Factsheet about Invasive Haemophilus influenzae disease

Factsheet

Haemophilus influenzae type b (Hib) is an obligate human pathogen and an important cause of invasive bacterial infections in both children and adults, with the highest incidence among young children. An effective and safe vaccine against Hib has been available since the 1980s and most but not all EU Member States have included Hib vaccine in their national immunisation programs. Most invasive Hib infections can be prevented with immunisation and, where it has been used, vaccination against Hib has dramatically reduced the rate of invasive Hib disease in young children.

The pathogen

• Haemophilus influenzae type b is an encapsulated, immotile and non-spore forming Gram-negative coccobacillus.

• H. influenzae is divided into capsulated and non-capsulated strains. Non-capsulated strains are sometimes referred to as “non-typeable”.
• Encapsulated strains express six antigenically distinct capsular polysaccharides which are classified as serotype a through f.
• Serotype b (Hib) has a polyribosyl ribitol phosphate (PRP) polysaccharide capsule that is a major virulence factor. 
• The PRP capsule protects the organism from phagocytosis in the absence of anticapsular antibodies and facilitates penetration to the blood stream and the cerebrospinal fluid. 
• Humans are the only known reservoir for Hib.

Clinical features and sequelae

• Haemophilus influenzae type b causes pneumonia, septicaemia, meningitis, epiglottitis, septic arthritis, cellulitis, otitis media, and purulent pericarditis, as well as less common invasive infections such as endocarditis, osteomyelitis, and peritonitis.
• Haemophilus influenzae type b infections are clinically indistinguishable from infections caused by other bacteria. 
• The EU case definition of invasive Hib infection (2002/253/EC) for the purpose of reporting communicable diseases to the community network can be found  here. Prior to widespread immunisation, Hib was the most common cause of bacterial meningitis in children in Europe, and remains the leading cause of meningitis morbidity and mortality in unimmunised populations around the world.
• The highest incidence of invasive Hib in unimmunised populations is in the 6–24 months age group. This is explained by the passive protection from maternal antibodies during the first months of life and the improving natural immunity after two years of age. 
• Symptoms and signs of Hib meningitis are indistinguishable from other causes of bacterial meningitis and include fever, headache, photophobia, stiff neck, vomiting and altered mental status. Severe cases may present with convulsions and coma. Infants often present with less characteristic symptoms such as, vomiting, refusal to feed and irritability. Severe cases may develop hypotonia, a tense or bulging fontanelle, a high-pitched or moaning cry and convulsions. 
• Haemophilus influenzae type b meningitis case fatality ratios in industrialised countries are around 5% but may be as high as 40% in developing countries. The risk of sequelae is high and 10–15% of survivors develop severe long-term complications, including cerebral palsy, hydrocephalus, epilepsy, blindness and bilateral sensorineural deafness. A further 15–20% will have less severe long-term sequelae such as partial deafness, behavioural and learning difficulties, and speech and language problems.
• Septicaemia is the second most common presentation, accounting for around a quarter of all confirmed cases of invasive Hib disease, and can affect all ages. 
• Haemophilus influenzae type b is an important cause of respiratory infections in childhood and randomized controlled vaccine probe studies have estimated that Hib is responsible for 21–47% of radiologically confirmed pneumonia in children. There are large variations across populations in the recorded incidence of both Hib pneumonia and meningitis, and one large study from the island of Lombok in Indonesia failed to show any protection against pneumonia from the conjugate Hib vaccine. 
• Epiglottitis is a life-threatening medical emergency; the result of an infection of the epiglottis and surrounding tissues that interferes with airflow. The peak incidence is in the 5–10 year age group. Patients typically present acutely with a short history of high fever, tachypnoea, inspiratory stridor and excessive drooling. Intubation and sometimes an emergency tracheotomy may be required to prevent airway obstruction and death.
• Other, less common, clinical manifestations of invasive Hib disease include cellulitis, septic arthritis, osteomyelitis, and pericarditis.

Epidemiology

• Haemophilus influenzae type b is responsible for 95% of all invasive H. influenzae infections in unimmunised populations and it is an important cause of severe and sometimes fatal infections, particularly in young children.
• Routine immunisation has resulted in a remarkable decline in serious Hib disease and has practically eliminated Hib meningitis among vaccinated infants and young children.
• The World Health Organization estimates that Hib causes three million episodes of serious disease and 400 000 deaths annually worldwide. Most cases are among unimmunised children and in economically developing countries.
• Age is an important risk factor for invasive Hib infections, and children younger than five years of age are at highest risk of Hib disease in unimmunised populations. Two-thirds of cases occur in children younger than two years of age and the peak incidence is at 10–12 months.
• In the pre-vaccine era, the combined annual average incidence of invasive Hib disease in children younger than five years of age was estimated at 40 per 100 000 population for Asia, 41 per 100 000 population for Europe, 60 pre 100 000 population for Latin America and 88 per 100 000 for the US. However, there was wide inter-population variation within the different regions.
• Ethnicity is a risk factor for certain populations: American Indians, Inuits, black Africans, Melanesians and African Americans are at increased risk of invasive Hib infections. Whether this is due to truly biological differences or other factors is not clear. 
• Medical conditions resulting in immunosuppression increase the risk of Hib infection. Hemoglobinopathies, asplenia, antibody deficiency, malignancies and HIV infection are all associated with increased incidence rates of invasive Hib disease.
• Breastfeeding is protective against Hib in children younger than six months of age and breast milk has been shown to contain secretory antibodies to the Hib PRP capsule.
• Other risk factors for invasive Hib disease in children include low socio-economic status, large household size and crowding. Daycare attendance has been associated with increased risk of invasive Hib disease in children younger than two years of age. 
• Childhood Hib immunization results in herd protection. Immunisation reduces oro-pharyngeal Hib carriage in immunized children thereby reducing exposure to and transmission of Hib to unimmunised individuals. 
• Information on the incidence of invasive Hib disease in Europe has been collated since 1999 by the European Union Invasive Bacterial Infections Surveillance (EU-IBIS) which, since 2007 is coordinated by ECDC. The data is presented in ECDC’s Annual Epidemiological Report on Communicable Diseases in Europe and available  here.
• There is no evidence that non type b strains have replaced Hib as a cause of invasive infections following mass Hib conjugate vaccination.

Transmission

• The incubation period is not known; however, susceptible individuals usually develop disease within seven days of exposure to Hib. 
• Carriers of Hib are infectious as long as organisms are present in the nasopharynx, which may be for a prolonged period even without nasal discharge. 
• Transmission from person to person occurs through respiratory droplets, but infection may also be acquired through contact with infected respiratory discharges. 
• In the pre-vaccine era, children younger than five years of age were the primary reservoirs of Hib, with nasopharyngeal colonisation rates of 3–9%. 
• The Hib conjugate vaccine is highly effective in eradicating asymptomatic Hib carriage and, in countries that routinely immunise against Hib in infancy, vaccinated children are rarely colonised. 
• Older children and adults are more likely to harbour the organism and may act as a primary reservoir for transmission of Hib to susceptible individuals. 
• Observational studies in the pre-vaccine era reported that household and daycare contacts of a case of invasive Hib disease were at a significantly increased risk of developing the infection compared with the general population. The groups at risk, however, were primarily children younger than five years of age and immunocompromised individuals.
• Secondary attack rates appear to be lower for daycare contacts than for household contacts. 
• Humans are the only known reservoirs for Hib.

Prevention

• Immunisation is the only public health intervention capable of preventing the majority serious Hib disease. 
• The Hib conjugate vaccine, which consists of the polyribosylribitol phosphate (PRP) polysaccharide from the Hib capsule conjugated to a protein carrier, prevents invasive Hib disease and reduces naso-pharyngeal carriage. 
• The World Health Organization recommends that Hib conjugate vaccine should be included in all routine childhood immunisation programs with a three-dose primary series given at the same time as diphtheria, tetanus and pertussis vaccines. A booster in the second year of life increases protection. 
• A single dose is sufficient in children older than 12 months of age who have not received their primary Hib immunisation in infancy. 
• Most but not all European countries have included Hib conjugate vaccine in their routine childhood immunisation programmes. The national immunization schedules can be found here.
• Household contacts of a case of invasive Hib have an increased risk of disease.  Children under 4 years of age and individuals with increased risk of Hib infection should receive chemoprophylaxis with rifampicin.  Unimmunized children should be vaccinated Hib conjugate vaccine. 
• Children treated for invasive Hib disease should have their Hib antibody levels checked after recovering and receive immunization as needed. If testing of Hib immunity is not an option, children below two years of age should be immunized following an episode of invasive Hib disease.
• National guidelines should be consulted for the management of cases and contacts of invasive Hib disease. Other useful references are the Immunisation against infectious diseases – The Green Book National Health Service UK and ‘The Red Book’ published by the American Academy of Pediatrics. 
• Patients treated with intravenous antibiotics effective against Hib are no longer infectious after 24 hours.
• Families of children attending the same pre-school or primary school as a patient with invasive Hib should be advised to seek medical advice if their child becomes unwell.
• In case of an outbreak (two or more cases of Hib disease within 120 days) in a pre-school or primary school, chemoprophylaxis should be offered to all room contacts, including staff. All unimmunised and partially immunised children should complete their primary immunisation.

Management and treatment

• Third generation intravenous cephalosporins, including cefotaxime and ceftriaxone, are the empiric treatment of choice for suspected invasive bacterial infections and are highly effective against Hib. 
• The adjuvant dexamethasone, especially if given before or with the first dose of antibiotic, will reduce the risk of long-term sequelae in patients with Hib meningitis. 
• Ampicillin alone should not be used for suspected invasive bacterial infections due to the high levels of resistance.

Note: The information contained in this fact sheet is intended for the purpose of general information and should not be used as a substitute for the individual expertise and judgement of healthcare professionals.

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