Haemophilus influenzae

Haemophilus influenzae is a Gram-negative, non-motile coccobacillus bacterium belonging to the Pasteurellaceae family of pathogens. In its encapsulated form, H. influenzae is relatively small, ranging from 0.2 to 0.8 μm in size, while the unencapsulated strain exhibits a longer, more threadlike morphology (Figure 1). The bacteria is transmitted through close contact with exposed individuals. Infants and young children are most at risk. The name Haemophilus influenzae refers to the bacteria's requirement of blood factors for growth and to its association with viral infections such as influenza.

Figure 1. A Photomicrograph of Haemophilus influenzae as seen using a Gram-stain technique.

H. influenzae is part of the natural flora of the respiratory tract and most children develop immunity. In fact, it is present in the nasopharynx of approximately 75% of healthy children and adults. It is usually the unencapsulated strain that is harbored by the natural flora of the respiratory tract, but a minority of healthy individuals intermittently harbor H. influenzae type-B (HiB), the encapsulated strain, in the upper respiratory tract. A large colony of HiB or a concomitant viral infection can trigger the invasive disease. Diseases from serotype-b H. influenzae are transmitted via direct contact with respiratory droplets from a nasopharyngeal carrier or an infected individual.

H. influenzae has a polysaccharide outer capsule consisting of repeating polymers of riboysl and ribitol phosphate. The presence of this capsular antigen in body fluids is used to diagnose the disease.

Figure 2. A diagram depicting the protective capsule of Haemophilus influenzae.

The H. influenzae is anti-phagocytic. Some strains of H. influenzae have developed a plasmid-mediated resistance to many antibiotics, including ampicillin, the primary therapy for the infection. The bacilli attach to the respiratory epithelium lining the alveoli. They enter the bloodstream by breaking down the tight junctions between the epithelial cells of the capillaries. In addition, the bacteria's outer membrane lipooligosaccharide (LOS) is also believed to participate in inflammation related to otitis media (ear infection). All virulent strains produce neuraminidase and an IgA (immunoglobulin-A) protease, but the function of these extracellular enzymes in invasion is unconfirmed. Fimbriae improve the adherence of the bacteria to human mucosal cells in vitro. They are also necessary for successful colonization of the nasopharynx. The Anton antigen present in red blood cells appears to be the receptor.

Metastatic seeding can lead to bacterial meningitis, pneumonia, and neurological disorders. 5% of invasive infections result in death, while 15% to 30% cause neurological handicaps. In the United States, up to 20% of H. influenzae-induced meningitis-surviving patients have permanent hearing loss. In addition, in children under the age of five, H. influenzae may also cause epiglottis, osteomyelitis, joint infections, ear infections, and sinusitis. HiB could also cause purulent pericarditis and endocarditis.

In order to protect oneself from this pathogen, a purified surface antigen vaccine is required for immunization. The H. influenzae capsular polysacchardise, unique to the type b strain, gives anti-phagocytic protection to the pathogen and contributes to the virulence of the disease.

The polyribosylribitol phosphate (PRP) polysaccharide vaccine was introduced in 1985. The polysaccharide alone was poorly immunogenic in young children and led to the development of the PRP-protein conjugate vaccines. The diphtheria toxoid is used as the protein moiety. Other conjugate preparations are more effective in infant immunization, such as the oligosaccharide-diphtheria variant conjugate, the PRP-Neisseria meningitidis outer membrane protein conjugate , and the PRP-tetanus toxoid conjugate. These vaccines are very effective and have few side effects.

References:

Pier, G.B., Lyczak, J.B., & Wetzler, L.M. (2004). Immunology, Infection, and Immunity. Washington: ASM Press.