Haemophilus influenzae

What is haemophilus influenzae?¹

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. Prior to routine immunisation, H. influenzae serotype b (Hib) accounted for more than 80% of invasive H. influenzae disease.

The most common presentation of invasive Hib disease is meningitis, frequently accompanied by bacteraemia. This presentation accounts for approximately 60% of all cases. 15% of cases present with epiglottitis. 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.

Non-typeable encapsulated strains can occasionally cause invasive disease. Non-encapsulated and non-typeable H. influenzae strains cause mucosal infections, including:

• Exacerbations of chronic obstructive pulmonary disease.

• Otitis media.

• Conjunctivitis.

• Sinusitis.

• Bronchitis.

• Pneumonia.

Hib is spread through coughing, sneezing or close contact with a carrier or an infected person. Individuals can carry Hib bacteria in their nose and throat without showing signs of the disease. Before Hib vaccine was introduced, about 4 in every 100 pre-school children carried the Hib organism. After the vaccine was introduced, carriage rates fell below the level of detection.

Haemophilus influenzae epidemiology²

• Cases of invasive Hib disease have declined since the introduction of the Hib conjugate vaccine in 1992 and have remained at low levels since the introduction of the 12-month booster in 2006. In 2020, invasive Hib disease continued to be well controlled across all age groups.

• During 2020, there were 344 laboratory-confirmed cases of invasive Haemophilus influenzae in England. This was a 42% decrease compared to the 591 cases
  confirmed in 2019 and also lower than the 2018 total.

• In England during 2020, most Hib cases were in the 15 years and over age group with 12 cases in 2019 and six cases in 2020. Hib cases were higher than in 2018 with seven cases in 2020 and six cases in 2019.

• The coronavirus (COVID-19) pandemic and implementation of social distancing measures and national lockdowns led to reductions across a number of infections, including invasive Haemophilus influenzae disease during 2020.

• Most cases of Haemophilus influenzae are in the 15 years and over age group, accounting for 82% in 2020, with 10% under 1 year of age, 6% between 1 to 4 years and the remaining 1% of cases were among the 5- to 14-year-old age group.

• This was similar to 2019 where 86% of cases were 15 years and over; 6% were under 1 year of age; 5% were 1- to 4-year-olds and the remaining 2% were between 5- to 14-year-olds.

• Despite this distribution, the incidence remained higher in under-5s compared to persons over 5 years of age (1.8 per 100,000 and 0.5 per 100,000 respectively in 2020) and it is very low overall (1.0 per 100,000 persons in 2019 and 0.6 per 100,000 in 2020).

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 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.³

• 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.

Haemophilus influenzae symptoms¹

• 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.

Investigations⁴

• 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.⁵

• 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.

Haemophilus influenzae treatment and management⁶

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: see the article on Epiglottitis.

• Exacerbations of chronic obstructive pulmonary disease (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.⁷ Some H. influenzae strains are tetracycline-resistant and 20% of H. influenzae strains are resistant to amoxicillin.

• Meningitis: see the article on Meningitis.

Prognosis¹

• The sequelae following Hib meningitis may include deafness, convulsions and intellectual impairment.

• The case fatality rate from Hib meningitis is 3-7%.⁸

• The mortality rate for epiglottitis is 5-10% (due to acute respiratory tract obstruction).

Prevention

Hib immunisation

See also separate articles Hib Vaccination and Immunisation Schedule (UK).

Prevention of a secondary Hib disease⁶

• With invasive Hib disease, there is a small, but significant risk of secondary Hib infection, particularly within six months of the first episode. Close contacts of the index case (mainly in a household, or a pre-school or primary school setting) are also at increased risk of developing invasive Hib disease, especially within the first week of the index case becoming ill.

• For confirmed or probable cases of invasive Hib disease in all children aged under 10 years, and in individuals of any age who have a vulnerable individual (any individual who is immunosuppressed or has asplenia, or any child aged under 10 years old) in their household, antibacterial prophylaxis should be given prior to hospital discharge.

• All household contacts of a confirmed or probable index case should be given antibacterial prophylaxis if there is a vulnerable individual in the household.

• For a pre-school or primary school setting that has an outbreak (two or more cases of invasive Hib disease within 120 days), antibacterial prophylaxis is recommended for all room contacts, including staff.

• For a pre-school or primary school setting where the levels of contact are similar to those in a household (eg, a small number of children attending the same childminder for several hours each day), antibacterial prophylaxis for the close contact group should be considered.

• For all eligible contacts, antibacterial prophylaxis should be offered up to four weeks after illness onset in the index case.

• In addition to antibacterial prophylaxis, vaccination with a Hib-containing vaccine should be considered following a case of invasive Hib disease.

• The first-line choice for antibacterial prophylaxis is rifampicin. If rifampicin is unsuitable, ceftriaxone, oral ciprofloxacin or azithromycin may be used, but effectiveness in healthy individuals has not been established.