Typical CaseIsla, an eight week-old previously healthy term baby girl is brought into the hospital with a ten-day history of coughing and choking spells. Her mother states that her daughter’s condition has worsened in the past 48 hours, as she vomited after the coughing fits and her lips turned blue. In addition to these symptoms, she also noticed her gasping for air and her deepening with some mucus secretions(Nicolai). She has not exhibited a fever. Her mother thought that Isla was just exhibiting symptoms of a common cold, but the new symptoms have caused her worry and brought her into the hospital.
The on-call pediatrician performs a physical examination of Isla, noting she appears to be a healthy, happy baby. Her vitals are normal, temperature is 37°C, respiration rate of 20 breaths per minute, and a pulse of 84 beats per minute. Some wheezing is evident upon auscultation. She coughs a bit during the examination, but does not have a coughing fit.
Her breathing is slightly labored. Based on the inconclusive physical examination and the severity of the symptoms her mother described, the doctor orders laboratory tests and a chest radiograph. A nasopharyngeal (NP) specimen was collected(Kerr). The laboratory conducted polymerase chain reaction (PCR) assays of the patient’s NP specimen. The infant’s test results came back positive, detecting the presence of Bordetella pertussis deoxyribonucleic acid (DNA)(Melo). The chest radiograph did not detect any radiographic abnormalities and showed that her trachea is normal and clear (Bellamy). The blood analysis revealed an increased leukocyte count of 15,000/µL with lymphocytosis. Description of Infectious AgentBordetella pertussis is a bacterium that causes pertussis, otherwise known as whooping cough. It belongs to the genus Bordetella in the Alcaligenaceae family (Finger and Koenig). Bordetella pertussis is a small encapsulated gram-negative bacterium. It is a coccobacillus that appears singly or in pairs. Bordetella pertussis is a strict aerobe that is non-motile and does not form spores. B. pertussis is an extracellular toxin that colonizes the cilia of the mammalian respiratory epithelium (Mattoo and Wykert and . Miller). The bacterium is sensitive to sunlight and drying, growing optimally at a temperature between 35- 37 °C. It can only survive outside the human body for a few days, dying quickly. Bordetella pertussis has fastidious growth requirements. Its growth can be easily inhibited by components found in laboratory media. Fatty acids, sulfies, peroxides, and metal ions also inhibit the growth of Bordetella pertussis. Due to its sensitivity, isolation of Bordetella pertussis requires it to grown on a rich media that contains blood, charcoal, or starch (Waters and Halperin). The genus Bordetella contains nine species, but only three of which are pathogenic to humans. B. pertussis and B. parapertussis are very similar as both cause pertussis in humans. These species are distinguished by the toxins they release during infection. The toxins released by B. parapertussis cause pertussis-like syndrome, but does not cause lymphocytosis, which is a distinguishing feature in identifying B. pertussis (Mattoo and Wykert and . Miller). Unlike B. pertussis and B. parapertussis , B. bronchiseptica is motile. Of the three, B. pertussis has the slowest growth and is most fastidious. Bordetella pertussis is strictly a human pathogen. It has no known animal or environmental reservoir (Mattoo and Cherry).EpidemiologyBordetella pertussis is the etiological bacterial pathogen of pertussis, a highly contagious respiratory tract infection. Pertussis, otherwise known as whooping cough, can infect anyone, but is most dangerous for infants and children. Infants under six months of age are at high risk, as many have not be vaccinated and others are only partially vaccinated. Pertussis has been reported in all populated areas of the world and does not have a seasonal pattern (Mattoo and Cherry). Although occurring worldwide, B. pertussis disease incidence is highest among young children in developing countries where vaccination is less common (Anderson, Salm, & Allen, 2016). B. pertussis transmission occurs through direct contact. It is spread though inhalation of aerosolized droplets expelled from infected individuals when coughing or sneezing (Tozzi). The portal of entry and exit of B. pertussis is the respiratory tract, via the mouth and nose. B. pertussis is not a normal microbiota component in the human body. Infection is characterized by colonization of ciliated respiratory epithelia in the trachea and bronchi epithelium (Mattoo, Wykurt, Cotter, Miller). The bacterium has exclusively adapted to the human host, with no evidence of an environmental or animal reservoir. Studies have shown that adolescents and adults are the main source of B. pertussis transmission to infants and children that are partially immunized, serving as a reservoir of the bacterium (Mattoo and Cherry). Pertussis is a cyclical disease. In the pre-vaccine era epidemic episodes occurred every two to five years. Pertussis whole-cell vaccinations (PwVs) were made available in the 1940’s, which dramatically decreased the incidence, morbidity, and mortality of pertussis worldwide (Hegerle and Nicolas). Despite modification of the vacation and widespread implementation programs, reported incidence of pertussis is on the rise. B. pertussis incidence has been increasing for over two decades in the United States. According to the World Health Organization, 48,277 cases of pertussis were reported in 2012, the highest in fifty years (CDC). The number of reported cases is much lower than the true occurrence. There are currently no reported epidemic outbreaks of whooping cough as a result B. pertussis. In 2018 so far, regional outbreaks have been reported across the country including New Hampshire, Vermont, Ohio, Pennsylvania, Idaho, Florida, Alabama, California, and most recently, Maine. In October, 64 pertussis cases were reported in Maine, 42% of which occurred in York county (Lawlor (Portland Press Herald)). PathogenesisThe infectious agent Bordetella pertussis exclusively causes pertussis or whooping cough. It affects the respiratory and immune systems. The specific organs affected by pertussis are the nose, pharynx, and larynx of the upper respiratory tract as well as the trachea, bronchial tree, and lungs of the lower respiratory tract (Anderson, Salm, & Allen, 2016). B. pertussis adheres to the cilia in the trachea and bronchi epithelium, inhibiting movement and causing damage. The damage to the cilia caused by B. pertussis leads to swelling of the airways and inflammation of blood vessels, tissues, lungs, and the bronchial tree (Nicolas and Guiso). Immune capacity is also lowered by the toxic effects of B. pertussis.Infection of B. pertussis occurs through four steps: attachment, evasion of host defenses, local damage, and systemic manifestations. Virulence factors associated with B. pertussis include proteins categorized as toxins and adhesins, and autotransporters. Upon inhalation of B. pertussis, the bacterium attaches to the ciliated epithelial cells of the upper respiratory tract, specifically the nasopharynx, trachea, bronchi, and bronchioles (Mattoo and Cherry). Attachment is aided by filamentous hemagglutinin (FHA), pertussis toxin (PT), pertactin (PRN), and fimbriae (FIM2 and FIM3) (Bassinet ). Filamentous hemagglutinin is a large surface protein that is the dominant adhesin produced by B. pertussis. PT functions as both an adhesion and toxin. Pertactin is an outer membrane protein that promote adhesion via RGD tripeptides and other patterns of peptides (Hewlett). Fimbriae are pili that extend from the bacterium’s surface that involved in adhesion to epithelial cells (Anderson, Salm, & Allen, 2016). B. pertussis produces a variety of toxins. Evasion of host defenses is facilitated by pertussis toxin and adenylate cyclase toxin (ACT). ACT accelerates the overproduction of cAMP by converting adenosine triphosphate (ATP) to Cyclic adenosine monophosphate (cAMP), intoxicating host cell, thus impeding phagocytosis and increasing mucus production (Mattoo and Cherry). PT is an A-B subunit protoxin that immunosuppresses and inhibits the migration of lymphocytes, neutrophils, monocytes and natural killer cells to areas of infection (Hewlett). Local tissue damage is caused by the toxins tracheal cytotoxin (TCT) and dermonectrotic toxin (DNT). TCT is a peptidoglycan fragment released by B. pertussis during growth that is toxic to ciliated epithelial cells, causing them to die, thus slowing ciliary action (Anderson, Salm, & Allen, 2016). DNT causes inflammation to the site where B. pertussis resides in the human body. The systemic manifestation of B. pertussis is leukocytosis with lymphocytosis caused by pertussis toxin (Mattoo and Cherry). Pertussis is comprised of three stages: catarrhal, paroxysmal, and convalescent. After a latent period of one to two weeks, the catarrhal stage begins. This stage lasts one to two weeks and is characterized by the onset of symptoms resembling the common cold or an upper respiratory infection, including runny nose, sneezing, mild cough, and a low-grade fever (Anderson, Salm, & Allen, 2016). The individual is most contagious during this stage of the disease. The subsequent paroxysmal stage lasts between one and six weeks, which is when the paroxysmal cough first appears. Intense coughing spasms occur frequently, followed intense effort to inhale accompanied by the characteristic high pitch whoop. Individuals may also experience exhaustion, vomiting, apnea, and cyanosis (CDC). The final stage of pertussis is the convalescent stage, usually lasting one to two weeks. Individuals are no longer contagious. Coughing attacks gradually diminish and the individual beings to recover (Anderson, Salm, & Allen, 2016). For months after the onset of pertussis, it is common for coughing fits to recur with subsequent respiratory infections. Infants are at the highest risk of post-pertussis complications, possibly experiencing pneumonia, slowed or stopped breathing, dehydration, anorexia, seizures, and brain damage which could result in death (CDC). Clinical complication most commonly experienced by adolescents and adults include weight loss, urinary incontinence, syncope, bruised or cracked ribs, abdominal hernias, and broken blood vessels in the skin or eyes. Other serious clinical complications that can occur in all ages are pneumothorax, rectal prolapse, subdural hematomas, and seizures (CDC). The majority of pertussis cases have a full recovery when proper medical treatment is administered. Prophylaxis/Treatment TreatmentThe recommended treatment for B. pertussis is administration of one of the following macrolides, a group of antibiotics with broad-spectrum activity: azithromycin, clarithromycin, and erythromycin (CDC). The selection of antimicrobial agent should be driven based on the following considerations: age of the patient, potential drug-related adverse events or interactions, tolerability, medication regimen adherence, and cost (Kilgore). The standard treatment of B. pertussis is a full dose of oral erythromycin for fourteen days. The full fourteen day erythromycin course is used to prevent relapse (Kilgore). Early treatment of pertussis has a strong positive correlation with recovery. The effectiveness of antibiotic therapy depends on the stage of pertussis in which therapy is initiated. Treatment given in catarrhal stage yields the most benefit, eliminating the organism from the respiratory tract, controlling the spread of the disease, and preventing secondary pneumonia. Unfortunately, due to the latent period of B. pertussis, patients tend not to be treated very early. Additionally, a positive laboratory confirmation of pertussis takes an extended period of time. Based on these factors, the CDC recommends that clinicians initiate antibiotic treatment based on their clinical judgement (CDC). Antibiotics are not effective in reducing the symptoms and severity of pertussis during the paroxysmal and convalescent stages of the disease, but are still recommended to reduce transmission (Kilgore). Infants under one year of age are at the highest risk of complications and permanent damage, which is why supportive treatment is crucial. In these cases infants are hospitalized, so that they can be monitored. Common supportive treatments include nasopharyngeal suction, oxygen therapy, and administration of fluids (Kerr and Matthews). Although there have been reports of antimicrobial resistance to B. pertussis, the estimated occurrence is less than one percent (Kilgore). Treatment options for pertussis are very limited. One novel potential treatment is the manipulation of airway anion channels using inhaled acetazolamide (ACTZ), which has previously been used to treat other exacerbated airway conditions (Scanlol, Skerry, Carbonetti, 2015). ACTZ is hypothesized to modulate pendrin function. Pendrin is an anion exchanger in the lungs. Overexpression of pendrin in the airways leads to increased mucus production, which causes airway inflammation Scanlol, Skerry, Carbonetti, 2015).The key method to prevent and control B. pertussis is vaccination. The vaccine DTaP contains acellular pertussis components (Mattoo and Cherry). DTaP helps children under the age of seven build immunity to diphtheria, pertussis, and tetanus (Warby). It is administered through a series of five doses. The CDC recommends doses be given at the following ages: two months, four months, six months, 15-18 months, and four to six years (CDC). A booster vaccine Tdap, tetanus, reduced diphtheria, and reduced acellular pertussis, is available for individuals over eleven years of age (Warby). Administration of Tdap is recommended at eleven or twelve years of age, as well as for pregnant women (CDC). Women should receive a Tdap shot during each pregnancy, between weeks 27-36 (CDC). Tdap is only protective for ten years, so adolescents and adults must insure they are up to date on their vaccinations to decrease their susceptibility.Immunity to pertussis through illness or vaccination, is not lifelong. 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