Alissa J. Wright

The Impact of Infection on Population Health: Results of the Ontario Burden of Infectious Diseases Study

Background Evidence-based priority setting is increasingly important for rationally distributing scarce health resources and for guiding future health research. We sought to quantify the contribution of a wide range of infectious diseases to the overall infectious disease burden in a high-income setting. Methodology/Principal Findings We used health-adjusted life years (HALYs), a composite measure comprising premature mortality and reduced functioning due to disease, to estimate the burden of 51 infectious diseases and associated syndromes in Ontario using 2005–2007 data. Deaths were estimated from vital statistics data and disease incidence was estimated from reportable disease, healthcare utilization, and cancer registry data, supplemented by local modeling studies and national and international epidemiologic studies. The 51 infectious agents and associated syndromes accounted for 729 lost HALYs, 44.2 deaths, and 58,987 incident cases per 100,000 population annually. The most burdensome infectious agents were: hepatitis C virus, Streptococcus pneumoniae, Escherichia coli, human papillomavirus, hepatitis B virus, human immunodeficiency virus, Staphylococcus aureus, influenza virus, Clostridium difficile, and rhinovirus. The top five, ten, and 20 pathogens accounted for 46%, 67%, and 75% of the total infectious disease burden, respectively. Marked sex-specific differences in disease burden were observed for some pathogens. The main limitations of this study were the exclusion of certain infectious diseases due to data availability issues, not considering the impact of co-infections and co-morbidity, and the inability to assess the burden of milder infections that do not result in healthcare utilization. Conclusions/Significance Infectious diseases continue to cause a substantial health burden in high-income settings such as Ontario. Most of this burden is attributable to a relatively small number of infectious agents, for which many effective interventions have been previously identified. Therefore, these findings should be used to guide public health policy, planning, and research.

Fecal microbiota transplantation for the intestinal decolonization of extensively antimicrobial-resistant opportunistic pathogens: a review

ABSTRACT Treatment options for multidrug-resistant (MDR) bacterial infections are limited and often less effective. Non-pharmacologic approaches to preventing or treating MDR infections are currently restricted to improved antimicrobial stewardship and infection control practices. Fecal microbiota transplantation (FMT), a highly effective treatment for recurrent Clostridium difficile infection, has emerged as a promising therapy for intestinal MDR bacterial decolonization. A total of eight case reports have been published showing FMT resulted in intestinal decolonization of extended spectrum β-lactamase (ESBL)-producing and carbapenemase-producing Enterobacteriaceae, vancomycin-resistant Enterococci, or methicillin-resistant Staphylococcus aureus. The procedure has been shown to work even in immunocompromised patients and those experiencing medical crises without any adverse events. Five trials are currently underway to further investigate the use of FMT for MDR bacterial decolonization. FMT is a completely novel way to eradicate drug-resistant bacteria from the intestinal reservoir and should be further investigated to address the global problem of difficult-to-treat, MDR bacterial infections.

Central Nervous System Syndromes in Solid Organ Transplant Recipients

Solid organ transplant recipients have a high incidence of central nervous system (CNS) complications, including both focal and diffuse neurologic deficits. In the immunocompromised host, the initial clinical evaluation must focus on both life-threatening CNS infections and vascular or anatomic lesions. The clinical signs and symptoms of CNS processes are modified by the immunosuppression required to prevent graft rejection. In this population, these etiologies often coexist with drug toxicities and metabolic abnormalities that complicate the development of a specific approach to clinical management. This review assesses the multiple risk factors for CNS processes in solid organ transplant recipients and establishes a timeline to assist in the evaluation and management of these complex patients.

Risk Factors for BK Polyoma Virus Treatment and Association of Treatment With Kidney Transplant Failure: Insights From a Paired Kidney Analysis.

Background Identification of risk factors for BK polyoma virus (BKPyV) without confounding by donor factors and era effects in paired analysis may inform strategies to prevent BKPyV. Methods In this analysis of 21,575 mate kidney pairs in the Scientific Registry of Transplant Recipients between 2004 and 2010, the presence of a treatment code for BKPyV virus in follow-up forms was used to identify pairs in which 1 of 2 mate kidneys was treated (discordant treatment) or both mate kidneys were treated (concordant treatment). Results Among 1975 discordant pairs, younger than 18 years or 60 years or older, male sex, HLA mismatch or 4 greater, acute rejection, and depleting antibody induction had a higher odds of treatment, whereas diabetes and sirolimus had a lower odds of treatment, and treatment was associated with a higher risk of allograft failure (hazards ratio, 2.01; 95% confidence interval, 1.63-2.48). The rate of concordant treatment (0.81%) was 2.8 times higher than expected. Concordant treatment was associated with nonwhite donor ethnicity, donation after circulatory death, transplantation after 2008, and transplantation of mate kidneys in the same center. Conclusions This analysis of kidneys from the same donor in which only 1 transplant was treated for BKPyV identifies specific risk factors (age <18 or ≥ 60 years, male sex, depleting antibody, HLA mismatch ≥ 4) for BKPyV and provides an estimate of the BKPyV-associated risk of allograft failure (hazards ratio = 2.01) without confounding by donor factors or era effects. The higher than expected rate of concordant treatment suggests the importance of donor factors in BKPyV pathogenesis and warrants further study.

Lamivudine compared with newer antivirals for prophylaxis of hepatitis B core antibody positive livers: a cost-effectiveness analysis.

There is concern over the development of de novo hepatitis B in patients receiving liver transplants from hepatitis B surface antigen negative, hepatitis B core antibody positive donors. Current practice is to place such patients on indefinite lamivudine prophylaxis; however, there is a small risk of breakthrough infection and newer antivirals for hepatitis B are available. The objective of this study was to determine the cost‐effectiveness of lamivudine compared with the newer agents, tenofovir and entecavir, in the prophylaxis setting using a Markov model. Three strategies were examined which consisted of either lamivudine or entecavir monoprophylaxis with tenofovir add‐on therapy after breakthrough or tenofovir monoprophylaxis with emtricitabine add‐on therapy after breakthrough. In the base case scenario, lamivudine was the most cost‐effective option at a threshold of

Strategies to prevent BK virus infection in kidney transplant recipients.

100 000 per quality‐adjusted life‐year and this remained robust despite parameter uncertainty. Tenofovir had an incremental cost‐effectiveness ratio of

Maternal antibiotic exposure and risk of antibiotic resistance in neonatal early-onset sepsis: a case-cohort study.

3 540 194.77 while other strategies were superior to entecavir therapy. Until drug costs decrease, lamivudine remains the most cost‐effective option for hepatitis B prophylaxis in the liver transplant setting.

Towards Improving the Transfer of Care of Kidney Transplant Recipients.

Purpose of review Despite improvements in posttransplant care, BK virus (BKV) remains one of the most challenging posttransplant infections in kidney transplant recipients with high rates of allograft failure. In the absence of well tolerated and efficacious viral specific therapeutics, treatment is primarily focused on reduction of immunosuppression, which poses a risk of rejection and fails to lead to viral clearance in a number of patients. Recent findings Recent work has turned toward preventive therapies analogous to those used for other infections like cytomegalovirus. These efforts have focused on the use of quinolone antibiotic prophylaxis to prevent BKV infection and pretransplant vaccination to boost humoral and cellular immunity. Summary Despite promising in-vitro and observational data, quinolone antibiotic prophylaxis has not been effective in preventing BKV infection in prospective studies. However, prophylaxis with newer less toxic viral specific agents such as brincidofovir – the lipid oral formulation of cidofovir – may yet prove effective. Strategies focused on eliciting a humoral immune response to recombinant virus-like particles or using adoptive transfer of BKV-specific T cells have also shown significant potential to prevent BKV infection in organ transplant recipients.

Infectious Considerations in the Pre-Transplant Evaluation of Cirrhotic Patients Awaiting Orthotopic Liver Transplantation

In a case-cohort study of early-onset sepsis, antibiotic resistance was more likely for infections in neonates born to mothers who were given antibiotics during pregnancy (odds ratio 4.6; 95% confidence interval: 1.1–19;P = 0.05). Risk of resistance increased with duration of antibiotics and number of antibiotic courses during pregnancy. Preterm birth and hospitalization during pregnancy were also associated with resistance. These risk factors should be considered when selecting empiric antibiotics for therapy of early-onset sepsis in infants.

Successful long‐term management of invasive cerebral fungal infection following liver transplantation

Kidney transplant recipients require specialized medical care and may be at risk for adverse health outcomes when their care is transferred. This document provides opinion‐based recommendations to facilitate safe and efficient transfers of care for kidney transplant recipients including minimizing the risk of rejection, avoidance of medication errors, ensuring patient access to immunosuppressant medications, avoidance of lapses in health insurance coverage, and communication of risks of donor disease transmission. The document summarizes information to be included in a medical transfer document and includes suggestions to help the patient establish an optimal therapeutic relationship with their new transplant care team. The document is intended as a starting point towards standardization of transfers of care involving kidney transplant recipients.