The Physician's Guide to Laboratory Test Selection and Interpretation

Bordetella pertussis - Whooping Cough

Key Points
Pertussis (Bordetella pertussis) Diagnosis CDC 2010 case definition and classification (see table below) CDC 2010 Case Definition Clinical Criteria Cough lasting >2 weeks One or more symptoms Paroxysms of cough Inspiratory whoop Posttussive vomiting In epidemic setting, acute coughing illness lasting >2 weeks Probable Meets clinical criteria definition Not laboratory confirmed Not epidemiologically linked to a laboratory-confirmed case Confirmed (one of the following) Acute cough illness of any duration with a positive culture for B. pertussis Meets clinical criteria and confirmed by PCR Meets clinical criteria and epidemiologically linked directly to a case confirmed by either culture or PCR Laboratory testing for pertussis diagnosis (see table below) Laboratory Testing PCR Optimal timing is <4 weeks post cough onset Highly sensitive Best sensitivity with nasopharyngeal (NP) swab or aspirate (do not use calcium alginate swabs shown to interfere with PCR) Optimal timing is <2 weeks post cough onset NP aspirates may allow better recovery than NP swabs (cotton swabs may inhibit B. pertussis) Decreased sensitivity in persons with cough >2 weeks, receiving antibiotics, of older age, immunosuppressed, or previously vaccinated Sensitivity is highly dependent on collection of acute and convalescent sera (single unpaired specimens are typically not useful) Not confirmatory for CDC case definition Low sensitivity Not confirmatory for CDC case definition Laboratory Criteria (one or both) Isolation of B. pertussis in culture Positive PCR test for B. pertussis

Case Classification

Culture

Serology (IgA, IgG, IgM)

DFA

Diagnosis

Indications for Testing

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Patients with predominant complaint of persistent cough, especially in the absence of fever, sore throat, hoarseness, tachypnea or wheeze Criteria for Diagnosis CDC criteria for Bordetella pertussis infection Laboratory Testing Refer to Key Points tab Differential Diagnosis Chlamydia pneumoniae Adenovirus Mycoplasma pneumoniae Parainfluenza Virus 1, 2, 3 Influenza Asthma Acute exacerbation of chronic bronchitis Cytomegalovirus Legionella pneumophila Hantavirus Metapneumovirus

Clinical Background

Pertussis is a highly infectious and contagious disease commonly referred to as whooping cough. It is caused by the bacterium Bordetella pertussis. Epidemiology Incidence 1-5/100,000 Recent resurgence of disease in industrialized countries Age peak incidence <6 months or >14 years of age Primarily seen in those with waning immunity from childhood vaccination (immunity begins to wane during early adolescence) Significant incidence in unimmunized infants <1 year Occurrence infection occurs most frequently in late spring and summer Transmission Adult and teenage children with common cold symptoms are significant reservoirs of the organism and the source of outbreaks in highly susceptible populations Transmitted by respiratory droplets (B. pertussis causes disease only in humans) Infection rates >90% in susceptible populations Organism B. pertussis is a gram-negative pleomorphic coccobacillus Multiple virulence factors are produced that aid in organism attachment and production of disease Pertussis toxin is responsible for many disease effects B. parapertussis is a related species that may cause a milder form of pertussis syndrome Clinical Presentation Nonspecific viral upper respiratory tract infection-like symptoms Disease spread often not recognized due to mild symptoms in immunized persons

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The Physician's Guide to Laboratory Test Selection and Interpretation

Secondary spread common in families and schools After 7-10 day incubation, a prolonged course ensues consisting of 3 overlapping stages Catarrhal (1-2 weeks post infection [PI]) Paroxysmal coughing (1-4 weeks PI) Convalescent (4-6 weeks PI) Partially immune persons and infants >6 months may not manifest all of the typical symptoms Paroxysmal coughing may be absent Classic pertussis is generally diagnosed clinically Inspiratory whoop Lymphocytosis Paroxysmal cough Posttussive vomiting Atypical pertussis may occur with mild or absent symptoms in adults and previously vaccinated children Atypical pertussis is common, endemic and usually unrecognized in adults Secondary complications Respiratory Bronchitis Laryngitis Pneumonia Pneumothorax Nonrespiratory Complications resulting from severe cough Epistaxis Rectal prolapse Rib fracture Subconjunctival hemorrhage Central nervous system Deafness Encephalopathy Seizures Hemolytic uremic syndrome Death fulminant course more common in very young infants Prevention Vaccination Pediatric age groups combined Hib and DTaP Adult revaccination ACP recommendation during teen years, in patients 11-64 years, and conditionally >65 years (Tdap)

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The Physician's Guide to Laboratory Test Selection and Interpretation

Lab Tests

Indications for Laboratory Testing Tests generally appear in the order most useful for common clinical situations. For test-specific information, refer to the test number in the ARUP Laboratory Test Directory on the ARUP Web site at www.aruplab.com. Test Name and Number Bordetella pertussis/ parapertussis by PCR 0065080 Method: Qualitative Polymerase Chain Reaction Recommended Use Method of choice for direct detection of B. pertussis or B. parapertussis for patients with cough and no previous antibiotic therapy Adult patients with persistent cough in whom pertussis is suspected Children with epidemiological and clinical features of disease Additionally, CDC recommends B. pertussis culture Limitations Patients with pertussis may remain PCR-positive for variable periods following treatment Negative result does not rule out the presence of B. pertussis DNA in concentrations below detection level of assay False positives for B. pertussis may occur in samples containing B. holmesii DNA; false positives for B. parapertussis may occur in samples containing B. bronchiseptica DNA Highly specific only in acute disease phase Follow Up

Bordetella pertussis Culture 0060117 Method: Culture/Identification

Gold standard test for diagnosing pertussis

May test for B. pertussis in adults Negative culture who have consistent epidemiological does not exclude and clinical features of disease the possibility of B. In addition, consider B. pertussis by pertussis infection PCR

Successful culture requires special media and incubation up to 7 days; also highly dependent on specimen collection, transportation and laboratory techniques Diagnostic sensitivity <60% when specimen obtained after early catarrhal stage or after treatment with certain antibiotics; reduced sensitivity in adults and vaccinated patients

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The Physician's Guide to Laboratory Test Selection and Interpretation

Bordetella pertussis Antibodies, IgA and IgG by ELISA with Reflex to Immunoblot 2001774 Method: Semi-Quantitative Enzyme-Linked Immunosorbent Assay/Qualitative Immunoblot Additional Tests Available Test Name and Number

May aid in diagnosis of pertussis in adults with prolonged cough in later stages of the disease; however, in most cases serologic testing is not recommended for diagnosis of active pertussis infection Positive or equivocal ELISA results are confirmed by immunoblot; if IgA 1.2 U/mL, IgA immunoblot will be added; if IgG 2.5 U/mL, IgG immunoblot will be added

Only use when paired (acute and convalescent) samples show significant change in antibody titer Test does not satisfy CDC criteria for diagnosing pertussis

Comments May aid in diagnosis of pertussis in adults with prolonged cough in later stages of the disease; cannot be used to confirm infection

Bordetella pertussis Antibodies, IgA, IgG, and IgM by Immunoblot 2004328 Method: Qualitative Immunoblot Bordetella pertussis Antibodies, IgA, IgG, and IgM by ELISA with Reflex to Immunoblot 2001775 Method: Semi-Quantitative Enzyme-Linked Immunosorbent Assay/Qualitative Immunoblot Bordetella pertussis Antibody, IgG by ELISA 2005268 Method: Semi-Quantitative Enzyme-Linked Immunosorbent Assay Bordetella pertussis Antibody, IgG by ELISA with Reflex to Immunoblot 2001768 Method: Semi-Quantitative Enzyme-Linked Immunosorbent Assay/Qualitative Immunoblot Bordetella pertussis Antibody, IgM by ELISA with Reflex to Immunoblot 2001769 Method: Semi-Quantitative Enzyme-Linked Immunosorbent Assay/Qualitative Immunoblot Gram Stain 0060101 Method: Stain/Microscopy

Cannot be used to confirm infection

Cannot be used to confirm infection

Cannot be used to confirm infection

Cannot be used to confirm infection

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The Physician's Guide to Laboratory Test Selection and Interpretation

Bordetella pertussis DFA 2004667 Method: Direct Fluorescent Antibody Stain Bordetella pertussis Antibodies, IgG and IgM by ELISA with Reflex to Immunoblot 2001784 Method: Semi-Quantitative Enzyme-Linked Immunosorbent Assay/Qualitative Immunoblot Bordetella pertussis Antibody, IgA by Immunoblot 2004316 Method: Qualitative Immunoblot Bordetella pertussis Antibody, IgG by Immunoblot 2004327 Method: Qualitative Immunoblot Bordetella pertussis Antibody, IgM by Immunoblot 2004326 Method: Qualitative Immunoblot Guidelines

DFA is not recommended; refer instead to culture or PCR

Cannot be used to confirm infection

Cannot be used to confirm infection

Cannot be used to confirm infection

Cannot be used to confirm infection

Centers for Disease Control and Prevention. Recommended immunization schedules for persons aged 0 through 18 years---United States, 2010. MMWR 2010;58(51&52). [Accessed: 28 Apr 2011] Faulkner A, Skoff T, Martin S, Cassiday P, Tondella ML, Liang J, Ejigiri OG. Chapter 10: Pertussis. Manual for the Surveillance of Vaccine-Preventable Diseases. Vaccines and Immunizations (5th Edition, 2011). Centers for Disease Control and Prevention. Atlanta, GA [Last Updated: 8 Jul 2011; Accessed: 7 Aug 2012] General References Bamberger ES, Srugo I. What is new in pertussis?.Eur J Pediatr. 2008; 167 (2) :133-139. Cornia PB, Hersh AL, Lipsky BA, Newman TB, Gonzales R. Does this coughing adolescent or adult patient have pertussis?.JAMA. 2010; 304 (8) :890-896. Heininger U. Update on pertussis in children.Expert Rev Anti Infect Ther. 2010; 8 (2) :163-173. Raguckas SE, VandenBussche HL, Jacobs C, Klepser ME. Pertussis resurgence: diagnosis, treatment, prevention, and beyond.Pharmacotherapy. 2007; 27 (1) :41-52. Zouari A, Smaoui H, Kechrid A. The diagnosis of pertussis: which method to choose?.Crit Rev Microbiol. 2011; :-. References from the ARUP Institute for Clinical and Experimental Pathology Cloud JL, Hymas W, Carroll KC. Impact of nasopharyngeal swab types on detection of Bordetella pertussis by PCR and culture.J Clin Microbiol. 2002; 40 (10) :3838-3840. Cloud JL, Hymas WC, Turlak A, Croft A, Reischl U, Daly JA, Carroll KC. Description of a multiplex Bordetella pertussis and Bordetella parapertussis LightCycler PCR assay with inhibition control.Diagn Microbiol Infect Dis. 2003; 46 (3) :189-195.
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The Physician's Guide to Laboratory Test Selection and Interpretation

Merrigan SD, Welch RJ, Litwin CM. Comparison of Western immunobloting to an enzyme-linked immunosorbent assay for the determination of anti-Bordetella pertussis antibodies.Clin Vaccine Immunol. 2011; 18 (4) :615-620. She RC, Billetdeaux E, Phansalkar AR, Petti CA. Limited applicability of direct fluorescent-antibody testing for Bordetella sp. and Legionella sp. specimens for the clinical microbiology laboratory.J Clin Microbiol. 2007; 45 (7) :2212-2214. Reviewed by Couturier, Marc Roger, PhD, D(ABMM). Medical Director Microbial Immunology, and Assistant Medical Director Parasitology/Fecal Testing and Infectious Disease Rapid Testing at ARUP Laboratories; Assistant Professor of Pathology, University of Utah Fisher, Mark A., PhD. Medical Director, Bacteriology, Antimicrobials, Parasitology, Infectious Disease Rapid Testing at ARUP Laboratories; Assistant Professor of Pathology, University of Utah Hillyard, David R., MD. Medical Director, Molecular Hepatitis and Retrovirus, Molecular Infectious Diseases, and Molecular Sequencing at ARUP Laboratories; Professor of Pathology, University of Utah Related Content Adenovirus Chlamydophila pneumoniae or psittaci Hantavirus Influenza Virus Legionella pneumophila Metapneumovirus - hMPV Mycoplasma pneumoniae Parainfluenza Virus 1, 2, 3, 4
Last Update: March 2013

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