Haemophilus influenzae Type b

Geographic Distribution and Disease Burden

Haemophilus influenzae is a pleomorphic, gram-negative coccobacillary human pathogen that can be transmitted person to person via respiratory droplets. It is the causative agent for a wide range of infections whose severity is related to the presence or lack of a bacterial capsule. Encapsulated (typeable) strains of H. influenzae account for the vast majority of invasive disease, with Hib being the predominant serotype, especially in children younger than 5 years of age. Before widespread availability of conjugate vaccine in 1991, Hib was a leading cause of bacterial meningitis, occult bacteremia, epiglottitis, pneumonia, empyema, cellulitis, septic arthritis, and pericarditis. Invasive Hib infections occurred in 1 in 200 children in the United States during the first 5 years of life. This incidence has dramatically declined to approximately 1 per 100,000 over the past 15 years, reflecting the success of Hib conjugate immunization. Among all age groups in the United States, nontypeable H. influenzae currently causes the majority of invasive H. influenzae disease. In 2012, the World Health Organization (WHO) estimated that Hib was the cause of 2% of child deaths younger than 5 years of age due to all causes. As of 2018, the WHO estimated the global vaccination coverage with three doses of Hib vaccine to be 72%.

Risk Factors

Antibodies against the Hib polysaccharide capsule, polyribosylribitol phosphate (PRP), are protective against invasive disease. Young age is a primary risk factor, with infants 6 to 18 months of age having the greatest risk for invasive Hib disease because of their paucity of PRP antibodies. Infants younger than 6 months of age likely have some protection from passively acquired maternal antibodies. Underlying conditions such as human immunodeficiency virus (HIV), sickle cell anemia, functional asplenia, antibody or complement deficiency syndromes, and malignancy are also risk factors for Hib disease. Environmental exposures such as crowding, household size, daycare attendance, low family income, and low parental education level are also risk factors. Conversely, breastfeeding has been demonstrated to be protective against invasive Hib disease. In the prevaccine era, Hib invasive disease was rare in children older than the age of 5 years, primarily related to antibody acquisition from natural exposure to the organism.

Significantly increased risk of invasive Hib disease has been reported in indigenous populations, including Australian Aboriginal children, Native Alaskan Eskimos, Native Americans, and Canadian First Nations children. These population differences potentially relate to a variety of factors, including early exposure, crowding, microbiologic differences in the circulating strains, socioeconomic factors, and possibly genetics. In adults, underlying conditions such as chronic obstructive pulmonary disease, smoking, HIV infection, alcoholism, pregnancy, splenectomy or functional asplenia, and malignancy increase the risk of invasive Hib disease.

Clinical Features

Although Hib can cause a variety of respiratory tract infections, in the prevaccine era it was notorious for causing significant invasive disease in infants and young children and may occur simultaneously at multiple sites. Although these infections are currently rare in immunized populations, practitioners should be familiar with their clinical manifestations because of possible resurgence of disease related to vaccine shortages and the potential for caring for unimmunized children, either due to vaccine refusal or coming from areas of the world without access to Hib vaccines. The following features are described as classically seen in the prevaccine era.

Epiglottitis

Classically, epiglottitis from Hib occurs in older children, 2 to 7 years of age. Signs may begin with abrupt onset of high fever and drooling, with rapid progression to significant respiratory distress with children assuming a tripod position (sitting leaning forward, with mouth open and tongue and jaw protruding) ( Fig. 4.1 ) to allow air entry. Approximately 70% to 90% of patients with epiglottitis have positive blood cultures. The mortality rate is 5% to 10%, and death is usually related to abrupt airway obstruction. Children in respiratory distress exhibiting the tripod position should not have their oropharynx examined without the presence of suitable personnel and equipment for rapid intubation. In children younger than 2 years of age, Hib epiglottitis typically has a rapid onset and progression leading to severe blockage of the airway.