European Centre for Disease Prevention and Control. Guidance and protocol for the serological diagnosis of human infection with Bordetella pertussis. https://ecdc.europa.eu/en/publications-data/guidance-and-protocol-serological-diagnosis-human-infection-bordetella-pertussis. doi: 10.2900/64470. Published 2012. Accessed March 14, 2019.
European Centre for Disease Prevention and Control. Guidance and protocol for the use of real-time PCR in laboratory diagnosis of human infection with Bordetella pertussis or Bordetella parapertussis. https://ecdc.europa.eu/en/publications-data/guidance-and-protocol-use-real-time-pcr-laboratory-diagnosis-human-infection. doi 10.2900/64134. Published 2012. Accessed March 14, 2019.
Guiso N, Berbers G, Fry NK, He Q, Riffelmann M, Wirsing von König CH; EU Pertstrain group. What to do and what not to do in serological diagnosis of pertussis: recommendations from EU reference laboratories. Eur J Clin Microbiol Infect Dis. 2011 Mar;30(3):307-12. doi: 10.1007/s10096-010-1104-y. Epub 2010 Nov 11. Review. PubMed PMID: 21069406; PubMed Central PMCID: PMC3034915.
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Definition and PathogenesisTop
Pertussis (whooping cough) is an infectious disease of bacterial etiology, which classically manifests as prolonged bronchitis with episodes of a severe paroxysmal cough (“violent cough”).
1. Etiologic agent: Bordetella pertussis, a gram–negative, aerobic bacillus that produces pertussis toxin (PT). The transmission route is via the upper respiratory tract droplets. PT induces necrosis of the respiratory epithelium (most prominent in the trachea), which results in abnormal secretion of respiratory mucus (making it very thick and viscous) and a powerful activation of the cough reflex.
2. Reservoir and transmission: Humans are the only host. The source of infection is sick individuals, including those previously vaccinated who eventually develop pertussis. The infection occurs mainly through inhalation of respiratory droplets expelled by a sick individual with cough.
3. Incubation and contagious period: The incubation period is 5 to 21 days (usually 7-14 days). Attack rates are high (up to 80%), particularly within the first 3 weeks of the disease (during the catarrhal and in the beginning of the paroxysmal phase).
Clinical manifestations resemble bronchitis with a chronic, paroxysmal cough. The clinical course and severity of signs and symptoms are variable (recurrent infections or infections in previously vaccinated individuals are milder and cause less typical clinical manifestations, with a dominant chronic atypical cough). Fever is most frequently mild or absent. Usually 3 phases may be distinguished:
1) Catarrhal phase (1-2 weeks): Flu-like symptoms, although fever is absent or low-grade. Cough appears at the end of this phase, initially at night, and later also during the day. It is dry at first and gradually becomes paroxysmal.
2) Paroxysmal phase (4-6 weeks): Attacks of a paroxysmal (“violent”) cough within a single expiration, which terminate with a loud laryngeal stridor (a “whoop”; common in children, less frequent in adolescents and adults). The thick and viscous mucus is usually expectorated at the end of the episode (in children it may be swallowed and subsequently vomited). The episodes may be accompanied by edema and cyanosis of the face as well as facial and conjunctival petechiae. Newborns and young children may develop apnea and generalized seizures. Although the attacks of cough cause fatigue, between the episodes patients may appear quite well. Clinical manifestations in adults are usually dominated by a chronic atypical cough.
3) Convalescent phase (3-4 months): The cough gradually resolves, although periodic exacerbations may be observed, particularly after exercise or during subsequent infections.
Infants (particularly those <6 months of age) generally have an atypical presentation associated with a shorter catarrhal phase that ends with the onset of gagging and apneic episodes, which may be associated with bradycardia. These episodes can be prolonged and may be associated with cardiac arrest.
Pertussis may be suspected on the basis of clinical manifestations (particularly cough lasting >3 weeks); however, diagnosis must be based on results of serologic or microbiological testing. In most regions pertussis is considered a notifiable disease and must be reported to public health units. Laboratory tests are not necessary for the diagnosis in individuals who have typical clinical manifestations and had documented contact with a patient with laboratory-confirmed pertussis.
1. Serology (enzyme-linked immunosorbent assay [ELISA]): Positive serum antibodies against PT (validity of the test is limited due to difficulty in interpreting the results). Positive IgG titers in older children and adults reflect prior infection or vaccination. In patients who have not been vaccinated in the preceding 12 to 24 months, elevated levels of IgG against PT in ≥1 sample suggest a recent infection. Diagnosis is also likely based on an increase ≥100% or a decrease ≥50% in the antibody levels in the second serum sample collected 2 to 4 weeks after the first sample.
1) The historic gold standard was B pertussis culture (eg, on Regan-Lowe or Bordet-Gengou medium) from secretions obtained by a nasopharyngeal aspirate or swab (use a Dacron or calcium alginate swab, not cotton swabs); however, it may yield up to 50% false-negative results (particularly in patients who have been vaccinated or treated with appropriate antibiotics).
2) Molecular studies (polymerase chain reaction [PCR]) that detect the genetic material of B pertussis in secretions have now become the most frequent means for the laboratory diagnosis of pertussis, given their rapid turnaround time and significantly improved sensitivity. Consult the local laboratory regarding accepted sample types for testing.
3. Complete blood count: White blood cell (WBC) counts between 20,000 and 30,000/microL with lymphocytes predominant in the differential blood count (although not pathognomonic, this feature is helpful in establishing diagnosis). WBC counts are often normal in adolescents and adults (particularly in the elderly). High WBC counts (ie, >30,000/microL) in infants have been associated with mortality.
Other causes of chronic cough, including Bordetella parapertussis and Bordetella bronchiseptica infections that can have a very similar presentation to B pertussis.
In adolescents and adults start therapy within 3 weeks of the onset of cough. An early intervention at the onset of the catarrhal phase alleviates the course of pertussis. Therapy instituted in the paroxysmal phase shortens the contagious period but has no effect on the clinical manifestations of the disease. First-line agents are oral macrolides: azithromycin 500 mg on day 1 followed by 250 mg once daily on days 2 to 5; clarithromycin 500 mg bid for 7 days or erythromycin 500 mg qid for 14 days. In patients allergic to or intolerant of macrolides, use sulfamethoxazole 800 mg/trimethoprim 160 mg bid for 14 days.
Patients with chronic comorbidities and young infants will often require hospitalization (they may have a severe course of infection and are at high risk for complications). Oxygen therapy or ventilatory support may be necessary in severe cases.
Infants (particularly <6 months of age) and patients with chronic comorbidities (particularly neuromuscular) are at the highest risk for complications, which include:
1) Pneumonia (secondary, of bacterial etiology), atelectasis, pneumothorax.
2) Neurologic complications (predominantly in infants, rarely in adults): Apneic episodes, seizures, cerebral edema, intracranial hemorrhage, subdural hemorrhage, ischemic encephalopathy (severe cognitive impairment, focal neurologic symptoms, focal or generalized seizures lasting >24 hours). These complications may lead to irreversible sequelae (mental retardation, deafness, epilepsy).
3) Other: Hernia, rectal prolapse, urinary incontinence, rib fractures, damage of the lingual frenulum, subconjunctival hemorrhages.
In neonates and infants, the course of pertussis is severe and associated with a high risk of death (~1% in patients <2 months, ~0.5% in patients 2-11 months of age) and complications. In older children and adults, the prognosis is good, but the disease is very exhausting and may lead to major impairment of general performance status. Neither vaccination nor exposure confer permanent immunity, but in such cases subsequent infections are usually milder.
1. Vaccination is the key prevention method. Note that multiple studies have suggested that the duration of protection afforded by acellular pertussis vaccines appears to be shorter than that associated with the previous whole-cell pertussis vaccine, despite the more favorable adverse-effect profile of acellular vaccines.
2. Management of exposures: All close contacts who are unvaccinated or partially vaccinated should be offered age-appropriate vaccination schedules as soon as possible. Some authorities recommend postexposure chemoprophylaxis (following one of the regimens used for treatment) for all close contacts regardless of their vaccination status, although high-risk contacts (eg, infants) should always be provided with prophylaxis. The prophylactic regimen is the same as that recommended for a therapeutic course (see Antimicrobial Treatment, above).
3. Isolation: Patients receiving effective antimicrobial therapy should be isolated for 5 days after initiation of appropriate antibiotic therapy. Patients not receiving antimicrobial treatment should be isolated for 3 weeks from the onset of the paroxysmal cough.