Pertussis (Whooping Cough)


Article Author:
Ashley Lauria


Article Editor:
Christopher Zabbo


Editors In Chief:
Jasleen Jhajj
Cliff Caudill
Evan Kaufman


Managing Editors:
Avais Raja
Orawan Chaigasame
Carrie Smith
Abdul Waheed
Khalid Alsayouri
Trevor Nezwek
Radia Jamil
Patrick Le
Anoosh Zafar Gondal
Saad Nazir
William Gossman
Hassam Zulfiqar
Hussain Sajjad
Steve Bhimji
Muhammad Hashmi
John Shell
Matthew Varacallo
Heba Mahdy
Ahmad Malik
Sarosh Vaqar
Mark Pellegrini
James Hughes
Beata Beatty
Beenish Sohail
Nazia Sadiq
Hajira Basit
Phillip Hynes


Updated:
6/3/2019 4:52:09 PM

Introduction

Pertussis, literally meaning “a violent cough,” and also known as whooping cough, or “the cough of 100 days,” was first described in the Paris epidemic of 1578. Bordetella pertussis, the causative organism, was discovered in 1906, and a vaccine was developed in the 1940s. Before the pertussis vaccine was developed, pertussis was a major cause of infant morbidity and mortality.[1][2][3]

Etiology

The causative organisms of pertussis are Bordetella pertussis and Bordetella parapertussis. Bordetella is spread by airborne droplets and is highly contagious. Pertussis often affects 100% of non-immune household contacts. Immunity wanes to 50% 12 years after completing a vaccination series. Immunocompromised persons can also contract Bordetella bronchiseptica, which typically affects animals and is commonly known as “a kennel cough.”[4][5][6]

Epidemiology

Reported pertussis cases are increasing in the United States and worldwide. The prevalence of pertussis in the United States sharply declined from 150,000 to 250,000 cases per year in the prevaccination era to 1010 cases reported in 1976. Since then, pertussis has been on the rise, which is partially attributed to waning adolescent and adult immunity. Although pertussis largely remains a pediatric disease, with 38% of cases occurring in infants younger than 6 months, and 71% of cases occurring in children younger than 5 years, adolescents and adults can also contract the disease, and are likely contributing to the increasing number of both adult and pediatric cases seen over the past three decades. Worldwide, there are over 24 million cases annually, with greater than 160,000 deaths. The Center for Disease Control and Prevention (CDC) reported over 48,000 cases in the United States in 2012, the most recent year for which this data is available. Due to difficulty in diagnosis, the CDC estimates likely underreporting.[7]

Pathophysiology

Bordetella is a gram-negative coccobacillus that adheres to ciliated respiratory epithelial cells. Local inflammatory changes occur in the mucosal lining of the respiratory tract. Released toxins (pertussis toxin, dermonecrotic toxin, adenylate cyclase toxin, and tracheal cytotoxin) act locally and systemically, although the organism itself does not fully penetrate the respiratory tract, and almost never is found in blood cultures.

History and Physical

After an incubation period of 1 to 3 weeks, pertussis infection typically progresses through three distinct stages: the catarrhal phase, the paroxysmal phase, and the convalescent phase.

The catarrhal phase presents similarly to other upper respiratory tract infections, with fever, fatigue, rhinorrhea, and conjunctival injection. The catarrhal phase lasts 1 to 2 weeks and is the most infectious stage of the disease.

The paroxysmal phase follows the catarrhal phase and is characterized by paroxysms of a staccato cough and resolution of fever. The patient typically coughs repeatedly, followed by forceful inspiration which creates the characteristic “whoop.” These episodes may be triggered by cold or noise, and are more common at night. Patients are nontoxic-appearing in between outbreaks, but during coughing episodes may exhibit cyanosis, diaphoresis, or apnea. Immediately following a paroxysm, patients may develop post-tussive vomiting, syncope, or apnea.

Finally, during the convalescent phase, a residual cough persists for weeks to months, usually triggered by exposure to another upper respiratory infection or irritant.

Atypical presentations are common in infants, and fever may not occur. Rather, tachypnea, apnea, cyanosis, and episodic bradycardia may be the presenting features.

Increased intrathoracic pressure from coughing may result in petechiae above the nipple line, subconjunctival hemorrhage, and epistaxis.

Breath sounds are variable; auscultation may reveal clear lungs or rhonchi, while rales suggest superimposed pneumonia.

Evaluation

Testing for pertussis is not readily available in the emergency department. Nasopharyngeal culture and PCR may make laboratory confirmation, but the fastidious and slow-growing Bordetella organisms require specialized media and cultures are typically not positive for 3 to 7 days. In adults, by the time the diagnosis is suspected, cultures are typically negative (96%), and overall culture sensitivity is only 20% to 40%. PCR is more sensitive and specific than culture, but testing is not widely available.[8][9][10]

In the emergency department, pertussis should be considered in patients with prolonged cough, especially occurring in paroxysms or with whoops, or post-tussive emesis. During the late catarrhal and early paroxysmal phases, leukocytosis (often 25,000 to 60,000 per mL) with lymphocytosis may raise suspicion for pertussis. In a study of 100 infants, less than 120 days old, and admitted to a pediatric intensive care unit, there was a significantly higher leukocytosis in the five fatal cases. Unfortunately, leukocytosis may be the only laboratory finding useful in the emergency department. Chest x-ray findings are nonspecific and may show peribronchial thickening, atelectasis, or infiltrate. The classic association, though not often seen, is a “shaggy” right heart border.

Treatment / Management

Treatment of pertussis is largely supportive, including oxygen, suctioning, hydration, and avoidance of respiratory irritants. Parenteral nutrition may be necessary as the disease tends to have a prolonged course.

Hospitalization is indicated for patients with superimposed pneumonia, hypoxia, central nervous system (CNS) complications, or who are unable to tolerate nutrition and hydration by mouth. Patients less than 1-year-old are not fully vaccinated and carry the greatest risk of morbidity and mortality; they should be hospitalized regardless of symptoms. Neonates should be admitted to an intensive care setting as life-threatening cardiopulmonary complications and arrest can occur unexpectedly.

Antibiotic effect on the duration or severity of disease is minimal when started in the catarrhal phase, and not proven effective when started in the paroxysmal phase. Rather, the primary goal of antibiotic treatment is to decrease carriage and spread of disease. Erythromycin (40 to 50 mg/kg per day, maximum 2 g per day, in 2 to 3 divided doses) is the first-line treatment for pertussis. Azithromycin (10 mg/kg per day on day 1 followed by 5 mg/kg on days 2 to 5) and clarithromycin (15 mg/kg per day in two divided doses) are alternative treatments. Trimethoprim-sulfamethoxazole (8 mg/kg per day of trimethoprim) has been used as an alternative in macrolide-allergic patients, but its efficacy has not been proven.

Strict isolation is important while the patient remains infectious. Pertussis is contagious throughout the catarrhal phase and for 3 weeks after the onset of the paroxysmal phase. In patients treated with antibiotics, isolation should be continued for at least 5 days after treatment is initiated. Postexposure prophylaxis with erythromycin is recommended for all household contacts.

Corticosteroids have not shown definite benefit in reducing severity and course of illness, but are sometimes given to critically-ill infants. Beta2-agonists, pertussis immune globulin, cough suppressants, and antihistamines are not effective. Exchange blood transfusion therapy for leukocytosis with lymphocytosis may be considered.

Differential Diagnosis

Pertussis initially presents similarly to other respiratory infections, such as viral upper respiratory infection, bronchiolitis, pneumonia, and tuberculosis. Key differentiating factors of pertussis include typical progression through the three phases and persistent cough without fever. Foreign body aspiration should be considered in younger patients, and exacerbation of chronic obstructive pulmonary disease should be considered in older patients with the appropriate history. The striking leukocytosis may also be confused for leukemia.

Prognosis

Most people infected with pertussis will fully recover, albeit usually after a prolonged illness of months. Infants and older adults tend to have the highest mortality and morbidity, respectively. Infant death rate is about 2% of cases and accounts for 96% of deaths related to pertussis. Older adults tend to have increased morbidity due to other chronic medical conditions, as well as an increased rate of complications, such as pneumonia.[11][12][13]

Complications

Secondary pneumonia or otitis media may occur. Superimposed pneumonia is a major cause of mortality in infants and young children, and may be caused by aspiration of gastric contents during paroxysms of cough or because of decreased respiratory clearance of pathogens. Fever should subside during the catarrhal phase, and its presence during the paroxysmal phase should raise suspicion for pneumonia. The most common causes of secondary bacterial pneumonia are Streptococcus pneumoniae, Streptococcus pyogenes, Haemophilus influenzae, and Staphylococcus aureus; although viral infections with the respiratory syncytial virus, cytomegalovirus, and adenovirus superinfections are also common.

Rarely (less than 2% of cases), CNS complications such as seizures and encephalopathy can occur, likely secondary to hypoxia, hypoglycemia, toxins, secondary infections, or cerebral bleeding from increased pressure during coughing. Sudden increases in intrathoracic and intraabdominal pressures can also result in periorbital edema, pneumothorax, pneumomediastinum, subcutaneous emphysema, diaphragmatic rupture, umbilical and inguinal hernias, and rectal prolapse.

Pertussis toxin also causes histamine hypersensitivity and increased insulin secretion.

Infants are particularly prone to bradycardia, hypotension, and cardiac arrest from pertussis. Development of pulmonary hypertension has been increasingly recognized as a factor contributing to infantile mortality, as it may lead to worsening systemic hypotension and hypoxia.

Deterrence and Patient Education

Pertussis vaccine exists in both whole-cell (DPT) and acellular (DTaP) forms. In 1991, the acellular formulation largely replaced the whole-cell vaccine, which had been associated with acute encephalopathy and prolonged seizures. The acellular form has fewer adverse effects and is as effective as the whole-cell formulation. As a result, the whole-cell preparation is only recommended when the acellular form is not available. Common adverse effects are mild and include fever, irritability, behavioral changes, and pain at the injection site. Less commonly, moderately severe reactions, including fever over 40 C, persistent and high-pitched crying, and seizures may occur. A recent study of over 50,000 patients vaccinated from 1981 to 2016 did not detect any new or unexpected adverse effects.

 

Pearls and Other Issues

Laboratory and radiographic confirmation of pertussis is a challenge in the emergency department setting. It is important to maintain a low threshold of suspicion for pertussis in any patient presenting with prolonged cough, regardless of immunization status. A complete blood count with attention to leukocytosis and lymphocytosis may be the best diagnostic screening tool in the emergency department.

Enhancing Healthcare Team Outcomes

The management of pertussis is best done with a multidisciplinary team that includes the pharmacist and nurse practitioner. With a strong anti-vaccine movement, patient education is key. Parents and caregivers have to be informed that the adverse effects of vaccine are rare.

Pertussis immunity wanes significantly about seven years after vaccination and about 15 years after natural infection. As a result, the CDC Advisory Committee on Immunization Practices recommends routine booster immunization, starting at age 11 to 18 years. A study of almost 70,000 patients showed no significant adverse effects for patients receiving Tdap instead of Td as a tetanus booster; in patients requiring a tetanus booster in the emergency department, adding the acellular pertussis component could be considered, especially in pregnant women. Mothers are often identified as the source of pertussis infection in newborns who have not completed their vaccination series, and preliminary data suggest that infants of mothers vaccinated against both influenza and pertussis may be at lower risk for contracting pertussis.


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Pertussis (Whooping Cough) - Questions

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During which season does pertussis generally occur?



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Patients with pertussis can expect to remain symptomatic with coughing spells for how long after the onset of symptoms?



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Which central nervous system complications is least likely to occur after pertussis?



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Which medication is used to treat pertussis?



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In a childcare setting, the use of prophylactic antibiotics would be most appropriate for which group of people?



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How is the diagnosis of pertussis made?



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Which of the following is the most appropriate prophylaxis for persons who have had contact with a proven case of pertussis?



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Which of the following infections needs droplet precautions?



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Which of the following statements about the treatment of pertussis is FALSE?



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Which of the following infections may cause lymphocytosis?



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What percentage of patients with pertussis will develop seizures?



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Which of the following statements about Bordetella pertussis infections is false?



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A 9-week old infant has proven pertussis. A 7-year-old sibling has received all scheduled immunizations. Which of the following would be the best treatment for the sibling?



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A 2-year-old child is diagnosed with pertussis. Which of the following regarding the prophylaxis for pertussis is incorrect?



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A 38-year-old, previously healthy, nonsmoker presents with a cough of two months duration. He had an upper respiratory infection that seemed to be resolving but then developed a cough with occasional posttussive emesis. The cough awakens him at night. He denies fever, chills, weight loss, night sweats, or history of allergies. He has no gastrointestinal or nasal symptoms. He has no occupational exposure and no travel history. His exam shows normal mucosa at the nose and oropharynx. The cardiopulmonary exam is unremarkable. A chest radiograph is normal. Pulmonary function tests show FEVI is 4.90 L (96 percent predicted) and forced vital capacity (FVC) is 6.30 (99 percent predicted). The FEVI/FVC ratio is 80 percent. Select the most appropriate management.



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Which of the following bacteria causes the "whooping cough" infection?



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Which of the following is correct about the laboratory diagnosis of whooping cough?



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A newborn is exposed to pertussis by a 4-year-old sibling. The mother received immunization as a child and is not ill now. Select the correct statement.



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Pertussis can cause neurotoxic effects like seizures. Which of the following is not a cause of the neurotoxicity?



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A 4-year-old with pertussis does not tolerate macrolides. Which antibiotic can be prescribed as an alternative?



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Pertussis (Whooping Cough) - References

References

Leong RNF,Wood JG,Turner RM,Newall AT, Estimating seasonal variation in Australian pertussis notifications from 1991 to 2016: evidence of spring to summer peaks. Epidemiology and infection. 2019 Jan;     [PubMed]
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Etskovitz H,Anastasio N,Green E,May M, Role of Evolutionary Selection Acting on Vaccine Antigens in the Re-Emergence of {i}Bordetella Pertussis{/i}. Diseases (Basel, Switzerland). 2019 Apr 16;     [PubMed]
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Toubiana J,Azarnoush S,Bouchez V,Landier A,Guillot S,Matczak S,Bonacorsi S,Brisse S, {i}Bordetella parapertussis{/i} Bacteremia: Clinical Expression and Bacterial Genomics. Open forum infectious diseases. 2019 Apr;     [PubMed]
Kandeil W,Atanasov P,Avramioti D,Fu J,Demarteau N,Li X, The burden of pertussis in older adults: what is the role of vaccination? A systematic literature review. Expert review of vaccines. 2019 May;     [PubMed]
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Forsyth KD,Tan T,von König CW,Heininger U,Chitkara AJ,Plotkin S, Recommendations to control pertussis prioritized relative to economies: A Global Pertussis Initiative update. Vaccine. 2018 Nov 19;     [PubMed]
Campbell H,Gupta S,Dolan GP,Kapadia SJ,Kumar Singh A,Andrews N,Amirthalingam G, Review of vaccination in pregnancy to prevent pertussis in early infancy. Journal of medical microbiology. 2018 Oct;     [PubMed]
Lumbreras Areta M,Martinez De Tejada B, [Preventing whooping cough in infants : vaccinated mother, protected newborn]. Revue medicale suisse. 2018 Oct 24;     [PubMed]

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