Haemophilus influenzae serotype B infection

Overview
Infection with the bacterium Haemophilus influenzae type b (Hib) can result in meningitis and other severe infections (e.g., pneumonia, bacteremia, cellulitis, septic arthritis, and epiglottitis) primarily among infants and children <5 years of age.

Related Key Words and Synonyms:

Hib disease

Epidemiology and Demographics
During 1980-1990, incidence was 40-100/100,000 children < 5 years old in the United States. Due to routine use of the Hib conjugate vaccine since 1990, the incidence of invasive Hib disease has decreased to 1.3/100,000 children. However, Hib remains a major cause of lower respiratory tract infections in infants and children in developing countries where vaccine is not widely used.

Invasive Hib disease is endemic throughout the world. In countries that have achieved high coverage with routine Hib vaccination programs, Hib disease has become rare. In 2004, most countries in Western Europe, South America, and Central America had initiated routine Hib vaccination (http://www.who.int/mediacentre/factsheets/fs294/en/). However, Hib disease remains common in many developing countries and is estimated to cause 2-3 million cases of serious disease in young children annually.

Hib disease is uncommon in anyone 5 years of age or older. Hib meningitis has a case-fatality ratio of 5-10% in the United States even with initiation of early antimicrobial therapy. As a result of the widespread use of conjugate Hib vaccines, the disease is now uncommon in the United States and is seen primarily in infants too young to be vaccinated and unvaccinated children. In 2004, the estimated annual incidence of Hib was 0.15 cases per 100,000 in children younger than 5 years of age.

Trends

Since licensure of conjugate vaccines for infants (1990) and children (1987), rates of disease among children <5 years old have declined by more than 95% in the United States, while rates for adults have remained stable. However, rates of disease among Alaskan natives remain higher than elsewhere in the United States.

Risk Factors
Infants and young children, household contacts, and day-care classmates are at higher tisk of aquiring Haemophilus influenzae serotype B infection.

Risk for travelers

Unvaccinated infants and children aged less than 5 years who travel may be at risk for serious Hib disease, especially if traveling to a country that does not use Hib vaccine. In addition, adults who have been splenectomized have an increased risk of infections.

Pathophysiology & Etiology
Etiologic agent

Haemophilus influenzae serotype b.

Transmission

Direct contact with respiratory droplets from nasopharyngeal carrier or case patient.

Natural History
Haemophilus influenzae, formerly called Pfeiffer's bacillus or Bacillus influenzae, is a non-motile Gram-negative coccobacillus first described in 1892 by Richard Pfeiffer during an influenza pandemic. It is generally aerobic, but can grow as a facultative anaerobe. H. influenzae was mistakenly considered to be the cause of the common flu until 1933, when the viral etiology of the flu became apparent. Still, H. influenzae is responsible for a wide range of clinical diseases.

Because of its small genome, H. influenzae became the first free-living organism with its entire genome sequenced. Its genome consists of 1,830,140 base pairs of DNA and contains 1740 genes. The method used was Whole genome shotgun. The sequencing project, completed and published in Science in 1995, was conducted at The Institute for Genomic Research.

History and Symptoms
Before the availability of the Haemophilus influenzae serotype b (Hib) conjugate vaccine in the United States and other industrialized countries, more than one-half of Hib cases presented as meningitis with fever, headache, and stiff neck. The remainder presented as cellulitis, arthritis, or sepsis. In developing countries, Hib is still a leading cause of bacterial pneumonia deaths in children.

Risk Stratification and Prognosis
3%-6% of cases are fatal; up to 20% of surviving patients have permanent hearing loss or other long-term sequelae.

Treatment
Specific parenteral antibiotic treatment is necessary for invasive Hib disease, and immediate airway stabilization is necessary for epiglottitis. Antibiotic prophylaxis with rifampin is indicated for all household contacts in the following circumstances: households with a contact aged 4 years or younger who is unimmunized or underimmunized, households with a child aged younger than 12 months who has not received the primary series, and households with an immunocompromised child. Chemoprophylaxis is not recommended for pregnant women or for child care contacts with a single index case, but the children’s vaccination history should be reviewed to ensure completion of the recommended schedule of Hib conjugate vaccine. A 4-day course of rifampin eradicates Hib carriage from the pharynx in approximately 95% of carriers.

Primary Prevention
Haemophilus Influenzae Type b (Hib) Vaccine

Future or Investigational Therapies
Challenges

Elimination of persistent Hib disease in the United States. Currently available conjugate vaccines differ in immuno-genicity in very young children and possibly in duration of antibody persistence, raising questions about long-term efficacy (>5 years), optimal use, and schedules. Monitoring the possible emergence of disease due to other serotypes. Problems with serotyping of H. influenzae in state health departments. Development of rapid molecular assays for detection and molecular subtyping of all Hi strains. The cost of Hib conjugate vaccines has limited their use in developing countries even though Hib is a major cause of morbidity and mortality.

Opportunities

Evaluating the characteristics of Hib vaccines associated with prevention of carriage and invasive disease will facilitate application of this technology to development of conjugate vaccines for other organisms with polysaccharide capsules (such as the meningococcus, pneumococcus, and group B streptococcus). Further evaluation of herd immunity effects may lead to insight into vaccination strategies that optimize protection against invasive disease and transmission of Hib organisms.

Acknowledgements
The content on this page was first contributed by: C. Michael Gibson, M.S., M.D.