Haemophilus influenzae

Overview
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.

Serotypes
In 1930, 2 major categories of H. influenzae were defined: the unencapsulated strains and the encapsulated strains. The pathogenesis of H. influenzae infections is not completely understood, although the presence of the encapsulated type b (Hib) is known to be the major factor in virulence. Their capsule allows them to resist phagocytosis and complement-mediated lysis in the non-immune host. Unencapsulated strains are less invasive, but they are able to induce an inflammatory response that causes disease, such as epiglottitis. Vaccination with Hib conjugate vaccines is effective in preventing infection, and several vaccines are now available for routine use.

Diseases
Most strains of H. influenzae are opportunistic pathogens - that is, they usually live in their host without causing disease, but cause problems only when other factors (such as a viral infection or reduced immune function) create an opportunity. There are six generally recognized types of H. influenzae: a, b, c, d, e, and f.

Naturally-acquired disease caused by H. influenzae seems to occur in humans only. In infants and young children, H. influenzae type b (Hib) causes bacteremia, and acute bacterial meningitis. Occasionally, it causes cellulitis, osteomyelitis, epiglottitis, and joint infections. Due to routine use of the Hib conjugate vaccine in the U.S. 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. Unencapsulated H. influenzae (non-B type) causes ear (otitis media) and eye (conjunctivitis) infections and sinusitis in children, and is associated with pneumonia.

Interaction with Streptococcus pneumoniae
Both H. influenzae and S. pneumoniae can be found in the upper respiratory system of humans. A study of competition in a laboratory revealed that, in a petri dish, S. pneumoniae always overpowered H. influenzae by attacking it with a hydrogen peroxide and stripping off the surface molecules H. influenzae needs for survival.

When both bacteria are placed together into a nasal cavity, within 2 weeks, only H. influenzae survives. When both are placed separately into a nasal cavity, each one survives. Upon examining the upper respiratory tissue from mice exposed to both bacteria species, an extraordinarily large number of neutrophils immune cells were found. In mice exposed to only one bacteria, the cells were not present.

Lab tests showed that neutrophils exposed to dead H. influenzae were more aggressive in attacking S. pneumoniae than unexposed neutrophils. Exposure to dead H. influenzae had no effect on live H. influenzae.

Two scenarios may be responsible for this response:


 * 1) When H. influenzae is attacked by S. pneumoniae, it signals the immune system to attack the S. pneumoniae
 * 2) The combination of the two species together triggers an immune system response that is not set off by either species individually.

It is unclear why H. influenzae is not affected by the immune response.