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Clinical Investigation
April 3, 2002

Nontypeable Haemophilus influenzae in Carriage and Disease: A Difference in IgA1 Protease Activity Levels

Author Affiliations

Author Affiliations: Division of Genomic Medicine, Infection and Immunity Group, Royal Hallamshire Hospital, Sheffield, England (Drs Vitovski and Sayers); and Public Health Laboratory, Gwynedd General Hospital, Bangor, Wales (Ms Dunkin and Dr Howard). Dr Howard is currently with the Department of Medical Microbiology and Public Health Laboratory, University Hospital of Wales, Heath Park, Cardiff.

JAMA. 2002;287(13):1699-1705. doi:10.1001/jama.287.13.1699

Context Nontypeable Haemophilus influenzae strains form part of the normal flora of the human upper respiratory tract but are also implicated in a wide range of diseases. Infections caused by nontypeable H influenzae are major health and socioeconomic burdens. No single bacterial trait has been associated with disease as opposed to colonization.

Objectives To compare IgA1 protease activity in nontypeable H influenzae strains isolated from patients with symptomatic Haemophilus infection (sputum, cerebrospinal fluid, blood, or normally sterile tissue) vs strains from throat swabs of asymptomatic carriers and to compare iga gene carriage and variability in nontypeable H influenzae strains.

Design and Setting Retrospective study of 63 strains (44 clinical and 19 carriage) collected between 1991 and 2000 and maintained at the Public Health Laboratory, Gwynedd General Hospital, Bangor, Wales.

Main Outcome Measures Levels of IgA1 protease activity produced by carriage strains and clinical isolates from symptomatic patients; the determination of the size and sequence of a variable region of the iga gene.

Results Bacterial IgA1 protease activity was significantly higher (P<.001) in strains isolated from sputum, blood, cerebrospinal fluid, or normally sterile tissue of symptomatic individuals (median, 155 mU; interquartile range [IQR], 80-220 mU; mean, 169 mU; 95% confidence interval [CI], 126-211 mU) than in those isolated from throat swabs of asymptomatic carriers (median, 30 mU; IQR, 15-90 mU; mean, 56 mU; 95% CI, 26-86 mU; assayed on secretory IgA). The iga gene was detected in 97% of all strains examined. Variations in the sizes and sequences of part of the iga genes were also apparent. This variable region encodes a polypeptide linker connecting the protease domain to the β-core autotranslocator, a porelike structure required for secretion of the protease.

Conclusions These findings reveal the importance of iga gene variability and expression levels in the establishment of disease phenotype. They identify nontypeable H influenzae IgA1 protease as a virulence factor and as a potential target for the development of new strategies to fight these important pathogens.