphilis is complex and should include a syphilis expert.
Jarisch-Herxheimer ReactionThe Jarisch-Herxheimer reaction is a self-limited reaction associated with initiation of antitreponemal therapy. This reaction represents a systemic inflammatory response following the antimicrobial treatment of T. pallidum—it is not an allergic reaction to penicillin. The Jarisch-Herxheimer reaction most often involves persons treated for early syphilis, particularly secondary syphilis, presumably because of the higher bacterial burden during the early stages.[26] When this reaction occurs, it typically begins within several hours after initiation of antimicrobial treatment and nearly always by 24 hours. The Jarisch-Herxheimer reaction is characterized by fever, malaise, nausea, vomiting, and, less frequently, chills, hypotension, or an exacerbation of a secondary syphilis rash.[78] This reaction can be mistaken as an allergic reaction to penicillin. Accordingly, it is important to carefully evaluate any reaction that begins within 24 hours after treatment of syphilis and carefully sort out the likelihood of a Jarisch-Herxheimer reaction versus an allergic reaction to penicillin. The management of Jarisch-Herxheimer is supportive care, primarily with fluids and antipyretics; typically, the reaction resolves spontaneously within 24 hours.[15] Post-Treatment Follow Up
Post-Treatment Follow-Up TestingThe follow-up of persons with syphilis is extremely important to document response to therapy and to reevaluate for reinfection. The following are general recommendations for follow-up after syphilis treatment.[26]
Follow-Up ManagementA key reason for close follow-up of persons treated for syphilis is to monitor signs, symptoms, or serologic changes in nontreponemal titers that indicate possible treatment failure or reinfection. Changes in nontreponemal titers are described as a quantitative fold increase (Figure 25) or quantitative fold decrease (Figure 26), based on the comparison of baseline and follow-up nontreponemal titers. In general, the goal is to achieve a 4-fold or greater decline in nontreponemal titer and this is often referred to as having an “adequate serologic response” or “serologic cure”. In contrast, the failure to achieve a 4-fold or greater decline in the nontreponemal titer within an appropriate timeframe after treatment is termed “inadequate serologic response” or “lack of serologic response” or “serologic nonresponse”.[26,81] Several factors have been identified with a lack of 4-fold decline in nontreponemal titers, including a lower pretreatment titer (e.g. less than 1:8), older age, and later stage of syphilis; a prior history of syphilis treatment is associated with a slower decline in titers.[81,82] The term “serofast” has also been used to describe any persistent nontreponemal titer after treatment, including inadequate serologic response and persistently positive nontreponemal titers despite an appropriate 4-fold decline in titers.[83,84] The following summarizes the recommended evaluation and management of several post-treatment scenarios.[26]
Management of Sex Partners
Evaluation and Treatment of Sex PartnersIn general, the transmission of T. pallidum between sex partners only occurs when the person with syphilis has mucocutaneous lesions. In general, all persons who have sexual contact with a person diagnosed with primary, secondary, or early latent syphilis infection should undergo evaluation, testing, and treatment for syphilis, as outlined below.[26]
Expedited Partner TherapyExpedited partner therapy is not recommended for sexual contacts of persons diagnosed with syphilis. Counseling and Education
The following summarizes key counseling messages for persons diagnosed with syphilis.
Summary Points
Check-On-Learning Questions Display OptionsThese quick questions are meant to keep you on track and check your understanding. They appear throughout the core concepts and are listed here for you to review. Inline Questions Disabled. Inline display of questions has been disabled. Click the Display Options button to change your preferences. Which one of the following statements is TRUE regarding the biology of Treponema pallidum?Check Which one of the following statements is TRUE regarding the biology of Treponema pallidum?Treponema pallidum can be cultured in most microbiology labs if special culture media is used Treponema pallidum can be visualized via standard light microscopy with a modified Gram's stain Treponema pallidum is a motile spirochete bacterium that is approximately 6 to 20 micrometers in length Treponema pallidum is an atypical gram-negative bacterium that lacks lipopolysaccharide and is approximately 0.1 to 0.3 micrometers in length Which one of the following statements is TRUE regarding transmission of Treponema pallidum?Check Which one of the following statements is TRUE regarding transmission of Treponema pallidum?Transmission most often occurs via airborne respiratory droplets during the secondary stage Transmission is frequently transmitted through fomites (contaminated objects) and with gastrointestinal secretions Transmission most often occurs during the early stages of syphilis through contact with infected mucosal surfaces or skin lesions Transmission can occur with about the same risk at any stage of syphilis What is condylomata lata?Check A 22-year-old man is diagnosed with syphilis and condylomata lata. What is condylomata lata?A term used to describe persons with primary syphilis who have large, irregular chancres Moist, wart-like papular lesions that develop in 10 to 20% of persons with secondary syphilis Multiple cauliflower-like warts that emerge in secondary syphilis as a result of Treponema pallidum upregulation of human papillomavirus in genital epithelial cells A rare cutaneous disorder manifested as growths on the scalp in persons with tertiary syphilis How would you classify the current stage of syphilis for this woman?Check A 31-year-old transgender woman with HIV presents for a routine follow-up visit. Five months ago she developed a maculopapular rash that resolved on its own; she now has a Rapid Plasma Reagin (RPR) titer of 1:128. She had a negative serologic test for syphilis 9 months ago. How would you classify the current stage of syphilis for this woman?Syphilis of unknown duration Early latent syphilis Late latent syphilis Tertiary syphilis Which one of the following statements is TRUE regarding neurosyphilis?Check Which one of the following statements is TRUE regarding neurosyphilis?Neurosyphilis occurs only in persons with late latent syphilis Neurosyphilis occurs only in persons with early latent syphilis Neurosyphilis can occur in persons with early or late latent syphilis, but not with secondary syphilis Neurosyphilis can occur in persons with secondary, early latent, or late latent syphilis What
is the prozone effect?Check A 22-year-old man has a clinical diagnosis of secondary syphilis but has a negative nontreponemal Rapid Plasma Reagin (RPR) test with a titer of 1:1. A clinician suspects the nontreponemal test is negative due to the “prozone effect.” What is the prozone effect?A false-negative nontreponemal syphilis test due to antigen excess from persons with autoimmune diseases A false-negative nontreponemal syphilis test due to delayed antibody response with Treponema palladium infection A false-negative nontreponemal syphilis test due to extremely high serum antibody levels in response to Treponema palladium infection A false-negative nontreponemal syphilis test due to immunodeficiency What is the recommended treatment for this man?Check A 29-year-old man develops a diffuse rash 5 weeks after having sexual contact with a new male partner. Testing for syphilis shows a positive Venereal Diseases Research Lab (VDRL) test of 1:256. He is diagnosed with secondary syphilis. He does not have any antibiotic allergies. What is the recommended treatment for this man?Azithromycin 1 g orally as a single dose Ceftriaxone 1 g IV as a single dose Benzathine penicillin G 2.4 million units IM in a single dose Benzathine penicillin G 7.2 million units total, administered as 3 doses of 2.4 million units IM each at 1-week intervals Which
one of the following regimens would you recommend for treatment?Check A 32-year-old man is diagnosed with secondary syphilis and neurosyphilis. He does not have any antibiotic allergies, and he recently had a negative HIV-1/2 antigen-antibody test. Which one of the following regimens would you recommend for treatment?Benzathine penicillin G 4.8 million units total, administered as 2 doses of 2.4 million units IM each at 1-week intervals Benzathine penicillin G 7.2 million units total, administered as 3 doses of 2.4 million units IM each at 1-week intervals 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 Ceftriaxone 1 g IV daily for 3 days Citations
Additional References
Figures Figure 2. Syphilis Cases, United States, 1941-2020 NOTE: Data collection for syphilis began in 1941; however, syphilis became nationally notifiable in 1944. This graphic shows the number of reported cases of syphilis for all stages, primary and secondary, and early non-primary non-secondary. Source: Centers for Disease Control and Prevention. Sexually Transmitted Disease Surveillance 2020. Syphilis. Atlanta: U.S. Department of Health and Human Services; April 2022. Figure 10. Treponema pallidum—Electron Micrograph This electron micrograph shows the 'corkscrew' shape of Treponema pallidum growing in cultures of cottontail rabbit epithelium cells. Source: Centers for Disease Control and Prevention Public Health Image Library (CDC/Dr. David Cox). Figure 11. Treponema pallidum—Photomicrograph This photomicrograph shows an isolated Treponema pallidum spirochete bacterium approximately 6 to 20 micrometers in length and 0.1 to 0.18 micrometers in width. Source: Centers for Disease Control and Prevention Public Health Image Library (CDC/Susan Lindsley, 1972). Figure 12. Primary Syphilis—Penile Chancre This patient with primary syphilis had a large firm ulcerated lesion on the penis accompanied by right-sided inguinal adenopathy. Photograph credit: Negusse Ocbamichael, PA; Public Health—Seattle & King County Sexual Health Clinic Figure 13. Primary Syphilis—Oral Chancre This woman with primary syphilis developed an oral chancre at the right corner of her mouth. Syphilitic chancres are typically round, firm, and painless. Photograph credit: Centers for Disease Control and Prevention Public Health Image Library (Robert E. Sumpter, 1967). Figure 14 (Image Series). Secondary Syphilis—Rash This patient with secondary syphilis developed a diffuse erythematous macular rash prominent on the chest, back, palms, and soles. Photograph credit: Negusse Ocbamichael, PA; Public Health—Seattle & King County Sexual Health Clinic Figure 14B. Diffuse Rash on Back This patient with secondary syphilis developed a diffuse erythematous macular rash prominent on the chest and back. Photograph credit: David H. Spach, MD Figure 15. Secondary Syphilis—Oral Lesions This patient with secondary syphilis had multiple shallow ulcerations on the tongue (black arrows). Photograph credit: Negusse Ocbamichael, PA; Public Health—Seattle & King County Sexual Health Clinic Figure 16. Secondary Syphilis—Condylomata lata This patient with secondary syphilis developed multiple vulvar and intertriginous condylomata lata lesions; these lesions typically appear as moist, gray, raised papules, often resembling warts (condyloma acuminata). Photograph credit: Centers for Disease Control and Prevention Public Health Image Library (CDC/J.Pledger, 1976). Figure 17. Normal Eye Anatomy The uvea includes three structures: iris, ciliary body, and choroid Illustration by David Ehlert, Cognition Studio, Inc. Figure 18. Congenital Syphilis — Reported Cases by Vital Status and Clinical Signs and Symptoms* of Infection, United States, 2015–2019 *Infants with signs/symptoms of congenital syphilis have documentation of at least one of the following: long bone changes consistent with congenital syphilis, snuffles, condyloma lata, syphilitic skin rash, pseudoparalysis, hepatosplenomegaly, edema, jaundice due to syphilitic hepatitis, reactive CSF-VDRL, elevated CSF WBC or protein, or evidence of direct detection of T. pallidum. Source: Centers for Disease Control and Prevention. Sexually Transmitted Disease Surveillance 2019. Syphilis. Atlanta: U.S. Department of Health and Human Services; April 2021. Figure 19. Congenital Syphilis—Palatal Perforation This photograph shows an intraoral view of a perforation in the hard palate caused by congenital syphilis. Photograph credit: Centers for Disease Control and Prevention Public Health Image Library (CDC/Robert E. Sumpter, 1967). Figure 20. Congenital Syphilis—Hutchinson's Teeth This photograph demonstrates the triangular-shaped deformity of an upper central incisor (top arrow) and a lower lateral incisor (lower arrow) dentition within the oral cavity of a person with a history of congenital syphilis. These dental abnormalities are known as Hutchinson incisors. Photograph credit: Centers for Disease Control and Prevention Public Health Image Library (CDCRobert E. Sumpter, 1967). Figure 21. Treponema pallidum—Dark-Field Microscopy This photomicrograph shows the typical 'corkscrew' appearance of several Treponema pallidum spirochetes with the dark-field microscopy technique. Source: Centers for Disease Control and Prevention Public Health Image Library (CDC/Renelle Woodall, 1969). Figure 22. Treponema pallidum Indirect Fluorescent Antibody (FA) Serologic Test The fluorescent treponemal antibody absorption (FTA-ABS) test uses indirect fluorescent antibody technique in serum samples. This image shows abundant Treponema pallidum spirochetes with the use of a sample treated with Fluorescent Treponemal Antibody (FTA) antigen. The specimen shown here is enhanced by ultraviolet (UV) illumination. Source: Centers for Disease Control and Prevention Public Health Image Library (CDC/Russell, 1967). Figure 23. Syphilis Serologic Screening—Traditional Sequence Algorithm The traditional (standard) serologic screening sequence algorithm uses a quantitative nontreponemal test (RPR or VDRL) for screening followed by a treponemal test for confirmation of positive screening tests. Source: Centers for Disease Control and Prevention (CDC). Discordant results from reverse sequence syphilis screening--five laboratories, United States, 2006-2010. MMWR Morb Mortal Wkly Rep. 2011;60:133-7. Figure 24. Syphilis Serologic Screening—Reverse Sequence Algorithm The reverse serologic screening algorithm uses an initial treponemal test for screening, followed by a nontreponemal test confirmation. A specimen with reactive EIA/CIA results should be tested reflexively with a quantitative nontreponemal test (RPR or VDRL). Source: Centers for Disease Control and Prevention (CDC). Discordant results from reverse sequence syphilis screening--five laboratories, United States, 2006-2010. MMWR Morb Mortal Wkly Rep. 2011;60:133-7. TablesTable 1. Sensitivity and Specificity of Common Serological Tests in Untreated Syphilis
Source:
Table 2. 2021 STI Treatment Guidelines: SyphilisTreatment of Primary and Secondary Syphilis Among Adults**Recommendations for treating syphilis among persons with HIV infection and pregnant women are not addressed in this table. Recommended Regimen Benzathine penicillin G Benzathine penicillin GTradename:Bicillin-LA 2.4 million units IM in a single dose Note: Available data demonstrate that use of additional doses of benzathine penicillin G, amoxicillin, or other antibiotics do not enhance efficacy when used to treat primary and secondary syphilis, regardless of HIV status. Source: Workowski KA, Bachmann LH, Chan PA, et al. Sexually transmitted infections treatment guidelines, 2021. Syphilis. MMWR Recomm Rep. 2021;70(No. RR-4):1-187. [2021 STI Treatment Guidelines] Table 3. 2021 STI Treatment Guidelines: SyphilisTreatment of Latent Syphilis Among Adults**Recommendations for treating syphilis in persons with HIV and pregnant women are not addressed in this table. Recommended Regimen for Early Latent Syphilis Benzathine penicillin G Benzathine penicillin GTradename:Bicillin-LA 2.4 million units IM in a single dose Note: Available data demonstrate that additional doses of benzathine penicillin G, amoxicillin, or other antibiotics in early latent syphilis do not enhance efficacy, regardless of HIV status. Recommended Regimen for Late Latent Syphilis Benzathine penicillin G Benzathine penicillin GTradename:Bicillin-LA 7.2 million units total, administered as 3 doses of 2.4 million units IM each at 1-week intervals Source: Workowski KA, Bachmann LH, Chan PA, et al. Sexually transmitted infections treatment guidelines, 2021. Syphilis. MMWR Recomm Rep. 2021;70(No. RR-4):1-187. [2021 STI Treatment Guidelines] Table 4. 2021 STI Treatment Guidelines: SyphilisTreatment of Tertiary Syphilis Among AdultsRecommended Regimen for Treatment of Tertiary Syphilis with Normal CSF Examination Benzathine penicillin G Benzathine penicillin GTradename:Bicillin-LA 7.2 million units total, administered as 3 doses of 2.4 million units IM each at 1-week intervals Pregnant women who are allergic to penicillin should be desensitized and treated with penicillin. Source: Workowski KA, Bachmann LH, Chan PA, et al. Sexually transmitted infections treatment guidelines, 2021. Syphilis. MMWR Recomm Rep. 2021;70(No. RR-4):1-187. [2021 STI Treatment Guidelines] Table 5. 2021 STI Treatment Guidelines: SyphilisTreatment of Neurosyphilis, Ocular Syphilis, or Otosyphilis Among AdultsRecommended Regimen Aqueous crystalline penicillin G Aqueous crystalline penicillin GTradename:Pfizerpen 18–24 million units per day, administered as 3–4 million units IV every 4 hours or continuous infusion, for 10–14 days Alternative Regimen Procaine penicillin G Procaine penicillin GTradename: 2.4 million units IM once daily for 10-14 days Probenecid 500 mg orally four times a day for 10–14 days+ Note: If compliance with therapy can be ensured, this alternative regimen might be considered. The durations of the recommended and alternative regimens for neurosyphilis are shorter than the duration of the regimen used for latent syphilis. Therefore, benzathine penicillin G, 2.4 million units IM once per week for up to 3 weeks, can be considered after completion of these neurosyphilis treatment regimens to provide a comparable total duration of therapy. Source: Workowski KA, Bachmann LH, Chan PA, et al. Sexually transmitted infections treatment guidelines, 2021. Syphilis. MMWR Recomm Rep. 2021;70(No. RR-4):1-187. [2021 STI Treatment Guidelines] Table 6. 2021 STI Treatment Guidelines: SyphilisTreatment of Syphilis Among Persons with HIV InfectionRecommended Regimen for Treatment of Primary and Secondary Syphilis Benzathine penicillin G Benzathine penicillin GTradename:Bicillin-LA 2.4 million units IM in a single dose Note: Available data demonstrate that additional doses of benzathine penicillin G, amoxicillin, or other antibiotics in primary and secondary syphilis among persons with HIV infection do not result in enhanced efficacy. Recommended Regimen for Treatment of Early Latent Syphilis Benzathine penicillin G Benzathine penicillin GTradename:Bicillin-LA 2.4 million units IM in a single dose Recommended Regimen for Treatment of Late Latent or Latent Syphilis of Unknown Duration Benzathine penicillin G Benzathine penicillin GTradename:Bicillin-LA 7.2 million units total, administered as 3 doses of 2.4 million units IM each at 1-week intervals Recommended Regimen for Treatment of Neurosyphilis, Ocular Syphilis, and Otic Syphilis Aqueous crystalline penicillin G Aqueous crystalline penicillin GTradename:Pfizerpen 18–24 million units per day, administered as 3–4 million units IV every 4 hours or continuous infusion, for 10–14 days Note: The durations of the recommended and alternative regimens for neurosyphilis are shorter than the duration of the regimen used for latent syphilis. Therefore, benzathine penicillin, 2.4 million units IM once per week for up to 3 weeks, can be considered after completion of these neurosyphilis treatment regimens to provide a comparable total duration of therapy. Alternative Regimen for Treatment of Neurosyphilis, Ocular Syphilis, and Otic Syphilis Procaine penicillin G Procaine penicillin GTradename: 2.4 million units IM once daily for 10-14 days Probenecid 500 mg orally four times a day for 10–14 days+ If compliance with therapy can be ensured, this alternative regimen might be considered. Note: The durations of the recommended and alternative regimens for neurosyphilis are shorter than the duration of the regimen used for latent syphilis. Therefore, benzathine penicillin G, 2.4 million units IM once per week for up to 3 weeks, can be considered after completion of these neurosyphilis treatment regimens to provide a comparable total duration of therapy. Source: Workowski KA, Bachmann LH, Chan PA, et al. Sexually transmitted infections treatment guidelines, 2021. Syphilis. MMWR Recomm Rep. 2021;70(No. RR-4):1-187. [2021 STI Treatment Guidelines] Table 7. 2021 STI Treatment Guidelines: SyphilisTreatment of Congenital Syphilis in NeonatesRecommended Regimens for Confirmed or Highly Probable Congenital Syphilis Aqueous crystalline penicillin G Aqueous crystalline penicillin GTradename:Pfizerpen 100,000–150,000 units/kg body weight/day, administered as 50,000 units/kg body weight/dose IV every 12 hours during the first 7 days of life and every 8 hours thereafter for a total of 10 days Recommended Regimens for Confirmed or Highly Probable Congenital Syphilis Procaine penicillin G Procaine penicillin GTradename: 50,000 units/kg body weight/dose IM in a single daily dose for 10 days Recommended Regimens for Possible Congenital Syphilis Aqueous crystalline penicillin G Aqueous crystalline penicillin GTradename:Pfizerpen 100,000–150,000 units/kg body weight/day, administered as 50,000 units/kg body weight/dose IV every 12 hours during the first 7 days of life and every 8 hours thereafter for a total of 10 days Recommended Regimens for Possible Congenital Syphilis Procaine penicillin G Procaine penicillin GTradename: 50,000 units/kg body weight/dose IM in a single daily dose for 10 days Recommended Regimens for Possible Congenital Syphilis Benzathine penicillin G Benzathine penicillin GTradename:Bicillin-LA 50,000 units/kg body weight/dose IM in a single dose Recommended Regimen when Congenital Syphilis Less Likely Benzathine penicillin G Benzathine penicillin GTradename:Bicillin-LA 50,000 units/kg body weight/dose IM in a single dose* Note: *Another approach involves not treating the newborn if follow-up is certain but providing close serologic follow-up every 2–3 months for 6 months for infants whose mothers’ nontreponemal titers decreased at least fourfold after therapy for early syphilis or remained stable for low- titer, latent syphilis (e.g. VDRL <1:2 or RPR <1:4). Recommended Regimen when Congenital Syphilis Unlikely Note: No treatment is required. However, any neonate with reactive nontreponemal tests should be followed serologically to ensure the nontreponemal test returns to negative. Benzathine penicillin G 50,000 units/kg body weight as a single IM injection might be considered, particularly if follow-up is uncertain and the neonate has a reactive nontreponemal test. Source: Workowski KA, Bachmann LH, Chan PA, et al. Sexually transmitted infections treatment guidelines, 2021. Syphilis. MMWR Recomm Rep. 2021;70(No. RR-4):1-187. [2021 STI Treatment Guidelines] Table 8. 2021 STI Treatment Guidelines: SyphilisTreatment of Congenital Syphilis Among Infants and ChildrenInfants and children aged ≥1 month who receive a syphilis diagnosis should have birth and maternal medical records reviewed to assess whether they have congenital or acquired syphilis. Recommended Regimen Aqueous crystalline penicillin G Aqueous crystalline penicillin GTradename:Pfizerpen 200,000–300,000 units/kg body weight/day by IV, administered as 50,000 units/kg body weight every 4–6 hours for 10 days Infants and children aged ≥1 month with primary or secondary syphilis should be managed by a pediatric infectious disease specialist and evaluated for sexual abuse (e.g. through consultation with child-protection services) Source: Workowski KA, Bachmann LH, Chan PA, et al. Sexually transmitted infections treatment guidelines, 2021. Syphilis. MMWR Recomm Rep. 2021;70(No. RR-4):1-187. [2021 STI Treatment Guidelines] Check The Check-on-Learning Questions are short and topic related. They are meant to help you stay on track throughout each lesson and check your understanding of key concepts. You must be signed in to customize your interaction with these questions.Since you've received 80% or better on this quiz, you may claim continuing education credit. You seem to have a popup blocker enabled. If you want to skip this dialog please Always allow popup windows for the online course. Current Version: nstdc-master-3b61e911-2022-11-16-004915 Which of the following is characteristic of the initial phase of syphilis?A single chancre marks the onset of the primary (first) stage of syphilis, but there may be multiple sores. The chancre is usually (but not always) firm, round, and painless. It appears at the location where syphilis enters the body.
What is true syphilis?Overview. Syphilis is a bacterial infection usually spread by sexual contact. The disease starts as a painless sore — typically on the genitals, rectum or mouth. Syphilis spreads from person to person via skin or mucous membrane contact with these sores.
Which one of the following tests has the highest sensitivity for detecting Neisseria gonorrhoeae from a sample of purulent cervical discharge?DIAGNOSTIC TECHNIQUES N. gonorrhoeae can be identified using several diagnostic modalities. The sensitivity and specificity of these techniques vary widely. Overall, nucleic acid amplification testing (NAAT) is the most accurate and thus the preferred diagnostic test for both genital and extragenital infection.
How is syphilis transmitted?The most common way of getting syphilis is by having unprotected sex (vaginal, anal or oral sex without a condom) with someone who's infected. You can get the infection if you come into contact with an ulcer on their penis, vagina, bottom (anus), or inside their mouth.
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Which one of the following statements is true regarding the biology of treponema pallidum?
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