Immunological determinants of the high burden of infections among Indigenous patients with end-stage renal disease in Northern Ontario
Chronic Care and Patient-Centred Care
Haemophilus A is an emerging pathogen in Indigenous populations in Northwest Ontario and elsewhere. This study examines of immunity in indigenous communities and provides an example of the kind of collaborative community engagement needed to conduct such a study.
In the post-Haemophilus influenzae type b (Hib) vaccine era, non-type b serotypes have emerged as significant etiological agents of invasive H. influenzae disease. Although invasive H. influenzae type a (Hia) disease is rare in general, some North American Indigenous populations suffer from disproportionately high rates of Hia infection. Importantly, nearly all adult cases involve patients suffering from a secondary immunodeficiency due to an underlying condition such as end-stage renal disease (ESRD).
Our goal was to determine whether an increased burden of invasive Hia infection in the Indigenous population of Northwestern Ontario is related to a decreased natural immunity to the pathogen in one group of immunocompromised patients, i.e. ESRD patients undergoing haemodialysis.
This study has involved engagement of Indigenous communities, including Kenora Metis Council, Asubpeeschoseewagong First Nation, Northwest Angle #37 First Nation, Wauzhushk Onigum First Nation, Saugeen First Nation, and others, i.e. travel to communities, meetings with community leaders and members, and presentations. Successful collaboration was developed with Meno Ya Win Health Centre to collect clinical isolates of H. influenzae for serotyping and characterization; and with Waasegiizhig Nanaandawe’Iyewigamig Health Access Centre for analysis of Hia seroprevalence.
The natural immunity of Indigenous and non-Indigenous ESRD patients was assessed by measuring the quantity of anti-Hia IgG and IgM via ELISA, and the functional activity of antibodies via a serum bactericidal assay (SBA) in over 200 participants. Unexpectedly, Indigenous patients had significantly higher anti-Hia functional antibody activity compared to non-Indigenous patients. Study of a large group of healthy individuals indicated that Indigenous adults had higher parameters of SBA and IgM antibody against Hia capsular polysaccharide compared to non-Indigenous ones.
Our results indicate that a high rate of Hia circulation within Indigenous communities rather than an inadequate response to Hia polysaccharide antigens is a major factor contributing to the elevated rates of invasive Hia infection. Our research has a major impact on the development of a new vaccine against Hia targeting Indigenous people that is underway as a joint initiative of the NRC, NML, and NOSM.