Ocular syphilis:a case series of four patients and a review of the literature

Background:The incidence of syphilis has been increasing in the United States over the last two decades,with a more recent increase among women.Ocular syphilis is an uncommon but important complication of syphilis,most often presenting as posterior or panuveitis in late or latent syphilis of unknown duration.Untreated ocular syphilis may lead to permanent vision loss,underscoring the importance of appropriate evaluation and treatment of ocular syphilis.Case Description:In a retrospective,non-contiguous case series,we highlight four patients diagnosed and treated with ocular syphilis at a single institution.Four presentations of ocular syphilis are illustrated:anterior and intermediate uveitis,optic neuritis,posterior uveitis,and panuveitis.All patients initially presented with a decreased visual acuity(VA).One patient had a previous diagnosis of human immunodeficiency virus(HIV).Three patients were treated with intravenous(IV)penicillin and one patient with IV ceftriaxone.All had a return to their baseline VA after their course of treatment.Conclusions:Syphilis may go undetected without a high index of clinical suspicion due to its nonspecific presentations.All patients with ocular inflammation should have syphilis testing as a part of their infectious workup with both treponemal and non-treponemal testing.Patients diagnosed with syphilis and are not known to be HIV-negative should undergo testing for HIV due to the high rate of co-infection.Early diagnosis and prompt treatment after onset of symptoms may contribute to a more favorable prognosis for ocular syphilis.

Syphilis and HIV Infection among Pregnant Women Previously Screened Negative during Their First Antenetal Care Visit (ANC) at Some Selected Health Facilities in the Buea Health District, Cameroon

Syphilis and HIV are amongst the world’s most widespread diseases, particularly in low-income countries. Syphilis and HIV infections during pregnancy have been associated with numerous adverse pregnancy outcomes. Of concern now are the rising rates of congenital syphilis and HIV in Cameroon. Cameroon only mandates testing pregnant women for syphilis and HIV during their first ANC visit. This study was aimed at determining the incidence of new syphilis and HIV infections and factors associated with pregnant women who previously tested negative during their first ANC visit. A cohort design was used, where 335 pregnant women were followed up for a period from December 2019 to August 2020. A blood sample was drawn and the serum was analyzed using the WANTAI ELISA and AIDTM HIV 1 + 2 Ag/Ab ELISAPlus test methods for syphilis and HIV respectively at three intervals. A questionnaire was used to identify risk factors. Data was analyzed using SPSS 23.0. Out of the 335 pregnant women who were followed up during this study, 49 (14.6%) were later diagnosed with syphilis (32 in 2nd trimester and 17 in 3rd trimester). 54 (16.1%) were diagnosed with HIV infection (13 at two months post-1st-trimester visit, 23 in the 2nd trimester and 18 in the 3rd trimester). Lastly, 10 (2%) were co-infected with syphilis and HIV of which 8 occurred during 2nd trimester and 2 in the 3rd trimester. The factors associated with contracting new syphilis infections include;younger age group aOR (1.302, 95% CI), leaving in an urban area aOR (3.158, 95% CI), lower level of education (Primary and no formal) with aOR of (9.055, 95% CI) (P = 0.001) and (6.764, 95% CI) (P = 0.006) respectively, inadequate knowledge on the diseases aOR (2.176, 95% CI), women unaware of their partner status aOR (3.190, 95% CI). Most factors associated with contracting new HIV infections were similar to the factors associated with contracting new syphilis infections post 1st ANC visit aOR (1.174, 95% CI) and pregnant women with more than one sexual partner aOR (7.342, 95% CI) were observed for HIV infection.. There is an increased incidence of new infection of syphilis and HIV post first ANC screening in the Buea Health District, Cameroon. The need for constant education on the identifiable factors and these diseases, and screening during every ANC visit irrespective of their previous laboratory results is warranted.

Community-based Survey of Prevalence and Risk Factors of Syphilis among Injection Drug Users in Sichuan Province, China

Objectives: To investigate prevalence and risk fac-tors of syphilis infection among injection drug users(IDUs) in Lianshan Yizu Autonomous Region ofSichuan province, China.Methods: From November 8th 2002 to November29th 2002, a community-based cross-sectional surveywas conducted to investigate the demographic charac-teristics and sexual behaviors of a population of IDUs.Blood samples were collected to test for syphilisinfection. A total of 379 subjects were recruitedfor the study through community outreach and peerrecruiting methods.Results: Of 379 IDUs, the syphilis prevalence amongIDUs was 15.3% (58/379). Gender, years of education,history of unprotected sex with non-steady sex part-ner in the last month, number of sex partners in thelast 6 months, frequency of sex with non-steady sexpartner in the last 6 months, and number of any newsex partner(s) in the last 6 months were associatedwith syphilis infection after univariate analysis usingthe chi-squared test. Multivariate logistic regressionanalysis showed that ethnicity (OR, 2.85; 95% CI,1.55-5.25), marriage (OR, 1.94; 95% CI, 1.04-3.62)and receiving money for sex in the last 6 months (OR, ,5.60; 95% CI, 2.65-11.85) were significantly associ-ated with syphilis infection among IDUs.Conclusions: This study found that receiving moneyfor sex in the last 6 months was significantly associ-ated with syphilis prevalence among IDUs. It isrecommended that further health education andintervention campaigns be focused on IDUs to promotesafe sexual practices.

Serum Treponema lgM Antibody Test for Syphilis Diagnoss

Objective: To evaluate the clinical utility of testingserum anti-treponema pallidum IgM antibody in thediagnosis of syphilis patients. Methods: Seventy-two cases of syphilis were testedfor specific IgM antibody with ELISA, and the resultswere compared with RPR and TPPA. Results: The sensitivity of IgM antibody was 73.3%(11/15) in primary syphilis, 88.9% (16/18) in sec-ondary syphilis, and there was no significant differ-ence between these values (x^2=1.6363, P>0.10). Thesensitivity of IgM antibody in diagnosing latent syphi-lis was only 26.1% (6/23), much lower than the detec-tion rate in symptomatic early syphilis (x^2=17.6189, P<0.005). RPR and TPPA were both 100% sensitive inlatent and early symptomatic syphilis. Two were posi-tive for IgM in the 16 cases who had received regulartreatments 2 to 24 months before enrolled. Conclusions: Specific IgM antibody detection doesnot appear superior to RPR and TPPA in diagnosingprimary syphilis. The diagnosis of latent syphilisshould mainly rely on RPR and TPPA, since there arelow titers of IgM antibody at that stage. IgM antibodytesting alone should not be recommended for monitor-ing syphilis development or treatment efficacy. Fur-ther studies should be concerned.

Analysis of Th1/Th2 and Tc1/Tc2 Balance from Peripheral Blood in Patients with Secondary Early Syphilis

Objective: To understand the change of Th1/Th2 and Tc1/Tc2 balance in patients with secondary early syphilis. Methods: Peripheral blood Th and Tc cell subpopu-lations were examined by three-color flow cytometry in 30 patients with secondary early syphilis and 20 healthy subjects. Results: Percentages of CD3+ CD4+ T cells and the ratio of CD4+CD8+ and NK cells in syphilitic patients were significantly lower than in the control group (P<0.001), but no statistical difference was found in percentages of CD8+ and CD19+ cells between the two groups (P > 0.05). The percentage of Th1 cells and ratios of Th1/Th2 and Tc1/Tc2 in syphilitic patients were clearly decreased as compared to those in controls (P<0.001-0.01), whereas percentages of Tc0 and Tc2 cells in syphilitics was higher than those in controls(P<0.001). Conclusion: There could be a disturbance of cellular immunity and the relatively intact function of humoral immunity in secondary syphilis. It is postulated that the polarization toward development of Th2 and Tc2 cells and their associated cytokines might be involved in the incomplete clearance of treponemes and the development of chronic infection.

Serum Levels of Interleukin-2 and -10 in Patients with Early Syphilis

Objective: To investigate the roles of interleukin-2(IL-2) and interleukin-10 (IL-10) in pathogenesis ofearly syphilis. Methods: The serum levels of IL-2 and IL-10 in 48patients with early syphilis were detected by ABC-ELISA. Results: (1) The level of IL-2 in the patients withearly syphilis was significantly higher than that inhealthy controls, while that of IL-10 was lower(P<0.001 and P<0.001). (2) The levels of IL-2 and IL-10 were almost identical in patients with primary andsecondary syphilis (P>0.05), as well as between dif-ferent RPR titers (P>0.05). (3) After therapy, the levelof IL-2 decreased markedly (P<0.05), while that of IL-10 increase (p>0.05). (4) A significant correlation wasfound between the serum levels of IL-2 and IL-10 (r=0.5385 P<0.05). Conclusions: Th1 up-regulation occurs in patientswith early syphilis, and plays an active role in fightingagainst TP infection.

Analysis of the Current situation of Syphilis in a Sexually Transmitted Disease Clinic

Objective： To analyze the current situation of syphilis in the sexually transmitted diseases （STDs） clinic, from January 1994 to December 2002 was studied. Methods： All syphilis patients were confirmed by history, physical examination, dark-field microscopy of samples taken from the chancre or satellite lymph nodes,or positive serological tests. Results： From 1994 to 2002, there were 2067 cases of early syphilis, accounting for 20.01% （2067/10330） of all STD cases. The annual proportion of syphilis cases among all STD cases from 1994 to 2002 was 0.57%, 0.53%, 3.54%, 16.20%, 31.29%, 27.88%, 25.63%, 17.11%, 10.48%, respectively. Of 2067 syphilis patients,49.64% （1026/2067） were male and 50.36% （1041/2067） were female. 44.75% （925/2067） of all cases presented with primary syphilis, 44.90% （928/2067） with secondary syphilis, 9.77% （202/2067） with latent syphilis （without any conspicuous clinical signs or symptoms）, and 0.58% （12/2067） with congenital syphilis. The 30-39 year old cohort accounted for the largest proportion, at 37.68% （779/2067） of all syphilis cases. The 20-29 year old cohort also accounted for a large proportion, at 37.20% （769/2067） of all cases,followed by the 40-49 year old cohort, at 17.95% （371/2067）. Syphilis was most prevalent among the unemployed,self-employed laborers, and office workers in decreasing order. The majority of cases were graduates of either primary school, high school, or college. Of all syphilis cases, 87.86% （1816/2067） were married, and 12.14%（251/2067, including children） were unmarried. 76.78% （1587/2067） of all cases were acquired through extramarital intercourse. 14.03% （290/2067） of cases were infected by their spouses. 0.58% （12/2067） of cases were due to vertical transmission. 8.61% （178） of cases were acquired through indirect contact. Conclusion： The proportion of syphilis infection among all STDs remained stable from 1994 to 1995,quickly and dramatically increased from 1996 to 1999,and then gradually tapered down from 2000 to 2002. The incidence of congenital syphilis infections increased throughout the study period.

Hepatitis C virus infection and biological falsepositive syphilis test:a single-center experience

BACKGROUND:Rapid plasma regain positive and/or treponema pallidum hemagglutination negative [RPR(+)/TPHA(-)] results were designated as biologic false-positive (BFP).There are limited data about BFP reactions against syphilis in patients with hepatitis C virus (HCV) infection.This study aimed to determine the prevalence of BFP reactions for syphilis in patients with HCV infection in a large sample and assess the relationship between BFP reactions and HCV infection.METHODS:A total of 2656 patients with positive anti-HCV and 5600 healthy control subjects were enrolled in this study.Hepatitis C serology was determined by a second generation ELISA test for HCV antibody.Syphilis serology was determined by the RPR test.Those subjects with reactive RPR positive underwent the TPHA test.Demographics and laboratory data were collected by trained clinicians.RESULTS:Among 2656 patients,111 (4.2%) had a reactive RPR test.Of the 111 patients who were subjected to reactive RPR test,30 (27.0%) showed HCV(+)/RPR(+).Of 5600 healthy controls,80 (1.4%) had a reactive RPR test.Fourteen (17.5%) controls with HCV(-)/RPR(+) had a non-reactive TPHA test.These represented 1.1% of all HCV-positive and 0.3% of all HCV-negative subjects (P<0.001).A significantly increased prevalence shown by false-positive tests for syphilis was observed in elderly HCV-seropositive patients.BFP-HCV positive group had a higher prevalence of eosinophilia.The eosinophil abnormality was compared between the patients and controls (66.7% vs 21.4%,P=0.0043).No significant results were observed in antinuclear antibodies,antiphospholipid and complement (C3,C4) (P>0.05).CONCLUSIONS:The data of this study demonstrate that HCV infection is associated with a false-positive RPR test.In this study BFPs were significantly more common in HCV positive patients compared to HCV-negative ones.Eosinophil abnormality can be considered as a predictor for BFP.Excessive BFPs must be considered in assessing the frequency of syphilis in a HCV-positive population and the importance of the treponemal specific serologic test should be emphasized for a diagnosis of syphilis in such population.

Tertiary syphilis mimicking hepatic metastases of underlying primary peritoneal serous carcinoma

Tertiary syphilis,especially in cases involving visceral gummatous disease,can be confused with cancer of the solid organs.We report a case of tertiary hepatic syphilis that manifested with intrahepatic masses in a patient who had an underlying primary peritoneal serous carcinoma (PPSC).The patient was diagnosed with PPSC and achieved a complete remission of PPSC following six cycles of platinum-based chemotherapy.Two hepatic nodules developed during the follow-up period and were initially labeled as hepatic metastases from the underlying PPSC,based on radiological findings.A resection of hepatic nodules was performed for therapeutic and diagnostic purposes,because there were no other metastatic foci except in the liver.Unex-pectedly,serology and histology confirmed tertiary sy philis.This rare case emphasizes the importance of including tertiary syphilis in the differential diagnosis of a space-occupying lesion,even with an existing diagn osis of underlying cancer.

Ocular syphilis: resurgence of an old disease in modern Malaysian society

Dear Editor,Syphilis is a spirochaetal bacterial sexually transmitted disease（STD） caused by Treponema pallidum. Outbreaks of syphilis have been described in Western communities, especially in men who have sex with men（MSM） and people infected with human immunodeficiency virus（HIV）^（[1]）. Reports of the condition from Asian countries remains limited.

CLINICAL EVALUATION OF FOUR RECOMBINANT TREPONEMA PALLIDUM ANTIGEN-BASED RAPID TESTS IN THE DIAGNOSIS OF SYPHILIS

Objective To assess the sensitivity, specificity, and feasibility of 4 recombinant Treponema pallidum antigenbased rapid tests in the diagnosis of syphilis. Methods A total of 970 outpatients were selected from the Sexually Transmitted Diseases Centre of Peking Union Medical College Hospital. Venous blood was collected and serum was extracted. T. paUidum antibodies in whole blood, anticoagulant whole blood, and serum were detected using 4 recombinant T. pallidum antigen-based rapid tests. T. pallidum haemagglutination test （TPHA） was considered as the gold standard for the detection of T. pallidum specific antibodies in serum. The sensitivities and specificities of four methods were analyzed. Results The sensitivities and specificities of Abbott Determine Syphilis TP test, SD-BIOLINE Syphilis 3.0 test, VISITECT-SYPHILIS test, and Syphicheck-WB test for serum specimens were 100% and 98. 9%, 95.7% and 98.0%, 94.6% and 98.2%, 68.1% and 98.9% ; for whole blood were 74. 1% and 99. 5%, 87.9% and 99.4% , 73.2% and 99.7%, 64. 7% and 99.7%. The observed sensitivities of the 4 rapid diagnosis tests were not significantly different with TPHA （ P 〉 0.05 ）. Conclusions The 4 rapid tests show good performance and characteristics in the diagnosis of syphilis. Furthermore, they are more sensitive for serum specimens than whole blood.

Malignant syphilis accompanied with neurosyphilis in a malnourished patient: A case report

BACKGROUND Syphilis is a common sexually transmitted disease caused by the Treponema pallidum (T.pallidum).Malignant syphilis is a rare presentation of secondary syphilis.Here,we present a case diagnosed with malignant syphilis accompanied with neurosyphilis.CASE SUMMARY A 56-year-old man present with a 2-mo history of spreading ulcerous and necrotic papules and nodules covered with thick crusts over the face,trunk,extremities,and genitalia.The patient was diagnosed with malignant syphilis accompanied by neurosyphilis based on the characteristic morphology of the lesions,positive serological and cerebrospinal fluid tests for syphilis,brain magnetic resonance imaging,and histopathology,along with resolution of the lesions following the institution of penicillin therapy.The lesions and neurological condition successfully resolved after a course of treatment with penicillin.CONCLUSION We suggest that neurosyphilis should be considered whenever people have psychiatric symptoms without cutaneous lesions or human immunodeficiency virus.

Peliosis and gummatous syphilis of the liver: A case report

Peliosis hepatis is a rare benign vascular disorder of the liver that may be associated with malignancy, infection and drugs. The imaging manifestation of this disorder is often variable and nonspecific making its diagnosis difficult. We describe a rare case of peliosis hepatis and gummatous syphilis of the liver with emphasis on CT findings. Image characteristics of our patient included pseudotumoral appearance of peliosis hepatis, isodensity to the adjacent liver parenchyma on unenhanced and dual-phase scanning. To our knowledge, peliosis hepatis associated with syphilis and unique enhancement pattern has not been reported. Considering the imaging features of peliosis hepatis, it should be considered in the differential diagnosis of atypical focal hepatic lesion.

Eliminating Mother-to-Child Transmission of Syphilis: Chinese Practice before and during COVID-19 Pandemics

Mother-to-child transmission(MTCT)of syphilis remains a leading cause of stillbirth and death among neonates in many developing countries.In 2007,World Health Orgernization launched the global elimination of MTCT(EMTCT)of syphilis.Given the high burden of congenital syphilis,China subsequently released the specific national EMTCT policies and programs to reduce MTCT of syphilis.The congenital syphilis incidence rate per 100,000 live births in China has markedly decreased from 69.9 in 2013 to 11.9 in 2019.However,due to the global pandemic of COVID-19,the current measures for eliminating MTCT of syphilis are greatly challenged.In this article,we summarize the strategies and measures for the EMTCT of syphilis in China in the past 20 years,the remarkable achievements by the policy support under the leadership of the government.In the context of COVID-19 pandemics,strengthening emergency response to the regional outbreaks of COVID-19,adopting safe,rapid,early and high-quality clinical care for 100%of pregnant women to receive prenatal syphilis testing services,ensuring the availability of Benzathine penicillin for the treatment,and strengthening the closed-loop management of pregnant women and newborns infected with syphilis are the key measures to determine the effectiveness of MTCT for syphilis.Lessons from China may be valuable for other countries that are planning to eliminate MTCT of syphilis.

Seroprevalence of syphilis in patients attending a tertiary care hospital in Southern India

Objective:To report our experience with two tests,anti-cardiolipin antibody test[venereal disease reasearch laboratory(VDRL) test]and specific treponemal test(Treponema pallidum hemagglutination assay),used for screening antenatal,high risk cases and cases from sexually transmitted infection in a tertiary care hospital from January 2006 till December 2008.Methods:A total of 14639 samples received from various patient groups including antenatal cases,patients attending sexually transmitted disease(STD) clinic,blood donors and HIV positive patients were screened.Results:Among the 14639 samples collected,103 were positive by VDRL test.Of these 89 cases were confirmed by quantitative VDRL test and Treponema pallidum hemagglutination assay.The cumulative seroprevalence over two years was found to be 0.61%in this study.The syphilis seroprevalence reduced from 0.88%in 2006 to 0.40%in 2008.Among the various sub-populations studied,patients attending the sexually transmitted infection clinic showed a seroprevalence of 2.62%.The seroprevalence decreased significantly from 4.00%in 2006 to1.39%in 2008.Conclusions:Our study showed a statistically significant declining rate of syphilis in STD clinics as well as the overall seroprevalence.These findings could be interpreted as indicators of improved programmes for prevention and management of STDs.

Ocular syphilis resurgence in an urban underserved community in the United States

AIM:To evaluate the clinical characteristics,demographics,and visual outcomes of patients with ocular syphilis at an urban hospital to increase awareness and assist in earlier diagnosis and treatment of the resurgent disease.METHODS:A retrospective chart review was performed on patients with ICD-9 and ICD-10 diagnosis codes correlating with syphilis or syphilis-related ocular diseases between 2010 and 2019.Variables evaluated included age,gender,race,vision,ocular findings,human immunodeficiency virus(HIV)status and men who have sex with men status,recreational drug and alcohol use.RESULTS:Ocular syphilis was diagnosed in 40 patients(53 eyes)of a total of 229 patients who tested positive for syphilis via serum and/or cerebrospinal fluid treponemal testing from 2010-2019.Among patients with ocular syphilis,most patients were males,aged 45 or above and Black,and had no diagnosed HIV infection.Approximately 50%patients had 20/40 vision or better.Nearly 50%had nongranulomatous anterior uveitis as their initial presentation,and 49%of patients had involvement of the posterior segment.Neovascular glaucoma(5.7%),papillitis(7.5%),vasculitis(5.7%),and retinal detachment(5.7%)were rarer presentations of the disease and were associated with a poorer visual prognosis.CONCLUSION:Given the increased prevalence and protean manifestations of syphilis,early diagnosis and treatment are paramount.More studies on ocular syphilis are warranted to understand this resurging disease.

Anti-N-methyl-D-aspartate-receptor antibody encephalitis combined with syphilis:A case report

BACKGROUND Anti-N-methyl-D-aspartate-receptor(NMDAR)encephalitis is a common type of autoimmune encephalitis characterized by complex clinical signs and variable imaging manifestations.The pathogenesis of the disease is unclear.Syphilis is an infectious disease caused by Treponema pallidum that can invade the nervous and immune systems and cause systemic symptoms.There are few reports of anti-NMDAR encephalitis with syphilis,and the association between them is unknown;both diseases are related to immune system damage.We report a case of anti-NMDAR encephalitis with syphilis.CASE SUMMARY A 32-year-old man was admitted to our hospital with complaints of cognitive decline,diplopia,and walking instability during the previous 6 mo.He developed dysarthria,difficulty swallowing,and involuntary shaking of his head,neck,and limbs during the month prior to presentation.Cranial magnetic resonance imaging showed symmetrical abnormal signals in the pons,midbrain,and bilateral basal ganglia,and inflammatory demyelination was considered.The diagnosis of syphilis was confirmed based on the syphilis diagnosis test and the syphilis rapid test.He was given anti-syphilis treatment,but the above symptoms gradually worsened.Anti-NMDAR antibody was positive in cerebrospinal fluid but was negative in serum.Due to the cerebrospinal fluid findings,anti-NMDAR encephalitis was a consideration.According to the patient’s weight,he was treated with intravenous methylprednisolone 1 g QD for 5 d,with the dose gradually decreased for 6 mo,and immunoglobulin 25 g QD for 5 d;his symptoms improved after treatment.CONCLUSION This case shows that anti-NMDAR encephalitis may be combined with syphilis,which should be recognized to avoid misdiagnosis and treatment delay.

Gastric syphilis mimicking gastric cancer: A case report

BACKGROUND The nonspecific clinical,radiological and pathological characteristics of gastric syphilis can establish it as an imitator of other gastric diseases.The absence of primary or secondary lubricating lesions should not prevent consideration of gastric syphilis.CASE SUMMARY A 63-year-old female patient presented to the hospital with dull pain in the middle and upper abdomen without apparent cause for one week,which was aggravated for two days.The patient had been sexually active with the same male partner for the past years,but her partner was promiscuous.Abdominal contrastenhanced computed tomography(CT)and positron emission tomography/CT suggested gastric cancer.The gastroscopy revealed an antral gastric ulcer with gastric retention,and also suggested gastric cancer.But no cancer cells were found in the biopsies taken during the two gastroscopies.Treponema pallidum(T.pallidum)antibodies:ELISA positive,rapid plasma reagin titer 1:16.Hematoxylin and eosin(HE)stain showed macrophage infiltration in the lamina propria.Numerous spirochetes were observed by immunohistochemical staining using a monoclonal antibody against T.pallidum.The patient was finally diagnosed with gastric syphilis.CONCLUSION Only a few cases of gastric syphilis have been misdiagnosed as gastric cancer.Penicillin can relieve symptoms of gastric syphilis.

Syphilis Serologic Follow-up After Regular Treatment

Objective： To understand the changes in syphilis serology after regular treatment. Methods： Patients with clinical evidence and credible medical history of syphilis were treated regularly. Their serologic tests were followed for two years. Results： At the end of half a year, 22.95% of patients had a negative USR but 26.23% remained positive even after 2 years. More than 3% of patients had a negative FTA-ABS result. These patients tended to be under 40 with a disease course of less than 2 years. Conclusion： The resolution rate was high for patients who were young, had a shorter course of disease and reacted strongly to the infection. In patients older than 40 with a long course of disease, the resolution rate was low.

Syphilis testing algorithms:A review

The methods and strategies used to screen for syp-hilis and to confirm initially reactive results can vary significantly across clinical laboratories. While the performance characteristics of these different appro-aches have been evaluated by multiple studies, there is not, as of yet, a single, universally recommendedalgorithm for syphilis testing. To clarify the currently available options for syphilis testing, this update will summarize the clinical challenges to diagnosis, review the specific performance characteristics of treponemal and non-treponemal tests, and fnally, summarize select studies published over the past decade which have evaluated these approaches. Specifcally, this review will discuss the traditional and reverse sequence syphilis screening algorithms commonly used in the United States, alongside a discussion of the European Centre for Disease Prevention and Control syphilis algorithm. Ultimately, in the United States, the decision of which algorithm to use is largely dependent on laboratory resources, the local incidence of syphilis and patient demographics. Key words： Syphilis; Treponemal infection; Immuno-assay; Reverse sequence screening; Rapid plasma regain; Treponema pallidum particle agglutination test; Automation; Algorithm; Primary infection; Late latent infection