Haemophilus, Bordetella & Legionella
Three fastidious gram-negatives of the airway, each with its own trick
Haemophilus influenzae: organism and virulence
The organism. H. influenzae is a small, pleomorphic gram-negative coccobacillus that colonizes the human nasopharynx and spreads by respiratory droplets. It is fastidious, requiring both X factor (hematin) and V factor (NAD+). Chocolate agar, made by heating blood so RBCs lyse, provides both. On ordinary sheep blood agar it grows only as tiny satellite colonies around a streak of S. aureus, which hemolyzes the RBCs (releasing hematin) and secretes NAD+.
Capsule. Encapsulated strains are grouped into serotypes a–f, and serotype b is the invasive one. The type b capsule is a polymer of polyribosylribitol phosphate (PRP) that resists phagocytosis and complement, allowing survival in the bloodstream. The organism also secretes an IgA1 protease that cleaves secretory IgA and eases mucosal colonization. Asplenia and sickle cell disease raise the risk of invasive disease.
Conjugate vaccine. A pure polysaccharide is a T-independent antigen that infants under about 2 years respond to poorly. The Hib vaccine links PRP to a protein carrier (for example, tetanus toxoid), so helper T cells are recruited, B cells class-switch to IgG, and memory forms. The series begins at 2 months with a booster at 12–15 months.
Haemophilus disease spectrum and treatment
Epiglottitis. Hib cellulitis of the epiglottis produces an abrupt, toxic illness: high fever, drooling, dysphagia, a muffled voice, inspiratory stridor, and a child who sits leaning forward in the tripod position. A lateral neck radiograph shows the swollen epiglottis as a thumb sign.
Do not examine the throat with a tongue depressor or agitate a child with suspected epiglottitis; the airway is secured first in a controlled setting.
Other invasive disease. Before routine vaccination, Hib was the leading cause of bacterial meningitis in young children (peak roughly 6 months to 2 years) and also caused bacteremia, septic arthritis, and facial cellulitis. Invasive disease now appears mainly in unvaccinated or incompletely vaccinated children and in asplenic hosts.
Nontypeable strains. Unencapsulated strains rarely invade the bloodstream. They spread contiguously from the nasopharynx to cause acute otitis media, sinusitis, conjunctivitis (sometimes as a combined conjunctivitis-otitis syndrome), and acute exacerbations of COPD. The Hib vaccine does not target them, so these infections remain common.
| Feature | Type b (Hib) | Nontypeable |
|---|---|---|
| Capsule | PRP polysaccharide | None |
| Spread | Bloodstream (invasive) | Contiguous mucosal |
| Diseases | Epiglottitis, meningitis, bacteremia, septic arthritis, cellulitis | Otitis media, sinusitis, conjunctivitis, COPD exacerbations |
| Vaccine | Prevented by conjugate Hib vaccine | Not prevented |
| Treatment | Ceftriaxone | Amoxicillin or amoxicillin-clavulanate |
Treatment and prophylaxis. Invasive disease is treated with a third-generation cephalosporin such as ceftriaxone. Many strains produce β-lactamase, so mucosal infections that fail amoxicillin are treated with amoxicillin-clavulanate. Rifampin eradicates nasopharyngeal carriage and is given to all household contacts when the home includes an unimmunized or incompletely immunized child under 4 years or an immunocompromised child.
Bordetella pertussis: toxins and pathogenesis
The organism. B. pertussis, a strictly aerobic gram-negative coccobacillus spread by droplets, attaches to ciliated respiratory epithelium and injures it with toxins without invading the bloodstream.
| Factor | Mechanism | Consequence |
|---|---|---|
| Pertussis toxin | A-B toxin that ADP-ribosylates Gi, removing its inhibition of adenylate cyclase (↑cAMP) | Impaired chemokine signaling, marked lymphocytosis, weakened phagocyte function |
| Adenylate cyclase toxin | Enters phagocytes and generates cAMP directly | Crippled chemotaxis, phagocytosis, and oxidative killing |
| Tracheal cytotoxin | Peptidoglycan fragment toxic to ciliated cells | Ciliary loss, impaired mucus clearance, cough |
| Filamentous hemagglutinin | Adhesin | Attachment to ciliated epithelium |
Lymphocytosis. Because Gi-coupled chemokine receptors stop signaling, lymphocytes cannot leave the circulation, and the white count rises with a strong lymphocyte predominance despite little fever. Contrast cholera toxin, which ADP-ribosylates Gs and locks it on; both toxins end with high cAMP.
Pertussis: course, diagnosis, and prevention
Clinical stages. After an incubation of about 7–10 days the illness evolves through three stages, often summarized as the 100-day cough.
- Catarrhal (1–2 weeks)rhinorrhea, mild cough, low-grade fever; the most contagious stage and the one in which culture is most often positive
- Paroxysmal (2–6 weeks)bursts of coughing ending in an inspiratory whoop, post-tussive emesis, cyanosis; the patient may look well between fits
- Convalescent (weeks to months)paroxysms gradually fade
Infants and adults. Infants under 6 months may never whoop; they present with apnea, cyanosis, and gagging and have the highest mortality, mostly from pneumonia, with seizures and encephalopathy as other serious complications. Forceful paroxysms can cause subconjunctival hemorrhage, rib fractures, hernias, and pneumothorax. Adolescents and adults, whose vaccine immunity has waned, often have only a prolonged cough and are the usual source for infants.
Diagnosis. A nasopharyngeal swab for PCR is the preferred test and is most sensitive in the first weeks of cough. Culture on Regan-Lowe (charcoal-horse blood) or Bordet-Gengou (potato-glycerol-blood) medium is specific but slow.
Treatment. Azithromycin is the drug of choice and is preferred in young infants because erythromycin is linked to infantile hypertrophic pyloric stenosis. Started in the catarrhal stage it can shorten the illness; once paroxysms have begun it mainly shortens contagiousness. The same regimen is given as postexposure prophylaxis to all close contacts regardless of vaccination status. TMP-SMX is the alternative for macrolide intolerance, but not before 2 months of age.
Prevention. Acellular vaccines replaced the more reactogenic whole-cell vaccine. Children receive DTaP at 2, 4, 6, and 15–18 months and 4–6 years, and Tdap at 11–12 years.
Legionella pneumophila
Ecology and pathogenesis. Legionella lives in warm fresh water and man-made water systems, often inside free-living amoebae. Infection follows inhalation of aerosols from cooling towers, hot tubs, showers, humidifiers, and decorative fountains, and there is no person-to-person transmission. It is a facultative intracellular gram-negative rod that uses a type IV secretion system to block phagolysosome fusion and replicates inside alveolar macrophages.
Laboratory. The organism stains poorly with Gram stain (sputum shows many neutrophils but few organisms), so a silver stain is used. It grows on buffered charcoal yeast extract (BCYE) agar supplemented with iron and cysteine. The rapid urinary antigen test detects only L. pneumophila serogroup 1, which causes most cases; culture and PCR detect other serogroups.
Clinical features. Risk factors are older age, smoking, chronic lung disease, heavy alcohol use, and immunosuppression (glucocorticoids, transplantation). Distinguishing clues include high fever with relative bradycardia, diarrhea, confusion or headache, hyponatremia, elevated liver enzymes, and hypophosphatemia.
| Feature | Legionnaires' disease | Pontiac fever |
|---|---|---|
| Illness | Severe, often multilobar pneumonia | Self-limited flu-like illness, no pneumonia |
| Host | Older, smokers, immunosuppressed; low attack rate | Healthy people; high attack rate |
| Incubation | 2–10 days | 1–3 days |
| Course | Can be fatal without therapy | Resolves in days without antibiotics |
Treatment. Azithromycin or levofloxacin (doxycycline is an alternative) because these drugs concentrate inside cells. β-Lactams are ineffective against this intracellular organism.
Pneumonia plus diarrhea, confusion, hyponatremia, and abnormal liver tests after water exposure: think Legionella.