Syphilis-the \"great simulator\" for classical venereologists-is re-emerging in Western countries despite adequate treatment; several contributing factors have been identified, including changes in sexual behaviour, which won\'t be the topic of this article though.In 2021, a total of 6613 new cases of syphilis were reported in Spain, representing an incidence of 13.9 x 100 000 inhabitants (90.5%, men). Rates have increased progressively since 2000.The clinical presentation of syphilis is heterogeneous. Although chancroid, syphilitic roseola and syphilitic nails are typical lesions, other forms of the disease can be present such as non-ulcerative primary lesions like Follmann balanitis, chancres in the oral cavity, patchy secondary lingual lesions, or enanthema on the palate and uvula, among many others.Regarding diagnosis, molecular assays such as PCR have been replacing dark-field microscopy in ulcerative lesions while automated treponemal tests (EIA, CLIA) are being used in serological tests, along with classical tests (such as RPR and HAART) for confirmation and follow-up purposes. The interpretation of these tests should be assessed in the epidemiological and clinical context of the patient. HIV serology and STI screening should be requested for anyone with syphilis.Follow-up of patients under treatment is important to ensure healing and detect reinfection. Serological response to treatment should be assessed with the same non-treponemal test (RPR/VDRL); 3-, 6-, 12-, and 24-month follow-up is a common practice in people living with HIV (PLHIV).Sexual contacts should be assessed and treated as appropriate.Screening is advised for pregnant women within the first trimester of pregnancy. Pregnant women with an abortion after week 20 should all be tested for syphilis.The treatment of choice for all forms of syphilis, including pregnant women and PLHIV, is penicillin. Macrolides are ill-advised because of potential resistance.

Syphilis, \'the great imitator\', caused by Treponema pallidum infection, remains a complex and multifaceted disease with a rich history of clinical diversity. This guideline aims to be a comprehensive guide for healthcare workers in Southern Africa, offering practical insights into the epidemiology, pathogenesis, clinical manifestations, diagnostic testing, therapeutic principles, and public health responses to syphilis. Although the syphilis burden has declined over the years, recent data indicate a troubling resurgence, particularly among pregnant women and neonates. This guideline highlights the diagnostic challenges posed by syphilis, stemming from the absence of a single high-sensitivity and -specificity test. While treatment with penicillin remains the cornerstone of treatment, alternative regimens may be used for specific scenarios. We highlight the importance of thorough patient follow-up and management of sex partners to ensure optimal care of syphilis cases. In the context of public health, we emphasise the need for concerted efforts to combat the increasing burden of syphilis, especially within high-risk populations, including people living with HIV.

Syphilis -the \"great simulator\" for classical venereologists-is re-emerging in Western countries despite adequate treatment; several contributing factors have been identified, including changes in sexual behaviour, which won\'t be the topic of this article though. In 2021, a total of 6613 new cases of syphilis were reported in Spain, representing an incidence of 13.9×100 000 inhabitants (90.5%, men). Rates have increased progressively since 2000. The clinical presentation of syphilis is heterogeneous. Although chancroid, syphilitic roseola and syphilitic nails are typical lesions, other forms of the disease can be present such as non-ulcerative primary lesions like Follmann balanitis, chancres in the oral cavity, patchy secondary lingual lesions, or enanthema on the palate and uvula, among many others. Regarding diagnosis, molecular assays such as PCR have been replacing dark-field microscopy in ulcerative lesions while automated treponemal tests (EIA, CLIA) are being used in serological tests, along with classical tests (such as RPR and HAART) for confirmation and follow-up purposes. The interpretation of these tests should be assessed in the epidemiological and clinical context of the patient. HIV serology and STI screening should be requested for anyone with syphilis. Follow-up of patients under treatment is important to ensure healing and detect reinfection. Serological response to treatment should be assessed with the same non-treponemal test (RPR/VDRL); 3-, 6-, 12-, and 24-month follow-up is a common practice in people living with HIV (PLHIV). Sexual contacts should be assessed and treated as appropriate. Screening is advised for pregnant women within the first trimester of pregnancy. Pregnant women with an abortion after week 20 should all be tested for syphilis. The treatment of choice for all forms of syphilis, including pregnant women and PLHIV, is penicillin. Macrolides are ill-advised because of potential resistance.

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A panel of experts generated 5 \"key questions\" in the management of adult syphilis. A systematic literature review was conducted and tables of evidence were constructed to answer these questions. Available data suggest no clinical benefit to >1 dose of benzathine penicillin G for early syphilis in human immunodeficiency virus (HIV)-infected patients. While penicillin remains the drug of choice to treat syphilis, doxycycline to treat early and late latent syphilis is an acceptable alternate option if penicillin cannot be used. There are very limited data regarding the impact of additional antibiotic doses on serologic responses in serofast patients and no data on the impact of additional antibiotic courses on long-term clinical outcomes. In patients with isolated ocular or otic signs and symptoms, reactive syphilis serologic results, and confirmed ocular/otic abnormalities at examination, a diagnostic cerebrospinal fluid (CSF) examination is not necessary, because up to 40% and 90% of patients, respectively, would have no CSF abnormalities. Based on the results of 2 studies, repeated CSF examinations are not necessary for HIV-uninfected patients or HIV-infected patients on antiretroviral therapy who exhibit appropriate serologic and clinical responses after treatment for neurosyphilis. Finally, several important gaps were identified and should be a priority for future research.

The Northern Territory (NT) of Australia is currently experiencing a syphilis epidemic. Neurosyphilis is commonly considered in the differential diagnosis for patients presenting with neurologic conditions such as dementia and stroke in the NT.
To explore the local epidemiologic, diagnostic and treatment complexities of neurosyphilis in the NT and produce a guideline for clinical practice.
A database search was undertaken and local and global neurosyphilis guidelines were analysed. A guideline was created based on findings of the critical review and consultation with local multidisciplinary experts.
Neurosyphilis is frequently encountered in the NT but studies suggest it is often undertreated. Dementia is the most common clinical presentation locally. Establishing a diagnosis of neurosyphilis is complex and requires stepwise evaluation of clinical, laboratory and radiological findings.
A clinical guideline and algorithm have been developed for the diagnosis and management of patients with neurosyphilis.

We reviewed the relevant syphilis diagnostic literature to address the following question: what are the performance characteristics, stratified by the stage of syphilis, for nontreponemal serologic tests? The database search included key terms related to syphilis and nontreponemal tests from 1960-2017, and for data related to the venereal disease research laboratory test from 1940-1960. Based on this review, we report the sensitivity and specificity for each stage of syphilis (primary, secondary, early latent, late latent, or unknown duration; tertiary as well as neurosyphilis, ocular syphilis, and otic syphilis). We also report on reactive nontreponemal tests in conditions other than syphilis, false negatives, and automated nontreponemal tests. Overall, many studies were limited by their sample size, lack of clearly documented clinical staging, and lack of well-defined gold standards. There is a need to better define the performance characteristics of nontreponemal tests, particularly in the late stages of syphilis, with clinically well-characterized samples. Published data are needed on automated nontreponemal tests. Evidence-based guidelines are needed for optimal prozone titrations. Finally, improved criteria and diagnostics for neurosyphilis (as well as ocular and otic syphilis) are needed.

A panel of experts generated 8 \"key questions\" in the management of adult syphilis. A systematic literature review was conducted and tables of evidence were constructed to answer these important questions. Penicillin is the drug of choice to treat syphilis. Doxycycline to treat early and late latent syphilis is an acceptable alternate option if penicillin cannot be used. There is no added benefit to enhanced antimicrobial therapy when treating human immunodeficiency virus-infected persons with syphilis. If a patient misses a dose of penicillin in a course of weekly therapy for late syphilis, clinical experience suggests that an interval of 10-14 days between doses might be acceptable before restarting the sequence of injections. Pharmacologic considerations suggest that an interval of 7-9 days between doses, if feasible, may be more optimal. Missed doses are not acceptable for pregnant women. A cerebrospinal fluid examination to diagnose neurosyphilis is recommended in persons diagnosed with tertiary syphilis (eg, cardiovascular syphilis or late benign syphilis), persons with neurological signs or symptoms consistent with neurosyphilis, and asymptomatic persons whose serological titers do not decline appropriately following recommended therapy and in whom reinfection is ruled out. Infection and reinfection rates, particularly among men who have sex with men, are high. Frequent serological screening of this population appears to be the most cost-efficient intervention. The Centers for Disease Control and Prevention continues to recommend the use of the traditional rapid plasma reagin-based screening algorithm. The positive predictive value for syphilis associated with an isolated unconfirmed reactive treponemal chemiluminescence assay or enzyme immunoassay is low if the epidemiological risk and clinical probability for syphilis are low. Among pregnant women with serodiscordant serologies (positive treponemal tests and a negative nontreponemal test), the risk of vertical transmission from mother to infant is low. Several important questions regarding the management of syphilis remain unanswered and should be a priority for future research.

Neurosyphilis refers to infection of the central nervous system by Treponema pallidum, which may occur at any stage. Neurosyphilis has been categorized in many ways including early and late, asymptomatic versus symptomatic and infectious versus non-infectious. Late neurosyphilis primarily affects the central nervous system parenchyma, and occurs beyond early latent syphilis, years to decades after the initial infection. Associated clinical syndromes include general paresis, tabes dorsalis, vision loss, hearing loss and psychiatric manifestations. Unique algorithms are recommended for HIV-infected and HIV-uninfected patients, as immunocompromised patients may present with serologic and cerebrospinal fluid findings that are different from immunocompetent hosts. Antibody assays include a VDRL assay and the FTA-Abs, while polymerase chain reaction for T. pallidum can be used as direct detection assays for some specimens. This chapter reviews guidelines for specimen types and sample collection, and identifies two possible algorithms for use with immunocompromised and immunocompetent hosts using currently available tests in Canada, along with a review of treatment response and laboratory testing follow-up.
La neurosyphilis désigne l’infection du système nerveux central par le Treponema pallidum à tout stade de la maladie. Elle est classée de diverses façons, y compris précoce ou tardive, asymptomatique ou symptomatique, infectieuse ou non infectieuse. La neurosyphilis tardive touche principalement le parenchyme du système nerveux central et se manifeste après une syphilis latente précoce, des années ou même des décennies après l’infection initiale. Des syndromes cliniques s’y associent, y compris la parésie générale, le tabes dorsalis, la perte d’acuité visuelle et auditive et les manifestations psychiatriques. Des algorithmes différents sont recommandés pour les patients infectés ou non infectés par le VIH, car les manifestations sérologiques et céphalorachidiennes des patients immunodéprimés peuvent différer de celles des patients immunocompétents. Les tests de détection des anticorps incluent le VDRL et le FTA-Abs, tandis que pour certains prélèvements, la réaction en chaîne de la polymérase peut servir de test de détection du T. pallidum. Ce chapitre traite des directives sur les types de prélèvement et leur collecte et présente deux algorithmes qui peuvent être utilisés auprès des hôtes immunodéprimés et immunocompétents à l’aide des tests offerts au Canada. Il contient également une analyse de la réponse thérapeutique et du suivi des tests de laboratoire.

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