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Pathogenesis

Pertussis is caused by a bacterium, Bordetella pertussis. B. pertussis is a Gram-negative aerobic cocobacillus that can attack the body in two ways (1). It has been found in alveolar macrophages, but primarily it attaches itself to the ciliated epithelium of the respiratory tract.

Once attached to the epithelium, B. pertussis then produces an A-B toxin (PTx) which is both cell-bound and secreted into the extracellular fluid (5). This toxin is composed of two units: the enzymatically active A unit (subunit 1) is toxic to the body, while the B oligomer unit (subunits 2, 3, 4, and 5) is nontoxic (5). The function of the B oligomer is to bind to cells so that the A unit can be activated. These toxins paralyze the cilia and cause inflammation. This tissue damage within the respiratory tract inhibits it from properly clearing pulmonary secretions.

Clinical Features

Pertussis is highly contagious through contact with droplets (4). It normally incubates within a person for 7-10 day although the incubation stage can range from 4-42 days (3). After this incubation period the disease passes through three stages.

The first stage is the catarrhal stage when the infection is highly communicable (3). In the early part of the catarrhal stage secondary attack rates are 90% in non-immune households (2). This stage is characterized by the attachment of B. pertussis to the epithelium of the respiratory tract. Clinical symptoms are very similar to that of a cold: runny nose, sneezing, low fever, and mild cough. The catarrhal stage lasts for 1-2 weeks.

Once B. pertussis begins to produce toxin it enters the paroxysmal stage (3, 2, 1). This stage is characterized by the infamous whooping cough. This is a number of rapid coughs, invoked because the body is encountering difficulty in removing thick mucous from the tracheobronchial tree. After the coughing fit the patient usually makes a high-pitched whoop sound in the effect to breath. Infants may not make a whooping sound because they are not yet strong enough. Patients can become cyanotic (turn blue from the lack of oxygen) and even exhausted or vomit after coughing fits. Patients typically suffer from about 15 coughing attacks a day. The paroxysmal stage normally lasts between one and six weeks. The first few weeks the coughing tends to increase. It can remain at this high level for 2-3 weeks, and then slowly decreases.

The final stage of the disease, the convalescent stage , is the gradual recovery of the patient (3, 2). Coughing fits become less severe and can disappear in two to three weeks. Despite a decrease in the clinical symptoms, respiratory infections months following the disease can trigger the recurrence of the paroxysm coughing fits.

As the effects of the vaccine wear off in adolescence and adulthood, those partially protected may become infected with B. pertussis (3). Instead of contracting the full-blown disease, they may present a persistent cough. This cough may linger for more than seven days, but is often indistinguishable from other respiratory infections. It is believed that seven percent of cough illnesses in older people are caused by B. pertussis.

The most common complication of pertussis is secondary bacterial pneumonia (3). This is responsible for the majority of pertussis fatalities. Between 1997-2000, pneumonia occurred in 5.2% of all reported cases, and in 11.8% of reported cases in infants under six months of age. Infants can suffer from periods of apnoea following coughing fits(WHO). Rarely pertussis also leads to seizures and encephalopathy due to hypoxia, a reduction in oxygen supply. Between 1997 and 2000, 20% of all cases needed hospitalization, while 63% of infant cases required hospitalization. Pertussis had a case rate mortality of 0.2% in the US between 1997-2000. Ninety percent of these deaths occurred in infants under six months old.

Laboratory Diagnosis

Diagnosis is primarily based on clinical features. While no laboratory test is found to be completely accurate, in some cases laboratory diagnosis can be helpful. The primary laboratory test is isolation of B. pertussis via culture (3). It is difficult to isolate. Swabs are taken from the nasopharynx using Dacron or calcium alginate and then plated unto a selective agar. Effectiveness decreases if the swab is not taken during the catarrhal stage, if the person has been vaccinated, or if prior pertussis antibiotic medications have been taken.

In addition Polymerase chain reaction (PCR) tests can be used for a more rapid diagnosis, but should not be used as a replacement for culture isolation (3). PCR testing is not standardized and currently is not widely available. Although it is currently not yet standardized, serological testing has been useful in clinical trials. It is still not widely available because the association between antibody levels and immunity to pertussis is difficult to determine. Elevated white lymphocyte count with lymphocytosis can also be used. A lymphocyte count over 20,000 is associated with pertussis, but there may be no lymphocytosis in infants, children, modified or mild cases.

Treatment

Antibiotics have limited usefulness in treating pertussis (3, 2, 1). Erythromycin is the primary drug used for treatment. It kills the bacteria, but the toxins are still effective. If the disease is diagnosed and treatment begins during the cattarhal stage, the symptoms can be lessened. Treatment after the cattarhal stage is ineffective in decreasing morbidity of the patient, but it can decrease communicability and is useful in households where there are children who have not been vaccinated. Erythromycin should be administered orally in doses of 40-50 mg/kg four times a day for 14 days. If treatment is administered to all household members and other close contacts it might prevent or minimized transmission. Children of under seven years of age who have not received a booster should be given one. In infants and potentially severe cases, the patient should be hospitalized for supportive care.

Immune Response

Infection with pertussis results in long-lasting immunity to the typical clinical manifestations (2). This natural immune response may however not be life-long or complete, and people with acquired immunity may become infected with an atypical strain. Therefore, occasional exposure to new strains of B. pertussis in those previously infected, may be crucial to maintaining immunity.

Fetus and newborns passively acquire immunity from their mothers (1). IgA antibodies pass to infants primarily through colostrums and breast milk, while IgG seems to pass primarily through serum. IgG antibodies which protect against B. pertussis antigens FHA, PT, AGG2, and AGG3 have been detected in the serum of children who have not yet been immunized. This provided newborns with a protective effect for the first months of life. Studies conducted during the 1940s, immunized pregnant mothers with 6 doses of vaccine equaling 150 million B. pertussis organisms. The majority of newborns accrued agglutinin and antibody titers equal or greater than that of their mothers.

"It is possible that success in controlling pertussis by immunization has altered its epidemiology by reducing the likelihood of repetitive casual exposure to pertussis and consequent reinforcement of the immune response" (1). In countries where there has been the most effective and widespread immunization programs, the incidence of pertussis has greatly decreased. Therefore people are far less likely to encounter the organism and received a natural immune booster. In these countries, seroprevalence is highest among age groups being covered by vaccination, and tends to decrease with age. By contrast, in countries where the vaccination coverage rate is low and pertussis has high incidence rates, infection in older persons causes seroprevalence to increase with age. This means that in countries with high coverage rate and low incidence, adults with low seroprevalence may become infected and spread the disease to children who have not yet be immunized.

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