Editing Australian funnel-web spider (section)

==Medical significance==
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Australian funnel-web spiders are one of the most medically significant groups of spiders in the world and are regarded by some to be the most deadly, both in terms of clinical cases and venom toxicity.<ref name="MJA2005-Isbister">{{cite journal |vauthors=Isbister G, Gray M, Balit C, Raven R, Stokes B, Porges K, Tankel A, Turner E, White J, Fisher M | title = Funnel-web spider bite: a systematic review of recorded clinical cases | journal = Med J Aust | volume = 182 | issue = #8 | pages = 407–11 | year = 2005 | pmid = 15850438|url=https://www.mja.com.au/journal/2005/182/8/funnel-web-spider-bite-systematic-review-recorded-clinical-cases?iframe=true | doi=10.5694/j.1326-5377.2005.tb06760.x| hdl = 2440/17349 | s2cid = 18066524 | hdl-access = free }}</ref><ref name="Vetter">{{cite journal |author1=Vetter, Richard S. |author2=Isbister, Geoffrey K. |title=Medical Aspects of Spider Bites |journal=[[Annual Review of Entomology]] |volume=53 |pages=409–29 |year=2008 |pmid=17877450 |doi= 10.1146/annurev.ento.53.103106.093503}}</ref> Six species have caused severe injuries to human victims: the Sydney funnel-web spider (''[[Sydney funnel-web spider|Atrax robustus]]''), the northern tree-dwelling funnel-web spider (''[[Hadronyche formidabilis]]''), the southern tree-dwelling funnel-web spider (''[[Hadronyche cerberea|H. cerberea]]''),<ref name="lancet">{{cite journal|author1=Isbister, Geoffrey K. |author2=Fan, Hui Wen |year=2011|title=Spider Bite|journal=The Lancet|volume=378|issue=9808|pages=2039–47|doi=10.1016/S0140-6736(10)62230-1|pmid=21762981|s2cid=27408940 }}</ref> the Blue Mountains funnel-web spider (''[[Hadronyche versuta|H. versuta]]''), the Darling Downs funnel-web spider (''[[Hadronyche infensa|H. infensa]]''), and the Port Macquarie funnel-web spider (''[[Hadronyche macquariensis|H. macquariensis]]'').

Examination of [[Spider bite|bite]] records has implicated wandering males in most, if not all, fatal Australian funnel-web spider bites to humans. Adult males, recognised by the modified terminal segment of the [[Pedipalp|palp]], tend to wander during the warmer months of the year, looking for receptive females for mating.<ref>{{cite journal |vauthors=Isbister G, Gray M | title = Bites by Australian mygalomorph spiders (Araneae, Mygalomorphae), including funnel-web spiders (Atracinae) and mouse spiders (Actinopodidae: Missulena spp) | journal = Toxicon | volume = 43 | issue = #2 | pages = 133–40 | year = 2004 | pmid = 15019472 | doi = 10.1016/j.toxicon.2003.11.009| bibcode = 2004Txcn...43..133I }}</ref> They are attracted to water, hence are often found in swimming pools, into which they often fall while wandering. The spiders can survive immersion in water for several hours and can deliver a bite when removed from the water.<ref name=gray>Gray, M. "The Distribution of Funnel-Web Spiders in Australia" in ''Toxic Plants and Animals: A Guide for Australia''. Queensland Museum Press, 1987. Page 313-22</ref> They also show up in garages and yards in suburban Sydney. Contrary to a commonly held belief, Australian funnel-web spiders are not able to jump, although they can run quickly.<ref name=gray/>

While some very venomous spiders do not always inject venom when they bite, these spiders most often do.{{Citation needed|date=July 2009|reason=Give dry bites more frequently, or less frequently?}} The volume of venom delivered to large animals is often small, possibly due to the angle of the fangs, which are not horizontally opposed, and because contact is often brief before the spider is brushed off. About 10 to 25% of bites are claimed to produce significant toxicity,<ref name="MJA2005-Isbister"/> but the likelihood cannot be predicted and all bites should be treated as potentially life-threatening.

Bites from Sydney funnel-web spiders have caused 13 documented deaths (seven in children).<ref name="MJA2005-Isbister"/> In all cases where the sex of the biting spider could be determined, it was found to be the male of the species.<ref name="ClinExp2002-Nicholson">{{cite journal |vauthors=Nicholson G, Graudins A | title = Spiders of medical importance in the Asia-Pacific: atracotoxin, latrotoxin and related spider neurotoxins | journal = Clin Exp Pharmacol Physiol | volume = 29 | issue = #9 | pages = 785–94 | year = 2002 | pmid = 12165044 | doi = 10.1046/j.1440-1681.2002.03741.x| s2cid = 12620544 }}</ref> One member of the genus ''Hadronyche'', the northern tree-dwelling funnel-web spider, has also been claimed to cause fatal envenomation,<ref name=csiro1/> but to date, this lacks the support of a specific medical report. Assays of venom from several ''Hadronyche'' species have shown it to be similar to ''Atrax'' venom.

In 2021 researchers from the [[University of Queensland]] announced that the venom from funnel-web spiders found on [[Fraser Island]] contains the molecule [[Hi1a]] that could block the cell death message after a heart attack, protecting the heart after major injury and potentially preventing or minimising muscle damage.<ref>{{Cite web|last=Hamilton-Smith|first=Lexy|date=2021-07-15|title=This funnel-web spider from Queensland has one of the world's deadliest venoms. It could also save lives|url=https://www.abc.net.au/news/2021-07-16/qld-funnel-web-venom-life-saving-treatment-heart-attack-fraser-i/100293714|url-status=live|access-date=2021-07-16|website=www.abc.net.au|language=en-AU|archive-url=https://web.archive.org/web/20210715213808/https://www.abc.net.au/news/2021-07-16/qld-funnel-web-venom-life-saving-treatment-heart-attack-fraser-i/100293714 |archive-date=2021-07-15 }}</ref>

===Toxins===
Many different [[toxin]]s are found in the venom of ''Atrax'' and ''Hadronyche'' spiders. Collectively, these [[spider toxin]]s are given the name atracotoxins (ACTX), as all these spiders belong to the family Atracidae. The first toxins isolated were the [[Delta atracotoxin|δ-ACTX toxins]] present in the venom of both ''A. robustus'' (δ-ACTX-Ar1, formerly known as [[robustoxin]] or atracotoxin) and ''H. versuta'' (δ-ACTX-Hv1a, formerly known as [[versutoxin]]). Both of these toxins produce the same effects in monkeys as those seen in humans, suggesting that they are responsible for the physiological effects seen with crude venom.<ref name="ClinExp2002-Nicholson"/>

[[File:Atrax robustus.jpg|thumb|Female Sydney funnel-web spider (''A. robustus'') in a warning posture]]
These toxins are thought to induce spontaneous, repetitive firing and prolongation of action potentials, resulting in continuous acetylcholine neurotransmitter release from somatic and autonomic [[presynaptic]] nerve endings. This leads to slower [[voltage-gated sodium channel]] inactivation and a hyperpolarizing shift in the voltage-dependence of activation. This in turn inhibits neurally mediated transmitter release, resulting in a surge of endogenous [[acetylcholine]], [[noradrenaline]], and [[adrenaline]].<ref>{{cite journal |vauthors=Harris J, Sutherland S, Zar M | title = Actions of the crude venom of the Sydney funnel-web spider (''Atrax robustus'') on autonomic neuromuscular transmission | journal = Br J Pharmacol | volume = 72 | issue = #2 | pages = 335–40 | year = 1981 | pmid = 6260279 | pmc = 2071519 | doi=10.1111/j.1476-5381.1981.tb09132.x}}</ref>

Although extremely toxic to primates, the venom appears to be fairly harmless to many other animals. These animals may be resistant to the venom's effects due to the presence of [[Immunoglobulin G|IgG]], and possibly cross-linked IgG and [[IgM]] inactivating factors in their [[blood plasma]] that bind to the toxins responsible and neutralise them.<ref>{{cite journal |vauthors=Sheumack D, Comis A, Claassens R, Mylecharane E, Spence I, Howden M | title = An endogenous antitoxin to the lethal venom of the funnel web spider, ''Atrax robustus'', in rabbit sera | journal = Comp Biochem Physiol C | volume = 99 | issue = #1–2 | pages = 157–61 | year = 1991 | pmid = 1675965 | doi = 10.1016/0742-8413(91)90093-9}}</ref>

The female's venom was thought to be only about a sixth as potent to humans as that of the male's.<ref>{{cite journal | author = Wiener S | title = The Sydney funnel-web spider (''Atrax robustus''): II. Venom yield and other characteristics of spiders in captivity | journal = Med J Aust | volume = 46 | issue = #2 | pages = 678–82 | year = 1959| pmid = 13844638| doi = 10.5694/j.1326-5377.1959.tb129426.x | s2cid = 2131853 }}</ref><ref>{{Cite book |last=Sutherland |first=Struan K. |title=Australian Animal Toxins |publisher=Oxford University Press |year=2001 |isbn=978-0195506433 |location=Melbourne |language=EN}}</ref> The bite of a female or juvenile may still be serious, but considerable variability occurs in venom toxicity between species, together with assumed degrees of inefficiency in the method of venom delivery.

===Symptoms===
Envenomation symptoms observed following bites by these spiders are very similar. The bite is initially very painful, due to the size of the fangs penetrating the skin.<ref name="lancet"/> Puncture marks and local bleeding are also usually visible. If substantial envenomation occurs, symptoms generally occur within minutes and progress rapidly.

Early symptoms of systemic envenomation include [[goose bumps]], [[Perspiration|sweating]], [[Paresthesia|tingling around the mouth and tongue]], [[Fasciculation|twitching]] (initially facial and [[Intercostal muscle|intercostal]]), salivation, [[Lacrimation|watery eyes]], [[Tachycardia|elevated heart rate]], and [[Hypertension|elevated blood pressure]]. As systemic envenomation progresses, symptoms include [[nausea]], [[vomiting]], [[dyspnoea|shortness of breath]] (caused by airway obstruction), [[Psychomotor agitation|agitation]], [[confusion]], writhing, grimacing, [[muscle spasm]]s, [[pulmonary oedema]] (of [[neurogenic]] or hypertensive origin), [[metabolic acidosis]], and extreme hypertension. The final stages of severe envenomation include [[Mydriasis|dilation of the pupils]] (often [[Blown pupil|fixed]]), uncontrolled generalised muscle twitching, [[unconsciousness]], elevated [[intracranial pressure]], and death. Death generally is a result of progressive [[hypotension]] or possibly elevated intracranial pressure consequent on [[cerebral oedema]].<ref name="MJA2005-Isbister"/><ref name="UoS">[https://web.archive.org/web/20110228150754/http://www.anaes.med.usyd.edu.au/venom/spiders.html Australian Spider and Insect Bites]; [[University of Sydney]]</ref><ref>{{cite journal |vauthors=Torda T, Loong E, Greaves I | title = Severe lung oedema and fatal consumption coagulopathy after funnel-web bite | journal = Med J Aust | volume = 2 | issue = #8 | pages = 442–4 | year = 1980 | pmid = 7010098| doi = 10.5694/j.1326-5377.1980.tb131914.x | s2cid = 20647927 }}</ref>

The onset of severe envenomation can be rapid. In one prospective study, the median time to onset of envenomation was 28 minutes, with only two cases having onset after two hours (both had pressure immobilisation bandages applied).<ref name="MJA2005-Isbister"/> Death may occur within a period ranging from 15 minutes<ref name="ClinExp2002-Nicholson"/> (this occurred when a small child was bitten) to three days.

===Treatment===
Owing to the severity of symptoms, and the speed with which they progress, in areas where these spiders are known to live, all bites from large, black spiders should be treated as though they were caused by Australian funnel-web spiders. First-aid<ref>{{Cite web |last= |first= |date=2022-09-22 |title=The Funnel-web Spider: Australia's Most Dangerous Arachnid |url=https://www.australiawidefirstaid.com.au/resources/funnel-web-spider |access-date=2023-09-29 |website=Australia Wide First Aid |language=en}}</ref> treatment for a suspected Australian funnel-web spider bite consists of immediately applying a [[Pressure immobilisation technique|pressure immobilization]]<ref>{{Cite web |last= |first= |date=2014-03-06 |title=Pressure Immobilisation Technique |url=https://www.australiawidefirstaid.com.au/resources/pressure-immobilisation-technique |access-date=2023-09-29 |website=Australia Wide First Aid |language=en}}</ref> bandage; a technique which consists of wrapping the bitten limb with a crepe bandage, as well as applying a [[Splint (medicine)|splint]] to limit movement of the limb. This technique was originally developed for [[snakebite]]s, but has also been shown to be effective at slowing venom movement and preventing systemic envenomation in case of an Australian funnel-web spider bite. Some evidence suggests that periods of prolonged localisation may slowly inactivate the venom.<ref name="UoS" /><ref>{{cite journal |vauthors=Sutherland S, Duncan A | title = New first-aid measures for envenomation: with special reference to bites by the Sydney funnel-web spider (''Atrax robustus'') | journal = Med J Aust | volume = 1 | issue = #8 | pages = 378–9 | year = 1980 | pmid = 6771503| doi = 10.5694/j.1326-5377.1980.tb134931.x | s2cid = 24213819 }}</ref>

Further supportive care may be necessary, but the mainstay of treatment is antivenom. Venom from the male Sydney funnel-web spider (''A. robustus'') is used in producing the antivenom, but it appears to be effective against the venom of all species of atracids.<ref>{{cite journal |vauthors=Graudins A, Wilson D, Alewood P, Broady K, Nicholson G | title = Cross-reactivity of Sydney funnel-web spider antivenom: neutralization of the ''in vitro'' toxicity of other Australian funnel-web (''Atrax'' and ''Hadronyche'') spider venoms | journal = Toxicon | volume = 40 | issue = #3 | pages = 259–66 | year = 2002 | pmid = 11711122 | doi = 10.1016/S0041-0101(01)00210-0| bibcode = 2002Txcn...40..259G }}</ref> Australian funnel-web spider antivenom has also been shown, ''in vitro'', to reverse the effects of eastern [[mouse spider]] (''Missulena bradleyi'') venom.<ref>{{cite journal |vauthors=Rash L, Birinyi-Strachan L, Nicholson G, Hodgson W | title = Neurotoxic activity of venom from the Australian eastern mouse spider (''Missulena bradleyi'') involves modulation of sodium channel gating | journal = Br J Pharmacol | volume = 130 | issue = #8 | pages = 1817–24 | year = 2000 | pmid = 10952670 | pmc = 1572261 | doi = 10.1038/sj.bjp.0703494}}</ref>

Before the introduction of antivenom, envenomation resulted in significant morbidity and mortality.<ref>{{cite journal |vauthors=Isbister G, Graudins A, White J, Warrell D | title = Antivenom treatment in arachnidism | journal = J Toxicol Clin Toxicol | volume = 41 | issue = #3 | pages = 291–300 | year = 2003 | pmid = 12807312 | doi = 10.1081/CLT-120021114| s2cid = 37946164 }}</ref> The purified rabbit [[Immunoglobulin G|IgG]] antivenom was developed in 1981 through a team effort led by Dr. [[Struan Sutherland]], head of immunology at the [[CSL Limited|Australian Commonwealth Serum Laboratories]] in [[Melbourne]].<ref>{{cite journal |vauthors=Fisher M, Raftos J, McGuinness R, Dicks I, Wong J, Burgess K, Sutherland S | title = Funnel-web spider (''Atrax robustus'') antivenom. 2. Early clinical experience | journal = Med J Aust | volume = 2 | issue = #10 | pages = 525–6 | year = 1981 | pmid = 7321948| doi = 10.5694/j.1326-5377.1981.tb112973.x }}</ref> The antivenom is fast-acting and highly and globally effective.<ref>{{cite journal |vauthors=Hartman L, Sutherland S | title = Funnel-web spider (''Atrax robustus'') antivenom in the treatment of human envenomation | journal = Med J Aust | volume = 141 | issue = #12–13 | pages = 796–9 | year = 1984| pmid = 6503783| doi = 10.5694/j.1326-5377.1984.tb132953.x | s2cid = 22059048 }}</ref> Antivenom therapy has shortened the course of envenomation effects; prior to its availability, the average length of hospital treatment for severe bites was about 14 days. Today, antivenom-treated patients are commonly discharged from hospital within one to three days.<ref name="ClinExp2002-Nicholson"/> No deaths are known since it became available.<ref name="MJA2005-Isbister"/>