Therapy For Syphilis Research Articles

Diagnostic Issues of Asymptomatic Neurosyphilis in HIV-Positive Patients: A Retrospective Study.

Introduction: Asymptomatic neurosyphilis (ANS) is a disease that is difficult to diagnose in people living with HIV (PLWH). The European Guidelines on the management of syphilis suggest that ANS should be suspected and thus the lumbar puncture (LP) should be performed in cases of (1) late syphilis (acquired >2 years previously), (2) CD4+ cells ≤ 350/mm3 and/or a serum Venereal Disease Research Laboratory/Rapid Plasma Reagin (VDRL/RPR) title > 1:32, (3) “serological failure” after syphilis therapy, and (4) the use of alternative treatment for syphilis. In the present study, we aimed to verify the accuracy of the guideline’s criteria for the indication of LP in the suspicion of ANS in a cohort of PLWH. Methods: This retrospective study was carried out in a cohort of PLWH referred at a single medical center of a large academic hospital in Italy. Clinical and laboratory data of patients diagnosed with late syphilis were extracted from the cohort and analyzed. The European Guidelines of syphilis were adopted for patient management. Results: Out of a cohort of 713 PLWH, only 51 (7%) had a diagnosis of late syphilis and were therefore included in the study. Thirty-one subjects (61%) met one or more diagnostic criteria to perform LP: 39% (12/31) of patients undergoing LP had a diagnosis of ANS. The accuracy of predictive criteria for ANS, suggested by the guidelines, was 62% for RPR > 1:32 and 74% for CD4+ ≤ 350 cc/µL. The simultaneous occurrence of both criteria (RPR > 1:32 plus CD4+ ≤ 350 cc/µL) achieved a diagnostic accuracy of 59%. Interestingly, only 17% of patients who underwent LP for serological failure were eventually diagnosed positive for ANS. Conclusion: Asymptomatic neurosyphilis represents a challenging, but not uncommon, diagnosis. Therefore, it requires a careful investigation. Low CD4+ cell count and RPR > 1:32 remain excellent predictors of neurosyphilis, but have become the only acceptable predictors of ANS in PLWH. “Serologic failure” should be regarded with caution as a criterion to perform LP in order to investigate possible ANS in HIV-syphilis coinfected patients asymptomatic for neurological disorders. The retrospective nature of this single-site study may represent a limit to the interpretation of the data. Thus, larger clinical studies on the topic are warranted.

Association of interleukin-10 promoter polymorphisms with serofast state after syphilis treatment

ObjectivesRecent studies suggested that upregulation of anti-inflammatory immune response during early syphilis may be associated with persistence of Treponema pallidum infection despite adequate treatment, resulting in a serofast state. The...

Complicated syphilis therapy by permanent fillers

The number of patients suffering from a sexually transmitted disease (STD) in Germany is rising steadily. Mostly MSM (men who have sex with men) are affected. We report the case of an HIV-positive patient with syphilis, in whom the implantation of permanent fillers into the buttocks and thighs, for cosmetic purposes, prevented standard therapy of syphilis by intramuscular penicillin administration. According to current guidelines intravenous ceftriaxone (2 g once daily) was administered instead.

Lack of antiretroviral therapy is associated with higher risk of neurosyphilis among HIV-infected patients who remain serofast after therapy for early syphilis.

Resolution of clinical symptoms and at least 4-fold decline in nontreponemal antibody titers after treatment of syphilis is regarded as “proof of cure.” However, a substantial proportion of patients demonstrates <4-fold reduction of titers after recommended therapy (serofast state). It remains unclear whether the serofast state is indicative of persistence of bacteria or only a residual immune response.The aim of the present study was to determine the association between the serofast state and the risk of neurosyphilis in human immunodeficiency virus (HIV)-infected individuals and to identify potential predictors of neurosyphilis.Thirty-three patients with early syphilis and HIV co-infection were included. One year after the recommended treatment of syphilis, all patients who did not achieve proper serologic response underwent lumbar puncture and cerebrospinal fluid (CSF) examination.Twelve months after completing therapy for syphilis, the proportion of patients with serofast state after syphilis therapy was 36.4% (n = 12). Among them, 5 (41.7%) had neurosyphilis. Individuals who remained serofast and had neurosyphilis (n = 5) when compared to those without neurosyphilis (n = 7) were characterized by significantly lower CD4+ cell count and higher HIV RNA levels (P < .05). Moreover, a significantly higher proportion of patients with neurosyphilis was not receiving antiretroviral therapy (ART). The nonreceipt of ART independently increased the risk of neurosyphilis in the analyzed group of serofast HIV-infected patients (odds ratio = 4.5; 95% confidence interval 1.5–13.59, P = .003).Patients co-infected with HIV require careful serologic and clinical follow-up after therapy for syphilis. In all of the patients who do not respond serologically after treatment for syphilis, especially in those who are not receiving ART, lumbar puncture and CSF examination should be considered.

Treponema pallidum-specific immune responses and autoimmunity in patients who remain serofast after treatment of syphilis.

IntroductionApproximately 15% of appropriately treated patients with early syphilis remain serofast. The pathogenesis and clinical significance of this phenomenon are unclear.AimTo determine the significance of Treponema pallidum-specific immune responses and autoimmunity in the treatment outcome of syphilis (serofast or proper serological response).Material and methodsForty-eight patients with secondary and early latent syphilis (ELS) were enrolled in this study. Reactivity of IgM/IgG antibodies to the treponemal antigens TpN47, TpN17, TpN15 and TmpA was evaluated before and 12 months after intramuscular penicillin therapy for syphilis. Additionally, the presence of antinuclear antibodies (ANA) was determined 12 months after treatment.ResultsAfter 1 year, patients were stratified into two groups based on their serological response: (1) serofast (n = 10) and (2) serologically-cured (n = 38) patients. The serological cure rate was 79.2% at 12 months after treatment. Weak pre- and post-treatment antibody reactivity to TpN47 antigen was found to be significantly associated with a higher risk of the serofast state (OR = 64; 95% CI: 5.01–817; p < 0.005). Patients who remained serofast had a significantly higher ANA prevalence and mean titer when compared to those with proper serological responses (100% vs. 5.3%, respectively, p < 0.005; 1 : 640 vs. 1 : 160, respectively, p < 0.005).ConclusionsWe demonstrate that baseline antigen-specific immune response to Treponema pallidum may be an important predictor of the treatment outcome. Further studies are warranted to identify the role of autoimmunity in the pathomechanism of the serofast state.

Specialty management differences of syphilis and toxoplasmosis surrounding pregnancy: a prospective cross-sectional study

BackgroundSyphilis and toxoplasmosis are two infectious conditions that can occur during pregnancy. Both these diseases can have ocular manifestations and thus are treated by ophthalmologists and obstetricians. We hypothesized that specialty training would affect the way physicians selected therapy.ResultsA total of 209 uveitis specialists and approximately 2500 obstetricians across the USA were surveyed using an online questionnaire distributed via listserv and social media posts. Survey respondents were given a series of clinical vignettes containing case examples of a female patient who was either contemplating pregnancy or in the first trimester and was diagnosed with either syphilis or toxoplasmosis. The questionnaire included a total of four case scenarios with questions relating to the management of these diseases, as well as pregnancy counseling. For the syphilis vignette, a total of 97 physicians responded to the survey questions. Choices of therapy between physician specialty differed significantly (p = 0.0001); however, pregnancy status did not seem to affect therapy choice in syphilis. A total of 96 physicians responded to the survey questions pertaining to the toxoplasmosis vignette. For a non-pregnant patient diagnosed with toxoplasmosis, the differences in therapy choice between specialties were not significant; however, when the patient was pregnant, therapy choice was significantly different between specialties (p = 0.0001).ConclusionsDifferences exist between ophthalmologists and obstetricians concerning the therapy for syphilis and toxoplasmosis during pregnancy. Inter-specialty collaboration is needed to develop consistent criteria to improve the management of these patients.

Cerebral Syphilitic Gumma Can Arise Within Months of Reinfection: A Case of Histologically Proven Treponema pallidum Strain Type 14b/f Infection With Human Immunodeficiency Virus Positivity

A 44-year-old man with human immunodeficiency virus positivity developed cerebral gumma 6 months after appropriate therapy for secondary syphilis. It was surgically resected and histologically, Treponema pallidum (14b/f, a relatively rare strain type) was proven. A complete set of modern techniques was performed to depict rare complication of this classic disease.

Clinical and laboratory characteristics of ocular syphilis, co-infection, and therapy response.

PurposeTo describe the clinical presentation of patients diagnosed with presumed latent ocular syphilis and congenital ocular syphilis at tertiary referral center in Turkey, and to compare the clinical findings with patients described in other studies, specifically focusing on demographics and co-infections.MethodsThis is a retrospective study reviewing the medical records of patients diagnosed with ocular inflammation between January 2012 and June 2014 at a tertiary referral center in Turkey. Ocular syphilis was diagnosed on the basis of non-treponemal and treponemal antibody tests, and cerebrospinal fluid analysis. All the patients diagnosed with ocular syphilis were tested for human immunodeficiency virus (HIV), Toxoplasma gondii, rubella, cytomegalovirus, and herpes.ResultsA total of 1,115 patients were evaluated between January 2012 and June 2014, and 12 patients (1.07%) were diagnosed with ocular syphilis based on the inclusion criteria. None of the patients were seropositive for HIV. Two patients were seropositive for T. gondii-specific IgG. Clinical presentations include non-necrotizing anterior scleritis, non-necrotizing sclerokeratitis, anterior uveitis, intermediate uveitis, posterior uveitis, panuveitis, and optic neuritis. All of the patients showed clinical improvement in the level of ocular inflammation with intravenous penicillin 24 million U/day for 10 days. Three patients received additional oral methotrexate as an adjunctive therapy. Two cases received low-dose trimethoprim–sulfamethoxazole.ConclusionOcular syphilis is an uncommon cause of ocular inflammation in HIV-negative patients. Central retinochoroiditis is the most common ocular manifestation, and it is the most common cause of visual impairment. Ocular syphilis might present associated with co-infections such as T. gondii in developing countries. Oral methotrexate might be beneficial as an adjunctive therapy for ocular syphilis in resolving the residual intraocular inflammation and cystoid macular edema after specific therapy with intravenous penicillin.

Management of Adult Syphilis: Key Questions to Inform the 2015 Centers for Disease Control and Prevention Sexually Transmitted Diseases Treatment Guidelines.

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.

S2k guideline* "Diagnosis and therapy of syphilis"--short version.

S2k guideline* "Diagnosis and therapy of syphilis"--short version.

Current standards for syphilis treatment: comparing the russian and foreign guidelines (part II)

The introduction of penicillin has been a breakthrough in the treatment of syphilis. For 70 years, penicillin remains the preferred drug for the treatment of all forms of the disease; its effectiveness has been proven by wide experience gained from clinical observations. However, a very limited number of published meta-analyzes, systematic reviews and data from randomized controlled trials on the comparative assessment of the effectiveness of various antibiotics and treatment regimens are currently available. Some aspects of syphilis treatment are insufficiently developed, particularly, the treatment schedules for neurosyphilis, syphilis in pregnancy, syphilis in HIV-infected individuals and persons allergic to penicillin. There are disagreements in the assessment of the clinical significance of serofast state after a course of antibiotic therapy. There is no uniform approach to the management of patients with treatment failures. This article compares the Russian standards for syphilis treatment set out in the «Federal guidelines for the management of patients with syphilis» with the current European recommendations of the International Union against Sexually Transmitted Infections (IUSTI) and the recommendations of the US Centers for Disease Control and Prevention (CDC). The peculiarities of these guidelines, their strengths and shortcomings, as well as controversial issues of syphilis therapy are discussed. The differences between the domestic and foreign recommendations are more significant in the section concerning the treatment of syphilis than in the section of diagnosis.

Serological test results of sexually transmitted diseases in patients with condyloma acuminata.

IntroductionHuman papillomavirus (HPV) is one of the most common causes of sexually transmitted diseases (STD). The incidence of condyloma acuminata (CA) has increased in recent years.AimTo determine demographical features and serological test results of STD in patients with CA.Material and methodsA cross-sectional survey was conducted on 94 patients presenting to a dermatology clinic in Ankara, Middle Anatolia, Turkey. Dermatological examinations were made and the patients completed a questionnaire which consisted of questions about their marital status, partners and condom use. In all cases, VDRL/RPR, anti-HIV, HBsAg, anti-HCV and in 57 cases – HSV type 1–2 IgM and IgG were studied. If the value of VDRL or RPR was positive, TPHA was conducted.ResultsIn our study, 83 men and 11 women had CA. We could not analyze whether our cases had multiple partners and a habit of condom use as some of the patients did not answer questions about their sexual life. We observed VDRL and TPHA positivity in 3 (3.1%) cases, none of those cases had clinical findings of syphilis and they denied using any therapy for syphilis. HBsAg positivity was found in 3 cases. No anti-HIV and anti-HCV antibody positivity was detected.ConclusionsThe seroprevalence of HBsAg in our study was similar to that of the general population of Turkey. But as we found positive syphilis serology in 3 patients, we suggest that syphilis serology should be investigated in patients with CA.

Successful Repair of a Syphilitic Aortic Arch Aneurysm Accompanied by Serious Cerebral Infarction

We present a 52-year-old male with a syphilitic aortic arch aneurysm accompanied by relevant extensive cerebral infarction. He was admitted to a local hospital for sudden loss of consciousness, where he was diagnosed with serious cerebral infarction. During his treatment, a multilocular aortic arch aneurysm involving the arch vessels was found incidentally. He was transferred to our hospital for surgical treatment. A preoperative routine laboratory test for syphilis was highly positive, which suggested that the aneurysm was likely caused by syphilis and the cerebral infarction was also induced by the involvement of syphilitic aortitis or arteritis. After 2 weeks of antibiotic therapy for syphilis, total arch replacement was performed successfully using meticulous brain protection with antegrade selective cerebral perfusion and deep hypothermia. He recovered without any further cerebral deficits. The pathological examination of the surgical specimen showed some characteristic changes of syphilitic aortitis.

Predicting Risk of Bladder Cancer Using Clinical and Demographic Information from Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial Participants

Effective screening and prevention strategies for bladder cancer require accurate risk stratification models. We developed models to predict the risk of bladder cancer based on clinical and sociodemographic data on participants in the Prostate, Lung, Colorectal, and Ovarian Cancer (PLCO) screening trial. Baseline clinical and sociodemographic data were obtained from 149,542 PLCO participants, ages 55 to 74 years, without a prior history of bladder cancer. Cox proportional hazards models were used to predict the risk of all bladder cancers (ABC) and of high-grade bladder cancers (HGBC) from baseline information. We used the HGBC risk model to design a hypothetical bladder cancer mortality prevention trial. Over a median follow-up of 12 years, 1,124 men and 259 women developed bladder cancer (including 392 and 72 with HGBC, respectively). The incidence in men and in women was 133.6 and 29.6 cases per 100,000 person-years, respectively. Nomograms constructed for predicting the risk of ABC and HGBC had c-indices of 0.746 and 0.759, respectively. Age, race, education, smoking (intensity and duration), comorbidity, prostatitis, syphilis, and hormone replacement therapy use were statistically significant predictors in the models. We show that our risk model can be used to design a bladder cancer mortality prevention trial half the size of a trial designed without risk stratification. Models to predict the risk of ABC and HGBC have been developed and validated. Using the upper 40th percentile from the HGBC model, a suitable cohort for a screening or chemoprevention trial could be identified, although the size and follow-up of such a trial would be costly.

Enhanced therapy for primary and secondary syphilis: a longitudinal retrospective analysis of cure rates and associated factors

For the treatment of early infectious syphilis, enhanced therapy with three dosages of benzathine penicillin G has been under consideration, particularly in the human immunodeficiency virus type 1 infected population (HIV-1). The serological outcome of 249 patients with primary and secondary syphilis treated with standard or enhanced therapy was analyzed retrospectively; 98% (139/142) achieved serological cure with a single dosage and 92% with enhanced therapy (P=0.033). In HIV-1 infected individuals, cure rates were 88% after a single dosage compared to 97% after three dosages (P=0.18). A fourfold decrease of Venereal Disease Research Laboratory (VDRL) titres was achieved within a median of 102 days after treatment initiation (SD=2; 95% CI=98-106). Patients aged over 40 years were 5.5 times (OR=5.52; 95% CI=1.43-21.32; P=0.013) and patients with low baseline VDRL titres (≤ 1:32) were 4 times (OR=4.25; 95% CI=1.21-14.87; P=0.024) more likely to experience serological failure.

Clinical management of early syphilis

Early syphilis therapy was a focus of intense research in the early 20th century with many and varied approaches being used. The development of penicillin and its efficacy in the treatment of syphilis transformed syphilis management for many with and at risk for infection. However, problems such as beta-lactam allergies and the desire for easily administered, alternate therapies have led to evaluation of multiple other drugs, with doxycycline currently recommended as the main alternative. Ceftriaxone and azithromycin have been shown to be effective, however, each has its own difficulties. Follow-up relies on serological testing, leading to concerns when these tests do not decline appropriately. Given concerns about the potential for increased risk for treatment failure, patients with HIV and pregnant women are of particular concern.

Psychotic Disorder Due to Neurosyphilis

Psychotic Disorder Due to Neurosyphilis

Reply to Yang et al

To the Editor—We appreciate the response from Drs Yang, Chang, and Hung to our article “Syphilis treatment response among HIV-discordant couples in Zambia and Rwanda” [1]. It is true that the calculated treatment response rate may be an underestimate or an overestimate based on the limitations of our retrospective analysis, although the size of the human immunodeficiency virus (HIV)–discordant cohort and the duration of extended follow-up adds to previously published literature confirming the utility of single-dose therapy to treat early syphilis in HIV-infected persons. Because we did not have any rapid plasma reagin (RPR) values, symptom information, or documentation of syphilis therapy prior to the period of the study, we decided to dichotomize clients into incident or prevalent disease. Among the group classified as prevalent disease, some had latent infection from >12 months prior and may have benefited from 2 additional weekly doses of benzathine penicillin, although others in this group likely had early-stage infection acquired prior to study onset or had serofast state following previous therapy. These latter 2 groups would likely not have benefited from additional penicillin therapy. Clinical information to allow more precise categorization of these cases would have been helpful but was not available to us. As often encountered in clinical practice, many positive samples had low titer RPR values. To increase testing specificity in our study design, we included only RPR titers ≥1:2 in our subsequent multivariate and Cox proportional hazard analyses. For the subset of samples with treponemal confirmatory testing available, most RPR titers ≥1:2 were confirmed and therefore were unlikely to be biological false-positive tests (see Table 3 [1]). Among those with >1 episode of positive RPR during the study period, the response rate was similar compared to those with a single episode (61% among those with >1 episode and 72% among those with 1 episode). Data presented in the article's Table 4 [1] show separate multivariate modeling for patients who had a single episode and those with >1 episode treated during the study period. Treatment response among coinfected patients remains an important area of research, and we certainly agree with the need for prospective randomized or observational trials in varying populations, including in men who have sex with men.

Serological Response to Treatment of Syphilis According to Disease Stage and HIV Status

Serology is the mainstay for syphilis diagnosis and treatment monitoring. We investigated serological response to treatment of syphilis according to disease stage and HIV status. A retrospective cohort study of 264 patients with syphilis was conducted, including 90 primary, 133 secondary, 33 latent, and 8 tertiary syphilis cases. Response to treatment as measured by the Venereal Disease Research Laboratory (VDRL) test and a specific IgM (immunoglobulin M) capture enzyme-linked immunosorbent assay (ELISA; Pathozyme-IgM) was assessed by Cox regression analysis. Forty-two percent of primary syphilis patients had a negative VDRL test at their diagnosis. Three months after treatment, 85%-100% of primary syphilis patients had reached the VDRL endpoint, compared with 76%-89% of patients with secondary syphilis and 44%-79% with latent syphilis. In the overall multivariate Cox regression analysis, serological response to treatment was not influenced by human immunodeficiency virus (HIV) infection and reinfection. However, within primary syphilis, HIV patients with a CD4 count of <500 cells/μL had a slower treatment response (P = .012). Compared with primary syphilis, secondary and latent syphilis showed a slower serological response of VDRL (P = .092 and P < .001) and Pathozyme-IgM tests (P < .001 and P = .012). The VDRL should not be recommended as a screening test owing to lack of sensitivity. The syphilis disease stage significantly influences treatment response whereas HIV coinfection only within primary syphilis has an impact. VDRL test titers should decline at least 4-fold within 3-6 months after therapy for primary or secondary syphilis, and within 12-24 months for latent syphilis. IgM ELISA might be a supplement for diagnosis and treatment monitoring.

Long-term neurological follow-up of HIV-positive patients diagnosed with syphilis

No cerebrospinal fluid (CSF) abnormalities are found in HIV-positive patients in long-term follow-up after standard syphilis treatment. Syphilis has been reported to have immunological effects on HIV infection and HIV is known to modulate both the manifestations of syphilis and the serological response to therapy. HIV-positive patients who had been diagnosed with and treated for syphilis prior to 2007 were identified. Patients were consented for lumbar puncture. Serum HIV viral load, CD4 count and CSF were recorded. Thirty-five patients with previously diagnosed and treated syphilis underwent lumbar puncture. Thirty-four patients had a normal neurological exam. Only one patient had an abnormal mean white cell count (10.7 cells per high-power field). The finding that those with previously diagnosed syphilis had normal CSF and clinical findings is reassuring and supports the practice of using standard syphilis therapy in HIV-positive patients.