Browsing by Author "Fonseca, Kevin"
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Item Open Access Community-Associated Methicillin-Resistant Staphylococcus aureus Necrotizing Pneumonia without Evidence of Antecedent Viral Upper Respiratory Infection(2014-01-01) Toro, Cristina Moran; Janvier, Jack; Zhang, Kunyan; Fonseca, Kevin; Gregson, Dan; Church, Deirdre; Laupland, Kevin; Rabin, Harvey; Elsayed, Sameer; Conly, JohnBACKGROUND: USA300 community-associated (CA) methicillin-resistant Staphylococcus aureus (MRSA) strains causing necrotizing pneumonia have been reported in association with antecedent viral upper respiratory tract infections (URI).METHODS: A case series of necrotizing pneumonia presenting as a primary or coprimary infection, secondary to CA-MRSA without evidence of antecedent viral URI, is presented. Cases were identified through the infectious diseases consultation service records. Clinical and radiographic data were collected by chart review and electronic records. MRSA strains were isolated from sputum, bronchoalveolar lavage, pleural fluid or blood cultures and confirmed using standard laboratory procedures. MRSA strains were characterized by susceptibility testing, pulsed-field gel electrophoresis, spa typing, agr typing and multilocus sequence typing. Testing for respiratory viruses was performed by appropriate serological testing of banked sera, or nucleic acid testing of nasopharyngeal or bronchoalveloar lavage specimens.RESULTS: Ten patients who presented or copresented with CA necrotizing pneumonia secondary to CA-MRSA from April 2004 to October 2011 were identified. The median length of stay was 22.5 days. Mortality was 20.0%. Classical risk factors for CA-MRSA were identified in seven of 10 (70.0%) cases. Chest tube placement occurred in seven of 10 patients with empyema. None of the patients had historical evidence of antecedent URI. In eight of 10 patients, serological or nucleic acid testing testing revealed no evidence of acute viral coinfection. Eight strains were CMRSA-10 (USA300). The remaining two strains were a USA300 genetically related strain and a USA1100 strain.CONCLUSION: Pneumonia secondary to CA-MRSA can occur in the absence of an antecedent URI. Infections due to CA-MRSA are associated with significant morbidity and mortality. Clinicians need to have an awareness of this clinical entity, particularly in patients who are in risk groups that predispose to exposure to this bacterium.Item Open Access Cytosine-guanosine deoxynucleotides (CpG DNA)-mediated Antiviral Response Against Avian Influenza Virus Infection(2016) Mohamed Abdul Cader, Mohamed Sarjoon; Abdul-Careem, Faizal; Schaetzl, Hermann; Fonseca, Kevin; Liljebjelke, KarenCytosine-guanosine deoxynucleotides (CpG DNA) can be used for the stimulation of toll-like receptor (TLR)21 signaling pathway in avian species, that ultimately leads to upregulation of gene transcription for pro-inflammatory molecules including nitric oxide (NO) and recruitment of innate immune cells. These innate immune mediators, play various roles in the innate immune system against viruses that infect mammals and avian species. The objective of the study was to determine the antiviral effect of NO, produced in response to in ovo delivery of CpG DNA, against H4N6 low pathogenic avian influenza virus (LPAIV) infection in the avian respiratory system. First, we observed that when CpG DNA is delivered at embryo day (ED)18 in ovo and subsequently challenged with H4N6 LPAIV at ED19 pre-hatch and day 1 post-hatch, CpG DNA reduces H4N6 LPAIV replication in the respiratory tract. Second, we observed that CpG DNA-mediated H4N6 LPAIV inhibition was attributable to NO production. Third, we observed that the antiviral response elicited by in ovo CpG DNA delivery is also associated with macrophage recruitment in the lungs. Finally, we showed that NO originated from macrophages is capable of eliciting antiviral response against H4N6 LPAIV infection in a dose-dependent manner. Altogether, CpG DNA-mediated antiviral response against H4N6 LPAIV infection is attributable to increased macrophage numbers in the lungs and elevated NO production originated from macrophages. The study provides insights into the mechanisms of CpG DNA-mediated antiviral response, particularly against H4N6 LPAIV infection in avian species.Item Open Access Experience with a triplex arbovirus nucleic acid test (NAT) at a Canadian Public Health Laboratory(2021-11-10) Choudhury, Saugata; Tellier, Raymond; Fonseca, Kevin; Berenger, Byron M.Abstract Background Dengue, chikungunya and zika infections occur in tropical and subtropical regions of the world. We describe the utilization of an in-house nucleic acid test (NAT) targeting all three viruses for febrile returning travelers in Alberta, Canada. Methods NAT was performed until 40 days from symptom onset or exposure due to the prolonged duration of zika virus RNA detection. From Sept 1, 2017 to August 31, 2019, 2552 specimens from 1932 patients were tested. Results Approximately 2% of patients tested were NAT positive for dengue virus (n = 42), chikungunya virus (n = 4), and zika virus (n = 1). The majority presented with fever, myalgia and rash. Regions with the most frequent travel included SouthEast Asia (68.5%), South America (25%) and the Caribbean (6.5%). Ct values were stronger (~ 1.5 logs) for patients within 1–3 days following onset of clinical symptoms than those presenting later. Nineteen patients had urine and plasma submitted; 5 were positive for both specimens and 2 were positive only for dengue virus in the urine. Also, Ct values were lower for plasma when compared to the corresponding urine. RNA was detected until 10 days and 5 days post-exposure in plasma and urine respectively for dengue virus. Conclusions Owing to dengue viremia detected beyond the conventional 7 days and low levels of circulating zika virus globally, a cutoff of 14 days from symptom onset to NAT is sufficient to diagnose acute cases. Inclusion of a zoonotic history form that collects appropriate clinical history results in improved test utilization.Item Open Access Hepatitis E in a Canadian Traveller(1995-01-01) Akai, Peter S; Fonseca, Kevin; Horne, Duff; Ho, MayHepatitis E is clinically indistinguishable from hepatitis A and is caused by an enterically transmitted rna virus that is endemic in developing countries of Asia, Africa, the Middle East and North America. This report describes a Canadian traveller to Nepal, Thailand and India with one of the first confirmed cases of hepatitis E reported in Canada. Although this disease is usually self-limited with no known sequelae, it may produce fulminant hepatitis with a high case fatality rate in pregnancy. Diagnosis can be confirmed by serological tests. Apart from strict food and beverage hygiene, there are presently no prophylactic measures against this disease, and pregnant women in the third trimester should avoid travel to endemic areas.Item Open Access Identification and Epidemiology of Severe Respiratory Disease due to Novel Swine-Origin Influenza A (H1N1) Virus Infection in Alberta(2010-01-01) Zahariadis, George; Joffe, Ari R; Talbot, James; deVilliers, Albert; Campbell, Patricia; Pabbaraju, Kanti; Wong, Sallene; Bastien, Nathalie; Li, Yan; Mitchell, Robyn L; Pang, Xiao-Li; Yanow, Stephanie; Chui, Linda; Predy, Gerald; Willans, David; Lee, Bonita E; Preiksaitis, Jutta K; Clement, Bev; Jacobs, Angela; Jaipaul, Joy; Fonseca, KevinBACKGROUND: In March 2009, global surveillance started detecting cases of influenza-like illness in Mexico. By mid-April 2009, two pediatric patients were identified in the United States who were confirmed to be infected by a novel influenza A (H1N1) strain. The present article describes the first identified severe respiratory infection and the first death associated with pandemic H1N1 (pH1N1) in Canada.METHODS: Enhanced public health and laboratory surveillance for pH1N1 was implemented throughout Alberta on April 24, 2009. Respiratory specimens from all patients with a respiratory illness and travel history or those presenting with a severe respiratory infection requiring hospitalization underwent screening for respiratory viruses using molecular methods. For the first severe case identified and the first death due to pH1N1, histocompatibility leukocyte antigens were compared by molecular methods.RESULTS: The first death (a 39-year-old woman) occurred on April 28, 2009, and on May 1, 2009, a 10-year-old child presented with severe respiratory distress due to pH1N1. Both patients had no travel or contact with anyone who had travelled to Mexico; the cases were not linked. Histocompatibility antigen comparison of both patients did not identify any notable similarity. pH1N1 strains identified in Alberta did not differ from the Mexican strain.CONCLUSION: Rapid transmission of pH1N1 continued to occur in Alberta following the first death and the first severe respiratory infection in Canada, which were identified without any apparent connection to Mexico or the United States. Contact tracing follow-up suggested that oseltamivir may have prevented ongoing transmission of pH1N1.Item Open Access Infectious laryngotracheitis infection in chickens raised in Western Canada: Molecular characterization and vaccine efficacy studies(2021-07-30) Barboza Solis, Catalina; Abdul Careem, Faizal; van der Meer, Frank; Fonseca, KevinGenomic surveillance of circulating infectious laryngotracheitis virus (ILTV) in specific geographical areas is vital for the control of the disease caused by ILTV, infectious laryngotracheitis (ILT). ILTV is endemic in backyard flocks in some Canadian provinces including Alberta (AB). Sporadic outbreaks of ILTV are reported throughout Canada in both commercial and non-commercial poultry flocks. However, there is a lack of information on the molecular nature of circulating ILTV strains associated with ILT in Canada. Vaccines are used for the control of ILT, and vaccination is employed only in certain provinces due to concerns of limitations of the currently available vaccines. In AB, only breeder flocks are vaccinated routinely in addition to a portion of the backyard flocks. Out of the two commercially available vaccines, the recombinant viral vector vaccines are considered the safest. This is due to their lack of bird-to-bird transmission and reversion to a virulent form. The first part of the thesis work was focussed on genotyping ILTV isolates linked to ILT clinical cases in AB and British Columbia (BC). Through partial sequencing of open reading frame (ORF) a and b using Sanger sequencing technology, we were able to genotype 27 ILTV isolates from AB and 5 ILTV isolates from BC. We demonstrated that the most common genotype causing ILT outbreaks in AB were chicken embryo origin (CEO) vaccine revertant ILTV strains and then, wild-type ILTV strains. In BC, we identified CEO vaccine and CEO revertant ILTV strains as cause of ILT outbreaks. The second part of this thesis was focussed on determining if recombinant herpesvirus of turkeys- laryngotracheitis (rHVT-LT) commercial vaccine could protect chickens from ILT induced by a wild-type ILTV strain isolated from AB. Our results showed that the rHVT-LT can decrease viral shedding though the oropharyngeal route. However, it did not mitigate clinical signs at the peak of the disease, and it failed to reduce viral replication in the feather tips. Overall, the work described in the thesis contributed to the knowledge on ILTV molecular epidemiology and vaccine-mediated control of ILT.Item Open Access Molecular characterization and pathogenicity studies of Canadian infectious laryngotracheitis virus isolates(2021-02-02) Perez Contreras, Ana Paulina; Abdul-Careem, Mohamed Faizal; Fonseca, Kevin; van der Meer, FrankThe extensive use of live-attenuated vaccines to control the upper respiratory tract viral infection in chicken known as infectious laryngotracheitis (ILT), has been associated with a surge in vaccine-related ILT outbreaks. It is documented that these ILT outbreaks are due to the regaining of virulence of the vaccine viruses due to multiple bird to bird passages following vaccination. These vaccine-originated infectious laryngotracheitis virus (ILTV) isolates are known as vaccine revertants. An additional concern is that the multiple live-attenuated vaccine ILTV and wild-type ILTV can recombine, resulting in ILTV strains with higher pathogenicity. To date, little is known about the molecular nature of the Canadian ILTV. The objectives of the present thesis work are to, 1) molecularly characterize the ILTV associated with ILT outbreaks in poultry flocks in Canada using a whole genome sequence approach and 2) study the pathogenicity of representative ILTV isolates in vivo. In achieving objective 1, It was found that most of the ILTV isolates of Canadian origin used in this study were genetically related to chicken embryo origin (CEO) live-attenuated vaccine ILTV strains. Evidence of recombination involving commonly used live-attenuated ILT vaccines was also detected in an ILTV isolate belonging to the British Columbia province. A second recombination event was found this time involving an ILTV isolate belonging to Alberta. This Alberta ILTV strain acted as a parental strain along with another live-attenuated ILT vaccine strain to give rise to an ILTV strain previously isolated in United States (US) territory. In objective 2, the pathogenicity of two wild-type and one CEO vaccine revertant ILTV isolates was compared, by infecting specific pathogen free chickens along with age-matched mock infected controls. We also used naïve contact chickens in order to determine the transmission potential of these ILTV isolates. It was found that the tested CEO vaccine revertant ILTV isolate can induce not only severe disease but also to transmit more efficiently than the wild-type ILTV isolates used for this study.Item Open Access Pediatric antibody responses to SARS-CoV-2 after infection and vaccination in Calgary, Canada(2024-07-18) Ricketson, Leah J.; Doucette, Emily J.; Alatorre, Isabella; Tarannum, Tarannum; Gray, Joslyn; Booth, William; Tipples, Graham; Charlton, Carmen; Kanji, Jamil N.; Fonseca, Kevin; Kellner, James D.Abstract Background There are few reports of longitudinal serologic responses in children following Sars-CoV-2 infection and vaccination. This study describes longitudinal SARS-CoV-2 antibody responses following infection, vaccination, or both (hybrid immunity) in a cohort of Canadian children. The objectives of our study were to compare antibody levels following SARS-CoV-2 infection, vaccination, and hybrid immunity and to examine antibody decline after final antigen exposure. Methods The Alberta Childhood COVID-19 Cohort (AB3C) study was a prospective longitudinal cohort study conducted from July 2020 to September 2022 with repeat sampling across 5 visits. Children under 18 years of age were enrolled for serial measurement of antibody responses to SARS-CoV-2 virus vaccine and infection. Results The final sample size was 919; participants were 50.5% female, 48.2% were > 12 years and 88.5% were white ethnicity. The median peak spike IgG level of those with only infection was not different from those with no vaccination or infection (233 AU/mL (IQR: 99–944 AU/mL) vs. 3 AU/mL (IQR: 1–5 AU/mL; P = 0.1765). Participants with infections after vaccination had higher IgG levels than those where infection preceded vaccination (median: 36,660 (IQR: 22,084 − 40,000 AU/mL) vs. 17,461 AU/mL (IQR: 10,617 − 33,212 AU/mL); P < 0.0001). In a linear mixed methods model, children with infection-only had low levels of antibody that stayed stable over the study duration without further antigen exposures. Those with infection after vaccination had the slowest rate of antibody decline over time at 4% (95%CI: 2-5%) per week, compared with children where infection preceded vaccine 7% (95%CI: 6-8%) per week. Conclusions Children with hybrid immunity conferred through vaccination (2 + doses) followed by a SARS-CoV-2 infection had the highest and longest lasting antibody levels, compared to children who had an infection followed by vaccination, vaccination-only, or infection-only. The longer-term clinical importance of these findings, related to prevention of repeated infections and severe outcomes and need for further vaccine doses, is not yet known.Item Open Access Prolonged SARS-CoV-2 infection following rituximab treatment: clinical course and response to therapeutic interventions correlated with quantitative viral cultures and cycle threshold values(2022-02-05) Thornton, Christina S.; Huntley, Kevin; Berenger, Byron M.; Bristow, Michael; Evans, David H.; Fonseca, Kevin; Franko, Angela; Gillrie, Mark R.; Lin, Yi-Chan; Povitz, Marcus; Shafey, Mona; Conly, John M.; Tremblay, AlainAbstract Background Detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA is completed through reverse transcriptase-PCR (RT-PCR) from either oropharyngeal or nasopharyngeal swabs, critically important for diagnostics but also from an infection control lens. Recent studies have suggested that COVID-19 patients can demonstrate prolonged viral shedding with immunosuppression as a key risk factor. Case presentation We present a case of an immunocompromised patient with SARS-CoV-2 infection demonstrating prolonged infectious viral shedding for 189 days with virus cultivability and clinical relapse with an identical strain based on whole genome sequencing, requiring a multi-modal therapeutic approach. We correlated clinical parameters, PCR cycle thresholds and viral culture until eventual resolution. Conclusions We successfully demonstrate resolution of viral shedding, administration of COVID-19 vaccination and maintenance of viral clearance. This case highlights implications in the immunosuppressed patient towards infection prevention and control that should consider those with prolonged viral shedding and may require ancillary testing to fully elucidate viral activity. Furthermore, this case raises several stimulating questions around complex COVID-19 patients around the role of steroids, effect of antiviral therapies in absence of B-cells, role for vaccination and the requirement of a multi-modal approach to eventually have successful clearance of the virus.Item Open Access Serological Response to Influenza Vaccination among Children Vaccinated for Multiple Influenza Seasons(PLoS, 2012-12-11) Rafiq, Sajjad; Russell, Margaret L.; Webby, Richard; Fonseca, Kevin; Smieja, Marek; Singh, Pardeep; Loeb, Mark