Haemophilus Influenzae

Haemophilus influenzae can cause serious invasive disease especially in young children. Invasive disease is usually caused by encapsulated strains of the organism. Six typeable capsular serotypes (a-f) are known to cause disease; non-typeable encapsulated strains can occasionally cause invasive disease.

• The most virulent strain is H. influenzae type b (Hib), which accounts for more than 95% of H. influenzae infections in children and half of infections in adults. Hib may cause bacteremia, meningitis, cellulitis, epiglottitis, septic arthritis, pneumonia, and pleural or gallbladder empyema.
• Less common Hib infections include endophthalmitis, urinary tract infection, abscesses, cervical adenitis, glossitis, osteomyelitis, and endocarditis.
• Non-encapsulated and non-typeable, H. influenzae strains cause mucosal infections, including exacerbations of chronic bronchitis,¹ otitis media, conjunctivitis, sinusitis, bronchitis, and pneumonia.

Risk factors

• Hib bacteria are carried in the nose and throat without showing any signs of infection. Hib is spread through coughing, sneezing or close contact with an infected person.
• Before Hib vaccine was introduced, about four in every 100 preschool children carried the Hib organism; after the vaccine was introduced, carriage rates fell below the level of detection.²
• Hib infections are uncommon in patients older than 6 years. However the frequency of Hib infections is increased in patients with asplenia, splenectomy, sickle cell disease, malignancies, and congenital or acquired immunodeficiencies.

• The most common presentation (60% of all cases) of invasive Hib disease is meningitis, frequently accompanied by bacteraemia. Hib meningitis primarily affects children younger than 2 years, with a peak frequency rate occurring in infants aged 6-9 months.
• Fifteen per cent of cases present with epiglottitis. Epiglottitis most commonly occurs in children aged 2-7 years but can also occur in adults.
• Bacteraemia, without any other concomitant infection, occurs in 10% of cases. The remainder is made up of cases of septic arthritis, osteomyelitis, cellulitis, pneumonia and pericarditis.
• Hib pneumonia typically occurs in children aged 4 months to 4 years.
• Hib causes septic arthritis and cellulitis in children younger than 2 years. Hib septic arthritis manifests in adults as well.
• Neonatal infection:
  • Often due to non-typeable H. influenzae, which colonises on the maternal genital tract.
  • Infection is associated with premature birth, premature rupture of membranes, low birth weight, and maternal chorioamnionitis.
  • Presentations include meningitis, pneumonia, respiratory distress, scalp abscess, conjunctivitis, and vesicular eruption.

• Gram stain: small, Gram-negative, pleomorphic coccobacilli with polymorphonuclear cells.
• Bacterial or other relevant body fluid culture: is the most confirmatory method of establishing the diagnosis.
• Slide agglutination with type-specific antisera is used for serotyping H. influenzae.
• Detection of the PRP polysaccharide capsule: methods include countercurrent immunoelectrophoresis and enzyme-linked immunosorbent assay; important for providing a rapid diagnosis. Not affected by prior antibiotics.
• CSF features in meningitis: pleocytosis with a predominance of neutrophils, decreased CSF glucose levels, increased CSF protein, detectable capsular antigen in 90%, and a positive CSF Gram stain result in 80%.
• CT scan: may be required, particularly to identify a possible subdural effusion, in patients with meningitis to exclude raised intracranial pressure, if there are focal neurological findings or failure of expected improvement with appropriate antibiotics.
• Chest x-ray: Hib pneumonia tends to cause more pleural and pericardial involvement compared with other bacterial pneumonias. Community-acquired pneumonias due to non-typeable H. influenzae are characterised by alveolar infiltrates in patchy or lobar distributions.
• Other investigations will depend on the site of infection, e.g. echocardiogram if pericarditis is suspected, joint aspiration for septic arthritis.

• H. influenzae epiglottitis: intravenous cefotaxime or chloramphenicol.
• Exacerbations of chronic bronchitis: amoxicillin, tetracycline or erythromycin; some H. influenzae strains are tetracycline-resistant and 15% of H. influenzae strains are resistant to amoxicillin.
• Meningitis: cefotaxime - treat for at least 10 days; use chloramphenicol instead if there is a history of anaphylaxis to penicillin or to cephalosporins or if organism resistant to cefotaxime; dexamethasone may also be required; give rifampicin for 4 days before hospital discharge.

• The sequelae following Hib meningitis may include deafness, convulsions and intellectual impairment.
• Between 8 and 11% of children who develop Hib meningitis will develop permanent neurological sequelae.⁴
• The case fatality ratio from Hib meningitis is 4 to 5%.⁴
• The mortality rate for epiglottitis is 5-10% (due to acute respiratory tract obstruction).
• The mortality rate for neonatal H. influenzae disease is 55%.

Hib immunisation

• Prevents infection in the vaccinated individual and reduces carriage and thus reduces chance of infection in those not vaccinated.⁵
• Apart from being part of the UK childhood vaccination programme, it is also indicated for those at risk: asplenia, sickle-cell disease, and malignancy.
• Hib vaccines are made from capsular polysaccharide that has been extracted from cultures of Hib bacteria.
• DTaP/IPV/Hib is recommended for all children from two months up to ten years of age.
• Although one dose of Hib vaccine is effective from one year of age, three doses of DTaP/IPV/Hib should be given in order to be fully protected against diphtheria, tetanus, pertussis and polio.
• If the primary course is interrupted it should be resumed but not repeated, allowing an interval of one month between the remaining doses.

Prevention of secondary case of H. influenzae type b disease

• Prophylactic antibiotics should be given to close contacts of patients who have invasive Hib disease.
• Adults: rifampicin 600 mg once daily for 4 days
• Child 1–3 months 10 mg/kg once daily for 4 days: over 3 months 20 mg/kg once daily for 4 days (max. 600 mg daily)