Legionella- an underappreciated but important pathogen in HIV
| dc.contributor.author | Head, Breanne | |
| dc.contributor.examiningcommittee | Fowke, Keith (Medical Microbiology and Infectious Diseases) | en_US |
| dc.contributor.examiningcommittee | Rueda, Zulma (Medical Microbiology and Infectious Diseases) | en_US |
| dc.contributor.examiningcommittee | Raouf, Afshin (Immunology) | en_US |
| dc.contributor.examiningcommittee | Av-Gay, Yossef (University of British Columbia) | en_US |
| dc.contributor.supervisor | Keynan, Yoav (Medical Microbiology and Infectious Diseases) | en_US |
| dc.date.accessioned | 2020-09-29T14:29:20Z | |
| dc.date.available | 2020-09-29T14:29:20Z | |
| dc.date.copyright | 2020-09-23 | |
| dc.date.issued | 2020 | en_US |
| dc.date.submitted | 2020-09-23T23:06:47Z | en_US |
| dc.degree.discipline | Medical Microbiology and Infectious Diseases | en_US |
| dc.degree.level | Doctor of Philosophy (Ph.D.) | en_US |
| dc.description.abstract | People living with HIV (PLHIV) have increased susceptibility to respiratory pathogens such as Legionella, however, research on Legionella in community-acquired pneumonia (CAP) in PLHIV remains limited. This study aimed to determine the contribution that Legionella have on lung inflammation, dysfunction, and disease in this population. We hypothesized that Legionella infections occur commonly among patients with HIV+CAP, and that Legionella-infected individuals have more lung inflammation, lung dysfunction, and worse outcomes compared to Legionella-negative individuals. We investigated Legionella in two cohorts in Medellin, Colombia: The Discovery cohort, which comprised HIV+CAP patients, and the Validation cohort, which followed HIV, CAP, and HIV+CAP patients for 1 year. Blood and bronchoalveolar lavage (BAL), and blood, induced sputum, BAL, and spirometry were collected at study admission in the Discovery and Validation cohorts, respectively. Blood, induced sputum, and spirometry were also collected at 1, 6, and 12-month follow-ups. Sample aliquots were shipped to Canada for analyses. Legionella detection was assessed in respiratory samples using real-time PCR, bacterial cultures, and an amoeba model. To determine the effect of Legionella co-infection on clinical outcome, a patient database was consulted, comparing laboratory results and outcomes between Legionella positive and negative individuals. Bead-based technology was used to determine cytokine profiles associated with Legionella co-infection while spirometry results were used to assess how Legionella affects lung function. Data indicate that Legionella are frequently (>25%) found in respiratory samples of HIV+CAP co-infected individuals in Medellin, Colombia, and oftentimes are non-L. pneumophila SG1. Legionella co-infected individuals had higher rates of intensive care unit admissions, acute respiratory failure, and mortality compared to Legionella-negative individuals. At baseline, Legionella-infected individuals also had lower forced vital capacity % predicted, although lung function recovered over time. Additionally, markers of monocyte/macrophage activation and differentiation (Eotaxin, MCP-1 and, IP-10) associated with Legionella infection and with worse patient outcomes. Clinicians should be aware of the possible presence of Legionella in CAP in PLHIV and their potential role in disease severity as a misdiagnosis/lack of appropriate antibiotic coverage have the potential to be fatal. If further investigation supports these findings, this could change the way CAP is managed in this population. | en_US |
| dc.description.note | February 2021 | en_US |
| dc.identifier.uri | http://hdl.handle.net/1993/35099 | |
| dc.language.iso | eng | en_US |
| dc.rights | open access | en_US |
| dc.subject | Legionella | en_US |
| dc.subject | HIV | en_US |
| dc.subject | Coinfection | en_US |
| dc.subject | Cytokines | en_US |
| dc.subject | Lung function | en_US |
| dc.subject | BAL | en_US |
| dc.title | Legionella- an underappreciated but important pathogen in HIV | en_US |
| dc.type | doctoral thesis | en_US |