PATHOGENESIS AND TREATMENT OF BORDETELLA PERTUSSIS INFECTION

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Bordetella pertussis is a Gram-negative, capsulated, non-motile, fastidious, toxigenic, aerobic and coccobacillus or rod-like bacterium found in the genus Bordetella. It is the main causative agent of pertussis (also known as whooping cough) in human population. B. pertussis inhabits the human upper respiratory tract, and the pathogen is morphologically similar to Haemophilus.Whooping cough is strictly a human disease, and has not been reported in animals. Other species of the genus Bordetella rarely cause disease in humans but they parasitize animals. The main route of spread of B. pertussis is through respiratory droplets especially those of infectious people. Whooping cough (pertussis) is a mild and serious respiratory disease in people of all age groups, but the disease is more common amongst children and infants who experience several respiratory clinical symptoms associated with the infection. The disease (pertussis) is known for its characteristic “whoop sound” or inspiratory gasp which distinguishes it from other respiratory diseases that are bacterial-related.  

PATHOGENESIS OF BORDETELLA PERTUSSIS INFECTION

Whooping cough (pertussis) is a vaccine-preventable communicable disease. The main route of transmission of the pathogen is via the inhalation of aerosols or respiratory droplets containing the infectious particle (i.e., B. pertussis). After inhalation, B. pertussis migrates to the upper respiratory tract where it attaches to the cilia of the respiratory epithelium. Attachment to ciliated cells provides sites for toxin production especially the pertussis toxin and invasive adenylate cyclase toxin amongst other virulence factors of the pathogen. B. pertussis multiplies rapidly at the epithelial surfaces of the bronchi and trachea after attachment; and this phenomenon greatly inhibits the cilliary action of the mucosal region of the upper respiratory tract. Thus, allowing the pathogen to thrive undeterred due to the killed or inhibited ciliated cells of the upper respiratory tract. The incubation period of whooping cough is usually about 6-10 or 14 days. The virulence of B. pertussis is facilitated by some virulence factors and extracellular enzymes such as filamentous hemagglutinin (FHA) and pertussis toxin (PTx), an exotoxin which the pathogen produces in vivo.

Pertussis toxin (PTx) is a lymphocytosis-promoting toxin that stimulates the adenylate cyclase by ribosylating regulatory protein molecules. In effect, PTx is an important toxin in the colonization of B. pertussis in that it disrupts the host’s adenylate cyclase activity and other cell regulation processes. The invasive adenylate cyclase toxin produced by B. pertussis enters the host cells and stimulates the synthesis of cyclic adenosine monophosphate (cAMP) from ATP. Invasive adenylate cyclase toxin also inhibits eukaryotic or host’s adenylate cyclase function as well as the functioning of the host’s immune system cells. cAMP promotes the damage of the host tissues through apoptosis, haemolysis and the inhibition of other cellular functions inclusive of immune function disruption. Increased cAMP production coupled with toxin production leads to hypoglycemia, shock and hypotension.

Persistent coughing, running nose, fever and malaise are some of the signs and symptoms associated with early colonization of the upper respiratory tract by B. pertussis (i.e., the catarrhal phase). As the disease process progresses especially without treatment, the paroxysmal stage of pertussis sets in. This later stage of whooping cough which is usually accompanied by a secondary or superinfcetion infection (e.g., pneumonia caused by Haemophilus or Pneumococci) is characterized by an inspiratory gasp or whoop sound due to difficulty in drawing in air by the affected individual. Recurrent coughing which may last up to 4 weeks, vomiting and apnea or inability to breathe are some of the symptoms associated with the later stages of pertussis (i.e., the paroxysmal stage of the disease). In summary, the two stages of pertussis in humans are: (1) the catarrhal stage and (2) the paroxysmal stage. Infants may experience convulsion in the paroxysmal stage of the disease. The catarrhal stage of pertussis is the most infectious stage of whooping cough than the later paroxysmal phase of the disease which is usually prolonged. Pertussis later assumes a convalescent phase during which the infected individual gradually recovers from the disease.       

LABORATORY DIAGNOSIS OF BORDETELLA PERTUSSIS INFECTION

The laboratory diagnosis of B. pertussis infection is usually based on the culture and isolation of the bacterium from clinical specimens. Nasopharyngeal secretions or swabs taken from the nose of an infected patient especially during the catarrhal stage of the disease are usually the best specimen for culture and other laboratory techniques. Fluorescent antibody staining of smears made from the nasopharyngeal swabs or secretions is also carried out for rapid diagnosis in addition to some serological tests. B. pertussis grows on Bordet-Gengou medium (blood-glycerol-potato), a non-selective medium and charcoal cephalexin blood agar, a selective agar medium, at 37oC. The agar medium is usually incubated for about 5-6 days because of the slow-growing nature of the organism. Small pin-point and β-haemolytic colonies are produced after incubation, and the isolates appear as Gram-negative coccobacilli under the microscope. Charcoal cephalexin blood agar is a selective medium, and the addition of cephalexin inhibits other normal bacteria flora of the upper respiratory tract. Polymerase chain reaction (PCR) can also be used for the rapid detection and/or diagnosis of B. pertussis infection. Biochemically, B. pertussis is oxidase-positive, urease-negative and the pathogen does not reduce nitrate. 

IMMUNITY TO BORDETELLA PERTUSSIS INFECTION

Prior infection with B. pertussis and recovery presents a stable immunity in affected individuals. Any reoccurrence of the disease is usually mild but can be severe in some adults. 

TREATMENT OF BORDETELLA PERTUSSIS INFECTION

The antibiotic of choice for treating whooping cough (pertussis) is usually the macrolides e.g., erythromycin and azithromycin. Early treatment of pertussis is critical to limit the spread of the disease to susceptible people. However, late treatment can prolong the disease especially when it enters the paroxysmal stage during which it may be difficult to eliminate some of the clinical episodes associated with the disease. Respirator should be used as supportive therapy in severe cases to maintain proper flow of air and/or oxygen in patients with difficulty in breathing.  

PREVENTION AND CONTROL OF BORDETELLA PERTUSSIS INFECTION

Pertussis (whooping cough) is a preventable bacterial disease. Several acellular pertussis vaccines such as the diphtheria-tetanus-pertussis vaccine (DTaP) exist for vaccination against whooping cough, and it is important to immunize infants and children at their first year of life. Booster doses should also be administered after the last dosage. Adequate immunization/vaccination of infants and children is important for the control and prevention of whooping cough in human population.  

Further reading

Brooks G.F., Butel J.S and Morse S.A (2004). Medical Microbiology, 23rd edition. McGraw Hill Publishers. USA.

Gilligan P.H, Shapiro D.S and Miller M.B (2014). Cases in Medical Microbiology and Infectious Diseases. Third edition. American Society of Microbiology Press, USA.

Madigan M.T., Martinko J.M., Dunlap P.V and Clark D.P (2009). Brock Biology of Microorganisms, 12th edition. Pearson Benjamin Cummings Inc, USA.

Mahon C. R, Lehman D.C and Manuselis G (2011). Textbook of Diagnostic Microbiology. Fourth edition. Saunders Publishers, USA.

Patrick R. Murray, Ellen Jo Baron, James H. Jorgensen, Marie Louise Landry, Michael A. Pfaller (2007). Manual of Clinical Microbiology, 9th ed.: American Society for Microbiology.

Wilson B. A, Salyers A.A, Whitt D.D and Winkler M.E (2011). Bacterial Pathogenesis: A molecular Approach. Third edition. American Society of Microbiology Press, USA.

Woods GL and Washington JA (1995). The Clinician and the Microbiology Laboratory. Mandell GL, Bennett JE, Dolin R (eds): Principles and Practice of Infectious Diseases. 4th ed. Churchill Livingstone, New York.

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