Until recently, the significance of invasive disease caused by Haemophilus influenzae serotype a (Hia), in contrast to H. influenzae serotype b (Hib), has been largely underestimated. However, during the last decade, Hia was recognized as an important pathogen causing severe infections in young children with a high case-fatality rate comparable to Hib disease before the introduction of pediatric immunization against this infection. Remarkably, the highest incidence rates of invasive Hia disease have been found in some indigenous populations, such as North American Indians and Inuit of Alaska and Northern Canada, reaching the order of magnitude of the incidence rates of Hib in the pre-Hib vaccine era. The reasons for an increased susceptibility to Hia infection among some specific populations groups are unknown. The goal of this paper is to summarize the current knowledge on Hia global epidemiology and to discuss potential prevention of this infection using specific immunization. 1. Introduction Haemophilus influenzae is an important human-restricted Gram-negative bacterial pathogen, which can cause severe invasive disease, such as meningitis, sepsis, and bacteremic pneumonia in susceptible individuals. Some strains of H. influenzae have a polysaccharide capsule representing the major virulence factor and antigen of this bacterial species. On the basis of the antigenic properties, six serotypes of encapsulated H. influenzae are distinguished (a, b, c, d, e, and f), and there are also nonencapsulated or nontypeable H. influenzae (NTHi). Encapsulated strains exhibit a higher ability to cause invasive disease because the capsule prevents complement-mediated bacteriolysis in the absence of opsonizing antibody [1]. Normal individuals can carry H. influenzae in their naso- and oropharynx, and the carriage is considered as the major factor inducing the development of natural immunity against the pathogen, along with exposure to some cross-reactive environmental antigens [2]. The invasive disease mostly affects young children (below 2 years of age), as well as the elderly and immunocompromised individuals. One particular serological variant, H. influenzae serotype b (Hib), was the major cause of bacterial meningitis in young children worldwide before the conjugate Hib vaccine became available in the late 1980s. Pediatric vaccination against Hib has resulted in a dramatic decrease in the incidence rates of invasive Hib disease in all countries where the vaccine has been included in the national immunization programs [3]. However, Hib vaccination does not confer
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