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 PCR-positive suspect cases with confirmed pertussis cases to determine differences in: Compare PCR-positive suspect cases with confirmed pertussis cases to determine differences in: DemographicsDemographics Measures of severity, outcome & antibiotic useMeasures of severity, outcome & antibiotic use SymptomsSymptoms Estimate sensitivity, specificity, & predictive value of Bordetella pertussis (Bp) PCR assays Estimate sensitivity, specificity, & predictive value of Bordetella pertussis (Bp) PCR assays WA State Public Health Laboratories (PHL), WA State Public Health Laboratories (PHL), Comparing results with standard cultureComparing results with standard culture Compare PCR-positive suspect cases with confirmed pertussis cases to determine differences in: Compare PCR-positive suspect cases with confirmed pertussis cases to determine differences in: DemographicsDemographics Measures of severity, outcome & antibiotic useMeasures of severity, outcome & antibiotic use SymptomsSymptoms Estimate sensitivity, specificity, & predictive value of Bordetella pertussis (Bp) PCR assays Estimate sensitivity, specificity, & predictive value of Bordetella pertussis (Bp) PCR assays WA State Public Health Laboratories (PHL), WA State Public Health Laboratories (PHL), Comparing results with standard cultureComparing results with standard culture

Case classification* Confirmed Isolate Bp from clinical specimen + cough of any duration, OR Isolate Bp from clinical specimen + cough of any duration, OR Detect Bp DNA by PCR + clinical case definition, OR Detect Bp DNA by PCR + clinical case definition, OR Link to lab-confirmed case + clinical case definition Link to lab-confirmed case + clinical case definitionProbable Meets clinical case definition but Meets clinical case definition but No Bp isolation or Bp DNA detected by PCR ANDNo Bp isolation or Bp DNA detected by PCR AND No link to a lab-confirmed caseNo link to a lab-confirmed caseConfirmed Isolate Bp from clinical specimen + cough of any duration, OR Isolate Bp from clinical specimen + cough of any duration, OR Detect Bp DNA by PCR + clinical case definition, OR Detect Bp DNA by PCR + clinical case definition, OR Link to lab-confirmed case + clinical case definition Link to lab-confirmed case + clinical case definitionProbable Meets clinical case definition but Meets clinical case definition but No Bp isolation or Bp DNA detected by PCR ANDNo Bp isolation or Bp DNA detected by PCR AND No link to a lab-confirmed caseNo link to a lab-confirmed case * Only confirmed or probable cases reported to CDC

Case classification (2) Clinical case definition Clinical case definition Cough ≥ 2 weeks PLUSone of followingCough ≥ 2 weeks PLUS one of following Cough paroxysmsCough paroxysms Inspiratory “whoop”Inspiratory “whoop” Post-tussive emesisPost-tussive emesis Bp PCR in WA Bp PCR in WA 1999: Bp PCR implemented at PHL1999: Bp PCR implemented at PHL By 2005, Bp PCR widely available at commercial labsBy 2005, Bp PCR widely available at commercial labs Clinical case definition Clinical case definition Cough ≥ 2 weeks PLUSone of followingCough ≥ 2 weeks PLUS one of following Cough paroxysmsCough paroxysms Inspiratory “whoop”Inspiratory “whoop” Post-tussive emesisPost-tussive emesis Bp PCR in WA Bp PCR in WA 1999: Bp PCR implemented at PHL1999: Bp PCR implemented at PHL By 2005, Bp PCR widely available at commercial labsBy 2005, Bp PCR widely available at commercial labs

Bp Culture & PCR in WA WA PHL, : WA PHL, : Of 9,623 samples sent for Bp culture, Bp isolated in only 318 (3.2%)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 5,369 samples sent for Bp PCR, Bp DNA detected in 422 (7.9%) Of these, 4,468 (83%) also culturedOf these, 4,468 (83%) also cultured 99 PCR results uninterpretable99 PCR results uninterpretable 4,372 with PCR result & culture result4,372 with PCR result & culture result WA PHL, : WA PHL, : Of 9,623 samples sent for Bp culture, Bp isolated in only 318 (3.2%)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 5,369 samples sent for Bp PCR, Bp DNA detected in 422 (7.9%) Of these, 4,468 (83%) also culturedOf these, 4,468 (83%) also cultured 99 PCR results uninterpretable99 PCR results uninterpretable 4,372 with PCR result & culture result4,372 with PCR result & culture result

Bp Culture Sample Submissions to WA PHL by Year, Year of Final Report Result * Number of Samples Submitted 3,5441,8901,3271,5831, Number Positive Percent Positive 5%3%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, Bp PCR Sample Submissions to WA PHL by Year, Year of Final Report Result * Samples Submitted1, ,0871,4211,04877 Result Obtained 1, ,0661,3861,02267 Number Positive Percent Positive 12%9%6%8%6%13% Number also cultured ,0001, %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, CULTURE “Gold Standard” PCR Result+-Total *4,0224,034 Total904,2824,372 * 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% Sensitivity: 87% Specificity: 94% Specificity: 94% PPV: 23% PPV: 23% NPV:100% NPV:100% Sensitivity: 87% Sensitivity: 87% Specificity: 94% Specificity: 94% PPV: 23% PPV: 23% NPV:100% NPV:100%

Changes in classification method for pertussis cases in WA 2005: Web-based electronic reporting system (PHIMS) start-up 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 Allows WA DOH & local health departments to jointly review/classify pertussis cases Improved classificationImproved classification : Many PCR-positive pertussis cases that do not meet clinical case definition : Many PCR-positive pertussis cases that do not meet clinical case definition 2005: Web-based electronic reporting system (PHIMS) start-up 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 Allows WA DOH & local health departments to jointly review/classify pertussis cases Improved classificationImproved classification : Many PCR-positive pertussis cases that do not meet clinical case definition : Many PCR-positive pertussis cases that do not meet clinical case definition

WA DOH defines “suspect” case Person whose initial symptoms suggest pertussis Person whose initial symptoms suggest pertussis Subsequent testing negative OR no testing doneSubsequent testing negative OR no testing done Cough duration < 2 weeks or cough duration undeterminedCough duration < 2 weeks or cough duration undetermined Person whose initial symptoms suggest pertussis Person whose initial symptoms suggest pertussis Subsequent testing negative OR no testing doneSubsequent testing negative OR no testing done Cough duration < 2 weeks or cough duration undeterminedCough 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”* 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” No two-week cough in a PCR-positive person → “suspect” For case & contact management, persons should be treated as if they had pertussis For case & contact management, persons should be treated as if they had pertussis Only confirmed & probable cases are reported to CDC 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”* 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” No two-week cough in a PCR-positive person → “suspect” For case & contact management, persons should be treated as if they had pertussis For case & contact management, persons should be treated as if they had pertussis Only confirmed & probable cases are reported to CDC Only confirmed & probable cases are reported to CDC *

Reported pertussis cases in WA, Confirmed cases:1466 (72%) Confirmed cases:1466 (72%) Probable cases: 375 (18%) Probable cases: 375 (18%) Suspect cases: 194 (10%) Suspect cases: 194 (10%) Among suspect cases, 81 (42%) Bp PCR-positive Confirmed cases:1466 (72%) Confirmed cases:1466 (72%) Probable cases: 375 (18%) Probable cases: 375 (18%) Suspect cases: 194 (10%) Suspect cases: 194 (10%) Among suspect cases, 81 (42%) Bp PCR-positive

Reported pertussis cases in WA by case classification, Case Classification Confirmed Probable Suspect PCR+ suspect Total reported cases* * Only confirmed or probable cases reported to CDC

Confirmed & PCR-positive suspect cases by age & gender, WA, ConfirmedPCR-positive Suspect Age (years)N=1,466n=81 Median age913 By age group <118%14% 1-416%17% %43% %23% %2% >651%0% Gendern=1,461n=81 Male46%51%

Confirmed & PCR-positive suspect cases by race, ethnicity & region of residence, WA, WA Confirmed (N = 1466) PCR-positive Suspect (N=81) Racen=945n=46 White86%93% Black4%2% Asian2%0% American Indian3%2% Other5%2% Ethnicityn=970n=49 Hispanic/Latino20%18% Residence (region)n=1,466n=81 Western80%75%

Comparing, case-defining symptoms, clinical syndrome & disease severity Case-defining symptoms (cough, whoop, vomit) Case-defining symptoms (cough, whoop, vomit) Clinical syndromes Clinical syndromes PneumoniaPneumonia EncephalitisEncephalitis Severity Severity Antibiotic receivedAntibiotic received ICU AdmissionICU Admission Hospitalized overnightHospitalized overnight Case fatality ratio Case fatality ratio Chronic lung disease in survivors Chronic lung disease in survivors Case-defining symptoms (cough, whoop, vomit) Case-defining symptoms (cough, whoop, vomit) Clinical syndromes Clinical syndromes PneumoniaPneumonia EncephalitisEncephalitis Severity Severity Antibiotic receivedAntibiotic received ICU AdmissionICU Admission Hospitalized overnightHospitalized overnight Case fatality ratio Case fatality ratio Chronic lung disease in survivors Chronic lung disease in survivors

Comparison of case-defining symptoms by case classification, WA, SymptomsConfirmed (n=1466) PCR+ Suspect (n=81) p-value Two-week cough98%32%< Paroxysmal cough89%27%< Whoop36%10%< Vomit57%12%<0.0001

Data completeness for clinically defining symptoms, SymptomsConfirmed (n=1466) PCR+ Suspect (n=81) No. records with data No. records with data Two-week cough1451(99%)65(80%) Paroxysmal cough1435(98%)70(86%) Inspiratory whoop1379(94%)71(88%) Post-tussive vomit1421(97%)73(90%)

Comparison of syndrome & outcome by case classification, WA, Syndrome/OutcomesConfirmed (n=1466) PCR+ Suspect (n=81) P-value* Pneumonia5%3%0.77 Encephalitis 0.1%0%1.00 Given antibiotic for Bp93%97%0.16 ICU Admission3% 0.71 Hospitalized overnight9%6%0.44 Case fatality rate 0.2%0%1.00 Chronic lung disease9%3%0.08 * Fisher’s Exact Test, one-tailed

Data completeness by case classification, Syndrome/outcomeConfirmed (n=1466) PCR+ Suspect (n=81) No. records with data (%) No. records with data (%) Pneumonia1313(90%)70(86%) Encephalitis1384(94%)72(89%) Received antibiotic1415(97%)77(95%) ICU Admission1328(91%)68(84%) Hospitalized overnight1465(100%)81(100%) Case fatality rate1466(100%)81(100%) Chronic lung disease1387(95%)73(90%) *

Proportion of Total Number of Confirmed & PCR+ Suspect Cases by Quarter of Onset, WA,

SummarySummary Increasing use of Bp PCR since 2005 Increasing use of Bp PCR since 2005 Bp PCR - 100% NPV for culture isolate Bp PCR - 100% NPV for culture isolate Of 194 suspect cases identified in WA in , 81 (42%) associated with positive Bp PCR assay Of 194 suspect cases identified in WA in , 81 (42%) associated with positive Bp PCR assay PCR+ suspect & confirmed cases markedly different symptoms PCR+ suspect & confirmed cases markedly different symptoms May be due to incomplete data entryMay be due to incomplete data entry PCR+ suspect & confirmed cases similar in PCR+ suspect & confirmed cases similar in AgeAge Race/ethnicityRace/ethnicity Geographic distributionGeographic distribution Clinical syndromeClinical syndrome Severity of illnessSeverity of illness OutcomeOutcome Increasing use of Bp PCR since 2005 Increasing use of Bp PCR since 2005 Bp PCR - 100% NPV for culture isolate Bp PCR - 100% NPV for culture isolate Of 194 suspect cases identified in WA in , 81 (42%) associated with positive Bp PCR assay Of 194 suspect cases identified in WA in , 81 (42%) associated with positive Bp PCR assay PCR+ suspect & confirmed cases markedly different symptoms PCR+ suspect & confirmed cases markedly different symptoms May be due to incomplete data entryMay be due to incomplete data entry PCR+ suspect & confirmed cases similar in PCR+ suspect & confirmed cases similar in AgeAge Race/ethnicityRace/ethnicity Geographic distributionGeographic distribution Clinical syndromeClinical syndrome Severity of illnessSeverity of illness OutcomeOutcome

Proposed actions If available, use Bp PCR result in algorithm to decide if culture should be pursued 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 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 resultsFor discussion: PHL versus commercial lab results If available, use Bp PCR result in algorithm to decide if culture should be pursued 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 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 resultsFor 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. Questions

Documentation of case-defining symptoms for PCR-positive suspect cases /81 (28%) were missing data for at least one clinical case-defining variable 23/81 (28%) were missing data for at least one clinical case-defining variable whoop, vomit, paroxysms, cough durationwhoop, vomit, paroxysms, cough duration For 17/81 (21%) the missing data were key to determining cases classification For 17/81 (21%) the missing data were key to determining cases classification 1 record missing all 4 clinical case defining criteria 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 symptoms4 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 duration12 (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 23/81 (28%) were missing data for at least one clinical case-defining variable whoop, vomit, paroxysms, cough durationwhoop, vomit, paroxysms, cough duration For 17/81 (21%) the missing data were key to determining cases classification For 17/81 (21%) the missing data were key to determining cases classification 1 record missing all 4 clinical case defining criteria 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 symptoms4 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 duration12 (15%) cases had at least one case-defining symptom, but were missing data for cough duration

Reported Pertussis in WA State by case classification Case Classification Confirmed Number PCR Percent PCR+ 59%67%69%68% Suspect Number PCR Percent PCR + 46% 35% 42%