Réjean Dion’s research while affiliated with Institut National de Santé Publique du Québec (INSPQ) and other places

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Publications (23)


415. A Whole Genome Sequencing Analysis of a Multi-unit Long-term Care Facility COVID-19 Outbreak
  • Article
  • Full-text available

December 2021

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99 Reads

Open Forum Infectious Diseases

Ling Yuan Kong

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Background The coronavirus disease (COVID-19) pandemic has affected residents in long-term care facilities (LTCF) significantly. Understanding transmission dynamics in this setting is crucial to control the spread of COVID-19 in this population. Using whole genome sequencing (WGS) of SARS-CoV-2, we aimed to delineate the points of introduction and transmission pathways in a large LTCF in Quebec, Canada. Methods Between 2020-10-28 and 2021-01-09, COVID-19 cases occurred in 102 residents and 111 HCW at a 387-bed LTCF; cases were distributed in 11 units on 6 floors. As part of outbreak analysis, SARS-CoV-2 isolates underwent WGS using the Oxford Nanopore Minion and the Artic V3 protocol. Lineage attribution and sequence types (ST, within 3 mutations) were assigned based on Pangolin classification and variant analysis. Epidemiologic data including date of positive PCR test, resident room number and HCW work location were collected. Self-reported high-risk exposures were collected by HCW questionnaire via phone interview after consent. Cases and their ST, geo-temporal relations and HCW-reported exposures were examined via network plots and geography-based epidemic curves to infer points of introduction and paths of transmission. Results Of 170 isolates available from 100/102 residents and 70/111 HCW, 130 (76.4%) were successfully sequenced. Phylogenetic analysis revealed 7 separate introductions to the LTCF. Grouping of ST by units was observed, with temporal appearance of ST supporting HCW introduction in 7/11 units. Proportion of phone interview completion was low at 35% (26/70). Few HCW recalled specific high-risk exposures. Recalled exposures supported by genetic linkage revealed potential between-unit introductions from HCW-to-HCW transmission at work and outside the workplace (e.g. carpooling). On one unit, a wandering resident was identified as a likely source of transmission to other residents (Figure 1). Network plot of cases clustered by geographic unit, colour-coded by sequence type. Circles represent residents; addition signs represent healthcare workers. Blue lines represent identified high-risk exposures. Node labels represent floor and unit identifiers; 2 units per floor. Conclusion We demonstrate the complex genomic epidemiology of a multi-unit LTCF outbreak, putting into evidence the importance of a multi-faceted approach to limit transmission. This analysis highlights the utility of using WGS to uncover unsuspected transmission routes, such as HCW contact outside work, which can prompt new infection control measures. Disclosures All Authors: No reported disclosures

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Timeline of COVID-19 cases and sequencing in Québec up to June 1. A Comparison of confirmed cases (grey) reported by public health authorities and high-quality sequences used in this study (blue) distributed by collection date. *Official lockdown included stay home orders and closure of schools and daycares. **Except schools in the city of Montreal. Timeline and control measures are from [15, 16]. Sample dates of sequences can be slightly offset from official daily case count due to reporting lags. B Age distribution of sequenced cases (mean and range shown). C Variation in viral epidemiological dynamics as estimated by Tajima’s D. Boxplots represent 99 resampled estimates of Tajima’s D from random resamplings of 20 genome sequences for each 2-week time period. Tajima’s D values are only estimated for PANGO lineages with at least 20 sequences in a given time period
Analysis of introduction events. A Introduction event origins as a percentage of the total inferred by each method. B Number of introduction events by region of origin inferred by self-reported travel history, phylogenetic ancestral state reconstruction, or both combined. For phylogeny-only and combined estimates, the points represent the ML estimate, while the bars indicate the difference between DELTRAN and ACCTRAN estimates (as lower and upper bounds). “Canada” refers to importations from other provinces into Québec. “Unclear” implies no travel history was available and ASR was ambiguous. C Travel-related sequences and the TMRCAs of inferred introductions into Québec over time by geographic origin. Dark densities: small points indicate sampling dates of sequenced cases with travel history. Large black points indicate the sampling date of the first sequenced case associated with each region. Pale densities: small points indicate the TMRCA of the inferred introductions using phylogeny and travel history (thus the date of introduction into Québec will be later). Triangles are the TMRCA of the first inferred introduction from each region into Québec, based on the phylogeny. Asterisks indicate uncertainty due to stem singletons in a large polytomy. The number of introductions is normalized to a relative density within each geographic category (rows). Grey bar is the spring break period in Québec
Phylogeny of SARS-CoV-2 genomes sampled from Québec in global context. A Pink dots on the time-scaled phylogeny show the most recent common ancestors (MRCA) of introduction events into Québec, inferred with ML ASR. Blue dots are all Québec sequences in the dataset. The heatmap shows Nextstrain clade designations for all sequences in the tree. B The same phylogeny, highlighting (blue branches) the eight Québec transmission lineages that gave rise to over 50 sequenced cases. Their introductions (large circles) are colored by their inferred region of origin. The colored heatmap shows the geographic origin of all sequences in the tree
A minority of introduction events are successful and spread across regions. A Distribution of Québec transmission lineage sizes, inferred using maximum likelihood ASR, n = 615. B Correlation between transmission lineage size and the number of Québec health regions in which it was sampled (Pearson’s r = 0.62, 95% CI = 0.57–0.67, p < 2.2 × 10⁻¹⁶). C Transmission lineage sizes generated by each PANGO lineage. Each point represents an independent introduction event into Québec. D Estimates of dN/dS for each PANGO lineage in Québec. For each PANGO lineage, the boxplots represent the distribution of dN/dS across sampled genomes compared to the ancestral reference genome (Wuhan-1; Genbank Accession MN908947.3)
Introduction and duration of the 12 largest Québec transmission lineages each responsible for 40 or more sequenced cases. Left: Timelines are colored by the health region in which each Québec transmission lineage predominantly spread, and which SARS-CoV-2 lineage (Pangolin nomenclature) was responsible. Squares represent the date the lineage was first sampled, colored by their inferred origin. Open circles show the median TMRCA of each transmission lineage, with whiskers showing HPD 95% intervals estimated with BEAST. Right: median and HPD 95% interval of the effective reproductive number, Re, for each transmission lineage, estimated using BEAST (Methods). These transmission lineages were inferred by ML ASR. See Figure S2 for TMRCA estimates for the 21 largest transmission lineages, represented by at least 20 sequences

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A small number of early introductions seeded widespread transmission of SARS-CoV-2 in Québec, Canada

October 2021

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155 Reads

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28 Citations

Genome Medicine

Background Québec was the Canadian province most impacted by COVID-19, with 401,462 cases as of September 24th, 2021, and 11,347 deaths due mostly to a very severe first pandemic wave. In April 2020, we assembled the Coronavirus Sequencing in Québec (CoVSeQ) consortium to sequence SARS-CoV-2 genomes in Québec to track viral introduction events and transmission within the province. Methods Using genomic epidemiology, we investigated the arrival of SARS-CoV-2 to Québec. We report 2921 high-quality SARS-CoV-2 genomes in the context of > 12,000 publicly available genomes sampled globally over the first pandemic wave (up to June 1st, 2020). By combining phylogenetic and phylodynamic analyses with epidemiological data, we quantify the number of introduction events into Québec, identify their origins, and characterize the spatiotemporal spread of the virus. Results Conservatively, we estimated approximately 600 independent introduction events, the majority of which happened from spring break until 2 weeks after the Canadian border closed for non-essential travel. Subsequent mass repatriations did not generate large transmission lineages (> 50 sequenced cases), likely due to mandatory quarantine measures in place at the time. Consistent with common spring break and “snowbird” destinations, most of the introductions were inferred to have originated from Europe via the Americas. Once introduced into Québec, viral lineage sizes were overdispersed, with a few lineages giving rise to most infections. Consistent with founder effects, the earliest lineages to arrive tended to spread most successfully. Fewer than 100 viral introductions arrived during spring break, of which 7–12 led to the largest transmission lineages of the first wave (accounting for 52–75% of all sequenced infections). These successful transmission lineages dispersed widely across the province. Transmission lineage size was greatly reduced after March 11th, when a quarantine order for returning travellers was enacted. While this suggests the effectiveness of early public health measures, the biggest transmission lineages had already been ignited prior to this order. Conclusions Combined, our results reinforce how, in the absence of tight travel restrictions or quarantine measures, fewer than 100 viral introductions in a week can ensure the establishment of extended transmission chains.


A small number of early introductions seeded widespread transmission of SARS-CoV-2 in Québec, Canada

March 2021

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100 Reads

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1 Citation

Using genomic epidemiology, we investigated the arrival of SARS-CoV-2 to Québec, the Canadian province most impacted by COVID-19, with >280,000 positive cases and >10,000 deaths in a population of 8.5 million as of March 1st, 2021. We report 2,921 high-quality SARS-CoV-2 genomes in the context of >12,000 publicly available genomes sampled globally over the first pandemic wave (up to June 1st, 2020). By combining phylogenetic and phylodynamic analyses with epidemiological data, we quantify the number of introduction events into Québec, identify their origins, and characterize the spatio-temporal spread of the virus. Conservatively, we estimated at least 500 independent introduction events, the majority of which happened from spring break until two weeks after the Canadian border closed for non-essential travel. Subsequent mass repatriations did not generate large transmission lineages (>50 cases), likely due to mandatory quarantine measures in place at the time. Consistent with common spring break and 'snowbird' destinations, most of the introductions were inferred to have originated from Europe via the Americas. Fewer than 100 viral introductions arrived during spring break, of which 5-10 led to the largest transmission lineages of the first wave (accounting for 36-58% of all sequenced infections). These successful viral transmission lineages dispersed widely across the province, consistent with founder effects and superspreading dynamics. Transmission lineage size was greatly reduced after March 11th, when a quarantine order for returning travelers was enacted. While this suggests the effectiveness of early public health measures, the biggest transmission lineages had already been ignited prior to this order. Combined, our results reinforce how, in the absence of tight travel restrictions or quarantine measures, fewer than 100 viral introductions in a week can ensure the establishment of extended transmission chains.


Cryptosporidium spp.: Human incidence, molecular characterization and associated exposures in Québec, Canada (2016-2017)

February 2020

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71 Reads

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18 Citations

The aim of this study was to describe the epidemiology of human cryptosporidiosis in Québec from 2016 to 2017 and to identify possible exposures associated with the disease, and the dominant Cryptosporidium species in circulation. A descriptive analysis was performed on data collected from the provincial notifiable infectious diseases registry and the epidemiological investigation. Fecal sample were sent to the Laboratoire de santé publique du Québec for molecular characterization. In Québec, from January 1, 2016 to December 31, 2017, a total of 201 confirmed cases of cryptosporidiosis were notified. A peak in the number of reported cases was observed at the end of the summer. The regional public health department with the highest adjusted incidence rate for sex and age group for both years was that of Nunavik, in the north of Québec. A higher average annual incidence rate was observed for females between the ages of 20 to 34 years compared to males. Overall, for both males and females the distribution appeared to be bimodal with a first peak in children younger than five years old and a second peak in adults from 20 to 30 years of age. Molecular characterization showed that 23% (11/47) of cases were infected with C. hominis while 74% (35/47) were infected with C. parvum. Meanwhile, subtyping results identified by gp60 sequencing, show that all C. parvum subtypes belonged to the IIa family, whereas the subtypes for C. hominis belonged to the Ia, Ib, and Id families. Finally, the epidemiological investigation showed that diarrhea was the most common reported symptom with 99% (72/73) of investigated cases having experienced it. This first brief epidemiological portrait of cryptosporidiosis in Québec has allowed for the description, both at the provincial and regional level, of the populations that could be particularly vulnerable to the disease.


Acute Toxoplasmosis among Canadian Deer Hunters Associated with Consumption of Undercooked Deer Meat Hunted in the United States

February 2020

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131 Reads

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53 Citations

Emerging Infectious Diseases

We conducted a recent investigation in Quebec, Canada, concerning Canadian deer hunters who went to the United States to hunt deer and returned with symptoms of fever, severe headache, myalgia, and articular pain of undetermined etiology. Further investigation identified that a group of 10 hunters from Quebec attended a hunting retreat in Illinois (USA) during November 22-December 4, 2018. Six of the 10 hunters had similar symptoms and illness onset dates. Serologic tests indicated a recent toxoplasmosis infection for all symptomatic hunters, and the risk factor identified was consumption of undercooked deer meat. Among asymptomatic hunters, 2 were already immune to toxoplasmosis, 1 was not immune, and the immune status of 1 remains unknown. Outbreaks of acute toxoplasmosis infection are rare in North America, but physicians should be aware that such outbreaks could become more common.


Molecular surveillance of hepatitis C virus genotypes identifies the emergence of a genotype 4d lineage among men in Quebec, 2001–2017

September 2019

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16 Reads

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6 Citations

Canada Communicable Disease Report

Background: Molecular phylogenetics are generally used to confirm hepatitis C virus (HCV) transmission events. In addition, the Laboratoire de santé publique du Québec (LSPQ) has been using molecular phylogenetics for surveillance of HCV genotyping since November 2001. Objectives: To describe the emergence of a specific lineage of HCV genotype 4d (G4d) and its characteristics using molecular phylogenetics as a surveillance tool for identifying HCV strain clustering. Methods: The LSPQ prospectively applied Sanger sequencing and phylogenetic analysis to determine the HCV genotype on samples collected from November 2001 to December 2017. When a major G4d cluster was identified, demographic information, HIV-infection status and syphilis test results were analyzed. Results: Phylogenetic analyses performed on approximately 22,000 cases identified 122 G4d cases. One major G4d cluster composed of 37 cases was singled out. Two cases were identified in 2010, 10 from 2011–2014 and 25 from 2015–2017. Cases in the cluster were concentrated in two urban health regions. Compared to the other G4d cases, cluster cases were all male (p<0.001) and more likely to be HIV-positive (adjusted risk ratio: 4.4; 95% confidence interval: 2.5–7.9). A positive syphilis test result was observed for 27 (73%) of the cluster cases. The sequences in this cluster and of four outlier cases were located on the same monophyletic lineage as G4d sequences reported in HIV-positive men who have sex with men (MSM) in Europe. Conclusion: Molecular phylogenetics enabled the identification and surveillance of ongoing transmission of a specific HCV G4d lineage in HIV-positive and HIV-negative men in Quebec and its cross-continental spread. This information can orient intervention strategies to avoid transmission of HCV in MSM.


Number, proportion and mean incidence rate of hepatitis C virus and number and proportion of hepatitis C virus genotype 4d cases among cluster A and others, by health regions, Quebec
Molecular surveillance of hepatitis C virus genotypes identifies the emergence of a genotype 4d lineage among men in Quebec, 2001–2017

September 2019

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54 Reads

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8 Citations

Canada Communicable Disease Report

Background: Molecular phylogenetics are generally used to confirm hepatitis C virus (HCV) transmission events. In addition, the Laboratoire de santé publique du Québec (LSPQ) has been using molecular phylogenetics for surveillance of HCV genotyping since November 2001. Objectives: To describe the emergence of a specific lineage of HCV genotype 4d (G4d) and its characteristics using molecular phylogenetics as a surveillance tool for identifying HCV strain clustering. Methods: The LSPQ prospectively applied Sanger sequencing and phylogenetic analysis to determine the HCV genotype on samples collected from November 2001 to December 2017. When a major G4d cluster was identified, demographic information, HIV-infection status and syphilis test results were analyzed. Results: Phylogenetic analyses performed on approximately 22,000 cases identified 122 G4d cases. One major G4d cluster composed of 37 cases was singled out. Two cases were identified in 2010, 10 from 2011-2014 and 25 from 2015-2017. Cases in the cluster were concentrated in two urban health regions. Compared to the other G4d cases, cluster cases were all male (p<0.001) and more likely to be HIV-positive (adjusted risk ratio: 4.4; 95% confidence interval: 2.5-7.9). A positive syphilis test result was observed for 27 (73%) of the cluster cases. The sequences in this cluster and of four outlier cases were located on the same monophyletic lineage as G4d sequences reported in HIV-positive men who have sex with men (MSM) in Europe. Conclusion: Molecular phylogenetics enabled the identification and surveillance of ongoing transmission of a specific HCV G4d lineage in HIV-positive and HIV-negative men in Quebec and its cross-continental spread. This information can orient intervention strategies to avoid transmission of HCV in MSM.



Results of a population screening intervention for tuberculosis in a Nunavik village, Quebec, 2015–2016

October 2018

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10 Reads

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4 Citations

Canada Communicable Disease Report

Background: A small village in Nunavik, Quebec experienced a tuberculosis (TB) outbreak in 2012-2013 and then a resurgence in 2015-2016. Cases were still occurring, despite the fact that contact tracing had already been conducted on one quarter of the population. A decision was taken to conduct large-scale screening of the population for TB. Objective: To describe the results of a population-based TB screening intervention designed to identify individuals with latent TB infection (LTBI) or active TB requiring treatment. Methodology: The history of TB infection (either active TB or LTBI, defined as a positive tuberculin skin test result of at least five mm induration) and treatment (considered adequate if at least 80% of prescribed doses were taken) were determined. Those who were two years of age and older and had not been included in contact tracing after June 1, 2015 were included for TB screening (n=1,026 eligible individuals). Screening included a nurse assessment, tuberculin skin test (TST) for those with previous negative TST or of unknown status and chest X-ray for the others. Results: Of the eligible individuals in the affected village, 1,004 (98%) participated in the screening. Of these, 30% had a history of previous TB infection. A TST screening was administered to 71% of the participants, 10% of whom had positive results. Assessments were performed on 425 participants and 385 underwent a chest X-ray. Fifty-two cases of previously diagnosed active TB and three cases of new active TB were documented. In addition, there were 247 individuals with LTBI who had been previously identified (191 were found to have had adequate LTBI treatment, 56 were found to have had inadequate LTBI treatment) and 69 were identified with de novo LTBI. In addition, 633 participants were found to have no TB infection. There were 125 participants who were referred for LTBI treatment. Follow-up information was available for 120 and 85 (71%) of these completed the treatment. Conclusion: Within this northern village, which had persistent TB transmission despite classic control measures, population-based screening had a high degree of coverage and was an effective way to detect additional cases of individuals with active TB and those with LTBI.



Citations (17)


... Une fois que la transmission à l'intérieur du pays a commencé, les modèles d'importation peuvent fournir des données sur les cas importés aux modèles de transmission communautaire(34,35). Comme on l'a vu lors de la pandémie de COVID-19, pour les provinces et territoires plus petits, l'accent peut être mis sur l'importation plutôt que sur la transmission communautaire. Il peut y avoir relativement peu d'itinéraires de voyage dans les petites régions, qui peuvent être surveillés et gérés pour prévenir les éclosions communautaires, au début et pendant une pandémie.Le couplage de l'analyse de la propagation géographique avec des analyses génomiques est de plus en plus utilisé pour modéliser la transmission et détecter les sources de nouveaux cas pour une variété d'agents pathogènes, notamment la COVID-19(36)(37)(38). Une utilisation pratique en temps réel de ces méthodes est Nextstrain (39), une plateforme et un tableau de bord à code source ouvert qui permet aux décideurs, aux scientifiques et au grand public de suivre, en temps réel, l'évolution et la propagation du virus à l'échelle mondiale. ...

Reference:

Modélisation mathématique pour la préparation aux pandémies au Canada : leçons de la COVID-19
A small number of early introductions seeded widespread transmission of SARS-CoV-2 in Québec, Canada

Genome Medicine

... In this study, C. parvum subtype IIaA17G2R1 was identified in dogs for the first time. In fact, molecular epidemiological studies of Cryptosporidium spp., revealed that subtype IIaA17G2R1 was relatively common in livestock, occurring mainly in cattle [72] but appearing occasionally in other animals including sheep, camels, goats, rodents, mustangs and fish [73][74][75][76][77][78]. This subtype has also been reported in human cases of cryptosporidiosis in Iran and Jordan [79,80]. ...

Cryptosporidium spp.: Human incidence, molecular characterization and associated exposures in Québec, Canada (2016-2017)

... For the majority of individuals, symptoms, if they occur, are generally mild and resemble other illnesses, such as influenza, Lyme disease, Q fever, haematological abnormalities, and mumps. As a result, it is likely that many individuals overlook these symptoms or experience a delay in receiving a diagnosis [3]. Individuals with impaired immune systems and foetuses infected during pregnancy are susceptible to infection, which can be fatal. ...

Acute Toxoplasmosis among Canadian Deer Hunters Associated with Consumption of Undercooked Deer Meat Hunted in the United States

Emerging Infectious Diseases

... The use of genomic data to infer and characterize transmission networks of various pathogens has grown in prominence in the past 2 decades, with applications to a growing list of pathogens, including viruses such as HIV (Paraskevis et al., 2016), hepatitis C virus (HCV) (Murphy et al., 2019a), or influenza A virus (IAV) (Jombart et al., 2011), and bacteria such as M. tuberculosis (Mai et al., 2018) or A. baumanii (Thoma et al., 2022). Notably, genomic surveillance had a prominent role during the COVID-19 pandemic, including the use of sequencing for the study of transmission clusters (von Rotz et al., 2023;Campigotto et al., 2023). ...

Molecular surveillance of hepatitis C virus genotypes identifies the emergence of a genotype 4d lineage among men in Quebec, 2001–2017
  • Citing Article
  • September 2019

Canada Communicable Disease Report

... Here, we obtained a further 17 ORFs of subtype HCV4d significantly increasing the number of sequences publicly available on GenBank. Previous works have found connections between the HCV4d transmission networks in MSM among several European countries as well as Australia and Canada, with one study finding that spread could not be attributed to IVDU [30,[51][52][53]. Of our 17 HCV4d sequences, 13 were in a cluster, 12 of which were HIV-positive MSM. ...

Molecular surveillance of hepatitis C virus genotypes identifies the emergence of a genotype 4d lineage among men in Quebec, 2001–2017

Canada Communicable Disease Report

... People with a TST result of at least 5 mm or who had a history of LTBI or active TB underwent chest radiography. 15 The NRBHSS worked with local staff as well as staff flown in to the villages to organize these screening campaigns. Additional details are provided in the Screening campaigns section of Appendix 1, available at www.cmaj.ca/lookup/ ...

Results of a population screening intervention for tuberculosis in a Nunavik village, Quebec, 2015–2016
  • Citing Article
  • October 2018

Canada Communicable Disease Report

... Therefore, Egyptians still favor fresh liver meals over those that are frozen. However, consuming veal liver was linked to an increased risk of campylobacteriosis, as indicated by the presence of priority pathogens such as Salmonella, Campylobacter, and Escherichia coli O157:H7 in veal liver samples collected from slaughterhouses and retail outlets (Gaulin et al., 2018). Microbiological criteria, which are also called performance standards, are made to set control limits for the contamination of pathogens in food or environments where food is produced along the supply chain using a certain sampling plan and measurement method (Gamil et al., 2024) with the end goal of lowering the number of foodborne illnesses. ...

Veal Liver as Food Vehicle for Human Campylobacter Infections

Emerging Infectious Diseases

... Эпидемиологическую эффективность вакцины Bexsero против гонореи в этом случае оценили в 59%. Более высокую эф фективность вакцины Bexsero, по сравнению с но возеландской, авторы объяснили присутствием добавочных белков [23,24]. По мере распростра нения вакцины Bexsero сходные сообщения стали поступать из разных частей света. ...

Possible Impact of Wide-scale Vaccination Against Serogroup B Neisseria Meningitidis on Gonorrhea Incidence Rates in One Region of Quebec, Canada

Open Forum Infectious Diseases

... CC1 and CC3 are representative genotypes found in hot springs and other bath facilities, respectively. ST1, belonging to CC4, is also the most predominant ST in cooling towers in Japan (Nakanishi et al. 2019) and is known to be environmentally and clinically predominant worldwide (Kozak-Muiznieks et al. 2014;Lévesque et al. 2016). Therefore, it is suggested that ST1 is widely present in artificial environmental waters, regardless of region. ...

Molecular Typing of Legionella pneumophila Isolates in the Province of Quebec from 2005 to 2015

... This prevalence was also higher than many previous studies conducted in the past and reported from different parts of the world including 18% in Canada, 21% in USA and 24% in Australia. 16,17,18 As per our study, no substantial evidence was seen between Cryptosporidiosis and gender groups and similar results were reported by Khan et.al., 15 Similar results were also reported in the studies conducted in Nepal and China 19,20 and they also reported a random distribution of the positive cases among males and females. ...

Cryptosporidium hominis Is a Newly Recognized Pathogen in the Arctic Region of Nunavik, Canada: Molecular Characterization of an Outbreak