Immunogenicity and safety of the 13-valent pneumococcal conjugate vaccine in 23-valent pneumococcal polysaccharide vaccine-naïve and previously immunized adult patients with severe chronic kidney disease.

Individuals with chronic kidney disease (CKD) are at high risk of pneumococcal infections and recommended to receive the 23-valent pneumococcal polysaccharide vaccine (PPV23). Although the 13-valent pneumococcal conjugate vaccine (PCV13) has been found to have higher immunogenicity compared to PPV23 in adults with some immunocompromising conditions, previous PPV23 immunization may decrease the immunogenicity of PCV13. We assessed immunogenicity and safety of PCV13 in 74 PPV23-naïve and 58 previously PPV23-immunized (>1 year ago) patients with severe (stage 4-5) CKD. Serum IgG, IgM, and IgA specific to seven serotypes, i.e. 3, 6B, 9V, 14, 19A, 19F, 23F were quantified pre- and 4 weeks and one year post-immunization. Baseline concentrations for most serotype-specific IgG and IgM, and serotype 3-specific IgA were higher in previously PPV23-immunized compared to PPV23-naïve patients. Immunization with PCV13 significantly increased almost all serotype-specific IgG, all IgA and some IgM; an increase in some serotype-specific IgG and IgM lasted for one year. Fold increases in antibody concentrations and the proportion of individuals with >2-fold increase post-immunization were generally larger in PPV23-naïve than previously immunized patients for most serotype-specific IgG and some IgA. The data show that in patients with CKD who received previous PPV23 immunization over one year ago, the antibody response to PCV13 was inferior compared to pneumococcal vaccine naïve study participants. In both groups, the lowest response to PCV13 was found for serotype 3. Patients of Indigenous ethnic background demonstrated a superior immune response to PCV13 compared to the non-Indigenous counterpart that could partially be related to Indigenous study participants' younger age. Although we found that previous PPV23 immunization could contribute to the more frequent occurrence of systemic adverse events post PCV13 immunization, those did not exceed the mild to moderate range.

Characterization of natural bactericidal antibody against Haemophilus influenzae type a in Canadian First Nations: A Canadian Immunization Research Network (CIRN) Clinical Trials Network (CTN) study.

During the last two decades, Haemophilus influenzae serotype a (Hia) emerged as an important cause of invasive disease in Canadian First Nations and Inuit, and Alaskan Native populations, with the highest rates reported in young children. Immunocompetent adults, in contrast to children, do not typically develop invasive Hia disease. To clarify factors responsible for an increased burden of invasive Hia disease in certain population groups we studied serum bactericidal activity (SBA) against Hia and quantified IgG and IgM specific to Hia capsular polysaccharide in healthy adult members of two First Nations communities: 1) with reported cases of invasive Hia disease (Northern Ontario, NO), and 2) without reported cases (Southern Ontario, SO), in comparison to non-First Nations living in proximity to the NO First Nations community, and non-First Nations elderly non-frail Canadians from across the country (total of 110 First Nations and 76 non-First Nations). To elucidate the specificity of bactericidal antibodies, sera were absorbed with various Hia antigens. Naturally acquired SBA against Hia was detected at higher rates in First Nations (NO, 80%; SO, 96%) than non-First Nations elderly Canadians (64%); the SBA titres in First Nations were higher than in non-First Nations elderly Canadians (P<0.001) and NO non-First Nations adults (P>0.05). Among First Nations, SBA was mediated predominantly by IgM, and by both antibodies specific to Hia capsular polysaccharide and lipooligosaccharide. CONCLUSIONS: The SBA against Hia is frequently present in sera of First Nations adults regardless of the burden of Hia disease observed in their community; it may represent part of the natural antibody repertoire, which is potentially formed in this population under the influence of certain epigenetic factors. Although the nature of these antibodies deserves further studies to understand their origin, the data suggest that they may represent important protective mechanism against invasive Hia disease.

Naturally acquired antibodies against Haemophilus influenzae type a in Aboriginal adults, Canada.

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.

Transforming health professional education through social accountability: Canada's Northern Ontario School of Medicine.

BACKGROUND: The Northern Ontario School of Medicine (NOSM) has a social accountability mandate to contribute to improving the health of the people and communities of Northern Ontario. NOSM recruits students from Northern Ontario or similar backgrounds and provides Distributed Community Engaged Learning in over 70 clinical and community settings located in the region, a vast underserved rural part of Canada. METHODS: NOSM and the Centre for Rural and Northern Health Research (CRaNHR) used mixed methods studies to track NOSM medical learners and dietetic interns, and to assess the socioeconomic impact of NOSM. RESULTS: Ninety-one percent of all MD students come from Northern Ontario with substantial inclusion of Aboriginal (7%) and Francophone (22%) students. Sixty-one percent of MD graduates have chosen family practice (predominantly rural) training. The socioeconomic impact of NOSM included new economic activity, more than double the School's budget; enhanced retention and recruitment for the universities and hospital/health services; and a sense of empowerment among community participants attributable in large part to NOSM. DISCUSSION: There are signs that NOSM is successful in graduating health professionals who have the skills and desire to practice in rural/remote communities and that NOSM is having a largely positive socioeconomic impact on Northern Ontario.

Immune response to Haemophilus influenzae type b vaccination in patients with chronic renal failure.

Adult chronic renal failure patients undergoing hemodialysis are at an increased risk of invasive Haemophilus influenzae type b (Hib) disease due to the lack of functionally active anti-Hib antibodies. The pediatric Hib polysaccharide-protein conjugate vaccine is highly immunogenic in these patients and can provide protection against invasive Hib infection for at least 1 year.

Canada's new medical school: The Northern Ontario School of Medicine: social accountability through distributed community engaged learning.

Like many rural regions around the world, Northern Ontario has a chronic shortage of doctors. Recognizing that medical graduates who have grown up in a rural area are more likely to practice in the rural setting, the Government of Ontario, Canada, decided in 2001 to establish a new medical school in the region with a social accountability mandate to contribute to improving the health of the people and communities of Northern Ontario. The Northern Ontario School of Medicine (NOSM) is a joint initiative of Laurentian University and Lakehead University, which are located 700 miles apart. This paper outlines the development and implementation of NOSM, Canada's first new medical school in more than 30 years. NOSM is a rural distributed community-based medical school which actively seeks to recruit students into its MD program who come from Northern Ontario or from similar northern, rural, remote, Aboriginal, Francophone backgrounds. The holistic, cohesive curriculum for the MD program relies heavily on electronic communications to support distributed community engaged learning. In the classroom and in clinical settings, students explore cases from the perspective of physicians in Northern Ontario. Clinical education takes place in a wide range of community and health service settings, so that the students experience the diversity of communities and cultures in Northern Ontario. NOSM graduates will be skilled physicians ready and able to undertake postgraduate training anywhere, but with a special affinity for and comfort with pursuing postgraduate training and clinical practice in Northern Ontario.