Student Presentation on:

Bordetella pertussis
"Whooping Cough"


by Kristin Santini

Encounter and Colonization

Bordetella pertussis is a highly communicable agent and is transmitted person-to-person via airborne droplets or direct contact with discharges from the respiratory mucous membranes of an infected person. This small, gram-negative coccobacillus is non-motile, aerobic and fastidious. B. pertussis colonizes the respiratory tract including the mouth, nose, throat and beginning of the lungs of young children worldwide. The bacteria bind to ciliated cells in the respiratory mucosa by producing adhesions. Filamentous hemagglutinin on the cell surface and pertussis toxin (Ptx) both help the bacteria in binding. Filamentous hemagglutinin binds to the galactose residues on the glycolipid of the ciliated cells. Ptx, in its cell-bound form, binds to the glycolipid lactosylceramide, which is also found on the ciliated cells. Ptx binds to the surface of phagocytes as well, causing phagocytosis of the bacteria. This mechanism may lead to enhanced survival as an intracellular parasite. Adding to its many purposes, Ptx deregulates the host cell adenylate cyclase activity. The A subunit of this AB toxin, affects the G protein responsible for inhibiting adenylate cyclase. This leads to an increase in cyclic adenosine monophosphate (cAMP) creating detrimental metabolic changes in the host cells.

Additional Toxins

Also contributing to the virulence of the bacteria are the exotoxins including invasive adenylate cyclase, tracheal cytotoxin, and lethal toxin. Invasive adenylate cyclase reduces local phagocytic activity as well as acting as a hemolysin. Tracheal toxin affects the ciliated respiratory epithelium by inhibiting the ciliary beating. This kills the cells and causes them to be eliminated from the mucosa. Tracheal toxin also stimulates the release of IL-1, which causes fever. Lastly, lethal toxin causes inflammation and local necrosis at infection sites.

Because B. pertussis is a gram-negative bacteria, it possesses the endotoxin lipopolysaccharide (LPS). However, its LPS is different from that of the other gram-negative bacteria, in that it is heterogeneous with an alternative form of the Lipid A, called Lipid X. Although not fully understood at the time, it seems that Lipid X has a greater capacity for virulence.

Pathogenesis

After an incubation period of five to ten days, or as long as 21 days, numerous symptoms can be observed. The symptoms come in two stages. The first stage consists of common cold symptoms such as sneezing, runny nose, low-grade fever, and a mild cough. It is during this time that the disease is most contagious, and it lasts from one to two weeks. The second stage is characterized by severe coughing episodes. These episodes consist of many rapid coughs followed by a characteristic whoop, which is caused by the intake of breath. During these coughing episodes, the face and lips turn blue. Also during the second stage, the patient can suffer from excessive mucus production and vomiting. Infection by B. pertussis may also produce symptoms including: edema, hemorrhages, and vascular plugs in the brain leading to neurological damage. The second stage can last from four to six weeks.

Diagnosis, Treatment and Prevention

The diagnosis of B. pertussis can by made by the characteristic symptoms. However, if the symptoms are not severe or characteristic, it is possible to overlook the infection. Definitive diagnosis can be made using an enzyme-linked immunosorbent assay (ELISA). Once diagnosed, it can be treated with antibiotics such as erythromycin. The antibiotics can also serve to shorten the length of the contagious period.

The best method of prevention is vaccination. It is recommended that the vaccination be given at the ages of two, four, six and 15-18 months of age, and then a booster between the ages of four and six years. This vaccination is given at the same time as those for diphtheria and tetanus in a vaccine cocktail. The vaccine used, DTP, is a dead, whole-cell vaccine. However, this vaccine causes side effects in about 20% of the infants it is administered to. In about 0.1% of the infants, irreversible brain damage may occur. Hence, in 1996, accelular vaccines consisting of purified proteins were developed, called DTaP.

Incidence

Major complications due to B. pertussis infection are most common among infants and young children. Children too young to have completed the primary vaccination series are at high risk for infection. Adolescents and adults become susceptible when their immunity wanes. In the United States, B. pertussis causes about nine deaths per year. It is endemic, causing epidemics every three to five years. The bacteria cause high morbidity and mortality. Since the 1980s, incidence of B. pertussis has increased steadily, reaching its highest since 1967 in 1996. During this year, 7796 cases were reported. Comparatively, un-immunized parts of the world report about 300,000 deaths per year due to B. pertussis.

 

References:

http://www.health.state.ny.us/nysdoh/consumer/pert.htm

http://s99.middlebury.edu/BI330A/projects/Pertussis

http://www.cdc.gov/ncidod/dbmd/diseaseinfo/pertussis_t.htm

 

© 2010, J.Graf. Site made by Kristin Santini, for comments please contact Joerg.Graf@uconn.edu