Download Variability in Syphilis Laboratory Testing Practices * Connecticut, 2010

Use of automated testing in syphilis
diagnosis and its impact on surveillance –
Connecticut, 2010
Kelley Bemis
CDC/CSTE Applied Epidemiology Fellowship
STD Control Program
Connecticut Department of Public Health
[email protected]
Background
National Plan to
Eliminate
Syphilis
implemented
Graph: Together We Can SEE: The National Plan to Eliminate Syphilis, CDC, 2006
Primary and Secondary Syphilis Cases 2002 - 2010
Connecticut Incidence
2010 Goal for National Incidence
National Incidence
Crude Incidence Per 100,000
5.00
4.50
National elimination plan
reframed
4.00
3.50
3.00
2.50
2.00
1.50
+177% from 2008
to 2010
1.00
0.50
0.00
2002
2003
2004
2005
2006
Years
2007
2008
2009
2010
Syphilis Surveillance

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
Understanding laboratory testing is
necessary for accurate surveillance
Syphilis Diagnosis
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
Traditional Screening Algorithm
Non-specific
test
(RPR or VDRL)
-
+
Specific test
(TPPA or FTAABS)
+
Syphilis
Syphilis unlikely
Syphilis unlikely
Challenge for Surveillance #1
Positive test ≠ Active infection

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 #2
A shift in testing paradigm:
Automated treponemal tests for screening

Treponemal EIAs and CIAs
gaining popularity

More expensive but less
manual labor needed

Still can’t distinguish
between active and past
infection
Photo credit: Reverse Sequence Syphilis Screening Webinar, CDC, 2011
Reverse Sequence Screening Algorithm
EIA or CIA
-
+
Non-specific
test
(RPR or VDRL)
Syphilis unlikely
Not identified with
traditional algorithm
-
+
Specific test
(TPPA)
Syphilis
+
Syphilis
(old or new)
Syphilis unlikely
(or do another
specific test)
1.
2.
3.
False positive
EIA or CIA
Previously
treated syphilis
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
To conduct a laboratory-focused evaluation
of syphilis surveillance in Connecticut

Determine type and volume of syphilis
testing performed by Connecticut
laboratories

Determine if current surveillance
procedures adequately monitors reported
tests for infectious cases
Methods, Part 1
Laboratory 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 2
Laboratory 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
Number of Laboratories
30
25
20
15
24
10
5
0
4
Using automated Using manual tests
tests
Number of Laboratories
Referring Samples is Common
16
14
12
10
8
9
15
6
4
4
2
0
Refers samples for
confirmatory testing
Labs Using Automated Tests
Does not refer
samples
Labs Using Manual Tests
Number of laboratories
Reporting Results
16
14
12
10
8
11
13
6
4
2
3
1
0
Reports both test
results*
Labs Using Automated Tests
Does not report
both test results
Labs Using Manual Tests
Laboratory Audit Results
Lab A
Lab B

Screens with a VDRL

Screens with an EIA

Confirms with a FTAABS


RPR and FTA-ABS
reported

RPR and TPPA
reported

693 (56%) of 1241
positive reportable
tests were not in the
state’s database

372 (29%) of 1299
positive reportable
tests were not in the
state’s database
Confirms all +’s with
RPR and TPPA
Laboratory Audit Results

Small sample of missing tests investigated
from both labs
Lab A
Lab B
•
Random sample (n=35
patients) representing
different months, tests,
and titers
•
All patients with both RPR
and TPPA missing (n=13)

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
+
RPR
&
TPPA
EIA
+
RPR
-
TPPA
&
EIA x2
CIA
CIA
+
+
RPR
RPR
-
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