Underestimating the burden of
pertussis in WA
2011 CSTE Annual Meeting
Pittsburgh, PA
Chas DeBolt RN, MPH
Azadeh Tasslimi, MPH
Washington State Department of Health
Objectives
•
Compare 2007-2010 PCR-positive suspect cases with
confirmed pertussis cases to determine differences in:
• Demographics
• Measures of severity, outcome & antibiotic use
• Symptoms
•
Estimate sensitivity, specificity, & predictive value of
Bordetella pertussis (Bp) PCR assays
• WA State Public Health Laboratories (PHL), 2005-2010
• Comparing results with standard culture
Case classification*
Confirmed
• Isolate Bp from clinical specimen + cough of any duration, OR
• Detect Bp DNA by PCR + clinical case definition, OR
• Link to lab-confirmed case + clinical case definition
Probable
• Meets clinical case definition but
• No Bp isolation or Bp DNA detected by PCR AND
• No link to a lab-confirmed case
* Only confirmed or probable cases reported to CDC
Case classification (2)
•
Clinical case definition
• Cough ≥ 2 weeks PLUS one of following
• Cough paroxysms
• Inspiratory “whoop”
• Post-tussive emesis
•
Bp PCR in WA
• 1999: Bp PCR implemented at PHL
• By 2005, Bp PCR widely available at commercial labs
Bp Culture & PCR in WA
•
WA PHL, 2005-2010:
• Of 9,623 samples sent for Bp culture, Bp isolated in
only 318 (3.2%)
• Of 5,369 samples sent for Bp PCR, Bp DNA detected
in 422 (7.9%)
• Of these, 4,468 (83%) also cultured
• 99 PCR results uninterpretable
• 4,372 with PCR result & culture result
Bp Culture Sample Submissions to
WA PHL by Year, 2005-2010
Year of Final Report Result
2005
2006
2007
2008
2009
2010*
3,544
1,890
1,327
1,583
1,207
72
Number
Positive
164
56
22
39
29
8
Percent
Positive
5%
3%
2%
2%
2%
11%
Number of
Samples
Submitted
* Policy change at PHL to only receive samples whose testing result will
be used to make public health decisions
Bp PCR Sample Submissions to WA
PHL by Year, 2005-2010
Year of Final Report Result
2005
2006
2007
2008
2009
2010*
1,124
612
1,087
1,421
1,048
77
1,102
580
1,066
1,386
1,022
67
Number
Positive
130
51
68
105
59
9
Percent
Positive
12%
9%
6%
8%
6%
13%
Number also
cultured
787
456
1,000
1,247
914
64
%
70%
75%
92%
88%
87%
83%
Samples Submitted
Result
Obtained
* Policy change at PHL to only receive samples whose testing result will
be used to make public health decisions
Paired Bp PCR & culture results, WA
PHL, 2005-2010
CULTURE
“Gold Standard”
PCR Result
+
-
+
78
260
-
12*
4,022
4,034
90
4,282
4,372
Total
Total
338
* Of these 12, 6 (50%) occurred during a single six-week period in Spring 2009
Performance of Bp PCR performance
compared to culture
•
•
•
•
Sensitivity:
87%
Specificity:
94%
PPV:
23%
NPV:
100%
Changes in classification method for
pertussis cases in WA
•
2005: Web-based electronic reporting system (PHIMS)
start-up in WA
•
Allows WA DOH & local health departments to jointly
review/classify pertussis cases
• Improved classification
•
2005-2006: Many PCR-positive pertussis cases that do
not meet clinical case definition
WA DOH defines “suspect” case
• Person whose initial symptoms suggest
pertussis
• Subsequent testing negative OR no
testing done
• Cough duration < 2 weeks or cough
duration undetermined
WA DOH establishes “suspect” case
classification
•
2007: DOH defines Bp PCR-positive persons that do not
meet clinical cases definitions as “suspect cases”*
•
•
No two-week cough in a PCR-positive person → “suspect”
•
Only confirmed & probable cases are reported to CDC
For case & contact management, persons should be
treated as if they had pertussis
* http://www.doh.wa.gov/notify/guidelines/pdf/pertussis.pdf
Reported pertussis cases in WA,
2007-2010
• Confirmed cases:
• Probable cases:
• Suspect cases:
1466 (72%)
375 (18%)
194 (10%)
Among suspect cases, 81 (42%)
Bp PCR-positive
Reported pertussis cases in WA by
case classification, 2007-2010
Case
Classification
2007
2008
2009
2010
Confirmed
388
363
237
478
Probable
94
97
54
130
Suspect
28
41
51
74
PCR+ suspect
13
19
18
31
482
460
291
608
Total reported
cases*
* Only confirmed or probable cases reported to CDC
Confirmed & PCR-positive suspect
cases by age & gender, WA, 2007-2010
Age (years)
Median age
By age group
<1
1-4
5-17
18-44
45-64
>65
Gender
Male
Confirmed
N=1,466
9
PCR-positive Suspect
n=81
13
18%
16%
40%
17%
7%
1%
14%
17%
43%
23%
2%
0%
n=1,461
46%
n=81
51%
Confirmed & PCR-positive suspect
cases by race, ethnicity & region of
residence, WA, 2007-2010 WA
Race
White
Black
Asian
American Indian
Other
Ethnicity
Hispanic/Latino
Residence (region)
Western
Confirmed
(N = 1466)
n=945
86%
4%
2%
3%
5%
n=970
20%
n=1,466
80%
PCR-positive Suspect
(N=81)
n=46
93%
2%
0%
2%
2%
n=49
18%
n=81
75%
Comparing, case-defining symptoms,
clinical syndrome & disease severity
•
•
Case-defining symptoms (cough, whoop, vomit)
Clinical syndromes
• Pneumonia
• Encephalitis
•
Severity
• Antibiotic received
• ICU Admission
• Hospitalized overnight
•
•
Case fatality ratio
Chronic lung disease in survivors
Comparison of case-defining symptoms
by case classification, WA, 2007 - 2010
Symptoms
Confirmed
(n=1466)
PCR+ Suspect p-value
(n=81)
Two-week cough
98%
32%
<0.0001
Paroxysmal cough
89%
27%
<0.0001
Whoop
36%
10%
<0.0001
Vomit
57%
12%
<0.0001
Data completeness for clinically
defining symptoms, 2007-2010
Symptoms
Confirmed
(n=1466)
PCR+ Suspect
(n=81)
No. records
with data
No. records
with data
Two-week cough
1451
(99%)
65
(80%)
Paroxysmal cough
1435
(98%)
70
(86%)
Inspiratory whoop
1379
(94%)
71
(88%)
Post-tussive vomit
1421
(97%)
73
(90%)
Comparison of syndrome & outcome
by case classification, WA, 2007-2010
Syndrome/Outcomes
Confirmed
(n=1466)
PCR+ Suspect
(n=81)
P-value*
Pneumonia
5%
3%
0.77
Encephalitis
0.1%
0%
1.00
Given antibiotic for Bp
93%
97%
0.16
ICU Admission
3%
3%
0.71
Hospitalized overnight
9%
6%
0.44
Case fatality rate
0.2%
0%
1.00
Chronic lung disease
9%
3%
0.08
* Fisher’s Exact Test, one-tailed
Data completeness by case
classification, 2007-2010
Syndrome/outcome
Confirmed
(n=1466)
PCR+ Suspect
(n=81)
No. records
with data (%)
No. records
with data (%)
Pneumonia
1313
(90%)
70
(86%)
Encephalitis
1384
(94%)
72
(89%)
Received antibiotic
1415
(97%)
77
(95%)
ICU Admission
1328
(91%)
68
(84%)
Hospitalized overnight
1465
(100%)
81
(100%)
Case fatality rate
1466
(100%)
81
(100%)
Chronic lung disease
1387
(95%)
73
(90%)
*
Proportion of Total Number of Confirmed & PCR+
Suspect Cases by Quarter of Onset, WA, 2007-2010
20
Proportion - Confirmed
Proportion - Suspect
18
16
Proportion (%)
14
12
10
8
6
4
2
0
Year and Quarter
Proportion of Total Number of Confirmed & PCR+
Suspect Cases by Quarter of Onset, WA, 2007-2010
20
Proportion-Confirmed
Proportion-PCR Suspect
18
16
Proportion (%)
14
12
10
8
6
4
2
0
Year and Quarter
Summary
•
•
•
Increasing use of Bp PCR since 2005
•
PCR+ suspect & confirmed cases markedly different symptoms
Bp PCR - 100% NPV for culture isolate
Of 194 suspect cases identified in WA in 2007-10, 81 (42%)
associated with positive Bp PCR assay
• May be due to incomplete data entry
•
PCR+ suspect & confirmed cases similar in
• Age
• Race/ethnicity
• Geographic distribution
• Clinical syndrome
• Severity of illness
• Outcome
Proposed actions
•
If available, use Bp PCR result in algorithm to decide if
culture should be pursued
•
Consider inclusion of PCR-positive cases as “probable
cases” when 2-week cough, epidemiologic link, or
association with an outbreak are not present
• For discussion: PHL versus commercial lab results
Acknowledgements
Dr. Anthony A Tellez-Marfin, Washington State
Department of Health
Ms. Yolanda Houze, Washington State Public Health
Laboratories
Dr. Brendon “Troy” Leader, Washington State Public
Health Laboratories
Health Officers and Disease Investigators of 35 WA State
local health jurisdictions
Thank you. Questions
Documentation of case-defining
symptoms for PCR-positive suspect
cases 2007-2010
• 23/81 (28%) were missing data for at least
one clinical case-defining variable
• whoop, vomit, paroxysms, cough duration
• For 17/81 (21%) the missing data were key to
determining cases classification
•
1 record missing all 4 clinical case defining criteria
• 4 cases had a cough duration greater than 2 weeks but
missing at least one of the other case-defining symptoms
• 12 (15%) cases had at least one case-defining symptom,
but were missing data for cough duration
Reported Pertussis in WA State by case
classification 2007-2010
Case
Classification
2007
2008
2009
2010
388
363
237
478
Number PCR+
227
245
163
323
Percent PCR+
59%
67%
69%
68%
28
41
51
74
13
19
18
31
46%
46%
35%
42%
Confirmed
Suspect
Number PCR+
Percent PCR +