Haemophilus Disease in Alaskan and Canadian Children

To the Editors: The recent report by Greenberg, et al.1 on invasive Haemophilusinfluenzae type b (Hib) disease in Canada raises several interesting points concerning Canadian Aboriginal and Alaska Native populations, both of which share a tendency toward very high invasive Hib rates. We are concerned about a possible misinterpretation of the data presented and a conclusion related to vaccine use in high-risk populations. On page 526, lines 8 to 10, the authors state “The rates of invasive Hib disease were similar among the Canadian Aboriginal population (0.8 cases per 100,000 per year) and Alaska Native population (1.0 cases per 100,000 per year).” Several aspects of this calculation and associated comparison of rates appear flawed. First, to calculate the quoted rates, the authors divided the number of cases in children less than 5 years of age in each population by the total number of people of all ages in that population (Table 1). The result is expressed as “cases/100,000 per year” but they have actually calculated “cases of disease in children less than 5 years of age per 100,000 persons of all ages per year.” Such rates are usually expressed by matching the numerator and denominator to the same age group. The author's nonstandard rate calculation does not provide the actual rate of Hib disease in this population. Since the proportion of children <5 in each of these populations is about 10%, the actual rate of Hib disease in children less than 5 is about 10 times higher than stated in this sentence. Secondly, the authors compared rates in Northern Canadian Aboriginal children from 2000 to 2004 with those in Alaska Native children from 2002 to 2006. Thus, in only 3 of the 7 years evaluated in the study both sites can be directly compared. A review of data from the International Circumpolar Surveillance (ICS) network showed 11 cases of invasive Hib disease in Northern Canadian Aboriginal children <5 years of age and 6 in Alaska Native children <5 years of age during the period 2001–2007, with rates of 17.0 and 6.0 cases/100,000 per year, respectively. These rates are not only much higher than the rates noted by the authors, but substantially higher than rates in children in the rest of Canada and the United States. On page 527, in the last sentence of the manuscript, the authors write “... 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.” This conclusion is problematic for 2 reasons. First, any presumption of equivalency of vaccines for specific high-risk populations, in the absence of clinical trials in that population, must be interpreted with caution. Readers may interpret Greenberg, et al.'s conclusion to mean that DTap-IPV/Hib (PRP-T) vaccine will provide the same level of protection for Alaska Native and American Indian children as the currently used PRP-OMP vaccine, which is likely to be incorrect. With use of the PRP-OMP vaccine, rates of invasive Hib disease in Alaska Native children–which were 6 to 10 times higher than in other US children–declined dramatically.2 Based on the high risk of invasive Hib disease within the first 6 months of life in Alaska Native and American Indian children, the Indian Health Service and the American Academy of Pediatrics recommend that the first dose of Hib conjugate vaccine contain PRP-OMP (single antigen vaccine or combination vaccine with other antigens).3 Administration of the first dose of PRP-OMP vaccine leads to more rapid development of protective antibody levels than HbOC or PRP-T vaccines4 which require 2 to 3 doses to achieve protective antibody levels in most children. During the mid 1990s, Alaska Native children began receiving HbOC instead of PRP-OMP, and experienced excess cases of Hib disease until the program switched back to PRP-OMP.2 The experience in Alaska demonstrates that the early protection offered by PRP-OMP vaccine is important in indigenous populations who experience early onset of Hib disease. Second, although DTap-IPV/Hib (PRP-T) vaccine has dramatically decreased Hib disease in Canadian populations, the rates of invasive Hib disease are actually higher in Northern Canadian Aboriginal children <5 than in Alaska Native children of the same age (as demonstrated above). Among Indigenous children <1 year of age (where impact of early seroconversion is most important), ICS data from 2001 to 2007 demonstrate rates of 71/100,000 in Northern Canada and 14/100,000 in Alaska (P < 0.008). Given the high risk of disease in young Aboriginal children, there may be a benefit in Northern Canadian jurisdictions to using a vaccine with properties similar to PRP-OMP for First Nations and Inuit children. This approach has also been used in Australia5 and New Zealand.6 Michael Bruce, MD, MPH Centers for Disease Control and Prevention Anchorage, Alaska Rosalyn Singleton, MD, MPH Alaska Native Medical Center Anchorage, Alaska Marcus Lem, MD, MHSc First Nations and Inunit Health Vancouver, British Columbia Tammy Zulz, MPH Jay Wenger, MD Thomas Hennessy, MD, MPH Centers for Disease Control and Prevention Anchorage, Alaska