Syphilis Testing in Northern California Kaiser

Transcription

1 Syphilis Testing in Northern California Kaiser Jen Shieh, MS, CLS Test Development Scientist Kaiser Permanente TPMG Regional Laboratory Microbiology Department

2 Kaiser Permanente 3.3 million members 22 medical centers 50 MOB and clinics

3 Microbiology Laboratory 144 CLS FTE Micro Lab 30 FTE Immuno-Diagnostic/Virology 24/7 operation M-F, clean up on Saturday, Sunday Maintenance TrepAb/RPRQ/TPPA 2 FTE, not including preanalytic

4 Syphilis Testing 2010 Volume Annually:148,972 Monthly:12,414 Daily: 564

5 Syphilis Testing annually annually monthly monthly daily daily

6 Old Algorithm Non-treponemal (RPR) Neg Not Syphilis Pos Do RPR Q & TPPA Report RPR titer & TPPA results

7 New Algorithm TrepAb Nonreactive Reactive or Equivocal Not Syphilis Nonreactive TP-PA RPR Q Reactive Nonreactive Reactive Syphilis Further investigation Further investigation Clinical correlation Clinical correlation required required

8 Syphilis Reaction Table Reaction of Non-Treponemal Serological Test (RPR) by Stages of Syphilis and Influence of Successful Treatment Early Syphilis Late Syphilis Primary Secondary Early Latent Late Latent Tertiary U T Becoming Negative Positive Negative Positive Negative Positive Negative Positive Serofast Positive (rarely Negative) Serofast Reaction of Treponemal Serological Test (TrepAB) by Stages of Syphilis and Influence of Successful Treatment Early Syphilis Late Syphilis U T Primary Negative Becoming Positive (early) Remains Positive (If initially Positive) Secondary Early Latent Late Latent Tertiary Positive Positive Positive Positive Positive Positive Positive Positive U: Untreated T: Successfully treated

9 Total = 2,377 Sensitivity & Specificity (2006) True True RPR ,261 LIAISON ,280 PS: True using TP-PA resolution RPR Liaison Sensitivity 73.3% 100% Specificity 98.6% 99.7% PPV 71.7% 92.8% NPV 98.9% 100%

10 Old vs New algorithm Old algorithm (Non-treponemal Antibodies) Detects active infection High rate of biologic false positives Confirmation with treponemal test o Use of both tests results in a high positive predictive value Can miss early primary and treated infection New algorithm (Treponemal Antibodies) Detects early primary and treated infection that might be missed with traditional screening Nontreponemal test needed to detect active infection CIA have higher specificity Generate false positive results Varies by risk of population

11 Challenges and limitations of the CIA Cannot distinguish between active disease and old disease (treated/untreated) Studies to compare test performance with other serologic tests are lacking Studies evaluating performance of EIA/CIA to detect IgM antibodies in early syphilis are lacking Confusion re: management of patients with discrepant serology (e.g., positive EIA/CIA and a negative RPR)

12 Syphilis Serologic Testing Guidelines for Interpretation 1. Since Treponemal tests may remain active for life in adequately treated patients, a positive TrepAb indicates exposure to syphilis and it may not indicate untreated syphilis. 2. If the RPR is also positive (especially at >1:8) and there is no history of treatment for syphilis, a diagnosis of syphilis is made and the patient should receive treatment. 3. Most people become negative for RPR with adequate treatment, though some patients who present with later stage disease may maintain a low titer RPR (<1:8) for life despite adequate treatment. This is the serofast state.

13 Syphilis Serologic Testing Guidelines for Interpretation (con d) 4. Initial screening may be negative in early primary syphilis. If the history is strongly suggestive of syphilis then an RPR should be done and/or repeat TrepAb in 1 week. The most common cause of a false negative syphilis serologic test is performance prior to the development of diagnostic antibodies. 5. Positive TrepAb with a non-reactive RPR and non-reactive TPPA is most likely a false positive TrepAb result. If clinical history suggests a risk for syphilis then TrepAb should be repeated in 3-4 weeks.

14 Syphilis Serologic Testing Guidelines for Interpretation (con d) 6. Positive TrepAb with a non-reactive RPR and REACTIVE TPPA is most consistent with old treated syphilis. If there is no clear history of syphilis treatment then 3 weekly shots of 2.4 million units of benzathine penicillin should be considered. Clinical correlation is required as in rare cases of late latent or tertiary syphilis the RPR may be negative. 7. The diagnosis of syphilis should not be made on the basis of a single test result. Clinical history, findings and symptoms should be taken into consideration.

15 DiaSorin LIAISON CIA Results from Aug-Oct 2007 N=21,623 specimens CIA + =2% CIA +/ RPR - =1.3% - 98% 34% Managed as CIA + n=151 in old algorithm + 2% n=439 RPR - 66% n=288 TPPA (n=255*) + - * 33 duplicate or infant tests 72% 28% Slide from Dr. Ina Park, CA dept. of Public Health n=184 n=71

16 Management based on initial serology and syphilis history CIA+ / RPR- / TP-PA+ N=184 Prior treated syphilis N=105 (57%) 10 (9%) received repeat treatment 95 (91%) no antibiotic treatment No prior syphilis N=79 (43%) 51 (65%) received treatment 28 (35%) no antibiotic treatment Slide from Dr. Ina Park, CA dept. of Public Health

17 Repeat Serology Testing Results CIA+ / RPR- / TP-PA+ N=184 Repeat Serology N=78 Initially treated n=31 (64%) 0 seroreverted to CIA- 27 (87%) remained CIA+/RPR-/TPPA+ 4 (13%) seroconverted to CIA+/RPR+ Not treated initially n=47 (36%) 0 seroreverted to CIA- 41 (87%) remained CIA+/RPR-/TPPA+ 6 (13%) seroconverted to CIA+/RPR+ Slide from Dr. Ina Park, CA dept. of Public Health

18 Management based on initial serology and syphilis history CIA+ / RPR- / TP-PA- N=71 Prior treated syphilis N=6 (8%) 2 (33%) received repeat treatment 4 (66%) no antibiotic treatment No prior syphilis N=65 (92%) 7 (11%) received treatment 58 (89%) no antibiotic treatment Slide from Dr. Ina Park, CA dept. of Public Health

19 Repeat Serology Testing Results CIA+/ RPR- / TP-PA- N=71 Repeat Serology N=31 Initially treated N=6 n=31(19%) 0 seroreverted 0 to to CIA- CIA- 6 (100%) 27 (87%) remained CIA+/RPR-/TPPA- CIA+/RPR-/TPPA+ 0 seroconverted 4 (13%) seroconverted to CIA+/RPR+ to CIA+/RPR+ Not treated initally N=25 (81%) 7 (28%) seroreverted to CIA- 17 (68%) remained CIA+/RPR-/TPPA- 1 (4%) seroconverted to CIA+/RPR+ Slide from Dr. Ina Park, CA dept. of Public Health

20 High EIA/CIA index values may predict TP-PA positivity (n=255) TPPA Negative TPPA Positive Proportion N=79 individuals with CIA index value >12.0; 100% of were TP-PA positive Cutoff Index Value Park IU et al. Journal of Infectious Diseases, In press 20

21 Reasons for discordant test results (i.e., CIA+ / RPR-) False-positive CIA CIAs are very sensitive But have lower specificity Treated syphilis Treponemal antibodies are detected by sensitive CIAs Seroreversion of nontreponemal antibodies Early primary syphilis Treponemal antibody titer rises before nontreponemal antibody titer MMWR / February 11, 2011 / Vol. 60 / No. 5

22 Conclusions CIA have high sensitivity but lower specificity All reactive CIA must be reflexly tested with a quantitative RPR Confirm reactive CIA Detect active infection Although test performance varies by prevalence of syphilis in the population, all discordant specimens (CIA+/RPR-) must be confirmed with a confirmatory treponemal test Confirmatory treponemal test must have at least equivalent sensitivity and higher specificity compared to the screening treponemal test TP-PA recommended FTA-ABS not recommended MMWR / February 11, 2011 / Vol. 60 / No. 5

23 Conclusions (Con d) Among CIA+/RPR- patients, reflex testing with a second treponemal test is useful in low prevalence settings to guide treatment decisions Conflicting treponemal results (CIA+/TP-PA-) and isolated CIA+ results with low index values may represent false positives. Repeat testing should be considered Among CIA+/RPR- patients at high risk, repeat testing should be performed to rule out early syphilis

24 Advantage to the Laboratory Automation including interfacing with LIS for reporting Random access improving workflow Improved the TAT (from 48 hours to <12 hours) Ergonomic (no more injuries) Cost (downstream saving) No false negative due to prozone Objective reading of results Provide better results to the providers

25 Advantage to the Clinicians May pick up primary syphilis earlier than non-treponemal tests May improve detection of latent disease New testing algorithm leads to fewer false positives and false negatives Faster TAT 25

26 Acknowledgments Kaiser Permanente Northern California Regional Laboratory Jeff Schapiro, MD Thomas Lorey, MD Mark Stanley, MPH All IDx Staff California Department of Public Health Ina Park, MD, MS Joan Chow, MPH, DrPH Gail Bolan, MD