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Haemophilus influenzae is a non-motile Gram-negative rod-shaped bacterium. H. 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 bacteraemia, meningitis, cellulitis, epiglottitis, septic arthritis, pneumonia, pleural or gallbladder empyema, endophthalmitis, urinary tract infection, abscesses, cervical adenitis, glossitis, osteomyelitis and endocarditis.
- The number of cases in children has dropped dramatically since the introduction of the Hib immunisation programme in the UK in 1992.
- Non-encapsulated and non-typeable H. influenzae strains cause mucosal infections, including:
- 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 the Hib vaccine was introduced, about four in every 100 pre-school children carried the Hib organism; after the vaccine was introduced, carriage rates fell below the level of detection.
- 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.
- 15% 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 also occurs in adults.
- Neonatal infection:
- Often due to non-typeable H. influenzae, which colonises 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 cultures.
- Slide agglutination with type-specific antisera is used for serotyping H. influenzae.
- Detection of the polyribosyl ribitol phosphate (PRP) polysaccharide capsule: methods include countercurrent immunoelectrophoresis and enzyme-linked immunosorbent assay; important for providing a rapid diagnosis and is not affected by prior antibiotics.
- Cerebrospinal fluid (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.
- CXR: 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 - eg, echocardiogram if pericarditis is suspected, joint aspiration for septic arthritis.
Management includes treating all aspects of the infection, including fever, dehydration and any other specific interventions such as oxygen therapy in respiratory tract infections. Recommendations for antibiotic treatment include:
- H. influenzae epiglottitis: intravenous cefotaxime or chloramphenicol.
- Exacerbations of chronic bronchitis (treat if there is increased sputum production, purulent sputum or dyspnoea): treat for five days (longer in severely ill patients) with amoxicillin, tetracycline or clarithromycin; some H. influenzae strains are tetracycline-resistant and 20% 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 the organism is resistant to cefotaxime; dexamethasone may also be required; give rifampicin for four 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.
- The case fatality rate from Hib meningitis is 4-5%.
- The mortality rate for epiglottitis is 5-10% (due to acute respiratory tract obstruction).
- There were no deaths in the UK in children under the age of 16 in the year 2012.
Prevention of a secondary case of Hib disease
- Prophylactic antibiotics should be given to close contacts of patients who have invasive Hib disease.
- Adults: rifampicin 600 mg once daily for four days.
- Child aged 1-3 months: 10 mg/kg once daily for four days; child aged over 3 months: 20 mg/kg once daily for four days (maximum 600 mg daily).
Further reading and references
Chest infections - adult; NICE CKS, August 2012 (UK access only)
Immunizations - childhood; NICE CKS, November 2012 (UK access only)
Haemophilus influenzae; Public Health England
Haemophilus influenzae and Hib Meningitis; Todar's Online Textbook of Bacteriology
Immunisation against infectious disease - the Green Book (latest edition); Public Health England
Graph showing Haemophilus influenzae type b laboratory reports: England, 1990-2012; Health Protection Agency
De Chiara M, Hood D, Muzzi A, et al; Genome sequencing of disease and carriage isolates of nontypeable Haemophilus influenzae identifies discrete population structure. Proc Natl Acad Sci U S A. 2014 Apr 8111(14):5439-44. doi: 10.1073/pnas.1403353111. Epub 2014 Mar 25.
McVernon J, Howard AJ, Slack MP, et al; Long-term impact of vaccination on Haemophilus influenzae type b (Hib) carriage in the United Kingdom. Epidemiol Infect. 2004 Aug132(4):765-7.
Bruce MG, Zulz T, DeByle C, et al; Haemophilus influenzae serotype a invasive disease, Alaska, USA, 1983-2011. Emerg Infect Dis. 2013 Jun19(6):932-7. doi: 10.3201/eid1906.121805.
Ishiwada N, Honda Y, Tanaka J, et al; Anti-polyribosylribitol phosphate antibody in pediatric patients with Haemophilus influenzae type b invasive disease. J Infect Chemother. 2011 Jun17(3):397-400. doi: 10.1007/s10156-010-0186-x. Epub 2010 Dec 25.
Tudor-Williams G, Frankland J, Isaacs D, et al; Haemophilus influenzae type b disease in the Oxford region. Arch Dis Child. 1989 Apr64(4):517-9.
Probst R et al; Basic Otorhinolaryngology: A Step-by-step Learning Guide, 2006.
Health Protection Report; Health Protection Agency, March 2013