Publications by authors named "Momar Ndao"

94 Publications

A low dose adenovirus vectored vaccine expressing Schistosoma mansoni Cathepsin B protects from intestinal schistosomiasis in mice.

EBioMedicine 2022 Apr 29;80:104036. Epub 2022 Apr 29.

Department of Medicine, Division of Experimental Medicine, McGill University, Montréal, Québec, Canada; Infectious Diseases and Immunity in Global Health Program, Research Institute of the McGill University Health Centre, Room: EM3.3244, 1001 Decarie Blvd, Montréal, Québec H4A 3J1, Canada; Department of Microbiology and Immunology, McGill University, Montréal, Québec, Canada; National Reference Centre for Parasitology, Research Institute of the McGill University Health Centre, Montréal, Québec, Canada. Electronic address:

Background: Schistosomiasis is an underestimated neglected tropical disease which affects over 236.6 million people worldwide. According to the CDC, the impact of this disease is second to only malaria as the most devastating parasitic infection. Affected individuals manifest chronic pathology due to egg granuloma formation, destroying the liver over time. The only FDA approved drug, praziquantel, does not protect individuals from reinfection, highlighting the need for a prophylactic vaccine. Schistosoma mansoni Cathepsin B (SmCB) is a parasitic gut peptidase necessary for helminth growth and maturation and confers protection as a vaccine target for intestinal schistosomiasis.

Methods: An SmCB expressing human adenovirus serotype 5 (AdSmCB) was constructed and delivered intramuscularly to female C57BL/6 mice in a heterologous prime and boost vaccine with recombinant protein. Vaccine induced immunity was described and subsequent protection from parasite infection was assessed by analysing parasite burden and liver pathology.

Findings: Substantially higher humoral and cell-mediated immune responses, consisting of IgG2c, Th1 effectors, and polyfunctional CD4 T cells, were induced by the heterologous administration of AdSmCB when compared to the other regimens. Though immune responses favoured Th1 immunity, Th2 responses provided by SmCB protein boosts were maintained. This mixed Th1/Th2 immune response resulted in significant protection from S. mansoni infection comparable to other vaccine formulations which are in clinical trials. Schistosomiasis associated liver pathology was also prevented in a murine model.

Interpretation: Our study provides missing preclinical data supporting the use of adenoviral vectoring in vaccines for S. mansoni infection. Our vaccination method significantly reduces parasite burden and its associated liver pathology - both of which are critical considerations for this helminth vaccine.

Funding: This work was supported by the Canadian Institutes of Health Research, R. Howard Webster Foundation, and the Foundation of the McGill University Health Centre.
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http://dx.doi.org/10.1016/j.ebiom.2022.104036DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9065910PMC
April 2022

Detection of Fusobacterium nucleatum subspecies in the saliva of pre-colorectal cancer patients, using tandem mass spectrometry.

Arch Oral Biol 2022 Feb 14;134:105337. Epub 2021 Dec 14.

Faculty of Dentistry, McGill University, Montreal, QC, Canada. Electronic address:

Objective: Rising evidence links Fusobacterium nucleatum (F. nucleatum) with its four subspecies; nucleatum, polymorphum, animalis, and vincentii, with the development of colorectal cancer (CRC) and its precursor colorectal adenoma (CRA). This study aims to optimize a technique for and explore the capability of matrix-assisted laser-desorption ionization-tandem time-of-flight mass spectrometry (MALDI-TOF/TOF MS) to detect F. nucleatum subspecies directly from the saliva samples of CRA patients and controls without preculturing.

Design: Saliva samples were collected from four CRA patients and eight controls. Proteins were extracted and subjected to solid-phase extraction fractionation, enzymatically digested, and analyzed by MALDI-TOF/TOF MS. F. nucleatum subspecies strains were cultured and used as a positive control.

Results: A proteomics approach was developed to identify F. nucleatum subspecies directly from saliva samples. With this approach, the bacterial culturing step, which could take up to seven days, was bypassed. Overall, 157 F. nucleatum subspecies proteins were detected in the saliva samples. F. nucleatum subsp. nucleatum was absent in the patients while detected in half of the controls.

Conclusion: This study presents a novel technique for detecting F. nucleatum subspecies from saliva specimens that could later be employed to better understand a potential role of those subspecies in CRC development.
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http://dx.doi.org/10.1016/j.archoralbio.2021.105337DOI Listing
February 2022

The Diverse Applications of Recombinant BCG-Based Vaccines to Target Infectious Diseases Other Than Tuberculosis: An Overview.

Front Microbiol 2021 21;12:757858. Epub 2021 Oct 21.

The Department of Microbiology & Immunology, McGill University, Montreal, QC, Canada.

Live attenuated Bacillus Calmette-Guérin (BCG) is the world's most widely used vaccine which is mainly administered for its protection against tuberculosis (TB), particularly in young children. However, since its initial use over 100years ago, it has also proven to offer a level of protection against various other pathogens, as a consequence of its non-specific immune enhancing effects. Thus, over the past few decades, recombinant BCG (rBCG) technology has been used as a vector to create rBCG vaccines expressing heterologous antigens that elicit immunity against a range of bacterial, viral, and parasitic diseases. Our goal with this mini-review is to provide an up-to-date survey of the various techniques, approaches, and applications of rBCG-based vaccines for targeting infectious diseases other than TB.
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http://dx.doi.org/10.3389/fmicb.2021.757858DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8566895PMC
October 2021

Specificity of SARS-CoV-2 Antibody Detection Assays against S and N Proteins among Pre-COVID-19 Sera from Patients with Protozoan and Helminth Parasitic Infections.

J Clin Microbiol 2022 01 20;60(1):e0171721. Epub 2021 Oct 20.

Division of Infectious Diseases, Department of Medicine, McGill Universitygrid.14709.3bgrid.63984.30 Health Centre, Montreal, Quebec, Canada.

We aimed to assess the specificity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody detection assays among people with tissue-borne parasitic infections. We tested three SARS-CoV-2 antibody-detection assays (cPass SARS-CoV-2 neutralization antibody detection kit [cPass], Abbott SARS-CoV-2 IgG assay [Abbott Architect], and Standard Q COVID-19 IgM/IgG combo rapid diagnostic test [SD RDT IgM/SD RDT IgG]) among 559 pre-COVID-19 seropositive sera for several parasitic infections. The specificity of assays was 95 to 98% overall. However, lower specificity was observed among sera from patients with protozoan infections of the reticuloendothelial system, such as human African trypanosomiasis (Abbott Architect; 88% [95% CI, 75 to 95]) and visceral leishmaniasis (SD RDT IgG; 80% [95% CI, 30 to 99]), and from patients with recent malaria in areas of Senegal where malaria is holoendemic (ranging from 91% for Abbott Architect and SD RDT IgM to 98 to 99% for cPass and SD RDT IgG). For specimens from patients with evidence of past or present helminth infection overall, test specificity estimates were all ≥96%. Sera collected from patients clinically suspected of parasitic infections that tested negative for these infections yielded a specificity of 98 to 100%. The majority (>85%) of false-positive results were positive by only one assay. The specificity of SARS-CoV-2 serological assays among sera from patients with tissue-borne parasitic infections was below the threshold required for decisions about individual patient care. Specificity is markedly increased by the use of confirmatory testing with a second assay. Finally, the SD RDT IgG proved similarly specific to laboratory-based assays and provides an option in low-resource settings when detection of anti-SARS-CoV-2 IgG is indicated.
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http://dx.doi.org/10.1128/JCM.01717-21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8769729PMC
January 2022

Will Auranofin Become a Golden New Treatment Against COVID-19?

Front Immunol 2021 22;12:683694. Epub 2021 Sep 22.

Infectious Diseases and Immunity in Global Health Program, Research Institute of the McGill University Health Centre, Montreal, QC, Canada.

Auranofin is an FDA-approved disease-modifying anti-rheumatic drug that has been used for decades for treatment of rheumatoid arthritis. This gold(I) compound has anti-inflammatory properties because it reduces IL-6 expression inhibition of the NF-κB-IL-6-STAT3 signaling pathway. Also, by inhibiting redox enzymes such as thioredoxin reductase, auranofin increases cellular oxidative stress and promotes apoptosis. Auranofin also possesses antiviral properties. Recently, it was reported that auranofin reduced by 95% SARS-CoV-2 RNA in infected human cells and decreased SARS-CoV-2-induced cytokine expression, including IL-6. During SARS-CoV-2 infection, a cytokine storm involving IL-6 increases severity of illness and worsens prognosis. Therefore, auranofin could, in our point of view, reduce pathology due to SARS-CoV-2-induced IL-6. COVID-19 is a rapidly-evolving respiratory disease now distributed worldwide. Strikingly high numbers of new COVID-19 cases are reported daily. We have begun a race to vaccinate people, but due to the complex logistics of this effort, the virus will continue to spread before all humans can be immunized, and new variants that may be less well contained by current vaccines are of concern. The COVID-19 pandemic has overwhelmed health care systems and new treatments to reduce mortality are urgently needed. We encourage to further evaluate the potential of auranofin in the treatment of COVID-19 and in animal models of SARS-CoV-2 infection and, if preliminary data are promising, in clinical trials with COVID-19 patients. In our opinion, auranofin has the potential to become a valuable addition to available therapies in this pandemic.
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http://dx.doi.org/10.3389/fimmu.2021.683694DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8492993PMC
October 2021

Promising Technologies in the Field of Helminth Vaccines.

Front Immunol 2021 19;12:711650. Epub 2021 Aug 19.

Division of Experimental Medicine, McGill University, Montreal, QC, Canada.

Helminths contribute a larger global burden of disease than both malaria and tuberculosis. These eukaryotes have caused human infections since before our earliest recorded history (i.e.: earlier than 1200 B.C. for spp.). Despite the prevalence and importance of these infections, helminths are considered a neglected tropical disease for which there are no vaccines approved for human use. Similar to other parasites, helminths are complex organisms which employ a plethora of features such as: complex life cycles, chronic infections, and antigenic mimicry to name a few, making them difficult to target by conventional vaccine strategies. With novel vaccine strategies such as viral vectors and genetic elements, numerous constructs are being defined for a wide range of helminth parasites; however, it has yet to be discussed which of these approaches may be the most effective. With human trials being conducted, and a pipeline of potential anti-helminthic antigens, greater understanding of helminth vaccine-induced immunity is necessary for the development of potent vaccine platforms and their optimal design. This review outlines the conventional and the most promising approaches in clinical and preclinical helminth vaccinology.
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http://dx.doi.org/10.3389/fimmu.2021.711650DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8418310PMC
December 2021

Babesia microti in a Canadian blood donor and lookback in a red blood cell recipient.

Vox Sang 2022 Mar 31;117(3):438-441. Epub 2021 Aug 31.

Medical Laboratory and Stem Cell Services, Canadian Blood Services, Vancouver, British Columbia, Canada.

Background And Objectives: We describe the third documented case of autochthonous human babesiosis in Canada and the second in a Canadian blood donor.

Materials And Methods: Multiple laboratory investigations were carried out on the donor and the immunocompromised recipient of an associated, potentially infectious red blood cell product.

Results: The donor had not travelled except for outdoor exposure in south-eastern Manitoba, followed by illness and hospital admission. The donor had a notable parasitaemia, positive for Babesia microti using whole blood nucleic acid testing (NAT). The recipient was negative for B. microti by both serology and NAT.

Conclusion: There was no evidence of transfusion-transmitted babesiosis.
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http://dx.doi.org/10.1111/vox.13198DOI Listing
March 2022

Therapeutic activity of a Salmonella-vectored Schistosoma mansoni vaccine in a mouse model of chronic infection.

Vaccine 2021 09 16;39(39):5580-5588. Epub 2021 Aug 16.

Department of Microbiology & Immunology, McGill University, Montreal, Canada; Infectious Diseases and Immunity in Global Health (IDIGH), Research Institute of the McGill University Health Centre, Montreal, Canada; Division of Experimental Medicine, McGill University, Montreal, Canada. Electronic address:

Schistosomiasis is an important fresh-water-borne parasitic disease caused by trematode worms of the genus Schistosoma. With > 250 million people infected worldwide and approximately 800 million people at risk, the World Health Organization considers schistosomiasis to be the most important human helminth infection. Several prophylactic non-living vaccines are in pre-clinical and clinical development, but only one has been assessed for therapeutic effect in an animal model with modest results. Live attenuated Salmonella have multiple potential advantages as vaccine vectors. We have engineered an attenuated Salmonella enterica Typhimurium strain (YS1646) to produce a vaccine that targets the parasite digestive enzyme Cathepsin B (CatB). A multi-modality immunization schedule was used in chronically infected mice that included three oral (PO) doses of this CatB-bearing YS1646 strain on days one, three, and five as well as an intramuscular (IM) dose of recombinant CatB on day one. Parasite burden (worm count, intestinal and liver egg numbers) were 46.5 - 50.3% lower than in control animals 1 month post-vaccination and relative reductions further increased to 63.9 - 73.3% at 2 months. Serum anti-CatB IgG increased significantly after vaccination with the development of a more balanced T1/T2 pattern of response (ie: a shift in the IgG1:IgG2c ratio). Compared to control animals, a broad and robust CatB-specific cytokine/chemokine response was seen in splenocytes isolated 1 month post-vaccination. A vaccine that has both prophylactic and therapeutic activity would be ideal for use in conjunction with mass treatment campaigns with praziquantel in schistosome-endemic countries.
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http://dx.doi.org/10.1016/j.vaccine.2021.08.031DOI Listing
September 2021

Epidemiology associated with the exposure to Toxoplasma gondii in Nunavik's Inuit population using the 2017 Qanuilirpitaa cross-sectional health survey.

Zoonoses Public Health 2021 11 12;68(7):803-814. Epub 2021 Jul 12.

Université Laval, Québec, QC, Canada.

Foci of high seroprevalence against Toxoplasma gondii are observed in Nunavik, the Inuit land of Northern Quebec (Canada). Considering the rare occurrence of felids in the region, exposure is suspected to be driven by water- and food-borne transmission routes. Hypotheses were that drinking untreated water from natural sources and eating country food mostly raw increased the risk of exposure to the parasite. Data from 1,300 Inuit participants of the 2017 Nunavik Health Survey were included in three weighted robust Poisson regression models. The effect of three types of exposure variables: (1) water treatment (yes/no) and if country food was mostly eaten raw (yes/no); (2) main source of drinking water (bottled/municipal/natural) and frequency of country food consumption (continuous) and (3) drinking water risk (low/intermediate/high) and frequency of a raw country food consumption (continuous), on the presence of Toxoplasma antibodies were estimated. Models were adjusted for age, sex and ecological region, with multiple sensitivity analyses being performed. Toxoplasma gondii seroprevalences were consistently correlated with age quadratically, sex (prevalence ratio = PR ranged from 1.18 to 1.22), ecological region (PR ranged from 2.18 to 2.41; PR ranged from 1.52 to 1.59) and consuming bivalve mollusc/urchin (PR varied from 1.02 to 1.21) across all three models. Each increase of two consumptions per month of beluga (PR ranged from 1.01 to 1.03), seal liver (PR ranged from 1.01 to 1.02) and goose (PR ranged from 1.01 to 1.02) were also associated with seropositivity, albeit more clearly in models 2 and 3, while drinking water mainly from natural (PR of 1.47) or municipal (PR = 1.42) sources compared to bottled water, was correlated with seroprevalence, although results were compatible with the null. Our results suggest that both the oocyst- (mollusc/urchin, drinking water) and cyst-borne (walrus, seal liver and goose) transmission pathways could be present in Nunavik.
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http://dx.doi.org/10.1111/zph.12870DOI Listing
November 2021

Canadian contributions to research on neglected tropical diseases.

PLoS Negl Trop Dis 2021 07 1;15(7):e0009476. Epub 2021 Jul 1.

Bruyère Research Institute, Ottawa, Canada.

Background: The World Health Organization's (WHO) Neglected Tropical Disease (NTD) Road Map for 2021-2030 was recently endorsed by all member states at the World Health Assembly in November 2020. Although only 3 of the 20 NTDs are endemic in Canada (i.e., echinococcosis, rabies, and scabies), the Canadian research community has contributed to advancing the knowledge base of all 20 NTDs. Previous research comprehensively detailed Canadian research on 11 NTDs between 1950 and 2010 using a network analysis approach. The specific objective of the present analysis was to update the publication record over the last decade (2010-2019) to include all 20 NTDs.

Materials And Methods: A bibliometric analysis was conducted in Scopus and Web of Science databases (for English or French articles published between January 1, 2010 and December 31, 2019) using appropriate search terms for each of the 20 NTDs and where at least 1 of the authors had a Canadian institution address. A 21st search was added to include publications including multiple NTDs or a discussion of NTDs in general. Following assessment of inclusion and exclusion criteria, 2 reviewers independently screened all abstracts, with discordant observations rereviewed to arrive at an agreement. Duplicates were removed.

Results: A total of 1,790 publications were retrieved (1,738 with a disease-specific NTD focus and 52 with a general NTD focus, resulting in 1,659 unique publications), giving an average of over 160 articles per year. Over 80% were classified as full-length research articles. The top 3 journals in terms of frequency were PLOS Neglected Tropical Diseases, PLOS ONE, and the American Journal of Tropical Medicine and Hygiene. Authors' institutions were from all Canadian provinces. While all 20 NTDs were addressed in these publications, the 5 most commonly studied were leishmaniasis, dengue fever and chikungunya, Chagas disease, soil-transmitted helminthiases, and rabies.

Conclusions: Canadian researchers across the country have contributed to the evidence base of all 20 NTDs, publishing an average of over 160 publications per year between 2010 and 2019. As WHO NTD Road Map 2021-2030 rolls out globally, the Canadian research community, in collaboration with its partners and in solidarity with people living in vulnerable circumstances in endemic regions worldwide, is well positioned to meet future research challenges so that the goal of eliminating the disease burden attributable to NTDs can be achieved.
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http://dx.doi.org/10.1371/journal.pntd.0009476DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8248598PMC
July 2021

Evaluation of a Commercial Culture-Free Neutralization Antibody Detection Kit for Severe Acute Respiratory Syndrome-Related Coronavirus-2 and Comparison With an Antireceptor-Binding Domain Enzyme-Linked Immunosorbent Assay.

Open Forum Infect Dis 2021 Jun 30;8(6):ofab220. Epub 2021 Apr 30.

Division of Microbiology, Department of Clinical Laboratory Medicine, Optilab Montreal - McGill University Health Centre, Montreal, Quebec, Canada.

Background: Severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) surrogate neutralization assays that obviate the need for viral culture offer substantial advantages regarding throughput and cost. The cPass SARS-CoV-2 Neutralization Antibody Detection Kit (GenScript) is the first such commercially available assay that detects antibodies that block receptor-binding domain (RBD)/angiotensin-converting enzyme (ACE)-2 interaction. We aimed to evaluate cPass to inform its use and assess its added value compared with anti-RBD enzyme-linked immunosorbent assays (ELISAs).

Methods: Serum reference panels comprising 205 specimens were used to compare cPass to plaque-reduction neutralization test (PRNT) and a pseudotyped lentiviral neutralization (PLV) assay for detection of neutralizing antibodies. We assessed the correlation of cPass with an ELISA detecting anti-RBD immunoglobulin (Ig)G, IgM, and IgA antibodies at a single timepoint and across intervals from onset of symptoms of SARS-CoV-2 infection.

Results: Compared with PRNT-50, cPass sensitivity ranged from 77% to 100% and specificity was 95% to 100%. Sensitivity was also high compared with the pseudotyped lentiviral neutralization assay (93%; 95% confidence interval [CI], 85-97), but specificity was lower (58%; 95% CI, 48-67). Highest agreement between cPass and ELISA was for anti-RBD IgG ( = 0.823). Against the pseudotyped lentiviral neutralization assay, anti-RBD IgG sensitivity (99%; 95% CI, 94-100) was very similar to that of cPass, but overall specificity was lower (37%; 95% CI, 28-47). Against PRNT-50, results of cPass and anti-RBD IgG were nearly identical.

Conclusions: The added value of cPass compared with an IgG anti-RBD ELISA was modest.
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http://dx.doi.org/10.1093/ofid/ofab220DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8135688PMC
June 2021

Adjuvanted -Cathepsin B With Sulfated Lactosyl Archaeol Archaeosomes or AddaVax™ Provides Protection in a Pre-Clinical Schistosomiasis Model.

Front Immunol 2020 16;11:605288. Epub 2020 Nov 16.

Division of Experimental Medicine, Department of Medicine, McGill University, Montreal, QC, Canada.

Schistosomiasis threatens 800 million people worldwide. Chronic pathology manifests as hepatosplenomegaly, and intestinal schistosomiasis caused by can lead to liver fibrosis, cirrhosis, and blood in the stool. To assist the only FDA-approved drug, praziquantel, in parasite elimination, the development of a vaccine would be of high value. Cathepsin B (SmCB) is a well-documented vaccine target for intestinal schistosomiasis. Herein, we test the increased efficacy and immunogenicity of SmCB when combined with sulfated lactosyl archaeol (SLA) archaeosomes or AddaVax™ (a squalene based oil-in-water emulsion). Both vaccine formulations resulted in robust humoral and cell mediated immune responses. Impressively, both formulations were able to reduce parasite burden greater than 40% (WHO standard), with AddaVax™ reaching 86.8%. Additionally, SmCB with both adjuvants were able to reduce granuloma size and the amount of larval parasite hatched from feces, which would reduce transmission. Our data support SmCB as a target for vaccination; especially when used in an adjuvanted formulation.
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http://dx.doi.org/10.3389/fimmu.2020.605288DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7701121PMC
June 2021

Fecal host biomarkers predicting severity of Clostridioides difficile infection.

JCI Insight 2021 01 11;6(1). Epub 2021 Jan 11.

Infectious Diseases and Immunity in Global Health Program, Research Institute of the McGill University Health Centre (RI-MUHC), Montréal, Québec, Canada.

Clostridioides difficile is a major cause of health care-associated diarrhea. Severity ranges from mild to life-threatening, but this variability remains poorly understood. Microbiologic diagnosis of C. difficile infection (CDI) is straightforward but offers little insight into the patient's prognosis or into pathophysiologic determinants of clinical trajectory. The aim of this study was to discover host-derived, CDI-specific fecal biomarkers involved in disease severity. Subjects without and with CDI diarrhea were recruited. CDI severity was based on Infectious Diseases Society of America/Society for Healthcare Epidemiology of America criteria. We developed a liquid chromatography tandem mass spectrometry approach to identify host-derived protein biomarkers from stool and applied it to diagnostic samples for cohort-wise comparison (CDI-negative vs. nonsevere CDI vs. severe CDI). Selected biomarkers were orthogonally confirmed and subsequently verified in a CDI mouse model. We identified a protein signature from stool, consisting of alpha-2-macroglobulin (A2MG), matrix metalloproteinase-7 (MMP-7), and alpha-1-antitrypsin (A1AT), that not only discriminates CDI-positive samples from non-CDI ones but also is potentially associated with disease severity. In the mouse model, this signature with the murine homologs of the corresponding proteins was also identified. A2MG, MMP-7, and A1AT serve as biomarkers in patients with CDI and define novel components of the host response that may determine disease severity.
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http://dx.doi.org/10.1172/jci.insight.142976DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7821589PMC
January 2021

Prevalence and distribution of schistosomiasis in human, livestock, and snail populations in northern Senegal: a One Health epidemiological study of a multi-host system.

Lancet Planet Health 2020 08;4(8):e330-e342

Centre for Emerging, Endemic and Exotic Diseases, Department of Pathobiology and Population Sciences, Royal Veterinary College, University of London, Hertfordshire, UK; London Centre for Neglected Tropical Disease Research, School of Public Health, Imperial College London, London, UK.

Background: Schistosomiasis is a neglected tropical disease of global medical and veterinary importance. As efforts to eliminate schistosomiasis as a public health problem and interrupt transmission gather momentum, the potential zoonotic risk posed by livestock Schistosoma species via viable hybridisation in sub-Saharan Africa have been largely overlooked. We aimed to investigate the prevalence, distribution, and multi-host, multiparasite transmission cycle of Haematobium group schistosomiasis in Senegal, West Africa.

Methods: In this epidemiological study, we carried out systematic surveys in definitive hosts (humans, cattle, sheep, and goats) and snail intermediate hosts, in 2016-18, in two areas of Northern Senegal: Richard Toll and Lac de Guiers, where transmission is perennial; and Barkedji and Linguère, where transmission is seasonal. The occurrence and distribution of Schistosoma species and hybrids were assessed by molecular analyses of parasitological specimens obtained from the different hosts. Children in the study villages aged 5-17 years and enrolled in school were selected from school registers. Adults (aged 18-78 years) were self-selecting volunteers. Livestock from the study villages in both areas were also randomly sampled, as were post-mortem samples from local abattoirs. Additionally, five malacological surveys of snail intermediate hosts were carried out at each site in open water sources used by the communities and their animals.

Findings: In May to August, 2016, we surveyed 375 children and 20 adults from Richard Toll and Lac de Guiers, and 201 children and 107 adults from Barkedji and Linguère; in October, 2017, to January, 2018, we surveyed 386 children and 88 adults from Richard Toll and Lac de Guiers, and 323 children and 85 adults from Barkedji and Linguère. In Richard Toll and Lac de Guiers the prevalence of urogenital schistosomiasis in children was estimated to be 87% (95% CI 80-95) in 2016 and 88% (82-95) in 2017-18. An estimated 63% (in 2016) and 72% (in 2017-18) of infected children were shedding Schistosoma haematobium-Schistosoma bovis hybrids. In adults in Richard Toll and Lac de Guiers, the prevalence of urogenital schistosomiasis was estimated to be 79% (52-97) in 2016 and 41% (30-54) in 2017-18, with 88% of infected samples containing S haematobium-S bovis hybrids. In Barkedji and Linguère the prevalence of urogenital schistosomiasis in children was estimated to be 30% (23-38) in 2016 and 42% (35-49) in 2017-18, with the proportion of infected children found to be shedding S haematobium-S bovis hybrid miracidia much lower than in Richard Toll and Lac de Guiers (11% in 2016 and 9% in 2017-18). In adults in Barkedji and Linguère, the prevalence of urogenital schistosomiasis was estimated to be 26% (17-36) in 2016 and 47% (34-60) in 2017-18, with 10% of infected samples containing S haematobium-S bovis hybrids. The prevalence of S bovis in the sympatric cattle population of Richard Toll and the Lac de Guiers was 92% (80-99), with S bovis also found in sheep (estimated prevalence 14% [5-31]) and goats (15% [5-33]). In Barkedji and Linguère the main schistosome species in livestock was Schistosoma curassoni, with an estimated prevalence of 73% (48-93) in sheep, 84% (61-98) in goats and 8% (2-24) in cattle. S haematobium-S bovis hybrids were not found in livestock. In Richard Toll and Lac de Guiers 35% of infected Bulinus spp snail intermediate hosts were found to be shedding S haematobium-S bovis hybrids (68% shedding S haematobium; 17% shedding S bovis); however, no snails were found to be shedding S haematobium hybrids in Barkedji and Linguère (29% shedding S haematobium; 71% shedding S curassoni).

Interpretation: Our findings suggest that hybrids originate in humans via zoonotic spillover from livestock populations, where schistosomiasis is co-endemic. Introgressive hybridisation, evolving host ranges, and wider ecosystem contexts could affect the transmission dynamics of schistosomiasis and other pathogens, demonstrating the need to consider control measures within a One Health framework.

Funding: Zoonoses and Emerging Livestock Systems programme (UK Biotechnology and Biological Sciences Research Council, UK Department for International Development, UK Economic and Social Research Council, UK Medical Research Council, UK Natural Environment Research Council, and UK Defence Science and Technology Laboratory).
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http://dx.doi.org/10.1016/S2542-5196(20)30129-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7443702PMC
August 2020

A Procedure for Analyzing the Proteomic Proteomics Profile of Schistosoma mansoni Cercariae.

Methods Mol Biol 2020 ;2151:75-84

National Reference Centre for Parasitology, Montreal, QC, Canada.

Schistosomiasis is one of the most important helminthic parasitic infections in the world, with over 700 million people at risk of infection. Species of Schistosoma have a complex life cycle involving the infection of freshwater snails before infecting their mammalian definitive host. Taking about 130,000 lives per annum, S. mansoni is the major cause of intestinal schistosomiasis worldwide. Within Biomphalaria glabrata snails, asexual replication of the parasite gives rise to cercariae larvae. Cercariae actively penetrate the host's skin to complete their life cycle and eventually transform into adult worms. If left untreated, intestinal schistosomiasis can lead to peripheral destruction of the portal vein system, gastric hemorrhage from esophageal varices, as well as hepatic failure. Mass spectrometry (MS) is the method of choice for proteomics analysis. The bottom-up proteomics approach-also known as "shotgun proteomics"-typically includes a protein extraction and solubilization step followed by proteolytic digestion and tandem MS (MS/MS) analysis. Proteins are later identified by peptide de novo sequencing upon MS and MS/MS spectra of digest peptides. In this chapter, we introduce an analytical workflow for proteome profiling of S. mansoni cercariae using bottom-up proteomics. The cercariae were isolated and lysed. Proteins were then extracted, enzymatically digested, and subjected to liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. Proteins were identified using MaxQuant software. Cercariae are the first life stage of the parasite S. mansoni which humans encounter, and conducting proteomic analysis on this life cycle stage can shed light on possible drug or vaccine candidates to help disable the parasite's ability to infect or arm the immune system for parasite clearance.
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http://dx.doi.org/10.1007/978-1-0716-0635-3_7DOI Listing
March 2021

A 9-Year-Old Female With a Cough and Cavitary Lung Lesion.

Clin Infect Dis 2019 08;69(4):705-708

Division of Infectious Diseases, Department of Medical Microbiology.

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http://dx.doi.org/10.1093/cid/ciy769DOI Listing
August 2019

Isolated muscular cystic echinococcosis mimicking neoplasia.

J Travel Med 2020 Jul;27(4)

Université de Montréal, Department of Microbiology, Infectious Diseases and Immunology, 2900 Edouard Montpetit Blvd, Montreal, Canada H3T 1J4.

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http://dx.doi.org/10.1093/jtm/taaa002DOI Listing
July 2020

Vaccination against the digestive enzyme Cathepsin B using a YS1646 Salmonella enterica Typhimurium vector provides almost complete protection against Schistosoma mansoni challenge in a mouse model.

PLoS Negl Trop Dis 2019 12 2;13(12):e0007490. Epub 2019 Dec 2.

Department of Microbiology and Immunology, McGill University, Montreal, Quebec, Canada.

Schistosoma mansoni threatens hundreds of millions of people in >50 countries. Schistosomulae migrate through the lung and adult worms reside in blood vessels adjacent to the intestinal mucosa. Current candidate vaccines aren't designed to elicit a mucosal response. We have repurposed an attenuated Salmonella enterica Typhimurium strain (YS1646) to produce such a vaccine targeting Cathepsin B (CatB), a digestive enzyme important for parasite survival. Promoter-Type 3 secretory signal pairs were screened for protein expression in vitro and transfected into YS1646 to generate candidate vaccine strains. Two strains were selected for in vivo evaluation (nirB_SspH1 and SspH1_SspH1). Female C57BL/6 mice were immunized twice, 3 weeks apart, using six strategies: i) saline gavage (control), ii) the 'empty' YS1646 vector orally (PO) followed by intramuscular (IM) recombinant CatB (20μg IM rCatB), iii) two doses of IM rCatB, iv) two PO doses of YS1646-CatB, v) IM rCatB then PO YS1646-CatB and vi) PO YS1646-CatB then IM rCatB. Serum IgG responses to CatB were monitored by ELISA. Three weeks after the second dose, mice were challenged with 150 cercariae and sacrificed 7 weeks later to assess adult worm and egg burden (liver and intestine), granuloma size and egg morphology. CatB-specific IgG antibodies were low/absent in the control and PO only groups but rose substantially in other groups (5898-6766ng/mL). The highest response was in animals that received nirB_SspH1 YS1646 PO then IM rCatB. In this group, reductions in worm and intestine/liver egg burden (vs. control) were 93.1% and 79.5%/90.3% respectively (all P < .0001). Granuloma size was reduced in all vaccinated groups (range 32.9-52.8 x103μm2) and most significantly in the nirB_SspH1 + CatB IM group (34.7±3.4 x103μm2vs. 62.2±6.1 x103μm2: vs. control P < .01). Many eggs in the vaccinated animals had abnormal morphology. Targeting CatB using a multi-modality approach can provide almost complete protection against S. mansoni challenge.
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http://dx.doi.org/10.1371/journal.pntd.0007490DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6907844PMC
December 2019

Mouse Models for Use in Cryptosporidium Infection Studies and Quantification of Parasite Burden Using Flow Cytometry, qPCR, and Histopathology.

Methods Mol Biol 2020 ;2052:229-251

National Reference Centre for Parasitology, Research Institute of the McGill University Health Centre, Montreal, QC, Canada.

Cryptosporidiosis threatens life of young children in developing countries and newborn calves around the world. No vaccine or therapy can prevent or cure this diarrhea-inducing enteric disease caused by Cryptosporidium spp. protozoan parasites. There is an essential need to discover new therapeutic drugs efficient in reducing parasite burden in infected individuals. Research therefore relies on reliable small animal models of cryptosporidiosis. Here, we present excellent mouse models which can efficiently mimic pathogenesis of human and bovine cryptosporidiosis. We also describe methods to purify C. parvum oocysts from stool and intestine of infected mice to facilitate oocyst quantification. Moreover, we present protocols using flow cytometry, quantitative polymerase chain reaction, and histopathology to accurately quantify parasite burden in stool or intestine samples.
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http://dx.doi.org/10.1007/978-1-4939-9748-0_14DOI Listing
November 2020

Cutaneous leishmaniasis in the 21st century: from the laboratory to the bedside.

Curr Opin Infect Dis 2019 10;32(5):419-425

Purpose Of Review: Despite modern advances in molecular diagnostic tools and a better understanding of its complex pathophysiology, cutaneous leishmaniasis, a neglected tropical disease, remains a major global health problem. Laboratory methods to inform prognosis and treatment are not widely available, the therapeutic options are limited and have significant adverse effects, and emergence of drug resistance is a further complication. New advances in the understanding of the role of Leishmania RNA virus (LRV) as a prognostic factor, speciation methods and antimicrobial resistance testing and their limitations will be discussed.

Recent Findings: LRV, an intracytoplasmic endosymbiont found mostly in Leishmania spp. associated with more severe disease, appears to play a role in modulating the host immune response and has been associated with treatment failure in some Viannia subgenus species. Proper speciation is an important guide to management. However, recent findings have demonstrated significant heterogeneity of results related to differences in genotyping methods.

Summary: Recognition of the role of LRV in immune modulation and response to treatment along with more accessible tools for its detection to guide management at the bedside should allow a better individualized approach. Improving accessibility and standardization of speciation methods and antimicrobial susceptibility testing should be major goals to improve cutaneous leishmaniasis management in the 21st century.
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http://dx.doi.org/10.1097/QCO.0000000000000579DOI Listing
October 2019

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

NPJ Vaccines 2019 15;4:17. Epub 2019 May 15.

2Infectious Diseases and Immunity in Global Health Program, Research Institute of McGill University Health Centre, Glen Site, 1001 Décarie Street, Montréal, QC H4A 3J1 Canada.

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.
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http://dx.doi.org/10.1038/s41541-019-0111-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6520342PMC
May 2019

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

Am J Trop Med Hyg 2019 07;101(1):123-125

Division of Infectious Diseases, Department of Medical Microbiology, McGill University Health Centre, Montreal, Canada.

We report the case of a 64-year-old woman found to have urban-acquired () 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 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 HAT.
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http://dx.doi.org/10.4269/ajtmh.18-0889DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6609208PMC
July 2019

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

Parasit Vectors 2019 Apr 3;12(1):155. Epub 2019 Apr 3.

Department of Veterinary Microbiology, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, S7H 5B4, Canada.

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.
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http://dx.doi.org/10.1186/s13071-019-3408-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6448294PMC
April 2019

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

PLoS Negl Trop Dis 2019 03 20;13(3):e0007259. Epub 2019 Mar 20.

National Reference Centre for Parasitology, Research Institute of the McGill University Health Centre, Montreal, QC, Canada.

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.
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http://dx.doi.org/10.1371/journal.pntd.0007259DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6443187PMC
March 2019

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

Methods Mol Biol 2019 ;1955:263-273

National Reference Centre for Parasitology, Research Institute of the McGill University Health Centre, Montreal, QC, Canada.

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.
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http://dx.doi.org/10.1007/978-1-4939-9148-8_20DOI Listing
July 2019

Validation of Apolipoprotein A-1 and Fibronectin Fragments as Markers of Parasitological Cure for Congenital Chagas Disease in Children Treated With Benznidazole.

Open Forum Infect Dis 2018 Nov 1;5(11):ofy236. Epub 2018 Nov 1.

National Reference Centre for Parasitology, The Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada.

Background: No reliable tests or validated biomarkers exist to ensure parasitological cure following treatment of Chagas disease (CD) patients chronically infected with . As seroreversion, the only marker of cure, happens more quickly in children, we investigated the correlation between previously identified biomarkers and seroreversion in children.

Methods: Thirty CD children (age 1 month to 10 years) diagnosed as positive (time point S0) were treated with benznidazole (BZ) 5-8 mg/kg/d for 60 days. At least 2 serological tests were used to evaluate treatment efficacy from the end of treatment (S1) until seroreversion (S2). Thirty children (age 1 month to 10 years) and 15 adults were used as healthy controls (HCs). Immunoblot and a proteomic-based assay were used to validate previously identified fragments of apolipoprotein A-1 (ApoA1) and fibronectin (FBN) as CD biomarkers.

Results: Correlation between seroreversion and absence of ApoA1 and FBN fragments by immunoblot was observed in 30/30 (100%) and 29/30 (96.6%) CD children, respectively. ApoA1 and FBN fragments were absent at the end of BZ treatment in 20/30 (66.6%) and 16/30 (53.3%) children, respectively. Absence of fragments in serum profiles was confirmed by mass spectrometry. Using intact protein analysis, a 28 109-Da protein identified as full-length ApoA1 by tandem mass spectrometry was detected in HC serum samples.

Conclusions: These data confirm that ApoA1 and FBN fragments can discriminate between healthy and -infected samples. Correlation with seroreversion was shown for the first time; results suggest predictive capacity potentially superior to serology, making them potentially useful as surrogate biomarkers.
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http://dx.doi.org/10.1093/ofid/ofy236DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6210386PMC
November 2018

Development of a sandwich ELISA to detect Leishmania 40S ribosomal protein S12 antigen from blood samples of visceral leishmaniasis patients.

BMC Infect Dis 2018 Oct 3;18(1):500. Epub 2018 Oct 3.

Department of Microbiology and Immunology, McGill University, 3775 University Street, Montreal, Quebec, H3A2B4, Canada.

Background: Visceral leishmaniasis (VL), caused by Leishmania donovani complex parasites, is a neglected parasitic disease that is generally fatal if untreated. Despite decades of research to develop a sensitive VL diagnostic test, definitive diagnosis of VL still mainly relies on the visualization of the parasite in aspirates from the spleen, liver or bone marrow, an invasive and dangerous process with variable sensitivity. A sensitive assay that can detect Leishmania antigen from blood samples will help confirm cause, cure or recurrence of VL.

Methods: In this study, rabbit polyclonal antibodies were raised against eight recombinant Leishmania proteins that are highly abundant in Leishmania. The antibodies were purified and labeled with biotin for developing a prototype sandwich enzyme-linked immunosorbent assay (ELISA).

Results: The ELISA for the Leishmania 40S ribosomal protein S12 detected target antigen with the highest sensitivity and specificity and could detect 1 pg of purified protein or as few as 60 L. donovani parasites. The 40S ribosomal protein S12 sandwich ELISA could detect the target antigen from Peripheral Blood Mononuclear Cell (PBMC) samples in 68% of VL patients and post-kala-azar dermal leishmaniasis (PKDL) patients, providing an estimation of parasitemia ranging from 15 to 80 amastigotes per ml of blood.

Conclusion: These results indicate that the 40S ribosomal protein S12 sandwich ELISA warrants further tests with more clinical samples of VL patients and other parasitic diseases. It is hopeful that this ELISA could become a useful tool for confirming VL diagnosis, monitoring treatment progress, disease recurrence and possibly detecting asymptomatic Leishmania infections with a high parasite load.
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http://dx.doi.org/10.1186/s12879-018-3420-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6171325PMC
October 2018

First Human Case of Metacestode Infection Caused by Versteria sp. in a Kidney Transplant Recipient.

Clin Infect Dis 2019 02;68(4):680-683

J.D. MacLean Centre for Tropical Diseases at McGill University.

Cestodes are emerging agents of severe opportunistic infections among immunocompromised patients. We describe the first case of human infection, with the recently-proposed genus Versteria causing an invasive, tumor-like hepatic infection with regional and distant extension in a 53-year-old female kidney transplant recipient from Atlantic Canada.
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http://dx.doi.org/10.1093/cid/ciy602DOI Listing
February 2019
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