Pertussis (Whooping Cough)

Pertussis, or whooping cough, is a potentially life-threatening highly contagious bacterial infection of the respiratory tract caused by Bordetella Bordetella Bordetella is a genus of obligate aerobic, Gram-negative coccobacilli. They are highly fastidious and difficult to isolate. The most important pathologic species is Bordetella pertussis (B. pertussis), which is commonly isolated on Bordet-Gengou agar. Bordetella pertussis. The disease has 3 clinical stages, the second and third of which are characterized by an intense paroxysmal cough, an inspiratory whoop, and post-tussive vomiting. Pertussis can be prevented by a vaccine Vaccine A vaccine is usually an antigenic, non-virulent form of a normally virulent microorganism. Vaccinations are a form of primary prevention and are the most effective form due to their safety, efficacy, low cost, and easy access. Vaccination that is administered as part of most routine vaccinations and usually started at the age of 6 weeks. Diagnosis is based on the clinical history and confirmed by the detection of the organism via culture or polymerase chain reaction. If pertussis is suspected, immediate antibiotic therapy with macrolides Macrolides Macrolides and ketolides are antibiotics that inhibit bacterial protein synthesis by binding to the 50S ribosomal subunit and blocking transpeptidation. These antibiotics have a broad spectrum of antimicrobial activity but are best known for their coverage of atypical microorganisms. Macrolides and Ketolides should be initiated, even if laboratory confirmation is pending.

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Editorial responsibility: Stanley Oiseth, Lindsay Jones, Evelin Maza

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Epidemiology and Etiology

Epidemiology

  • Incidence worldwide: 24 million cases per year
  • Deaths worldwide: approximately 161,000 per year
  • Incidence in the United States: 15,000 cases in 2018
  • More common in developing countries, with the highest mortality rate in infants 
  • Common and more severe in infants < 1 year of age (usually no or scant maternal passive immunity unless the mother was given a Tdap booster vaccine Vaccine A vaccine is usually an antigenic, non-virulent form of a normally virulent microorganism. Vaccinations are a form of primary prevention and are the most effective form due to their safety, efficacy, low cost, and easy access. Vaccination in the early third trimester)
    • Increasingly more common in adolescents, as protective immunity of vaccination Vaccination Vaccination is the administration of a substance to induce the immune system to develop protection against a disease. Unlike passive immunization, which involves the administration of pre-performed antibodies, active immunization constitutes the administration of a vaccine to stimulate the body to produce its own antibodies. Vaccination wanes after 4–12 years

Etiology

  • Infection with the bacterium Bordetella Bordetella Bordetella is a genus of obligate aerobic, Gram-negative coccobacilli. They are highly fastidious and difficult to isolate. The most important pathologic species is Bordetella pertussis (B. pertussis), which is commonly isolated on Bordet-Gengou agar. Bordetella pertussis (a gram-negative coccobacillus)
  • Transmission occurs through airborne droplets (coughing, sneezing, or speaking) or direct contact with oral or nasal secretions of an infected individual.
  • High infectivity for approximately 3 weeks after the cough begins if untreated (only 5 days with treatment)
  • Incubation period: 7–10 days

Pathophysiology

  • Infection through the inhalation of airborne droplets containing B. pertussis 
  • Bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology: Overview adhere to and damage the ciliated epithelium Epithelium The epithelium is a complex of specialized cellular organizations arranged into sheets and lining cavities and covering the surfaces of the body. The cells exhibit polarity, having an apical and a basal pole. Structures important for the epithelial integrity and function involve the basement membrane, the semipermeable sheet on which the cells rest, and interdigitations, as well as cellular junctions. Surface Epithelium of the nasopharynx, causing inhibition of the mucociliary elevator (may spread to the bronchial tree Bronchial tree The collective term "bronchial tree" refers to the bronchi and all of their subsequent branches. The bronchi are the airways of the lower respiratory tract. At the level of the 3rd or 4th thoracic vertebra, the trachea bifurcates into the left and right main bronchi. Both of these bronchi continue to divide into secondary or lobar bronchi that bifurcate further and further. Bronchial Tree and lungs Lungs Lungs are the main organs of the respiratory system. Lungs are paired viscera located in the thoracic cavity and are composed of spongy tissue. The primary function of the lungs is to oxygenate blood and eliminate CO2. Lungs in severe cases).
    • Bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology: Overview also evade intracellular digestion and thereby evade the immune system of the host.
  • Virulence factors (e.g., tracheal cytotoxin, dermonecrotic toxin, adenylate cyclase ) cause inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body's defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation and destruction of the cilia.
    → secretion of inflammatory exudate into the respiratory tract (RT)
    → impairs the removal of mucus and debris from the RT → higher risk of secondary infections
  • Organisms have been found in alveolar macrophages as well as the ciliated respiratory epithelial cells of the lower RT, which may explain the prolonged duration of cough. 
  • Pertussis toxin produces most of the systemic manifestations associated with whooping cough (e.g., lymphocytosis Lymphocytosis WBCs develop from stem cells in the bone marrow and are called leukocytes when circulating in the bloodstream. Lymphocytes are 1 of the 5 subclasses of WBCs. Lymphocytosis is an increase in the number or proportion of the lymphocyte subclass of WBCs, often as a result of an immune response to infection (known as reactive lymphocytosis). Lymphocytosis, pulmonary hypertension Pulmonary Hypertension Pulmonary hypertension (PH) or pulmonary arterial hypertension (PAH) is characterized by elevated pulmonary arterial pressure, which can lead to chronic progressive right heart failure. Pulmonary hypertension is grouped into 5 categories based on etiology, which include primary PAH, and PH due to cardiac disease, lung or hypoxic disease, chronic thromboembolic disease, and multifactorial or unclear etiologies. Pulmonary Hypertension).
Bordetella pertussis causing whooping cough

Pathophysiology of Bordetella Bordetella Bordetella is a genus of obligate aerobic, Gram-negative coccobacilli. They are highly fastidious and difficult to isolate. The most important pathologic species is Bordetella pertussis (B. pertussis), which is commonly isolated on Bordet-Gengou agar. Bordetella pertussis causing whooping cough

Image by Lecturio.

Clinical Presentation

First stage: catarrhal

  • Lasts 1–2 weeks
  • Presents with nonspecific symptoms of an upper respiratory tract infection:
    • Mild cough
    • Low-grade fevers
    • Coryza (i.e., runny nose Nose The nose is the human body's primary organ of smell and functions as part of the upper respiratory system. The nose may be best known for inhaling oxygen and exhaling carbon dioxide, but it also contributes to other important functions, such as tasting. The anatomy of the nose can be divided into the external nose and the nasal cavity. Anatomy of the Nose)
    • Sneezing
    • Conjunctivitis Conjunctivitis Conjunctivitis is a common inflammation of the bulbar and/or palpebral conjunctiva. It can be classified into infectious (mostly viral) and noninfectious conjunctivitis, which includes allergic causes. Patients commonly present with red eyes, increased tearing, burning, foreign body sensation, and photophobia. Conjunctivitis

Second stage: paroxysmal

  • Lasts 2–8 weeks 
  • Presents with characteristic paroxysms of intense cough followed by an inspiratory “whooping” sound
    • Typically absent in infants, who instead present with periods of apnea due to the inability of their respiratory muscles to produce strong coughing
  • Post-tussive vomiting, shortness of breath ( dyspnea Dyspnea Dyspnea is the subjective sensation of breathing discomfort. Dyspnea is a normal manifestation of heavy physical or psychological exertion, but also may be caused by underlying conditions (both pulmonary and extrapulmonary). Dyspnea), and cyanosis can occur

Third stage: convalescent

  • Lasts 4 weeks on average, but may extend for months
  • Characterized by the progressive reduction of all symptoms

Diagnosis

  • Diagnosis is strongly suspected with clinical history but requires laboratory confirmation.
  • History: possible contact with other “whooping cough” cases and vaccination Vaccination Vaccination is the administration of a substance to induce the immune system to develop protection against a disease. Unlike passive immunization, which involves the administration of pre-performed antibodies, active immunization constitutes the administration of a vaccine to stimulate the body to produce its own antibodies. Vaccination (as the vaccine Vaccine A vaccine is usually an antigenic, non-virulent form of a normally virulent microorganism. Vaccinations are a form of primary prevention and are the most effective form due to their safety, efficacy, low cost, and easy access. Vaccination does not provide full protection, pertussis needs to be considered even in vaccinated children!)
  • Laboratory tests:
    • Nasopharyngeal swab → culture (gold standard) or polymerase chain reaction
      • Only reliable during the first 2–3 weeks of the infection
    • Complete blood count shows nonspecific lymphocytosis Lymphocytosis WBCs develop from stem cells in the bone marrow and are called leukocytes when circulating in the bloodstream. Lymphocytes are 1 of the 5 subclasses of WBCs. Lymphocytosis is an increase in the number or proportion of the lymphocyte subclass of WBCs, often as a result of an immune response to infection (known as reactive lymphocytosis). Lymphocytosis.
    • Serology testing can be used up to several weeks after the onset of symptoms.
      • A 2-fold rise in the antibody titer against pertussis is diagnostic.
Gram stain of the bacteria bordetella pertussis

Gram stain of the bacteria Bordetella Bordetella Bordetella is a genus of obligate aerobic, Gram-negative coccobacilli. They are highly fastidious and difficult to isolate. The most important pathologic species is Bordetella pertussis (B. pertussis), which is commonly isolated on Bordet-Gengou agar. Bordetella pertussis

Image: “Gram stain of the bacteria Bordetella Bordetella Bordetella is a genus of obligate aerobic, Gram-negative coccobacilli. They are highly fastidious and difficult to isolate. The most important pathologic species is Bordetella pertussis (B. pertussis), which is commonly isolated on Bordet-Gengou agar. Bordetella pertussis” by CDC/Public Health Image Library. License: Public Domain

Management and Prevention

Supportive care

  • Hospitalization may be required for infants who present with apnea and respiratory distress.
  • Oxygen administration may be required in severe cases.
  • Antitussive therapy has not been shown to be effective.

Medical therapy

  • Macrolides (e.g., azithromycin, clarithromycin, erythromycin)
    • Reduce the spread of pertussis but do not affect the clinical course
    • Azithromycin as first-line choice for infants < 1 month of age
    • In the case of allergies to macrolides Macrolides Macrolides and ketolides are antibiotics that inhibit bacterial protein synthesis by binding to the 50S ribosomal subunit and blocking transpeptidation. These antibiotics have a broad spectrum of antimicrobial activity but are best known for their coverage of atypical microorganisms. Macrolides and Ketolides, trimethoprim Trimethoprim The sulfonamides are a class of antimicrobial drugs inhibiting folic acid synthesize in pathogens. The prototypical drug in the class is sulfamethoxazole. Although not technically sulfonamides, trimethoprim, dapsone, and pyrimethamine are also important antimicrobial agents inhibiting folic acid synthesis. The agents are often combined with sulfonamides, resulting in a synergistic effect. Sulfonamides and Trimethoprim-sulfamethoxazole is used.

Prevention

  • Active immunization through the administration of diphtheria Diphtheria Diphtheria is an infectious disease caused by Corynebacterium diphtheriae that most often results in respiratory disease with membranous inflammation of the pharynx, sore throat, fever, swollen glands, and weakness. The hallmark sign is a sheet of thick, gray material covering the back of the throat. Diphtheria- tetanus Tetanus Tetanus is a bacterial infection caused by Clostridium tetani, a gram-positive obligate anaerobic bacterium commonly found in soil that enters the body through a contaminated wound. C. tetani produces a neurotoxin that blocks the release of inhibitory neurotransmitters and causes prolonged tonic muscle contractions. Tetanus toxoids and acellular pertussis vaccine Vaccine A vaccine is usually an antigenic, non-virulent form of a normally virulent microorganism. Vaccinations are a form of primary prevention and are the most effective form due to their safety, efficacy, low cost, and easy access. Vaccination (DTaP)
    • Only 80%–90% effective
    • 5 doses in total (at ages 2, 4, 6, and 18 months; and 5 years)
    • Booster vaccine Vaccine A vaccine is usually an antigenic, non-virulent form of a normally virulent microorganism. Vaccinations are a form of primary prevention and are the most effective form due to their safety, efficacy, low cost, and easy access. Vaccination needed at 11–18 years of age (10 years following the last dose) or in pregnant women (in the third trimester) with the tetanus Tetanus Tetanus is a bacterial infection caused by Clostridium tetani, a gram-positive obligate anaerobic bacterium commonly found in soil that enters the body through a contaminated wound. C. tetani produces a neurotoxin that blocks the release of inhibitory neurotransmitters and causes prolonged tonic muscle contractions. Tetanus toxoid, reduced diphtheria Diphtheria Diphtheria is an infectious disease caused by Corynebacterium diphtheriae that most often results in respiratory disease with membranous inflammation of the pharynx, sore throat, fever, swollen glands, and weakness. The hallmark sign is a sheet of thick, gray material covering the back of the throat. Diphtheria toxoid, and acellular pertussis vaccine Vaccine A vaccine is usually an antigenic, non-virulent form of a normally virulent microorganism. Vaccinations are a form of primary prevention and are the most effective form due to their safety, efficacy, low cost, and easy access. Vaccination (Tdap)

Differential Diagnosis

  • Bronchitis: a lower respiratory tract infection that leads to inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body's defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation of the bronchi
  • Pneumonia Pneumonia Pneumonia or pulmonary inflammation is an acute or chronic inflammation of lung tissue. Causes include infection with bacteria, viruses, or fungi. In more rare cases, pneumonia can also be caused through toxic triggers through inhalation of toxic substances, immunological processes, or in the course of radiotherapy. Pneumonia: a respiratory infection characterized by inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body's defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation of the alveolar space and/or the interstitial tissue of the lungs Lungs Lungs are the main organs of the respiratory system. Lungs are paired viscera located in the thoracic cavity and are composed of spongy tissue. The primary function of the lungs is to oxygenate blood and eliminate CO2. Lungs
  • Croup Croup Croup, also known as laryngotracheobronchitis, is a disease most commonly caused by a viral infection that leads to severe inflammation of the upper airway. It usually presents in children < 5 years of age. Patients develop a hoarse, "seal-like" barking cough and inspiratory stridor. Croup: also known as laryngotracheobronchitis Laryngotracheobronchitis Croup, also known as laryngotracheobronchitis, is a disease most commonly caused by a viral infection that leads to severe inflammation of the upper airway. It usually presents in children < 5 years of age. Patients develop a hoarse, "seal-like" barking cough and inspiratory stridor. Croup, a disease usually caused by a viral infection or, rarely, by a bacterial infection that results in swelling inside the trachea Trachea The trachea is a tubular structure that forms part of the lower respiratory tract. The trachea is continuous superiorly with the larynx and inferiorly becomes the bronchial tree within the lungs. The trachea consists of a support frame of semicircular, or C-shaped, rings made out of hyaline cartilage and reinforced by collagenous connective tissue. Trachea; interferes with normal breathing
  • Foreign body aspiration Foreign body aspiration Foreign body aspiration can lead to choking and death by obstructing airflow at the larynx or trachea. Foreign bodies may also become lodged deeper in the bronchi; this may not affect breathing but can cause infection or erosion of bronchial walls. Foreign Body Aspiration: the aspiration of an object that becomes lodged in the larynx Larynx The larynx, also commonly called the voice box, is a cylindrical space located in the neck at the level of the C3-C6 vertebrae. The major structures forming the framework of the larynx are the thyroid cartilage, cricoid cartilage, and epiglottis. The larynx serves to produce sound (phonation), conducts air to the trachea, and prevents large molecules from reaching the lungs. Larynx, trachea Trachea The trachea is a tubular structure that forms part of the lower respiratory tract. The trachea is continuous superiorly with the larynx and inferiorly becomes the bronchial tree within the lungs. The trachea consists of a support frame of semicircular, or C-shaped, rings made out of hyaline cartilage and reinforced by collagenous connective tissue. Trachea, or bronchi. A potentially life-threatening emergency that usually occurs in children < 3 years of age

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