Recent publications from TDC authors

Suboptimal immunization coverage among Canadian rheumatology patients in routine clinical care.

J Rheumatol. 2019 Jul 15;:

Authors: Qendro T, de la Torre ML, Panopalis P, Hazel E, Ward BJ, Colmegna I, Hudson M

Abstract
OBJECTIVE: To assess vaccination coverage and predictors of vaccination among a Canadian population of rheumatology patients in routine clinical care.
METHODS: In this cross-sectional study, consecutive adult patients presenting to a tertiary rheumatology clinic at the McGill University Health Center between May and September 2015 were asked to fill a survey on vaccination. Patients self-identified as having rheumatoid arthritis (RA), systemic autoimmune rheumatic diseases (SARD), spondyloarthropathies (SpA), or other diseases (OD). Multivariate logistical regression analyses were performed to evaluate patient and physician factors associated with vaccination (influenza, pneumococcal, hepatitis B virus [HBV]). Published Quebec general population influenza and pneumococcal vaccination rates in those aged ≥ 65 were used as comparative baseline rates.
RESULTS: 352 patients were included in the analysis (RA:136, SARD:113, SpA:47, OD:56). Vaccination rates were reported as: (1) influenza: RA:48.5%, SARD:42.0%, SpA:31.9%, OD:88.9%, Quebec general population:58.5%; (2) pneumococcal: RA:42.0%, SARD:37.8%, SpA:29.7%, OD:33.3%, Quebec general population:53.2%; (3) HBV: RA:33.6%, SARD:55.6%, SpA:73.5%, OD:36.8%; and (4) herpes zoster: RA:5.6%, SARD:28.6%, SpA:25.0%, OD:16.7%. Physician recommendation was the strongest independent predictor of vaccination across all vaccine types (influenza: OR 8.56, 95% CI 2.80-26.2, p<0.001; pneumococcal: OR 314, 95% CI 73.0-1353, p<0.001; HBV: OR 12.8, 95% CI 5.27-31.1, p<0.001). Disease group, disease duration, comorbidities, treatment type, and being followed by a primary care physician were not significantly associated with vaccination.
CONCLUSION: There is suboptimal immunization coverage among ambulatory rheumatology patients. An important role for patient and physician education is highlighted from our study, especially as physician recommendation of vaccination was strongly predictive of vaccine uptake.

PMID: 31308211 [PubMed - as supplied by publisher]

Fractional dosing of yellow fever vaccine during shortages: perspective from Canada.

J Travel Med. 2018 01 01;25(1):

Authors: Teitelbaum P, Bui YG, Libman M, McCarthy A

PMID: 30346564 [PubMed - indexed for MEDLINE]

Infectious diseases acquired by international travellers visiting the USA.

J Travel Med. 2018 08 01;25(1):

Authors: Stoney RJ, Esposito DH, Kozarsky P, Hamer DH, Grobusch MP, Gkrania-Klotsas E, Libman M, Gautret P, Lim PL, Leder K, Schwartz E, Sotir MJ, Licitra C, GeoSentinel Surveillance Network

Abstract
Background: Estimates of travel-related illness have focused predominantly on populations from highly developed countries visiting low- or middle-income countries, yet travel to and within high-income countries is very frequent. Despite being a top international tourist destination, few sources describe the spectrum of infectious diseases acquired among travellers to the USA.
Methods: We performed a descriptive analysis summarizing demographic and travel characteristics, and clinical diagnoses among non-US-resident international travellers seen during or after travel to the USA at a GeoSentinel clinic from 1 January 1997 through 31 December 2016.
Results: There were 1222 ill non-US-resident travellers with 1393 diagnoses recorded during the 20-year analysis period. Median age was 40 (range 0-86 years); 52% were female. Patients visited from 63 countries and territories, most commonly Canada (31%), Germany (14%), France (9%) and Japan (7%). Travellers presented with a range of illnesses; skin and soft tissue infections of unspecified aetiology were the most frequently reported during travel (29 diagnoses, 14% of during-travel diagnoses); arthropod bite/sting was the most frequently reported after travel (173 diagnoses, 15% after-travel diagnoses). Lyme disease was the most frequently reported arthropod-borne disease after travel (42, 4%). Nonspecific respiratory, gastrointestinal and systemic infections were also among the most frequently reported diagnoses overall. Low-frequency illnesses (<2% of cases) made up over half of diagnoses during travel and 41% of diagnoses after travel, including 13 cases of coccidioidomycosis and mosquito-borne infections like West Nile, dengue and Zika virus diseases.
Conclusions: International travellers to the USA acquired a diverse array of mostly cosmopolitan infectious diseases, including nonspecific respiratory, gastrointestinal, dermatologic and systemic infections comparable to what has been reported among travellers to low- and middle-income countries. Clinicians should consider the specific health risks when preparing visitors to the USA and when evaluating and treating those who become ill.

PMID: 30124885 [PubMed - indexed for MEDLINE]

Epidemiological aspects of travel-related systemic endemic mycoses: a GeoSentinel analysis, 1997-2017.

J Travel Med. 2018 08 01;25(1):

Authors: Salzer HJF, Stoney RJ, Angelo KM, Rolling T, Grobusch MP, Libman M, López-Vélez R, Duvignaud A, Ásgeirsson H, Crespillo-Andújar C, Schwartz E, Gautret P, Bottieau E, Jordan S, Lange C, Hamer DH, GeoSentinel Surveillance Network

Abstract
Background: International travel has increased in the past few decades, placing more travellers at risk of acquiring systemic endemic mycoses. There are limited published data on systemic endemic mycoses among international travellers. We report epidemiological characteristics of non-migrant, international travellers who acquired systemic endemic mycoses during travel.
Methods: We analysed records of non-migrant international travellers with a confirmed diagnosis of histoplasmosis, coccidioidomycosis, paracoccidioidomycosis, blastomycosis or talaromycosis reported from 1997 through 2017 to GeoSentinel, a global surveillance network now consisting of 70 travel or tropical medicine centres in 31 countries.
Results: Sixty-nine records met the inclusion criteria. Histoplasmosis was most frequently reported; the 51 travellers with histoplasmosis had the lowest median age (30 years; range: 8-85) and shortest median duration of travel (12 days; range: 5-154). Coccidioidomycosis was reported in 14 travellers; travellers with coccidioidomycosis were older (median 62 years; range: 22-78) and had the longest median number of days between return from travel and presentation to a GeoSentinel site (55 days; range: 17-273). Almost all travellers with coccidioidomycosis were exposed in the USA. Other systemic endemic mycoses were less frequently reported, including blastomycosis (three travellers) and talaromycosis (one traveller).
Conclusions: Although relatively rare, systemic endemic mycoses should be considered as potential travel-related infections in non-migrant international travellers. Epidemiological exposures should be used to guide diagnostic evaluations and treatment.

PMID: 30085265 [PubMed - indexed for MEDLINE]

Promoting the health of migrants: what is the role of the travel medicine community?

J Travel Med. 2018 01 01;25(1):

Authors: Greenaway C

PMID: 30060128 [PubMed - indexed for MEDLINE]

Validation of the Seegene RV15 multiplex PCR for the detection of influenza A subtypes and influenza B lineages during national influenza surveillance in hospitalized adults.

J Med Microbiol. 2019 Jul 02;:

Authors: LeBlanc JJ, ElSherif M, Mulpuru S, Warhuus M, Ambrose A, Andrew M, Boivin G, Bowie W, Chit A, Dos Santos G, Green K, Halperin SA, Hatchette TF, Ibarguchi B, Johnstone J, Katz K, Langley JM, Lagacé-Wiens P, Loeb M, Lund A, MacKinnon-Cameron D, McCarthy A, McElhaney JE, McGeer A, Poirier A, Powis J, Richardson D, Semret M, Shinde V, Smyth D, Trottier S, Valiquette L, Webster D, Ye L, McNeil SA

Abstract
BACKGROUND: The Serious Outcomes Surveillance Network of the Canadian Immunization Research Network (CIRN SOS) has been performing active influenza surveillance since 2009 (ClinicalTrials.gov identifier: NCT01517191). Influenza A and B viruses are identified and characterized using real-time reverse-transcriptase polymerase chain reaction (RT-PCR), and multiplex testing has been performed on a subset of patients to identify other respiratory virus aetiologies. Since both methods can identify influenza A and B, a direct comparison was performed.
METHODS: Validated real-time RT-PCRs from the World Health Organization (WHO) to identify influenza A and B viruses, characterize influenza A viruses into the H1N1 or H3N2 subtypes and describe influenza B viruses belonging to the Yamagata or Victoria lineages. In a subset of patients, the Seeplex RV15 One-Step ACE Detection assay (RV15) kit was also used for the detection of other respiratory viruses.
RESULTS: In total, 1111 nasopharyngeal swabs were tested by RV15 and real-time RT-PCRs for influenza A and B identification and characterization. For influenza A, RV15 showed 98.0 % sensitivity, 100 % specificity and 99.7 % accuracy. The performance characteristics of RV15 were similar for influenza A subtypes H1N1 and H3N2. For influenza B, RV15 had 99.2 % sensitivity, 100 % specificity and 99.8 % accuracy, with similar assay performance being shown for both the Yamagata and Victoria lineages.
CONCLUSIONS: Overall, the detection of circulating subtypes of influenza A and lineages of influenza B by RV15 was similar to detection by real-time RT-PCR. Multiplex testing with RV15 allows for a more comprehensive respiratory virus surveillance in hospitalized adults, without significantly compromising the reliability of influenza A or B virus detection.

PMID: 31264957 [PubMed - as supplied by publisher]

Evolutionary genomics of anthroponosis in Cryptosporidium.

Nat Microbiol. 2019 05;4(5):826-836

Authors: Nader JL, Mathers TC, Ward BJ, Pachebat JA, Swain MT, Robinson G, Chalmers RM, Hunter PR, van Oosterhout C, Tyler KM

Abstract
Human cryptosporidiosis is the leading protozoan cause of diarrhoeal mortality worldwide, and a preponderance of infections is caused by Cryptosporidium hominis and C. parvum. Both species consist of several subtypes with distinct geographical distributions and host preferences (that is, generalist zoonotic and specialist anthroponotic subtypes). The evolutionary processes that drive the adaptation to the human host and the population structures of Cryptosporidium remain unknown. In this study, we analyse 21 whole-genome sequences to elucidate the evolution of anthroponosis. We show that Cryptosporidium parvum splits into two subclades and that the specialist anthroponotic subtype IIc-a shares a subset of loci with C. hominis that is undergoing rapid convergent evolution driven by positive selection. C. parvum subtype IIc-a also has an elevated level of insertion and deletion mutations in the peri-telomeric genes, which is also a characteristic of other specialist subtypes. Genetic exchange between Cryptosporidium subtypes plays a prominent role throughout the evolution of the genus. Interestingly, recombinant regions are enriched for positively selected genes and potential virulence factors, which indicates adaptive introgression. Analysis of 467 gp60 sequences collected from locations across the world shows that the population genetic structure differs markedly between the main zoonotic subtype (isolation-by-distance) and the anthroponotic subtype (admixed population structure). We also show that introgression between the four anthroponotic Cryptosporidium subtypes and species included in this study has occurred recently, probably within the past millennium.

PMID: 30833731 [PubMed - indexed for MEDLINE]

The rise in travel-associated measles infections - GeoSentinel, 2015-2019.

J Travel Med. 2019 Jun 20;:

Authors: Angelo KM, Libman M, Gautret P, Barnett E, Grobusch MP, Hagmann SHF, Gobbi F, Schwartz E, van Genderen PJJ, Asgeirsson H, Hamer DH, GeoSentinel Network

PMID: 31218359 [PubMed - as supplied by publisher]

Assessment of population immunity to measles in Ontario, Canada: A Canadian Immunization Research Network (CIRN) Study.

Hum Vaccin Immunother. 2019 Jun 11;:

Authors: Bolotin S, Severini A, Hatchette T, McLachlan E, Savage R, Hughes SL, Wang J, Deeks SL, Wilson S, Brisson M, Halperin SA, Gubbay J, Mazzulli T, Serhir B, Ward BJ, Crowcroft N, Immunity of Canadians and Risk of Epidemics (iCARE) Network

Abstract
Canada eliminated measles in 1998. We conducted a sero-epidemiology study to estimate population immunity to measles in the province of Ontario, Canada and to identify groups at higher risk of outbreaks. We used a previously developed modified enzyme immunoassay to test 1,199 residual sera from patients aged 1-39 years. We re-tested negative and equivocal sera using a plaque reduction neutralization assay. We interpreted our results in the context of Ontario's immunization program and vaccine coverage data. Of 1,199 sera, 1035 (86.3%, 95% confidence interval (CI) 84.4, 88.2) were above the measles threshold for protection, 70 (5.8%, 95% CI 4.5, 7.2) were equivocal and 94 (7.8%, 95% CI 6.3, 9.4) were negative. The proportion of positive sera was highest for those 1-5 years, with 180/199 (90.5%, 95% CI 86.4, 94.5) positive sera, and lowest for those age 12-19 years, at 158/199 (79.4%, 95% CI 73.8, 85.0). Adjusted for age, females were more likely than males to have antibody titres above the threshold of protection (odds ratio = 1.60, 95% CI 1.14, 2.24). Most of the study cohort was eligible for two measles vaccine doses, and vaccine uptake in Ontario is >90% for school-aged cohorts. We observed a higher than expected proportion of sera with antibody levels below the threshold of protection, suggesting that immunity in some Ontario age-groups may be waning, despite high vaccine coverage. Alternatively, the traditional measles correlate of protection may not be an appropriate measure of population protection in measles-eliminated settings.

PMID: 31184979 [PubMed - as supplied by publisher]

Immunogenicity and safety of a quadrivalent plant-derived virus like particle influenza vaccine candidate-Two randomized Phase II clinical trials in 18 to 49 and ≥50 years old adults.

PLoS One. 2019;14(6):e0216533

Authors: Pillet S, Couillard J, Trépanier S, Poulin JF, Yassine-Diab B, Guy B, Ward BJ, Landry N

Abstract
BACKGROUND: New influenza vaccines eliciting more effective protection are needed, particularly for the elderly who paid a large and disproportional toll of hospitalization and dead during seasonal influenza epidemics. Low (≤15 μg/strain) doses of a new plant-derived virus-like-particle (VLP) vaccine candidate have been shown to induce humoral and cellular responses against both homologous and heterologous strains in healthy adults 18-64 years of age. The two clinical trials reported here addressed the safety and immunogenicity of higher doses (≥15 μg/strain) of quadrivalent VLP candidate vaccine on 18-49 years old and ≥50 years old subjects. We also investigated the impact of alum on the immunogenicity induced by lower doses of the vaccine candidate.
METHOD: In the first Phase II trial reported here (NCT02233816), 18-49 year old subjects received 15, 30 or 60 μg/strain of a hemagglutinin-bearing quadrivalent virus-like particle (QVLP) vaccine or placebo. In the second trial (NCT02236052), ≥50 years old subjects received QVLP as above or placebo with additional groups receiving 7.5 or 15 μg/strain with alum. Along with safety recording, the humoral and cell-mediated immune responses were analyzed.
RESULTS: Local and systemic side-effects were similar to those reported previously. The QVLP vaccine induced significant homologous and heterologous antibody responses at the two higher doses, the addition of alum having little-to-no effect. Serologic outcomes tended to be lower in ≥50 years old subjects previously vaccinated. The candidate vaccine also consistently elicited both homologous and heterologous antigen-specific CD4+ T cells characterized by their production of interferon-gamma (IFN-γ), interleukine-2 (IL-2) and/or tumor-necrosis factor alpha (TNF-α) upon ex vivo antigenic restimulation.
CONCLUSION: Overall, the 30 μg dose produced the most consistent humoral and cellular responses in both 18-49 and ≥50 years old subjects, strongly supporting the clinical development of this candidate vaccine. That particular dose was chosen to test in the ongoing Phase III clinical trial.

PMID: 31166987 [PubMed - in process]

Characterization of the innate stimulatory capacity of plant-derived virus-like particles bearing influenza hemagglutinin.

Vaccine. 2018 12 18;36(52):8028-8038

Authors: Won SY, Hunt K, Guak H, Hasaj B, Charland N, Landry N, Ward BJ, Krawczyk CM

Abstract
Cell-mediated immunity is an important component of immediate and long-term anti-viral protection. Dendritic cells (DCs) are essential for the induction of cell-mediated immunity by instructing the activation and differentiation of antigen-specific T cell responses. Activated DCs that express co-stimulatory molecules and pro-inflammatory cytokines are necessary to promote the development of type 1 immune responses required for viral control. Here we report that plant-derived virus-like particles (VLPs) bearing influenza hemagglutinins (HA) directly stimulate mouse and human DCs. DCs exposed to H1- and, to a lesser extent, H5-VLPs in vitro rapidly express co-stimulatory molecules and produce pro-inflammatory cytokines including IL-12, IL-6 and TNFα. Furthermore, these VLPs support the activation and differentiation of antigen-specific T cell responses. Mechanistically, H1-VLPs stimulate the activation of kinases typically activated downstream of pattern recognition receptors including AKT, p38, and p42/44 ERK. In vivo, immunization with plant-derived VLPs induce the accumulation of both cDC1s and cDC2 in the draining lymph node and a corresponding increase in T and B cells. VLPs devoid of HA protein activate DCs, suggesting they are intrinsically immunostimulatory. Together, the results demonstrate that these candidate plant-derived VLP vaccines have an inherent and direct stimulatory effect on DCs and can enhance the ability of DCs to promote Type 1 immune responses.

PMID: 30448064 [PubMed - indexed for MEDLINE]

Opportunities and barriers to implementing antibiotic stewardship in low and middle-income countries: Lessons from a mixed-methods study in a tertiary care hospital in Ethiopia.

PLoS One. 2018;13(12):e0208447

Authors: Gebretekle GB, Haile Mariam D, Abebe W, Amogne W, Tenna A, Fenta TG, Libman M, Yansouni CP, Semret M

Abstract
BACKGROUND: Global action plans to tackle antimicrobial resistance (AMR) include implementation of antimicrobial stewardship (AMS), but few studies have directly addressed the challenges faced by low and middle-income countries (LMICs). Our aim was to explore healthcare providers' knowledge and perceptions on AMR, and barriers/facilitators to successful implementation of a pharmacist-led AMS intervention in a referral hospital in Ethiopia.
METHODS: Tikur Anbessa Specialized Hospital (TASH) is an 800-bed tertiary center in Addis Ababa, and the site of an ongoing 4-year study on AMR. Between May and July 2017, using a mixed approach of quantitative and qualitative methods, we performed a cross-sectional survey of pharmacists and physicians using a pre-tested questionnaire and semi-structured interviews of purposively selected respondents until thematic saturation. We analyzed differences in proportions of agreement between physicians and pharmacists using χ2 and fisher exact tests. Qualitative data was analyzed thematically.
FINDINGS: A total of 406 survey respondents (358 physicians, 48 pharmacists), and 35 key informants (21 physicians and 14 pharmacists) were enrolled. The majority of survey respondents (>90%) strongly agreed with statements regarding the global scope of AMR, the need for stewardship, surveillance and education, but their perceptions on factors contributing to AMR and their knowledge of institutional resistance profiles for common bacteria were less uniform. Close to 60% stated that a significant proportion of S. aureus infections were caused by methicillin-resistant strains (an incorrect statement), while only 48% thought a large proportion of gram-negative infections were caused by cephalosporin-resistant strains (a true statement). Differences were noted between physicians and pharmacists: more pharmacists agreed with statements on links between use of broad-spectrum antibiotics and AMR (p<0.022), but physicians were more aware that lack of diagnostic tests led to antibiotic overuse (p<0.01). More than cost, fear of treatment failure and of retribution from senior physicians were major drivers of antibiotic prescription behavior particularly among junior physicians. All respondents identified high turnover of pharmacists, poor communication between the laboratory, pharmacists and clinicians as potential challenges; but the existing hierarchical culture and academic setting were touted as opportunities to implement AMS in Ethiopia.
CONCLUSIONS: This knowledge and perceptions survey identified specific educational priorities and implementation strategies for AMS in our setting. This is likely also true in other LMICs, where expertise and infrastructure may be lacking.

PMID: 30571688 [PubMed - indexed for MEDLINE]

Vaccination against Clostridium difficile using an attenuated Salmonella Typhimurium vector (YS1646) protects mice from lethal challenge.

Infect Immun. 2019 May 28;:

Authors: Winter K, Xing L, Kassardjian A, Ward BJ

Abstract
Clostridium difficile disease is mediated primarily by toxins A and B (TcdA and TcdB). The receptor binding domains (RBD) of TcdA and TcdB are immunogenic and anti-RBD antibodies are protective. Since these toxins act locally, an optimal C. difficile vaccine would generate both systemic and mucosal responses. We have repurposed an attenuated Salmonella enterica serovar Typhimurium strain (YS1646) to produce such a vaccine. Plasmid-based candidates expressing either the TcdA or TcdB RBD were screened. Different vaccine routes and schedules were tested to achieve detectable serum and mucosal antibody titers in C57BL/6J mice. When given in a multimodality schedule over 1 week (day 0 IM+PO, days 2 and 4 PO), several candidates provided 100% protection against lethal challenge. Substantial protection (82%) was achieved with combined PO TcdA/TcdB vaccination alone (d0, 2 and 4). These data demonstrate the potential of the YS1646-based vaccines for C. difficile and strongly support their further development.

PMID: 31138615 [PubMed - as supplied by publisher]

Effectiveness of Screening and Treatment Approaches for Schistosomiasis and Strongyloidiasis in Newly-Arrived Migrants from Endemic Countries in the EU/EEA: A Systematic Review.

Int J Environ Res Public Health. 2018 12 20;16(1):

Authors: Agbata EN, Morton RL, Bisoffi Z, Bottieau E, Greenaway C, Biggs BA, Montero N, Tran A, Rowbotham N, Arevalo-Rodriguez I, Myran DT, Noori T, Alonso-Coello P, Pottie K, Requena-Méndez A

Abstract
We aimed to evaluate the evidence on screening and treatment for two parasitic infections-schistosomiasis and strongyloidiasis-among migrants from endemic countries arriving in the European Union and European Economic Area (EU/EEA). We conducted a systematic search of multiple databases to identify systematic reviews and meta-analyses published between 1 January 1993 and 30 May 2016 presenting evidence on diagnostic and treatment efficacy and cost-effectiveness. We conducted additional systematic search for individual studies published between 2010 and 2017. We assessed the methodological quality of reviews and studies using the AMSTAR, Newcastle⁻Ottawa Scale and QUADAS-II tools. Study synthesis and assessment of the certainty of the evidence was performed using GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. We included 28 systematic reviews and individual studies in this review. The GRADE certainty of evidence was low for the effectiveness of screening techniques and moderate to high for treatment efficacy. Antibody-detecting serological tests are the most effective screening tests for detection of both schistosomiasis and strongyloidiasis in low-endemicity settings, because they have higher sensitivity than conventional parasitological methods. Short courses of praziquantel and ivermectin were safe and highly effective and cost-effective in treating schistosomiasis and strongyloidiasis, respectively. Economic modelling suggests presumptive single-dose treatment of strongyloidiasis with ivermectin for all migrants is likely cost-effective, but feasibility of this strategy has yet to be demonstrated in clinical studies. The evidence supports screening and treatment for schistosomiasis and strongyloidiasis in migrants from endemic countries, to reduce morbidity and mortality.

PMID: 30577567 [PubMed - indexed for MEDLINE]

[Epidemiology of primary lung cancer among non-smokers in Senegal].

Rev Mal Respir. 2019 Jan;36(1):15-21

Authors: Thiam K, Touré NO, Ndiaye EM, Baddredine H, Ndiaye M, Diop M, Niang A, Ba O, Dia Kane Y, Diatta A, Cissé MF, Mbaye FBR, Wayzani M, Niang S, Sagne JMAN, Dia S, Ndao M, Ka W

Abstract
INTRODUCTION: According to global data for 2002, one quarter of new cases of primary bronchopulmonary cancer were non-smokers. We undertook this study with the aim of describing the epidemiological characteristics of non-smokers with primary bronchopulmonary cancer in the Dakar region of Senegal.
METHODS: A multicenter descriptive study that included all non-smokers who presented with primary bronchopulmonary cancer between January 1st 2014 and December 31st 2015. The data were captured on an Excel file and then transferred to Epi InfoTM 7 software for analysis.
RESULTS: The rate of diagnosis for primary bronchopulmonary cancers was 72.1 %. The prevalence of non-smokers was 33.3 %. The sex ratio was 1.27. The average age was 54.6 years. More than a third of the sample were housewives. Carpenters and craftsmen exposed to metals predominated. Exposure to cooking oils was reported in one case. Three patients presented sequelae of pulmonary tuberculosis. Adenocarcinoma was the most common histological type and predominated in young subjects.
CONCLUSION: The proportion of primary bronchopulmonary cancers diagnosed among non-smokers is increasing in Dakar. An analytical study of suspected risk factors would be helpful for prevention.

PMID: 30413327 [PubMed - indexed for MEDLINE]

Plant-derived virus-like particle vaccines drive cross-presentation of influenza A hemagglutinin peptides by human monocyte-derived macrophages.

NPJ Vaccines. 2019;4:17

Authors: Makarkov AI, Golizeh M, Ruiz-Lancheros E, Gopal AA, Costas-Cancelas IN, Chierzi S, Pillet S, Charland N, Landry N, Rouiller I, Wiseman PW, Ndao M, Ward BJ

Abstract
A growing body of evidence supports the importance of T cell responses to protect against severe influenza, promote viral clearance, and ensure long-term immunity. Plant-derived virus-like particle (VLP) vaccines bearing influenza hemagglutinin (HA) have been shown to elicit strong humoral and CD4+ T cell responses in both pre-clinical and clinical studies. To better understand the immunogenicity of these vaccines, we tracked the intracellular fate of a model HA (A/California/07/2009 H1N1) in human monocyte-derived macrophages (MDMs) following delivery either as VLPs (H1-VLP) or in soluble form. Compared to exposure to soluble HA, pulsing with VLPs resulted in ~3-fold greater intracellular accumulation of HA at 15 min that was driven by clathrin-mediated and clathrin-independent endocytosis as well as macropinocytosis/phagocytosis. At 45 min, soluble HA had largely disappeared suggesting its handling primarily by high-degradative endosomal pathways. Although the overall fluorescence intensity/cell had declined 25% at 45 min after H1-VLP exposure, the endosomal distribution pattern and degree of aggregation suggested that HA delivered by VLP had entered both high-degradative late and low-degradative static early and/or recycling endosomal pathways. At 45 min in the cells pulsed with VLPs, HA was strongly co-localized with Rab5, Rab7, Rab11, MHC II, and MHC I. High-resolution tandem mass spectrometry identified 115 HA-derived peptides associated with MHC I in the H1-VLP-treated MDMs. These data suggest that HA delivery to antigen-presenting cells on plant-derived VLPs facilitates antigen uptake, endosomal processing, and cross-presentation. These observations may help to explain the broad and cross-reactive immune responses generated by these vaccines.

PMID: 31123605 [PubMed]

The ash dieback invasion of Europe was founded by two genetically divergent individuals.

Nat Ecol Evol. 2018 06;2(6):1000-1008

Authors: McMullan M, Rafiqi M, Kaithakottil G, Clavijo BJ, Bilham L, Orton E, Percival-Alwyn L, Ward BJ, Edwards A, Saunders DGO, Garcia Accinelli G, Wright J, Verweij W, Koutsovoulos G, Yoshida K, Hosoya T, Williamson L, Jennings P, Ioos R, Husson C, Hietala AM, Vivian-Smith A, Solheim H, MaClean D, Fosker C, Hall N, Brown JKM, Swarbreck D, Blaxter M, Downie JA, Clark MD

Abstract
Accelerating international trade and climate change make pathogen spread an increasing concern. Hymenoscyphus fraxineus, the causal agent of ash dieback, is a fungal pathogen that has been moving across continents and hosts from Asian to European ash. Most European common ash trees (Fraxinus excelsior) are highly susceptible to H. fraxineus, although a minority (~5%) have partial resistance to dieback. Here, we assemble and annotate a H. fraxineus draft genome, which approaches chromosome scale. Pathogen genetic diversity across Europe and in Japan, reveals a strong bottleneck in Europe, though a signal of adaptive diversity remains in key host interaction genes. We find that the European population was founded by two divergent haploid individuals. Divergence between these haplotypes represents the ancestral polymorphism within a large source population. Subsequent introduction from this source would greatly increase adaptive potential of the pathogen. Thus, further introgression of H. fraxineus into Europe represents a potential threat and Europe-wide biological security measures are needed to manage this disease.

PMID: 29686237 [PubMed - indexed for MEDLINE]

Reply to Dobler.

Clin Infect Dis. 2017 10 15;65(8):1423-1424

Authors: Greenaway C, Shrier I, Abou Chakra CN, Cnossen S, Cheng MP, Yansouni CP, Menzies D

PMID: 29017250 [PubMed - indexed for MEDLINE]

Case Report: Trypanosoma brucei Gambiense Human African Trypanosomiasis as the Cause of Fever in an Inpatient with Multiple Myeloma and HIV-1 Coinfection.

Am J Trop Med Hyg. 2019 May 06;:

Authors: Boodman C, Libman M, Ndao M, Yansouni CP

Abstract
We report the case of a 64-year-old woman found to have urban-acquired Trypanosoma brucei (T.b.) gambiense human African trypanosomiasis (HAT) as the cause of sustained fever starting 9 months after returning to Canada from Democratic Republic of the Congo, in the context of concomitant multiple myeloma and HIV-1 coinfection. Approaches for the management of both clinical stages of T.b. gambiense HAT are well defined for endemic settings using current diagnostics and treatments. However, few data inform the diagnosis and management of patients with bone marrow suppression from active malignancy, recent anticancer therapy, or HIV coinfection. We discuss the implications of immunosuppression for diagnosis and management of T.b. gambiense HAT.

PMID: 31074413 [PubMed - as supplied by publisher]

Clinical bacteriology in low-resource settings: today's solutions.

Lancet Infect Dis. 2018 08;18(8):e248-e258

Authors: Ombelet S, Ronat JB, Walsh T, Yansouni CP, Cox J, Vlieghe E, Martiny D, Semret M, Vandenberg O, Jacobs J, Bacteriology in Low Resource Settings working group

Abstract
Low-resource settings are disproportionately burdened by infectious diseases and antimicrobial resistance. Good quality clinical bacteriology through a well functioning reference laboratory network is necessary for effective resistance control, but low-resource settings face infrastructural, technical, and behavioural challenges in the implementation of clinical bacteriology. In this Personal View, we explore what constitutes successful implementation of clinical bacteriology in low-resource settings and describe a framework for implementation that is suitable for general referral hospitals in low-income and middle-income countries with a moderate infrastructure. Most microbiological techniques and equipment are not developed for the specific needs of such settings. Pending the arrival of a new generation diagnostics for these settings, we suggest focus on improving, adapting, and implementing conventional, culture-based techniques. Priorities in low-resource settings include harmonised, quality assured, and tropicalised equipment, consumables, and techniques, and rationalised bacterial identification and testing for antimicrobial resistance. Diagnostics should be integrated into clinical care and patient management; clinically relevant specimens must be appropriately selected and prioritised. Open-access training materials and information management tools should be developed. Also important is the need for onsite validation and field adoption of diagnostics in low-resource settings, with considerable shortening of the time between development and implementation of diagnostics. We argue that the implementation of clinical bacteriology in low-resource settings improves patient management, provides valuable surveillance for local antibiotic treatment guidelines and national policies, and supports containment of antimicrobial resistance and the prevention and control of hospital-acquired infections.

PMID: 29519767 [PubMed - indexed for MEDLINE]