Pertussis

Introduction

Pertussis, or "whooping cough," is a respiratory illness caused by the bacterium Bordetella pertussis.  Pertussis can impact patients of all ages, but is especially dangerous for infants. A recent resurgence of clinical pertussis has resulted in new recommendations about vaccination. 

Epidemiology

  • Pertussis is an endemic disease in the U.S., with periodic epidemics every 3-5 years and more frequent outbreaks
  • Increasing incidence has been noted in the U.S. and worldwide despite widespread immunization. In developing countries, pertussis remains one of the top 10 causes of mortality under 1 year of age.   
  • According to the CDC, 50% of infants under one year of age who become infected with pertussis will require hospitalization. Of these, 50% will develop pneumonia, and 1% will die from complications of the infection. 
  • Pertussis morbidity and mortality is most significant for infants under 2 months of age 
  • In the U.S. and other industrialized countries, the resurgence of pertussis is being seen in very young infants who have not been fully immunized, and in children and teens over the age of 10. There is evidence that infants and children are being infected by adults with subclinical infections due to waning immunity. This concern has lead to new vaccination strategies, also known as "cocooning." 

Pathophysiology

  • Bordetella pertussis is a small, aerobic gram-negative coccobacillus. B pertussis is fastidious and difficult to grow in culture; it grows best between 35-37 degrees C on media that contains charcoal, blood and starch (either Bordet-Gengou or Regan-Lowe) 
  • B. pertussis infects the ciliated epithelium that lines the respiratory tract, leading to irritation and inflammation. The damage to the epithelium leads to recruitment of macrophages, which results in reactive lymphoid hyperplasia in the peribronchial and tracheobronchial nodes
  •  B. pertussis is armed with a number of virulence factors and toxins:
    -Filamentous hemagglutinin and fimbriae are adhesins that aid in tracheal colonization (both are highly immunogenic and are major components of acellular vaccines)
    -Pertactin and the pertussis toxin (PT) also act as adhesins
    -The PT toxin has a number of other roles which are not entirely understood. PT can interrupt cell signaling pathways in the lung, delaying recruitment of neutophils. PT can also cause leukocytosis and may be linked to encephalophathy. PT can also sensitize the beta-islet cells of the pancreas, leading to hyperinsulinemia and resistant hypoglycemia. 
    -Adenylate cyclase toxin inhibits migration and activation of phagocytes and T cells

Clinical Course

  • Pertussis is spread by aerosolized droplets. Many infants who develop pertussis are infected by older siblings, parents, or caregivers (who usually only have mild symptoms)
  • The incubation period is 7-14 days
  • Catarrhal Phase:
    -Nonspecific complaints for 1-2 weeks: mild fever, cough, URI symptoms
    -During this phase, the symptoms are difficult to distinguish from a viral URI 
    -The cough gradually worsens 
  • Paroxysmal Phase:
    -Lasts 2-6 weeks
    -Characterized by bouts of coughing, often described as "staccato"
    -The patient may cough 5-10 times in rapid succession, and then the characteristic "whoop" is heard when the patient draws a breath 
    -Paroxysms of cough followed by a "whoop" are more common in young  children. Adults and teens rarely produce the classic "whoop." Infants under 6 months of age rarely "whoop," but may present with apnea, gasping, or gagging
    -Coughing bouts can occur many times per hour, and may be accompanied by cyanosis, lacrimation, salivation, and post-tussive emesis
    -Sleep is often interrupted by coughing
    -Patients may appear relatively well between coughing bouts 
  • Convalescent phase:
    -This phase may last for weeks-months
    -The coughing bouts gradually decrease in severity and frequency
  • Complications: 
    -Apnea
    -Seizures
    -Encephalopathy
    -Pneumonia: may be primary or due to a secondary coinfection. Coinfection with influenza or RSV often leads to a more complicated clinical course
    -Death 
    -Pressure-related complications, due to paroxysms of cough: pneumothorax, pneumomediastinum, subcutaneous emphysema, petechial hemorrhage, rib fracture, rectal prolapse, and intracranial hemorrhage

Diagnosis

  • A clinical case is defined as a cough illness that persists for at least 2 weeks, with one of the following: paroxysms of cough, an inspiratory whoop, or post-tussive vomiting that cannot otherwise be explained
  • A confirmed case is defined as a cough illness in which B pertussis is isolated in culture:
    -Gold standard: nasopharyngeal swab or aspirate cultured on specialized media. Culture time is about 2 weeks. Successful culture is more likely early in the illness. Adults and teens rarely have positive cultures, as they tend to present later in their illness. Infants with a high bacterial load who are cultured early, however, may have positive cultures in 72 hours
    -PCR: while nasopharyngeal swab and culture are still considered the gold standard, PCR is replacing culture in many clinical settings. PCR is rapid, specific, and will remain positive later in the illness. Some concerns about the standardization of PCR do exist; false-positives on PCR have been implicated in some "pseudo outbreaks" 
  • Serologic testing does exist, but is not standardized and therefore should not be used as a form of laboratory confirmation
  • Findings on CBC:
    -Leukocytosis with an absolute lymphocytosis 
    -WBC counts may be as high as 30-60
  • Differential diagnosis: RSV, influenza, adenoviruses, c. trachomatis, c. pneumoniae and m. pneumoniae (in teens with prolonged cough)
     

Treatment

  • If left untreated, many patients will clear the bacteria from their nasopharynx in 2-4 weeks. However, some patients will remain contagious carriers for more than 6 weeks
  • When started during the catarrhal stage, antibiotics can shorten the course and reduce the severity of the illness. Once the paroxsysmal stage begins, antibiotics have little effect because the symptoms at that point are toxin-mediated. Treatment with antibiotics is indicated, however, because they can reduce the duration of nasopharyngeal colonization and therefore shorten the contagious period
    -Pertussis was traditionally treated with erythromycin. Given its GI side effects and link to pyloric stenosis in infants, a 5 day course of azithromycin is now preferred
    -For individuals over 2 months of age who cannot take macrolides, a 14 day course of TMP-SMX has been shown to be equally effective 
  • Prophylaxis: prophylaxis for exposed individuals (close household contacts) may prevent illness if it is given within 21 days of symptom onset in the index case. The antibiotics and dosing regimens for prophylaxis are the same as treatment dosing
  • Patients (especially infants) may require hospitalization. Management includes close monitoring of fluid/nutritional status and respiratory support. 

Control Measures

  • Patients with suspected pertussis should be isolated until the infection is confirmed or ruled out. These patients should wear a mask in waiting rooms and during transport
  • Patients with confirmed or suspected pertussis should be excused from child care or school until they have completed 5 days of an appropriate antibiotic. Untreated patients should be excused from child care or school until 21 days after the onset of cough
  • Vaccination: Available vaccines are effective at preventing ~80% of illnesses. Vaccinated children who become infected tend to have a less severe clinical course
    -All currently available vaccines are combined with tetanus and diptheria toxoids. The pertussis component of the vaccine is acellular, containing various amounts of PT, fimbriae, hemagglutinin, and pertactin. 
    -Primary vaccination: 3 DTaP doses given at 2, 4, and 6 months, with boosters at 15-18 months and another at 4-6 years. As immunity from DTap has been shown to wane, another booster with TDap is given between 11 to 18 years (ideally, between 11-12 years of age) 
    -Pregnancy: immunization with Tdap confers protection to the newborn, so a Tdap is recommended for for pregnant women after 20 weeks gestation who have not already received it or whose vaccination status is unknown 
    -Adults: depending on age, DTaP or TDap is recommended for all caregivers of infants, including individuals over 65 years old. This "cocoon" strategy is intended to prevent infection of the newborn 

References

  1. Snyder J and Fisher D. Pertussis in Childhood. Pediatrics in Review. 2012;33:412. 
  2. Hauk L. CDC Releases Best Practices for the Use of PCR Testing for Diagnosing Pertussis. American Academy of Family Physicians Website, 2011. 
  3. Bell E. Pertussis Disease Rates and the Role of Tdap Vaccines. Infectious Diseases in Children Healio website, 2011. 
  4. Cherry, J. Epidemic Pertussis in 2012-- The Resurgence of a Vaccine-Preventable Disease. New England Journal of Medicine. 2012;367;9:785.

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