Bordetella Pertussis : Clinical Features, Complications, Laboratory Diagnosis, Medical Management
B. pertussis is a small, aerobic gram-negative rod. It is fastidious and requires special media for isolation (see Laboratory Diagnosis).
B. pertussis produces multiple antigenic and biologically active products, including pertussis toxin (PT), filamentous hemagglutinin (FHA), agglutinogens, adenylate cyclase, pertactin, and tracheal cytotoxin. These products are responsible for the clinical features of pertussis disease, and an immune response to one or more produces immunity following infection. Immunity following B. pertussis infection does not appear to be permanent.
Pathogenesis
Pertussis is primarily a toxin-mediated disease. The bacteria attach to the cilia of the respiratory epithelial cells, produce toxins that paralyze the cilia, and cause inflammation of the respiratory tract, which interferes with the clearing of pulmonary secretions. Pertussis antigens appear to allow the organism to evade host defenses, in that lymphocytosis is promoted but chemotaxis is impaired. Until recently it was thought that B. pertussis did not invade the tissues. However, recent studies have shown the bacteria to be present in alveolar macrophages.
Clinical Features
The incubation period of pertussis is commonly 7–10 days, with a range of 4–21 days, and rarely may be as long as 42 days. The clinical course of the illness is divided into three stages.
The first stage, the catarrhal stage, is characterized by the insidious onset of coryza (runny nose), sneezing, low-grade fever, and a mild, occasional cough, similar to the common cold. The cough gradually becomes more severe, and after 1–2 weeks, the second, or paroxysmal stage, begins. Fever is generally minimal throughout the course of the illness.
It is during the paroxysmal stage that the diagnosis of pertussis is usually suspected.
Characteristically, the patient has bursts, or paroxysms, of numerous, rapid coughs, apparently due to difficulty expelling thick mucus from the tracheobronchial tree. At the end of the paroxysm, a long inspiratory effort is usually accompanied by a characteristic high-pitched whoop. During such an attack, the patient may become cyanotic (turn blue). Children and young infants, especially, appear very ill and distressed. Vomiting and exhaustion commonly follow the episode. The person does not appear to be ill between attacks.
Paroxysmal attacks occur more frequently at night, with an average of 15 attacks per 24 hours. During the first 1 or 2 weeks of this stage, the attacks increase in frequency, remain at the same level for 2 to 3 weeks, and then gradually decrease. The paroxysmal stage usually lasts 1 to 6 weeks but may persist for up to 10 weeks. Infants younger than 6 months of age may not have the strength to have a whoop, but they do have paroxysms of coughing.
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In the convalescent stage, recovery is gradual. The cough becomes less paroxysmal and disappears in 2 to 3 weeks. However, paroxysms often recur with subsequent respiratory infections for many months after the onset of pertussis.
Adolescents, adults and children partially protected by the vaccine may become infected with B. pertussis but may have milder disease than infants and young children. Pertussis infection in these persons may be asymptomatic, or present as illness ranging from a mild cough illness to classic pertussis with persistent cough (i.e., lasting more than 7 days). Inspiratory whoop is not common.
Even though the disease may be milder in older persons, those who are infected may transmit the disease to other susceptible persons, including unimmunized or incompletely immunized infants. Older persons are often found to have the first case in a household with multiple pertussis cases, and are often the source of infection for children.
Complications
The most common complication, and the cause of most pertussis-related deaths, is secondary bacterial pneumonia. Young infants are at highest risk for acquiring pertussis- associated complications. Data from 1997–2000 indicate that pneumonia occurred in 5.2% of all reported pertussis cases, and among 11.8% of infants younger than 6 months of age.
Neurologic complications such as seizures and encephalopathy (a diffuse disorder of the brain) may occur as a result of hypoxia (reduction of oxygen supply) from coughing, or possibly from toxin. Neurologic complications of pertussis are more common among infants. Other less serious complications of pertussis include otitis media, anorexia, and dehydration. Complications resulting from pressure effects of severe paroxysms include pneumothorax, epistaxis, subdural hematomas, hernias, and rectal prolapse.
In 2008 through 2011 a total of 72 deaths from pertussis were reported to CDC. Children 3 months of age or younger accounted for 60 (83%) of these deaths. During 2008-2011, the annual mean of pertussis cases in infants was 3,132 (range 2,230 - 4,298), the mean of hospitalizations was 1,158 (range 687-1,459) and the mean of deaths was 16 (range 11-25).]
Adolescents and adults may also develop complications of pertussis, such as difficulty sleeping, urinary incontinence, pneumonia, and rib fracture.
Laboratory Diagnosis
The diagnosis of pertussis is based on a characteristic clinical history (cough for more than 2 weeks with whoop, paroxysms, or posttussive vomiting) as well as a variety of laboratory tests (culture, polymerase chain reaction [PCR], and serology).
Culture is considered the gold standard laboratory test and is the most specific of the laboratory tests for pertussis. However, fastidious growth requirements make B. pertussis difficult to culture. The yield of culture can be affected by specimen collection, transportation, and isolation techniques. Specimens from the posterior nasopharynx, not the throat, should be obtained using Dacron® or calcium alginate (not cotton) swabs. Isolation rates are highest during the first 2 weeks of illness (catarrhal and early paroxysmal stages).
Cultures are variably positive (30%–50%) and may take as long as 2 weeks, so results may be too late for clinical usefulness. Cultures are less likely to be positive if performed later in the course of illness (more than 2 weeks after cough onset) or on specimens from persons who have received antibiotics or have been vaccinated. Since adolescents and adults have often been coughing for several weeks before they seek medical attention, it is often too late for culture to be useful.
Polymerase chain reaction (PCR) is a rapid test and has excellent sensitivity. PCR tests vary in specificity, so obtaining culture confirmation of pertussis for at least one suspicious case is recommended any time there is suspicion of a pertussis outbreak. Results should be interpreted along with the clinical symptoms and epidemiological information. PCR should be tested from nasopharyngeal specimens taken at 0-3 weeks following cough onset, but may provide accurate results for up to 4 weeks of cough in infants or unvaccinated persons.
After the fourth week of cough, the amount of bacterial DNA rapidly diminishes, which increases the risk of obtaining falsely-negative results. PCR assay protocols that include multiple targets allow for speciation among Bordetella species. The high sensitivity of PCR increases the risk of false-positivity, but following some simple best practices can reduce the risk of obtaining inaccurate results (http://www.cdc.gov/pertussis/clinical/ diagnostic-testing/diagnosis-pcr-bestpractices.html).
An elevated white blood cell count with a lymphocytosis is usually present in classical disease of infants. The absolute lymphocyte count often reaches 20,000 or greater. However, there may be no lymphocytosis in some infants and children or in persons with mild or modified cases of pertussis.
Medical Management
The medical management of pertussis cases is primarily supportive, although antibiotics are of some value. This therapy eradicates the organism from secretions, thereby decreasing communicability and, if initiated early, may modify the course of the illness. Recommended antibiotics are azithromycin, clarithromycin, and erythromycin. Trimethoprim-sulfamethoxasole can also be used.
An antibiotic effective against pertussis should be administered to all close contacts of persons with pertussis, regardless of age and vaccination status. Revised treatment and postexposure prophylaxis recommendations were published in December 2005 (see reference list). All close contacts younger than 7 years of age who have not completed the four-dose primary series should complete the series with the minimal intervals. (see table in Appendix A). Close contacts who are 4–6 years of age and who have not yet received the second booster dose (usually the fifth dose of DTaP) should be vaccinated. The administration of Tdap to persons who have been exposed to a person with pertussis is not contraindicated, but the efficacy of postexposure use of Tdap is unknown.
Epidemiology
Occurrence
Pertussis occurs worldwide.
Reservoir
Pertussis is a human disease. No animal or insect source or vector is known to exist. Adolescents and adults are an important reservoir for B. pertussis and are often the source of infection for infants.
Transmission
Transmission most commonly occurs by the respiratory route through contact with respiratory droplets, or by contact with airborne droplets of respiratory secretions. Transmission occurs less frequently by contact with freshly contaminated articles of an infected person.
Temporal Pattern
Pertussis has no distinct seasonal pattern, but it may increase in the summer and fall.
Communicability
Pertussis is highly communicable, as evidenced by secondary attack rates of 80% among susceptible household contacts. Persons with pertussis are most infectious during the catarrhal period and the first 2 weeks after cough onset (i.e., approximately 21 days).
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