Bordetella pertussis - Whooping Cough

Pertussis, also known as whooping cough, is an acute infectious disease caused by the Bordetella pertussis bacterium. In babies and young children, pertussis is especially dangerous and can result in potentially deadly complications such as pneumonia, apnea, and encephalopathy. The CDC recommends vaccination against whooping cough for young children, preteens, pregnant women, and unvaccinated adults.  The protective power of a pertussis vaccine fades over time, so being up-to-date with vaccination is important, particularly for families and caregivers of new babies. The early diagnosis and treatment of pertussis are extremely important to limit disease spread. Laboratory tests such as polymerase chain reaction (PCR), culture, and serology can detect the presence of the B. pertussis bacterium. These tests are highly dependent on the time that has elapsed since initial infection, so the testing strategy should be developed in reference to the time of disease onset. The CDC-recommended laboratory tests for pertussis diagnosis are blood culture and PCR, but serology may be appropriate for late-stage pertussis.  

Quick Answers for Clinicians

What is the importance of laboratory testing for the diagnosis and surveillance of pertussis?

Early diagnosis and treatment of pertussis (whooping cough) limit its spread to other susceptible people. According to the most recent case definition for pertussis, a positive culture or polymerase chain reaction (PCR) laboratory result is a required criterion for diagnosis.  Laboratory testing enables the collection of accurate surveillance data to assess the impact of pertussis and monitor changes in its epidemiology over time. The CDC recommends testing for patients with both high and low suspicion of pertussis for this reason. It is important to note that clinicians should not delay prophylactic treatment for close contacts, especially pregnant women and infants, pending laboratory test results. 

Which sample types are appropriate for polymerase chain reaction and serology testing for pertussis diagnosis?

A posterior nasopharyngeal (NP) swab or aspirate should be obtained from all persons with a suspected case of pertussis (whooping cough). A posterior NP swab is the preferred sample for adults and adolescents, whereas aspirates are preferable for neonates, infants, and young children. A properly obtained NP swab or aspirate is essential for optimal results. Throat swabs and anterior nasal swabs have an unacceptably low rate of DNA and bacteria recovery and should not be used for pertussis diagnosis. The CDC provides detailed information and instructional videos on best practices for specimen collection on their website. 

Where can I find more information about pertussis?

The Council of State and Territorial Epidemiologists (CSTE) published an approved case definition for pertussis (whooping cough) in position statement 13-ID-15.  The CDC also provides this definition on their website. 

There are many other useful, up-to-date CDC resources for clinicians  and patients.  Resources of note include vaccination information for pregnant women  and grandparents  to limit the spread of pertussis to infants and young children, and Tdap vaccination dosage recommendations  for adults.

Indications for Testing

Patients who have a cough lasting ≥2 weeks with one or more of the following signs or symptoms should be tested for pertussis  :

  • Paroxysms of cough
  • Inspiratory whoop
  • Posttussive vomiting
  • Apnea with or without cyanosis (in infants younger than 1 year)

However, because early diagnosis and treatment of pertussis might limit its spread, and laboratory testing methods are highly time dependent (see below), it may be appropriate to begin testing in cases of strong suspicion of pertussis earlier than 2 weeks from cough onset. 

Laboratory Testing

Laboratory testing is extremely important for the diagnosis and surveillance of pertussis. However, when pertussis is strongly suspected, prophylaxis should be provided to household and other close contacts at high risk without waiting for laboratory confirmation. 

The sensitivity of PCR, culture, and serology is heavily impacted by the time from disease onset. Therefore, selection of appropriate laboratory testing strategies is time dependent. The figure below depicts the optimal timing for PCR, culture, and serology testing for pertussis diagnosis.


Figure adapted from CDC 

PCR

PCR is a highly sensitive CDC-recommended laboratory test that is especially useful for the timely diagnosis of pertussis. Patients with signs and symptoms consistent with pertussis should be tested by PCR to confirm the diagnosis.  Specimens for PCR testing should be obtained by aspiration or by swabbing the posterior nasopharynx.  Unlike culture, PCR testing does not require live bacteria for accurate results. The optimal time to collect a sample for PCR testing is in the first 3 weeks of illness while bacterial DNA is still present in the nasopharynx. After the fourth week of illness, the amount of bacteria in the nasopharynx diminishes quickly, which increases the risk of a false-negative result.  Although PCR is a powerful test due to its high sensitivity, the CDC recommends that it be ordered in conjunction with culture when feasible. PCR testing is not recommended for asymptomatic patients because false-positive results are more likely in these individuals. 

Culture

Bacterial culture is a highly specific CDC-recommended laboratory test and is considered the gold standard for pertussis diagnosis because it allows for strain identification and antimicrobial resistance testing. Patients with suspected cases of pertussis should have a nasopharyngeal swab or aspirate obtained from the posterior nasopharynx to confirm the diagnosis.   The optimal time to collect a culture specimen is during the first 2 weeks of illness because this is when viable bacteria are present in the nasopharynx. Culture specimens taken after 2 weeks have low specificity and are more likely to produce false-negative results. If the patient has received antibiotic therapy or previous vaccination against B. pertussis, the sensitivity of bacterial culture decreases. Physicians should consider concurrent PCR testing. 

Serology

Serology is not a CDC-recommended test; however, it is often useful for the diagnosis of late-stage pertussis. The optimal time to collect a sample for serology is 2-8 weeks following cough onset. This is when the antibody titers are highest. However, serology can be performed on samples collected up to 12 weeks after the onset of illness. 

Several factors can contribute to inaccurate serology results. These include recent vaccination, previous infection, and cross-reactivity with other Bordetella species.  Serology is often ineffective in infants younger than 6 months due to interference from maternal antibodies.  As of March 2017, positive serology results from commercial laboratories were no longer considered confirmatory for the purpose of reporting; for that reason, serology is not a CDC-recommended test for pertussis diagnosis. 

Serology can be used to determine immune status. Please see the Immunization Status topic for more information.

Comparison of Pertussis Testing Methodologies

Test Methodology Advantages Disadvantages
PCR CDC-recommended test

High sensitivity

Does not require live bacteria for accurate result

Must be performed during first 3 weeks of illness for accurate results

Specificity varies

Increased risk of false positivity

Culture CDC-recommended test

High specificity

Allows for strain identification and antimicrobial resistance testing

Must be performed during first 2 weeks of illness for accurate results

Low sensitivity

Requires live bacteria

Serology Can be performed up to 12 weeks after disease onset

Can determine previous exposure to B. pertussis

Not a CDC-recommended test

Recent vaccination, previous infection, and cross-reactivity with other Bordetella species may cause inaccurate results

Is often ineffective in infants younger than 6 mos

Sources: CDC        ,  ; Van der Zee, 2015 ; Nieves, 2016 

ARUP Lab Tests

CDC-Recommended First-Line Tests for B. pertussis Diagnosis
Evaluate Late-Stage (Lasting >4 Weeks) B. pertussis
Assess Immunization Status

May be useful as evidence of vaccination or past infection; does not determine immunity to B. pertussis

See Immunization Status for more information

Medical Experts

Contributor

Couturier

Marc Roger Couturier, PhD, D(ABMM)
Associate Professor of Clinical Pathology, University of Utah
Medical Director, Parasitology/Fecal Testing, Infectious Disease Antigen Testing, Bacteriology, and Molecular Amplified Detection, ARUP Laboratories

References

Additional Resources
Resources from the ARUP Institute for Clinical and Experimental Pathology®