NONTYPABLE HAEMOPHILUS-INFLUENZAE - PATHOGENESIS AND PREVENTION

In this paper, we describe the ability of nontypeable Haemophilus infl uenzae (NTHi) to coexist with the human host and the devastating resul ts associated with disruption of the delicate state of balanced pathog enesis, resulting in both acute and chronic respiratory tract infectio ns. It has been seen that the strains of NTHi causing disease show a m arked genetic and phenotypic diversity but that changes in the lipooli gosaccharide (LOS) and protein size and antigenicity in chronically in fected individuals indicate that individual strains of NTHi can remain and adapt themselves to avoid expulsion from their infective niche. T he lack of reliance of NTHi on a single mechanism of attachment and it s ability to interact with the host with rapid responses to its enviro nment confirmed the success of this organism as both a colonizer and a pathogen. In vitro experiments on cell and organ cultures, combined w ith otitis media and pulmonary models in chinchillas, mts, and mice, h ave allowed investigations into individual interactions between NTHi a nd the mammalian host. The host-organism interaction appears to be a t wo-way process, with NTHi using cell surface structures to directly in teract with the mammalian host and using secreted proteins and LOS to change the mammalian host in order to pave the way for colonization an d invasion. Many experiments have also noted that immune system evasio n through antigenic variation secretion of enzymes and epithelial cell invasion allowed NTHi to survive for longer periods despite a specifi c immune response being mounted to infection. Several outer membrane p roteins and LOS derivatives are discussed in relation to their efficac y in preventing pulmonary infections and otitis media in animals. Gene ral host responses with respect to age, genetic makeup, and vaccine de livery routes are considered, and a mucosal vaccine strategy is sugges ted.