121: Pertussis

Pertussis is an infection caused by the gram-negative bacteria Bordetella pertussis. In children it often presents with respiratory symptoms, including the classic whooping cough, but in neonates it tends to have an atypical and more severe presentation.

The overall incidence of pertussis has been increasing in recent years, with the highest incidence seen in infants <6 months of age in the United States. There are an estimated 300,000 deaths due to pertussis worldwide each year, mostly affecting young infants. The incidence of pertussis in pregnant women is thought to be similar to that of the general population.

Transmission of Bordetella pertussis occurs through the respiratory route via close contact with respiratory secretions or aerosolized droplets. The parents of infants are estimated to be the source of infection in 25% of cases, and household members are thought to be the source in about 80% of cases. Bordetella pertussis produces multiple toxins including the pertussis toxin, which inhibits neutrophil migration to the lungs, and tracheal cytotoxin, which damages cilia in the respiratory epithelium via a nitric oxide synthase (NOS)-dependent pathway. The lymphocytosis seen in cases of pertussis is attributed to the potent mitogen, lymphocytosis-promoting factor. The aggregation of leukocytes in the pulmonary circulation is thought to cause the refractory pulmonary hypertension seen in severe cases of neonatal pertussis.

Infants <6 months of age are at highest risk for severe pertussis and complications or death from pertussis, especially if they are unvaccinated. Other risk factors include preterm (<37 weeks' gestation) and low birthweight infants. Infection during pregnancy does not appear to increase either maternal or fetal morbidity.

The 3 phases of classic pertussis, namely catarrhal (1–2 weeks), paroxysmal (2–6 weeks), and convalescent (2–6 weeks), are not typically observed in infants. Neonatal cases tend to present with paroxysmal cough, gagging, bradycardia, gasping, apnea, and cyanotic spells, but not fever and tachypnea. They do not have the characteristic “whoop” due to lack of prolonged inspiratory effort at the end of a paroxysm. Infants <6 months of age tend to have a shorter catarrhal and longer convalescent phase. The following complications may be observed in neonates and young infants with pertussis:

1. Secondary infections. Pertussis can be complicated by secondary infections such as pneumonia (22–25% of cases), meningoencephalitis, and otitis media.

2. Ophthalmologic complications. The forceful coughing paroxysms characteristic of pertussis can also result in ophthalmologic complications such as subconjunctival, scleral, and rarely retinal hemorrhages.

3. Central nervous system manifestations. Intraventricular and subarachnoid hemorrhages may result from increased intracranial pressure secondary to the Valsalva effect of paroxysmal coughing. Seizures (2–4% of cases) are attributed to hypoxemia from apnea or relentless coughing, but may also be due to hyponatremia secondary to pneumonia-induced syndrome of inappropriate antidiuretic hormone secretion. Encephalopathy is estimated to occur in 0.5–1% of cases and usually occurs during the paroxysmal stage. It can present with fever, convulsions, focal neurological signs including blindness and deafness, pareses and plegias, and altered mental state progressing to coma. Pertussis encephalopathy is fatal in one-third of patients and leads to neurodevelopmental delay in another third of patients.

4. Respiratory complications. Infants with pertussis are at increased risk for severe pulmonary hypertension due to pulmonary vasoconstriction from hypoxia and acidosis secondary to recurrent prolonged apnea, as well as restriction of pulmonary blood flow from leukocyte thrombi. Neonates with pertussis have a greater need for mechanical ventilation due to frequent apnea, respiratory compromise during paroxysms of coughing, and pulmonary hypertension.

5. Miscellaneous. The increased intrathoracic and intra-abdominal pressures associated with paroxysmal coughing can result in other physical sequelae such as epistaxis, upper body petechiae, pneumothorax, and umbilical and inguinal hernias. Post-tussive emesis can lead to alkalosis, dehydration, and malnutrition.

Pertussis should be differentiated from other infectious causes of respiratory distress in neonates. Adenoviral infections can produce apnea and intractable coughing but usually present with fever, lethargy, maculopapular rash, pharyngitis, conjunctivitis, and coagulopathy. Mycoplasma pneumoniae can present with protracted cough and pneumonia. Chlamydia trachomatis infections may present with conjunctivitis, nasal congestion, pneumonia, and a staccato cough in afebrile patients. Respiratory syncytial virus (RSV) can present with apnea and lower respiratory tract infection. Pertussis and RSV, as coexisting infections, is not infrequent.

1. Laboratory studies

   1. Complete blood count (CBC) with differential. Leukocytosis (white blood cell count of ≥20,000 cells/mm³) with lymphocytosis (≥50% lymphocytes) is suggestive of pertussis.

   2. Bacterial culture. The gold standard for diagnosis is bacterial culture of a nasopharyngeal specimen placed in a special transport medium (Regan-Lowe). While this method is 100% specific, false-negative cultures can occur if the specimen is obtained within or later than the third week of illness, or in pretreated or vaccinated patients.

   3. Polymerase chain reaction (PCR). Testing for pertussis by PCR has increased sensitivity over bacterial culture, especially in later stages of the disease and in pretreated individuals. False-positive PCR results have been noted and appear to be related to an absence of standardized procedures and laboratory variability.

2. Imaging studies

   1. Chest radiograph. Infants with uncomplicated pertussis usually have normal findings. Radiographic evidence of pneumonia may be seen in severe or complicated cases.

1. Antimicrobial therapy. Macrolide antibiotics alleviate disease severity if given during the initial catarrhal stage. Treatment in later phases is still recommended to reduce the risk of contagion. Due to an association between orally administered erythromycin and infantile hypertrophic pyloric stenosis, azithromycin (10 mg/kg/d in a single dose daily for 5 days) is the current drug of choice for treatment or prophylaxis of pertussis in infants <1 month of age.

2. Supportive care. Infants <3 months of age should be hospitalized with close monitoring of respiratory, hydration, and nutrition status.

3. Respiratory support

   1. Mechanical ventilation. Intubation and mechanical ventilation are often necessary due to frequent apnea or respiratory failure.

   2. Airway therapies. Bronchodilators, inhaled steroids, and cough suppressants are not routinely recommended.

   3. Inhaled nitric oxide (iNO). Pulmonary hypertension resulting from pertussis is thought to be refractory to iNO, because vasodilator therapy does not address the issue of leukocyte thrombi in the pulmonary vasculature. Current literature suggests caution in the use of iNO in the setting of pertussis; it is thought that tracheal cytotoxin induces NOS via generation of the cytokine interleukin (IL)-1, leading to increased levels of endogenous NO production that then diffuses to ciliated cells and causes the specific ciliated-cell cytopathology characteristic of B. pertussis infection.

   4. Double volume exchange transfusion. Early consideration prior to the onset of hypotension and shock is suggested to alleviate the hyperleukocytosis contributing to severe cases of pulmonary hypertension, hypoxia, and cardiac failure. See Chapter 30.

   5. Extracorporeal membrane oxygenation/extracorporeal life support (ECMO/ECLS). ECMO/ECLS should be considered for neonates with refractory respiratory failure and pulmonary hypertension. Survival after ECMO/ECLS is estimated at 20–30%, with a high neutrophil count at presentation and multiorgan dysfunction suggestive of a poor prognosis. The low survival rate has led to speculation that different pathophysiologic mechanisms are at play in pertussis other than those seen in neonatal persistent pulmonary hypertension. See Chapter 18.

4. Prevention/control measures

   1. Isolation. Standard precaution is recommended for the entire course of illness. Droplet precaution is recommended for 5 days after initiation of effective therapy.

   2. Chemoprophylaxis. Early chemoprophylaxis is recommended for all household contacts and other close contacts. Due to limited efficacy, late chemoprophylaxis (after 21 days) is only recommended for high-risk contacts (pregnant women and young infants or their contacts).

   3. Immunizations. Six doses of pertussis vaccine (at 2, 4, and 6 months; 15–18 months; 4–6 years; 11 years) are recommended universally. Preterm birth is not a contraindication to the pertussis vaccine. See Appendix E.

   4. Newborn exposure. Due to an increasing occurrence of outbreaks of pertussis (eg, California in 2011), immunization of pregnant women in either the second or third trimester has been endorsed by the American Congress of Obstetricians and Gynecologists and the Centers for Disease Control and Prevention (CDC). The intention is to prevent maternal pertussis from occurring in the immediate postpartum period should exposure occur, or in the event of exposure subsequently in the newborn and infant periods prior to routine immunizations beginning at 2 months of age. Secondarily, some passive transfer of maternal antibodies may protect the newborn. Additionally, the CDC, American Academy of Pediatrics, and American College of Obstetricians and Gynecologists advocate “cocooning” of newborns by providing postpartum immunization of all close family contacts and any family contacts that may have exposure to children 1 year of age or younger (the most actively infected population identified in recent outbreaks). Finally, immunization of newborn infants in the immediate postnatal period has been suggested as a possible consideration based on recent evidence of greater newborn immunocompetence than previously known. To date, no U.S.-based organizational approval has been established to support such a recommendation. However, in the face of a proximal community outbreak of pertussis, early infant immunization schedules at 6 weeks of age may be undertaken instead of 2 months (CDC, 2011).

Neonates with pertussis have demonstrated a need for longer hospitalization when compared to those with nonpertussis respiratory illnesses. A case fatality rate of 1% is reported for infants <2 months of age.