underestimating the burden of pertussis in wa 2011 cste annual meeting pittsburgh, pa chas debolt...
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Underestimating the burden of pertussis in WA
2011 CSTE Annual Meeting Pittsburgh, PA
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
Chas DeBolt RN, MPH
Azadeh Tasslimi, MPH
Washington State Department of Health
ObjectivesObjectives
• 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
• 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*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
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)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
•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 WABp 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
• 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
Bp Culture Sample Submissions to WA PHL by Year, 2005-2010
Year of Final Report Result
2005 2006 2007 2008 2009 2010*
Number of Samples
Submitted3,544 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%
* 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
Bp PCR Sample Submissions to WA PHL by Year, 2005-2010
Year of Final Report Result
2005 2006 2007 2008 2009 2010*
Samples Submitted 1,124 612 1,087 1,421 1,048 77
Result Obtained
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%
* 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
Paired Bp PCR & culture results, WA PHL, 2005-2010
CULTURE“Gold Standard”
PCR Result + - Total
+ 78 260 338
- 12* 4,022 4,034
Total 90 4,282 4,372
* Of these 12, 6 (50%) occurred during a single six-week period in Spring 2009
Performance of Bp PCR performance compared to culture
Performance of Bp PCR performance compared to culture
• Sensitivity: 87%
• Specificity: 94%
• PPV: 23%
• NPV:100%
• Sensitivity: 87%
• Specificity: 94%
• PPV: 23%
• NPV:100%
Changes in classification method for pertussis cases in WA
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
• 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” caseWA 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
• 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
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”
• For case & contact management, persons should be treated as if they had pertussis
• Only confirmed & probable cases are reported to CDC
• 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”
• For case & contact management, persons should be treated as if they had pertussis
• Only confirmed & probable cases are reported to CDC
* http://www.doh.wa.gov/notify/guidelines/pdf/pertussis.pdf
Reported pertussis cases in WA, 2007-2010
Reported pertussis cases in WA, 2007-2010
• Confirmed cases: 1466 (72%)
• Probable cases: 375 (18%)
• Suspect cases: 194 (10%)
Among suspect cases, 81 (42%)
Bp PCR-positive
• Confirmed cases: 1466 (72%)
• Probable cases: 375 (18%)
• Suspect cases: 194 (10%)
Among suspect cases, 81 (42%)
Bp PCR-positive
Reported pertussis cases in WA by case classification, 2007-2010
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
Total reported cases* 482 460 291 608
* Only confirmed or probable cases reported to CDC
Confirmed & PCR-positive suspect cases by age & gender, WA, 2007-2010
Confirmed & PCR-positive suspect cases by age & gender, WA, 2007-2010
Confirmed PCR-positive SuspectAge (years) N=1,466 n=81
Median age 9 13By age group
<1 18% 14%1-4 16% 17%5-17 40% 43%18-44 17% 23%45-64 7% 2%>65 1% 0%
Gender n=1,461 n=81
Male 46% 51%
Confirmed & PCR-positive suspect cases by race, ethnicity & region of
residence, WA, 2007-2010 WA
Confirmed & PCR-positive suspect cases by race, ethnicity & region of
residence, WA, 2007-2010 WA
Confirmed(N = 1466)
PCR-positive Suspect(N=81)
Race n=945 n=46
White 86% 93%
Black 4% 2%
Asian 2% 0%
American Indian 3% 2%
Other 5% 2%
Ethnicity n=970 n=49
Hispanic/Latino 20% 18%
Residence (region) n=1,466 n=81
Western 80% 75%
Comparing, case-defining symptoms, clinical syndrome & disease severityComparing, 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
• 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
Comparison of case-defining symptoms by case classification, WA, 2007 - 2010
Symptoms Confirmed(n=1466)
PCR+ Suspect(n=81)
p-value
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
Data completeness for clinically defining symptoms, 2007-2010
Symptoms Confirmed(n=1466)
PCR+ Suspect(n=81)
No. recordswith data
No. recordswith 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, 2007-2010Comparison 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
Data completeness by case classification, 2007-2010
Syndrome/outcome Confirmed(n=1466)
PCR+ Suspect(n=81)
No. recordswith data (%)
No. recordswith 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
Proportion of Total Number of Confirmed & PCR+ Suspect Cases by Quarter of Onset, WA, 2007-2010
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Proportion of Total Number of Confirmed & PCR+ Suspect Cases by Quarter of Onset, WA, 2007-2010
Proportion of Total Number of Confirmed & PCR+ Suspect Cases by Quarter of Onset, WA, 2007-2010
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SummarySummary• Increasing use of Bp PCR since 2005
• 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
• PCR+ suspect & confirmed cases markedly different symptoms
• May be due to incomplete data entry
• PCR+ suspect & confirmed cases similar in
• Age
• Race/ethnicity
• Geographic distribution
• Clinical syndrome
• Severity of illness
• Outcome
• Increasing use of Bp PCR since 2005
• 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
• PCR+ suspect & confirmed cases markedly different symptoms
• 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 actionsProposed 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
• 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
AcknowledgementsAcknowledgements
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
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. QuestionsThank you. Questions
Documentation of case-defining symptoms for PCR-positive suspect
cases 2007-2010
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
• 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
Reported Pertussis in WA State by case classification 2007-2010
Case Classification
2007 2008 2009 2010
Confirmed 388 363 237 478
Number PCR+ 227 245 163 323
Percent PCR+ 59% 67% 69% 68%
Suspect 28 41 51 74
Number PCR+ 13 19 18 31
Percent PCR + 46% 46% 35% 42%