Kelley Bemis

Use of automated testing in syphilis diagnosis and its impact on surveillance –

Connecticut, 2010

CDC/CSTE Applied Epidemiology FellowshipSTD Control Program

Connecticut Department of Public Healthkelley.bemis@ct.gov

Background

Graph: Together We Can SEE: The National Plan to Eliminate Syphilis, CDC, 2006

National Plan to Eliminate Syphilis implemented

Primary and Secondary Syphilis Cases - 2002 - 2010

2002 2003 2004 2005 2006 2007 2008 2009 20100.00

0.50

1.00

1.50

2.00

2.50

3.00

3.50

4.00

4.50

5.00

Connecticut Incidence 2010 Goal for National IncidenceNational Incidence

Years

Cru

de In

cide

nce

Per 1

00,0

00

+177% from 2008 to 2010

National elimination plan reframed

Crucial for syphilis elimination• Identify infectious patients (laboratory confirmed)

for partner notification• Identify outbreaks and target interventions

Mainly laboratory reporting• Labs must report positive tests in 48 hours• Mail reports to DPH

Syphilis Surveillance

Understanding laboratory testing is necessary for accurate surveillance

Usually two serologic tests Non-specific test

• e.g. rapid plasma reagin test (RPR), Venereal Disease Research Laboratory test (VDRL)

• Detects antibodies against host lipoidal antigens• Indicates active infection• Inexpensive, simple, manual

Specific test• e.g. T. pallidum particle agglutination (TPPA),

fluorescent treponemal antibody absorption assay (FTA-ABS)

• Detects antibodies against treponemal antigens• Indicates infection, past or present

Syphilis Diagnosis

Traditional Screening Algorithm

Syphilis unlikely

+ -

Syphilis unlikelySyphilis

+ -

Non-specific test

(RPR or VDRL)

Specific test (TPPA or FTA-

ABS)

One positive doesn’t confirm infection• Surveillance must monitor for two positives

Non-specific titers vary with age and stage of infection• Surveillance must consider past test results and

likelihood of infectiousness

Challenge for Surveillance #1

Positive test ≠ Active infection

Challenge for Surveillance #2

Photo credit: Reverse Sequence Syphilis Screening Webinar, CDC, 2011

Treponemal EIAs and CIAs gaining popularity

More expensive but less manual labor needed

Still can’t distinguish between active and past infection

A shift in testing paradigm: Automated treponemal tests for screening

Reverse Sequence Screening Algorithm

+Syphilis

-Specific test

(TPPA)

Syphilis (old or new)

+

EIA or CIA

Non-specific test

(RPR or VDRL)

+

Syphilis unlikely

-

Syphilis unlikely (or do another specific test)

-

Not identified with traditional algorithm

1. False positive EIA or CIA

2. Previously treated syphilis

3. Early primary syphilis

Challenge for Surveillance #2

Increased testing volume

New questions for surveillance• How should EIAs and CIAs be reported?• Should discordant results be investigated?

Increased DPH workload

Objectives

Determine type and volume of syphilis testing performed by Connecticut laboratories

Determine if current surveillance procedures adequately monitors reported tests for infectious cases

To conduct a laboratory-focused evaluation of syphilis surveillance in Connecticut

Methods, Part 1Laboratory Survey Web survey emailed to all hospital and

commercial labs in Connecticut (n=30)• Number of tests performed in 2010• Testing algorithm• Reporting practices

Responses analyzed with descriptive statistics

Methods, Part 2Laboratory Audit Requested records from two commercial

laboratories• All patients with a positive test in 2010

Compared against records in state’s surveillance database

Investigated selection of tests missing from state’s database

Laboratory Survey Results

30 of 30 (100%) labs completed the survey

28 of 30 (93%) perform syphilis testing

Over 196,700 screening tests performed in 2010

Uptake of Automated Tests

Using automated tests

Using manual tests

0

5

10

15

20

25

30

4

24

Num

ber o

f Lab

orat

orie

s

Referring Samples is Common

Refers samples for confirmatory test-

ing

Does not refer samples

0

2

4

6

8

10

12

14

16

15 9

4

Labs Using Automated TestsLabs Using Manual Tests

Num

ber o

f Lab

orat

orie

s

Reporting Results

Reports both test results*

Does not report both test results

0

2

4

6

8

10

12

14

16

3 1

11 13

Labs Using Automated Tests Labs Using Manual Tests

Num

ber o

f lab

orat

orie

s

Laboratory Audit Results

Lab B Screens with an EIA

Confirms all +’s with RPR and TPPA

RPR and TPPA reported

372 (29%) of 1299 positive reportable tests were not in the state’s database

Lab A Screens with a VDRL

Confirms with a FTA-ABS

RPR and FTA-ABS reported

693 (56%) of 1241 positive reportable tests were not in the state’s database

Laboratory Audit Results

Lab B• All patients with both RPR

and TPPA missing (n=13)

Lab A• Random sample (n=35

patients) representing different months, tests, and titers

Small sample of missing tests investigated from both labs

Most patients did not merit field investigation

We concluded that entry into state database is not consistent for these tests

Conclusions Uptake of automated tests is moderate, but

increasing

Automated testing algorithms are variable

Referring specimens is common

Labs do not always report both types of tests used for diagnosis

Standard protocols for entering lab tests do not exist or are not enforced

Recommendations

Create protocols for entering tests into the surveillance database

• All non-specific tests are entered• Treponemal results may be entered only once• Negative tests will be entered if reported

Recommendations

Establish provisional procedures for monitoring EIA/CIA’s and discordant results

• EIA/CIA’s do not need to be reported unless a manual treponemal test was not performed

• Discordant results will not be investigated

Recommendations

Offer training on interpretation of EIA/CIA’s• Internal meetings with DPH Disease

Intervention Specialists (DIS)• Newsletters to local health epidemiologists

and clinicians

Recommendations

Offer training on reporting requirements to laboratories

• Newsletter to Laboratory Response Network

Acknowledgments

Virginia Kristie, MT ASCP

Mark Lobato, MD

Lynn Sosa, MD

Connecticut laboratories

This study was supported in part by an appointment to the Applied Epidemiology Fellowship Program administered by the Council of State and Territorial Epidemiologists (CSTE) and funded by the Centers for Disease Control and Prevention (CDC) Cooperative Agreement Number 5U38HM000414.

Extra Slides

Reporting of Referral Samples

From the OLC-15 Reporting Form:

From the Public Health Code:

Test Sensitivity and Specificity

Credit: Seña, A.C., White, B.L. & Sparling, P.F. Novel Treponema pallidum Serologic Tests: A Paradigm Shift in Syphilis Screening for the 21st Century. CID 51, 700-708 (2010).

EIA/CIA Algorithms in Connecticut

EIA

EIA

CIA

CIA

RPR

TPPA

+&

+

+

+ RPR

RPR-

TPPA

RPR

&EIA x2

-TPPA

Sero-reactivity in Syphilis Tests

Credit: Peeling et al. / Bulletin of the World Health Organization / 2004 / Vol. 82 / No. 6 via CDC Reverse Sequence Screening Webinar