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Ahead of Print -Naturally Acquired Antibodies against Haemophilus influenzae Type a in Aboriginal Adults, Canada - Volume 21, Number 2—February 2015 - Emerging Infectious Disease journal - CDC

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Ahead of Print -Naturally Acquired Antibodies against Haemophilus influenzae Type a in Aboriginal Adults, Canada - Volume 21, Number 2—February 2015 - Emerging Infectious Disease journal - CDC

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Volume 21, Number 2—February 2015


Naturally Acquired Antibodies against Haemophilus influenzae Type a in Aboriginal Adults, Canada

Eli B. Nix, Kylie Williams, Andrew D. Cox, Frank St. Michael, Sandra Romero-Steiner, Daniel S. Schmidt, William G. McCready, and Marina UlanovaComments to Author 
Author affiliations: Northern Ontario School of Medicine, Thunder Bay, Ontario, Canada (E.-B. Nix, K.Williams, W.G. McCready, M. Ulanova)National Research Council, Ottawa, Ontario (A.-D. Cox, F. St. Michael)Centers for Disease Control and Prevention, Atlanta, Georgia, USA (S. Romero-Steiner, D.S. Schmidt)


In the post-Haemophilus influenzae type b (Hib) vaccine era that began in the 1980's, H. influenzae type a (Hia) emerged as a prominent cause of invasive disease in North American Aboriginal populations. To test whether a lack of naturally acquired antibodies may underlie increased rates of invasive Hia disease, we compared serum bactericidal activity against Hia and Hib and IgG and IgM against capsular polysaccharide between Canadian Aboriginal and non-Aboriginal healthy and immunocompromised adults. Both healthy and immunocompromised Aboriginal adults exhibited significantly higher bactericidal antibody titers against Hia than did non-Aboriginal adults (p = 0.042 and 0.045 respectively), with no difference in functional antibody activity against Hib. IgM concentrations against Hia were higher than IgG in most study groups; the inverse was true for antibody concentrations against Hib. Our results indicate that Aboriginal adults possess substantial serum bactericidal activity against Hia that is mostly due to IgM antibodies. The presence of sustained IgM against Hia suggests recent Hia exposure.
Haemophilus influenzae is a human-restricted gram-negative bacterial pathogen that causes serious infectious diseases, including meningitis, sepsis, and pneumonia. Some strains express a polysaccharide capsule, a principal virulence factor that protects bacteria from immune defenses, e.g., complement-dependent bacteriolysis. On the basis of the chemical structure of the capsular polysaccharides, H. influenzae are divided into 6 serotypes (a, b, c, d, e, and f), and unencapsulated strains lacking the cap gene are referred to as nontypeable (1). H. influenzae type b (Hib) is the most virulent serotype; H. influenzae type a (Hia) is the second most virulent (2). Before the development of Hib conjugate vaccines in the 1980s, Hib was a major cause of pediatric meningitis (3). Hib conjugate vaccines induce production of antibodies against capsular polysaccharide capable of bactericidal activity providing protection against invasive disease (46). Rates of invasive Hib disease have been reduced by >90% in all countries where Hib vaccination programs have been introduced (reviewed in [7,8]).
Vaccination against Hib does not offer protection against other H. influenzae serotypes; in the post-Hib vaccine era, non–type b strains have become important in the etiology of invasive H. influenzae disease (reviewed by [7]). The course and severity of invasive Hia disease closely resemble the conditions caused by Hib (9).
Although invasive Hia disease is rare in most of the world, it is prevalent in specific geographic areas including Northern and Western Canada, Alaska, and the southwestern United States; furthermore, the burden of disease falls almost exclusively on Indigenous peoples living within these regions (1012). In the region of this study (Northern Ontario), invasive Hia disease was reported at rates of 7/100,000 in 2004–2008 and between 7.7–23.2/100,000 among children <5 years of age during 2002–2008 (13,14). Recent analysis of invasive H. influenzae disease, including Hia, in a population of Canada that included a large proportion of Aboriginal persons found that 54% of adult case-patients had some serious underlying medical conditions, such as chronic renal failure (CRF) (13). We hypothesized that a lack of naturally acquired antibodies against Hia may contribute to the higher rates of invasive Hia disease in this regional population. To test this hypothesis, we measured concentration of serum IgG and IgM against capsular polysaccharide and functional antibody activity against both Hia and Hib in healthy adults and patients of Aboriginal background with confirmed CRF. Measured antibodies in Aboriginal persons were compared to those present in serum samples from non-Aboriginal persons residing in the same region.
Dr. Nix is a postdoctoral fellow at the Northern Ontario School of Medicine, Thunder Bay, Ontario, Canada. His primary research interests are the immunology of invasive bacterial infections and Aboriginal health.


We thank the study volunteers and Joanne Robin, Bonnie Cava, and Kanita Johnson as well as the rest of the staff of Thunder Bay Regional Health Sciences Centre Renal unit. We thank Raymond Tsang (National Microbiology Laboratory, Winnipeg, Manitoba) for donating Hia and Hib strains, and Donna Newhouse (NOSM, Thunder Bay) for drawing blood samples.
This study was supported by the Northern Ontario Academic Medicine Association and the Canadian Institutes of Health Research post-doctoral fellowship awarded to E.B.N.


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Suggested citation for this article: Nix EB, Williams K, Cox AD, St Michael F, Romero-Steiner S, Schmidt DS. Naturally acquired antibodies againstHaemophilus influenzae type a in Aboriginal adults, Canada. Emerg Infect Dis. 2015 Feb [date cited]. http://dx.doi.org/10.3201/eid2102.140722
DOI: 10.3201/eid2102.140722

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