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Dr. David Williams
Australian Venom Research Unit, Department of Pharmacology and Therapeutics, University of Melbourne, Melbourne, Australia

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Research Keywords & Expertise

0 Clinical Trials
0 Antivenom design, development and production
0 Clinical toxinology of animal
0 First aid for snake bites
0 Health worker training and education

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Clinical Trials
Clinical toxinology of animal
First aid for snake bites

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Review
Published: 16 July 2021 in Toxicon: X
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Community empowerment and engagement is one of the four strategic aims highlighted in the WHO strategy to prevent and control snakebite envenoming. Inappropriate health-seeking behaviours contribute to adverse outcomes, and community engagement is key in driving behavioural change. WHO has highlighted East Africa as a geographical area of concern for snakebite envenoming. The overall aim of the project is to develop a community engagement toolkit for snakebite envenoming and other NTDs. The objective of this scoping review was to identify current practices in recent community engagement in rural East Africa; the applicability of these results to snakebite envenoming are discussed. PubMed, Web of Science, PsycINFO and Google Scholar were searched from 1 January 2017 to 3 September 2020. Search terms were used to identify publications which related to rural communities and health or disease, for both humans and animals. After reviewing the full papers for all geographical areas, 112 publications were included, 30 of which were conducted in East Africa. Papers included nine different countries and covered a broad range of health topics; notably, water, sanitation and hygiene, nutrition, and maternal and child health. Only one publication considered animal health. The most common form of engagement was in the context of a group meeting, lecture, presentation, discussion or question and answer session (63.3%). A variety of locations within the community were used to engage with people, the most common being an individual's household (23.3%). Communication factors was the key influencer for engagement, both positively and negatively. Key barriers to engagement include local languages and health beliefs, literacy levels, mobile phone ownership and the level of mobile Internet coverage, burden of agricultural work and weather conditions. This study provides an extensive overview of recent public health community engagement in East Africa, which will serve as a useful resource for any group seeking to plan an intervention in remote and rural areas in East Africa. Furthermore, it serves as a guide to help tailor community engagement to snakebite envenoming.

ACS Style

Bethany Moos; David Williams; Isabelle Bolon; Denise Mupfasoni; Bernadette Abela-Ridder; Rafael Ruiz de Castaneda. A scoping review of current practices on community engagement in rural East Africa: Recommendations for snakebite envenoming. Toxicon: X 2021, 11, 100073 .

AMA Style

Bethany Moos, David Williams, Isabelle Bolon, Denise Mupfasoni, Bernadette Abela-Ridder, Rafael Ruiz de Castaneda. A scoping review of current practices on community engagement in rural East Africa: Recommendations for snakebite envenoming. Toxicon: X. 2021; 11 ():100073.

Chicago/Turabian Style

Bethany Moos; David Williams; Isabelle Bolon; Denise Mupfasoni; Bernadette Abela-Ridder; Rafael Ruiz de Castaneda. 2021. "A scoping review of current practices on community engagement in rural East Africa: Recommendations for snakebite envenoming." Toxicon: X 11, no. : 100073.

Journal article
Published: 12 June 2021 in Toxicon: X
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Snakebite envenoming is a neglected tropical disease that may claim over 100,000 human lives annually worldwide. Snakebite occurs as the result of an interaction between a human and a snake that elicits either a defensive response from the snake or, more rarely, a feeding response as the result of mistaken identity. Snakebite envenoming is therefore a biological and, more specifically, an ecological problem. Snake venom itself is often described as a “cocktail”, as it is a heterogenous mixture of molecules including the toxins (which are typically proteinaceous) responsible for the pathophysiological consequences of envenoming. The primary function of venom in snake ecology is pre-subjugation, with defensive deployment of the secretion typically considered a secondary function. The particular composition of any given venom cocktail is shaped by evolutionary forces that include phylogenetic constraints associated with the snake's lineage and adaptive responses to the snake's ecological context, including the taxa it preys upon and by which it is predated upon. In the present article, we describe how conceptual frameworks from ecology and evolutionary biology can enter into a mutually enlightening relationship with clinical toxinology by enabling the consideration of snakebite envenoming from an “ecological stance”. We detail the insights that may emerge from such a perspective and highlight the ways in which the high-fidelity descriptive knowledge emerging from applications of -omics era technologies – “venomics” and “antivenomics” – can combine with evolutionary explanations to deliver a detailed understanding of this multifactorial health crisis.

ACS Style

Juan J. Calvete; Bruno Lomonte; Anthony J. Saviola; Fabián Bonilla; Mahmood Sasa; David J. Williams; Eivind A.B. Undheim; Kartik Sunagar; Timothy N.W. Jackson. Mutual enlightenment: A toolbox of concepts and methods for integrating evolutionary and clinical toxinology via snake venomics and the contextual stance. Toxicon: X 2021, 9-10, 100070 .

AMA Style

Juan J. Calvete, Bruno Lomonte, Anthony J. Saviola, Fabián Bonilla, Mahmood Sasa, David J. Williams, Eivind A.B. Undheim, Kartik Sunagar, Timothy N.W. Jackson. Mutual enlightenment: A toolbox of concepts and methods for integrating evolutionary and clinical toxinology via snake venomics and the contextual stance. Toxicon: X. 2021; 9-10 ():100070.

Chicago/Turabian Style

Juan J. Calvete; Bruno Lomonte; Anthony J. Saviola; Fabián Bonilla; Mahmood Sasa; David J. Williams; Eivind A.B. Undheim; Kartik Sunagar; Timothy N.W. Jackson. 2021. "Mutual enlightenment: A toolbox of concepts and methods for integrating evolutionary and clinical toxinology via snake venomics and the contextual stance." Toxicon: X 9-10, no. : 100070.

Journal article
Published: 20 February 2020 in Toxins
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The phospholipase A2 (PLA2) inhibitor Varespladib (LY315920) and its orally bioavailable prodrug, methyl-Varespladib (LY333013) inhibit PLA2 activity of a wide variety of snake venoms. In this study, the ability of these two forms of Varespladib to halt or delay lethality of potent neurotoxic snake venoms was tested in a mouse model. The venoms of Notechis scutatus, Crotalus durissus terrificus, Bungarus multicinctus, and Oxyuranus scutellatus, all of which have potent presynaptically acting neurotoxic PLA2s of variable quaternary structure, were used to evaluate simple dosing regimens. A supralethal dose of each venom was injected subcutaneously in mice, followed by the bolus intravenous (LY315920) or oral (LY333013) administration of the inhibitors, immediately and at various time intervals after envenoming. Control mice receiving venom alone died within 3 h of envenoming. Mice injected with O. scutellatus venom and treated with LY315920 or LY333013 survived the 24 h observation period, whereas those receiving C. d. terrificus and B. multicinctus venoms survived at 3 h or 6 h with a single dose of either form of Varespladib, but not at 24 h. In contrast, mice receiving N. scutatus venom and then the inhibitors died within 3 h, similarly to the control animals injected with venom alone. LY315920 was able to reverse the severe paralytic manifestations in mice injected with venoms of O. scutellatus, B. multicinctus, and C. d. terrificus. Overall, results suggest that the two forms of Varespladib are effective in abrogating, or delaying, neurotoxic manifestations induced by some venoms whose neurotoxicity is mainly dependent on presynaptically acting PLA2s. LY315920 is able to reverse paralytic manifestations in severely envenomed mice, but further work is needed to understand the significance of species-specific differences in animal models as they compare to clinical syndromes in human and for potential use in veterinary medicine.

ACS Style

José María Gutiérrez; Matthew R. Lewin; David. J. Williams; Bruno Lomonte. Varespladib (LY315920) and Methyl Varespladib (LY333013) Abrogate or Delay Lethality Induced by Presynaptically Acting Neurotoxic Snake Venoms. Toxins 2020, 12, 131 .

AMA Style

José María Gutiérrez, Matthew R. Lewin, David. J. Williams, Bruno Lomonte. Varespladib (LY315920) and Methyl Varespladib (LY333013) Abrogate or Delay Lethality Induced by Presynaptically Acting Neurotoxic Snake Venoms. Toxins. 2020; 12 (2):131.

Chicago/Turabian Style

José María Gutiérrez; Matthew R. Lewin; David. J. Williams; Bruno Lomonte. 2020. "Varespladib (LY315920) and Methyl Varespladib (LY333013) Abrogate or Delay Lethality Induced by Presynaptically Acting Neurotoxic Snake Venoms." Toxins 12, no. 2: 131.

Journal article
Published: 14 September 2019 in Transactions of The Royal Society of Tropical Medicine and Hygiene
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ACS Style

Robert A Harrison; David Williams. Outlining progress since the first International Snakebite Awareness Day and some key challenges for next year. Transactions of The Royal Society of Tropical Medicine and Hygiene 2019, 113, 577 -578.

AMA Style

Robert A Harrison, David Williams. Outlining progress since the first International Snakebite Awareness Day and some key challenges for next year. Transactions of The Royal Society of Tropical Medicine and Hygiene. 2019; 113 (10):577-578.

Chicago/Turabian Style

Robert A Harrison; David Williams. 2019. "Outlining progress since the first International Snakebite Awareness Day and some key challenges for next year." Transactions of The Royal Society of Tropical Medicine and Hygiene 113, no. 10: 577-578.

Journal article
Published: 23 July 2019 in Nature
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ACS Style

Rafael Ruiz De Castañeda; François Grey; David J. Williams. Citizen science could map snakebite risk. Nature 2019, 571, 478 -478.

AMA Style

Rafael Ruiz De Castañeda, François Grey, David J. Williams. Citizen science could map snakebite risk. Nature. 2019; 571 (7766):478-478.

Chicago/Turabian Style

Rafael Ruiz De Castañeda; François Grey; David J. Williams. 2019. "Citizen science could map snakebite risk." Nature 571, no. 7766: 478-478.

Journal article
Published: 22 March 2019 in Toxicology in Vitro
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Snakebite is a neglected tropical disease that disproportionately affects the poor. Antivenom is the only specific and effective treatment for snakebite, but its distribution is severely limited by several factors, including the prohibitive cost of some products. Papua New Guinea (PNG) is a snakebite hotspot but the high costs of Australian antivenoms (thousands of dollars per treatment) makes it unaffordable in PNG. A more economical taipan antivenom has recently been developed at the Instituto Clodomiro Picado (ICP) in Costa Rica for PNG and is currently undergoing clinical trials for the treatment of envenomations by coastal taipans (Oxyuranus scutellatus). In addition to potentially having the capacity to neutralise the effects of envenomations of non-PNG taipans, this antivenom may have the capacity to neutralise coagulotoxins in venom from closely related brown snakes (Pseudonaja spp.) also found in PNG. Consequently, we investigated the cross-reactivity of taipan antivenom across the venoms of all Oxyuranus and Pseudonaja species. In addition, to ascertain differences in venom biochemistry that influence variation in antivenom efficacy, we tested for relative cofactor dependence. We found that the new ICP taipan antivenom exhibited high selectivity for Oxyuranus venoms and only low to moderate cross-reactivity with any Pseudonaja venoms. Consistent with this genus level distinction in antivenom efficacy were fundamental differences in the venom biochemistry. Not only were the Pseudonaja venoms significantly more procoagulant, but they were also much less dependent upon the cofactors calcium and phospholipid. There was a strong correlation between antivenom efficacy, clotting time and cofactor dependence. This study sheds light on the structure-function relationships of the procoagulant toxins within these venoms and may have important clinical implications including for the design of next-generation antivenoms.

ACS Style

Christina N. Zdenek; Chris Hay; Kevin Arbuckle; Timothy N.W. Jackson; Mettine Bos; Bianca Op Den Brouw; Jordan Debono; Luke Allen; Nathan Dunstan; Terry Morley; María Herrera; José M. Gutiérrez; David Williams; Bryan G. Fry. Coagulotoxic effects by brown snake (Pseudonaja) and taipan (Oxyuranus) venoms, and the efficacy of a new antivenom. Toxicology in Vitro 2019, 58, 97 -109.

AMA Style

Christina N. Zdenek, Chris Hay, Kevin Arbuckle, Timothy N.W. Jackson, Mettine Bos, Bianca Op Den Brouw, Jordan Debono, Luke Allen, Nathan Dunstan, Terry Morley, María Herrera, José M. Gutiérrez, David Williams, Bryan G. Fry. Coagulotoxic effects by brown snake (Pseudonaja) and taipan (Oxyuranus) venoms, and the efficacy of a new antivenom. Toxicology in Vitro. 2019; 58 ():97-109.

Chicago/Turabian Style

Christina N. Zdenek; Chris Hay; Kevin Arbuckle; Timothy N.W. Jackson; Mettine Bos; Bianca Op Den Brouw; Jordan Debono; Luke Allen; Nathan Dunstan; Terry Morley; María Herrera; José M. Gutiérrez; David Williams; Bryan G. Fry. 2019. "Coagulotoxic effects by brown snake (Pseudonaja) and taipan (Oxyuranus) venoms, and the efficacy of a new antivenom." Toxicology in Vitro 58, no. : 97-109.

Policy platform
Published: 21 February 2019 in PLoS Neglected Tropical Diseases
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David J. Williams; Mohd Abul Faiz; Bernadette Abela-Ridder; Stuart Ainsworth; Tommaso C. Bulfone; Andrea D. Nickerson; Abdulrazaq G. Habib; Thomas Junghanss; Hui Wen Fan; Michael Turner; Robert A. Harrison; David A. Warrell. Strategy for a globally coordinated response to a priority neglected tropical disease: Snakebite envenoming. PLoS Neglected Tropical Diseases 2019, 13, e0007059 .

AMA Style

David J. Williams, Mohd Abul Faiz, Bernadette Abela-Ridder, Stuart Ainsworth, Tommaso C. Bulfone, Andrea D. Nickerson, Abdulrazaq G. Habib, Thomas Junghanss, Hui Wen Fan, Michael Turner, Robert A. Harrison, David A. Warrell. Strategy for a globally coordinated response to a priority neglected tropical disease: Snakebite envenoming. PLoS Neglected Tropical Diseases. 2019; 13 (2):e0007059.

Chicago/Turabian Style

David J. Williams; Mohd Abul Faiz; Bernadette Abela-Ridder; Stuart Ainsworth; Tommaso C. Bulfone; Andrea D. Nickerson; Abdulrazaq G. Habib; Thomas Junghanss; Hui Wen Fan; Michael Turner; Robert A. Harrison; David A. Warrell. 2019. "Strategy for a globally coordinated response to a priority neglected tropical disease: Snakebite envenoming." PLoS Neglected Tropical Diseases 13, no. 2: e0007059.

Communication
Published: 20 September 2018 in Toxins
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There is an unmet need for economical snakebite therapies with long shelf lives that are effective even with delays in treatment. The orally bioavailable, heat-stable, secretory phospholipase A2 (sPLA2) inhibitor, LY333013, demonstrates antidotal characteristics for severe snakebite envenoming in both field and hospital use. A murine model of lethal envenoming by a Papuan taipan (Oxyuranus scutellatus) demonstrates that LY333013, even with delayed oral administration, improves the chances of survival. Furthermore, LY333013 improves the performance of antivenom even after it no longer reverses neurotoxic signs. Our study is the first demonstration that neurotoxicity from presynaptic venom sPLA2S can be treated successfully, even after the window of therapeutic antivenom has closed. These results suggest that sPLA2 inhibitors have the potential to reduce death and disability and should be considered for the initial and adjunct treatment of snakebite envenoming. The scope and capacity of the sPLA2 inhibitors ability to achieve these endpoints requires further investigation and development efforts.

ACS Style

Matthew R. Lewin; José María Gutiérrez; Stephen P. Samuel; María Herrera; Wendy Bryan-Quirós; Bruno Lomonte; Philip E. Bickler; Tommaso C. Bulfone; David J. Williams. Delayed Oral LY333013 Rescues Mice from Highly Neurotoxic, Lethal Doses of Papuan Taipan (Oxyuranus scutellatus) Venom. Toxins 2018, 10, 380 .

AMA Style

Matthew R. Lewin, José María Gutiérrez, Stephen P. Samuel, María Herrera, Wendy Bryan-Quirós, Bruno Lomonte, Philip E. Bickler, Tommaso C. Bulfone, David J. Williams. Delayed Oral LY333013 Rescues Mice from Highly Neurotoxic, Lethal Doses of Papuan Taipan (Oxyuranus scutellatus) Venom. Toxins. 2018; 10 (10):380.

Chicago/Turabian Style

Matthew R. Lewin; José María Gutiérrez; Stephen P. Samuel; María Herrera; Wendy Bryan-Quirós; Bruno Lomonte; Philip E. Bickler; Tommaso C. Bulfone; David J. Williams. 2018. "Delayed Oral LY333013 Rescues Mice from Highly Neurotoxic, Lethal Doses of Papuan Taipan (Oxyuranus scutellatus) Venom." Toxins 10, no. 10: 380.

Journal article
Published: 12 July 2018 in The Lancet
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Summary Background Snakebite envenoming is a frequently overlooked cause of mortality and morbidity. Data for snake ecology and existing snakebite interventions are scarce, limiting accurate burden estimation initiatives. Low global awareness stunts new interventions, adequate health resources, and available health care. Therefore, we aimed to synthesise currently available data to identify the most vulnerable populations at risk of snakebite, and where additional data to manage this global problem are needed. Methods We assembled a list of snake species using WHO guidelines. Where relevant, we obtained expert opinion range (EOR) maps from WHO or the Clinical Toxinology Resources. We also obtained occurrence data for each snake species from a variety of websites, such as VertNet and iNaturalist, using the spocc R package (version 0.7.0). We removed duplicate occurrence data and categorised snakes into three groups: group A (no available EOR map or species occurrence records), group B (EOR map but Findings We provide a map showing the ranges of 278 snake species globally. Although about 6·85 billion people worldwide live within range of areas inhabited by snakes, about 146·70 million live within remote areas lacking quality health-care provisioning. Comparing opposite ends of the HAQ Index, 272·91 million individuals (65·25%) of the population within the lowest decile are at risk of exposure to any snake for which no effective therapy exists compared with 519·46 million individuals (27·79%) within the highest HAQ Index decile, showing a disproportionate coverage in reported antivenom availability. Antivenoms were available for 119 (43%) of 278 snake species evaluated by WHO, while globally 750·19 million (10·95%) of those living within snake ranges live more than 1 h from population centres. In total, we identify about 92·66 million people living within these vulnerable geographies, including many sub-Saharan countries, Indonesia, and other parts of southeast Asia. Interpretation Identifying exact populations vulnerable to the most severe outcomes of snakebite envenoming at a subnational level is important for prioritising new data collection and collation, reinforcing envenoming treatment, existing health-care systems, and deploying currently available and future interventions. These maps can guide future research efforts on snakebite envenoming from both ecological and public health perspectives and better target future estimates of the burden of this neglected tropical disease. Funding Bill & Melinda Gates Foundation.

ACS Style

Joshua Longbottom; Freya M Shearer; Maria Devine; Gabriel Alcoba; Francois Chappuis; Daniel J Weiss; Sarah Ray; Nicolas Ray; David A Warrell; Rafael Ruiz de Castañeda; David Williams; Simon I Hay; David M Pigott. Vulnerability to snakebite envenoming: a global mapping of hotspots. The Lancet 2018, 392, 673 -684.

AMA Style

Joshua Longbottom, Freya M Shearer, Maria Devine, Gabriel Alcoba, Francois Chappuis, Daniel J Weiss, Sarah Ray, Nicolas Ray, David A Warrell, Rafael Ruiz de Castañeda, David Williams, Simon I Hay, David M Pigott. Vulnerability to snakebite envenoming: a global mapping of hotspots. The Lancet. 2018; 392 (10148):673-684.

Chicago/Turabian Style

Joshua Longbottom; Freya M Shearer; Maria Devine; Gabriel Alcoba; Francois Chappuis; Daniel J Weiss; Sarah Ray; Nicolas Ray; David A Warrell; Rafael Ruiz de Castañeda; David Williams; Simon I Hay; David M Pigott. 2018. "Vulnerability to snakebite envenoming: a global mapping of hotspots." The Lancet 392, no. 10148: 673-684.

Journal article
Published: 07 May 2018 in Toxicon
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In the 1890s, hyperimmune sera proved effective in animals against challenge by the snake venom against which they had been raised. They were first used, apparently successfully, in a human patient in about 1895. Since then, antivenoms have become accepted as the only reliable specific treatment for snake-bite envenoming. Despite decades of accumulated clinical experience and a number of published randomized comparative and observational studies, the clinical effectiveness and safety of some antivenoms remain open to question, due to a lack of robust randomized controlled trial data. Antivenoms in some poorly regulated markets may have high rates of potentially fatal adverse effects and their use must be balanced by demonstrable effectiveness. Even those manufactured to strict regulatory requirements may pose a rare risk of severe adverse reactions. Most antivenoms currently marketed around the world were registered without first being studied clinically. There is increasing pressure to subject antivenoms, even those that are long-established, to the same protocols of rigorous pre-clinical and clinical assessment that are standard regulatory requirements for other drugs. Conventional clinical testing progresses through Phases I, II, III to IV. Most authorities consider antivenoms too dangerous to be used in Phase I studies in healthy volunteers. An alternative method for preliminary estimation of safety, dose-finding and effectiveness, is proposed - the “3 + 3” dose escalation or de-escalation design, in volunteer patients, as used in oncology to test cytotoxic drugs. Antivenoms are so widely used and well trusted, that there are few ethical justifications for placebo controls. However, placebo might be ethically justified if there were no proven effective treatment and or if withholding or delaying treatment posed acceptably negligible risks to the participants. Antivenom trials are most urgently needed in low-to middle-income countries where there are many practical, logistical and funding challenges. Basic requirements for clinical trials include identification of the biting species of snake in every case; the use of objective, clinically-relevant endpoints, such as restoration of blood coagulability; definition of inclusion, exclusion and withdrawal criteria; assurance of antivenom safety; ethical considerations; inclusion of one or more control (comparator) groups; and analysis based on intention to treat. The highest quality evidence comes from Phase II and larger Phase III studies that have been designed as statistically powerful, randomized, controlled trials (RCTs), ideally with blinding of patients and investigators to avoid bias. Because of the challenges to carrying out clinical trials of antivenoms, Phase IV trials (post-marketing surveillance) are potentially more important and useful than for most other drugs.

ACS Style

David J. Williams; Abdulrazaq G. Habib; David A. Warrell. Clinical studies of the effectiveness and safety of antivenoms. Toxicon 2018, 150, 1 -10.

AMA Style

David J. Williams, Abdulrazaq G. Habib, David A. Warrell. Clinical studies of the effectiveness and safety of antivenoms. Toxicon. 2018; 150 ():1-10.

Chicago/Turabian Style

David J. Williams; Abdulrazaq G. Habib; David A. Warrell. 2018. "Clinical studies of the effectiveness and safety of antivenoms." Toxicon 150, no. : 1-10.

Correction
Published: 05 October 2017 in Nature Reviews Disease Primers
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This corrects the article DOI: 10.1038/nrdp.2017.63.

ACS Style

José María Gutiérrez; Juan Calvete; Abdulrazaq G. Habib; Robert A. Harrison; David Williams; David A. Warrell. Correction: Snakebite envenoming. Nature Reviews Disease Primers 2017, 3, nrdp201779 -17079.

AMA Style

José María Gutiérrez, Juan Calvete, Abdulrazaq G. Habib, Robert A. Harrison, David Williams, David A. Warrell. Correction: Snakebite envenoming. Nature Reviews Disease Primers. 2017; 3 (1):nrdp201779-17079.

Chicago/Turabian Style

José María Gutiérrez; Juan Calvete; Abdulrazaq G. Habib; Robert A. Harrison; David Williams; David A. Warrell. 2017. "Correction: Snakebite envenoming." Nature Reviews Disease Primers 3, no. 1: nrdp201779-17079.

Primer
Published: 14 September 2017 in Nature Reviews Disease Primers
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Snakebite envenoming is a neglected tropical disease that kills >100,000 people and maims >400,000 people every year. Impoverished populations living in the rural tropics are particularly vulnerable; snakebite envenoming perpetuates the cycle of poverty. Snake venoms are complex mixtures of proteins that exert a wide range of toxic actions. The high variability in snake venom composition is responsible for the various clinical manifestations in envenomings, ranging from local tissue damage to potentially life-threatening systemic effects. Intravenous administration of antivenom is the only specific treatment to counteract envenoming. Analgesics, ventilator support, fluid therapy, haemodialysis and antibiotic therapy are also used. Novel therapeutic alternatives based on recombinant antibody technologies and new toxin inhibitors are being explored. Confronting snakebite envenoming at a global level demands the implementation of an integrated intervention strategy involving the WHO, the research community, antivenom manufacturers, regulatory agencies, national and regional health authorities, professional health organizations, international funding agencies, advocacy groups and civil society institutions.

ACS Style

José María Gutiérrez; Juan Calvete; Abdulrazaq G. Habib; Robert A. Harrison; David Williams; David A. Warrell. Snakebite envenoming. Nature Reviews Disease Primers 2017, 3, nrdp201763 .

AMA Style

José María Gutiérrez, Juan Calvete, Abdulrazaq G. Habib, Robert A. Harrison, David Williams, David A. Warrell. Snakebite envenoming. Nature Reviews Disease Primers. 2017; 3 (1):nrdp201763.

Chicago/Turabian Style

José María Gutiérrez; Juan Calvete; Abdulrazaq G. Habib; Robert A. Harrison; David Williams; David A. Warrell. 2017. "Snakebite envenoming." Nature Reviews Disease Primers 3, no. 1: nrdp201763.

Journal article
Published: 28 February 2017 in Osong Public Health and Research Perspectives
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The first meeting of the National Control Laboratories for Vaccines and Biologicals in the Western Pacific Region was held on September 1–2, 2016 in Seoul, the Republic of Korea. The meeting objectives were to share results of current research and to promote collaboration between the National Control Laboratories. To this end, we first discussed each country’s current status of research on quality control of biologicals. Next, we reviewed quality control of snake venom and antivenom production and the progress of a collaborative study on the Korean reference standard candidate for snake venom. We also discussed the establishment of the second regional reference standard antivenom and the characterization of the Vero cell genome landscape and its application to quality control. Moreover, we also reflected on the importance of collaboration among interested parties participating in this meeting. In conclusion, the meeting initiated networking between the national control laboratories in the Western Pacific region and paved the way to continue collaboration, which will eventually improve the region’s capacity for quality control of biologicals.

ACS Style

Hokyung Oh; Jinho Shin; Manabu Ato; Xiao Ma; David Williams; Kiwon Han; Yang Jin Kim; Hyunggoo Kang; Kikyung Jung; Kentaro Hanada; Masaki Ochiai; Pham Van Hung; Sangmi Park; Chiyoung Ahn. The First Meeting of the National Control Laboratories for Vaccines and Biologicals in the Western Pacific in 2016. Osong Public Health and Research Perspectives 2017, 8, 91 -103.

AMA Style

Hokyung Oh, Jinho Shin, Manabu Ato, Xiao Ma, David Williams, Kiwon Han, Yang Jin Kim, Hyunggoo Kang, Kikyung Jung, Kentaro Hanada, Masaki Ochiai, Pham Van Hung, Sangmi Park, Chiyoung Ahn. The First Meeting of the National Control Laboratories for Vaccines and Biologicals in the Western Pacific in 2016. Osong Public Health and Research Perspectives. 2017; 8 (1):91-103.

Chicago/Turabian Style

Hokyung Oh; Jinho Shin; Manabu Ato; Xiao Ma; David Williams; Kiwon Han; Yang Jin Kim; Hyunggoo Kang; Kikyung Jung; Kentaro Hanada; Masaki Ochiai; Pham Van Hung; Sangmi Park; Chiyoung Ahn. 2017. "The First Meeting of the National Control Laboratories for Vaccines and Biologicals in the Western Pacific in 2016." Osong Public Health and Research Perspectives 8, no. 1: 91-103.

Journal article
Published: 01 February 2017 in Molecular Phylogenetics and Evolution
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Genetic analyses of Australasian organisms have resulted in the identification of extensive cryptic diversity across the continent. The venomous elapid snakes are among the best-studied organismal groups in this region, but many knowledge gaps persist: for instance, despite their iconic status, the species-level diversity among Australo-Papuan blacksnakes (Pseudechis) has remained poorly understood due to the existence of a group of cryptic species within the P. australis species complex, collectively termed "pygmy mulga snakes". Using two mitochondrial and three nuclear loci we assess species boundaries within the genus using Bayesian species delimitation methods and reconstruct their phylogenetic history using multispecies coalescent approaches. Our analyses support the recognition of 10 species, including all of the currently described pygmy mulga snakes and one undescribed species from the Northern Territory of Australia. Phylogenetic relationships within the genus are broadly consistent with previous work, with the recognition of three major groups, the viviparous red-bellied black snake P. porphyriacus forming the sister species to two clades consisting of ovoviviparous species.

ACS Style

Simon T. Maddock; Aaron Childerstone; Bryan Grieg Fry; David Williams; Axel Barlow; Wolfgang Wüster. Multi-locus phylogeny and species delimitation of Australo-Papuan blacksnakes (Pseudechis Wagler, 1830: Elapidae: Serpentes). Molecular Phylogenetics and Evolution 2017, 107, 48 -55.

AMA Style

Simon T. Maddock, Aaron Childerstone, Bryan Grieg Fry, David Williams, Axel Barlow, Wolfgang Wüster. Multi-locus phylogeny and species delimitation of Australo-Papuan blacksnakes (Pseudechis Wagler, 1830: Elapidae: Serpentes). Molecular Phylogenetics and Evolution. 2017; 107 ():48-55.

Chicago/Turabian Style

Simon T. Maddock; Aaron Childerstone; Bryan Grieg Fry; David Williams; Axel Barlow; Wolfgang Wüster. 2017. "Multi-locus phylogeny and species delimitation of Australo-Papuan blacksnakes (Pseudechis Wagler, 1830: Elapidae: Serpentes)." Molecular Phylogenetics and Evolution 107, no. : 48-55.

Journal article
Published: 01 January 2017 in Journal of Proteomics
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The Papuan black snake (Pseudechis papuanus Serpentes: Elapidae) is endemic to Papua New Guinea, Indonesian Papua and Australia's Torres Strait Islands. We have investigated the biological activity and proteomic composition of its venom. The P. papuanus venom proteome is dominated by a variety (n≥18) of PLA2s, which together account for ~90% of the venom proteins, and a set of low relative abundance proteins, including a short-neurotoxic 3FTx (3.1%), 3-4 PIII-SVMPs (2.8%), 3 cysteine-rich secretory proteins (CRISP; 2.3%) 1-3 l-amino acid oxidase (LAAO) molecules (1.6%). Probing of a P. papuanus cDNA library with specific primers resulted in the elucidation of the full-length nucleotide sequences of six new toxins, including vespryn and NGF not found in the venom proteome, and a calglandulin protein involved in toxin expression with the venom glands. Intravenous injection of P. papuanus venom in mice induced lethality, intravascular haemolysis, pulmonary congestion and oedema, and anticoagulation after intravenous injection, and these effects are mainly due to the action of PLA2s. This study also evaluated the in vivo preclinical efficacy of Australian black snake and polyvalent Seqirus antivenoms. These antivenoms were effective in neutralising the lethal, PLA2 and anticoagulant activities of P. papuanus venom in mice. On the other hand, all of the Seqirus antivenoms tested using an antivenomic approach exhibited strong immunorecognition of all the venom components. These preclinical results suggest that Australian Seqirus1 antivenoms may provide paraspecific protection against P. papuanus venom in humans. The toxicological profile and proteomic composition of the venom of the Papuan black snake, Pseudechis papuanus, a large diurnal snake endemic to the southern coast of New Guinea and a handful of close offshore islands, were investigated. Intravenous injection of P. papuanus venom in mice induced intravascular hemolysis, pulmonary congestion and edema, anticoagulation, and death. These activities could be assigned to the set of PLA2 molecules, which dominate the P. papuanus venom proteome. This study also showed that Australian Seqirus black snake or polyvalent antivenoms were effective in neutralising the lethal, PLA2 and anticoagulant activities of the venom. These preclinical results support the continued recommendation of these Seqirus antivenoms in the clinical management of P. papuanus envenoming in Australia, Papua New Guinea or Indonesian Papua Province.

ACS Style

Davinia Pla; Benjamin W. Bande; Ronelle E. Welton; Owen K. Paiva; Libia Sanz; Álvaro Segura; Christine Wright; Juan J. Calvete; José María Gutiérrez; David J. Williams. Proteomics and antivenomics of Papuan black snake ( Pseudechis papuanus ) venom with analysis of its toxicological profile and the preclinical efficacy of Australian antivenoms. Journal of Proteomics 2017, 150, 201 -215.

AMA Style

Davinia Pla, Benjamin W. Bande, Ronelle E. Welton, Owen K. Paiva, Libia Sanz, Álvaro Segura, Christine Wright, Juan J. Calvete, José María Gutiérrez, David J. Williams. Proteomics and antivenomics of Papuan black snake ( Pseudechis papuanus ) venom with analysis of its toxicological profile and the preclinical efficacy of Australian antivenoms. Journal of Proteomics. 2017; 150 ():201-215.

Chicago/Turabian Style

Davinia Pla; Benjamin W. Bande; Ronelle E. Welton; Owen K. Paiva; Libia Sanz; Álvaro Segura; Christine Wright; Juan J. Calvete; José María Gutiérrez; David J. Williams. 2017. "Proteomics and antivenomics of Papuan black snake ( Pseudechis papuanus ) venom with analysis of its toxicological profile and the preclinical efficacy of Australian antivenoms." Journal of Proteomics 150, no. : 201-215.

Review
Published: 17 October 2016 in Emergency Medicine Australasia
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Signs of Irukandji syndrome (IS) suggest an underlying catecholamine storm with research demonstrating that Carukia barnesi venom causes a significant rise in adrenaline/noradrenaline serum levels. A systematic review was undertaken to ascertain the current evidence in treating IS with magnesium salts. A literature search was conducted using Scopus, Medline and ScienceDirect. Further articles were discarded via title description and/or abstract details. The remaining were read in full, and those identified as not having sufficient information regarding magnesium and patient outcomes were removed. Nine articles were identified. One article was a randomised controlled trial, which concluded that there appears to be no beneficial difference between those patients who received the magnesium sulphate (MgSO4) and those who received the placebo and recommended against the use of MgSO4 in IS. Of the remaining eight, one reported the failure of MgSO4 and the remaining seven were case series reporting varying success in its use. This systematic review found insufficient evidence to support any clear recommendation regarding the use of magnesium, but nor was there clear evidence to recommend against its use in IS. Two case series describe significant reduction in key symptoms and hypertension but are a non-randomised albeit prospective series with the limitations accompanying this. The reporting of recrudescence of symptoms with reduction of dose does suggest a dose–response relationship. The evidence for the use of MgSO4 is at best anecdotal, and further research is required to either confirm its benefit or confirm the randomised controlled trial.

ACS Style

John Rathbone; Richard Franklin; Clinton Gibbs; David Williams. Review article: Role of magnesium sulphate in the management of Irukandji syndrome: A systematic review. Emergency Medicine Australasia 2016, 29, 9 -17.

AMA Style

John Rathbone, Richard Franklin, Clinton Gibbs, David Williams. Review article: Role of magnesium sulphate in the management of Irukandji syndrome: A systematic review. Emergency Medicine Australasia. 2016; 29 (1):9-17.

Chicago/Turabian Style

John Rathbone; Richard Franklin; Clinton Gibbs; David Williams. 2016. "Review article: Role of magnesium sulphate in the management of Irukandji syndrome: A systematic review." Emergency Medicine Australasia 29, no. 1: 9-17.

Original article
Published: 17 October 2016 in Internal Medicine Journal
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Background Accidental injury is a major public health problem in developed countries with 20 years elapsed since a national overview of venomous bites undertaken in Australia. Aim Provide the first contemporary epidemiological insight into venomous injuries based on demographics and geography nationally in Australia in the period 2000–2013. Methods An analysis of national hospitalisation and mortality data was undertaken to examine the incidence of injury and death due to envenoming in Australia. Rates were calculated using the intercensal population for all Australian age groups. Results Over the study period, deaths occurred due to an anaphylactic event (0.16 per 100 000), snake envenoming (0.13 per 100 000) or box jellyfish envenoming (0.01 per 100 000). Only 44% of cases involving anaphylaxis reached medical care prior to death, compared to 74% of those envenomed by snakes. Over half of all deaths (52%) occurred at home, and 64% of these occurred within a major city or inner regional area, with 48% of work‐related anaphylaxis deaths. Hospital admission rates of 199 per 100 000 persons over the 11 years were caused by contact with wasps or bees (31%), spiders (30%) and snakes (15%), with a predominant age range of 30–44 years. Conclusions The greatest burden of injury due to envenoming was caused by arthropods and snakes. Causes of death were led by anaphylaxis subsequent to an arthropod bite or sting, followed by death from snake envenoming. Over half the incidents resulting in death occurred at home, in areas where healthcare is accessible. Operational data routinely collected are informative, with variations of injury incidence between the States and Territories, indicating a need for a more localised approach to the management of this injury.

ACS Style

R. E. Welton; David Williams; D. Liew. Injury trends from envenoming in Australia, 2000-2013. Internal Medicine Journal 2016, 47, 170 -176.

AMA Style

R. E. Welton, David Williams, D. Liew. Injury trends from envenoming in Australia, 2000-2013. Internal Medicine Journal. 2016; 47 (2):170-176.

Chicago/Turabian Style

R. E. Welton; David Williams; D. Liew. 2016. "Injury trends from envenoming in Australia, 2000-2013." Internal Medicine Journal 47, no. 2: 170-176.

Comparative study
Published: 01 September 2016 in Toxicon
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A chicken-derived antivenom (ChDAv) towards taipan snake (Oxyuranus scutellatus) venom was produced by purifying anti-taipan IgY from egg yolks of hens immunized with taipan venom. The productivity, antivenomic profile, neutralization ability, pharmacokinetic properties and immunogenicity of the ChDAv were compared with those of an antivenom produced in horses (EDAv). We found that 382 eggs are required to produce the mass of anti-taipan antibodies contained in one liter of equine hyperimmune plasma, and that 63 chickens would be needed to generate the amount of anti-taipan antibodies annually produced by one horse. It was estimated that, in Costa Rica, the production of anti-taipan antibodies could be 40% cheaper if chickens were used as immunoglobulin source, instead of horses. During antivenomic assessment, ChDAv showed lower ability to immunocapture the α subunit of taipoxin, the most important neurotoxin in the venom. ChDAv showed a lower ability to neutralize the coagulant and lethal activities of taipan venom. ChDAv was more immunogenic in rabbits than EDAv, probably due to the fact that chickens are phylogenetically more distant to rabbits than horses. This finding may explain why clearance from rabbit bloodstream was faster for chicken-IgY than for equine-IgG in a pharmacokinetic study. In conclusion, the production of anti-taipan antivenom was less effective when chicken egg yolks were used as source of immunoglobulins instead of horses.

ACS Style

Diego Navarro; Mariángela Vargas; María Herrera; Álvaro Segura; Aarón Gómez; Mauren Villalta; Nils Ramírez; David Williams; José María Gutiérrez; Guillermo León. Development of a chicken-derived antivenom against the taipan snake (Oxyuranus scutellatus) venom and comparison with an equine antivenom. Toxicon 2016, 120, 1 -8.

AMA Style

Diego Navarro, Mariángela Vargas, María Herrera, Álvaro Segura, Aarón Gómez, Mauren Villalta, Nils Ramírez, David Williams, José María Gutiérrez, Guillermo León. Development of a chicken-derived antivenom against the taipan snake (Oxyuranus scutellatus) venom and comparison with an equine antivenom. Toxicon. 2016; 120 ():1-8.

Chicago/Turabian Style

Diego Navarro; Mariángela Vargas; María Herrera; Álvaro Segura; Aarón Gómez; Mauren Villalta; Nils Ramírez; David Williams; José María Gutiérrez; Guillermo León. 2016. "Development of a chicken-derived antivenom against the taipan snake (Oxyuranus scutellatus) venom and comparison with an equine antivenom." Toxicon 120, no. : 1-8.

Journal article
Published: 01 January 2016 in Toxicology Letters
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The neuromuscular junction activity of Oxyuranus scutellatus venom and its presynaptic neurotoxin, taipoxin, and their neutralization by two antivenoms were examined in mouse phrenic nerve-diaphragm preparations. The action of taipoxin was also studied at 21 °C. The efficacy of the antivenoms was also assessed in an in vivo mouse model. Both antivenoms were effective in neutralizing the neuromuscular blocking activity in preincubation-type experiments. In experiments involving independent addition of venom and antivenoms, neutralization depended on the time interval between venom addition and antivenom application. When taipoxin was incubated for 5, 10 or 20 min at 21 °C, and antivenom added and temperature increased to 37 °C, neutralization was achieved only when the toxin was incubated for 5 or 10 min. The neutralization by the two antivenoms in an in vivo model showed that both whole IgG and F(ab′)2 antivenoms were effective in neutralizing lethality. Our findings highlight the very rapid action of taipan venom at the nerve terminal, and the poor capacity of antivenoms to revert neurotoxicity as the time interval between venom or taipoxin application and antivenom addition increased. Additionally the disparity between molecular masses of the active substances of the two antivenoms did not result in differences in neutralization.

ACS Style

María Herrera; Rita De Cássia De O. Collaço; Mauren Villalta; Álvaro Segura; Mariángela Vargas; Christine E. Wright; Owen K. Paiva; Teatulohi Matainaho; Simon D. Jensen; Guillermo León; David J. Williams; Léa Rodrigues-Simioni; José María Gutiérrez. Neutralization of the neuromuscular inhibition of venom and taipoxin from the taipan ( Oxyuranus scutellatus ) by F(ab′) 2 and whole IgG antivenoms. Toxicology Letters 2016, 241, 175 -183.

AMA Style

María Herrera, Rita De Cássia De O. Collaço, Mauren Villalta, Álvaro Segura, Mariángela Vargas, Christine E. Wright, Owen K. Paiva, Teatulohi Matainaho, Simon D. Jensen, Guillermo León, David J. Williams, Léa Rodrigues-Simioni, José María Gutiérrez. Neutralization of the neuromuscular inhibition of venom and taipoxin from the taipan ( Oxyuranus scutellatus ) by F(ab′) 2 and whole IgG antivenoms. Toxicology Letters. 2016; 241 ():175-183.

Chicago/Turabian Style

María Herrera; Rita De Cássia De O. Collaço; Mauren Villalta; Álvaro Segura; Mariángela Vargas; Christine E. Wright; Owen K. Paiva; Teatulohi Matainaho; Simon D. Jensen; Guillermo León; David J. Williams; Léa Rodrigues-Simioni; José María Gutiérrez. 2016. "Neutralization of the neuromuscular inhibition of venom and taipoxin from the taipan ( Oxyuranus scutellatus ) by F(ab′) 2 and whole IgG antivenoms." Toxicology Letters 241, no. : 175-183.

Editorials
Published: 27 October 2015 in BMJ
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Vulnerable populations need urgent access to effective and affordable treatments For many years snake bite experts have sought to raise the profile of this forgotten problem with public health authorities and donors. Lamentably, however, it has taken news of the departure of antivenom manufacturer Sanofi-Pasteur from the sub-Saharan African market to focus the spotlight on the calamity of snake bite among the world’s poorest people. Nevertheless, beyond this successful media storm,1 2 the reality is that for the majority of people bitten by snakes in Africa the loss of Sanofi’s FAV-Afrique polyvalent antivenom will mean little, if anything at all. This is because the product simply never reached them in the first place. In a region where median gross domestic product per capita is $550 (£360; €490), Sanofi’s product was simply too expensive (a four vial treatment cost about $540) and produced in insufficient quantities to meet the needs of more than a small part of the African continent.3 4 The harsh fact is that the continent is largely devoid of safe, effective, and affordable treatments for something that is eminently treatable. For decades there have …

ACS Style

David J Williams. Snake bite: a global failure to act costs thousands of lives each year. BMJ 2015, 351, h5378 .

AMA Style

David J Williams. Snake bite: a global failure to act costs thousands of lives each year. BMJ. 2015; 351 ():h5378.

Chicago/Turabian Style

David J Williams. 2015. "Snake bite: a global failure to act costs thousands of lives each year." BMJ 351, no. : h5378.