Draft genome sequences of four citrobacter isolates recovered from wild australian shorebirds
- Smith, Hannah, Bean, David, Pitchers, William, Valcanis, Mary, Clarke, Rohan, Loyn, Richard, Hassell, Chris, Greenhill, Andrew
- Authors: Smith, Hannah , Bean, David , Pitchers, William , Valcanis, Mary , Clarke, Rohan , Loyn, Richard , Hassell, Chris , Greenhill, Andrew
- Date: 2021
- Type: Text , Journal article
- Relation: Microbiology Resource Announcements Vol. 10, no. 1 (2021), p.
- Full Text:
- Reviewed:
- Description: Citrobacter is a ubiquitous bacterial genus whose members inhabit a variety of niches. Some species are clinically important for both antimicrobial resistance (AMR) carriage and as the cause of nosocomial infections. Surveillance of Citrobacter species in the environment can provide indicators of the spread of AMR genes outside clinical spaces. In this study, we present draft genome sequences of four Citrobacter isolates obtained from three species of wild Australian shorebirds. Copyright © 2021 Smith et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.
- Authors: Smith, Hannah , Bean, David , Pitchers, William , Valcanis, Mary , Clarke, Rohan , Loyn, Richard , Hassell, Chris , Greenhill, Andrew
- Date: 2021
- Type: Text , Journal article
- Relation: Microbiology Resource Announcements Vol. 10, no. 1 (2021), p.
- Full Text:
- Reviewed:
- Description: Citrobacter is a ubiquitous bacterial genus whose members inhabit a variety of niches. Some species are clinically important for both antimicrobial resistance (AMR) carriage and as the cause of nosocomial infections. Surveillance of Citrobacter species in the environment can provide indicators of the spread of AMR genes outside clinical spaces. In this study, we present draft genome sequences of four Citrobacter isolates obtained from three species of wild Australian shorebirds. Copyright © 2021 Smith et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.
Sensitive universal detection of blood parasites by selective pathogen-DNA enrichment and deep amplicon sequencing
- Flaherty, Briana, Barratt, Joel, Lane, Meredith, Talundzic, Eldin, Bradbury, Richard
- Authors: Flaherty, Briana , Barratt, Joel , Lane, Meredith , Talundzic, Eldin , Bradbury, Richard
- Date: 2021
- Type: Text , Journal article
- Relation: Microbiome Vol. 9, no. 1 (2021), p.
- Full Text:
- Reviewed:
- Description: Background: Targeted amplicon deep sequencing (TADS) has enabled characterization of diverse bacterial communities, yet the application of TADS to communities of parasites has been relatively slow to advance. The greatest obstacle to this has been the genetic diversity of parasitic agents, which include helminths, protozoa, arthropods, and some acanthocephalans. Meanwhile, universal amplification of conserved loci from all parasites without amplifying host DNA has proven challenging. Pan-eukaryotic PCRs preferentially amplify the more abundant host DNA, obscuring parasite-derived reads following TADS. Flaherty et al. (2018) described a pan-parasitic TADS method involving amplification of eukaryotic 18S rDNA regions possessing restriction sites only in vertebrates. Using this method, host DNA in total DNA extracts could be selectively digested prior to PCR using restriction enzymes, thereby increasing the number of parasite-derived reads obtained following NGS. This approach showed promise though was only as sensitive as conventional PCR. Results: Here, we expand on this work by designing a second set of pan-eukaryotic primers flanking the priming sites already described, enabling nested PCR amplification of the established 18S rDNA target. This nested approach facilitated introduction of a second restriction digestion between the first and second PCR, reducing the proportional mass of amplifiable host-derived DNA while increasing the number of PCR amplification cycles. We applied this method to blood specimens containing Babesia, Plasmodium, various kinetoplastids, and filarial nematodes and confirmed its limit of detection (LOD) to be approximately 10-fold lower than previously described, falling within the range of most qPCR methods. Conclusions: The assay detects and differentiates the major malaria parasites of humans, along with several other clinically important blood parasites. This represents an important step towards a TADS-based universal parasite diagnostic (UPDx) test with a sufficient LOD for routine applications. [MediaObject not available: see fulltext.]. © 2021, The Author(s).
- Authors: Flaherty, Briana , Barratt, Joel , Lane, Meredith , Talundzic, Eldin , Bradbury, Richard
- Date: 2021
- Type: Text , Journal article
- Relation: Microbiome Vol. 9, no. 1 (2021), p.
- Full Text:
- Reviewed:
- Description: Background: Targeted amplicon deep sequencing (TADS) has enabled characterization of diverse bacterial communities, yet the application of TADS to communities of parasites has been relatively slow to advance. The greatest obstacle to this has been the genetic diversity of parasitic agents, which include helminths, protozoa, arthropods, and some acanthocephalans. Meanwhile, universal amplification of conserved loci from all parasites without amplifying host DNA has proven challenging. Pan-eukaryotic PCRs preferentially amplify the more abundant host DNA, obscuring parasite-derived reads following TADS. Flaherty et al. (2018) described a pan-parasitic TADS method involving amplification of eukaryotic 18S rDNA regions possessing restriction sites only in vertebrates. Using this method, host DNA in total DNA extracts could be selectively digested prior to PCR using restriction enzymes, thereby increasing the number of parasite-derived reads obtained following NGS. This approach showed promise though was only as sensitive as conventional PCR. Results: Here, we expand on this work by designing a second set of pan-eukaryotic primers flanking the priming sites already described, enabling nested PCR amplification of the established 18S rDNA target. This nested approach facilitated introduction of a second restriction digestion between the first and second PCR, reducing the proportional mass of amplifiable host-derived DNA while increasing the number of PCR amplification cycles. We applied this method to blood specimens containing Babesia, Plasmodium, various kinetoplastids, and filarial nematodes and confirmed its limit of detection (LOD) to be approximately 10-fold lower than previously described, falling within the range of most qPCR methods. Conclusions: The assay detects and differentiates the major malaria parasites of humans, along with several other clinically important blood parasites. This represents an important step towards a TADS-based universal parasite diagnostic (UPDx) test with a sufficient LOD for routine applications. [MediaObject not available: see fulltext.]. © 2021, The Author(s).
The health belief model predicts intention to receive the covid-19 vaccine in Saudi Arabia : results from a cross-sectional survey
- Mahmud, Ilias, Kabir, Russell, Rahman, Muhammad Aziz, Alradie-Mohamed, Angi, Vinnakota, Divya, Al-Mohaimeed, Abdulrahman
- Authors: Mahmud, Ilias , Kabir, Russell , Rahman, Muhammad Aziz , Alradie-Mohamed, Angi , Vinnakota, Divya , Al-Mohaimeed, Abdulrahman
- Date: 2021
- Type: Text , Journal article
- Relation: Vaccines Vol. 9, no. 8 (2021), p.
- Full Text:
- Reviewed:
- Description: We examined the intention and predictors of accepting the COVID-19 vaccine in Saudi Arabia. We conducted a nation-wide, cross-sectional online survey between February and March 2021. A total of 1387 people (≥18 years) participated. Only 27.3% adults had a definite and 30.2% had a probable vaccination intent; 26.8% and 15.6% had a probable and definite negative vaccination intent. Older people (≥50 years) (p < 0.01), healthcare workers/professionals (p < 0.001), and those who received flu vaccine (p < 0.001) were more likely to have a positive intent. People from Riyadh were less likely to receive the vaccine (p < 0.05). Among the health belief model constructs, perceived susceptibility to and severity of COVID-19 (p < 0.001), and perceived benefit of the vaccine (p < 0.001) were positively associated with vaccination intent, whereas perceived barriers had a negative association (p < 0.001). Individuals were more likely to receive the vaccine after obtaining complete information (p < 0.001) and when the vaccine uptake would be more common amongst the public (p < 0.001). © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).
- Authors: Mahmud, Ilias , Kabir, Russell , Rahman, Muhammad Aziz , Alradie-Mohamed, Angi , Vinnakota, Divya , Al-Mohaimeed, Abdulrahman
- Date: 2021
- Type: Text , Journal article
- Relation: Vaccines Vol. 9, no. 8 (2021), p.
- Full Text:
- Reviewed:
- Description: We examined the intention and predictors of accepting the COVID-19 vaccine in Saudi Arabia. We conducted a nation-wide, cross-sectional online survey between February and March 2021. A total of 1387 people (≥18 years) participated. Only 27.3% adults had a definite and 30.2% had a probable vaccination intent; 26.8% and 15.6% had a probable and definite negative vaccination intent. Older people (≥50 years) (p < 0.01), healthcare workers/professionals (p < 0.001), and those who received flu vaccine (p < 0.001) were more likely to have a positive intent. People from Riyadh were less likely to receive the vaccine (p < 0.05). Among the health belief model constructs, perceived susceptibility to and severity of COVID-19 (p < 0.001), and perceived benefit of the vaccine (p < 0.001) were positively associated with vaccination intent, whereas perceived barriers had a negative association (p < 0.001). Individuals were more likely to receive the vaccine after obtaining complete information (p < 0.001) and when the vaccine uptake would be more common amongst the public (p < 0.001). © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).
A role for MAIT cells in colorectal cancer
- Berzins, Stuart, Wallace, Morgan, Kannourakis, George, Kelly, Jason
- Authors: Berzins, Stuart , Wallace, Morgan , Kannourakis, George , Kelly, Jason
- Date: 2020
- Type: Text , Journal article , Review
- Relation: Frontiers in Immunology Vol. 11, no. (2020), p.
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- Description: MAIT cells are MR1-restricted T cells that are well-known for their anti-microbial properties, but they have recently been associated with different forms of cancer. Several studies have reported activated MAIT cells within the microenvironment of colorectal tumors, but there is conjecture about the nature of their response and whether they are contributing to anti-tumor immunity, or to the progression of the disease. We have reviewed the current state of knowledge about the role of MAIT cells in colorectal cancer, including their likely influence when activated and potential sources of stimulation in the tumor microenvironment. The prospects for MAIT cells being used in clinical settings as biomarkers or as targets of new immunotherapies designed to harness their function are discussed. © Copyright © 2020 Berzins, Wallace, Kannourakis and Kelly.
- Authors: Berzins, Stuart , Wallace, Morgan , Kannourakis, George , Kelly, Jason
- Date: 2020
- Type: Text , Journal article , Review
- Relation: Frontiers in Immunology Vol. 11, no. (2020), p.
- Full Text:
- Reviewed:
- Description: MAIT cells are MR1-restricted T cells that are well-known for their anti-microbial properties, but they have recently been associated with different forms of cancer. Several studies have reported activated MAIT cells within the microenvironment of colorectal tumors, but there is conjecture about the nature of their response and whether they are contributing to anti-tumor immunity, or to the progression of the disease. We have reviewed the current state of knowledge about the role of MAIT cells in colorectal cancer, including their likely influence when activated and potential sources of stimulation in the tumor microenvironment. The prospects for MAIT cells being used in clinical settings as biomarkers or as targets of new immunotherapies designed to harness their function are discussed. © Copyright © 2020 Berzins, Wallace, Kannourakis and Kelly.
Increased susceptibility to Haemonchus contortus infection by interleukin-5 modulation of eosinophil responses in sheep
- Hernández, Julia, Meeusen, Els, Rodríguez, Francisco, Piedrafita, David, González, Jorge
- Authors: Hernández, Julia , Meeusen, Els , Rodríguez, Francisco , Piedrafita, David , González, Jorge
- Date: 2020
- Type: Text , Journal article
- Relation: Parasite Immunology Vol. 42, no. 1 (2020), p.
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- Description: Eosinophils are prominent effector cells in immune responses against gastrointestinal nematode infections in ruminants, but their in vivo role has been hard to establish in large animals. Interleukin-5 is a key cytokine in the induction and stimulation of anti-parasitic eosinophil responses. This study attempted to modulate the eosinophil response in sheep through vaccination with recombinant interleukin-5 (rIL-5) and determine the effect on subsequent Haemonchus contortus infection. Nematode-resistant Canaria Hair Breed (CHB) sheep vaccinated with rIL-5 in Quil-A adjuvant, had lower blood eosinophil counts and higher mean worm burdens than control sheep vaccinated with Quil-A adjuvant alone. In addition, adult worms in IL-5-vaccinated sheep were significantly longer with higher eggs in utero in female worms, supporting an active role of eosinophils against adult parasites in CHB sheep. These results confirm that eosinophils can play a direct role in effective control of H contortus infection in sheep and offer a new approach to study immune responses in ruminants. © 2019 John Wiley & Sons Ltd
- Authors: Hernández, Julia , Meeusen, Els , Rodríguez, Francisco , Piedrafita, David , González, Jorge
- Date: 2020
- Type: Text , Journal article
- Relation: Parasite Immunology Vol. 42, no. 1 (2020), p.
- Full Text:
- Reviewed:
- Description: Eosinophils are prominent effector cells in immune responses against gastrointestinal nematode infections in ruminants, but their in vivo role has been hard to establish in large animals. Interleukin-5 is a key cytokine in the induction and stimulation of anti-parasitic eosinophil responses. This study attempted to modulate the eosinophil response in sheep through vaccination with recombinant interleukin-5 (rIL-5) and determine the effect on subsequent Haemonchus contortus infection. Nematode-resistant Canaria Hair Breed (CHB) sheep vaccinated with rIL-5 in Quil-A adjuvant, had lower blood eosinophil counts and higher mean worm burdens than control sheep vaccinated with Quil-A adjuvant alone. In addition, adult worms in IL-5-vaccinated sheep were significantly longer with higher eggs in utero in female worms, supporting an active role of eosinophils against adult parasites in CHB sheep. These results confirm that eosinophils can play a direct role in effective control of H contortus infection in sheep and offer a new approach to study immune responses in ruminants. © 2019 John Wiley & Sons Ltd
A novel plasmid-mediated polymyxin resistance determinant (mcr-1.8) in escherichia coli recovered from broiler chickens in Brunei Darussalam
- Momin, Abdul, Liakopoulos, Apostolos, Bean, David, Phee, Lynette, Wareham, David
- Authors: Momin, Abdul , Liakopoulos, Apostolos , Bean, David , Phee, Lynette , Wareham, David
- Date: 2019
- Type: Text , Journal article , Letter
- Relation: Journal of Antimicrobial Chemotherapy Vol. 74, no. 11 (2019), p. 3392-3394
- Full Text:
- Reviewed:
- Description: Sir, MDR Gram-negative bacteria are identified as critical pathogens and their effective treatment increasingly relies on the polymyxins (polymyxin B, colistin), either alone or as part of unorthodox combination therapies.1 The rapid emergence of polymyxin resistance due to mutations/insertions in genes involved in LPS modifications (lpxCAD, pmrA/B, mgrB, phoP/Q, ccrAB) has been reported among individuals exposed to or treated with polymyxins.1Of greater concern are increasing reports of resistance due to the acquisition of phosphoethanolamine (PEtN) transferases, enzymes that catalyse the addition of phosphoethanolamine to lipid A, resulting in lower binding affinity of polymyxins.1 Since the first identification in China,1 multiple gene variants have been reported in diverse bacterial genera recovered from a range of human, retail food, foodproducing animal and environmental sources.2 Here, we report a novel variant of PEtN transferase, designated MCR-1.8, and its genetic context in an MDR Escherichia coli isolate recovered from poultry in Brunei Darussalam.
- Authors: Momin, Abdul , Liakopoulos, Apostolos , Bean, David , Phee, Lynette , Wareham, David
- Date: 2019
- Type: Text , Journal article , Letter
- Relation: Journal of Antimicrobial Chemotherapy Vol. 74, no. 11 (2019), p. 3392-3394
- Full Text:
- Reviewed:
- Description: Sir, MDR Gram-negative bacteria are identified as critical pathogens and their effective treatment increasingly relies on the polymyxins (polymyxin B, colistin), either alone or as part of unorthodox combination therapies.1 The rapid emergence of polymyxin resistance due to mutations/insertions in genes involved in LPS modifications (lpxCAD, pmrA/B, mgrB, phoP/Q, ccrAB) has been reported among individuals exposed to or treated with polymyxins.1Of greater concern are increasing reports of resistance due to the acquisition of phosphoethanolamine (PEtN) transferases, enzymes that catalyse the addition of phosphoethanolamine to lipid A, resulting in lower binding affinity of polymyxins.1 Since the first identification in China,1 multiple gene variants have been reported in diverse bacterial genera recovered from a range of human, retail food, foodproducing animal and environmental sources.2 Here, we report a novel variant of PEtN transferase, designated MCR-1.8, and its genetic context in an MDR Escherichia coli isolate recovered from poultry in Brunei Darussalam.
Divergent Barmah forest virus from Papua New Guinea
- Caly, Leon, Horwood, Paul, Dhanasekaran, VijaykrishnaLynch, Stacey, Greenhill, Andrew, Pomat, William, Rai, Glennis, Kisa, Debbie, Bande, Grace, Druce, Julian, Abdad, Mohammad
- Authors: Caly, Leon , Horwood, Paul , Dhanasekaran, VijaykrishnaLynch, Stacey , Greenhill, Andrew , Pomat, William , Rai, Glennis , Kisa, Debbie , Bande, Grace , Druce, Julian , Abdad, Mohammad
- Date: 2019
- Type: Text , Journal article
- Relation: Emerging Infectious Diseases Vol. 25, no. 12 (2019), p. 2266-2269
- Full Text:
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- Description: We report a case of Barmah Forest virus infection in a child from Central Province, Papua New Guinea, who had no previous travel history. Genomic characterization of the virus showed divergent origin compared with viruses previously detected, supporting the hypothesis that the range of Barmah Forest virus extends beyond Australia. © 2019 Centers for Disease Control and Prevention (CDC). All rights reserved.
- Authors: Caly, Leon , Horwood, Paul , Dhanasekaran, VijaykrishnaLynch, Stacey , Greenhill, Andrew , Pomat, William , Rai, Glennis , Kisa, Debbie , Bande, Grace , Druce, Julian , Abdad, Mohammad
- Date: 2019
- Type: Text , Journal article
- Relation: Emerging Infectious Diseases Vol. 25, no. 12 (2019), p. 2266-2269
- Full Text:
- Reviewed:
- Description: We report a case of Barmah Forest virus infection in a child from Central Province, Papua New Guinea, who had no previous travel history. Genomic characterization of the virus showed divergent origin compared with viruses previously detected, supporting the hypothesis that the range of Barmah Forest virus extends beyond Australia. © 2019 Centers for Disease Control and Prevention (CDC). All rights reserved.
Health challenges of the pacific region : Insights from history, geography, social determinants, genetics, and the microbiome
- Horwood, Paul, Tarantola, Arnaud, Goarant, Cyrille, Matsui, Mariko, Klement, Elise, Umezaki, Masahiro, Navarro, Severine, Greenhill, Andrew
- Authors: Horwood, Paul , Tarantola, Arnaud , Goarant, Cyrille , Matsui, Mariko , Klement, Elise , Umezaki, Masahiro , Navarro, Severine , Greenhill, Andrew
- Date: 2019
- Type: Text , Journal article , Review
- Relation: Frontiers in Immunology Vol. 10, no. (2019), p. 1-16
- Full Text:
- Reviewed:
- Description: The Pacific region, also referred to as Oceania, is a geographically widespread region populated by people of diverse cultures and ethnicities. Indigenous people in the region (Melanesians, Polynesians, Micronesians, Papuans, and Indigenous Australians) are over-represented on national, regional, and global scales for the burden of infectious and non-communicable diseases. Although social and environmental factors such as poverty, education, and access to health-care are assumed to be major drivers of this disease burden, there is also developing evidence that genetic and microbiotic factors should also be considered. To date, studies investigating genetic and/or microbiotic links with vulnerabilities to infectious and non-communicable diseases have mostly focused on populations in Europe, Asia, and USA, with uncertain associations for other populations such as indigenous communities in Oceania. Recent developments in personalized medicine have shown that identifying ethnicity-linked genetic vulnerabilities can be important for medical management. Although our understanding of the impacts of the gut microbiome on health is still in the early stages, it is likely that equivalent vulnerabilities will also be identified through the interaction between gut microbiome composition and function with pathogens and the host immune system. As rapid economic, dietary, and cultural changes occur throughout Oceania it becomes increasingly important that further research is conducted within indigenous populations to address the double burden of high rates of infectious diseases and rapidly rising non-communicable diseases so that comprehensive development goals can be planned. In this article, we review the current knowledge on the impact of nutrition, genetics, and the gut microbiome on infectious diseases in indigenous people of the Pacific region.
- Authors: Horwood, Paul , Tarantola, Arnaud , Goarant, Cyrille , Matsui, Mariko , Klement, Elise , Umezaki, Masahiro , Navarro, Severine , Greenhill, Andrew
- Date: 2019
- Type: Text , Journal article , Review
- Relation: Frontiers in Immunology Vol. 10, no. (2019), p. 1-16
- Full Text:
- Reviewed:
- Description: The Pacific region, also referred to as Oceania, is a geographically widespread region populated by people of diverse cultures and ethnicities. Indigenous people in the region (Melanesians, Polynesians, Micronesians, Papuans, and Indigenous Australians) are over-represented on national, regional, and global scales for the burden of infectious and non-communicable diseases. Although social and environmental factors such as poverty, education, and access to health-care are assumed to be major drivers of this disease burden, there is also developing evidence that genetic and microbiotic factors should also be considered. To date, studies investigating genetic and/or microbiotic links with vulnerabilities to infectious and non-communicable diseases have mostly focused on populations in Europe, Asia, and USA, with uncertain associations for other populations such as indigenous communities in Oceania. Recent developments in personalized medicine have shown that identifying ethnicity-linked genetic vulnerabilities can be important for medical management. Although our understanding of the impacts of the gut microbiome on health is still in the early stages, it is likely that equivalent vulnerabilities will also be identified through the interaction between gut microbiome composition and function with pathogens and the host immune system. As rapid economic, dietary, and cultural changes occur throughout Oceania it becomes increasingly important that further research is conducted within indigenous populations to address the double burden of high rates of infectious diseases and rapidly rising non-communicable diseases so that comprehensive development goals can be planned. In this article, we review the current knowledge on the impact of nutrition, genetics, and the gut microbiome on infectious diseases in indigenous people of the Pacific region.
Phenotypic screening of the 'Kurz-box' of chemicals identifies two compounds (BLK127 and HBK4) with anthelmintic activity in vitro against parasitic larval stages of Haemonchus contortus
- Nguyen, Linh, Kurz, Thomas, Preston, Sarah, Brueckmann, Hjoerdis, Lungerich, Beate, Herath, Dilrukshi, Koehler, Anson, Wang, Tao, Skalova, Lenka, Jabbar, Abdul, Gasser, Robin
- Authors: Nguyen, Linh , Kurz, Thomas , Preston, Sarah , Brueckmann, Hjoerdis , Lungerich, Beate , Herath, Dilrukshi , Koehler, Anson , Wang, Tao , Skalova, Lenka , Jabbar, Abdul , Gasser, Robin
- Date: 2019
- Type: Text , Journal article
- Relation: Parasites & Vectors Vol. 12, no. (2019), p. 1-9
- Full Text:
- Reviewed:
- Description: BackgroundDue to anthelmintic resistance problems, there is a need to discover and develop new drugs for the treatment and control of economically important and pathogenic nematodes of livestock animals. With this focus in mind, we screened 236 compounds from a library (called the Kurz-box') representing chemically diverse classes such as heterocyclic compounds (e.g. thiazoles, pyrroles, quinolines, pyrimidines, benzo[1,4]diazepines), hydoxamic acid-based metalloenzyme inhibitors, peptidomimetics (bis- and tris-pyrimidoneamides, alkoxyamides) and various intermediates on Haemonchus contortus, one of the most important parasitic nematodes of ruminants.MethodsIn the present study, we tested these compounds, and measured the inhibition of larval motility and development of exsheathed third-stage (xL3) and fourth-stage (L4) larvae of H. contortus using an optimised, whole-organism phenotypic screening assay.ResultsOf the 236 compounds, we identified two active compounds (called BLK127 and HBK4) that induced marked phenotypic changes in the worm in vitro. Compound BLK127 induced an eviscerated' phenotype in the xL3 stage and also inhibited L4 development. Compound HBK4 exerted a curved' phenotype in both xL3s and L4s.ConclusionsThe findings from this study provide a basis for future work on the chemical optimisation of these compounds, on assessing the activity of optimised compounds on adult stages of H. contortus both in vitro and in vivo (in the host animal) and against other parasitic worms of veterinary and medical importance.
- Authors: Nguyen, Linh , Kurz, Thomas , Preston, Sarah , Brueckmann, Hjoerdis , Lungerich, Beate , Herath, Dilrukshi , Koehler, Anson , Wang, Tao , Skalova, Lenka , Jabbar, Abdul , Gasser, Robin
- Date: 2019
- Type: Text , Journal article
- Relation: Parasites & Vectors Vol. 12, no. (2019), p. 1-9
- Full Text:
- Reviewed:
- Description: BackgroundDue to anthelmintic resistance problems, there is a need to discover and develop new drugs for the treatment and control of economically important and pathogenic nematodes of livestock animals. With this focus in mind, we screened 236 compounds from a library (called the Kurz-box') representing chemically diverse classes such as heterocyclic compounds (e.g. thiazoles, pyrroles, quinolines, pyrimidines, benzo[1,4]diazepines), hydoxamic acid-based metalloenzyme inhibitors, peptidomimetics (bis- and tris-pyrimidoneamides, alkoxyamides) and various intermediates on Haemonchus contortus, one of the most important parasitic nematodes of ruminants.MethodsIn the present study, we tested these compounds, and measured the inhibition of larval motility and development of exsheathed third-stage (xL3) and fourth-stage (L4) larvae of H. contortus using an optimised, whole-organism phenotypic screening assay.ResultsOf the 236 compounds, we identified two active compounds (called BLK127 and HBK4) that induced marked phenotypic changes in the worm in vitro. Compound BLK127 induced an eviscerated' phenotype in the xL3 stage and also inhibited L4 development. Compound HBK4 exerted a curved' phenotype in both xL3s and L4s.ConclusionsThe findings from this study provide a basis for future work on the chemical optimisation of these compounds, on assessing the activity of optimised compounds on adult stages of H. contortus both in vitro and in vivo (in the host animal) and against other parasitic worms of veterinary and medical importance.
Selected alpha-pyrones from the plants Cryptocarya novoguineensis (Lauraceae) and Piper methysticum (Piperaceae) with activity against Haemonchus contortus in vitro
- Herath, Dilrukshi, Preston, Sarah, Jabbar, Abdul, Garcia-Bustos, Jose, Addison, Russell, Hayes, Sasha, Rali, Topul, Wang, Tao, Koehler, Anson, Chang, Bill, Hofmann, Andreas, Davis, Rohan, Gasser, Robin
- Authors: Herath, Dilrukshi , Preston, Sarah , Jabbar, Abdul , Garcia-Bustos, Jose , Addison, Russell , Hayes, Sasha , Rali, Topul , Wang, Tao , Koehler, Anson , Chang, Bill , Hofmann, Andreas , Davis, Rohan , Gasser, Robin
- Date: 2019
- Type: Text , Journal article
- Relation: International Journal for Parasitology-Drugs and Drug Resistance Vol. 9, no. (2019), p. 72-79
- Full Text:
- Reviewed:
- Description: Due to the widespread occurrence and spread of anthelmintic resistance, there is a need to develop new drugs against resistant parasitic nematodes of livestock animals. The Nobel Prize-winning discovery and development of the anti-parasitic drugs avermectin and artemisinin has renewed the interest in exploring natural products as anthelmintics. In the present study, we screened 7500 plant extracts for in vitro-activity against the barber's pole worm, Haemonchus contortus, a highly significant pathogen of ruminants. The anthelmintic extracts from two plants, Cryptocarya novoguineensis and Piper methysticum, were fractionated by high-performance liquid chromatography (HPLC). Subsequently, compounds were purified from fractions with significant biological activity. Four alpha-pyrones, namely goniothalamin (GNT), dihydrokavain (DHK), desmethoxyyangonin (DMY) and yangonin (YGN), were purified from fractions from the two plants, GNT from C. novoguineensis, and DHK, DMY and YGN (= kavalactones) from P. methysticum. The three kavalactones induced a lethal, eviscerated (Evi) phenotype in treated exsheathed third-stage larvae (xL3s), and DMY and YGN had moderate potencies (IC50 values of 31.7 +/- 0.23 mu M and 23.7 +/- 2.05 mu M, respectively) at inhibiting the development of xL3s to fourth-stage larvae (L4s). Although GNT had limited potency (IC50 of 200-300 mu M) at inhibiting L4 development, it was the only compound that reduced L4 motility (IC50 of 6.25-12.50 mu M). The compounds purified from each plant affected H. contortus in an irreversible manner. These findings suggest that structure-activity relationship studies of alpha-pyrones should be pursued to assess their potential as anthelmintics.
- Authors: Herath, Dilrukshi , Preston, Sarah , Jabbar, Abdul , Garcia-Bustos, Jose , Addison, Russell , Hayes, Sasha , Rali, Topul , Wang, Tao , Koehler, Anson , Chang, Bill , Hofmann, Andreas , Davis, Rohan , Gasser, Robin
- Date: 2019
- Type: Text , Journal article
- Relation: International Journal for Parasitology-Drugs and Drug Resistance Vol. 9, no. (2019), p. 72-79
- Full Text:
- Reviewed:
- Description: Due to the widespread occurrence and spread of anthelmintic resistance, there is a need to develop new drugs against resistant parasitic nematodes of livestock animals. The Nobel Prize-winning discovery and development of the anti-parasitic drugs avermectin and artemisinin has renewed the interest in exploring natural products as anthelmintics. In the present study, we screened 7500 plant extracts for in vitro-activity against the barber's pole worm, Haemonchus contortus, a highly significant pathogen of ruminants. The anthelmintic extracts from two plants, Cryptocarya novoguineensis and Piper methysticum, were fractionated by high-performance liquid chromatography (HPLC). Subsequently, compounds were purified from fractions with significant biological activity. Four alpha-pyrones, namely goniothalamin (GNT), dihydrokavain (DHK), desmethoxyyangonin (DMY) and yangonin (YGN), were purified from fractions from the two plants, GNT from C. novoguineensis, and DHK, DMY and YGN (= kavalactones) from P. methysticum. The three kavalactones induced a lethal, eviscerated (Evi) phenotype in treated exsheathed third-stage larvae (xL3s), and DMY and YGN had moderate potencies (IC50 values of 31.7 +/- 0.23 mu M and 23.7 +/- 2.05 mu M, respectively) at inhibiting the development of xL3s to fourth-stage larvae (L4s). Although GNT had limited potency (IC50 of 200-300 mu M) at inhibiting L4 development, it was the only compound that reduced L4 motility (IC50 of 6.25-12.50 mu M). The compounds purified from each plant affected H. contortus in an irreversible manner. These findings suggest that structure-activity relationship studies of alpha-pyrones should be pursued to assess their potential as anthelmintics.
Arylpyrrole and fipronil analogues that inhibit the motility and/or development of Haemonchus contortus in vitro
- Herath, Dilrukshi, Song, Hongjian, Preston, Sarah, Jabbar, Abdul, Wang, Tao, McGee, Sean, Hofmann, Andreas, Garcia-Bustos, Jose, Chang, Bill, Koehler, Anson, Liu, Yuxiu, Ma, Qiaoqiao, Zhang, Penqxiang, Zhao, Qiqi, Wang, Qingmin, Gasser, Robin
- Authors: Herath, Dilrukshi , Song, Hongjian , Preston, Sarah , Jabbar, Abdul , Wang, Tao , McGee, Sean , Hofmann, Andreas , Garcia-Bustos, Jose , Chang, Bill , Koehler, Anson , Liu, Yuxiu , Ma, Qiaoqiao , Zhang, Penqxiang , Zhao, Qiqi , Wang, Qingmin , Gasser, Robin
- Date: 2018
- Type: Text , Journal article
- Relation: International Journal for Parasitology: Drugs and Drug Resistance Vol. 8, no. 3 (2018), p. 379-385
- Full Text:
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- Description: Due to widespread drug resistance in parasitic nematodes, there is a need to develop new anthelmintics. Given the cost and time involved in developing a new drug, the repurposing of known chemicals can be a promising, alternative approach. In this context, we tested a library (n = 600) of natural product-inspired pesticide analogues against exsheathed third stage-larvae (xL3s) of Haemonchus contortus (barber's pole worm) using a whole-organism, phenotypic screening technique that measures the inhibition of motility and development in treated larvae. In the primary screen, we identified 32 active analogues derived from chemical scaffolds of arylpyrrole or fipronil. The seven most promising compounds, selected based on their anthelmintic activity and/or limited cytotoxicity, are arylpyrroles that reduced the motility of fourth-stage larvae (L4s) with significant potency (IC 50 values ranged from 0.04 ± 0.01
- Authors: Herath, Dilrukshi , Song, Hongjian , Preston, Sarah , Jabbar, Abdul , Wang, Tao , McGee, Sean , Hofmann, Andreas , Garcia-Bustos, Jose , Chang, Bill , Koehler, Anson , Liu, Yuxiu , Ma, Qiaoqiao , Zhang, Penqxiang , Zhao, Qiqi , Wang, Qingmin , Gasser, Robin
- Date: 2018
- Type: Text , Journal article
- Relation: International Journal for Parasitology: Drugs and Drug Resistance Vol. 8, no. 3 (2018), p. 379-385
- Full Text:
- Reviewed:
- Description: Due to widespread drug resistance in parasitic nematodes, there is a need to develop new anthelmintics. Given the cost and time involved in developing a new drug, the repurposing of known chemicals can be a promising, alternative approach. In this context, we tested a library (n = 600) of natural product-inspired pesticide analogues against exsheathed third stage-larvae (xL3s) of Haemonchus contortus (barber's pole worm) using a whole-organism, phenotypic screening technique that measures the inhibition of motility and development in treated larvae. In the primary screen, we identified 32 active analogues derived from chemical scaffolds of arylpyrrole or fipronil. The seven most promising compounds, selected based on their anthelmintic activity and/or limited cytotoxicity, are arylpyrroles that reduced the motility of fourth-stage larvae (L4s) with significant potency (IC 50 values ranged from 0.04 ± 0.01
Co-circulation of influenza A H5, H7, and H9 viruses and co-infected poultry in live bird markets, Cambodia
- Horwood, Paul, Horm, Srey, Suttie, Annika, Thet, Sopheak, Rith, Phalla, Sorn, San, Holl, Davun, Tum, Sothyra, Ly, Sowath, Karlsson, Erik, Tarantola, Arnaud, Dussart, Philippe
- Authors: Horwood, Paul , Horm, Srey , Suttie, Annika , Thet, Sopheak , Rith, Phalla , Sorn, San , Holl, Davun , Tum, Sothyra , Ly, Sowath , Karlsson, Erik , Tarantola, Arnaud , Dussart, Philippe
- Date: 2018
- Type: Text , Journal article
- Relation: Emerging Infectious Diseases Vol. 24, no. 2 (2018), p. 352-355
- Full Text:
- Reviewed:
- Description: Longitudinal surveillance of 2 live bird markets in Cambodia revealed year-round, high co-circulation of H5, H7, and H9 influenza viruses. We detected influenza A viruses in 51.3% of ducks and 39.6% of chickens, and co-infections, mainly by H5 and H9 viruses, in 0.8% of ducks and 4.5% of chickens. © 2018 Centers for Disease Control and Prevention (CDC). All rights Reserved.
- Authors: Horwood, Paul , Horm, Srey , Suttie, Annika , Thet, Sopheak , Rith, Phalla , Sorn, San , Holl, Davun , Tum, Sothyra , Ly, Sowath , Karlsson, Erik , Tarantola, Arnaud , Dussart, Philippe
- Date: 2018
- Type: Text , Journal article
- Relation: Emerging Infectious Diseases Vol. 24, no. 2 (2018), p. 352-355
- Full Text:
- Reviewed:
- Description: Longitudinal surveillance of 2 live bird markets in Cambodia revealed year-round, high co-circulation of H5, H7, and H9 influenza viruses. We detected influenza A viruses in 51.3% of ducks and 39.6% of chickens, and co-infections, mainly by H5 and H9 viruses, in 0.8% of ducks and 4.5% of chickens. © 2018 Centers for Disease Control and Prevention (CDC). All rights Reserved.
Temporal regulation of natural Killer T cell interferon gamma responses by β-catenin-dependent and -independent Wnt signaling
- Kling, Jessica, Jordan, Margaret, Pitt, Lauren, Meiners, Jana, Thanh-Tran, Thao, Tran, Le Son, Nguyen, Tam, Mittal, Deepak, Villani, Rehan, Steptoe, Raymond, Khosrotehrani, Kiarash, Berzins, Stuart, Baxter, Alan, Godrey, Dale, Blumental, Antje
- Authors: Kling, Jessica , Jordan, Margaret , Pitt, Lauren , Meiners, Jana , Thanh-Tran, Thao , Tran, Le Son , Nguyen, Tam , Mittal, Deepak , Villani, Rehan , Steptoe, Raymond , Khosrotehrani, Kiarash , Berzins, Stuart , Baxter, Alan , Godrey, Dale , Blumental, Antje
- Date: 2018
- Type: Text , Journal article
- Relation: Frontiers in Immunology Vol. 9, no. (2018), p. 1-13
- Full Text:
- Reviewed:
- Description: Natural killer T (NKT) cells are prominent innate-like lymphocytes in the liver with critical roles in immune responses during infection, cancer, and autoimmunity. Interferon gamma (IFN-γ) and IL-4 are key cytokines rapidly produced by NKT cells upon recognition of glycolipid antigens presented by antigen-presenting cells (APCs). It has previously been reported that the transcriptional coactivator β-catenin regulates NKT cell differentiation and functionally biases NKT cell responses toward IL-4, at the expense of IFN-γ production. β-Catenin is not only a central effector of Wnt signaling but also contributes to other signaling networks. It is currently unknown whether Wnt ligands regulate NKT cell functions. We thus investigated how Wnt ligands and β-catenin activity shape liver NKT cell functions in vivo in response to the glycolipid antigen, α-galactosylceramide (α-GalCer) using a mouse model. Pharmacologic targeting of β-catenin activity with ICG001, as well as myeloid-specific genetic ablation of Wntless (Wls), to specifically target Wnt protein release by APCs, enhanced early IFN-γ responses. By contrast, within several hours of α-GalCer challenge, myeloid-specific Wls deficiency, as well as pharmacologic targeting of Wnt release using the small molecule inhibitor IWP-2 impaired α-GalCer-induced IFN-γ responses, independent of β-catenin activity. These data suggest that myeloid cell-derived Wnt ligands drive early Wnt/β-catenin signaling that curbs IFN-γ responses, but that, subsequently, Wnt ligands sustain IFN-γ expression independent of β-catenin activity. Our analyses in ICG001-treated mice confirmed a role for β-catenin activity in driving early IL-4 responses by liver NKT cells. However, neither pharmacologic nor genetic perturbation of Wnt production affected the IL-4 response, suggesting that IL-4 production by NKT cells in response to α-GalCer is not driven by released Wnt ligands. Collectively, these data reveal complex temporal roles of Wnt ligands and β-catenin signaling in the regulation of liver NKT cell activation, and highlight Wnt-dependent and -independent contributions of β-catenin to NKT cell functions.
- Description: Natural killer T (NKT) cells are prominent innate-like lymphocytes in the liver with critical roles in immune responses during infection, cancer, and autoimmunity. Interferon gamma (IFN-
- Authors: Kling, Jessica , Jordan, Margaret , Pitt, Lauren , Meiners, Jana , Thanh-Tran, Thao , Tran, Le Son , Nguyen, Tam , Mittal, Deepak , Villani, Rehan , Steptoe, Raymond , Khosrotehrani, Kiarash , Berzins, Stuart , Baxter, Alan , Godrey, Dale , Blumental, Antje
- Date: 2018
- Type: Text , Journal article
- Relation: Frontiers in Immunology Vol. 9, no. (2018), p. 1-13
- Full Text:
- Reviewed:
- Description: Natural killer T (NKT) cells are prominent innate-like lymphocytes in the liver with critical roles in immune responses during infection, cancer, and autoimmunity. Interferon gamma (IFN-γ) and IL-4 are key cytokines rapidly produced by NKT cells upon recognition of glycolipid antigens presented by antigen-presenting cells (APCs). It has previously been reported that the transcriptional coactivator β-catenin regulates NKT cell differentiation and functionally biases NKT cell responses toward IL-4, at the expense of IFN-γ production. β-Catenin is not only a central effector of Wnt signaling but also contributes to other signaling networks. It is currently unknown whether Wnt ligands regulate NKT cell functions. We thus investigated how Wnt ligands and β-catenin activity shape liver NKT cell functions in vivo in response to the glycolipid antigen, α-galactosylceramide (α-GalCer) using a mouse model. Pharmacologic targeting of β-catenin activity with ICG001, as well as myeloid-specific genetic ablation of Wntless (Wls), to specifically target Wnt protein release by APCs, enhanced early IFN-γ responses. By contrast, within several hours of α-GalCer challenge, myeloid-specific Wls deficiency, as well as pharmacologic targeting of Wnt release using the small molecule inhibitor IWP-2 impaired α-GalCer-induced IFN-γ responses, independent of β-catenin activity. These data suggest that myeloid cell-derived Wnt ligands drive early Wnt/β-catenin signaling that curbs IFN-γ responses, but that, subsequently, Wnt ligands sustain IFN-γ expression independent of β-catenin activity. Our analyses in ICG001-treated mice confirmed a role for β-catenin activity in driving early IL-4 responses by liver NKT cells. However, neither pharmacologic nor genetic perturbation of Wnt production affected the IL-4 response, suggesting that IL-4 production by NKT cells in response to α-GalCer is not driven by released Wnt ligands. Collectively, these data reveal complex temporal roles of Wnt ligands and β-catenin signaling in the regulation of liver NKT cell activation, and highlight Wnt-dependent and -independent contributions of β-catenin to NKT cell functions.
- Description: Natural killer T (NKT) cells are prominent innate-like lymphocytes in the liver with critical roles in immune responses during infection, cancer, and autoimmunity. Interferon gamma (IFN-
Assessing the anthelmintic activity of pyrazole-5-carboxamide derivatives against Haemonchus contortus
- Jiao, Yaqing, Preston, Sarah, Song, Hongjian, Jabbar, Abdul, Liu, Yuxiu, Baell, Jonathan, Hofmann, Andreas, Hutchinson, Dana, Wang, Tao, Koehler, Anson, Fisher, Gillian, Andrews, Katherine, Laleu, Benoit, Palmer, Michael, Burrows, Jeremy, Wells, Timothy, Wang, Qingmin, Gasser, Robin
- Authors: Jiao, Yaqing , Preston, Sarah , Song, Hongjian , Jabbar, Abdul , Liu, Yuxiu , Baell, Jonathan , Hofmann, Andreas , Hutchinson, Dana , Wang, Tao , Koehler, Anson , Fisher, Gillian , Andrews, Katherine , Laleu, Benoit , Palmer, Michael , Burrows, Jeremy , Wells, Timothy , Wang, Qingmin , Gasser, Robin
- Date: 2017
- Type: Text , Journal article
- Relation: Parasites and Vectors Vol. 10, no. 1 (2017), p. 1-7
- Full Text:
- Reviewed:
- Description: Background: In this study, we tested five series of pyrazole-5-carboxamide compounds (n = 55) for activity against parasitic stages of the nematode Haemonchus contortus (barber’s pole worm), one of the most pathogenic parasites of ruminants. Methods: In an optimised, whole-organism screening assay, using exsheathed third-stage (xL3) and fourth-stage (L4) larvae, we measured the inhibition of larval motility and development of H. contortus. Results: Amongst the 55 compounds, we identified two compounds (designated a-15 and a-17) that reproducibly inhibit xL3 motility as well as L4 motility and development, with IC50 values ranging between ~3.4 and 55.6 μM. We studied the effect of these two ‘hit’ compounds on mitochondrial function by measuring oxygen consumption. This assessment showed that xL3s exposed to each of these compounds consumed significantly less oxygen and had less mitochondrial activity than untreated xL3s, which was consistent with specific inhibition of complex I of the respiratory electron transport chain in arthropods. Conclusions: The present findings provide a sound basis for future work, aimed at identifying the targets of compounds a-15 and a-17 and establishing the modes of action of these chemicals in H. contortus. © 2017 The Author(s).
- Authors: Jiao, Yaqing , Preston, Sarah , Song, Hongjian , Jabbar, Abdul , Liu, Yuxiu , Baell, Jonathan , Hofmann, Andreas , Hutchinson, Dana , Wang, Tao , Koehler, Anson , Fisher, Gillian , Andrews, Katherine , Laleu, Benoit , Palmer, Michael , Burrows, Jeremy , Wells, Timothy , Wang, Qingmin , Gasser, Robin
- Date: 2017
- Type: Text , Journal article
- Relation: Parasites and Vectors Vol. 10, no. 1 (2017), p. 1-7
- Full Text:
- Reviewed:
- Description: Background: In this study, we tested five series of pyrazole-5-carboxamide compounds (n = 55) for activity against parasitic stages of the nematode Haemonchus contortus (barber’s pole worm), one of the most pathogenic parasites of ruminants. Methods: In an optimised, whole-organism screening assay, using exsheathed third-stage (xL3) and fourth-stage (L4) larvae, we measured the inhibition of larval motility and development of H. contortus. Results: Amongst the 55 compounds, we identified two compounds (designated a-15 and a-17) that reproducibly inhibit xL3 motility as well as L4 motility and development, with IC50 values ranging between ~3.4 and 55.6 μM. We studied the effect of these two ‘hit’ compounds on mitochondrial function by measuring oxygen consumption. This assessment showed that xL3s exposed to each of these compounds consumed significantly less oxygen and had less mitochondrial activity than untreated xL3s, which was consistent with specific inhibition of complex I of the respiratory electron transport chain in arthropods. Conclusions: The present findings provide a sound basis for future work, aimed at identifying the targets of compounds a-15 and a-17 and establishing the modes of action of these chemicals in H. contortus. © 2017 The Author(s).
Anthelmintic activity of selected ethno-medicinal plant extracts on parasitic stages of Haemonchus contortus
- Kumarasingha, Rasika, Preston, Sarah, Yeo, Tiong-Chia, Lim, Diana, Tu, Chu-Lee, Palombo, Enzo, Shaw, Jillian, Gasser, Robin, Boag, Peter
- Authors: Kumarasingha, Rasika , Preston, Sarah , Yeo, Tiong-Chia , Lim, Diana , Tu, Chu-Lee , Palombo, Enzo , Shaw, Jillian , Gasser, Robin , Boag, Peter
- Date: 2016
- Type: Text , Journal article
- Relation: Parasites and Vectors Vol. 9, no. 1 (2016), p. 1-7
- Full Text:
- Reviewed:
- Description: Background: Parasitic roundworms (nematodes) cause substantial morbidity and mortality in livestock animals globally, and considerable productivity losses to farmers. The control of these nematodes has relied largely on the use of a limited number of anthelmintics. However, resistance to many of these these anthelmintics is now widespread, and, therefore, there is a need to find new drugs to ensure sustained and effective treatment and control into the future. Methods: Recently, we developed a screening assay to test natural, plant extracts with known inhibitory effects against the free-living worm Caenorhabditis elegans. Using this assay, we assessed here the effects of the extracts on motility and development of parasitic larval stages of Haemonchus contortus, one of the most important nematodes of small ruminants worldwide. Results: The study showed that two of five extracts from Picria fel-terrae Lour. have a significant inhibitory effect (at concentrations of 3-5 mg/ml) on the motility and development of H. contortus larvae. Although the two extracts originated from the same plant, they displayed different levels of inhibition on motility and development, which might relate to the presence of various active constituents in these extracts, or the same constituents at different concentrations in distinct parts of the plant. Conclusions: These results suggest that extracts from P. fel-terrae Lour. have promising anthelmintic activity and that more broadly, plant extracts are a potential rich source of anthelmintics to combat helminthic diseases. © 2016 Kumarasingha et al.
- Authors: Kumarasingha, Rasika , Preston, Sarah , Yeo, Tiong-Chia , Lim, Diana , Tu, Chu-Lee , Palombo, Enzo , Shaw, Jillian , Gasser, Robin , Boag, Peter
- Date: 2016
- Type: Text , Journal article
- Relation: Parasites and Vectors Vol. 9, no. 1 (2016), p. 1-7
- Full Text:
- Reviewed:
- Description: Background: Parasitic roundworms (nematodes) cause substantial morbidity and mortality in livestock animals globally, and considerable productivity losses to farmers. The control of these nematodes has relied largely on the use of a limited number of anthelmintics. However, resistance to many of these these anthelmintics is now widespread, and, therefore, there is a need to find new drugs to ensure sustained and effective treatment and control into the future. Methods: Recently, we developed a screening assay to test natural, plant extracts with known inhibitory effects against the free-living worm Caenorhabditis elegans. Using this assay, we assessed here the effects of the extracts on motility and development of parasitic larval stages of Haemonchus contortus, one of the most important nematodes of small ruminants worldwide. Results: The study showed that two of five extracts from Picria fel-terrae Lour. have a significant inhibitory effect (at concentrations of 3-5 mg/ml) on the motility and development of H. contortus larvae. Although the two extracts originated from the same plant, they displayed different levels of inhibition on motility and development, which might relate to the presence of various active constituents in these extracts, or the same constituents at different concentrations in distinct parts of the plant. Conclusions: These results suggest that extracts from P. fel-terrae Lour. have promising anthelmintic activity and that more broadly, plant extracts are a potential rich source of anthelmintics to combat helminthic diseases. © 2016 Kumarasingha et al.
Predicting the geographical distributions of the macaque hosts and mosquito vectors of Plasmodium knowlesi malaria in forested and non-forested areas
- Moyes, Catherine, Shearer, Freya, Huang, Zhi, Wiebe, Antoinette, Gibson, Harry, Nijman, Vincent, Mohd-Azlan, Jayasilan, Brodie, Jebediah, Malaivijitnond, Suchinda, Linkie, Matthew, Samejima, Hiromitsu, O'Brien, Timothy, Trainor, Colin, Hamada, Yuzuru, Giordano, Anthony, Kinnaird, Margaret, Elyazar, Iqbal, Sinka, Marianne, Vythilingam, Indra, Bangs, Michael, Pigott, David, Weiss, Daniel, Golding, Nick, Hay, Simon
- Authors: Moyes, Catherine , Shearer, Freya , Huang, Zhi , Wiebe, Antoinette , Gibson, Harry , Nijman, Vincent , Mohd-Azlan, Jayasilan , Brodie, Jebediah , Malaivijitnond, Suchinda , Linkie, Matthew , Samejima, Hiromitsu , O'Brien, Timothy , Trainor, Colin , Hamada, Yuzuru , Giordano, Anthony , Kinnaird, Margaret , Elyazar, Iqbal , Sinka, Marianne , Vythilingam, Indra , Bangs, Michael , Pigott, David , Weiss, Daniel , Golding, Nick , Hay, Simon
- Date: 2016
- Type: Text , Journal article
- Relation: Parasites and Vectors Vol. 9, no. 1 (2016), p. 1-12
- Full Text:
- Reviewed:
- Description: Background: Plasmodium knowlesi is a zoonotic pathogen, transmitted among macaques and to humans by anopheline mosquitoes. Information on P. knowlesi malaria is lacking in most regions so the first step to understand the geographical distribution of disease risk is to define the distributions of the reservoir and vector species. Methods: We used macaque and mosquito species presence data, background data that captured sampling bias in the presence data, a boosted regression tree model and environmental datasets, including annual data for land classes, to predict the distributions of each vector and host species. We then compared the predicted distribution of each species with cover of each land class. Results: Fine-scale distribution maps were generated for three macaque host species (Macaca fascicularis, M. nemestrina and M. leonina) and two mosquito vector complexes (the Dirus Complex and the Leucosphyrus Complex). The Leucosphyrus Complex was predicted to occur in areas with disturbed, but not intact, forest cover (> 60 % tree cover) whereas the Dirus Complex was predicted to occur in areas with 10-100 % tree cover as well as vegetation mosaics and cropland. Of the macaque species, M. nemestrina was mainly predicted to occur in forested areas whereas M. fascicularis was predicted to occur in vegetation mosaics, cropland, wetland and urban areas in addition to forested areas. Conclusions: The predicted M. fascicularis distribution encompassed a wide range of habitats where humans are found. This is of most significance in the northern part of its range where members of the Dirus Complex are the main P. knowlesi vectors because these mosquitoes were also predicted to occur in a wider range of habitats. Our results support the hypothesis that conversion of intact forest into disturbed forest (for example plantations or timber concessions), or the creation of vegetation mosaics, will increase the probability that members of the Leucosphyrus Complex occur at these locations, as well as bringing humans into these areas. An explicit analysis of disease risk itself using infection data is required to explore this further. The species distributions generated here can now be included in future analyses of P. knowlesi infection risk. © 2016 Moyes et al.
- Authors: Moyes, Catherine , Shearer, Freya , Huang, Zhi , Wiebe, Antoinette , Gibson, Harry , Nijman, Vincent , Mohd-Azlan, Jayasilan , Brodie, Jebediah , Malaivijitnond, Suchinda , Linkie, Matthew , Samejima, Hiromitsu , O'Brien, Timothy , Trainor, Colin , Hamada, Yuzuru , Giordano, Anthony , Kinnaird, Margaret , Elyazar, Iqbal , Sinka, Marianne , Vythilingam, Indra , Bangs, Michael , Pigott, David , Weiss, Daniel , Golding, Nick , Hay, Simon
- Date: 2016
- Type: Text , Journal article
- Relation: Parasites and Vectors Vol. 9, no. 1 (2016), p. 1-12
- Full Text:
- Reviewed:
- Description: Background: Plasmodium knowlesi is a zoonotic pathogen, transmitted among macaques and to humans by anopheline mosquitoes. Information on P. knowlesi malaria is lacking in most regions so the first step to understand the geographical distribution of disease risk is to define the distributions of the reservoir and vector species. Methods: We used macaque and mosquito species presence data, background data that captured sampling bias in the presence data, a boosted regression tree model and environmental datasets, including annual data for land classes, to predict the distributions of each vector and host species. We then compared the predicted distribution of each species with cover of each land class. Results: Fine-scale distribution maps were generated for three macaque host species (Macaca fascicularis, M. nemestrina and M. leonina) and two mosquito vector complexes (the Dirus Complex and the Leucosphyrus Complex). The Leucosphyrus Complex was predicted to occur in areas with disturbed, but not intact, forest cover (> 60 % tree cover) whereas the Dirus Complex was predicted to occur in areas with 10-100 % tree cover as well as vegetation mosaics and cropland. Of the macaque species, M. nemestrina was mainly predicted to occur in forested areas whereas M. fascicularis was predicted to occur in vegetation mosaics, cropland, wetland and urban areas in addition to forested areas. Conclusions: The predicted M. fascicularis distribution encompassed a wide range of habitats where humans are found. This is of most significance in the northern part of its range where members of the Dirus Complex are the main P. knowlesi vectors because these mosquitoes were also predicted to occur in a wider range of habitats. Our results support the hypothesis that conversion of intact forest into disturbed forest (for example plantations or timber concessions), or the creation of vegetation mosaics, will increase the probability that members of the Leucosphyrus Complex occur at these locations, as well as bringing humans into these areas. An explicit analysis of disease risk itself using infection data is required to explore this further. The species distributions generated here can now be included in future analyses of P. knowlesi infection risk. © 2016 Moyes et al.
Streptococcus pneumoniae and Haemophilus influenzae in paediatric meningitis patients at Goroka General Hospital, Papua New Guinea : Serotype distribution and antimicrobial susceptibility in the pre-vaccine era
- Greenhill, Andrew, Phuanukoonnon, Suparat, Michael, Audrey, Yoannes, Mition, Orami, Tilda, Smith, Helen, Murphy, Denise, Blyth, Christopher, Reeder, John, Siba, Peter, Pomat, William, Lehmann, Deborah
- Authors: Greenhill, Andrew , Phuanukoonnon, Suparat , Michael, Audrey , Yoannes, Mition , Orami, Tilda , Smith, Helen , Murphy, Denise , Blyth, Christopher , Reeder, John , Siba, Peter , Pomat, William , Lehmann, Deborah
- Date: 2015
- Type: Text , Journal article
- Relation: BMC Infectious Diseases Vol. 15, no. 485 (2015), p. 1-8
- Full Text:
- Reviewed:
- Description: Background: Bacterial meningitis remains an important infection globally, with the greatest burden in children in low-income settings, including Papua New Guinea (PNG). We present serotype, antimicrobial susceptibility and outcome data from paediatric meningitis patients prior to introduction of Haemophilus influenzae type b (Hib) and pneumococcal conjugate vaccines (PCVs) in PNG, providing a baseline for evaluation of immunisation programs. Methods: Cerebrospinal fluid (CSF) was collected from children admitted to Goroka General Hospital with suspected meningitis between 1996 and 2005. Culture and sensitivity was conducted, and pneumococci and H. influenzae were serotyped. Laboratory findings were linked to clinical outcomes. Results: We enrolled 1884 children. A recognised pathogen was identified in 375 children (19.9%). Streptococcus pneumoniae (n = 180) and Hib (n = 153) accounted for 88.8% of pathogens isolated. 24 different pneumococcal serogroups were identified; non-PCV types 2, 24 and 46 accounted for 31.6% of pneumococcal meningitis. 10- and 13-valent PCVs would cover 44.1% and 45.4% of pneumococcal meningitis respectively. Pneumococcal isolates were commonly resistant to penicillin (21.5%) and 23% of Hib isolates were simultaneously resistant to ampicillin, co-trimoxazole and chloramphenicol. The case fatality rate in patients with a recognised bacterial pathogen was 13.4% compared to 8.5% in culture-negative patients. Conclusions: If implemented in routine expanded programme of immunisation (EPI) with high coverage, current PCVs could prevent almost half of pneumococcal meningitis cases. Given the diversity of circulating serotypes in PNG serotype replacement is of concern. Ongoing surveillance is imperative to monitor the impact of vaccines. In the longer term vaccines providing broader protection against pneumococcal meningitis will be needed. © 2015 Greenhill et al.
- Authors: Greenhill, Andrew , Phuanukoonnon, Suparat , Michael, Audrey , Yoannes, Mition , Orami, Tilda , Smith, Helen , Murphy, Denise , Blyth, Christopher , Reeder, John , Siba, Peter , Pomat, William , Lehmann, Deborah
- Date: 2015
- Type: Text , Journal article
- Relation: BMC Infectious Diseases Vol. 15, no. 485 (2015), p. 1-8
- Full Text:
- Reviewed:
- Description: Background: Bacterial meningitis remains an important infection globally, with the greatest burden in children in low-income settings, including Papua New Guinea (PNG). We present serotype, antimicrobial susceptibility and outcome data from paediatric meningitis patients prior to introduction of Haemophilus influenzae type b (Hib) and pneumococcal conjugate vaccines (PCVs) in PNG, providing a baseline for evaluation of immunisation programs. Methods: Cerebrospinal fluid (CSF) was collected from children admitted to Goroka General Hospital with suspected meningitis between 1996 and 2005. Culture and sensitivity was conducted, and pneumococci and H. influenzae were serotyped. Laboratory findings were linked to clinical outcomes. Results: We enrolled 1884 children. A recognised pathogen was identified in 375 children (19.9%). Streptococcus pneumoniae (n = 180) and Hib (n = 153) accounted for 88.8% of pathogens isolated. 24 different pneumococcal serogroups were identified; non-PCV types 2, 24 and 46 accounted for 31.6% of pneumococcal meningitis. 10- and 13-valent PCVs would cover 44.1% and 45.4% of pneumococcal meningitis respectively. Pneumococcal isolates were commonly resistant to penicillin (21.5%) and 23% of Hib isolates were simultaneously resistant to ampicillin, co-trimoxazole and chloramphenicol. The case fatality rate in patients with a recognised bacterial pathogen was 13.4% compared to 8.5% in culture-negative patients. Conclusions: If implemented in routine expanded programme of immunisation (EPI) with high coverage, current PCVs could prevent almost half of pneumococcal meningitis cases. Given the diversity of circulating serotypes in PNG serotype replacement is of concern. Ongoing surveillance is imperative to monitor the impact of vaccines. In the longer term vaccines providing broader protection against pneumococcal meningitis will be needed. © 2015 Greenhill et al.
Antibiotic resistant Shigella is a major cause of diarrhoea in the Highlands of Papua New Guinea
- Greenhill, Andrew, Guwada, Carlton, Siba, Valentine, Michael, Audrey, Yoannes, Mution, Wawarie, Yolandah, Ford, Rebecca, Siba, Peter, Horwood, Paul
- Authors: Greenhill, Andrew , Guwada, Carlton , Siba, Valentine , Michael, Audrey , Yoannes, Mution , Wawarie, Yolandah , Ford, Rebecca , Siba, Peter , Horwood, Paul
- Date: 2014
- Type: Text , Journal article
- Relation: Journal of Infection in Developing Countries Vol. 8, no. 11 (2014), p. 1391-1397
- Full Text:
- Reviewed:
- Description: Introduction: Diarrhoea remains a major cause of illness in Papua New Guinea (PNG); however, little is known about its aetiology. As a result of the cholera outbreak that spread throughout PNG in 2009-2011, we conducted diarrhoeal surveillance in Eastern Highlands Province. Methodology: Following informed consent and a brief questionnaire, participants provided a stool sample or duplicate rectal swabs. Samples were tested for common bacterial pathogens Salmonella spp., Shigella spp., Vibrio spp., Campylobacter spp. and Yersinia enterocolitica using established culture methods. Enteric parasites were detected using microscopy. Results: A total of 216 participants were enrolled; where age was recorded, 42% were under 5 years of age, 6.7% were 5 to 17 years of age and 51.3% ≥18 years of age. One or more pathogens were detected in 68 (31.5%) participants, with Shigella (primarily S. flexneri) being the most commonly isolated (47 of 216 participants). Enteric parasites were detected in 23 of the 216 participants, occurring as a co-infection with another pathogen in 12 of 23 cases. No Vibrio cholerae was detected. Shigella isolates were commonly resistant to ampicillin, tetracycline, co-trimoxazole and chloramphenicol. Conclusions: Shigellae, specifically S. flexneri, are important pathogens in the highlands of PNG. While most studies in low-income settings focus on childhood aetiology, we have demonstrated the importance of Shigella in both children and adults. Enteric parasites remain present and presumably contribute to the burden of gastrointestinal illness. While improvements in sanitation and hygiene would help lower the burden of all aetiologies of infectious diarrhoea, additional control strategies targeting Shigella may also be warranted. © 2014 Greenhill et al.
- Authors: Greenhill, Andrew , Guwada, Carlton , Siba, Valentine , Michael, Audrey , Yoannes, Mution , Wawarie, Yolandah , Ford, Rebecca , Siba, Peter , Horwood, Paul
- Date: 2014
- Type: Text , Journal article
- Relation: Journal of Infection in Developing Countries Vol. 8, no. 11 (2014), p. 1391-1397
- Full Text:
- Reviewed:
- Description: Introduction: Diarrhoea remains a major cause of illness in Papua New Guinea (PNG); however, little is known about its aetiology. As a result of the cholera outbreak that spread throughout PNG in 2009-2011, we conducted diarrhoeal surveillance in Eastern Highlands Province. Methodology: Following informed consent and a brief questionnaire, participants provided a stool sample or duplicate rectal swabs. Samples were tested for common bacterial pathogens Salmonella spp., Shigella spp., Vibrio spp., Campylobacter spp. and Yersinia enterocolitica using established culture methods. Enteric parasites were detected using microscopy. Results: A total of 216 participants were enrolled; where age was recorded, 42% were under 5 years of age, 6.7% were 5 to 17 years of age and 51.3% ≥18 years of age. One or more pathogens were detected in 68 (31.5%) participants, with Shigella (primarily S. flexneri) being the most commonly isolated (47 of 216 participants). Enteric parasites were detected in 23 of the 216 participants, occurring as a co-infection with another pathogen in 12 of 23 cases. No Vibrio cholerae was detected. Shigella isolates were commonly resistant to ampicillin, tetracycline, co-trimoxazole and chloramphenicol. Conclusions: Shigellae, specifically S. flexneri, are important pathogens in the highlands of PNG. While most studies in low-income settings focus on childhood aetiology, we have demonstrated the importance of Shigella in both children and adults. Enteric parasites remain present and presumably contribute to the burden of gastrointestinal illness. While improvements in sanitation and hygiene would help lower the burden of all aetiologies of infectious diarrhoea, additional control strategies targeting Shigella may also be warranted. © 2014 Greenhill et al.
Detection of enteric viral and bacterial pathogens associated with paediatric diarrhoea in Goroka, Papua New Guinea
- Soli, Kevin, Maure, Tobias, Kas, Monalisa, Bande, Grace, Bebes, Sauli, Luang-Suarkia, Dagwin, Siba, Peter, Morita, Ayako, Umezaki, Masahiro, Greenhill, Andrew, Horwood, Paul
- Authors: Soli, Kevin , Maure, Tobias , Kas, Monalisa , Bande, Grace , Bebes, Sauli , Luang-Suarkia, Dagwin , Siba, Peter , Morita, Ayako , Umezaki, Masahiro , Greenhill, Andrew , Horwood, Paul
- Date: 2014
- Type: Text , Journal article
- Relation: International Journal of Infectious Diseases Vol. 27, no. (2014), p. 54-58
- Full Text:
- Reviewed:
- Description: Objectives: The aim of this study was to investigate the viral and bacterial causes of acute watery diarrhoea in hospitalized children in Papua New Guinea. Methods: A retrospective analysis was conducted on stool samples collected from 199 children (age > 5 years) admitted to the paediatric ward of Goroka General Hospital from August 2009 through November 2010. A large range of viral and bacterial enteric pathogens were targeted using real-time PCR/RT-PCR assays. Results: Young children were much more likely to be admitted with acute gastroenteritis, with 62.8% of patients aged >1 year and 88.4% aged >2 years. An enteric pathogen was detected in 69.8% (n= 138) of patients. The most commonly detected pathogens were Shigella spp (26.6%), rotavirus (25.6%), adenovirus types 40/41 (11.6%), enterotoxigenic Escherichia coli (11.1%), enteropathogenic E. coli (8.5%), norovirus G2 (6.0%), and Campylobacter spp (4.0%). Norovirus G1, sapovirus, and Salmonella spp were also detected, but below our statistical limit of detection. Vibrio cholerae and astrovirus were not detected in any patients. Mixed infections were detected in 22.1% of patients, with Shigella and rotavirus most commonly detected in co-infections with other pathogens. Conclusions: This study demonstrates that Shigella and rotavirus are the major pathogens associated with acute paediatric gastroenteritis in this setting. © 2014 The Authors.
- Authors: Soli, Kevin , Maure, Tobias , Kas, Monalisa , Bande, Grace , Bebes, Sauli , Luang-Suarkia, Dagwin , Siba, Peter , Morita, Ayako , Umezaki, Masahiro , Greenhill, Andrew , Horwood, Paul
- Date: 2014
- Type: Text , Journal article
- Relation: International Journal of Infectious Diseases Vol. 27, no. (2014), p. 54-58
- Full Text:
- Reviewed:
- Description: Objectives: The aim of this study was to investigate the viral and bacterial causes of acute watery diarrhoea in hospitalized children in Papua New Guinea. Methods: A retrospective analysis was conducted on stool samples collected from 199 children (age > 5 years) admitted to the paediatric ward of Goroka General Hospital from August 2009 through November 2010. A large range of viral and bacterial enteric pathogens were targeted using real-time PCR/RT-PCR assays. Results: Young children were much more likely to be admitted with acute gastroenteritis, with 62.8% of patients aged >1 year and 88.4% aged >2 years. An enteric pathogen was detected in 69.8% (n= 138) of patients. The most commonly detected pathogens were Shigella spp (26.6%), rotavirus (25.6%), adenovirus types 40/41 (11.6%), enterotoxigenic Escherichia coli (11.1%), enteropathogenic E. coli (8.5%), norovirus G2 (6.0%), and Campylobacter spp (4.0%). Norovirus G1, sapovirus, and Salmonella spp were also detected, but below our statistical limit of detection. Vibrio cholerae and astrovirus were not detected in any patients. Mixed infections were detected in 22.1% of patients, with Shigella and rotavirus most commonly detected in co-infections with other pathogens. Conclusions: This study demonstrates that Shigella and rotavirus are the major pathogens associated with acute paediatric gastroenteritis in this setting. © 2014 The Authors.
Discovery of novel Schistosoma japonicum antigens using a targeted protein microarray approach
- McWilliam, Hamish, Driguez, Patrick, Piedrafita, David, McManus, Donald, Meeusen, Els
- Authors: McWilliam, Hamish , Driguez, Patrick , Piedrafita, David , McManus, Donald , Meeusen, Els
- Date: 2014
- Type: Text , Journal article
- Relation: Parasites and Vectors Vol. 7, no. 1 (2014), p. 1-11
- Full Text:
- Reviewed:
- Description: Background: Novel vaccine candidates against Schistosoma japonicum are required, and antigens present in the vulnerable larval developmental stage are attractive targets. Post-genomic technologies are now available which can contribute to such antigen discovery. Methods. A schistosome-specific protein microarray was probed using the local antibody response against migrating larvae. Antigens were assessed for their novelty and predicted larval expression and host-exposed features. One antigen was further characterised and its sequence and structure were analysed in silico. Real-time polymerase chain reaction was used to analyse transcript expression throughout development, and immunoblotting and enzyme-linked immunosorbent assays employed to determine antigen recognition by antibody samples. Results: Several known and novel antigens were discovered, two of which showed up-regulated transcription in schistosomula. One novel antigen, termed S. japonicum Ly-6-like protein 1 (Sj-L6L-1), was further characterised and shown to share structural and sequence features with the Ly-6 protein family. It was found to be present in the worm tegument and expressed in both the larval and adult worms, but was found to be antigenic only in the lungs that the larvae migrate to and traverse. Conclusions: This study represents a novel approach to vaccine antigen discovery and may contribute to schistosome vaccine development against this important group of human and veterinary pathogens. © 2014 McWilliam et al.; licensee BioMed Central Ltd.
- Authors: McWilliam, Hamish , Driguez, Patrick , Piedrafita, David , McManus, Donald , Meeusen, Els
- Date: 2014
- Type: Text , Journal article
- Relation: Parasites and Vectors Vol. 7, no. 1 (2014), p. 1-11
- Full Text:
- Reviewed:
- Description: Background: Novel vaccine candidates against Schistosoma japonicum are required, and antigens present in the vulnerable larval developmental stage are attractive targets. Post-genomic technologies are now available which can contribute to such antigen discovery. Methods. A schistosome-specific protein microarray was probed using the local antibody response against migrating larvae. Antigens were assessed for their novelty and predicted larval expression and host-exposed features. One antigen was further characterised and its sequence and structure were analysed in silico. Real-time polymerase chain reaction was used to analyse transcript expression throughout development, and immunoblotting and enzyme-linked immunosorbent assays employed to determine antigen recognition by antibody samples. Results: Several known and novel antigens were discovered, two of which showed up-regulated transcription in schistosomula. One novel antigen, termed S. japonicum Ly-6-like protein 1 (Sj-L6L-1), was further characterised and shown to share structural and sequence features with the Ly-6 protein family. It was found to be present in the worm tegument and expressed in both the larval and adult worms, but was found to be antigenic only in the lungs that the larvae migrate to and traverse. Conclusions: This study represents a novel approach to vaccine antigen discovery and may contribute to schistosome vaccine development against this important group of human and veterinary pathogens. © 2014 McWilliam et al.; licensee BioMed Central Ltd.