Quantified Detection of Treponema pallidum DNA by PCR Assays in Urine and Plasma of Syphilis Patients.

Treponema pallidum can invade any organ, and T. pallidum DNA can be detected in various tissues and fluids. However, the knowledge of the presence and loads of T. pallidum DNA in urine is limited. For this study, we enrolled 208 syphilis patients (34 primary syphilis, 61 secondary syphilis, 68 latent syphilis, and 45 symptomatic neurosyphilis) and collected urine and plasma samples from them. polA and Tpp47 genes were amplified in urine supernatant, urine sediment, and plasma using nested PCR and droplet digital PCR assays. The detection rates were 14.9% (31 of 208) and 24.2% (50 of 207) in urine supernatant and sediment, respectively (P = 0.017). The detection rates of T. pallidum DNA in urine sediment were 47.1, 47.5, 4.4, and 4.5% for primary, secondary, latent, and symptomatic neurosyphilis, respectively. After treatment, T. pallidum DNA in urine in 20 syphilis patients turned negative. Loads of T. pallidum DNA in urine sediment were significantly higher than those in plasma and urine supernatant (both P < 0.05). Our study indicated that T. pallidum DNA in urine could be found in patients at all stages of syphilis and showed high loads in urine sediment. Though it is unlikely to improve the routine diagnostic algorithm, the detection of T. pallidum DNA in urine may play certain roles in cases difficult to diagnose. In addition, urine is abundant and convenient to collect; therefore, urine sediment could be an ideal specimen for acquiring an amount of T. pallidum DNA that can be supplement samples for the detection of molecular typing of T. pallidum. IMPORTANCE Syphilis is a sexually transmitted disease caused by Treponema pallidum sub. pallidum. T. pallidum can invade many organs, and T. pallidum DNA can be detected in various tissues and fluids. The results reported here demonstrated that T. pallidum DNA could be detected in urine in patients at all stages of syphilis. The detection rate and loads of T. pallidum DNA in urine sediment were significantly higher than those in urine supernatant. Urine is abundant, and its collection is noninvasive and convenient; therefore, urine is an ideal sample for acquiring a large amount of T. pallidum DNA, which can be supplement samples for the detection of molecular typing of T. pallidum.

Syphilis-related rapidly progressive glomerulonephritis: a case presentation.

BACKGROUND: Syphilis is a multisystemic infection that causes a wide variety of symptoms and thus has been dubbed one of the great medical mimickers. Due to recent global re-emergence of syphilis, it has become important to recognize its various presentations. Relative to the kidney, syphilitic infections generally present themselves with nephrotic range proteinuria, and are most often associated with pathological features of a membranous glomerulonephritis with subepithelial immune complex deposition. However, other rare renal presentations have been reported. One of these includes a rapidly progressive glomerulonephritis picture. All described cases have been successfully resolved with the treatment of the underlying syphilis infection. CASE PRESENTATION: The patient was an elderly woman of Caribbean descent who presented with lower extremity weakness, anasarca and proteinuria, hematuria with progressive renal failure. On kidney biopsy, she was found to have a pauci-immune crescentic glomerulonephritis pattern and a concomitant acute tubulointerstitial nephritis. She had a positive Treponema pallidum particle agglutination test and a negative syphilis rapid plasma reagin test with clinical evidence of polyneuropathy suggestive chronic syphilis infection. CONCLUSION AND DISCUSSION: It is important in the context of pauci-immune crescentic glomerulonephritis to explore all differential diagnoses. Given the positive syphilis serologies, clinical context and presence of tubulointerstitial nephritis, she was determined to have syphilitic glomerulonephritis that resolved with a course of both penicillin and steroids.

Don't forget syphilis in membranous nephropathy before immunosuppressants: Latent syphilis in a patient with proteinuria / No olvide la sífilis en la nefropatía membranosa antes de los inmunosupresores

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[Late congenital syphilis: case report]. / Sífilis congénita tardía: a propósito de un caso.

Syphilis shows marked increase in its prevalence in Argentina and the world. The World Health Organization estimates that annually there are 12 million people infected in the world, 270,000 corresponding to newborns with congenital syphilis. We describe an 8-year-old girl who was undergoing mononucleosis due to Epstein-Barr virus and presented syphilis as a diagnostic finding, confirmed by two different positive treponemal tests, assuming a compatible picture of late latent congenital asymptomatic syphilis.

La sífilis presenta un marcado aumento de su prevalencia en Argentina y en el mundo. La Organización Mundial de la Salud estima que, por año, hay 12 millones de personas infectadas mundialmente, y 270 000 corresponden a recién nacidos con sífilis congènita. Se presenta a una niña de 8 años de edad con mononucleosis por virus de Epstein-Barr, que mostró como hallazgo diagnóstico sífilis confirmada por dos pruebas treponémicas positivas; se interpretó el cuadro como compatible con sífilis congènita latente tardía asintomática.

A Novel Nested Real-time Polymerase Chain Reaction for Treponema pallidum DNA in Syphilis Biospecimens.

BACKGROUND: Early diagnosis of Treponema pallidum infection is helpful for disease management, and conventional PCR is suitable for lesion swabs of patients with probable early syphilis. We thus tested nested and real-time PCR (NR-PCR) in various biosamples from syphilitic patients. METHODS: Samples were collected from syphilis patients before treatment. Specific primer sequences targeting the T. pallidum gene polA were designed for NR-PCR. RESULTS: Across syphilis types, most samples assayed with NR-PCR returned a positive result, including earlobe blood (92.0%), cerebrospinal fluid (CSF) (90.2%), lesion swabs (74.3%), serum (66.9%), and whole blood (64.2%). No significant differences were observed in positive samples for whole blood, serum, and lesion swabs between primary and secondary syphilis (P > 0.05 for all comparisons). However, more whole-blood samples from patients with secondary syphilis were positive for NR-PCR than whole blood samples from patients with tertiary and latent syphilis (P < 0.05 for all comparisons). For neurosyphilis patients, significantly more earlobe blood samples tested positive than did whole-blood samples (P < 0.05), but there was no difference in positive results for earlobe blood and whole blood in latent syphilis. Significantly more serum samples tested positive in latent syphilis patients with rapid plasma regain (RPR) titers of 1:8 or greater, compared to those with RPR of 1:4 or less. CONCLUSIONS: Nested and real-time PCR can be used to identify T. pallidum DNA in biosamples from syphilitic patients, especially earlobe blood.

Reactor Grids for Prioritizing Syphilis Investigations: Are Primary Syphilis Cases Being Missed?

BACKGROUND: Health departments prioritize investigations of reported reactive serologic tests based on age, gender, and titer using reactor grids. We wondered how reactor grids are used in different programs, and if administratively closing investigations of low-titer tests could lead to missed primary syphilis cases. METHODS: We obtained a convenience sample of reactor grids from 13 health departments. Interviews with staff from several jurisdictions described the role of grids in surveillance and intervention. From 5 jurisdictions, trends in reactive nontreponemal tests and syphilis cases over time (2006-2015) were assessed by gender, age, and titer. In addition, nationally-reported primary syphilis cases (2013-2015) were analyzed to determine what proportion had low titers (≤1:4) that might be administratively closed by grids without further investigation. RESULTS: Grids and follow-up approaches varied widely. Health departments in the study received a total of 48,573 to 496,503 reactive serologies over a 10-year period (3044-57,242 per year). In 2006 to 2015, the number of reactive serologies increased 37% to 169%. Increases were largely driven by tests for men although the ratios of tests per reported case remained stable over time. Almost one quarter of reported primary syphilis had low titers that would be excluded by most grids. The number of potentially missed primary syphilis cases varied by gender and age with 41- to 54-year-old men accounting for most. CONCLUSIONS: Reactor grids that close tests with low titers or from older individuals may miss some primary syphilis cases. Automatic, computerized record searches of all reactive serologic tests could help improve prioritization.

Misdiagnosed neurosyphilis associated with prolonged psychosis.

OBJECTIVE: After the prevalence of syphilis had reached historic lows, the Center for Disease Control devised a plan to eradicate syphilis in the United States. Since that decree there has been a dramatic rise in new cases. Psychosis is an ominous symptom of neurosyphilis. METHODS: We report a case of neurosyphilis that was misdiagnosed and staged incorrectly. RESULTS: Failure to diagnose neurosyphilis was associated with prolonged psychosis that has been refractory to antipsychotic treatment. CONCLUSION: Psychiatrists should renew their vigilance for neurosyphilis in the setting of a positive screening test and psychosis.

Syphilitic hepatitis uncommon presentation of an old scourge.

BACKGROUND: Giant cell hepatitis is a rare entity in adults, accounting for 0.1% to 0.25% of liver disease in adults. Postinfantile giant cell hepatitis is often characterized by multinucleated giant cells on liver biopsy and a fulminant hepatitis. CASE REPORT: An active duty 36-year-old African-American male deployed to Kabul, Afghanistan, presented with jaundice 2 weeks after starting a testosterone analogue. He discontinued the supplement, but his jaundice persisted with up-trending bilirubin. Serologic testing was negative for hepatitis A, B, C, and E; cytomegalovirus; Epstein-Barr virus; herpes simplex virus; and human immunodeficiency virus. Evaluation for autoimmune hepatitis was negative. Magnetic resonance cholangiopancreatography was negative for obstruction. Liver biopsy revealed giant cell transformation of numerous hepatocytes and cholestatic hepatitis. Rapid plasma reagin was positive without physical findings. Treponema pallidum hemagglutination assays confirmed the diagnosis of latent syphilis. He was started on penicillin treatment with rapid improvement of bilirubin, creatinine, and hepatic synthetic function, all of which eventually normalized. CONCLUSION: Postinfantile giant cell hepatitis is a severe form of hepatitis that has several different potential etiologies, 2 of which were present in this patient: androgenic supplements and infection. This case highlights syphilis as an unusual but treatable cause of giant cell hepatitis. Testing for syphilis should be considered in any persistent liver injury.

Late latent syphilis in a patient with end-stage renal disease and presumptive penicillin allergy.

PURPOSE: Pharmacotherapy challenges in a case of late latent syphilis complicated by end-stage renal disease and presumptive penicillin allergy are described. SUMMARY: A 58-year-old white woman was admitted to the hospital for symptoms including altered mental status, shortness of breath, and chest pain. The initial workup isolated syphilis immunoglobulin G antibody. A treponemal test was reactive, and a nontreponemal test was nonreactive; analysis of cerebrospinal fluid did not indicate neurosyphilis. The patient was diagnosed as having late latent syphilis of unknown duration, for which the standard treatment is intramuscular penicillin G benzathine 2.4 million units once weekly for three weeks. Given the patient's advanced renal disease and other serious comorbidities, there were concerns about the potential need for renal dosage adjustment and repeated desensitization. However, given the slow absorption and long half-life of penicillin G and published data indicating its safe use in the context of hemodialysis, the treating clinicians decided to proceed with penicillin G therapy at the usual dose after an oral penicillin desensitization protocol; repeat desensitization before two subsequent injections was not performed. The patient completed the full course of penicillin G without incident. Notably, skin testing was not performed to definitively establish penicillin allergy. Microbiological testing to determine a cure of syphilis was not performed. CONCLUSION: After the completion of an oral desensitization protocol, the standard three-dose regimen of intramuscular penicillin G for late latent syphilis was safely administered to a hemodialysis patient without dosage adjustment or repeated desensitization.

The role of methotrexate in resolving ocular inflammation after specific therapy for presumed latent syphilitic uveitis and presumed tuberculosis-related uveitis.

PURPOSE: This study was designed to investigate whether the antiinflammatory and antiproliferative activity of oral and intravitreal methotrexate (MTX) suppresses intraocular inflammation in patients with presumed latent syphilitic uveitis and presumed tuberculosis-related uveitis. METHODS: Interventional prospective study including three cases with presumed latent syphilitic uveitis treated with intravenous penicillin and oral MTX, and two cases with presumed tuberculosis-related uveitis treated with standard antituberculosis therapy and intravitreal MTX injections. Treatment efficacy of all cases was assessed by best-corrected visual acuity, fundus fluorescein angiography, and optical coherence tomography. RESULTS: Four eyes of 3 patients with presumed latent syphilitic uveitis had improved best-corrected visual acuity, suppression of intraocular inflammation, and resolution of cystoid macular edema in 6 months with oral MTX therapy. No recurrence of intraocular inflammation was observed in 6 months to 18 months of follow-up period after cessation of MTX. Two eyes of two patients with presumed tuberculosis-related uveitis showed improved best-corrected visual acuity, suppression of intraocular inflammation, and resolution of cystoid macular edema after intravitreal injections of MTX. No recurrence of intraocular inflammation was observed in 6 months to 8 months of follow-up period after cessation of antituberculous therapy. CONCLUSION: For the first time in the treatment of presumed latent syphilitic uveitis and presumed tuberculosis-related uveitis, we believe that MTX might have an adjunctive role to suppress intraocular inflammation, reduce uveitic macular edema, and prevent the recurrences of the diseases.

Detection of Treponema pallidum by semi-nested PCR in the cerebrospinal fluid of asymptomatic HIV-infected patients with latent syphilis.

BACKGROUND: Neurosyphilis diagnosis is frequently dependent upon the results of serological tests and cerebrospinal fluid abnormalities, but the reliability of findings in patients with HIV-1 infection has been questioned, especially in asymptomatic patients with latent syphilis. In this study, we present the data on the presence of T. pallidum DNA in CSF from asymptomatic HIV-infected patients with the diagnosis of syphilis. METHODS: CSF and serum samples were collected from 12 HIV-infected patients attending a tertiary care clinic located in southern Brazil, during the period 2012 to 2013. RESULTS: In CSF samples from five of 12 patients (40%), we detected T. pallidum DNA. Unexpectedly, in these patients, the CSF cell count, protein and glucose levels were normal. In addition, none of these 5 CSF samples presented a positive VDRL reaction. Serum VDRL titers were similar between patients with positive and negative CSF T. pallidum DNA. Most patients with detectable T. pallidum DNA presented low serum VDRL titers. A higher serum VDRL titer of 1:64 was observed in only one patient. CONCLUSIONS: Our results have shown that asymptomatic HIV-infected patients with evidence of latent syphilis and normal CSF might present detectable T. pallidum DNA in the CSF. The detection of T. pallidum DNA by our seminested PCR provides additional information beyond conventional CSF analysis for the diagnosis of neurosyphilis. The detection of T. pallidum DNA in CSF despite normal CSF findings in HIV-infected patients could also provide a different therapeutic approach including the use of intravenous aqueous crystalline penicillin.

[Syphilis and pregnancy: study of 94 cases]. / Sífilis y embarazo: estudio de 94 casos.

BACKGROUND AND OBJECTIVE: To study the epidemiology, diagnosis, treatment strategies and perinatal outcomes of gestational syphilis. PATIENTS AND METHOD: We performed a retrospective study of 94 pregnant women with syphilis whose gestation and delivery were monitored in a Department of Obstetrics from 2002 to 2010 among a total of 85,806 births of women without syphilis in the same period. RESULTS: The prevalence of gestational syphilis was 0.11%. Most of the women were foreign and the most prevalent type was late latent syphilis. Only 57 patients underwent right treatment despite adequate prescription. Maternal complications were confirmed in 31 pregnant women and 16 cases had fetal complications. We diagnosed 4 cases of neonatal syphilis, 3 of them with syphilitic meningitis, whose mothers had not completed the treatment correctly. CONCLUSIONS: The implementation of a mandatory syphilis serology in the pregnancy has enabled us to diagnose many cases of late latent syphilis. The successful completion of treatment must be ensured to prevent vertical transmission.

Characteristics of patients with primary and late latent syphilis patients who were initially non-reactive to the rapid plasma reagin test.

We aimed at determining the characteristics of patients with primary and late latent syphilis who were non-reactive on initial screening by rapid plasma reagin (RPR) but reactive by treponemal tests. We collected the RPR test results of all primary and late latent syphilis patients in our hospital from December 2000 to March 2012. The characteristics of syphilis patients who were non-reactive by RPR testing were compared to those of reactive patients. Multiple logistic regression was used to identify factors associated with non-reactive RPR results. Among primary syphilis patients, 37 (16.5%) were non-reactive on initial RPR and were compared with the 187 reactive cases. Age >35 years was an independent factor associated with a non-reactive result in primary cases (odds ratio [OR], 95% confidence intervals [CI] = 3.55 [1.39-9.07]). Of the late latent patients, 61 (8.8%) were non-reactive by RPR and 636 were reactive. Age >34 years was also an independent factor associated with a non-reactive result in late latent cases (OR [95% CI] = 4.30 [2.28-8.12]). This study suggests that RPR testing alone is insufficient to diagnose primary and late latent infections, especially in middle-aged and elderly individuals. Syphilis detection was lower for patients with primary syphilis than for those with late latent syphilis based on the results of the RPR.

[Syphilis]. / Syphilis.

Syphilis is back since 2000. Early syphilis comprises primary syphilis, secondary syphilis and early latent syphilis (less than 1 year duration). During early phases of syphilis, patients are more contagious and neurologic complications are rare. Early neurosyphilis are mostly represented by uveitis or cranial nerves lesions. Treatment of non-neurologic syphilis are based on intramusculary injection of benzathine-penicilline G: one injection in case of early syphilis, three injections in case of late syphilis. The follow-up after treatment is based on clinical evolution and the titer of VDRL. Intravenously infusion of penicillin G is the only treatment recommended for neurosyphilis.