Pertussis (Last Updated - 4/30/2005)
-aka "whooping cough" or "the 100-day cough"
-acute
-highly infectious
-char. by paroxysmal coughing episodes ending in whooping inspiration
-Epidemiology:
-1-2% mortality in children < 1 y.o. (highest in 1st month of life)
-71% of cases --> children < 5 y.o.
-38% of cases --> children < 6 months old
-Incidence:
-~15,000 per yr. in US
-peaks in summer & fall (although occurs year-round)
-cyclical outbreaks Q 3-5 yrs. (despite vaccination)
-affex 80-100% of un-immunized household contacts
-affex ~20% of well-immunized household contacts
-no animal or environmental reservoir
-Causative Agent:
-aspiration of: Bordetella pertussis
-Gram neg. bacillus (rod)
-differentiated from other Bordetella species via oxidase pos. and urease neg.
-fastidious --> requires charcoal-horse blood agar medium plus nicotinamide
-slow-growing
-non-motile
-strictly aerobic
-non-fermentative --> does not ferment carb's
-invades oropharyngeal mucosa --> increased mucous secretion
-Virulence Factors:
1) Pertussis Toxin
-bacterial exotoxin
-composed of a B oligomer-binding subunit and an enzymatically-active A protomer
-it ADP-ribosylates a Gi protein in target cells
-guanine nucleotide-binding regulatory protein
-via permanent adenylate cyclase stimulation by ADP ribosylation --> increased cAMP --> increased mucous production
-serves as an adhesin for bacterial binding to ciliated resp. epithelium
-also affex circulation of lymphocytes --> inhibits chemokine receptors --> lymphocytosis
-induces high-titer Ab's (antitoxins) --> toxoids used as vaccines
2) Filamentous Hemaglutinin
-cell-wall component
-bacterial adhsein
3) Pertactin
-outer-membrane protein
-bacterial adhesin
4) Fimbriae
-bacterial appendages --> role in bacterial adhesion
-major Ag's to which Ab's are directed
5) Tracheal Cytotoxin
-induces resp. epithelial damage
6) Adenylate Cylcase Toxin
-impairs host immune cell function
7) Dermonecrotic Toxin
-contributes to resp. epithelial damage
8) Lipo-oligosaccharide
-bacterial endotoxin
-Incubation Period:
-7-10 days
-Stages:
-lasts 6-10 wks. (avg = 7 wks.)
1) Catarrhal --> inflammation of mucous membranes (esp. throat)
-symptoms suggestive of common cold:
-fever
-sneeze
-rhinitis
-dry cough
-irritability
-decreased appetite
-difficult to distinguish from bronchitis or influenza at this stage
2) Paroxysmal --> sudden periodic attack or recurrence of symptoms
-occurs after ~2 wks.
-cough is more violent proceeding to inspiratory whoop (or choking in infants)
-whoop is caused by spasmodic contraction of the glottis
-whoop is uncommon in children < 6 months old & frequently absent in older children & adults
-present in only ~50% of all cases
-posttussive vomiting is common at end of paroxysmal coughing episodes
-may see:
-face becomes cyanosed
-eyes become injected
-veins become distended
-epistaxis (nosebleed)
-subconjunctival hemorrhages
-may also see anywhere from 3-50 paroxysmal coughing episodes QD
-coughing fits often worse @ night
3) Convalescent / Decline
-occurs after several wks.
-cough progressively ceases
-Diagnosis:
-suspect pertussis in anyone w/ cough for < 14 days
A) nasopharyngeal cultures positive in 80-90% of cases --> gold standard
-nasopharyngeal aspirates preferred or use synthetic fiber swabs (calcium-alginate or Dacron)
-NOT cotton swabs --> cotton contains FAcids --> toxic to B. pertussis
-must innoculate immediately (at the bedside) onto charcoal-horse blood agar medium
-otherwise sample will quickly dry out and die
-results take ~5 days
B) pertussis PCR
C) microscopy via DFA (Direct Fluorescent Ab's)
-only ~50% sensitive & specific --> not recommended for use
-Differential Diagnosis:
1) Bronchitis
2) Influenza
3) TB
4) Adenovirus Infec.
5) RSV (Respiratory Syncytial Virus) Infec.
6) Pneumonia
-Mycoplasma or
-Chlamydia
7) ACE Inhibitor-Induced cough
8) Reactive Airway Disease (Ex.) Asthma)
9) GERD
-Labs:
-lymphocytosis --> WBC 15,000-20,000 (usually) --> 60-80% lymphocytes
-may be normal though
-Treatment:
-symptomatic and supportive
-may treat close contacts (esp. high-risk pts. --> children < 1 y.o.) with PO erythromycin 12.5 mg/kg QID x 7 or 14 days (not to exceed 2 g/day)
-treat ONLY during the incubation period --> no benefit of tx if cough has already started
-erythromycin decreases length of infectivity
-studies have shown no added benefit to treating for 14 days as opposed to 7 days
-bacteria are cleared after 5 days
-use Bactrim (Trimethoprim-Sulfamethoxazole) in pts. unable to tolerate erythromycin
-4 / 20 mg/kg/day BID x 7 or 14 days
-Prevention / Chemoprophylaxis:
-immunization (80-85% effective) (DTaP or DTP x 5 IM doses):
A) 1st dose - 2 months
B) 2nd dose - 4 months
C) 3rd dose - 6 months
D) 4th dose (booster) - 15-18 months (may be given as early as 12 months if 6 months have passed since 3rd dose)
E) 5th dose (booster) - 4-6 yrs.
-natural infection likely does NOT confer life-long immunity
A) DTaP --> Diptheria, Tetanus & acellular Pertussis
-preferred over DTP (or DTwP) --> less adverse effex
-no data on long-term immunity (likely not more than 15 yrs.)
B) DTP (or DTwP)--> Diptheria, Tetanus & whole-cell Pertussis
-more adverse effex than DTaP
-contraindicated in children & adults > 7 y.o.
-short-lived long-term immunity --> 10-12 yrs.
-prevent spread after onset of symptoms --> isolation
-treat close contacts (esp. high-risk pts. --> children < 1 y.o.) with PO erythromycin 12.5 mg/kg QID x 14 days (not to exceed 2 g/day)
-treat ONLY during incubation period --> no benefit if cough is already present
-erythromycin decreases length of infectivity
-studies have shown no added benefit to treating for 14 days as opposed to 7 days
-bacteria are cleared after 5 days
-use Bactrim (Trimethoprim-Sulfamethoxazole) in pts. unable to tolerate erythromycin
-4 / 20 mg/kg/day BID x 7 or 14 days
Complications:
1) Bronchopneumonia --> most common cause of pertussis-induced death (may be confused with SIDS)
-usually diffuse bilateral primary infec. in infants
-in older children & adults pneumonia often due to 2nd-ary bacterial infec. (staph or strep)
2) Petechial Hemorrhages --> from cough
-subconjunctival, facial or truncal
3) Syncope
-likely from cough-induced hypoxia
4) Seizures
-likely from cough-induced hypoxia
5) Encephalopathy
-likely from cough-induced hypoxia
6) Asphyxia (esp. in infants)
7) Pneumothorax --> increased intrathoracic pressures during coughing episodes
8) Atelectasis --> mucous plugs clog bronchioles
9) Umbilical Hernia
-likely from increased abdominal pressure during the coughing fits
10) Rectal Prolapse
-likely from increased abdominal pressure during the coughing fits
11) Otitis Media (esp. in children)
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References:
1) Taber's Cyclopedic Medical Dictionary: 19th Edition. 1997: pg. 1631-1632
2) First Aid For The USMLE Step 1. Bhushan et al. 2002. pg. 179-180, 188
3) The Merck Manual: 17th Edition. 1999: pg. 1123, 2096-2097, 2306-2308
4) Medical Microbiology: 3rd Edition. 1998: pg. 265-269
5) Harrison's Principles Of Internal Medicine: 15th Edition. 2001: pg. 949-952