Underestimating the burden of pertussis in WA

2011 CSTE Annual Meeting Pittsburgh, PA

Chas DeBolt RN, MPHAzadeh 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*

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

 

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

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

• 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”

• 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

• 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

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 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(N = 1466)

PCR-positive Suspect(N=81)

Race n=945 n=46White 86% 93%Black 4% 2%Asian 2% 0%American Indian 3% 2%Other 5% 2%

Ethnicity n=970 n=49Hispanic/Latino 20% 18%

Residence (region) n=1,466 n=81Western 80% 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(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

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, 2007-2010

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. 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

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Proportion of Total Number of Confirmed & PCR+ Suspect Cases by Quarter of Onset, WA, 2007-2010

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Summary• 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 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

AcknowledgementsDr. 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

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 31Percent PCR + 46% 46% 35% 42%