Haemophilus Disease in Alaskan and Canadian Children

Reply: We thank Dr. Bruce et al for their interest in our recent report of the epidemiology of pertussis and invasive Haemophilusinfluenzae type b (Hib) disease among Canadian children.1 They correctly point out that the denominators used for calculating incidence rates of invasive Hib disease among Canadian and Alaskan children were the total native populations in the respective regions. As we did not have access to census data for Canadian Aboriginal children <5 years of age, we instead used publically available census data for the respective native populations. Dr. Bruce et al estimate that approximately 10% of both the Canadian and Alaskan native populations consist of children <5 years of age. Therefore, the rates we published were underestimated by the same factor for each population and the relative comparison between groups is unchanged (ie, the rates of invasive Hib disease among children <5 years of age during the specified years of surveillance were essentially equivalent for Canadian Aboriginal children immunized with diphtheria, tetanus, pertussis, inactivated poliovirus, Hib [DTaP-IPV/Hib] vaccine and Alaska native children immunized with polyribosylribitol phosphate-meningococcal outer membrane protein complex [PRP-OMP] vaccine). As indicated in our publication,1 to provide the most appropriate comparison of the 2 Hib-containing vaccines in the respective native populations, we analyzed data for invasive Hib disease among Canadian Aboriginal children exclusively given DTaP-IPV/Hib vaccine during 2000 to 2004 and among Alaska native children exclusively given PRP-OMP vaccine during 2002 to 2006. For the Canadian population, 2004 was the most recent year for which we had access to epidemiologic data; for the Alaskan population, 2006 was the most recent year. We analyzed epidemiologic data for Alaskan children beginning in 2002 because, before such time, a sequential schedule was used: first dose of PRP-OMP vaccine followed by subsequent doses of Hib oligosaccharide conjugate HbOC vaccine. Given that these factors limited our analysis of Alaska native data to a 5-year interval, we similarly analyzed Canadian Aboriginal data for a 5-year interval. The data provided by Dr. Bruce of 11 cases among Canadian Aboriginal children during 2001 to 2007 are intriguing; these data must not have been available when he reviewed our draft manuscript. As explained in the publication,1 our conclusion that DTaP-IPV/Hib vaccine is “expected to provide the same level of protection in the United States as experienced with this combination vaccine in Canada, and as currently experienced in the United States with separate vaccines” is based on similar epidemiologic patterns of pertussis and invasive Hib diseases, similar immunization schedules, and similar vaccination coverage rates in the 2 countries, and similar responses to the pertussis and Hib components compared with administration of separate vaccines. This was a general conclusion not specific to any particular subpopulation in either country. Comparative effectiveness of 2 vaccines in a specific population ideally should be evaluated in a randomized, double blind, controlled clinical trial. Such a study of Hib-containing vaccines is not feasible among Alaska natives because of the very low rate of invasive disease among the vaccinated target population. As a surrogate, we were able to analyze population-based epidemiologic data among similar high-risk children given different Hib-containing vaccines through routine immunization practices. For the reasons expressed by Bruce et al, we fully support recommendations of the Indian Health Service and American Academy of Pediatrics to administer a first dose of PRP-OMP vaccine to Alaska native and American Indian children.2 It is interesting to note that the distribution of Hib vaccine failures among high risk native children (Table 1 of our publication)1 is consistent with the expected kinetic antibody responses to the 2 different Hib-containing vaccines, as described in multiple studies conducted more than 15 years ago. For example, these studies demonstrated only modest antibody responses to the first 2 doses of polysaccharide tetanus conjugate (PRP-T) vaccine administered at 2 and 4 months of age, but very high antibody titers after the third dose administered at 6 months of age.3–5 Among the 4 Canadian Aboriginal children <5 years of age with invasive Hib disease during 2000 to 2004, 3 were <4 months of age at the time of disease onset. One of these children was unvaccinated but the other 2 children developed disease at a very young age, likely because DTaP-IPV/Hib vaccine failed to induce high enough antibody titers after the first 1 or 2 doses. However, at older ages when Canadian children are expected to have received 3 or 4 doses of DTaP-IPV/Hib vaccine, only 1 breakthrough case was reported. In multiple publications, Scheifele et al have reported a similar pattern of Hib epidemiology for all Canadian children <5 years of age, most recently updated in 2008.6 In contrast, previous studies demonstrated a robust antibody response to the first dose of PRP-OMP vaccine, although a full infant series and booster dose of this vaccine generally did not generate titers as high as those achieved with PRP-T vaccine.3–5,7 Among the 7 Alaska native children <5 years of age with invasive Hib disease during 2002 to 2006, 6 occurred after the complete infant series of 2 doses or after the third booster dose, typically given at 12 to 15 months of age. The patterns of vaccine failures to the 2 vaccines mirror the known antibody kinetic data quite well; vaccine failures are expected at a very young age with PRP-T vaccine and at older ages with PRP-OMP vaccine. David P. Greenberg, MD Scientific and Medical Affairs Sanofi Pasteur Inc Swiftwater, PA Department of Pediatrics University of Pittsburgh School of Medicine Pittsburgh, PA Martha Doemland, PhD Scientific and Medical Affairs Sanofi Pasteur Inc Swiftwater, PA Julie A. Bettinger, PhD, MPH Vaccine Evaluation Center BC Children's Hospital University of British Columbia Vancouver, BC Scott A. Halperin, MD Clinical Trials Research Center IWK Health Center Dalhousie University Halifax, Nova Scotia Valerie Waters, MD Division of Infectious Diseases Hospital for Sick Children Toronto, ON Kami Kandola, MD, MPH Stanton Territorial Health Authority Yellowknife, NT

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