Publications by authors named "David M Forrest"

5 Publications

  • Page 1 of 1

Proteomic analysis of exosomes derived from procyclic and metacyclic-like cultured Leishmania infantum chagasi.

J Proteomics 2020 09 14;227:103902. Epub 2020 Jul 14.

Laboratório de Biologia Molecular de Parasitas e Vetores, Instituto Oswaldo Cruz-Fiocruz, Av. Brasil 4365, 21045-900 Rio de Janeiro, RJ, Brazil. Electronic address:

Leishmania infantum chagasi is the primary etiological agent of visceral leishmaniasis in Latin America, a lethal disease that afflicts hundreds of thousands of people worldwide every year. Previous studies have shown that the parasite releases microvesicles known as exosomes, which prolong and exacerbate infection in the vertebrate vector. However, little is known of their role in the insect vector, the sand fly Lutzomyia longipalpis. Exosomes were isolated from cultured L. i. chagasi in logarithmic (procyclic) (LOG) and stationary phase (metacyclic-like) (STAT) growth stages, which are the parasite stages found in the vector, and submitted to proteomic analysis. Our studies showed that exosomes from LOG and STAT L. i. chagasi display discrete protein profiles. The presence of approximately 50 known virulence factors was detected, including molecules for immunomodulation and evasion (GP63, EF1α, Oligopeptidase), increased pathogenicity (Casein kinase, KMP-11, Cysteine Peptidase and BiP) and parasite protection (Peroxidoxin). Additionally, the majority of ontological terms were associated with both exosome phases, and no substantial ontological enrichment was observed associated with any of the two exosomal stages. We demonstrated that LOG exosomes show a marked increase in protein number and abundance, including many virulence factors, compared to STAT L. i. chagasi exosomes. SIGNIFICANCE: The knowledge of the role of Leishmania exosomes on leishmaniasis opened up a new world of potential and complexity regarding our understanding of the disease. In Brazil the majority of visceral leishmaniasis cases are caused by the parasite Leishmania infantum chagasi and transmitted by the vector Lutzomyia longipalpis. While Leishmania exosomes were found to play an active role in the mammalian host, little is understood about their effects on the sand fly, or how they might impact on the insect infection by the parasite. For this reason, we isolated exosomes from two developmental stages of L. i. chagasi that occur within the insect with a view to identifying and describing the alterations they undergo. We have identified many hundreds of proteins within both exosome phases and have developed a structure by which to examine potential candidates. Our findings regarding the composition of the exosome proteome raise many questions regarding their function and provide compelling evidence that exosomes play an active role in the parasite's development within the sand fly.
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http://dx.doi.org/10.1016/j.jprot.2020.103902DOI Listing
September 2020

Recurrent sterile abscesses in a case of X-linked neutropenia.

Pediatr Dermatol 2020 Jul 23;37(4):742-744. Epub 2020 Mar 23.

Division of Allergy & Immunology, University of British Columbia, Vancouver, BC, Canada.

Cutaneous manifestations are common in monogenic immune disorders, including both infectious and non-infectious etiologies. We report follow-up of a case initially published in Pediatric Dermatology in 2001 of a 13-year-old boy with a history of inflammatory skin lesions and neutropenia who developed neutrophilic dermatoses precipitated by G-CSF. Whole exome sequencing performed at 36 years of age revealed a gain-of-function mutation in the WAS gene, leading to a diagnosis of X-linked neutropenia. This case report provides closure on a decades-long diagnostic odyssey and underscores the importance of genetic sequencing in patients who present with unusual dermatologic findings.
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http://dx.doi.org/10.1111/pde.14146DOI Listing
July 2020

Longitudinal clinical findings and outcome among patients with Cryptococcus gattii infection in British Columbia.

Clin Infect Dis 2015 May 28;60(9):1368-76. Epub 2015 Jan 28.

British Columbia Centre for Disease Control.

Background: Cryptococcus gattii (Cg) infection emerged in British Columbia in 1999. A longitudinal, clinical description of patients has not been reported.

Methods: Medical records were reviewed for Cg patients identified through surveillance (1999-2007). Risk factors for Cg mortality were explored using multivariate Cox regression; longitudinal patterns in serum cryptococcal antigen (SCrAg) titers and the probability of chest cryptococcomas over time were estimated using cubic B-splines in mixed-effects regression models.

Results: Among 152 patients, 111 (73.0%) were culture confirmed. Isolated lung infection was present in 105 (69.1%) patients; 47 (30.9%) had central nervous system infection, with or without lung involvement. Malignancy was the provisional diagnosis in 64 (42.1%) patients. Underlying diseases were present in 91 (59.9%) patients; 23 (15.1%) were immunocompromised, and 23 (15.1%) had asymptomatic disease. There were only 2 (1.8%) culture positive relapses, both within 12 months of follow-up. The estimated median time to resolution of lung cryptococcomas and decline in SCrAg titer to <1:8 was 2.8 and 2.9 years, respectively. Cg-related and all-cause mortality among culture-confirmed cases at 12 months' follow-up was 23.3% and 27.2%, respectively. Cg-related mortality was associated with age >50 years (hazard ratio [HR], 15.6; 95% confidence interval [CI], 1.9-130.5) and immunocompromise (HR, 5.8; CI, 1.5-21.6). All Cg-related mortality occurred among culture-positive cases within 1 year of diagnosis.

Conclusions: Cryptococcomas and serum antigenemia were slow to resolve. However, late onset of failed therapy or relapse was uncommon, suggesting that delayed resolution of these findings does not require prolongation of treatment beyond that recommended by guidelines.
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http://dx.doi.org/10.1093/cid/civ041DOI Listing
May 2015

Cutaneous leishmaniasis in a returning traveller.

CMAJ 2013 May 25;185(8):681-3. Epub 2013 Mar 25.

Biology Department, Vancouver Island University, Nanaimo, BC.

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http://dx.doi.org/10.1503/cmaj.120694DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3652938PMC
May 2013

Imaging features of pulmonary Kaposi sarcoma-associated immune reconstitution syndrome.

AJR Am J Roentgenol 2007 Oct;189(4):956-65

Department of Radiology, St. Paul's Hospital, University of British Columbia, Vancouver, BC, Canada.

Objective: The purpose of this study was to analyze the radiologic features of pulmonary Kaposi sarcoma-associated immune reconstitution syndrome. The syndrome is a phenomenon characterized by clinical deterioration of the condition of HIV-positive patients after initiation of highly active antiretroviral therapy.

Materials And Methods: The study included four patients at our institution who fulfilled the diagnostic criteria for pulmonary Kaposi sarcoma-associated immune reconstitution syndrome from 2001 to 2006. All patients were men (mean age, 43 years; range, 31-59 years). Images reviewed included chest radiographs obtained before highly active antiretroviral therapy, radiographs and chest CT scans obtained at appearance of the symptoms of Kaposi sarcoma-associated immune reconstitution syndrome, and follow-up radiographs and chest CT scans during immune reconstitution syndrome.

Results: The radiographic findings of Kaposi sarcoma-associated immune reconstitution syndrome included reticular and reticulonodular opacities (n = 4), areas of consolidation (n = 3), septal lines (n = 3), and pleural effusion (n = 3). The CT findings in all four patients were ill-defined pulmonary nodules and interlobular septal thickening. Three of the patients had a CT halo sign, areas of consolidation, ground-glass opacities, lymphadenopathy, and pleural effusion. The areas of consolidation in three subjects who did not receive chemotherapy increased markedly after 14-20 days. CT performed during the initial symptoms of immune reconstitution syndrome in these three subjects showed less than 5% parenchymal involvement. Follow-up CT showed 26-50% involvement in two patients and more than 50% involvement in one patient.

Conclusion: The radiologic findings of pulmonary Kaposi sarcoma-associated immune reconstitution syndrome are similar to the findings described in patients with Kaposi sarcoma without the syndrome, but the extent of abnormalities tends to increase with the development of the syndrome.
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http://dx.doi.org/10.2214/AJR.07.2458DOI Listing
October 2007