We ranked the burden of disease associated with infectious pathogens and syndromes in the Canadian province of Ontario, determined that most of the burden was from premature mortality rather than morbidity, observed a number of sex-specific differences, and quantified the burden of syndromes caused by multiple pathogens. Some noteworthy themes among the top ten include pathogens with oncogenic potential (HCV, HBV, HPV), healthcare-associated infections (e.g., C. difficile, S. aureus), microorganisms present in the normal human microbiologic flora (e.g., E. coli, S. aureus), and diseases that are preventable by vaccines (HPV, HBV, S. pneumoniae, influenza virus). Notably absent among the top pathogens are those that have been successfully prevented through routine childhood vaccination (e.g. measles), a testament to the success of such programs.
Our annual estimated burden associated with infectious disease of 729 HALYs per 100,000 population is close to one-quarter of the 3017 HALYs per 100,000 population estimated for all cancers combined in a Canadian study using similar methodology. 
This suggests that infectious diseases still contribute substantially to morbidity and mortality in high-income settings. One caveat for this comparison is that the burden of HPV-related cancers and hepatocellular carcinoma were included in both studies.
Our ranking of infectious pathogens is relatively consistent with a pilot study conducted by the European Centre for Disease Prevention and Control (ECDC) to determine the burden of influenza, measles, HIV, tuberculosis, campylobacterosis, salmonellosis, and enterohaemorrhagic E. coli
in Europe. 
The seven infectious diseases were ranked in a similar order, except for influenza, which was ranked lower in the ECDC study because their primary analysis only considered laboratory-confirmed cases, which dramatically underestimates the burden. 
In contrast to previous studies reporting a slight dominance of the contribution of premature mortality over morbidity for infections, 
we found most of the burden was from premature mortality. This discrepancy relates to methodological differences in calculating ONBOIDS HALYs and GBD DALYs, with the use of more severe disability weights, discounting, age-weighting, and standard life expectancy all impacting the relative contribution of morbidity versus premature mortality. Despite uncertainty regarding which method should be considered the gold standard, it is reassuring that the rankings of these infectious diseases were similar.
The overall burden of infectious diseases was comparable in males and females, with marked differences for certain pathogens. Some differences have clear biological explanations, such as the differential burden of HPV (cervical cancer in females), and E. coli
(anatomical differences resulting in more urinary tract infections in females). The difference for HIV is related to behaviours (i.e., anal intercourse among men who have sex with men and injection drug use, more prevalent among males). 
For HBV and HCV, the differences may be due to a combination of biological and behavioural risk factors. 
The syndrome-based results can guide prioritization of ‘horizontal’ prevention methods that are independent of the causative pathogen (e.g., smoking cessation and hand hygiene as methods of preventing pneumonia). Further work is needed to assess the benefits of possible interventions to prevent each of the syndromes and pathogens. Part of such an analysis could address the possibility of clustering of risk factors including social determinants of health.
The level of public concern and media attention for some pathogens is disproportionate to their actual disease burden. For example, substantial media attention has been directed to recent outbreaks of Listeria monocytogenes
and West Nile virus in Ontario, 
but these pathogens accounted for only a small proportion (0.04% and 0.07%, respectively) of the total infectious disease burden. In contrast, top pathogens such as HCV, HBV, and S. pneumoniae
receive little media coverage, yet are both burdensome and preventable. Since media reports often influence decision-makers, generating robust estimates of disease burden may improve decision-making.
With the exception of linkable healthcare utilization data, the data used in this study are readily available in most high-income settings. Studies like ONBOIDS could be conducted in many other jurisdictions with similar data sources by adapting the methods and parameter estimates used in ONBOIDS.
One major assumption of burden of disease studies is that the relationship between incidence and mortality remains constant over time. This may be less applicable to infectious diseases as incidence and severity frequently vary over time. We also did not consider the impact of co-infections (e.g., HIV and HCV) and other co-morbidities (e.g., diabetes and influenza virus). Important synergies exist between infectious diseases; notably, HIV can interact with other infectious diseases in terms of natural history and transmissibility. 
While ONBOIDS is the most comprehensive examination of infectious diseases to our knowledge, the study was not exhaustive. We excluded certain pathogens (e.g., norovirus), syndromes (e.g., surgical site infections), and health states (e.g., amputations due to serious infection). The most significant exclusions may have been the oncogenic pathogens Helicobacter pylori
and Epstein-Barr virus, given our finding that other oncogenic pathogens are among the most burdensome infectious agents. We also were unable to assess many milder infections that do not result in healthcare utilization, or take a societal perspective in assessing the impact of outbreaks (e.g., economic, psychological). Other important limitations include: the uncertain validity of the diagnostic codes for ascertaining infectious diseases; the assumption that etiologic agent distributions from studies of non-fatal outcomes also apply to fatal outcomes; reliance on a single underlying cause of death, which may have led to underestimation of the true burden of infectious diseases (e.g., deaths hastened or precipitated by infectious diseases would likely be attributed to pre-existing conditions); and the missed burden of undiagnosed infections. Finally, data were extracted from multiple sources of varying quality. Further details concerning the limitations of this work are described in the ONBOIDS technical report.
Despite these limitations, our study represents the most thorough examination of the population burden of infectious diseases to date. These results provide a crude ordering of infectious diseases that can be used to guide policy, planning, and research. Although data limitations preclude a greater level of precision and quantification of uncertainty, these results provide a sense of the relative importance of the infectious diseases studied. Less important than the precise position on the list is the fact that the top 20 agents capture such a large proportion of the total burden and that some recent high profile infections are absent.
The next step is to translate these findings into information that is tailored for local decision-making. The WHO GBD project has had significant impacts on global and regional agencies, but a provincial analysis such as ONBOIDS provides information closer to the level of government responsible for healthcare policy-setting and funding. However, these findings are likely generalizable to other high-income settings. In translating findings such as these into policy, decision-makers must appreciate the “herd-dynamic” aspects of infectious diseases, such that, for example, funding for highly successful vaccination programs is not diverted towards the high-impact diseases identified here. The communicable nature of vaccine-preventable diseases means that ongoing investment is necessary to maintain existing successes. Also, while novel interventions (e.g., new vaccines) are required to further reduce the burden of infectious diseases, much of the burden can already be reduced by improved implementation of existing interventions (e.g., hand hygiene, improved vaccine uptake, safe injection sites). Setting priorities requires knowledge of disease burden as well as critical evaluation of the feasibility, cost, and impact of available interventions, and knowledge translation for decision-makers. Future work should assess the economic and other broad societal burdens associated with infectious diseases.