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.

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.

Periodontal health is defined by absence of clinically detectable inflammation. There is a biological level of immune surveillance that is consistent with clinical gingival health and homeostasis. Clinical gingival health may be found in a periodontium that is intact, i.e. without clinical attachment loss or bone loss, and on a reduced periodontium in either a non-periodontitis patient (e.g. in patients with some form of gingival recession or following crown lengthening surgery) or in a patient with a history of periodontitis who is currently periodontally stable. Clinical gingival health can be restored following treatment of gingivitis and periodontitis. However, the treated and stable periodontitis patient with current gingival health remains at increased risk of recurrent periodontitis, and accordingly, must be closely monitored. Two broad categories of gingival diseases include non-dental plaque biofilm-induced gingival diseases and dental plaque-induced gingivitis. Non-dental plaque biofilm-induced gingival diseases include a variety of conditions that are not caused by plaque and usually do not resolve following plaque removal. Such lesions may be manifestations of a systemic condition or may be localized to the oral cavity. Dental plaque-induced gingivitis has a variety of clinical signs and symptoms, and both local predisposing factors and systemic modifying factors can affect its extent, severity, and progression. Dental plaque-induced gingivitis may arise on an intact periodontium or on a reduced periodontium in either a non-periodontitis patient or in a currently stable \"periodontitis patient\" i.e. successfully treated, in whom clinical inflammation has been eliminated (or substantially reduced). A periodontitis patient with gingival inflammation remains a periodontitis patient (Figure 1), and comprehensive risk assessment and management are imperative to ensure early prevention and/or treatment of recurrent/progressive periodontitis. Precision dental medicine defines a patient-centered approach to care, and therefore, creates differences in the way in which a \"case\" of gingival health or gingivitis is defined for clinical practice as opposed to epidemiologically in population prevalence surveys. Thus, case definitions of gingival health and gingivitis are presented for both purposes. While gingival health and gingivitis have many clinical features, case definitions are primarily predicated on presence or absence of bleeding on probing. Here we classify gingival health and gingival diseases/conditions, along with a summary table of diagnostic features for defining health and gingivitis in various clinical situations.

Periodontal health is defined by absence of clinically detectable inflammation. There is a biological level of immune surveillance that is consistent with clinical gingival health and homeostasis. Clinical gingival health may be found in a periodontium that is intact, i.e. without clinical attachment loss or bone loss, and on a reduced periodontium in either a non-periodontitis patient (e.g. in patients with some form of gingival recession or following crown lengthening surgery) or in a patient with a history of periodontitis who is currently periodontally stable. Clinical gingival health can be restored following treatment of gingivitis and periodontitis. However, the treated and stable periodontitis patient with current gingival health remains at increased risk of recurrent periodontitis, and accordingly, must be closely monitored. Two broad categories of gingival diseases include non-dental plaque biofilm-induced gingival diseases and dental plaque-induced gingivitis. Non-dental plaque biofilm-induced gingival diseases include a variety of conditions that are not caused by plaque and usually do not resolve following plaque removal. Such lesions may be manifestations of a systemic condition or may be localized to the oral cavity. Dental plaque-induced gingivitis has a variety of clinical signs and symptoms, and both local predisposing factors and systemic modifying factors can affect its extent, severity, and progression. Dental plaque-induced gingivitis may arise on an intact periodontium or on a reduced periodontium in either a non-periodontitis patient or in a currently stable \"periodontitis patient\" i.e. successfully treated, in whom clinical inflammation has been eliminated (or substantially reduced). A periodontitis patient with gingival inflammation remains a periodontitis patient (Figure 1), and comprehensive risk assessment and management are imperative to ensure early prevention and/or treatment of recurrent/progressive periodontitis. Precision dental medicine defines a patient-centered approach to care, and therefore, creates differences in the way in which a \"case\" of gingival health or gingivitis is defined for clinical practice as opposed to epidemiologically in population prevalence surveys. Thus, case definitions of gingival health and gingivitis are presented for both purposes. While gingival health and gingivitis have many clinical features, case definitions are primarily predicated on presence or absence of bleeding on probing. Here we classify gingival health and gingival diseases/conditions, along with a summary table of diagnostic features for defining health and gingivitis in various clinical situations.

UNASSIGNED: Automated analyzer-based nontreponemal serological tests for syphilis (STS) have been used for several decades.
UNASSIGNED: In this study, we evaluated serological responses to treatment and proposed clinical guidelines for automated STS.
UNASSIGNED: This retrospective cohort study analyzed human immunodeficiency virus-negative syphilis patients who were diagnosed with automated rapid plasma reagin (auto RPR) tests as a nontreponemal STS, and who also received the fluorescent treponemal antibody-absorption test as a confirmatory test. The ratio of auto RPR values after treatment against those at baseline was defined as the auto RPR ratio for the analysis of the serological response to treatment. The cutoff value for reliable seroreversion prediction was assessed with receiver-operating-characteristic curves.
UNASSIGNED: Overall, 89.7% of participants (78/87) seroreverted and 10.3% of participants (9/87) remained serofast during the two-year follow-up period. We were unable to describe trends in the changes among auto RPR values within six months after treatment because of high variation. All of the patients who had an auto RPR ratio ≥1.0 after six months continuously had positive serologic results during their 24-month follow-up and were classified as a serofast group. The receiver-operating-characteristic curves revealed a 25% reduction in auto RPR values nine months after treatment and predicted seroreversion with a sensitivity of 96.2% and a specificity of 100%.
UNASSIGNED: The most important primary checkpoint for syphilis treatment response is an increase in automated nontreponemal STS six months after treatment. Thus, we recommend monitoring the treatment response with an auto RPR.

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These guidelines are an update for 2015 of the 2008 UK guidelines for the management of syphilis. The writing group have piloted the new BASHH guideline methodology, notably using the GRADE system for assessing evidence and making recommendations. We have made significant changes to the recommendations for screening infants born to mothers with positive syphilis serology and to facilitate accurate and timely communication between the teams caring for mother and baby we have developed a birth plan. Procaine penicillin is now an alternative, not preferred treatment, for all stages of syphilis except neurosyphilis, but the length of treatment for this is shortened. Other changes are summarised at the start of the guideline.

Congenital syphilis (CS) is a disease that continues to persist in the United States despite its preventable nature. Mother-to-child transmission of CS can be avoided with appropriate maternal diagnosis and treatment during the pregnancy. Diagnosing CS and determining the therapeutic course can be challenging. This review covers the recent guidelines for the diagnosis and treatment of CS and the various factors that affect management decisions. These factors include the mother\'s antenatal management, the infant\'s clinical presentation and results, laboratory and serologic testing, and more.

Syphilis, caused by the bacterium Treponema pallidum subsp. pallidum, is an infection recognized since antiquity. It was first reported at the end of the 15th century in Europe. Infections may be sexually transmitted as well as spread from an infected mother to her fetus or through blood transfusions. The laboratory diagnosis of syphilis infection is complex. Because this organism cannot be cultured, serology is used as the principal diagnostic method. Some of the issues related to serological diagnoses are that antibodies take time to appear after infection, and serology screening tests require several secondary confirmatory tests that can produce complex results needing interpretation by experts in the field. Traditionally, syphilis screening was performed using either rapid plasma reagin or Venereal Disease Research Laboratory tests, and confirmed by treponemal tests such as MHA-TP, TPPA or FTA-Abs. Currently, that trend is reversed, ie, most of the laboratories in Canada now screen for syphilis using treponemal enzyme immunoassays and confirm the status of infection using rapid plasma reagin or Venereal Disease Research Laboratory tests; this approach is often referred to as the reverse algorithm. This chapter reviews guidelines for specimen types and sample collection, treponemal and non-treponemal tests utilized in Canada, the current status of serological tests for syphilis in Canada, the complexity of serological diagnosis of syphilis infection and serological testing algorithms. Both traditional and reverse sequence algorithms are recommended and the algorithm used should be based on a combination of local disease epidemiology, test volumes, performance of the proposed assays and available resources.
La syphilis, causée par la bactérie Treponema pallidum sous-espèce pallidum, est une infection connue depuis l’antiquité. Elle a été signalée pour la première fois en Europe, à la fin du XVe siècle. Les infections peuvent être transmises sexuellement, par une mère infectée à son fœtus ou par des transfusions sanguines. Il est difficile de diagnostiquer la syphilis en laboratoire. Puisque cet organisme ne peut pas être mis en culture, la sérologie est la principale méthode diagnostique. Parmi les problèmes liés aux diagnostics sérologiques, soulignons qu’il faut du temps pour que les anticorps fassent leur apparition après l’infection et que les tests de dépistage sérologique doivent s’associer à plusieurs tests de confirmation secondaires qui peuvent produire des résultats complexes devant être interprétés par des experts dans le domaine. Habituellement, la syphilis était dépistée au moyen du test rapide de la réagine plasmatique ou du test Veneral Disease Research Laboratory et était confirmée par les tests tréponémiques comme le MHA-TP, le TP-PA ou le FTA-Abs. Cette tendance s’inverse actuellement, car la plupart des laboratoires du Canada dépistent la syphilis au moyen d’épreuves immunoenzymatiques tréponémiques et confirment le statut de l’infection au moyen du test rapide de la réagine plasmatique ou du test Veneral Disease Reseach Laboratory. Cette approche est souvent désignée par le terme algorithme inversé. Ce chapitre analyse les directives sur les types de prélèvements et la collecte des échantillons, les tests tréponémiques et non tréponémiques utilisés au Canada, le statut actuel des tests sérologiques de la syphilis au Canada, la complexité du diagnostic sérologique d’infection par la syphilis et les algorithmes des tests sérologiques. Tant l’algorithme habituel que l’algorithme inversé sont recommandés, et l’algorithme utilisé devrait tenir compte à la fois de l’épidémiologie locale de la maladie, du volume de tests, de l’exécution des tests proposés et des ressources disponibles.