Incorporating Time Delays in the Mathematical Modelling of the Human Immune Response in Viral Infections.

Mathematical modelling helps to describe the functional and causal relationships between objects in the physical world. The complexity of these models increases as more components and variables are added to maintain and observe. Differential equations are regularly used in these models, as they are able to display the interactions between several variables and describe non-linear behaviour. Differential equations are commonly used in immune response mathematical models to help describe these complex and dynamic interactions within the immune system of the organism. Time delays in the immune system are common and are often disregarded due to the low-resolution of models, which provide limited description of the specific section of immune system being studied. The few models that incorporate time delays are mostly at the epidemiological level, to track the spread of the virus in the population. In this paper we review the applications of the models based on differential equations and describe their potential utilization for the studies of immune response in SARS-CoV-2.

Risk of bloodstream infection in patients with renal dysfunction: a population-based cohort study.

Although patients with end-stage renal disease (ESRD) are known to be at high risk for developing bloodstream infections (BSI), the risk associated with lesser degrees of renal dysfunction is not well defined. We sought to determine the risk for acquiring and dying from community-onset BSIs among patients with renal dysfunction. A retrospective, population-based cohort study was conducted among adult residents without ESRD in the western interior of British Columbia. Estimated glomerular filtration rates (eGFR) were determined for cases and incidence rate ratios (IRR) were calculated using prevalence estimates. Overall, 1553 episodes of community-onset BSI were included of which 39%, 32%, 17%, 9%, 2% and 1% had preceding eGFRs of ≥90, 60-89, 45-59, 30-44, 15-29 and <15 ml/min/m2, respectively. As compared to those with eGFR ≥60 ml/min/m2, patients with eGFR 30-59 ml/min/m2 (IRR 4.4; 95% confidence interval (CI) 3.9-4.9) and eGFR <30 ml/min/m2 (IRR 7.0; 95% CI 5.0-9.5) were at significantly increased risk for the development of community-onset BSI. An eGFR <30 ml/min/m2 was an independent risk factor for death (odds ratio 2.3; 95% CI 1.01-5.15). Patients with renal dysfunction are at increased risk for developing and dying from community-onset BSI that is related to the degree of dysfunction.

Population-based risk factors for community-onset bloodstream infections.

Although a number of comorbidities have been associated with development of bloodstream infection, actual risk factors have not been well defined and quantified in nonselected populations. We sought to quantify population-based risk factors for development of community-onset bloodstream infection (COBSI). Surveillance was conducted among all residents of the Western Interior of British Columbia, Canada, during 2011-2018. Risks were expressed as incidence rate ratios (IRR) with 95% confidence intervals (CI). The annual incidence was 147.1 per 100,000 and older individuals, and males were at overall higher risk. The median Charlson score was 2 (IQR, 0-3), and this was higher among those with healthcare-associated (2; IQR, 1-4) as compared to community-associated (1; IQR, 0-2; P < 0.0001) COBSI. Risk factors for development of COBSI included (IRR; 95% CI): HIV infection (8.89; 5.17-14.27), cancer (6.80; 6.13-7.54), congestive heart failure (4.68; 4.00-5.46), dementia (3.31; 2.82-3.87), diabetes mellitus (3.10; 2.80-3.42), cerebrovascular accident (2.79; 2.34-3.31), renal dysfunction (2.75; 2.33-3.22), chronic lung disease (2.03; 1.79-2.28), peripheral vascular disease (1.68; 1.39-2.01), and rheumatic disease (1.44; 1.14-1.79). Patients with multiple comorbid illnesses were older, more likely to be male, and have healthcare-associated BSI, higher rates of antimicrobial resistance, and different clinical foci of infection. A number of demographic and comorbid conditions significantly increase the risk for development of COBSI.

Inhospital death is a biased measure of fatal outcome from bloodstream infection.

PURPOSE: Inhospital death is commonly used as an outcome measure. However, it may be a biased measure of overall fatal outcome. The objective of this study was to evaluate inhospital death as a measure of all-cause 30-day case fatality in patients with bloodstream infection (BSI). PATIENTS AND METHODS: A population-based surveillance cohort study was conducted, and patients who died in hospital within 30 days (30-day inhospital death) were compared with those who died in any location by day 30 post BSI diagnosis (30-day all-cause case fatality). RESULTS: A total of 1,773 residents had first incident episodes of BSI. Overall, 299 patients died for a 30-day all-cause case fatality rate of 16.9%. Most (1,587; 89.5%) of the patients were admitted to hospital, and ten (5.4%) of the 186 patients not admitted to hospital died. Of the 1,587 admitted patients, 242 died for a 30-day inhospital death rate of 15.2%. A further 47 patients admitted to hospital died after discharge but within 30 days of BSI diagnosis for a 30-day case fatality rate among admitted patients of 18.2%. Patients who died following discharge within 30 days were older and more likely to have dementia. CONCLUSION: The use of inhospital death is a biased measure of true case fatality.

Risk factors associated with bloodstream infections in end-stage renal disease patients: a population-based study.

BACKGROUND: Bloodstream infections (BSI) commonly complicate end-stage renal disease (ESRD) and are the second most common cause of death in these patients. The objective of this study was to define risk factors for development of BSI and its outcome among ESRD patients. METHODS: A retrospective, population-based, matched cohort design was utilized. All adult (18 or older) residents of the western interior of British Columbia with ESRD who had a first BSI between April 2010 and March 2017 were included. Subject cases were then matched 1:1 with an ESRD patient from the regional registry who did not have a BSI. RESULTS: During the study period a total of 53 cases of incident BSI were identified among patients with ESRD. The median age was 70.7 (interquartile range, 61.9-79.6) years and 28 (53%) were male. The most common organism isolated was Staphylococcus aureus (17 cases; 32%). Compared to controls, case patients were significantly (p < .05) more likely to have higher Charlson comorbidity scores (mean difference (MD): 1.4; 95% CI (0.5, 2.2)), and have lower serum albumin (MD: -3.3; 95% CI (-5.5, -1.2)). Diabetes was not significant; however, cases were twice as likely to be diabetic (OR: 2.0; 95% CI (0.9, 4.8)). Case fatality rates for 30- and 90-days were 8/53 (15%) and 13/53 (25%) respectively, whereas no control patients died (p < .05). CONCLUSIONS: ESRD patients with higher co-morbid illness, and lower serum albumin are at an increased risk for development of a BSI. Development of BSI among ESRD patients is associated with higher fatality rates.

Streptococcus anginosus group bloodstream infections in the western interior of British Columbia, Canada.

BACKGROUND: The epidemiology of Streptococcus anginosus group (SaG) bloodstream infections (BSI) has not been well defined in non-selected populations. The objective of this study was to determine the incidence, risk factors and outcome associated with SaG BSI. METHODS: Population-based surveillance was conducted in the western interior region of British Columbia, Canada between 1 April 2010 and 31 March 2017. RESULTS: Forty-six episodes were identified for an overall annual incidence of 3.7 per 100,000 population. The incidence increased with older age and males were at significantly higher risk (5.2 vs. 2.1 per 100,000; incidence rate ratio, 2.5; 95% confidence interval, 1.3-5.1; p = .004). Nearly one-half (22; 48%) of patients had no chronic co-morbid illness, whereas 17 (40%) had 1-2, six (13%) had 3-4 and one (2%) had 5 Charlson scores with diabetes and cancer being the most common. Predisposing factors for development of SaG BSI were identified in 30 (65%) cases. The gastro-intestinal tract was the most common focus of infection (13; 28%) followed by cardiovascular and skin/soft tissue (six cases each; 13%) and in seven (15%) cases no focus was identified. Drainage procedures were required in 21 (46%) patients of whom seven (15%) patients had percutaneous drains and 14 (30%) required surgical operations. Forty-one (89%) patients were admitted to hospital for a median hospital length stay of 11 (interquartile range, 7-18) days. The in-hospital and 30-day all cause case-fatality rates were 3/41 (7%) and 4/46 (9%), respectively. CONCLUSION: SaG BSI is an important cause of morbidity and mortality.