Pertussis is suggested by a prolonged cough illness, especially with a paroxysmal cough, inspiratory whoop, posttussive emesis, and, in infants, apnea or cyanosis.[10]American Academy of Pediatrics. Red book 2024-2027: report of the committee on infectious diseases. May 2024 [internet publication].
https://publications.aap.org/redbook?autologincheck=redirected
[26]Public Health England. Pertussis (whooping cough): information for healthcare professionals. Dec 2018 [internet publication].
https://www.gov.uk/government/publications/pertussis-whooping-cough-factsheet-for-healthcare-professionals
The diagnosis may be confirmed by culture, nucleic acid amplification test (NAAT), or serology. The sensitivity and specificity of these tests depends on the time elapsed since the onset of the illness, individual patient characteristics, and the quality of specimen collection and transportation.
History and examination
Classically, primary pertussis infection in infants and children has three distinctive phases.[1]Havers FP, Moro PL, Hariri S, et al. Pertussis. In: Hall E, Wodi AP, Hamborsky J, et al, eds. Centers for Disease Control and Prevention. Epidemiology and prevention of vaccine-preventable diseases (the Pink Book). 14th ed. Washington, DC: Public Health Foundation; 2021. Updated Apr 2024.
https://www.cdc.gov/pinkbook/hcp/table-of-contents/chapter-16-pertussis.html
[2]Kilgore PE, Salim AM, Zervos MJ, et al. Pertussis: microbiology, disease, treatment, and prevention. Clin Microbiol Rev. 2016 Jul;29(3):449-86.
https://journals.asm.org/doi/10.1128/CMR.00083-15
http://www.ncbi.nlm.nih.gov/pubmed/27029594?tool=bestpractice.com
[10]American Academy of Pediatrics. Red book 2024-2027: report of the committee on infectious diseases. May 2024 [internet publication].
https://publications.aap.org/redbook?autologincheck=redirected
Stage 1: catarrhal stage
Typical duration is 1-2 weeks.
Symptoms are those of a nonspecific upper respiratory tract infection, including rhinorrhea, sneezing, and mild cough. Fever is uncommon and low-grade.
Patients are most infectious in this stage.
Stage 2: paroxysmal stage
Typical duration is 1-6 weeks, but it can persist for up to 10 weeks.
Coughing spells gradually become more severe during the first 1-2 weeks, plateau for 2-3 weeks, and then gradually decrease in frequency.
Paroxysms of coughing are often associated with an inspiratory whoop and posttussive emesis. These symptoms are highly characteristic of the disease and should trigger clinical suspicion for pertussis. Most diagnoses are made during this stage.
Stage 3: convalescent stage
Typical duration is 2-3 weeks.
Cough becomes less paroxysmal and slowly resolves, but recurrent cough may be triggered over the next several months by new upper respiratory tract infections.
Diagnostic tests are insensitive after the fourth week of infection.
Overall, complications occur in about 6% of patients, but in about one quarter of children ages <6 months.[1]Havers FP, Moro PL, Hariri S, et al. Pertussis. In: Hall E, Wodi AP, Hamborsky J, et al, eds. Centers for Disease Control and Prevention. Epidemiology and prevention of vaccine-preventable diseases (the Pink Book). 14th ed. Washington, DC: Public Health Foundation; 2021. Updated Apr 2024.
https://www.cdc.gov/pinkbook/hcp/table-of-contents/chapter-16-pertussis.html
[10]American Academy of Pediatrics. Red book 2024-2027: report of the committee on infectious diseases. May 2024 [internet publication].
https://publications.aap.org/redbook?autologincheck=redirected
[27]Heininger U, Klich K, Stehr K, et al. Clinical findings in Bordetella pertussis infections: results of a prospective multicenter surveillance study. Pediatrics. 1997 Dec;100(6):E10.
http://www.ncbi.nlm.nih.gov/pubmed/9382911?tool=bestpractice.com
The most common complication is secondary bacterial pneumonia, which may be further complicated by respiratory failure, sometimes accompanied by pulmonary hypertension, severe lymphocytosis, and shock. Apnea, respiratory failure, seizures, and encephalopathy are also more frequent in infants and may be related to bacterial toxins or to hypoxia associated with severe coughing episodes.[10]American Academy of Pediatrics. Red book 2024-2027: report of the committee on infectious diseases. May 2024 [internet publication].
https://publications.aap.org/redbook?autologincheck=redirected
Vaccinated individuals, those who have had prior pertussis infection, and adolescents and adults may be asymptomatic or have a mild and nonparoxysmal cough.[4]Cherry JD. The 112-year odyssey of pertussis and pertussis vaccines - mistakes made and implications for the future. J Pediatric Infect Dis Soc. 2019 Sep 25;8(4):334-41.
https://academic.oup.com/jpids/article/8/4/334/5359449
http://www.ncbi.nlm.nih.gov/pubmed/30793754?tool=bestpractice.com
[10]American Academy of Pediatrics. Red book 2024-2027: report of the committee on infectious diseases. May 2024 [internet publication].
https://publications.aap.org/redbook?autologincheck=redirected
[28]McNamara LA, Skoff T, Faulkner A, et al. Reduced severity of pertussis in persons with age-appropriate pertussis vaccination - United States, 2010-2012. Clin Infect Dis. 2017 Sep 1;65(5):811-8.
https://academic.oup.com/cid/article/65/5/811/3939810
http://www.ncbi.nlm.nih.gov/pubmed/29017283?tool=bestpractice.com
The absence of classical symptoms of pertussis in these patients may lead to underdiagnosis; unsuspected illness in asymptomatic or mildly ill adolescents and adults may then serve as a reservoir for infection of young children, in whom illness may be more severe.
In infants under ages 1 year and particularly those less than ages 6 months, cough may be absent or not paroxysmal.[1]Havers FP, Moro PL, Hariri S, et al. Pertussis. In: Hall E, Wodi AP, Hamborsky J, et al, eds. Centers for Disease Control and Prevention. Epidemiology and prevention of vaccine-preventable diseases (the Pink Book). 14th ed. Washington, DC: Public Health Foundation; 2021. Updated Apr 2024.
https://www.cdc.gov/pinkbook/hcp/table-of-contents/chapter-16-pertussis.html
[2]Kilgore PE, Salim AM, Zervos MJ, et al. Pertussis: microbiology, disease, treatment, and prevention. Clin Microbiol Rev. 2016 Jul;29(3):449-86.
https://journals.asm.org/doi/10.1128/CMR.00083-15
http://www.ncbi.nlm.nih.gov/pubmed/27029594?tool=bestpractice.com
[10]American Academy of Pediatrics. Red book 2024-2027: report of the committee on infectious diseases. May 2024 [internet publication].
https://publications.aap.org/redbook?autologincheck=redirected
This cohort may present with other atypical manifestations of early disease, including a short catarrhal stage, gagging, gasping, or apnea.[3]Centers for Disease Control and Prevention. CDC Yellow Book 2024: health information for international travel. Section 5: travel-associated infections & diseases - pertussis/whooping cough. May 2023 [internet publication].
https://wwwnc.cdc.gov/travel/yellowbook/2024/infections-diseases/pertussis-whooping-cough
Laboratory evaluation
The diagnosis of pertussis is based on the clinical history and specific diagnostic laboratory tests. The most characteristic general laboratory findings in pertussis are a leukocytosis and lymphocytosis, which are seen in up to 75% of patients, most commonly in children.[2]Kilgore PE, Salim AM, Zervos MJ, et al. Pertussis: microbiology, disease, treatment, and prevention. Clin Microbiol Rev. 2016 Jul;29(3):449-86.
https://journals.asm.org/doi/10.1128/CMR.00083-15
http://www.ncbi.nlm.nih.gov/pubmed/27029594?tool=bestpractice.com
The white blood cell count and lymphocytosis may be accentuated in young infants (leukemoid reaction) and may parallel the severity of clinical disease in this age group. Chest radiographs are usually unremarkable or may demonstrate nonspecific perihilar infiltrates or atelectasis.
The definitive test for diagnosis is culture of Bordetella pertussis from a posterior nasopharyngeal swab or nasopharyngeal aspirate.[1]Havers FP, Moro PL, Hariri S, et al. Pertussis. In: Hall E, Wodi AP, Hamborsky J, et al, eds. Centers for Disease Control and Prevention. Epidemiology and prevention of vaccine-preventable diseases (the Pink Book). 14th ed. Washington, DC: Public Health Foundation; 2021. Updated Apr 2024.
https://www.cdc.gov/pinkbook/hcp/table-of-contents/chapter-16-pertussis.html
[2]Kilgore PE, Salim AM, Zervos MJ, et al. Pertussis: microbiology, disease, treatment, and prevention. Clin Microbiol Rev. 2016 Jul;29(3):449-86.
https://journals.asm.org/doi/10.1128/CMR.00083-15
http://www.ncbi.nlm.nih.gov/pubmed/27029594?tool=bestpractice.com
[10]American Academy of Pediatrics. Red book 2024-2027: report of the committee on infectious diseases. May 2024 [internet publication].
https://publications.aap.org/redbook?autologincheck=redirected
[26]Public Health England. Pertussis (whooping cough): information for healthcare professionals. Dec 2018 [internet publication].
https://www.gov.uk/government/publications/pertussis-whooping-cough-factsheet-for-healthcare-professionals
[29]Centers for Disease Control and Prevention. Clinical overview of pertussis. Apr 2024 [internet publication].
https://www.cdc.gov/pertussis/hcp/clinical-overview
While culture is highly specific, sensitivity is reduced if specimens are obtained from patients who have partial immunity to pertussis or who have received antimicrobials that are effective against pertussis, if cultures are obtained >2 weeks after the onset of cough, and if they are not collected and transported appropriately. Nevertheless, positive cultures are highly specific and may permit strain identification and confirmation of antimicrobial susceptibilities, so cultures should be obtained if cough has been present for <2 weeks. Polyethylene terephthalate or calcium alginate swabs should be used, and specimens should be placed in transport media if they cannot be processed promptly.
Nucleic acid amplification tests, including polymerase chain reaction (PCR) assays, have increased sensitivity relative to culture, and can be obtained up to 4 weeks following the onset of cough.[29]Centers for Disease Control and Prevention. Clinical overview of pertussis. Apr 2024 [internet publication].
https://www.cdc.gov/pertussis/hcp/clinical-overview
False positives may result from B pertussis DNA contamination of the environment, including from B pertussis vaccines. If the timeframe allows (i.e., <2 weeks from cough onset), culture and NAAT should both be obtained.[29]Centers for Disease Control and Prevention. Clinical overview of pertussis. Apr 2024 [internet publication].
https://www.cdc.gov/pertussis/hcp/clinical-overview
Note that nasopharyngeal specimens for PCR testing should be collected using a polyethylene terephthalate swab or nasopharyngeal wash or aspirate. Calcium alginate swabs can be inhibitory to PCR and should not be used.
Serology is also available, although it is not standardized and not frequently used. A serum anti-pertussis toxin antibody concentration of >100 IU/mL 2-8 weeks after the onset of cough is suggestive of infection.[10]American Academy of Pediatrics. Red book 2024-2027: report of the committee on infectious diseases. May 2024 [internet publication].
https://publications.aap.org/redbook?autologincheck=redirected
False positive results may occur in people vaccinated with a pertussis-containing vaccine in the preceding 6 months to 1 year.
Detection of anti-pertussis toxin immunoglobulin G (IgG) in oral fluid is used in the UK to diagnose pertussis in children and adolescents who have had cough for >14 days. As with serum IgG anti-pertussis antibody, false positive results may occur in people recently vaccinated with a pertussis-containing vaccine.[26]Public Health England. Pertussis (whooping cough): information for healthcare professionals. Dec 2018 [internet publication].
https://www.gov.uk/government/publications/pertussis-whooping-cough-factsheet-for-healthcare-professionals
Direct fluorescent detection of B pertussis in nasopharyngeal secretions is not recommended for diagnosis because of low test sensitivity and specificity.