Interpreting Syphilis Serology

Transcription

1 Interpreting Syphilis Serology Dr Beng Goh Royal London Hospital Barts & The London NHS Trust

2 Serological Tests for Syphilis: Principles Screening Confirmation Staging of infection Retest discrepant results Surveillance data

3 Serological Tests for Syphilis Serology Indirect confirmation of treponemal infection by antibody detection Antibody detection Non-treponemal : phospholipid or cardiolipin abs [non-specific] Treponemal : cannot differentiate between T.pallidum & other pathogenic treponemes

4 Serological Tests for Syphilis: Screening EIA TPPA/TPHA TPPA/TPHA + RPR/VDRL Confirm positive

5 Predictive value: a measure of the utility of a diagnostic test Predictive value is influenced by Sensitivity; specificity; prevalence Positive predictive value (PPV) the probability that a + result is a true result for the infection being tested for Negative predictive value (NPV) the probability that a negative result is a true result & excludes the infection being tested for

6 Effect of prevalence on PPV for kits of differing specificity Screening situation 100 Positive Predictive Value (%) % 0.50% 1% Prevalence Specificity 99.9% Specificity 99.5% Specificity 99% Specificity 95%

7 Effect of prevalence on PPV for kits of differing specificity 100 Confirmatory situation Positive Predictive Value (%) Prevalence Specificity 99.9% Specificity 99.5% Specificity 99% Specificity 95%

8 +STS: Syphilis or other Treponematoses eg. Yaws? History : Born & brought up in endemic area eg.caribbean : Yaws as a child Clinical : Tissue paper scars on shins Exclude signs of syphilis Serology: VDRL/TPPA >I:8 Syphilis likely

9 +STS: Acquired or Congenital History : Syphilis? Patient: Misty Vision as a child Clutton joints Family history: Parents/Siblings Clinical : Stigmata of Congenital Syphilis Slit lamp CVS acquired syphilis

10 What is the outcome of treponemal serological tests following Rx?? Specific treponemal tests (EIA, TPPA,TPHA, FTA-abs): Remain positive for life (EIA, TPPA,TPHA, FTAabs):

11 What is the outcome of Cardiolipin (RPR/VDRL) tests following Rx? RPR/VDRL? Effective Rx in early syphilis >4 fold (2 dilution) 3-6 months >8 fold (3 dilution) 6-12 months Late syphilis - neg or + - Brown et al JAMA 1985; 253: Romanowski Ann Intern Med 1991; 114:1005-9

12 RPR Seroreversion Following Treatment at Three Years Stage of Infection Primary Secondary Early latent Overall (Romanowski et al 1991) % Seroreversion 72% 56% 26% 63%

13 Serological Tests for Syphilis: Reinfection/Reactivation VDRL/RPR titres increase by more than 8 folds (2 dilutions) eg VDRL/RPR neg +1:4 +1:2 +1:16

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15 EIA+ TPPA+ VDRL + Treated or Untreated Syphilis: any stage

16 EIA+ TPPA+ VDRL - Untreated Syphilis: Primary, late latent & late syphilis Untreated Secondary/Early latent Syphilis with prozone Treated Syphilis: any stage

17 EIA+ TPPA- VDRL - Untreated Syphilis: Primary Treated syphilis False Positive

18 EIA- TPPA- VDRL + Biological False Positive (BFP) Untreated Syphilis: Primary Treated syphilis

19 EIA- TPPA+ VDRL - False positive Untreated Syphilis: Primary Treated syphilis

20 EIA- TPPA- FTA-abs+ VDRL - Untreated Syphilis: Primary Treated syphilis False Positive

21 Serological Tests for Syphilis: Serofast (+) following effective treatment Explanation to patient - Serological scar No further treatment required Explanation letter to patient to avoid unnecessary repeat treatment

22 Intrepretation: Summary Decide whether: Syphilis or other Treponematoses eg.yaws? Acquired or Congenital? or Untreated? Treated Which stage? History Clinical examination Investigations

23 Conclusions Reactive screening tests require confirmation with a different treponemal test of equal sensitivity & (greater) specificity Discrepant treponemal test results need further testing