Whooping Cough and Other Bordetella Infections

Definition

Whooping cough, also known as pertussis, is a toxin-mediated, highly contagious respiratory illness that affects all age groups and is characterized by distinctive, violent, paroxysmal coughing episodes, which end in the classic inspiratory whoop that gives the disease its name. Each paroxysm may last several minutes, and patients often feel entirely normal between paroxysms. Severe and fatal disease is concentrated among infants, in whom pertussis may be manifested by spells of apnea and cyanosis, alone or in conjunction with coughing. Whooping cough is primarily caused by infection with Bordetella pertussis or, much less frequently, Bordetella parapertussis or Bordetella bronchiseptica .

Epidemiology

Historically, pertussis was a childhood illness. Although children below 1 year of age are at the highest risk of death, more than 50% of cases in the United States now occur in individuals over 10 years of age. However, reported cases likely represent only 5 to 10% of total cases, and the population burden of disease is uncertain. The first-generation whole-cell pertussis vaccines, beginning in the 1940s, reduced total cases by 99% and also shifted the age distribution of disease to adolescents and adults. In unvaccinated populations, pertussis was contracted throughout childhood; although the resultant immunity was not lifelong, continued exposure to pertussis in the population allowed such unvaccinated individuals to reinforce their immunity with little or no subsequent clinical disease. The introduction of acellular pertussis vaccines for infants and children resulted in a marked reduction of disease, except in infants too young to have acquired immunity from vaccination, but the incidence of pertussis increased relatively and absolutely in adolescents and adults, partly due to the relatively brief duration of protection offered by the acellular vaccines, with failure rates approaching 50% after 2 to 3 years.

Beginning in the 1990s, the transition from whole-cell products to acellular pertussis vaccines in response to concerns about the safety of the former contributed to major increases in pertussis, which is now resurgent in the United States and elsewhere in the world. About 20,000 cases of pertussis are now reported annually in the United States, and approximately 60% of these cases are in adolescents and adults. Some of these cases are detected by polymerase chain reaction (PCR) testing only, which explains an increase in the detection of milder and atypical cases. For example, even in developed countries with high rates of immunization, about 5% of patients with subacute cough have pertussis detectable in nasal swabs by PCR testing. Nevertheless, severe and fatal disease in infants has also increased, thereby suggesting the overall increased burden of disease is real and not an artifact of detection bias.

Pertussis remains endemic even in countries with high rates of vaccination, with spikes in reported cases occurring in the United States in 3- to 5-year cycles, an interval that is postulated to reflect the accumulation of susceptible individuals in the population. The fact that whole-cell pertussis vaccines resulted in a longer interepidemic cycle time strongly suggests that they were more effective than acellular vaccines for interfering with person-to-person transmission, as well as preventing clinical disease. Animal data also indicate that both whole-cell and acellular vaccines block symptomatic disease, but whole-cell vaccines also reduce the density and duration of mucosal carriage, thereby impeding person-to-person spread. Furthermore, infant baboons who have received acellular vaccines remain contagious and easily spread their infection to unvaccinated cage mates.

Worldwide, pertussis continues to be a major problem not only in developed countries with vaccine programs, especially for individuals with chronic health conditions, ^, but also in developing countries. For example, Zambia, Pakistan, and South Africa have had ongoing transmission of pertussis. Fortunately, most detected cases were clinically mild and did not progress to classic pertussis, thereby suggesting that the existing vaccine programs are preventing severe disease but not all transmission.

Although B. pertussis is a relatively fastidious organism that is not easily cultured, pertussis is a highly contagious infection, with spread believed to be primarily by aerosol droplets from both symptomatic and asymptomatic hosts. Transmission by asymptomatic hosts occurs frequently in adults and in infants, in whom asymptomatic infections are far more common than symptomatic infections.

Pathobiology

Pertussis usually is not a tissue-invasive disease; rather, its pathogenesis is mediated indirectly through its toxins acting in situ or, in the case of pertussis toxin, systemically. B. pertussis and related organisms produce a number of toxins, and interdiction of pertussis toxin, as, for example, by vaccines that target pertussis toxin can prevent severe disease. The precise molecular mechanisms underlying the classic paroxysmal cough still have not been identified, but bradykinin-induced inflammation and pertussis toxin–mediated interference with the anti-inflammatory effects of sphingosine-1-phosphate appear to be contributing factors.

Knowledge about the toxins and adhesins is important both for their potential roles in pathogenesis and for their use as antigens in acellular pertussis vaccines. Filamentous hemagglutinin, pertactin, and fimbriae are adhesins that are components in most of the acellular vaccines, and all currently available vaccines include pertussis toxoid. Pertussis toxin is a soluble toxin with local and systemic effects, including direct induction of leuko-lymphocytosis and enhancement of glucose-stimulated insulin secretion, both of which may contribute to the pertussis syndrome. Pertussis toxin also has an immunomodulatory effect that promotes prolonged survival of B. pertussis in the respiratory tract. Early in disease, pertussis toxin downregulates immune responses and likely perpetuates infection by inhibiting alveolar macrophages on mucosal surfaces and interfering with the recruitment of neutrophils. Later in the disease, pertussis toxin upregulates inflammatory responses, perhaps as a mechanism to enhance shedding and infectivity. Adenylate cyclase toxin binds to CR3 to enter host cells and produce supraphysiologic levels of cyclic adenosine monophosphate (cAMP). The antibacterial functions of macrophages and neutrophils are inhibited by the increased cAMP, thereby leading to limited immunosuppression, which likely enhances the survival of B. pertussis .

Bacteria adherent to the cilia cause damage to respiratory epithelial cells, some of which are lost from the mucosa. Mucus secretion is prominent, especially during later stages of the illness. Intracellular B. pertussis organisms have been demonstrated, but their significance remains unknown.

Clinical Manifestations

Following exposure to a patient with active pertussis, typically by aerosol from coughing or sneezing but also likely through asymptomatic chains of transmission, an infected individual will experience an onset of nonspecific upper respiratory symptoms (mainly coryza) about 1 to almost 3 weeks later. Clinical signs that indicate onset of the catarrhal phase (rhinorrhea, increased lacrimation, conjunctival injection, and sometimes low-grade fever) are nonspecific and may be self-resolving. Furthermore, clinically trivial or asymptomatic infections occur commonly, particularly in adults and to a lesser degree in infants, thereby suggesting that asymptomatic adults may be responsible for a substantial fraction of overall transmissions.

Although the classic paroxysmal cough of pertussis is striking and unforgettable, not all symptomatic children or adults experience it. The diagnosis of pertussis often is not even considered until a patient manifests the striking cough, which consists of a series of uncontrollable expirations, followed by gasping inhalation that is responsible for the “whooping” sound. Episodes of coughing can be associated with cyanosis and end with gagging and vomiting. Eighty percent or more of adolescents and adults with classic pertussis have paroxysmal cough, but the frequency of whoop and post-tussive vomiting is variable. This paroxysmal stage can persist more than 4 weeks, and the development of fever or worsening pulmonary function during this time suggests the possibility of secondary bacterial pneumonia. During the paroxysmal stage, adults may experience atypical symptoms, such as a scratchy throat and episodes of sweating.

A reduction in the frequency and severity of coughing marks the transition to the convalescent phase, which can persist several months. It is often during this time that adults present to the health care system with a chronic cough ( Chapter 71 ) and may be evaluated for conditions such as asthma ( Chapter 75 ), tuberculosis ( Chapter 299 ), other chronic lung diseases, malignancies, and gastroesophageal reflux ( Chapter 124 ). After the cough appears to have ended, patients may experience return of paroxysmal cough in conjunction with an unrelated upper respiratory illness, which is often incorrectly interpreted as a recurrence of pertussis.

Although B. pertussis and B. parapertussis can rarely cause bacteremia, infections with these organisms are principally localized to the respiratory tract.