Correction: Validation of Serological Tests for the Detection of Antibodies Against Treponema pallidum in Nonhuman Primates

ABSTRACT Syphilitic plasma can be salvaged from discarded blood donations and converted to serum by defibrination. Sixty-nine units of plasma were treated with a stock solution of 100 U of thrombin per ml in 1 M calcium chloride and then with a 10% (wt/vol) solution of kaolin. Fibrinogen concentrations detected in initial plasma samples ranged from 94 to 4,970 mg/liter (mean, 2,532 mg/liter) for samples that were reactive by the rapid plasma reagin circle card test (RPR) and from 314 to 2,742 mg/liter (mean 1,528 mg/liter) for samples that were not reactive by the RPR. The treated samples showed no measurable fibrinogen remaining after the defibrination process. In the nontreponemal RPR for syphilis, 86% of the treated plasma samples retained the same endpoint titer as that of the initial plasma sample. When the Treponema pallidum passive-particle-agglutination test was used, 98% retained the same reactivity. In the Captia Syphilis-G enzyme immunoassay, 89% of the treated samples demonstrated no change in reactivity index, and in the fluorescent treponemal antibody absorption test, 96% showed no reduction in fluorescence. Human sera containing antibodies to syphilis are used at the Centers for Disease Control and Prevention for the preparation of reference controls or as samples for proficiency testing. Finding reactive sera is becoming more difficult due to the general decline of syphilis cases in the United States. The decreasing availability of these sera can be alleviated by salvaging plasma and converting it to serum.

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Evaluation of the recombinant protein Tp0965 of Treponema pallidum as candidate antigen for serological diagnosis of syphilis

Annals of the Russian academy of medical sciences ◽

10.15690/vramn653 ◽

2016 ◽

Vol 71 (2) ◽

pp. 109-113 ◽

Cited By ~ 3

Author(s):

A. V. Runina ◽

A. S. Starovoitova ◽

D. G. Deryabin ◽

A. A. Kubanov

Keyword(s):

Recombinant Protein ◽

Metal Chelate ◽

Treponema Pallidum ◽

Serological Diagnosis ◽

Serological Tests ◽

Isolation And Purification ◽

Sensitivity Specificity ◽

Candidate Antigen ◽

Latent Syphilis

Backgraund: Treponemal tests based on detection of antibodies against the T. pallidum antigens are the most specific methods for serological diagnosis of syphilis. Due to inability to cultivate this bacterium in vitro, the most promising sources of its antigens for diagnostic reactions are recombinant proteins of T. pallidum. Cloning and evaluation of the analytical value of certain T. pallidum proteins is the approach to improve the sensitivity, specificity, and reproducibility of serological tests for syphilis, including possibilities of differential diagnosis of various forms of the disease.Objective: The aim of present study was to evaluate the analytical values (sensitivity and specificity) of Tp0965 recombinant protein of T. pallidum as a candidate antigen for serological diagnosis of syphilis.Methods: Tp0965 gene was amplified by polymerase chain reaction from T. pallidum genomic DNA (Nichol's strain) and the nucleotide sequence was cloned into the expression vector pET28a. E. coli BL-21 (DE3) cells were transformed with this plasmid, and the recombinant protein production was induced by isopropyl-β-D-1-thiogalactopyranoside. Isolation and purification of Tp0965 recombinant protein from bacterial lysate was performed by metal‐chelate affinity chromatography using Ni-NTA Sepharose. The collected protein was seeded on high binding 96-well plates, which were used for ELISA with sera of patients with various forms of syphilis in comparison with healthy donors.Results: High frequency of positive ELISA results was shown with serum of patients with syphilis, compared with a group of healthy donors. The sensitivity of serological reactions using recombinant protein Tr0965 was 98.8%, specificity - 87.5%. The highest sensitivity (100%) was detected in the groups of patients with primary, secondary and early latent syphilis, while in the group of patients with late latent syphilis it decreased to 95.2%.Conclusions: We concluded that due to their specificity the recombinant protein Tp0965 T.pallidum can be used as a candidate antigen for development of syphilis serological diagnostic assays.

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Previous Syphilis Alters the Course of Subsequent Episodes of Syphilis

Clinical Infectious Diseases ◽

10.1093/cid/ciz943 ◽

2019 ◽

Vol 71 (5) ◽

pp. 1243-1247 ◽

Cited By ~ 1

Author(s):

Christina M Marra ◽

Clare L Maxwell ◽

Sharon K Sahi ◽

Lauren C Tantalo ◽

Shelia B Dunaway ◽

...

Keyword(s):

Public Health ◽

Polymerase Chain Reaction ◽

Cerebrospinal Fluid ◽

Logistic Regression ◽

Treponema Pallidum ◽

Chain Reaction ◽

Serological Tests ◽

Health Records ◽

Polymerase Chain ◽

Diagnosis Date

Abstract Background Individuals with previous syphilis may be more likely to be asymptomatic when they are reinfected with Treponema pallidum. Methods Individuals enrolled in a study of cerebrospinal fluid (CSF) abnormalities in syphilis were allowed to enroll in the study again with subsequent syphilis. For each participant, the index episode was defined as the most recent syphilis episode for which the study entry visit was performed within 30 days of the syphilis diagnosis date. Venipuncture and lumbar puncture were performed. The total number of syphilis episodes was determined by review of medical and public health records. Treponema pallidum DNA in blood and rRNA in CSF were detected using polymerase chain reaction (PCR) and reverse transcriptase PCR. Odds ratios (ORs) with 95% confidence intervals (CIs) were determined using logistic regression. Results 701 individuals had 1 (n = 478), 2 (n = 155), or ≥3 (n = 68) episodes of syphilis. The proportion of individuals whose index episode was asymptomatic significantly increased with increased number of syphilis episodes (P < .001). This difference was not explained by frequency of serological tests. Adjusted ORs (aORs) of detection of T. pallidum DNA in blood or rRNA in CSF at the index episode were significantly lower in those with previous syphilis (0.13; 95% CI, .08–.23, and 0.06, 95% CI, .02–.17). The aOR of neurosyphilis at the index episode was also significantly lower in individuals with previous syphilis (0.43; 95% CI, .27–.68). Conclusions Previous syphilis attenuates clinical and laboratory manifestations of infection with T. pallidum.

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Treponema pallidum PCR testing for diagnosis of mucocutaneous ulcers suspicious for syphilis

Sexually Transmitted Infections ◽

10.1136/sextrans-2021-055192 ◽

2021 ◽

pp. sextrans-2021-055192

Author(s):

Muhammad Hyder Junejo ◽

Mark Collery ◽

Gary Whitlock ◽

Alan McOwan ◽

Victoria Tittle ◽

...

Keyword(s):

Demographic Data ◽

Treponema Pallidum ◽

Added Value ◽

Contact Tracing ◽

Bisexual Men ◽

Electronic Patient Records ◽

Serological Tests ◽

Syphilis Infection ◽

Cross Sectional ◽

History Of

BackgroundPrimary syphilis is characterised by the appearance of an ulcerated lesion (chancre) on the anogenital or oral mucosa from which Treponema pallidum DNA may be detectable by PCR. Serological tests for syphilis may be non-reactive in early infection, even after the appearance of a chancre. We reviewed the use of a multiplex-PCR (M-PCR) test to determine the added value of T. pallidum DNA detection in the management of individuals presenting with mucocutaneous ulceration at a sexual health service in central London.MethodsWe performed a cross-sectional analysis of all individuals with detectable T. pallidum DNA from September 2019 to April 2020. Electronic patient records were reviewed and concomitant results for treponemal serology and/or rapid plasma reagin (RPR) extracted, along with demographic data, history of syphilis and indices of sexual behaviour including number of sexual partners contacted. Any subsequent treponemal serology and RPR results were also reviewed.ResultsM-PCR swab specimens were performed in 450 individuals, of whom 63 (14%) had detectable T. pallidum DNA; 60 of 63 (95%) were gay or bisexual men and 11 of 63 (17%) were living with HIV. A history of treated syphilis was present in 17 of 63 (27%). Same-day treponemal serology/RPR testing was performed in 58 of 63 (92%) patients. Of the 58 who had same-day syphilis serology/RPR, 9 (16%) had their syphilis infection confirmed by treponemal DNA PCR alone. A total of 165 partners were traced as contacts of infection, of whom 25 (15%) were contacts of individuals diagnosed by M-PCR testing alone.ConclusionIn individuals with T. pallidum PCR-positive lesions, around one in six in our cohort were negative on standard diagnostic serological tests for syphilis. Treponemal DNA testing is an important addition to serological assays in individuals with mucocutaneous ulceration who are at risk of recent syphilis infection and facilitates early diagnosis and contact tracing.

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Neurosyphilis presenting as psychiatric symptoms: an unusual case report

Acta Neuropsychiatrica ◽

10.1111/j.1601-5215.2007.00209.x ◽

2007 ◽

Vol 19 (4) ◽

pp. 251-253 ◽

Cited By ~ 4

Author(s):

Hasan Mirsal ◽

Ayhan Kalyoncu ◽

Özkan Pektaş ◽

Mansur Beyazyürek

Keyword(s):

Psychiatric Symptoms ◽

Treponema Pallidum ◽

Antibody Test ◽

Risk Groups ◽

Serological Tests ◽

Case Presentation ◽

Antibody Absorption ◽

Gradual Loss ◽

Neuropsychiatric Diseases ◽

Organic Brain

Objective:Neurosyphilis remains a differential diagnosis for a wide variety of psychiatric syndromes, including dementia, mood disorders and psychosis. However, the incidence of neurosyphilis presenting initially with psychiatric symptomalogy is unclear. In this article, a clinical case is reported so as to illustrate some of the issues involved.Case presentation:A 33-year-old married man was admitted because of a depressive episode associated with somatic preoccupations and a gradual loss of ability to function a year prior to his admission. The symptoms described above raised the question of an organic brain syndrome associated with the psychotic depression. Some laboratory and additional examinations were performed. Serological tests for syphilis were positive for both the hemagglutination test, Treponema pallidum hemaglutination (TPHA), and the immunofluorescent antibody test, fluorescent treponemal antibody-absorption (FTA-ABS). Based on these findings, the diagnosis of neurosyphilis was made. The patient was treated with benzathine penicillin (2 400 000 units i.m. once a week) for 3 weeks and venlafaxine (150 mg daily) and olanzapine (5 mg daily). His depression disappeared gradually, and he was discharged in partial remission.Conclusion:High-risk groups such as patients with neuropsychiatric diseases should be screened with serological tests so as to prevent morbidity and help eliminate syphilis.

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Further support from an Irish psychiatric hospital for lack of value of routine serological tests for syphilis

Irish Journal of Psychological Medicine ◽

10.1017/s0790966700015494 ◽

1989 ◽

Vol 6 (2) ◽

pp. 142-143 ◽

Cited By ~ 3

Author(s):

Therese O'Neill ◽

Brian McCaffrey

Keyword(s):

Research Laboratory ◽

Psychiatric Illness ◽

Venereal Disease ◽

Treponema Pallidum ◽

Venereal Disease Research Laboratory ◽

Serological Tests ◽

Infected Blood ◽

Disease Research ◽

Previous Infection ◽

Antibody Tests

AbstractSince the establishment of St. Brendan's Hospital in 1815 many changes have been seen in the pattern of psychiatric illness but none as dramatic as that of neurosyphilis. When Professor John Dunne first worked there in 1922, 20% of the patients suffered from general paralysis of the insane (G.P.I.) for which there was no cure. Around this time Wagner Von Jauregg – a Viennese physician, observed that patients who had suffered malaria during war did not suffer from G.P.I. He introduced malarial therapy successfully for which he received the Nobel Prize in 1927. Professor Dunne introduced this therapy into St. Brendan's after visiting Wagner Von Jauregg in Vienna. Unfortunately the mosquitos used would not bite! He resorted to injecting malarial infected blood. Only benign tertian malaria was effective and it is believed that the high temperatures induced – 40-41°C killed the spirochaete. This was followed by quinine treatment for malaria. The treatment was very successful but superceded in latter years by penicillin. The incidence of syphilis fell dramatically from 1942-1977, although recently it has been reported that it is rising in females and heterosexual males.One hundred consecutive samples routinely tested for syphilis (using the Venereal Disease Research Laboratory (VDRL) and Treponema Pallidum Haemagglutination (TPHA) test), between January and April 1988 were examined. Ninety-eight were negative for VDRL and TPHA. Two patients, both male, revealed evidence of previous infection i.e. VDRL neg, TPHA positive with Fluorescent Treponema Antibody tests (FTABS) reactive and FTA IGM negative in both cases. Neither of the two patients had any signs or symptoms suggestive of neurosyphilis.

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Development and research of a model for differential diagnosis of latent late syphilis and false-positive serological reactions on immunochips with a panel of 12 Treponema pallidum antigens

Vestnik dermatologii i venerologii ◽

10.25208/vdv1229 ◽

2021 ◽

Vol 97 (3) ◽

pp. 39-46

Author(s):

Marina V. Shpilevaya ◽

Georgiy L. Katunin ◽

Alexey A. Kubanov

Keyword(s):

Discriminant Analysis ◽

False Positive ◽

Treponema Pallidum ◽

Serum Samples ◽

Serological Tests ◽

Multivariate Discriminant Analysis ◽

Degree Of Confidence ◽

High Degree ◽

Multivariate Discriminant ◽

Latent Syphilis

The aim - to find the optimal attributing rules to distinguish groups of latent stages of syphilis and false positive serological tests of using multivariate discriminant analysis Material and methods. The objects of the study were serum samples from patients with late latent (N=34) syphilis and false positive serological tests (N=31). The samples were studied to determine IgG and IgM levels using indirect immunofluorescent reaction with immunochip containing recombinant antigens T. pallidum Results The mathematical model allows to differentiate with a high degree of confidence patients with late latent syphilis and with false-positive serological reactions to syphilis. Conclusions. . Multivariate discriminant analysis makes possible to create reliable mathematical models to classify patients with late latent syphilis and with false-positive serological reactions to syphilis.

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African nonhuman primates are infected with the yaws bacterium Treponema pallidum subsp. pertenue

10.1101/135491 ◽

2017 ◽

Cited By ~ 4

Author(s):

Sascha Knauf ◽

Jan F. Gogarten ◽

Verena J. Schuenemann ◽

Hélène M. De Nys ◽

Ariane Düx ◽

...

Keyword(s):

Nonhuman Primates ◽

Genomic Structure ◽

Treponema Pallidum ◽

Genetic Studies ◽

Hybridization Capture ◽

Naturally Occurring ◽

The Pacific ◽

Treponemal Infection ◽

Long Range Pcr ◽

Global Eradication

AbstractTreponema pallidum subsp. pertenue (TPE) is the causative agent of yaws. The disease was subject to global eradication efforts in the mid 20th century but reemerged in West Africa, Southern Asia, and the Pacific region. Despite its importance for eradication, detailed data on possible nonhuman disease reservoirs are missing. A number of African nonhuman primates (NHPs) have been reported to show skin ulcerations suggestive of treponemal infection in humans. Furthermore antibodies against Treponema pallidum (TP) have been repeatedly detected in wild NHP populations. While genetic studies confirmed that NHPs are infected with TP strains, subspecies identification was only possible once for a strain isolated in 1966, pinpointing the involvement of TPE. We therefore collected a number of recently isolated simian TP strains and determined eight whole genome sequences using hybridization capture or long-range PCR combined with next-generation sequencing. These new genomes were compared with those of known human TP isolates. Our results show that naturally occurring simian TP strains circulating in three African NHP species all cluster with human TPE strains and show the same genomic structure as human TPE strains. These data indicate that humans are not the exclusive host for the yaws bacterium and that a One Health approach is required to achieve sustainable eradication of human yaws.

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270. New Onset Seizure Presented as Neurosyphilis

Open Forum Infectious Diseases ◽

10.1093/ofid/ofab466.472 ◽

2021 ◽

Vol 8 (Supplement_1) ◽

pp. S241-S242

Author(s):

Shwe S Phyo ◽

Cho T Zin ◽

Zeyar Thet

Keyword(s):

Brain Mri ◽

Venereal Disease ◽

False Negative ◽

Treponema Pallidum ◽

Clonic Seizure ◽

Penicillin G ◽

Serological Tests ◽

History Of ◽

The Brain ◽

New Onset

Abstract Background The term “neurosyphilis” refers to infection of the central nervous system (CNS) by Treponema pallidum. It can occur at any time after initial infection. Early in the course of syphilis, the most common forms of neurosyphilis involve the cerebrospinal fluid (CSF), meninges, and vasculature (asymptomatic meningitis, symptomatic meningitis, and meningovascular disease). Late in disease, the most common forms involve the brain and spinal cord parenchyma (general paralysis of the insane and tabes dorsalis). Methods A 31-year-old man who suddenly developed a new onset generalized tonic clonic seizure, was admitted to the emergency department. He had no history of epilepsy and denied any vision or gait problems. The brain MRI showed no abnormalities. He had a history of rapid plasma reagent (RPR) titer 1:32 and a positive fluorescent treponemal antibody absorption (FTA-ABS) test in 2017. However, the RPR result was non-reactive when he retested a week later and therefore was not diagnosed with syphilis and did not get treated at that time. His most recent RPR titer was 1:16. HIV serology and other STD tests were all negative. His wife and his 3 kids were negative for syphilis. Due to serological evidence of syphilis and neurological symptoms, we arranged him to get a lumbar puncture to rule out neurosyphilis. Results His CSF study showed positive venereal disease research laboratory (VDRL), WBC cell count 44 cells/ul (lymphocytes 80%, Neutrophil 20%), Glucose 50 mg/dl, Protein 75 mg/dl. Based on the CSF study, he was diagnosed with neurosyphilis and was treated with intravenous Penicillin G 3-4 million units every 4 hours for 14 days, followed by Benzathine Penicillin 2.4million units intramuscularly on day 21. Conclusion This is an unusual case because his false negative RPR result has hindered the prompt diagnosis and management of syphilis. RPR is a nontreponemal test and therefore it is not always reliable as a diagnostic criteria. False negatives in RPR may occur in certain conditions such as in early primary or in late stage syphilis and prozone phenomenon. This case illustrates the importance of using a reverse sequence algorithm in diagnosing syphilis. Thorough history taking is also crucial in conjunction with serological tests to determine the diagnosis and to ensure appropriate treatment. Disclosures All Authors: No reported disclosures

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