88 research outputs found
Can I borrow a microbiome? : Life-saving poop and the ethics of microbiome therapies
No full textWhat if we could transplant healthy bacteria into patients to fight diseases without using antibiotics? What might some of the implications be for society if we did this on a broad scale? This talk featured School of Population and Public Health Associate Professor Amee Manges, who speaks about fecal microbiota transplants (FMTs) and how this therapy can save lives, as well as University of Guelph Associate Professor Kieran O’Doherty who discussed the ethics of introducing such therapies across populations, including the possible consequences of changing many people’s normal microbiomes. The talk was MC’d by SPPH Assistant Professor Jennifer Gardy and was presented on September 22nd at UBC.Medicine, Faculty ofNon UBCPopulation and Public Health (SPPH), School ofUnreviewedFacult
Antibiotic usage and resistance gene carriage in children with severe acute malnutrition and human immunodeficiency syndrome co-morbidities living in low-resource settings
No full textAntibiotic resistance is the third largest contributor to mortality worldwide, and 30% of these deaths occur in newborns. The burden of resistant infections in children is disproportionately higher in low- and middle-income countries (LMICs) due to the overuse of antibiotics in food, food animals and health care settings. The prevalence of childhood co-morbidities like severe acute malnutrition (SAM) and human immunodeficiency virus (HIV) in LMICs increases the need for treatment and prophylactic antibiotic use. These conditions also increase the likelihood of secondary disease, thereby further increasing the need for antibiotics. Antibiotic resistance genes (ARGs) are the primary source of resistance in pathogens and are amplified with antibiotic exposure. There is an urgent need to understand the role of ARGs in diseases amongst infants and children, especially in LMICs, where their impact on mortality and morbidity is large. In this dissertation, chapter one reviews previous knowledge about the presence or carriage of ARGs and the impact ARGs have on morbidity and mortality in LMICs, especially morbidity and mortality due to SAM and HIV. Chapter 2 examines the natural acquisition of ARGs in healthy children living in rural areas of a LMIC using longitudinal data from the Sanitation Hygiene and Infant Nutrition Efficacy (SHINE) trial. Chapter 3 examines the changes in ARG carriage during hospitalization with SAM and HIV, and during SAM recovery using longitudinal data from the Health Outcomes, Pathogenesis and Epidemiology of Severe Acute Malnutrition (HOPE-SAM) observational study. Chapter 4 investigates the impact of stopping or continuing prophylactic antibiotic use in HIV-positive children using data from the Antiretroviral Research for Watoto (ARROW) trial. I find that healthy children acquire a diverse array of ARGs upon birth, ARG carriage decreases significantly with age in healthy children, and most ARGs are closely associated with the abundance of Enterobacteriaceae that colonize the infant gut. Hospitalization for SAM leads to a less mature microbiota, associated with increases in Enterobacteriaceae-related ARG abundance. This effect was transient and decayed over time following hospital discharge. Continued prophylactic antibiotic treatment in HIV-positive children does not significantly alter ARG carriage but does selectively increase resistance specific to antibiotics used.Medicine, Faculty ofMedicine, Department ofGraduat
The role of the infant microbiota and childhood stunting in rural Zimbabwe
No full textChildhood stunting or linear growth failure is a major global health issue, affecting 22% of children under 5 years of age worldwide. Stunting impacts people across the life course. Stunting is associated with a greater number of infections, reduced childhood survival, impaired cognitive development, and reduced adulthood productivity, and contributes to an intergenerational cycle of poor growth and development. Decreased linear growth has been associated with community-level changes in the gut microbiome as well as specific changes in individual bacterial and decreased overall microbial diversity. However, the literature addressing the role of the gut microbiome on poor child linear growth is limited. We conducted an analysis of the infant fecal microbiota composition from 1-18 months of life from infants participating in the Sanitation, Hygiene, Infant Nutrition Efficacy (SHINE) Trial, a large cluster-randomized trial, designed to evaluate the impact of improved household water quality, sanitation, and hygiene (WASH), and improved infant and young child feeding (IYCF) on linear growth and anaemia during the first 18 months of infant life in rural Zimbabwe. Using whole metagenomic sequencing, we were able to describe the infant fecal microbiota composition of SHINE Trial infants and examine relationships between the microbiota composition and HIV exposure status, SHINE trial interventions, and stunting status.
As expected, age was the major driver of microbiota composition and diversity. No major differences in the infant fecal microbiota by HIV exposure status, SHINE trial interventions, or stunting status were observed. These results highlight the complex nature of linear growth and demonstrate that infant fecal microbiota composition plays a smaller direct role on growth in SHINE infants. Our study also confirms that the SHINE WASH intervention did not influence infant growth through alterations to the fecal microbiota composition, confirming the primary SHINE results. However, the functional potential of the infant fecal microbiota of SHINE infants will be examined in future analyses; this may uncover relationships separate from microbiota composition and diversity alone.Science, Faculty ofMicrobiology and Immunology, Department ofGraduat
Applications of metagenomic sequencing for virus detection and characterization of upper respiratory infections
No full textThe application of next-generation sequencing technologies to answer more routine
diagnostic and applied microbiological questions is becoming increasingly feasible. Current
reference-standard molecular diagnostic strategies are limited in that they require a priori
knowledge of a pathogen’s genome. Metagenomic next generation sequencing (mNGS) is a
pathogen-agnostic diagnostic approach that can be used for detection of viral pathogens and
characterization of viral infections. Chapter 1 of this thesis describes technological advancements
in mNGS technology for viral pathogen detection and diagnosis. This narrative review highlights
technical, logistical, and translational barriers to the widespread use of this technology in clinical
settings. In chapter 2, I describe the use of full-length 16S rRNA nanopore sequencing for
characterization of the upper respiratory tract microbiome in hospitalized and community-dwelling
individuals with and without active SARS-CoV-2 infection. We found significant
differences in beta-diversity, but not alpha-diversity in our study groups and identified several
differentially abundant taxa associated with SARS-CoV-2 infection status and disease severity.
Chapter 3 outlines the feasibility and performance of long-read mNGS as a diagnostic tool for
detection and characterization of SARS-CoV-2. We reported that mNGS is a highly specific
method for SARS-CoV-2 detection and is sensitive for specimens with higher viral loads. We
showed that this technology can also be used to characterize viral genomes. Finally, chapters 4
and 5 outline the development, optimization, and validation of a novel mNGS assay for detection
of viral pathogens. This assay was developed to address translational barriers to mNGS adoption.
We developed and clinically validated an assay that is sensitive, specific, rapid, cost-effective,
and inclusive. In addition to successfully detecting four known viral pathogens, the assay
detected a total of nine respiratory pathogens that were missed by conventional molecular
diagnostic testing when originally tested. In summary, the work presented in this thesis
highlights the feasibility of using next-generation sequencing workflows in routine clinical
service for diagnosis of viral pathogens and characterization of viral infections. This thesis
represents novel, applied work that contributes to the field of microbiology and can have
immediate impact on clinical microbiology and diagnostic services for human and animal health
and public health surveillance.Science, Faculty ofMicrobiology and Immunology, Department ofGraduat
Design and validation of a sinonasal endoscopic score (SiNES) for chronic rhinosinusitis outcome assessment
No full textChronic rhinosinusitis (CRS) is a debilitating disease that affects the sinonasal cavity and significantly reduces patients’ quality of life. Sinonasal endoscopy is the main strategy for evaluating and monitoring CRS patients. There are several endoscopic grading systems available, but they all have important shortcomings and limitations. There is an urgent need for a reliable score that can accurately reflect patient’s disease burden that is easy to use and applicable to all CRS subtypes.
In chapter 1 of this thesis, I review the main endoscopic scoring systems and describe their main advantages and disadvantages. Based on these findings, Chapter 2 describes the design and validation of the SiNonasal Endoscopic Score (SiNES), a new scoring system that incorporates the strengths of previous scores while addressing their limitations. This chapter further investigates the relationship between the newly developed SiNES and patient reported outcome measures (PROMs).
Chapter 3 explores the minimal clinical important difference (MCID) for the SiNES. This chapter incorporates the perspectives of both surgeons and patients and produces an MCID value that can be used for clinical trial development and patient monitoring.
Chapter 4 further validates the SiNES using data from the first 45 participants in the SinoNasal Microbiota Transfer (SNMT) trial, a landmark study that will determine whether SNMT can improve the health of recalcitrant CRS patients. The chapter includes data on how the SiNES correlates with objective olfactory outcomes, quality of life measures, and a diverse set of type 2 and non-type 2 cytokines.
Finally, Chapter 5 consolidates the findings of the entire thesis and gives some perspectives on future research directions.Medicine, Faculty ofMedicine, Department ofGraduat
Impact of direct-acting antivirals on extrahepatic manifestations and ethnic disparities : insights from a large population-based cohort using linked health administrative data
No full textBackground: Direct-acting antivirals (DAAs) have demonstrated efficacy in reducing morbidity and mortality related to extrahepatic outcomes of chronic hepatitis C (HCV) infection. However, population-based evidence assessing the impact of DAA treatment on extrahepatic manifestations (EHMs) and their burden across ethnic groups remains limited.
Objective: We evaluated the impact of DAA treatment on incident EHMs and EHM-related mortality risks, while also assessing ethnic disparities in EHMs among people diagnosed with HCV in British Columbia (BC).
Methods: We used data from the BC Hepatitis Testers Cohort, including ~1.3 million people tested for or diagnosed with HCV between 1990 and 2015. To assess the impact of DAA treatment on EHMs, we created a 1:1 matched study population of individuals who were treated with DAAs and those who were never treated. We applied inverse probability of treatment weights and competing risk modelling to assess DAA treatment effects on incident EHMs and EHM-related mortality. Ethnic disparities in incident EHMs were examined across East Asians, South Asians, and Other ethnicities, further stratified by HCV treatment status (never treated, before treatment, after treatment, and spontaneously cleared).
Results: Successful DAA treatment was associated with reduced risks of renal, cerebrovascular, cardiovascular and neurocognitive conditions (36-48%), but not type 2 diabetes. It also decreased EHM-related mortality risks by 78-84% for all EHMs. In BC, South and East Asians had higher EHM incidence rates compared to other ethnicities, especially among untreated individuals. Following treatment completion, these rates decreased in both Asian groups. Adjusted analyses showed that South Asians had the highest risk of renal diseases and type 2 diabetes, while East Asians had lower risks of cardiovascular diseases and neurocognitive disorders. HCV treatment mitigated ethnic disparities in EHMs, except for diabetes.
Conclusions: DAA treatment can significantly reduce the risks of EHMs and EHM-related mortality, while mitigating most ethnic disparities in EHM incidence among Asian populations. These findings emphasize the importance of expanding strategies to diagnose and treat individuals living with HCV as early as possible to improve health outcomes and address ethnic disparities related to EHMs.Medicine, Faculty ofPopulation and Public Health (SPPH), School ofGraduat
Antimicrobial Use, Human Gut Microbiota and Clostridium difficile Colonization and Infection
No full textClostridium difficile infection (CDI) is the most important cause of nosocomial diarrhea. Broad-spectrum antimicrobials have profound detrimental effects on the structure and diversity of the indigenous intestinal microbiota. These alterations often impair colonization resistance, allowing the establishment and proliferation of C. difficile in the gut. Studies involving animal models have begun to decipher the precise mechanisms by which the intestinal microbiota mediates colonization resistance against C. difficile and numerous investigations have described gut microbiota alterations associated with C. difficile colonization or infection in human subjects. Fecal microbiota transplantation (FMT) is a highly effective approach for the treatment of recurrent CDI that allows the restoration of a healthy intestinal ecosystem via infusion of fecal material from a healthy donor. The recovery of the intestinal microbiota after FMT has been examined in a few reports and work is being done to develop custom bacterial community preparations that could be used as a replacement for fecal material
Emerg Infect Dis
No full textWomen with urinary tract infections (UTIs) in California, USA (1999-2001), were infected with closely related or indistinguishable strains of Escherichia coli (clonal groups), which suggests point source dissemination. We compared strains of UTI-causing E. coli in California with strains causing such infections in Montr\ue9al, Qu\ue9bec, Canada. Urine specimens from women with community-acquired UTIs in Montr\ue9al (2006) were cultured for E. coli. Isolates that caused 256 consecutive episodes of UTI were characterized by antimicrobial drug susceptibility profile, enterobacterial repetitive intergenic consensus 2 PCR, serotyping, XbaI and NotI pulsed-field gel electrophoresis, multilocus sequence typing, and phylogenetic typing. We confirmed the presence of drug-resistant, genetically related, and temporally clustered E. coli clonal groups that caused community-acquired UTIs in unrelated women in 2 locations and 2 different times. Two clonal groups were identified in both locations. Epidemic transmission followed by endemic transmission of UTI-causing clonal groups may explain these clusters of UTI cases
Die aktive Beteiligung deutschsprachiger Länder an den Konferenzen der Association for Medical Education in Europe (AMEE) zwischen 2005 und 2013: Spiegelbild der Entwicklung der medizinischen Ausbildungsforschung?
No full text[english] Objectives: Medical education is gaining in significance internationally. A growing interest in the field has been observed in German-speaking countries (Austria, Germany, Switzerland) since the early 2000s. This interest is not, however, reflected in an increase in the number of publications on medical education of German-speaking authors in international professional journals. The following investigation examines the potential use of active participant numbers of German-speaking researchers at AMEE conferences as a means of measuring said development. Methods: The AMEE conference proceedings from the categories and from the years 2005-2013 were examined for evidence of Austrian, German and Swiss participation. The abstracts were subsequently analysed in terms of content and categorised according to , and .Results: Of the 9,446 analysed abstracts, 549 contributions show at least one first, last or co-author from Austria, Germany or Switzerland. The absolute number of contributions per conference varied between 44 in 2010 and 77 in 2013. The percentage fluctuated between 10% in 2005 and 4.1% in 2010. From the year 2010 onwards, however, participation increased continually. The research was predominantly descriptive (62.7%). Studies on fundamental questions of teaching and learning () were less frequent (4.0%). For the most part, quantitative methods (51.9%) were implemented in addressing subjects such as (33%), (22.4%) or (14.4%). The study population was usually comprised of students (52.5%).Conclusions: The number of contributions from Austria, Germany and Switzerland peak at the beginning and at the end of the evaluated period of time. A continual increase in active participation since 2005 was not observed. These observations do not reflect the actual increase of interest in medical education research in German-speaking countries
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