Chapter VI.10. Pertussis
Jason C. Seto
May 2022

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The editors and current author would like to thank and acknowledge the significant contribution of the previous author of this chapter from the 2004 first edition, Dr. Leo U. Pascua. This current third edition chapter is a revision and update of the original author's work.

A 6 week old female presents with fever, frequent coughing, and difficulty breathing that had worsened over the previous 10 days. The child was born at term and previously healthy. Her parents and 3 year old sister immigrated from Honduras. This sister has experienced cough and congestion 2 weeks previously, but this has now resolved.

Exam: VS T38.3, P110, R42, BP 100/60, oxygen saturation 97% in RA. She exhibits labored breathing with slight retractions and brief apnea episodes. Lungs reveal diffuse crackles.

A chest radiograph shows a normal heart size and increased markings consistent with infiltrates versus atelectasis. A CBC shows a white blood count of 15,800 with 78% lymphocytes. A blood culture is pending. IV ceftriaxone is administered in the ER. A nebulized albuterol treatment is administered which helps minimally. A nasal swab for RSV (respiratory syncytial virus), influenza, and COVID-19 return negative. A PCR study for Bordetella pertussis is ordered on the swab.

Due to ongoing apnea episodes and difficult breathing, she is admitted to the intensive care unit for further management. She tires and requires intubation for impending respiratory failure. The B. pertussis study returns positive and she is started on azithromycin. The child’s ventilation is supported and she gradually improves. Following extubation, she continues to gradually improve. She coughs frequently and exhibits noisy breathing when resting. After a prolonged hospitalization, she is discharged with moderate respiratory symptoms.

Bordetella pertussis is a gram-negative, pleomorphic, fastidious bacillus and the cause of pertussis. A similar syndrome can be caused by related Bordetella organisms such as Bordetella parapertussis, and others. Pertussis starts as an non-specific upper respiratory illness that then progresses to protracted (prolonged) and frequent coughing. Pertussis is also known as the 100 day cough (a reference to its prolonged course) and whooping cough (a reference to its characteristic inspiratory sound) (1,2). Other pathogens that can cause protracted coughing include Mycoplasma, parainfluenza, influenza, enteroviruses, respiratory syncytial virus, and adenoviruses. Pertussis is extremely contagious, with high attack rates among susceptible individuals exposed to aerosol droplets at close range, such as occurs in the household environment and day care center (3). Pertussis vaccination and/or natural pertussis provides significant immunity but this is not lifelong (4). Protection against disease begins to wane as early as 2 years after vaccination and is can be undetectable after 12 years. As a consequence, adults in the United States (e.g., day care center operators, baby-sitters, etc.), may have inadequate immunity to B. pertussis (2) unless they are recently vaccinated or exposed to wild disease.

Prior to pertussis vaccination development, pertussis was the leading cause of infectious disease death in U.S. children. Whole cell pertussis vaccine led to a substantial reduction in pertussis cases. Acellular pertussis vaccine has since replaced whole cell vaccine, since it has fewer adverse effects (4).

B. pertussis produces many biologically active virulence factors that mediate attachment of the bacteria to ciliated respiratory epithelial cells, inhibit clearance of the organisms, and induce local epithelial damage. In addition, B. pertussis incites histamine sensitivity, insulin secretion, and leukocyte dysfunction (1,2).

Exposure is followed by an incubation period of 7 to 10 days. The catarrhal stage is the first symptomatic stage, characterized by congestion, rhinorrhea, low grade fever, sneezing, and lacrimation, which mimics an upper respiratory infection. Individuals in the catarrhal stage are very contagious, even before it is realized they may have pertussis. The paroxysmal coughing stage follows, which is characterized by one or more of the following: intermittent, irritative hacking paroxysmal coughing; choking, gasping, watering and bulging eyes; occasional coughing up of mucous plugs; post-tussive exhaustion; and, coughing in long spasms with the face turning red, or sometimes blue (cyanotic, which signifies more serious disease). This stage is often characterized by a whoop sound at the end of each coughing episode, resulting from air rushing back during inspiration to refill lungs emptied by the severe coughing. Older infants and children less commonly present with these classical symptoms. During the convalescent stage, the coughing wanes and improves. Each stage lasts about 2 weeks, with a total duration of 6 to 8 weeks. Disease is significantly less severe and shorter following a primary immunizing series (2,4).

Pertussis should be suspected in a patient who complains of severe coughing for 2 weeks, especially if no other accompanying findings are noted. Other etiologies to consider are serial respiratory viral infections, adenovirus, Mycoplasma pneumoniae, Chlamydia trachomatis, etc. Leukocytosis (normal small cells, rather than the large atypical lymphocytes seen with viral infections) due to absolute lymphocytosis occurs in the late catarrhal and paroxysmal stages of pertussis. The presence of neutrophilia would suggest a different diagnosis or secondary bacterial infection (2).

In children with pertussis, the chest radiograph shows perihilar infiltrates or edema and variable degrees of atelectasis. Parenchymal consolidation suggests secondary bacterial infection. Pneumothorax, pneumomediastinum, and subcutaneous emphysema (air in soft tissues) sometimes occur (4).

The gold standard for the diagnosis of pertussis is nucleic acid amplification tests (NAAT), usually polymerase chain reaction (PCR). The PCR test is most sensitive if obtained within the first 3 to 4 weeks of illness. Cultures are less sensitive and laborious, but may be positive during the catarrhal stage and initiation of the paroxysmal stage. A false negative culture can be seen in those who have received antibiotics (e.g., amoxicillin for otitis media) or present late (more than 3 to 4 weeks after illness). The direct fluorescent antibody (DFA) testing of nasopharyngeal secretions is another diagnostic option, but this is an older test that has been replaced by NAATs (2).

Infants under 6 months of age have a higher morbidity and mortality. Those under 2 months of age have the highest reported rates of pertussis associated hospitalization, pneumonia, seizures, encephalopathy, and death. The main complications of pertussis are: apnea, respiratory failure, secondary infections (such as pneumonia), and physical damage due to forceful coughing. Hospitalization is indicated for patients who have difficulty feeding, breathing, cyanosis, apnea, or seizures. Additionally, some experts recommend hospitalization for younger infants under 4 to 6 months for close monitoring (4).

Secondary bacterial pneumonia (Staphylococcus aureus, Streptococcus pneumoniae) can result in fever, and worsening respiratory distress between coughing paroxysms. Coughing transiently increases the intrathoracic and intra-abdominal pressure and can result in conjunctival hemorrhages, petechiae on the upper body, epistaxis, hemorrhage in the central nervous system and retina, pneumothorax, pneumomediastinum, subcutaneous emphysema, and umbilical and inguinal hernias. Central nervous system abnormalities occur and are almost always the result of hypoxemia and hemorrhage associated with coughing or apnea in young infants (due to laryngospasm, vagal stimulation just before a coughing episode, obstruction during an episode, or from hypoxemia following an episode). Seizures are usually the result of hypoxemia; pneumonia can also precipitate SIADH (syndrome of inappropriate antidiuretic hormone, resulting in hyponatremic seizures. Reversible bronchiectasis or pseudo bronchiectasis occurs commonly after pertussis. The bronchi may appear cylindrically dilated on bronchography, but usually resolve in about 4 months (1,4).

Azithromycin is the preferred antibiotic treatment. Alternative treatments include erythromycin, clarithromycin or trimethoprim-sulfamethoxazole. Once the paroxysmal cough is established, antibiotic treatment has no effect on the course of the illness sustained by the patient, but it does reduce contagiousness. If pertussis is suspected in earlier non-specific catarrhal stage (perhaps based on the history of a contact), antibiotics should be started prior to confirmatory testing since antibiotics have therapeutic efficacy for the pertussis patient only if treatment is started in the catarrhal stage (1,4,5).

Patients with suspected pertussis should be under droplet (in addition to standard) precautions for 5 days after initiating therapy or 21 days after illness onset if no therapy is given. Individuals who are exposed to a person with pertussis should be monitored for signs of illness for 21 days and should avoid crowded settings for 5 days after initiating prophylaxis or 21 days if they do not take prophylactic therapy (2).

When a child with proven or likely pertussis is hospitalized, the following orders are suggested (4):
Frequent cardiorespiratory monitoring, continuous pulse oximetry, and apnea monitor
Detailed cough records (cyanosis, tachycardia, bradycardia, presence of coughed up mucus plug; post-tussive exhaustion and/or unresponsiveness)
Documentation of feeding, vomiting, and weight change
As needed oxygen, stimulation, or suctioning (note: suctioning of nose, oropharynx, or trachea frequently precipitates coughing, occasionally causes bronchospasm or apnea, and should be done only if needed)
Small, frequent feedings, as tolerated

Also, the following should be recommended for household and other close contacts (2,5):
All household and other close contacts (e.g., day care) should be provided treatment, regardless of presence/absence of symptoms, or immunization status
Detailed cough records (cyanosis, tachycardia, bradycardia, presence of coughed up mucus plug; post-tussive exhaustion and/or unresponsiveness)
Azithromycin (preferred): age appropriate doses, as noted above
In addition to antimicrobial prophylaxis, all unimmunized contacts, or those that have not completed immunization appropriate for their age, should receive a pertussis containing vaccine (either DTaP or Tdap according to age)

A child with pertussis can be discharged from the hospital once respiratory difficulty has improved, no intervention is required during coughing episodes, oral intake (including nutrition) has improved, complications have been avoided or treated, and the care takers are prepared for further home care (4).

Primary prevention with pertussis vaccine is very effective. Acellular pertussis (aP) vaccine is composed of a suspension of select B. pertussis antigens combined with diphtheria and tetanus (DT) toxoids and aluminum adjuvants (so called DTaP vaccine) (6).

The recommendation is a five-dose schedule of the DTaP vaccine administered at age 2, 4, 6, 15 to 18 months, and 4 to 6 years. Contraindications to DTaP vaccination include severe allergic reaction to a previous dose or vaccine component and encephalopathy (1).

Pertussis immunity declines substantially with age, rendering most teens and adults susceptible, even if they were immunized as children. Although teens and adults with pertussis will manifest with only mild to moderate respiratory symptoms, they represent a large population reservoir of susceptible individuals who can sustain transmission, exposing unimmunized infants and children, who may then experience severe infections and complications. For this reason, adolescents are recommended to receive a booster dose of Tdap (tetanus plus reduced dose diphtheria and pertussis) vaccine at 11 to 12 years, followed by Tdap boosters every 10 years (instead of Td vaccine). Similarly, persons who are pregnant should receive a booster dose of Tdap with each pregnancy; this intervention is meant to protect the pregnant person, but more significantly, passively protect the newborn, at least until 2 months of age when infant immunization with DTaP should be started (4).

1. During which phase of the illness are patients with Pertussis most infections?
   a. Incubation Period
   b. Catarrhal Phase
   c. Paroxysmal Phase
   d. Convalescent Phase

2. What is the age group among children that has the highest morbidity and mortality with Pertussis?
   a. Less than 6 month of age
   b. 6 to 12 months of age
   c. 1 to 5 years of age
   d. 6 to 12 years of age
   e. 13 to 18 years of age

3. Which of the following antibiotics is the drug of choice for post exposure prophylaxis?
   a. Azithromycin
   b. Ceftriaxone
   c. Penicillin
   d. Streptomycin

4. A 4-month old is hospitalized with clinical findings most consistent with pertussis. A pertussis culture returns negative. Which of the following factors can lead to a false negative culture?
   a. No previous pertussis vaccination
   b. Respiratory failure
   c. Common variable hypogammaglobulinemia
   d. Previous amoxicillin treatment for otitis media

1. Nieves DJ, Heininger U. Bordetella pertussis. Microbiol Spectr. 2016;4(3). doi: 10.1128/microbiolspec.EI10-0008-2015. PMID: 27337481.
2. Daniels HL, Sabella C. Bordetella pertussis (Pertussis). Pediatr Rev. 2018;39(5):247-257. doi: 10.1542/pir.2017-0229. PMID: 29716967.
3. Nguyen VTN, Simon L. Pertussis: The Whooping Cough. Prim Care. 2018;45(3):423-431. doi: 10.1016/j.pop.2018.05.003. PMID: 30115332.
4. Souder E, Long SS. Chapter 224. Pertussis (Bordetella pertussis and Bordetella parapertussis). In: Kliegman R, Stanton B, St. Geme JW, et al (eds). Nelson Textbook of Pediatrics, 21st Edition. 2020. Elsevier, Philadelphia. pp: 1492-1496.e1
5. Pertussis (Whopping Cough). In: Committee on Infectious Diseases, American Academy of Pediatrics; Kimberlin DW, Barnett ED, Lynfield R, Sawyer MH (eds). Red Book 2021-2024 Report of the Committee on Infectious Disease, 32nd Edition. 2021. American Academy of Pediatrics, Itasca, IL. pp. 578-589.
6. Centers for Disease Control and Prevention. Birth-18 Years Immunization Schedule., accessed on March 24, 2022.

Answers to questions
1.b, 2.a, 3.a, 4.d

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