Recent publications from TDC authors

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NCBI: db=pubmed; Term=(Yansouni C[Author]) OR (Iqbal A[Author] parasitology) OR (Ndao M[Author]) OR (Ward BJ[Author]) OR (Semret M[Author]) OR (Libman M[Author]) OR (Greenaway C[author]) OR (Barkati S[Author])
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Assessment of population immunity to measles in Ontario, Canada: A Canadian Immunization Research Network (CIRN) Study.

Wed, 06/12/2019 - 06:27

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.

Fri, 06/07/2019 - 01:15
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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.

Wed, 06/05/2019 - 01:20
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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.

Sat, 06/01/2019 - 00:33
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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.

Fri, 05/31/2019 - 00:54
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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.

Thu, 05/30/2019 - 01:09
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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].

Thu, 05/30/2019 - 01:09
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[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.

Wed, 05/29/2019 - 01:17
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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.

Fri, 05/24/2019 - 00:53
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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.

Wed, 05/15/2019 - 01:12
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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.

Sun, 05/12/2019 - 00:48
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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.

Wed, 04/24/2019 - 00:41
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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]

Resilience from the ground up: how are local resilience perceptions and global frameworks aligned?

Sat, 04/06/2019 - 01:09
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Resilience from the ground up: how are local resilience perceptions and global frameworks aligned?

Disasters. 2019 Apr;43 Suppl 3:S295-S317

Authors: Beauchamp E, Abdella J, Fisher S, McPeak J, Patnaik H, Koulibaly P, Cissé D, Touré M, Bocoum A, Ndao M, Deme Y, Gueye B

Abstract
Numerous resilience measurement frameworks for climate programmes have emerged over the past decade to operationalise the concept and aggregate results within and between programmes. Proxies of resilience, including subjective measures using perception data, have been proposed to measure resilience, but there is limited evidence on their validity and use for policy and practice. This article draws on research on the Decentralising Climate Funds project of the Building Resilience and Adaptation to Climate Extremes and Disasters programme, which supports communities in Mali and Senegal to improve climate resilience through locally controlled adaptation funds. It explores attributes of resilience from this bottom-up perspective to assess its predictors and alignment with food security, as a proxy of well-being. We find different patterns when comparing resilience and the well-being proxy, illustrating that the interplay between the two is still unclear. Results also point to the importance of contextualising resilience, raising implications for aggregating results.

PMID: 30945764 [PubMed - in process]

Serological and molecular detection of Toxoplasma gondii in terrestrial and marine wildlife harvested for food in Nunavik, Canada.

Sat, 04/06/2019 - 01:09
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Serological and molecular detection of Toxoplasma gondii in terrestrial and marine wildlife harvested for food in Nunavik, Canada.

Parasit Vectors. 2019 Apr 03;12(1):155

Authors: Bachand N, Ravel A, Leighton P, Stephen C, Ndao M, Avard E, Jenkins E

Abstract
BACKGROUND: Toxoplasma gondii, a zoonotic protozoan parasite, infects mammals and birds worldwide. Infection in humans is often asymptomatic, though illnesses can occur in immunocompromised hosts and the fetuses of susceptible women infected during pregnancy. In Nunavik, Canada, 60% of the Inuit population has measurable antibodies against T. gondii. Handling and consumption of wildlife have been identified as risk factors for exposure. Serological evidence of exposure has been reported for wildlife in Nunavik; however, T. gondii has not been detected in wildlife tissues commonly consumed by Inuit.
METHODS: We used a magnetic capture DNA extraction and real-time PCR protocol to extract and amplify T. gondii DNA from large quantities of tissues (up to 100 g) of 441 individual animals in Nunavik: 166 ptarmigan (Lagopus lagopus), 156 geese (Branta canadensis and Chen caerulescens), 61 ringed seals (Pusa hispida), 31 caribou (Rangifer tarandus) and 27 walruses (Odobenus rosmarus).
RESULTS: DNA from T. gondii was detected in 9% (95% CI: 3-15%) of geese from four communities in western and southern Nunavik, but DNA was not detected in other wildlife species including 20% (95% CI: 12-31%) of ringed seals and 26% (95% CI: 14-43%) of caribou positive on a commercial modified agglutination test (MAT) using thawed heart muscle juice. In geese, tissue parasite burden was highest in heart, followed by brain, breast muscle, liver and gizzard. Serological results did not correlate well with tissue infection status for any wildlife species.
CONCLUSIONS: To our knowledge, this is the first report on the detection, quantification, and characterization of DNA of T. gondii (clonal lineage II in one goose) from wildlife harvested for food in Nunavik, which supports the hypothesis that migratory geese can carry T. gondii into Nunavik where feline definitive hosts are rare. This study suggests that direct detection methods may be useful for detection of T. gondii in wildlife harvested for human consumption and provides data needed for a quantitative exposure assessment that will determine the risk of T. gondii exposure for Inuit who harvest and consume geese in Nunavik.

PMID: 30944016 [PubMed - in process]

Reply: regarding business travelers.

Fri, 03/29/2019 - 00:50
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Reply: regarding business travelers.

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

Authors: Chen LH, Leder K, Schlagenhauf P, Libman M, Keystone J, Mendelson M, Gautret P, Schwartz E, Shaw M, MacDonald S, McCarthy A, Connor BA, Hamer DH, Wilson ME, GeoSentinel Surveillance Network

PMID: 29741699 [PubMed - indexed for MEDLINE]

A protocol to count Cryptosporidium oocysts by flow cytometry without antibody staining.

Fri, 03/22/2019 - 00:49
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A protocol to count Cryptosporidium oocysts by flow cytometry without antibody staining.

PLoS Negl Trop Dis. 2019 Mar 20;13(3):e0007259

Authors: Sonzogni-Desautels K, Di Lenardo TZ, Renteria AE, Gascon MA, Geary TG, Ndao M

Abstract
Cryptosporidiosis caused by the protozoan parasites Cryptosporidium hominis and C. parvum, threatens the lives of young children in developing countries. In veterinary medicine, C. parvum causes life-threatening diarrhea and dehydration in newborn dairy calves. Protocols to detect Cryptosporidium spp. oocysts using flow cytometry have been reported; however, these protocols use antibodies against the parasite and typically focus on detection of oocysts, not quantification. These techniques are not well-suited for studies that generate large variations in oocyst burdens because the amount of antibody required is proportional to the number of oocysts expected in samples. Also, oocysts are lost in washes in the staining protocol, reducing accuracy of oocyst counts. Moreover, these protocols require costly fluorochrome-conjugated monoclonal antibodies and are not optimal for studies involving large numbers of samples. Here we present an optimized protocol for purifying oocysts from mouse stool and intestine samples combined with a reliable method to quantify oocysts in a relatively pure population without the need for antibody staining. We used morphology (SSC-A vs FSC-A) and the innate characteristics of C. parvum oocysts compared to fecal and intestinal contaminants to develop a two-step gating strategy that can differentiate oocysts from debris. This method is a fast, reliable, and high-throughput technique to promote research projects on C. parvum infections in mice and potentially other animal hosts.

PMID: 30893302 [PubMed - as supplied by publisher]

Apolipoprotein A1 and Fibronectin Fragments as Markers of Cure for the Chagas Disease.

Sat, 03/16/2019 - 01:54
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Apolipoprotein A1 and Fibronectin Fragments as Markers of Cure for the Chagas Disease.

Methods Mol Biol. 2019;1955:263-273

Authors: Ruiz-Lancheros E, Golizeh M, Ndao M

Abstract
Chagas disease (CD), endemic from Latin America, affects more than 8 million people, and the disease keeps spreading around the world due to population migrations. The treatment options for CD are currently limited to two drugs, benznidazole (BZ) and nifurtimox (Nfx), which are often unsatisfactory in chronically infected patients. To date, the only accepted marker of the cure is seroconversion (the disappearance of Trypanosoma cruzi antibodies in the patient's serum), which can take decades to occur, if ever. The lack of posttreatment test-of-cure often prevents appropriate patient counseling and limits the development of new drugs. Without a doubt, reliable biomarkers for parasitological cure are urgently needed. Several pieces of evidence suggest that apolipoprotein A1 and fibronectin fragments are produced during the infection as part of the process of T. cruzi cell invasion and can thus be used as its surrogate biomarkers. In this chapter, we present a standardized method to evaluate these fragments in serum using mass spectrometry and immunoblotting in CD patients for diagnosis, prognosis, and treatment assessment purposes.

PMID: 30868534 [PubMed - in process]

A REDOR ssNMR Investigation of the Role of an N-Terminus Lysine in R5 Silica Recognition.

Sat, 03/16/2019 - 01:54
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A REDOR ssNMR Investigation of the Role of an N-Terminus Lysine in R5 Silica Recognition.

Langmuir. 2018 07 24;34(29):8678-8684

Authors: Ndao M, Goobes G, Emani PS, Drobny GP

Abstract
Diatoms are unicellular algae that construct cell walls called frustules by the precipitation of silica, using special proteins that order the silica into a wide variety of nanostructures. The diatom species Cylindrotheca fusiformis contains proteins called silaffins within its frustules, which are believed to assemble into supramolecular matrices that serve as both accelerators and templates for silica deposition. Studying the properties of these biosilicification proteins has allowed the design of new protein and peptide systems that generate customizable silica nanostructures, with potential generalization to other mineral systems. It is essential to understand the mechanisms of aggregation of the protein and its coprecipitation with silica. We continue previous investigations into the peptide R5, derived from silaffin protein sil1p, shown to independently catalyze the precipitation of silica nanospheres in vitro. We used the solid-state NMR technique 13C{29Si} and 15N{29Si} REDOR to investigate the structure and interactions of R5 in complex with coprecipitated silica. These experiments are sensitive to the strength of magnetic dipole-dipole interactions between the 13C nuclei in R5 and the 29Si nuclei in the silica and thus yield distance between parts of R5 and 29Si in silica. Our data show strong interactions and short internuclear distances of 3.74 ± 0.20 Å between 13C═O Lys3 and silica. On the other hand, the Cα and Cβ nuclei show little or no interaction with 29Si. This selective proximity between the K3 C═O and the silica supports a previously proposed mechanism of rapid silicification of the antimicrobial peptide KSL (KKVVFKVKFK) through an imidate intermediate. This study reports for the first time a direct interaction between the N-terminus of R5 and silica, leading us to believe that the N-terminus of R5 is a key component in the molecular recognition process and a major factor in silica morphogenesis.

PMID: 27039990 [PubMed - indexed for MEDLINE]

Accessibility and Acceptability of Infectious Disease Interventions Among Migrants in the EU/EEA: A CERQual Systematic Review.

Thu, 03/14/2019 - 01:03
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Accessibility and Acceptability of Infectious Disease Interventions Among Migrants in the EU/EEA: A CERQual Systematic Review.

Int J Environ Res Public Health. 2018 10 23;15(11):

Authors: Driedger M, Mayhew A, Welch V, Agbata E, Gruner D, Greenaway C, Noori T, Sandu M, Sangou T, Mathew C, Kaur H, Pareek M, Pottie K

Abstract
In the EU/EEA, subgroups of international migrants have an increased prevalence of certain infectious diseases. The objective of this study was to examine migrants' acceptability, value placed on outcomes, and accessibility of infectious disease interventions. We conducted a systematic review of qualitative reviews adhering to the PRISMA reporting guidelines. We searched MEDLINE, EMBASE, CINAHL, DARE, and CDSR, and assessed review quality using AMSTAR. We conducted a framework analysis based on the Health Beliefs Model, which was used to organize our preliminary findings with respect to the beliefs that underlie preventive health behavior, including knowledge of risk factors, perceived susceptibility, severity and barriers, and cues to action. We assessed confidence in findings using an adapted GRADE CERQual tool. We included 11 qualitative systematic reviews from 2111 articles. In these studies, migrants report several facilitators to public health interventions. Acceptability depended on migrants' relationship with healthcare practitioners, knowledge of the disease, and degree of disease-related stigma. Facilitators to public health interventions relevant for migrant populations may provide clues for implementation. Trust, cultural sensitivity, and communication skills also have implications for linkage to care and public health practitioner education. Recommendations from practitioners continue to play a key role in the acceptance of infectious disease interventions.

PMID: 30360472 [PubMed - indexed for MEDLINE]

Peptidyl-prolyl cis-trans isomerase A - A novel biomarker of multi-episodic (recurrent) ocular toxoplasmosis.

Fri, 03/08/2019 - 00:26
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Peptidyl-prolyl cis-trans isomerase A - A novel biomarker of multi-episodic (recurrent) ocular toxoplasmosis.

Exp Eye Res. 2018 12;177:104-111

Authors: Isenberg J, Golizeh M, Belfort RN, da Silva AJ, Burnier MN, Ndao M

Abstract
Ocular toxoplasmosis (OT) is the most common etiology of posterior uveitis. The high incidence of macular scarring associated with OT is a leading cause of visual morbidity. Serum biomarkers of the disease would aid in its diagnosis. This study sought, for the first time, to elucidate serum biomarkers for OT by mass spectrometry. Blood samples were collected from four groups of nine patients each; toxoplasmosis IgG-with no history of uveitis, non-toxoplasmosis uveitis, first episode OT, and symptomatic recurrent OT. Serum was isolated and subjected to proteomics analysis using 2-dimensional gel electrophoresis (2D-GE) and surface-enhanced laser desorption ionization mass spectrometry (SELDI-MS). Selected proteins were further separated by SDS-PAGE and sequenced using tandem MS. Results were cross-validated with a T. gondii outbreak biomarker database that occurred in Brazil. Fifty markers of OT and 46 markers of recurrent disease were discovered by SELDI-MS of which 30 and 15, respectively, were cross-validated. 2D-GE analysis yielded 57 bands, selected based on the intensity of the bands, leading to the identification of 20 proteins. Eleven of those identified candidates were also found by SELDI-MS. Four candidates were chosen for immunoblotting. One serum protein, peptidyl-prolyl cis-trans isomerase A (PPIA), was confirmed as a biomarker of multi-episodic OT by immunoblotting in patients. PPIA can identify the patient with active recurrent OT from acute OT, other forms of uveitis and other parasitic infections. A validated PPIA assay may have a role in the diagnosis of the atypical OT patient before more invasive anterior chamber or vitreous tap is performed for PCR analysis or for Goldmann-Witner coefficient calculations. Base-line PPIA levels need to be studied to understand its possible use when deciding for prophylactic antibiotic use in the immunosuppressed sero-positive patient.

PMID: 30063883 [PubMed - indexed for MEDLINE]

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