Haemophilus influenzae-induced acute otitis media. Aspects of virulence and protection in an animal model

Sammanfattning: Acute otitis media (AOM) is the most common illness diagnosed during early childhood. One of the major etiologic agents is Haemophilus influenzae. Apart from AOM, this organism can cause a broad range of infectious diseases such as meningitis, epiglottitis, arthritis, and pneumonia. Despite the importance of H.influenzae, the mechanisms by which this heterogenous group of bacteria mediates the infectious process and how the host responds to them remain poorly defined. In this study an animal model of AOM induced by H.influenzae was established to investigate aspects of virulence and protection. The results showed that encapsulated and nontypeable (NTHi) strains yielded two different clinical courses in the rat. The most severe infections were, as in man, caused by strains that possessed the type b capsule, the most important virulence factor. In addition, there were differences in virulence between NTHi strains. In some strains these differences were possibly associated with the lipopolysaccharide. By developing a chromosomally mediated resistance to beta-lactams the bacterium could increase its power indirectly. Without any significant loss of virulence, the chromosomally altered NTHi could persist at the infectious site during antibiotic treatment and cause long-lasting structural changes in the middle ear. The host responses were dependent on whether the causative strain was encapsulated or not. A resolved H.influenzae type b (Hib) AOM induced a better protection against reinfections than an NTHi AOM, and the Hib infection conferred cross-protection against NTHi strains. A resolved pneumococcal AOM could also cross-protect but not subcutaneous whole cell immunizations, indicating that non-specific and local reactions may have been involved in the cross-protection. Finally, the commercially available conjugated Hib vaccine ACT-HIB® prevented experimental Hib AOM.