A. Organism
- Bordetella pertussis or (less commonly) B. parapertussis
- Fastidious Gram negative rod
- Lives in tracheobronchial tree
- Culture requires selective media
- Virulence factors
- Pertussis toxin
- Tracheal cytotoxin
- Pili
- Fillamentous hemagglutinin
- No animal reservoir
- Both children and adults susceptible to organism
- In 2003, 11,647 cases of pertussis reported in USA
- Worldwide, >300,000 deaths annually in children, mainly in underdeveloped nations
B. Pathogenesis
- B. pertussis produces one major specific toxin
- This toxin is an enzyme that catalyzes ADP-ribose attachment to a G-protein
- Thus, ADP-ribose is attached to a cysteine in the C-terminus of G(i)alpha protein
- This leads to inhibition of receptors coupled to the G(i)alpha protein
- Unclear how this inhibition actually leads to symptoms
- Likely, however, that inhibited signalling leads to excess mucous production, irritation
C. Phases of Illness
- Catarrhal Phase 1-2 weeks
- Mild cough
- 1-2 weeks rhinorrhea
- Conjunctivitis
- Paroxysmal Phase 2-4 weeks
- Cough, paroxysms usually with "whoop"
- Inspiratory wheezing
- Conjunctival Hemorrhage
- Lymphocytosis
- Convalescent Phase - slow resolution of symptoms
- In adults, chronic cough may be the major (or only) symptom of infection
- Increasing incidence in adult population, particularly in patients with cough >2 weeks [3]
D. Complicated Disease
- Failure to thrive
- Vomiting
- Atelectasis and frank pneumonia
- CNS - hyperinsulinemia, decreased glucose, seizures, hypoxemia
E. Differential Diagnosis
- Refractory Cough Syndromes
- Adenovirus Infection
- Mycoplasma Infection
F. Diagnosis
- Clinical Presentation
- Consider risk for exposure
- Vaccinated persons, older children, adults, may have simple (not "whooping") cough
- Culture
- Gold standard within 3 weeks of onset of cough
- Use sputum, bronchoalveolar lavage fluid
- Relatively insensitive
- Nasopharyngeal swab on calcium alginate tip - notify lab to look for pertussis
- Acute and Convalescent Serology
- Pertussis Toxin Antibody
- Antibody to Filamentous Hemagglutinin
- ELISA - elevated (acute) IgG levels, particularly in setting of chronic cough
- Polymerase chain reaction (PCR) - within 3 weeks of cough onset; some false positives
- Combinations of diagnostic tests are usually used
G. Treatment
- Macrolides are first line
- Erythromycin is active against organism, 500mg po or iv q6 hours x 7 days
- Azithromycin 10mg/kg (maximum 500mg) x 1, then 5mg/kg (maximum 250mg) qd x 4
- Clarithromycin 10mg/kg (maximum 500mg) bid x 7 days
- Doxycycline 100mg po bid (or iv) is also effective
- Trimethoprim/sulfamethoxazole (TMP/SMX) bid x 7 days also effective
- Ampicillin does not clear the organism from the respiratory tract
- Treatment is instituted in patients with up to 3-4 weeks of cough (but not longer)
H. Vaccination
- Original Vaccine
- Killed whole bacterial cells
- Causes local and systemic reactions in high proportion of vaccine recipients
- Used in adults only in outbreaks (generally avoided due to severe reactions)
- Acellular Vaccine
- New, acellular vaccine (aP) is very effective (>70%) with few side effects [4,5]
- Vaccine efficacy after household exposure was >75% and well tolerated [6]
- Can be given to adults with minimal reactions
- Five-component vaccine is great improvement 3 component and whole-cell vaccines [7]
- Two component vaccines are less effective than 5 component vaccines [5]
- Tricomponent acellular pertussis vaccine is effective in 92% of adolescents and adults [9]
- Combination DTaP is available and all Td boosters should be replaced with TDaP [10]
- Specific booster versions of DTaP are now available (Adacel®, Boostrix®) [10]
- Increasing incidence of disease suggests need for booster in adults with acellular vaccine
- Combined Tetanus/Diphtheria/Pertussis (5 component) Vaccine (Tdap) [8]
- Increasing reports of pertussis in adults have driven this combination vaccine
- 94% of volunteers vaccinees with Tdap have protective antibody concentrations
- Similar incidence of local and systemic reactions with Td versus Tdap vaccines
- Bordetella infections can occur in immunized populations
- Bordetella parapertussis may be increasing in populations immunized to B. pertussis
References
- Hewlett EL and Edwards KM. 2005. NEJM. 352(12):1215
- Crowcroft NS and Pebody RG. 2006. Lancet. 367(9526):1926
- Nennig ME, Shinefield HR, Edwards KM, et al. 1996. JAMA. 275(21):1672
- Greco D, Salmaso S, Mastrantonio P, et al. 1996. NEJM. 334(6):341
- Gustafsson L, Hallander HO, Olin P, et al. 1996. NEJM. 334(6):349
- Schmitt HJ, von Konig CHW, Neiss A, et al. 1996. JAMA. 275(1):37
- Olin P, Rasmussen F, Gustafsson L, et al. 1997. Lancet. 350(9090):1569
- Pichichero ME, Rennels MB, Edwards KM, et al. 2005. 293(24):3003
- Ward JI, Cherry JD, Chang SJ, et al. 2005. NEJM. 353(15):1555
- TDaP Vaccines for Adolescents and Adults. 2006. Med Let. 48(1226):5