Pertussis Diagnosis in 2018

By Prof Miles H Beaman, Medical Director, Western Diagnostic Pathology, Clin/Prof UWA and UND.

Pertussis is a potentially-fatal infection which continues to occur despite worldwide access to an effective vaccine. Annually there are ~48 million pertussis cases and ~300,000 deaths worldwide. The 10-year Australian average for annual notifications is 20,834 (1834 for WA). Our state has experienced epidemics in 1997, 2004 and 2011 and 710 cases have been notified this year to date.

In the pre-vaccine era pertussis was an endemic disease with epidemic cycles every 3-5 years and most cases occurred in the 1-12 year age group. The illness classically had three clinical phases (catarrhal, paroxysmal and convalescent lasting up to 6 months) following a 1-3 week incubation.

Transmission is by aerosols and the secondary attack rate in households is 50-100%.

In the vaccination era, the epidemiology has shifted to involve infants <12 months (previously protected by maternal antibodies) and adults. The spectrum of disease now includes attenuated illnesses and later clinical presentations.

Laboratory testing

Culture of Bordetella pertussis, is insensitive as the organism requires immediate culture on a selective medium. The optimum specimen is a naso-pharyngeal aspirate, as the organism is only found in ciliated respiratory epithelium. Nose and throat swabs have a significantly reduced culture rate.

Polymerase chain reaction (PCR) is a more sensitive test for diagnosis, but is usually only positive for the first three weeks of illness (which correlates with antibiotic responsiveness). The changing epidemiology results in many patients (especially adults) presenting late with negative PCR tests.

Blood serology with whole-cell antigen [WC] (similar to that used in the previous vaccine), has recently been replaced by a pertussis-toxin [PT] antigen because of low specificity of the WC assay. PT-IgA in serum is moderately sensitive but is used as an adjunct to PCR when an NPA cannot be performed. It is NOT a suitable test for immunity to pertussis (and no such test exists).

We previously offered B. pertussis-specific IgA antibody (WC) testing in naso-pharyngeal aspirate (NPA). This has a higher diagnostic yield than PCR because of the persistence of mucosal antibodies after the disappearance of nucleic acid. NPA is well tolerated compared to alternative sampling methods such as nasopharyngeal swabs and are collected in 11 of our community collection centres.

Recently we reported inferior sensitivity of WC B. pertussis-specific IgA assay compared to our new Pertussis-Toxin (PT) B. pertussis antibody assay in NPA. Since implementation of the new protocol, we have tested 2386 samples and 851 definite cases of pertussis were identified. NPA IgA had sensitivity of 95.4% and specificity of 96.4% (compared to 9.7% and 100% for PCR). The average duration of cough in this study was 4.7 weeks, which explains the low rate of detection with PCR. This showed the superior diagnostic yield of NPA IgA testing compared to PCR alone (especially if only a respiratory swab is collected).

Laboratory investigations are assessed with the clinical case definition of pertussis (i.e. contact with a confirmed case, cough duration of 2 weeks or more, coughing paroxysms, or post-tussive whooping or vomiting).

Treatment

This is with macrolide antibiotics which achieve adequate levels in respiratory secretions (i.e. clarithromycin or azithromycin, NOT roxithromycin). As toddlers are at highest risk in an infected household, pre-emptive treatment on public health grounds is indicated.

Key Messages

  • Pertussis is still a potentially-fatal prevalent infection despite a national vaccine program.
  • The investigation of choice is NPA for PCR and mucosal IgA level. Where NPA is not available, nasopharyngeal swab for PCR plus serum for blood IgA level is reasonable.
  • Dry throat or nose swabs are NOT adequate samples for diagnosis.
  • Requests should include clinical data including fulfilment of the case definition of pertussis.
  • Macrolides (clarithromycin, azithromycin) are indicated in PCR-positive cases and household contacts under 5 years of age

References available on request

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