Publications by authors named "Malcolm K Jones"

122 Publications

Innovations and Advances in Schistosome Stem Cell Research.

Front Immunol 2021 5;12:599014. Epub 2021 Mar 5.

Department of Immunology, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.

Schistosomes infect about 250 million people globally causing the devastating and persistent disease of schistosomiasis. These blood flukes have a complicated life cycle involving alternating infection of freshwater snail intermediate and definitive mammalian hosts. To survive and flourish in these diverse environments, schistosomes transition through a number of distinct life-cycle stages as a result of which they change their body plan in order to quickly adapt to each new environment. Current research suggests that stem cells, present in adults and larvae, are key in aiding schistosomes to facilitate these changes. Given the recent advances in our understanding of schistosome stem cell biology, we review the key roles that two major classes of cells play in the different life cycle stages during intramolluscan and intramammalian development; these include the germinal cells of sporocysts involved in asexual reproduction in molluscan hosts and the neoblasts of adult worms involved in sexual reproduction in human and other mammalian hosts. These studies shed considerable new light in revealing the stem cell heterogeneity driving the propagation of the schistosome life cycle. We also consider the possibility and value of establishing stem cell lines in schistosomes to advance schistosomiasis research. The availability of such self-renewable resources will provide new platforms to study stem cell behavior and regulation, and to address fundamental aspects of schistosome biology, reproductive development and survival. In turn, such studies will create new avenues to unravel individual gene function and to optimize genome-editing processes in blood flukes, which may lead to the design of novel intervention strategies for schistosomiasis.
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http://dx.doi.org/10.3389/fimmu.2021.599014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7973109PMC
March 2021

Perceptions of dog owners towards canine gastrointestinal parasitism and associated human health risk in Southeast Queensland.

One Health 2021 Jun 16;12:100226. Epub 2021 Feb 16.

The University of Queensland, School of Veterinary Science, Veterinary Parasitology & Ecology, Gatton 4343, Queensland, Australia.

Canine companion animals can carry a number of zoonotic parasites which can adversely impact both human and animal health. Previous studies in Australia indicated that while parasitic infections in dogs are still common and there is variability in the awareness and perception of zoonotic risks among pet owners, the likely contribution of sociodemographic factors to the variation in awareness and perception needs to be further explored. The primary objective of this study is to quantify the relationship between dog owners' knowledge and beliefs about dog parasites and their sociodemographic characteristics. In this study, we surveyed a total of 281 dog owners in SE Queensland between April 2019 to March 2020 and the relationship between dog owners' perception of gastrointestinal parasite infection was assessed using an adaptation of the Health Belief Model, social cognitive framework for health protection. The model looked into the role of dog owners' demography on their perceived severity and susceptibility to zoonotic canine parasites and their likelihood of performing actions associated with worm control of their pets. Our results indicate that owners perceptions about parasitic disease severity in their pets was 26% higher in female dog owners compared to males, in respondents owning dogs over 10 years (27% higher than those owning a dog <3 years) and those owners that regularly deworm their pets and report faeces disposal. Our study indicates that the perceptions of pet owners towards zoonotic canine parasites varies demographically and owner education is important to prevent infection among dogs and control the zoonotic transmission to owners and the community. Finally, there was evidence that increased frequency of visits to veterinary clinics can increase the likelihood of owners performing worm treatment, proper faecal disposal, and cooking meat before feeding it to dogs.
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http://dx.doi.org/10.1016/j.onehlt.2021.100226DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7903457PMC
June 2021

A unique group of scabies mite pseudoproteases promotes cutaneous blood coagulation and delays plasmin-induced fibrinolysis.

PLoS Negl Trop Dis 2021 01 6;15(1):e0008997. Epub 2021 Jan 6.

Cell and Molecular Biology Department, Infectious Diseases Program, QIMR Berghofer Medical Research Institute, Brisbane, Australia.

Background: Scabies, a highly contagious skin disease affecting more than 200 million people worldwide at any time, is caused by the parasitic mite Sarcoptes scabiei. In the absence of molecular markers, diagnosis requires experience making surveillance and control challenging. Superficial microthrombi in the absence of vasculitis in scabies-affected skin are a recognised, yet unexplained histopathological differential of scabies infection. This study demonstrates that a family of Scabies Mite Inactivated Cysteine Protease Paralogues (SMIPP-Cs) excreted by the mites plays a role in formation of scabies-induced superficial microthrombi.

Methodology/principal Findings: A series of in vitro and ex vivo experiments involving two representative recombinant SMIPP-Cs was carried out. In the presence of SMIPP-Cs, the thrombin clotting time (TCT), fibrin formation and plasmin induced fibrinolysis were monitored in vitro. The ultrastructure of the SMIPP-C-modulated fibrin was analysed by Scanning Electron Microscopy (SEM). Immuno-histological analyses were performed ex vivo, to localise the SMIPP-C proteins within scabies infected skin biopsies. SMIPP-Cs displayed pro-coagulant properties. They bound calcium ions, reduced the thrombin clotting time, enhanced the fibrin formation rate and delayed plasmin-induced fibrinolysis. The SMIPP-Cs associated with fibrin clots during fibrinogen polymerisation and did not bind to preformed fibrin. Scanning electron microscopy revealed that the fibrin clots formed in the presence of SMIPP-Cs were aberrant and denser than normal fibrin clots. SMIPP-Cs were detected in microthrombi which are commonly seen in scabietic skin.

Conclusions/significance: The SMIPP-Cs are the first scabies mite proteins found in sub-epidermal skin layers and their pro-coagulant properties promote superficial microthrombi formation in scabetic skin. Further research is needed to evaluate their potential as diagnostic or therapeutic target.
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http://dx.doi.org/10.1371/journal.pntd.0008997DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7815109PMC
January 2021

CRISPR/Cas9-mediated genome editing of Schistosoma mansoni acetylcholinesterase.

FASEB J 2021 01;35(1):e21205

Immunology Department, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.

CRISPR/Cas9-mediated genome editing shows cogent potential for the genetic modification of helminth parasites. We report successful gene knock-in (KI) into the genome of the egg of Schistosoma mansoni by combining CRISPR/Cas9 with single-stranded oligodeoxynucleotides (ssODNs). We edited the acetylcholinesterase (AChE) gene of S. mansoni targeting two guide RNAs (gRNAs), X5 and X7, located on exon 5 and exon 7 of Smp_154600, respectively. Eggs recovered from livers of experimentally infected mice were transfected by electroporation with a CRISPR/Cas9-vector encoding gRNA X5 or X7 combining with/ without a ssODN donor. Next generation sequencing analysis of reads of amplicon libraries spanning targeted regions revealed that the major modifications induced by CRISPR/Cas9 in the eggs were generated by homology directed repair (HDR). Furthermore, soluble egg antigen from AChE-edited eggs exhibited markedly reduced AChE activity, indicative that programed Cas9 cleavage mutated the AChE gene. Following injection of AChE-edited schistosome eggs into the tail veins of mice, an significantly enhanced Th2 response involving IL-4, -5, -10, and-13 was detected in lung cells and splenocytes in mice injected with X5-KI eggs in comparison to control mice injected with unmutated eggs. A Th2-predominant response, with increased levels of IL-4, -13, and GATA3, also was induced by X5 KI eggs in small intestine-draining mesenteric lymph node cells when the gene-edited eggs were introduced into the subserosa of the ileum of the mice. These findings confirmed the potential and the utility of CRISPR/Cas9-mediated genome editing for functional genomics in schistosomes.
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http://dx.doi.org/10.1096/fj.202001745RRDOI Listing
January 2021

CRISPR/Cas9: A new tool for the study and control of helminth parasites.

Bioessays 2021 Jan 4;43(1):e2000185. Epub 2020 Nov 4.

Immunology Department, QIMR Berghofer Medical Research Institute, Herston, Brisbane, Queensland, Australia.

Recent reports of CRISPR/Cas9 genome editing in parasitic helminths open up new avenues for research on these dangerous pathogens. However, the complex morphology and life cycles inherent to these parasites present obstacles for the efficient application of CRISPR/Cas9-targeted mutagenesis. This is especially true with the trematode flukes where only modest levels of gene mutation efficiency have been achieved. Current major challenges in the application of CRISPR/Cas9 for study of parasitic worms thus lie in enhancing gene mutation efficiency and overcoming issues involved in host passage so that mutated parasites survive. Strategies developed for CRISPR/Cas9 studies on Caenorhabditis elegans, protozoa and mammalian cells, including novel delivery methods, the choice of selectable markers, and refining mutation precision represent novel tactics whereby these impediments can be overcome. Furthermore, employing CRISPR/Cas9-mediated gene drive to interfere with vector transmission represents a novel approach for the control of parasitic worms that is worthy of further exploration.
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http://dx.doi.org/10.1002/bies.202000185DOI Listing
January 2021

Use of kinase inhibitors against schistosomes to improve and broaden praziquantel efficacy.

Parasitology 2020 11 3;147(13):1488-1498. Epub 2020 Aug 3.

QIMR Berghofer Medical Research Institute, Herston, Australia.

Praziquantel (PZQ) is the drug of choice for schistosomiasis. The potential drug resistance necessitates the search for adjunct or alternative therapies to PZQ. Previous functional genomics has shown that RNAi inhibition of Ca2+/calmodulin-dependent protein kinase II (CaMKII) gene in Schistosoma adult worms significantly improved the effectiveness of PZQ. Here we tested the in vitro efficacy of 15 selective and non-selective CaMK inhibitors against Schistosoma mansoni and showed that PZQ efficacy was improved against refractory juvenile parasites when combined with these CaMK inhibitors. By measuring CaMK activity and the mobility of adult S. mansoni, we identified two non-selective CaMK inhibitors, Staurosporine (STSP) and 1Naphthyl PP1 (1NAPP1), as promising candidates for further study. The impact of STSP and 1NAPP1 was investigated in mice infected with S. mansoni in the presence or absence of a sub-lethal dose of PZQ against 2- and 7-day-old schistosomula and adults. Treatment with STSP/PZQ induced a significant (47-68%) liver egg burden reduction compared with mice treated with PZQ alone. The findings indicate that the combination of STSP and PZQ dosages significantly improved anti-schistosomal activity compared to PZQ alone, demonstrating the potential of selective and non-selective CaMK/kinase inhibitors as a combination therapy with PZQ in treating schistosomiasis.
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http://dx.doi.org/10.1017/S0031182020001250DOI Listing
November 2020

A new diagnostic strategy which uses a luminol-H2O2 system to detect helminth eggs in fecal sediments processed by the Helmintex method.

PLoS Negl Trop Dis 2020 07 30;14(7):e0008500. Epub 2020 Jul 30.

Research Group on Biomedical Parasitology, School of health and life sciences, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, Brazil.

Schistosomiasis remains a serious public health problem in tropical regions, affecting more than 250 million people. Sensitive diagnostic methods represent key tools for disease elimination, in particular in areas with low endemicity. Advances in the use of luminol-based chemiluminescent techniques have enabled greater sensitivity and speed in obtaining results in different diagnostic settings. In this study, we developed a luminol-H2O2 chemiluminescence (CL) method to detect Schistosoma mansoni eggs in human fecal sediments processed by the Helmintex (HTX) method. After S. mansoni eggs were incubated with a solution of luminol-H2O2 the light emission was detected and measured by spectrophotometry at 431 nm for 5 min, using detection and counts of eggs by bright field optical microscopy as a reference. CL intensity was found to correlate with different sources and numbers of eggs. Furthermore, our results showed that the CL method can distinguish positive from negative samples with 100% sensitivity and 71% specificity. To our knowledge, this is the first study to report the use of CL for the diagnosis of helminths from fecal samples. The combination of the HTX method with CL represents an important advance in providing a reference method with the highest standards of sensitivity.
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http://dx.doi.org/10.1371/journal.pntd.0008500DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7437924PMC
July 2020

Systematic review of registered trials of Hydroxychloroquine prophylaxis for COVID-19 health-care workers at the first third of 2020.

One Health 2020 Dec 19;10:100141. Epub 2020 May 19.

Univ Lyon, Malaria Research Unit, ICBMS, UMR 5246 CNRS INSA CPE, F-69100, Lyon, France.

In the absence of a vaccine the medical and scientific community is looking intensely at utilizing a pre or post exposure drug that could decrease viremia. The search for a medication that could reduce risk of serious disease, and ideally of any manifestation of disease from SARS-CoV2, and of asymptomatic shedding of SARS-CoV2 is of urgent interest. Repurposing existing pharmaceuticals is among the approaches to achieve these ends. We performed a systematic review of all interventional studies registered in ClinicalTrials.gov with a focus on one repurposed drug, Hydroxychloroquine (HCQ). The detailed analysis of these studies, some of them already recruiting, provide an overall picture of HCQ use as a COVID-19 prophylaxis around the world. Among the included studies, all but three were randomized and parallel and most of them (74%, 23/31) were double-blinded to quadruple-blinded studies. We found a great diversity in dosing and nearly all the possible scientifically reasonable regimens are under evaluation. This diversity offers benefits as well as challenges. Importantly, the final analysis of these trials should be done through an extensive reading of the results in regard to the clinical design, it will be crucial to carefully read and evaluate the results of each study in regards to the clinical design rather than quickly glancing a 140 characters-based social media message announcing the failure or success of a drug against a disease.
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http://dx.doi.org/10.1016/j.onehlt.2020.100141DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7235596PMC
December 2020

COVID-19 and globalization.

One Health 2020 Jun 10;9:100132. Epub 2020 Apr 10.

Health Travel Medicine Program, Vaccine Clinic, Emergency Response Team Development, Florida International University, Miami, USA.

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http://dx.doi.org/10.1016/j.onehlt.2020.100132DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7184197PMC
June 2020

Coalition: Advocacy for prospective clinical trials to test the post-exposure potential of hydroxychloroquine against COVID-19.

One Health 2020 Jun 4;9:100131. Epub 2020 Apr 4.

Departamento de Parasitología, Facultad de Farmacia, Universidad de Valencia, 46100, Valencia, Spain.

Our coalition of public health experts, doctors, and scientists worldwide want to draw attention to the need for high-quality evaluation protocols of the potential beneficial effect of hydroxychloroquine (HCQ) as a post-exposure drug for exposed people. In the absence of an approved, recognized effective pre or post-exposure prophylactic drug or vaccine for COVID-19, nor of any approved and validated therapeutic drug, coupled with social and political pressure raised by publicity both regarding the potential beneficial effect of hydroxychloroquine (HCQ) as well as potential risks from HCQ, we urge the immediate proper clinical trials. Specifically, we mean using HCQ for post-exposure of people with close contact with patients with positive COVID19 rtPCR, including home and medical caregivers. We have reviewed the mechanisms of antiviral effect of HCQ, the risk-benefit ratio taking into consideration the PK/PD of HCQ and the thresholds of efficacy. We have studied its use as an antimalarial, an antiviral, and an immunomodulating drug and concluded that the use of HCQ at doses matching that of the standard treatment of Systemic Lupus erythematous, which has proven safety and efficacy in terms of HCQ blood and tissue concentration adapted to bodyweight (2,3), at 6 mg/kg/day 1 (loading dose) followed by 5 mg/kg/ day, with a maximum limit of 600 mg/day in all cases should swiftly be clinically evaluated as a post-exposure drug for exposed people.
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http://dx.doi.org/10.1016/j.onehlt.2020.100131DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7128742PMC
June 2020

The novel Coronavirus (SARS-CoV-2) is a one health issue.

One Health 2020 Jun 14;9:100123. Epub 2020 Feb 14.

School of Veterinary Science, The University of Queensland, Brisbane, Qld 4072, Australia.

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http://dx.doi.org/10.1016/j.onehlt.2020.100123DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7049657PMC
June 2020

The mitochondrial genome of is distinct from and .

Parasitology 2020 05 13;147(6):681-688. Epub 2020 Feb 13.

Sydney School of Veterinary Science, Faculty of Science, University of Sydney, 2006, New South Wales, Australia.

The native rat lungworm (Angiostrongylus mackerrasae) and the invasive rat lungworm (Angiostrongylus cantonensis) occur in eastern Australia. The species identity of A. mackerrasae remained unquestioned until relatively recently, when compilation of mtDNA data indicated that A. mackerrasae sensu Aghazadeh et al. (2015b) clusters within A. cantonensis based on their mitochondrial genomes (mtDNA). To re-evaluate the species identity of A. mackerrasae, we sought material that would be morphologically conspecific with A. mackerrasae. We combined morphological and molecular approaches to confirm or refute the specific status of A. mackerrasae. Nematodes conspecific with A. mackerrasae from Rattus fuscipes and Rattus rattus were collected in Queensland, Australia. Morphologically identified A. mackerrasae voucher specimens were characterized using amplification of cox1 followed by the generation of reference complete mtDNA. The morphologically distinct A. cantonensis, A. mackerrasae and A. malaysiensis are genetically distinguishable forming a monophyletic mtDNA lineage. We conclude that A. mackerrasae sensu Aghazadeh et al. (2015b) is a misidentified specimen of A. cantonensis. The availability of the mtDNA genome of A. mackerrasae enables its unequivocal genetic identification and differentiation from other Angiostrongylus species.
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http://dx.doi.org/10.1017/S0031182020000232DOI Listing
May 2020

The Challenge of Developing a Single-Dose Treatment for Scabies.

Trends Parasitol 2019 11 29;35(11):931-943. Epub 2019 Aug 29.

QIMR Berghofer Medical Research Institute, Infectious Diseases Program, 300 Herston Road, Herston, Brisbane 4006, Australia. Electronic address:

Scabies is a common skin disease with an estimated worldwide incidence of 200 million people infected per year. Its morbidity and mortality is principally due to secondary bacterial infections, a link now well recognized and prompting the recent inclusion of this disease-complex in the WHO list of neglected tropical diseases. The few treatments available are poorly effective against Sarcoptes scabiei eggs and appear to induce resistance in the parasite. An ideal alternative would be a single-dose regimen that kills all developmental stages, including eggs. Drugs used in the veterinary field and applied to other arthropods could be tested experimentally in an established pig-scabies model. Moreover, functional genomics combined with target validation through biochemical research should assist in identifying new drugs.
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http://dx.doi.org/10.1016/j.pt.2019.08.002DOI Listing
November 2019

Synergistic Toxicity of Plant Essential Oils Combined with Pyrethroid Insecticides against Blow Flies and the House Fly.

Insects 2019 Jun 21;10(6). Epub 2019 Jun 21.

Department of Parasitology, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand.

Blow flies (Diptera: Calliphoridae) and the house fly (Diptera: Muscidae) are filth flies of medical importance, and control of their population is needed. As insecticide applications have resulted in fly resistance, and the exploration of plant essential oils (EOs) has increased against filth flies, this study assessed the combination of EOs with pyrethoids to enhance toxic efficacy. The EOs of five effective plants were screened initially against the house fly ( L.). Their chemical constituent was performed using gas chromatography-mass spectrometry (GC-MS) analysis. The main components of (Zingiberaceae) rhizome, (Zingiberaceae) rhizome, (Rutaceae) fruit peel, (Lamiaceae) seed, and (Rutaceae) fruit were δ-3-caren (35.25%), β-turmerone (51.68%), β-pinene (26.56%), p-cumic aldehyde (58.21%), and dipentene (60.22%), respectively. The screening test revealed that the three most effective plant EOs were from , and , which were selected for the combination with two pyrethroid insecticides (permethrin and deltamethrin), in order to enhance their synergistic efficacy against the blow flies, Fabricius, Macquart, and Wiedemann, and the house fly. Synergistic action was presented in almost all of the flies tested with permenthrin/deltamethrin/EOs mixtures. It was interesting that the combination of deltamethrin with three EOs showed a synergistic effect on all of the tested flies. However, an antagonistic effect was observed in and treated with permethrin- and treated with permethrin-. The LD of insecticides decreased when combined with plant EOs. This alternative strategy will be helpful in developing a formula for effective fly control management.
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http://dx.doi.org/10.3390/insects10060178DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6627951PMC
June 2019

Glycans in the roles of parasitological diagnosis and host-parasite interplay.

Parasitology 2019 09 6;146(10):1217-1232. Epub 2019 May 6.

Escola de Ciências, Pontifícia Universidade Católica do Rio Grande do Sul, Av. Ipiranga 6681, Porto Alegre RS 90619-900 Rio Grande do Sul, Brazil.

The investigation of the glycan repertoire of several organisms has revealed a wide variation in terms of structures and abundance of glycan moieties. Among the parasites, it is possible to observe different sets of glycoconjugates across taxa and developmental stages within a species. The presence of distinct glycoconjugates throughout the life cycle of a parasite could relate to the ability of that organism to adapt and survive in different hosts and environments. Carbohydrates on the surface, and in excretory-secretory products of parasites, play essential roles in host-parasite interactions. Carbohydrate portions of complex molecules of parasites stimulate and modulate host immune responses, mainly through interactions with specific receptors on the surface of dendritic cells, leading to the generation of a pattern of response that may benefit parasite survival. Available data reviewed here also show the frequent aspect of parasite immunomodulation of mammalian responses through specific glycan interactions, which ultimately makes these molecules promising in the fields of diagnostics and vaccinology.
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http://dx.doi.org/10.1017/S0031182019000465DOI Listing
September 2019

Qualitative and quantitative proteomic analyses of Schistosoma japonicum eggs and egg-derived secretory-excretory proteins.

Parasit Vectors 2019 Apr 16;12(1):173. Epub 2019 Apr 16.

School of Veterinary Science, The University of Queensland, Brisbane, QLD, Australia.

Background: Schistosome parasites lay up to a thousand eggs per day inside the veins of their mammalian hosts. The immature eggs deposited by females against endothelia of venules will embryonate within days. Approximately 30% of the eggs will migrate to the lumen of the intestine to continue the parasite life-cycle. Many eggs, however, are trapped in the liver and intestine causing the main pathology associated with schistosomiasis mansoni and japonica, the liver granulomatous response. Excretory-secretory egg proteins drive much of egg-induced pathogenesis of schistosomiasis mansoni, and Schistosoma japonicum induce a markedly distinct granulomatous response to that of S. mansoni.

Methods: To explore the basis of variations in this responsiveness, we investigated the proteome of eggs of S. japonicum. Using mass spectrometry qualitative and quantitative (SWATH) analyses, we describe the protein composition of S. japonicum eggs secretory proteins (ESP), and the differential expression of proteins by fully mature and immature eggs, isolated from faeces and ex vivo adults.

Results: Of 957 egg-related proteins identified, 95 were exclusively found in S. japonicum ESP which imply that they are accessible to host immune system effector elements. An in-silico analysis implies that ESP are able of stimulating the innate and adaptive immune system through several different pathways. While quantitative SWATH analysis revealed 124 proteins that are differentially expressed by mature and immature S. japonicum eggs, illuminating some important aspects of eggs biology and infection, we also show that mature eggs are more likely than immature eggs to stimulate host immune responses.

Conclusions: Here we present a list of potential targets that can be used to develop better strategies to avoid severe morbidity during S. japonicum infection, as well as improving diagnosis, treatment and control of schistosomiasis japonica.
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http://dx.doi.org/10.1186/s13071-019-3403-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6469072PMC
April 2019

Gene Expression in Developmental Stages of Provides Further Insight into the Importance of the Schistosome Insulin-Like Peptide.

Int J Mol Sci 2019 Mar 28;20(7). Epub 2019 Mar 28.

Molecular Parasitology Laboratory, QIMR Berghofer Medical Research Institute, Queensland 4006, Australia.

We showed previously that the insulin-like peptide (SjILP) binds the worm insulin receptors, thereby, activating the parasite's insulin pathway and emphasizing its important role in regulating uptake of glucose, a nutrient essential for parasite survival. Here we show that SjILP is differentially expressed in the schistosome life cycle and is especially highly transcribed in eggs, miracidia, and adult female worms. RNA inference was employed to knockdown SjILP in adults in vitro, with suppression confirmed by significantly reduced protein production, declined adenosine diphosphate levels, and reduction in glucose consumption. Immunolocalization showed that SjILP is located to lateral gland cells of mature intra-ovular miracidia in the schistosome egg, and is distributed on the ciliated epithelium and internal cell masses of newly transformed miracidia. In schistosomula, SjILP is present on the tegument in two antero-lateral points, indicating highly polarized expression during cercarial transformation. Analysis of serum from -infected mice by ELISA using a recombinant form of SjILP as an antigen revealed IgG immunoreactivity to this molecule at 7 weeks post-infection indicating it is likely secreted from mature eggs into the host circulation. These findings provide further insights on ILP function in schistosomes and its essential roles in parasite survival and growth in different development stages.
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http://dx.doi.org/10.3390/ijms20071565DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6480100PMC
March 2019

Whole-genome sequence of the bovine blood fluke Schistosoma bovis supports interspecific hybridization with S. haematobium.

PLoS Pathog 2019 01 23;15(1):e1007513. Epub 2019 Jan 23.

The University of Queensland Diamantina Institute, The University of Queensland, Brisbane, QLD, Australia.

Mesenteric infection by the parasitic blood fluke Schistosoma bovis is a common veterinary problem in Africa and the Middle East and occasionally in the Mediterranean Region. The species also has the ability to form interspecific hybrids with the human parasite S. haematobium with natural hybridisation observed in West Africa, presenting possible zoonotic transmission. Additionally, this exchange of alleles between species may dramatically influence disease dynamics and parasite evolution. We have generated a 374 Mb assembly of the S. bovis genome using Illumina and PacBio-based technologies. Despite infecting different hosts and organs, the genome sequences of S. bovis and S. haematobium appeared strikingly similar with 97% sequence identity. The two species share 98% of protein-coding genes, with an average sequence identity of 97.3% at the amino acid level. Genome comparison identified large continuous parts of the genome (up to several 100 kb) showing almost 100% sequence identity between S. bovis and S. haematobium. It is unlikely that this is a result of genome conservation and provides further evidence of natural interspecific hybridization between S. bovis and S. haematobium. Our results suggest that foreign DNA obtained by interspecific hybridization was maintained in the population through multiple meiosis cycles and that hybrids were sexually reproductive, producing viable offspring. The S. bovis genome assembly forms a highly valuable resource for studying schistosome evolution and exploring genetic regions that are associated with species-specific phenotypic traits.
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http://dx.doi.org/10.1371/journal.ppat.1007513DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6361461PMC
January 2019

Whole-genome sequence of the oriental lung fluke Paragonimus westermani.

Gigascience 2019 01 1;8(1). Epub 2019 Jan 1.

The University of Queensland Diamantina Institute, Faculty of Medicine, The University of Queensland, 37 Kent St, Translational Research Institute (TRI), Wooloongabba, QLD 4102.

Background: Foodborne infections caused by lung flukes of the genus Paragonimus are a significant and widespread public health problem in tropical areas. Approximately 50 Paragonimus species have been reported to infect animals and humans, but Paragonimus westermani is responsible for the bulk of human disease. Despite their medical and economic importance, no genome sequence for any Paragonimus species is available.

Results: We sequenced and assembled the genome of P. westermani, which is among the largest of the known pathogen genomes with an estimated size of 1.1 Gb. A 922.8 Mb genome assembly was generated from Illumina and Pacific Biosciences (PacBio) sequence data, covering 84% of the estimated genome size. The genome has a high proportion (45%) of repeat-derived DNA, particularly of the long interspersed element and long terminal repeat subtypes, and the expansion of these elements may explain some of the large size. We predicted 12,852 protein coding genes, showing a high level of conservation with related trematode species. The majority of proteins (80%) had homologs in the human liver fluke Opisthorchis viverrini, with an average sequence identity of 64.1%. Assembly of the P. westermani mitochondrial genome from long PacBio reads resulted in a single high-quality circularized 20.6 kb contig. The contig harbored a 6.9 kb region of non-coding repetitive DNA comprised of three distinct repeat units. Our results suggest that the region is highly polymorphic in P. westermani, possibly even within single worm isolates.

Conclusions: The generated assembly represents the first Paragonimus genome sequence and will facilitate future molecular studies of this important, but neglected, parasite group.
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http://dx.doi.org/10.1093/gigascience/giy146DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6329441PMC
January 2019

Calcium and Ca/Calmodulin-dependent kinase II as targets for helminth parasite control.

Biochem Soc Trans 2018 12 12;46(6):1743-1751. Epub 2018 Nov 12.

School of Biological Sciences, Queen's University Belfast, Belfast, U.K.

In eukaryotes, effective calcium homeostasis is critical for many key biological processes. There is an added level of complexity in parasites, particularly multicellular helminth worms, which modulate calcium levels while inhabiting the host microenvironment. Parasites ensure efficient calcium homeostasis through gene products, such as the calmodulin-dependent kinases (CaMK), the main focus of this review. The importance of CaMK is becoming increasingly apparent from recent functional studies of helminth and protozoan parasites. Investigations on the molecular regulation of calcium and the role of CaMK are important for both supplementing current drug regimens and finding new antiparasitic compounds. Whereas calcium regulators, including CaMK, are well characterised in mammalian systems, knowledge of their functional properties in parasites is increasing but is still in its infancy.
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http://dx.doi.org/10.1042/BST20180480DOI Listing
December 2018

The History of Bancroftian Lymphatic Filariasis in Australasia and Oceania: Is There a Threat of Re-Occurrence in Mainland Australia?

Trop Med Infect Dis 2018 Jun 4;3(2). Epub 2018 Jun 4.

Molecular Parasitology Laboratory, QIMR Berghofer Medical Research Institute, Brisbane, QLD 4006, Australia.

Lymphatic filariasis (LF) infects an estimated 120 million people worldwide, with a further 856 million considered at risk of infection and requiring preventative chemotherapy. The majority of LF infections are caused by , named in honour of the Australian physician Joseph Bancroft, with the remainder due to and . Infection with LF through the bite of an infected mosquito, can lead to the development of the condition known as elephantiasis, where swelling due to oedema leads to loss of function in the affected area and thickening of the skin, 'like an elephant'. LF has previously been endemic in Australia, although currently, no autochthonous cases occur there. Human immigration to Australia from LF-endemic countries, including those close to Australia, and the presence of susceptible mosquitoes that can act as suitable vectors, heighten the possibility of the reintroduction of LF into this country. In this review, we examine the history of LF in Australia and Oceania and weigh up the potential risk of its re-occurrence on mainland Australia.
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http://dx.doi.org/10.3390/tropicalmed3020058DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6073764PMC
June 2018

Soil-Transmitted Helminths in Tropical Australia and Asia.

Trop Med Infect Dis 2017 Oct 23;2(4). Epub 2017 Oct 23.

QIMR Berghofer Medical Research Institute, Molecular Parasitology Laboratory, Queensland 4006, Australia.

Soil-transmitted helminths (STH) infect 2 billion people worldwide including significant numbers in South-East Asia (SEA). In Australia, STH are of less concern; however, indigenous communities are endemic for STH, including , as well as for serious clinical infections due to other helminths such as spp. The zoonotic hookworm is also present in Australia and SEA, and may contribute to human infections particularly among pet owners. High human immigration rates to Australia from SEA, which is highly endemic for STH and , has resulted in a high prevalence of these helminthic infections in immigrant communities, particularly since such individuals are not screened for worm infections upon entry. In this review, we consider the current state of STH infections in Australia and SEA.
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http://dx.doi.org/10.3390/tropicalmed2040056DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6082059PMC
October 2017

Exploring Structural and Physical Properties of Schistosome Eggs: Potential Pathways for Novel Diagnostics?

Adv Parasitol 2018 20;100:209-237. Epub 2018 Apr 20.

School of Veterinary Sciences, The University of Queensland, Brisbane, QLD, Australia.

In this era of increasing demand for sensitive techniques to diagnose schistosomiasis, there is a need for an increased focus on the properties of the parasite eggs. The eggs are not only directly linked to the morbidity of chronic infection but are also potential key targets for accurate diagnostics. Eggs were the primary target of diagnostic tools in the past and we argue they could be the target of highly sensitive tools in the future if we focus on characteristics of their structure and shell surface that could be exploited for enhanced detection. In this review, we discuss the current state of knowledge of the physical structures of schistosome eggs and eggshells with a view to identifying pathways to a comprehensive understanding of their role in the host-parasite relationship and pathogenesis of infection, and pathways to new strategies for development of diagnostics.
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http://dx.doi.org/10.1016/bs.apar.2018.03.003DOI Listing
July 2019

Study of diagnostic accuracy of Helmintex, Kato-Katz, and POC-CCA methods for diagnosing intestinal schistosomiasis in Candeal, a low intensity transmission area in northeastern Brazil.

PLoS Negl Trop Dis 2018 03 8;12(3):e0006274. Epub 2018 Mar 8.

Laboratório de Biologia Parasitária, School of Sciences, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, Brazil.

Control initiatives have successfully reduced the prevalence and intensity of schistosomiasis transmission in several localities around the world. However, individuals that release low numbers of eggs in their feces may not be detected by classical methods that are limited by low sensitivity. Given that accurate estimates of prevalence are key to implementing planning control actions for the elimination of schistosomiasis, new diagnostic tools are needed to effectively monitor infections and confirm transmission interruption. The World Health Organization recommends the Kato-Katz (KK) thick smear as a parasitological test for epidemiological surveys, even though this method has been demonstrated to underestimate prevalence when egg burdens are low. The point-of-care immunodiagnostic for detecting schistosome cathodic circulating antigen (POC-CCA) method has been proposed as a more sensitive substitute for KK in prevalence estimations. An alternative diagnostic, the Helmintex (HTX) method, isolates eggs from fecal samples with the use of paramagnetic particles in a magnetic field. Here, a population-based study involving 461 individuals from Candeal, Sergipe State, Brazil, was conducted to evaluate these three methods comparatively by latent class analysis (LCA). The prevalence of schistosomiasis mansoni was determined to be 71% with POC-CCA, 40.% with HTX and 11% with KK. Most of the egg burdens of the individuals tested (70%) were < 1 epg, thereby revealing a dissociation between prevalence and intensity in this locality. Therefore, the present results confirm that the HTX method is a highly sensitive egg detection procedure and support its use as a reference method for diagnosing intestinal schistosomiasis and for comparative evaluation of other tests.
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http://dx.doi.org/10.1371/journal.pntd.0006274DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5843168PMC
March 2018

Eggs and Magnetism: New Approaches for Schistosomiasis Diagnosis.

Trends Parasitol 2018 04 6;34(4):267-271. Epub 2018 Feb 6.

School of Veterinary Sciences, The University of Queensland, Brisbane, Australia.

To date, reliable techniques that can provide accurate information on the local and global prevalence of schistosomiasis are still associated with high costs or labour-intensive processes. Here we discuss old and new concepts for diagnostic approaches, and we highlight structural properties of schistosome eggshells that result in their affinity for magnetic materials as a new diagnostic approach.
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http://dx.doi.org/10.1016/j.pt.2018.01.003DOI Listing
April 2018

Diagnosing and Understanding Angiostrongyliasis, A Zoonotic Cause of Meningitis.

ACS Chem Neurosci 2018 03 7;9(3):393-394. Epub 2018 Feb 7.

School of Veterinary Science , University of Queensland , Brisbane , Queensland 4072 , Australia.

Eosinophilic meningitis caused by Angiostrongylus cantonensis is spreading worldwide, and it can manifest as a severe neurological disease. Angiostrongyliasis is a food- and water-borne parasitosis that usually exhibits a seasonal and circumscribed geographical distribution. To improve control and treatment of these infections, further studies of transmission dynamics under natural conditions and the development of better diagnostic tools and treatment options are needed.
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http://dx.doi.org/10.1021/acschemneuro.8b00018DOI Listing
March 2018

Optimization of the Helmintex method for schistosomiasis diagnosis.

Exp Parasitol 2017 Jun 19;177:28-34. Epub 2017 Apr 19.

Laboratório de Biologia Parasitária, Faculdade de Biociências e Laboratório de Parasitologia Molecular, Instituto de Pesquisas Biomédicas, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, Brazil.

A diagnostic test that is reliable, sensitive, and applicable in the field is extremely important in epidemiological surveys, during medical treatment for schistosomiasis, and for the control and elimination of schistosomiasis. The Helmintex (HTX) method is based on the use of magnetic beads to trap eggs in a magnetic field. This technique is highly sensitive, but the screening of fecal samples consumes lots of time, thus delaying the results, especially in field studies. The objective of this work was to determine the effects of incorporation of the detergent Tween-20 into the method in an attempt to decrease the final pellet volume produced by the HTX method as well as the use of ninhydrin to stain the Schistosoma mansoni eggs. We showed that these modifications reduced the final volume of the fecal sediment produced in the last step of the HTX method by up to 69% and decreased the screening time to an average of 10.1 min per sample. The use of Tween 20 and ninhydrin led to a high percentage of egg recovery (27.2%). The data obtained herein demonstrate that the addition of detergent and the use of ninhydrin to the HTX process can optimize the screening step and also improve egg recovery, thus justifying the insertion of these steps into the HTX method.
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http://dx.doi.org/10.1016/j.exppara.2017.04.001DOI Listing
June 2017

Exploring the molecular mechanisms of parasite-host interactions with a view towards new therapeutics and vaccines.

Postepy Biochem 2016;62(3):370-376

Structural Chemistry Program, Eskitis Institute, Griffith University, Nathan, Queensland, Australia.

Despite the massive disease burden worldwide caused by parasitic nematodes and other infectious pathogens, the molecular basis of many infectious diseases caused by these pathogens has been unduly neglected for a long time. Therefore, accelerated progress towards novel therapeutics, and ultimately control of such infectious diseases, is of crucial importance. Capitalising on the wealth of data becoming available from proteomic and genomic studies, new protein targets at the pathogen-host interface can be identified and subjected to protein-based explorations of the molecular basis of pathogen-host interactions. By combining the use of systems and structural biology methodologies, insights into the structural and molecular mechanisms of these interactions can assist in the development of therapeutics and/or vaccines. This brief review examines two different proteins from the body wall of blood flukes - annexins and the stress-induced phosphoprotein 1 - both of which are presently interesting targets for the development of therapeutics.
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December 2017

A Plasmodium falciparum S33 proline aminopeptidase is associated with changes in erythrocyte deformability.

Exp Parasitol 2016 Oct 30;169:13-21. Epub 2016 Jun 30.

School of Natural Sciences, Griffith University, Brisbane, Queensland 4111, Australia; Eskitis Institute for Drug Discovery, Griffith University, Queensland, Australia. Electronic address:

Infection with the apicomplexan parasite Plasmodium falciparum is a major cause of morbidity and mortality worldwide. One of the striking features of this parasite is its ability to remodel and decrease the deformability of host red blood cells, a process that contributes to disease. To further understand the virulence of Pf we investigated the biochemistry and function of a putative Pf S33 proline aminopeptidase (PfPAP). Unlike other P. falciparum aminopeptidases, PfPAP contains a predicted protein export element that is non-syntenic with other human infecting Plasmodium species. Characterization of PfPAP demonstrated that it is exported into the host red blood cell and that it is a prolyl aminopeptidase with a preference for N-terminal proline substrates. In addition genetic deletion of this exopeptidase was shown to lead to an increase in the deformability of parasite-infected red cells and in reduced adherence to the endothelial cell receptor CD36 under flow conditions. Our studies suggest that PfPAP plays a role in the rigidification and adhesion of infected red blood cells to endothelial surface receptors, a role that may make this protein a novel target for anti-disease interventions strategies.
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http://dx.doi.org/10.1016/j.exppara.2016.06.013DOI Listing
October 2016

Functional characterisation of Schistosoma japonicum acetylcholinesterase.

Parasit Vectors 2016 06 10;9(1):328. Epub 2016 Jun 10.

Molecular Parasitology Laboratory, Infectious Diseases Division, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.

Background: Acetylcholinesterase (AChE) is an important metabolic enzyme of schistosomes present in the musculature and on the surface of the blood stage where it has been implicated in the modulation of glucose scavenging from mammalian host blood. As both a target for the antischistosomal drug metrifonate and as a potential vaccine candidate, AChE has been characterised in the schistosome species Schistosoma mansoni, S. haematobium and S. bovis, but not in S. japonicum. Recently, using a schistosome protein microarray, a predicted S. japonicum acetylcholinesterase precursor was significantly targeted by protective IgG1 immune responses in S. haematobium-exposed individuals that had acquired drug-induced resistance to schistosomiasis after praziquantel treatment.

Results: We report the full-length cDNA sequence and describe phylogenetic and molecular structural analysis to facilitate understanding of the biological function of AChE (SjAChE) in S. japonicum. The protein has high sequence identity (88 %) with the AChEs in S. mansoni, S. haematobium and S. bovis and has 25 % sequence similarity with human AChE, suggestive of a highly specialised role for the enzyme in both parasite and host. We immunolocalized SjAChE and demonstrated its presence on the surface of adult worms and schistosomula, as well as its lower expression in parenchymal regions. The relatively abundance of AChE activity (90 %) present on the surface of adult S. japonicum when compared with that reported in other schistosomes suggests SjAChE may be a more effective drug or immunological target against this species. We also demonstrate that the classical inhibitor of AChE, BW285c51, inhibited AChE activity in tegumental extracts of paired worms, single males and single females by 59, 22 and 50 %, respectively, after 24 h incubation with 200 μM BW284c51.

Conclusions: These results build on previous studies in other schistosome species indicating major differences in the enzyme between parasite and mammalian host, and provide further support for the design of an anti-schistosome intervention targeting AChE.
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http://dx.doi.org/10.1186/s13071-016-1615-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4901427PMC
June 2016