Syphilis Antibody

Aka: Syphilis Antibody, Syphilis Serology, Syphilis Screening, Syphilis False Positive, Syphilis Testing, Syphilis Diagnosis, Treponema test, Non-Treponemal Test

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II. Indication

  1. Syphilis (Treponema pallidum) detection
  2. Syphilis Screening at least annually for all Men who have Sex with Men and others at high risk of Syphilis
  3. Skin lesions or other clinical findings suggestive of Syphilis
  4. Confirmation of positive Screening Test
  5. Genital Ulcer

III. Background

  1. Antigen Extracts from beef heart (cardiolipin) are used for Non-Treponemal Tests
    1. Non-specific Syphilis antibodies bind cardiolipin

IV. Labs: Tests for detection of Treponemal Pallidum Antibody

  1. Non-Treponemal Derived Substance precipitates Antibody (False Negatives in first 4 weeks)
    1. Venereal Disease Research Laboratory (VDRL)
    2. Rapid Plasma Reagin (RPR)
    3. Automated Reagin Test (ART)
    4. Standard Test for Syphilis (STS)
  2. Treponemal Antigen precipitates Antibody (False Negatives in the first 2 weeks)
    1. Fluorescent Treponemal Antibody (FTA-ABS)
      1. Test Sensitivity: 80%
    2. Microhemagglutination - Treponema pallidum (MHA-TP)
      1. Test Sensitivity: 65% to 70%

V. Labs: Non-Antibody Tests

  1. Dark-field Microscopy
    1. Most specific if Chancre or condyloma is present
    2. Can result in immediate diagnosis in the first week without the 3 week delay witing for IgM to develop
    3. Accuracy varies with experience of technician and a negative test does not exclude Syphilis
    4. May detect Syphilis at any stage

VI. Labs: Reverse Sequence Syphilis Screening

  1. Protocol employed by many U.S. labs as of 2022
  2. Step 1: Automated Treponemal Antibody Test
    1. Testing by enzyme immunoassay (EIA, CLIA) or similar allows for rapid, high volume sample screening
    2. Risk of False Positives in low risk populations
    3. Treponemal Antibody tests are positive for life after initial infection (regardless of treatment)
  3. Step 2: Nontreponemal Tests (e.g. RPR or VDRL)
    1. Confirmation testing that is labor and time intensive, and may take 6 weeks for a positive result
    2. Levels fall with treatment and over time since infection
    3. Four fold increase in titers suggests reinfection

VII. Protocol: Testing

  1. Screening
    1. Nontreponemal tests (RPR or VDRL)
      1. Syphilis Screening (positive within 3 weeks of developing primary Chancre)
      2. Syphilis RPR positive test will be returned with titer (e.g. 1:16)
      3. After treatment, by 6 months, RPR should fall by a factor of 4 (e.g. 1:4)
      4. On subsequent infection, expect the RPR titer to once again rise
    2. HIV Screening (test all patients who are positive for Syphilis)
      1. HIV coinfection with Syphilis is common
      2. HIV patients are at higher risk of Neurosyphilis
  2. Negative test with lesions present or other strong clinical indicators
    1. Repeat screening in 2-3 weeks
  3. Confirmation of positive Screening Test
    1. Fluorescent Treponemal Antibody (FTA-ABS)
    2. Microhemagglutination - Treponema pallidum (MHA-TP)
  4. Neurosyphilis CSF Evaluation
    1. See Neurosyphilis
    2. Indications for Lumbar Puncture with CSF Exam
      1. All patients with Syphilis and neurologic symptoms
      2. All patients with serologic or exam findings consistent with treatment failure
      3. HIV patient specific criteria
        1. CD4 Count <350 cells/mm3 or
        2. Rapid plasmin reagin (RPR) >1:32
  5. Monitoring response to treatment
    1. Non-Treponemal Antibody test (e.g. RPR) will normalize after treament
      1. Levels decline overtime, and then increase >4 fold with reinfection
    2. Treponemal tests (Antibody) will remain positive for life despite treatment

VIII. Interpretation: False Positives with the Non-Treponemal Tests

  1. Systemic Lupus Erythematosus
  2. Malaria
  3. Measles
  4. Endocarditis
  5. Infectious Mononucleosis
  6. Infectious Hepatitis
  7. Leprosy
  8. Lymphoma
  9. Brucellosis
  10. Atypical Pneumonia
  11. Miliary Tuberculosis
  12. Typhus
  13. Cohorts
    1. Pregnancy
    2. Advanced age
    3. Intravenous Drug Abuse
    4. Post-Vaccination state
  14. Related Treponemal infection
    1. Yaws
    2. Pinta
    3. Bejel

IX. Interpretation: False Positives with Treponemal tests

  1. Other Spirochete infections (Leptospirosis, Lyme Disease, rat bite fever)

X. Efficacy

  1. Diagnostic Test Sensitivity in Primary Syphilis
    1. Dark-field Exam of Chancre: 80%
    2. Non-Treponemal Tests (e.g. RPR): 78-86%
    3. Treponemal tests (e.g. FTA-ABS): 76-84%
  2. Diagnostic Test Sensitivity in Secondary Syphilis
    1. Dark-field Exam of Chancre: 80%
    2. Non-Treponemal Tests (e.g. RPR): 100%
    3. Treponemal tests (e.g. FTA-ABS): 100%
  3. Diagnostic Test Sensitivity in Latent Syphilis
    1. Non-Treponemal Tests (e.g. RPR): 95-100%
    2. Treponemal tests (e.g. FTA-ABS): 97-100%
  4. Diagnostic Test Sensitivity in Tertiary Syphilis
    1. CSF evaluation required (see below)
    2. Non-Treponemal Tests (e.g. RPR): 71-73%
    3. Treponemal tests (e.g. FTA-ABS): 94-96%

XI. Resources

  1. Diagnostic Tests for Syphilis
    1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4999316/

XII. Reference

  1. Kirk, McHugh and Parnell (2023) Crit Dec Emerg Med 37(8): 23-9
  2. Mason and von Reinhart (2018) EM:Rap 18(6): 19-20
  3. Bakerman (1984) ABCs of Interpretive Lab Data, p. 392
  4. Larsen (1995) Clin Microbiol Rev 8:1-21 [PubMed]

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Related Studies

Ontology: False-positive serological test for syphilis (C0159128)

Concepts Finding (T033)
ICD9 795.6
ICD10 R76.2
SnomedCT 207499000, 207501008, 158689005, 158687007, 274684006
English False pos.serol.syph. NOS, False posit.serol.syph.test, False positive serological syphilis test, False positive serological syphilis test NOS, [D]False positive serological syphilis test (context-dependent category), [D]False positive serological syphilis test NOS (context-dependent category), [D]False pos.serol.syph. NOS, [D]False posit.serol.syph.test, [D]False positive serological syphilis test, [D]False positive serological syphilis test NOS, False-pos serol test-syphilis, False pos sero test-syph, False positive serological test for syphilis, [D]False positive serological syphilis test NOS (situation), [D]False positive serological syphilis test (situation), False-positive serological test for syphilis, False-positive serological test for syphilis (finding), false-positive; serology for syphilis, false; positive serological test for syphilis, positive serological test for syphilis; false, positive; serology for syphilis, false, serology; syphilis, false-positive, serology; syphilis, positive, false, syphilis; serology, false-positive
Spanish [D]resultado falso positivo en prueba serológica para sífilis (categoría dependiente del contexto), [D]resultado falso positivo de prueba serológica para sífilis, SAI (categoría dependiente del contexto), [D]resultado falso positivo de prueba serológica para sífilis, SAI, [D]resultado falso positivo en prueba serológica para sífilis, [D]resultado falso positivo en prueba serológica para sífilis (situación), [D]resultado falso positivo de prueba serológica para sífilis, SAI (situación), Prueba serológica para la sífilis falsamente positiva, prueba serológica para sífilis: falso positivo (hallazgo), prueba serológica para sífilis: falso positivo
German Falsch-positiver serologischer Syphilistest, falsch positive Luesserologie
Korean 매독의 가양성 혈청 시험
Portuguese Teste serológico falso-positivo da sífilis
Czech Sérologická reakce na syfilis falešně pozitivní
Dutch vals positieve serologische test voor syfilis, positief; serologie voor syfilis, vals, positieve serologische test voor syfilis; vals, serologie; syfilis, positief, vals, serologie; syfilis, vals-positief, syfilis; serologie, vals-positief, vals-positief; serologie voor syfilis, vals; positieve serologische test voor syfilis, Vals positieve serologisch test voor syfilis
Italian Reazione sierologica falsamente positiva della sifilide
French Test sérologique faussement positif pour la syphilis
Japanese 梅毒血清反応偽陽性, ﾊﾞｲﾄﾞｸｹｯｾｲﾊﾝﾉｳｷﾞﾖｳｾｲ
Hungarian Álpozitív szifilisz szerológiai vizsgálat
Derived from the NIH UMLS (Unified Medical Language System)

Ontology: Treponema pallidum antibody measurement (C0919842)

Definition (MSH) Serologic tests for syphilis.
Concepts Laboratory Procedure (T059)
MSH D013588
SnomedCT 165779003, 269830006, 143185008, 165787002, 143194002, 165788007, 40675008, 269828009
CPT 86780
English Serodiagnoses, Syphilis, Serodiagnosis, Syphilis, Syphilis Serodiagnoses, Syphilis Serodiagnosis, syphilis serodiagnosis, Syphilis titer test NOS, Syphilis titre test NOS, SERODIAG SYPHILIS, SYPHILIS SERODIAG, syphilis test, syphilis test (lab test), Antibody; Treponema pallidum, TREPONEMA PALLIDUM, ANTIBODY TREPONEMA PALLIDUM, Treponema pallidum, Treponema pallidum antibody, Syphilis test, Syphilis test NOS, syphilis serology, test syphilis, syphilis tests, Test;syphilis serology, syphilis testing, serologic syphilis test, serologic test for syphilis, serology syphilis, Treponema pallidum antibody measurement, Assay for Treponema pallidum antibody, Analysis for antibody, Treponema pallidum, Syphilis infect. titer, Syphilis infect. titre, Syphilis serology (procedure), Syphilis titer test NOS (procedure), Serum Syphilis Test, Serologic test for syphilis, Syphilis infectious titer test, Syphilis infectious titre test, Syphilis serology, Serologic test for syphilis (procedure), Syphilis infectious titer test (procedure), Serologic test for syphilis, NOS, Treponema pallidum antibody measurement, NOS, syphilis serology test
Swedish Syfilisserodiagnostik
Czech syfilis - sérodiagnóza, Vyšetření na syfilis NOS, Protilátky proti Treponema pallidum, Reakce na syfilis
Finnish Kupan serodiagnoosi
French Sérodiagnostic de syphilis, Sérodiagnostic de la syphilis, Anticorps anti-treponema pallidum, Test de la syphilis SAI, Test de la syphilis
Russian VASSERMANA REAKTSIIA, KANA REAKTSIIA, SIFILISA SERODIAGNOSTIKA, ВАССЕРМАНА РЕАКЦИЯ, КАНА РЕАКЦИЯ, СИФИЛИСА СЕРОДИАГНОСТИКА
Japanese カーンテスト, 梅毒血清テスト, 梅毒血清学的テスト, Wassermann反応, ワッセルマン反応, ﾊﾞｲﾄﾞｸｹﾝｻNOS, ﾊﾞｲﾄﾞｸﾄﾚﾎﾟﾈｰﾏｺｳﾀｲ, ﾊﾞｲﾄﾞｸｹﾝｻ, 梅毒検査, 梅毒検査ＮＯＳ, 梅毒トレポネーマ抗体, Kahnテスト, 梅毒血清反応
Croatian LUES, SERODIJAGNOSTIKA
Spanish Prueba de sífilis NEOM, Prueba de sífilis, Anticuerpos anti-Treponema Pallidum, ensayo de titulación para diagnostico de sífilis, SAI, ensayo de titulación para diagnostico de sífilis, SAI (procedimiento), Diagnóstico Serológico de la Sífilis, medición de anticuerpos anti - Treponema pallidum, prueba para diagnóstico de títulos infecciosos de T. pallidum (procedimiento), prueba para diagnóstico de títulos infecciosos de T. pallidum, prueba serológica para la detección de sífilis (procedimiento), prueba serológica para la detección de sífilis, Serodiagnóstico de la Sífilis
Portuguese Análise de sífilis, Análise de sífilis NE, Anticorpo de Treponema pallidum, Sorodiagnóstico da Sífilis
Italian Test per la sifilide NAS, Anticorpo anti-treponema pallidum, Test per la sifilide, Sierodiagnosi della sifilide
Dutch syfilistest NAO, syfilistest, Treponema pallidum-antistof, Syfilis, serodiagnose, Syfilis, serologische diagnostiek
German Syphilistest, Syphilistest NNB, Treponema pallidum-Antikoerper, Syphilis-Serodiagnostik
Polish Odczyn Kahna, Serodiagnostyka kiły, Odczyn Wassermanna
Hungarian Syphilis vizsgálat k.m.n., Treponema pallidum antitest, Syphilis vizsgálat
Norwegian Serologisk syfilistest, Serodiagnostikk, syfilis
Derived from the NIH UMLS (Unified Medical Language System)

Ontology: Treponema test positive (C2748134)

Concepts Laboratory or Test Result (T034)
English Treponema test positive
Spanish Prueba de Treponema positiva
Portuguese Teste de Treponema positivo
Italian Test per Treponema positivo
French Test Treponema positif
German Treponema-Test positiv
Dutch Treponema-test positief
Czech Test na průkaz treponema pozitivní
Japanese ﾄﾚﾎﾟﾈｰﾏｹﾝｻﾖｳｾｲ, トレポネーマ検査陽性
Hungarian Treponema vizsgálat pozitív
Derived from the NIH UMLS (Unified Medical Language System)

Ontology: Treponema test (C2748338)

Concepts Laboratory Procedure (T059)
English Treponema test
Spanish Prueba de Treponema
Portuguese Teste de Treponema
French Test Treponema
Dutch Treponema-test
Italian Test per Treponema
German Treponema-Test
Czech Test na průkaz treponema
Japanese ﾄﾚﾎﾟﾈｰﾏｹﾝｻ, トレポネーマ検査
Hungarian Treponema vizsgálat
Derived from the NIH UMLS (Unified Medical Language System)

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