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Background Treponema pallidum prevalence and burden at oral and lesion sites in adults with early syphilis were assessed by quantitative polymerase chain reaction (qPCR). Factors associated with oral shedding were also examined. Methods Pretreatment oral and lesion swabs were collected from adults with early syphilis in a US multicenter syphilis treatment trial. Oral swabs were collected in the presence and absence of oral lesions. Following DNA extraction, qPCR and whole-genome sequencing (WGS) were performed to assess burden and strain variability. Results All 32 participants were male, mean age was 35 years, and 90.6% with human immunodeficiency virus (HIV). T. pallidum oral PCR positivity varied by stage: 16.7% primary, 44.4% secondary, and 62.5% in early latent syphilis. Median oral T. pallidum burden was highest in secondary syphilis at 63.2 copies/µL. Lesion PCR positivity was similar in primary (40.0%) and secondary syphilis (38.5%). Age 18–29 years was significantly associated with oral shedding (vs age 40+ years) in adjusted models. WGS identified 2 distinct strains. Conclusions T. pallidum DNA was directly detected at oral and lesion sites in a significant proportion of men with early syphilis. Younger age was associated with oral shedding. Ease of oral specimen collection and increased PCR availability suggest opportunities to improve syphilis diagnostic testing. Clinical Trials Registration. NCT03637660. [ABSTRACT FROM AUTHOR]

BackgroundStarting in 2010, the Chinese government initiated a 10-year syphilis control plan, called the national syphilis control plan (NSCP), to address the emerging threat of syphilis. We aimed to evaluate the effect of the NSCP plan on syphilis control in Jiangsu, China.MethodsThe temporal trends of syphilis incidence, prevalence and rate of condom use were estimated by Joinpoint regression with average annual percent change (APC) and average annual percentage (APPC). A Chi-square test was conducted to analyze the outcomes in different subgroups. ArcGIS was used to analyze the spatiotemporal distribution of syphilis incidence.ResultsGeographically, early and congenital syphilis incidence decreased significantly in all areas of the province during the period of NSCP. Early syphilis incidence decreased from 21.1 to 8.8 (APC: −7.5, 95%CI: −8.6, −6.5, p

A 66-year-old unemployed unmarried male with known men sex men activity since the age of 20 years presented with an erythematous well-defined ulcer on the lower lip and multiple discrete papulo-squamous lesions on the palms, soles, and scrotum. The patient was also in dysphoric mood with grandiose ideas with normal higher function. Knee and ankle jerk reflexes were absent and there was impaired tandem walking. Venereal Disease Research Laboratory (VDRL) and treponema pallidum hemagglutination assay were positive. Cerebrospinal fluid-VDRL was positive with grossly elevated proteins and glucose. HIV test was negative. Magnetic resonance imaging scan of the brain was normal. We made a diagnosis of neurosphilis – General paralysis of insane (GPI) with co-existing early syphilis. The patient was started on crystalline penicillin for 14 days after which there was significant improvement in behavior. We are reporting a rare case of GPI with early syphilis. [ABSTRACT FROM AUTHOR]

BackgroundThe widespread occurrence of syphilis remains a global public health problem. Although penicillin has been recommended as the first-line therapy for syphilis for more than 70 years, treatment failure occurs in 10–20% of patients with early syphilis. Recent studies have reported varied single-nucleotide polymorphisms (SNPs) of Treponema pallidum related to penicillin resistance. The clinical relevance of these SNPs to treatment failure in patients with early syphilis is unresolved. In this work, a protocol is developed to evaluate the association between treatment failure in patients with early syphilis and penicillin resistance-related gene mutations of T. pallidum.MethodsA multicentre nested case–control study is designed, and patients who are diagnosed with early syphilis and treated with penicillin will be recruited for the study cohort. Before the first treatment, baseline information and biological specimens will be collected from the subjects, and serological tests for syphilis will be performed. Each participant will be followed up at 1, 3, 6, 9, and 12 months after the first treatment, and the clinical manifestations and serum non-treponemal test titres will be evaluated at each follow-up. Patients who will fail treatment are defined as cases, and those who will respond to treatment are defined as controls. Tests for SNPs related to penicillin-binding proteins and Tp47 will be performed in these cases and controls. Survival analysis is used performed to identify gene mutations of T. pallidum related to penicillin resistance and their combinations associated with treatment failure.DiscussionThis protocol provides a practical clinical study design that illustrates the role of gene mutations of T. pallidum related to penicillin resistance in the treatment outcome of patients with early syphilis.

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., (Copyright © 2024 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.)

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., (Copyright © 2024 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.)

Abstract Background Syphilis rates have been increasing both in the USA and internationally with incidence higher among men-who-have-sex-with-men and people living with human immunodeficiency virus (HIV) infection. Currently, benzathine penicillin is the recommended treatment for syphilis in all patients. Global shortages and cost increases in benzathine penicillin call for alternative treatment options. This study evaluates the efficacy of oral cefixime for the treatment of early syphilis. Methods We are conducting a randomized, multisite, open-label, non-comparative clinical trial in Los Angeles and Oakland, CA. Eligible participants are ≥ 18 years old, with primary, secondary, or early latent syphilis (rapid plasma reagin [RPR] titer ≥ 1:8). Patients with HIV infection must have a viral load ≤ 200 copies/mL and CD4+ T cell count ≥ 350 cells/μL during the past 6 months. Participants are randomized to receive either 2.4 M IU benzathine penicillin G intramuscularly once or cefixime 400 mg orally twice a day for 10 days. Participants return at 3, 6, and 12 months post-treatment for follow-up RPR serological testing. The primary outcome is the proportion of participants who achieve ≥ 4-fold RPR titer decrease at 3 or 6 months post-treatment. Discussion Clinical trials evaluating the efficacy of alternative antibiotics to penicillin are urgently needed. Trial registration Clinicaltrials.gov NCT03660488 . Registered on 4 September 2018.

Syphilitic osteitis is one of the rare and often under-reported complications of early syphilis. Recognizing this entity is important as it may mimic other conditions like multiple myeloma, lymphoma, or metastatic malignancies. Misdiagnosis and delayed management can lead to irreversible destructive lesions. We herein report a case of calvaria syphilitic osteitis that was initially investigated for possible lymphoma and later diagnosed as secondary syphilis.

Background: The global resurgence of syphilis necessitates vaccine development., Methods: We collected ulcer exudates and blood from 17 primary syphilis (PS) participants and skin biopsies and blood from 51 secondary syphilis (SS) participants in Guangzhou, China for Treponema pallidum subsp. pallidum (TPA) qPCR, whole genome sequencing (WGS), and isolation of TPA in rabbits., Results: TPA DNA was detected in 15 of 17 ulcer exudates and 3 of 17 blood PS specimens. TPA DNA was detected in 50 of 51 SS skin biopsies and 27 of 51 blood specimens. TPA was isolated from 47 rabbits with success rates of 71% (12/17) and 69% (35/51), respectively, from ulcer exudates and SS bloods. We obtained paired genomic sequences from 24 clinical samples and corresponding rabbit isolates. Six SS14- and two Nichols-clade genome pairs contained rare discordances. Forty-one of the 51 unique TPA genomes clustered within SS14 subgroups largely from East Asia, while 10 fell into Nichols C and E subgroups., Conclusions: Our TPA detection rate was high from PS ulcer exudates and SS skin biopsies and over 50% from SS blood, with TPA isolation in over two-thirds of samples. Our results support the use of WGS from rabbit isolates to inform vaccine development., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Safe and efficacious alternative treatment options for syphilis are necessary. This randomized, 2-arm, noncomparative pilot study evaluated the efficacy of oral cefixime 400 mg in achieving a ≥4-fold rapid plasma reagin titer decrease by 3 or 6 months after treatment. The proportion of cefixime arm participants treated successfully was 87% (95% confidence interval, 69%–100%; 13/15). Clinical Trials Registration. NCT03752112. [ABSTRACT FROM AUTHOR]

The objective of this study was to examine the trends of primary and secondary syphilis in Tokyo between 2007 and 2016 using national infectious disease surveillance data. We analysed all 3269 cases reported during these 10 years. A statistically significant increase in cases was observed after 2010 with a more rapid rate of increase after 2014 mainly in urban areas in Tokyo. The notification rates per 100 000 population in 2010, 2014 and 2016 were 0.9 (n = 113), 2.2 (n = 295) and 8.7 (n = 1190), respectively. Domestic syphilis transmission was suspected in 92.6–99.3% of cases during the period 2007–2016. Until 2013, the increase was mainly observed among men who have sex with men (MSM); however, heterosexual transmission became more dominant and eventually surpassed transmission among MSM in 2015. In 2016, the notified cases of infections through heterosexual contact were 22.3 and 40.4 times higher in men and women, respectively, compared to those in 2010. The median ages of affected heterosexual men and women were 37 (interquartile range: 28–46) and 26 (interquartile range: 22–32) years, respectively. Reports of oropharyngeal lesions have been increasing among both men and women with syphilis. The number of congenital syphilis cases reported in Tokyo was 0 to 3 cases per year during the study period. More information and further analysis are needed to explain the reason for this increase.

Background Neurosyphilis, a complication of syphilis, can occur at any stage of infection. Measuring the prevalence of neurosyphilis is challenging, and there are limited data on the prevalence of neurologic or ocular symptoms among patients with syphilis. We sought to describe the prevalence of neurologic and/or ocular symptoms among early syphilis (ES) cases and the clinical management of symptomatic cases enrolled in the STD Surveillance Network (SSuN) Neuro/Ocular Syphilis Surveillance project. Methods Persons diagnosed with ES were selected for interviews based on current health department protocols in 5 participating SSuN jurisdictions from November 2016 through October 2017. All interviewed ES cases were screened for self-reported neurologic and/or ocular symptoms. Additional clinical information on diagnostic testing and treatment for cases concerning for neurosyphilis/ocular syphilis was obtained from providers. Results Among 9123 patients with ES who were interviewed, 151 (1.7%; 95% confidence interval [CI], 1.4%–1.9%) reported ≥ 1 neurologic or ocular symptom. Of the 53 (35%) who underwent lumbar puncture, 22 (42%) had documented abnormal cerebrospinal fluid, of which 21 (95%) were treated for neurosyphilis/ocular syphilis. Among the remaining 98 symptomatic patients with no documented lumbar puncture (65%), 12 (12%) were treated for and/or clinically diagnosed with neurosyphilis/ocular syphilis. Conclusions We observed a low prevalence of self-reported neurologic and/or ocular symptoms in interviewed ES cases. Approximately one-third of ES cases who self-reported symptoms underwent further recommended diagnostic evaluation. Understanding barriers to appropriate clinical evaluation is important to ensuring appropriate management of patients with possible neurologic and/or ocular manifestations of syphilis. [ABSTRACT FROM AUTHOR]

Background: Syphilis rates have been increasing both in the USA and internationally with incidence higher among men-who-have-sex-with-men and people living with human immunodeficiency virus (HIV) infection. Currently, benzathine penicillin is the recommended treatment for syphilis in all patients. Global shortages and cost increases in benzathine penicillin call for alternative treatment options. This study evaluates the efficacy of oral cefixime for the treatment of early syphilis.Methods: We are conducting a randomized, multisite, open-label, non-comparative clinical trial in Los Angeles and Oakland, CA. Eligible participants are ≥ 18 years old, with primary, secondary, or early latent syphilis (rapid plasma reagin [RPR] titer ≥ 1:8). Patients with HIV infection must have a viral load ≤ 200 copies/mL and CD4+ T cell count ≥ 350 cells/μL during the past 6 months. Participants are randomized to receive either 2.4 M IU benzathine penicillin G intramuscularly once or cefixime 400 mg orally twice a day for 10 days. Participants return at 3, 6, and 12 months post-treatment for follow-up RPR serological testing. The primary outcome is the proportion of participants who achieve ≥ 4-fold RPR titer decrease at 3 or 6 months post-treatment.Discussion: Clinical trials evaluating the efficacy of alternative antibiotics to penicillin are urgently needed.Trial Registration: Clinicaltrials.gov NCT03660488 . Registered on 4 September 2018. [ABSTRACT FROM AUTHOR]

Background: Starting in 2010, the Chinese government initiated a 10-year syphilis control plan, called the national syphilis control plan (NSCP), to address the emerging threat of syphilis. We aimed to evaluate the effect of the NSCP plan on syphilis control in Jiangsu, China., Methods: The temporal trends of syphilis incidence, prevalence and rate of condom use were estimated by Joinpoint regression with average annual percent change (APC) and average annual percentage (APPC). A Chi-square test was conducted to analyze the outcomes in different subgroups. ArcGIS was used to analyze the spatiotemporal distribution of syphilis incidence., Results: Geographically, early and congenital syphilis incidence decreased significantly in all areas of the province during the period of NSCP. Early syphilis incidence decreased from 21.1 to 8.8 (APC: -7.5, 95%CI: -8.6, -6.5, p  < 0.001) per 100,000 people, and congenital syphilis decreased from 63.6 to 4.1 (APC: -14.8, 95%CI: -20.8, -8.4, p  < 0.01) per 100,000 newborns from 2010 to 2020. Also, syphilis prevalence reduced from 13.4 to 3.8% (APC: -8.7, 95%CI: -12.1, -5.0, p  = 0.001) among men who have sex with men, from 5.3 to 1.7% (APC: -7.9, 95%CI: -11.7, -3.8, p  = 0.002) among female sex workers and remained under 1.0% with slight variations among pregnant women (APC: 0.3, 95%CI: -4.3, 5.1, p  = 0.877) from 2010 to 2020. 0.2% (2,436) of pregnant women who received free syphilis testing during pregnancy were diagnosed with current syphilis infection, and 97.0% (2,555) of newborns in the province were delivered to women diagnosed with syphilis. 91.8% (2,346) of live babies and about 90% of diagnosed patients received complete standard syphilis diagnosis and treatment services., Conclusion: Trends of early syphilis incidence and syphilis prevalence show a considerable decreasing trend among almost all the key populations after implementing NSCP. Congenital syphilis has significantly decreased as well and hence, the NSCP program should be sustained and strengthened to control the syphilis epidemic in China further., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Shi, Chen, Liu, Hu, Chen, Chen, Zhang, Zhou, Lu, Yang and Guan.)

Background: Some patients with early syphilis who receive appropriate treatment do not reach a serological cure and have a persistent titer which does not meet the criteria for treatment failure (serofast state). Aims: This retrospective study aimed to determine the prevalence of serological cure and the serofast state as well as the factors associated with serological cure after treatment of patients with early syphilis. Methods: A serological cure was defined as occurring when there was a =4-fold decrease in nontreponemal titer, whereas patients with a =4-fold increase were considered as having either a treatment failure or reinfection. Nontreponemal titers that neither increased nor decreased =4-fold after treatment were considered to be in a serofast state. Seroreversion was defined as occurring when there was a negative test within 12 months of treatment. Results: There were 179 patients with a mean age of 31.9 years; 174 (97.2%) were men, and 125 (70%) were HIV patients. Of the total, 174 (98%; 95% confidence interval 94.82-99.42%) patients achieved a serological cure, whereas five were in a serofast state 12 months after treatment. Those five serofast patients were all HIV-positive men, of which 4 (80%) had secondary-stage syphilis, a CD4 count =200 cells/µl and a titer <1:8. In a bivariate analysis, a serological cure was associated with a baseline Venereal Disease Research Laboratory >1:16 titers (P = 0.018), and a CD4 cell count >200 cells/µl in 6 months preceding treatment (P = 0.016). The median time to a serological cure was 96 days. Only 22 (12.3%) of the patients achieved seroreversion at 12 months after treatment. Limitations: A retrospective medical record review is likely to have a selection bias, and in our study, 196 (52%) patients were excluded due to missing information. Conclusions: Most patients with early syphilis who achieved a serological cure at 12 months after treatment had high baseline Venereal Disease Research Laboratory titers and CD4 cell counts. However, only 22 (12.3%) had a negative Venereal Disease Research Laboratory titer after 1 year of treatment. [ABSTRACT FROM AUTHOR]

Background: Some syphilitic patients remain in a serologically positive state after the recommended therapy. Although we often retreat patients in clinical practice, the optimal treatment protocol remains uncertain due to the paucity of data regarding serological response to retreatment and long-term outcomes.Methods: We examined rapid plasma reagin serological test results of 70 serofast early syphilis cases who were retreated with 2.4 million units of benzathine penicillin weekly for 3 weeks. Serological retreatment success was defined as a minimum 4-fold decrease in baseline rapid plasma reagin test antibody titre within 6 months.Results: Thirty-four (48.6%) of the patients who failed to achieve serological cure at 6 months after initial therapy achieved serological cure at 12 months. Patients who had higher non-treponemal titres at baseline and at 6 months were more likely to exhibit serological cure after retreatment than those with lower titres.Conclusions: Our results suggest that the incremental benefit of retreating serofast patients with early syphilis is moderate, considering the almost 1:1 ratio of serological response to serofast state at follow-up. [ABSTRACT FROM AUTHOR]

Introduction. Sociometric studies based on the evaluation of structures forming interpersonal network earned widespread recognition in sexually transmitted diseases (STD) epidemiology. Objective . The aim of this work is to assess the importance of epidemiological studies of infection sources, contacts and the network of connections created by them in the detection of early syphilis infections in the Bialystok province (1989–2010). Material and methods . Material for the study was the documentation of 316 patients diagnosed with early syphilis and 265 registered contacts declared by them, observed and treated in STD clinics. Epidemiological assessment was based on the basic parameters. Social Network Analysis was based on parameters of Seidman k-core. Results . Epidemiological studies showed that 67.4% of 316 patients with early syphilis reported registered contacts (index 0.83). 87.5% of these contacts have been tested and in more than a half (53%) of them early syphilis has been diagnosed. The remaining 16.8% of patients (with their consent) were subjected to prophylactic treatment, and the rest (after an appropriate time of control) were considered to be not infected. Thirty-three persons (12.5%) could not be found. Social Network Analysis of 316 patients showed that as many as 176 (53.7%) did not show any links in epidemiologic investigations. One hundred and twenty-two patients had 2–6 personal links without creating a k-core. Only in 1995, during a syphilis microepidemic (in town C), has a typical network of sexual relationships with a k-core consisting of 18 patients been revealed. Conclusions . The results of the study indicate major shortcomings in the work of STD clinics in Podlaskie Province in the years 1999–2010. Analysis of the structure of sexual networks is a valuable method for enriching the methodology of epidemiological investigations in detecting sources of infection and their contacts, provided very detailed epidemiological investigations are performed and there is close cooperation with other STD clinics. Social Network Analysis of infection sources and their sexual contacts allows forecasting the morbidity, as well as selecting groups according to their sexual behavior, regions in which infections may appear and patients’ social and ethnic group.

Background. The aim of this study was to assess the efficacy of ceftriaxone and benzathine penicillin G (BPG) in nonpregnant, immunocompetent adults with early syphilis because there is a lack of clinical evidence supporting ceftriaxone as an alternative treatment for early syphilis without an human immunodeficiency virus coinfection. Methods. A randomized, open-label controlled study evaluating the efficacy of ceftriaxone and BPG was conducted in 4 hospitals in Jiangsu Province. Treatment comprised either ceftriaxone (1.0 g, given intravenously, once daily for 10 days) or BPG (2.4 million units, given intramuscularly, once weekly for 2 weeks). A serological response was defined as a ≥4-fold decline in the rapid plasma reagin (RPR) titer. Results. In all, 301 patients with early syphilis were enrolled in this study; 230 subjects completed the follow-ups. The serological response at 6 months of follow up was observed in 90.2% in ceftriaxone group and 78.0% in BPG group (P = .01). There was no significant difference between treatment groups in patients with primary or early latent syphilis, but among patients with secondary syphilis the difference was highly significant (95.8% vs 76.2%; P < .01). Moreover, patients exhibiting a Jarisch-Herxheimer reaction after treatment might have a shorter period before a serological response (P = .03). Conclusions. In this study, ceftriaxone regimen was noninferior to the BPG regimen in nonpregnant, immunocompetent patients with early syphilis. [ABSTRACT FROM AUTHOR]

Background: Standard therapy for early syphilis involves intramuscular injections of penicillin G, which frequently faces shortages in several countries. Fourteen-day amoxicillin therapy has been suggested as an alternative to benzathine penicillin G, but the optimal duration of amoxicillin therapy remains unclear and could theoretically be shortened to less than 14 days. The aim of this study was to explore the effectiveness of short-term amoxicillin therapy for early syphilis., Methods: We retrospectively explored the effectiveness of short-term amoxicillin therapy for early syphilis. The treatment data of patients who had received amoxicillin therapy for less than 14 days for unintended reasons were reviewed. Diagnosis was confirmed based on either the physician's description or clinical presentation. Successful treatment was defined as a fourfold or greater decline in the rapid plasma reagin titer or sero-reversion to negative within 12 months., Results: Of 295 patients, 8 received short-term amoxicillin treatment. All were men who had sex with men and people living with human immunodeficiency virus. Their median age, CD4 count, and treatment duration were 34 years (range, 26-40), 258/mL (range, 112-930), and 9.5 days (range, 5-11), respectively. One patient had primary syphilis, six had secondary syphilis, and one had early latent syphilis. All patients, except one who showed reinfection, demonstrated a serological response within 4 months. The median time for serological response was 112 days., Conclusion: The results indicate that early syphilis could potentially be treated with 5-11 days of amoxicillin therapy combined with probenecid. This suggests that short-term amoxicillin therapy might be a sufficient treatment for early syphilis instead of the standard 14-day course., Competing Interests: The authors declare that there is no conflict of interest., (© The Author(s), 2023.)

Syphilis is considered as one of the most devastating sexually transmitted diseases in human history. Based on historical records, the (German for ) spread through Europe after 1495 and shared symptoms with what we know today as syphilis. Many cities took measures to protect their population. Here, transliterations of archival documents from the 15 and 16 century (provided in the appendix) are used to trace the steps taken by the governing authorities in Zurich to deal with this emerging infectious disease. One of the central measures taken by the city was to establish a quarantine facility referred to as the The city doctors, including the well-known physician and naturalist Conrad Gessner, oversaw the obligatory quarantine and treatment of patients with symptoms. Treatment could range from better nutrition, herbal remedies and skin ointments to aggressive heat therapy and “smoking”. Furthermore, the affliction was suspected as a sexually acquired disease, hence prostitutes and infected foreigners were extradited from the city. Meanwhile, the church used its social influence to promote a more “Christian” behavior. In several respects, the public health measures taken in the 16 century against a new and menacing epidemic do not diverge in their basic rationale from approaches used during the 20 century and today.