Array ( [0] => {{short description|Antiparasitic drugs that expel parasitic worms (helminths) from the body}} [1] => [[File:Anthelmintic effect of papain on Heligmosomoides bakeri.ogv|thumb|Anthelmintic effect of [[papain]] on ''[[Heligmosomoides bakeri]]'']] [2] => '''Anthelmintics''' or '''antihelminthics''' are a group of [[antiparasitic|antiparasitic drugs]] that expel parasitic worms ([[helminths]]) and other internal parasites from the body by either stunning or killing them and without causing significant damage to the host. They may also be called '''vermifuges''' (those that stun) or '''vermicides''' (those that kill). Anthelmintics are used to treat people who are infected by helminths, a condition called [[helminthiasis]]. These drugs are also used to treat infected animals, particularly small [[Ruminant|ruminants]] such as [[Goat|goats]] and [[sheep]]. [3] => [4] => Anthelmintic medication is also used in [[mass deworming]] campaigns of school-aged children in many developing countries.{{cite book |author= WHO |year=2006|title= Preventive chemotherapy in human helminthiasis: coordinated use of anthelminthic drugs in control interventions: a manual for health professionals and programme managers| url= http://whqlibdoc.who.int/publications/2006/9241547103_eng.pdf |publisher= WHO Press, World Health Organization, Geneva, Switzerland |pages=1–61 |isbn= 9241547103}}{{cite journal|last1=Albonico|first1=Marco|last2=Allen|first2=Henrietta|last3=Chitsulo|first3=Lester|last4=Engels|first4=Dirk|last5=Gabrielli|first5=Albis-Francesco|last6=Savioli|first6=Lorenzo|last7=Brooker|first7=Simon|title=Controlling Soil-Transmitted Helminthiasis in Pre-School-Age Children through Preventive Chemotherapy|journal=PLOS Neglected Tropical Diseases|date=2008|volume=2|issue=3|pages=e126|doi=10.1371/journal.pntd.0000126|pmid=18365031|pmc=2274864 |doi-access=free }} Anthelmintics are also used for mass deworming of livestock. The drugs of choice for soil-transmitted helminths are [[mebendazole]] and [[albendazole]];{{Cite journal|last1=Taylor-Robinson|first1=David C.|last2=Maayan|first2=Nicola|last3=Donegan|first3=Sarah|last4=Chaplin|first4=Marty|last5=Garner|first5=Paul|date=11 September 2019|title=Public health deworming programmes for soil-transmitted helminths in children living in endemic areas|journal=The Cochrane Database of Systematic Reviews|volume=9|issue=11|pages=CD000371|doi=10.1002/14651858.CD000371.pub7|issn=1469-493X|pmc=6737502|pmid=31508807}} for [[schistosomiasis]] and [[tapeworm]]s it is [[praziquantel]].{{cite web|title=Helminth control in school-age children|url=http://whqlibdoc.who.int/publications/2011/9789241548267_eng.pdf?ua=1|website=World Health Organization|access-date=28 July 2015|date=2011}} [5] => [6] => ==Types== [7] => Many early treatments were herbal, such as the oil of herbs of the genus ''[[Chenopodium]]'' that were given as anthelmintic treatment for centuries. In 1908 it was found that the active constituent was [[ascaridole]].{{Cite journal |last=Bennet-Jenkins |first=E. |last2=Bryant |first2=C. |date=1996 |title=Novel sources of anthelmintics |url=https://pubmed.ncbi.nlm.nih.gov/8923141/ |journal=International Journal for Parasitology |volume=26 |issue=8-9 |pages=937–947 |doi=10.1016/s0020-7519(96)80068-3 |issn=0020-7519 |pmid=8923141}} From the 1920s to the 1970s, halogenated hydrocarbons were used in a string of continually more efficacious anthelmintics, until their underlying host toxicity was revealed. The modern broad-spectrum anthelmintics were developed by pharmaceutical companies that can afford the screening programs and testing systems that modern drug development involves.{{Cite journal |last=Williams |first=J. C. |date=November 1997b|title=Anthelmintic treatment strategies: current status and future |url=https://pubmed.ncbi.nlm.nih.gov/9460212/ |journal=Veterinary Parasitology |volume=72 |issue=3-4 |pages=461–470; discussion 470–477 |doi=10.1016/s0304-4017(97)00111-8 |issn=0304-4017 |pmid=9460212}} [8] => [9] => Historically, there have been three main classes of broad-spectrum anthelmintics.{{Cite journal |last=Gilleard |first=John Stuart |date=October 2006 |title=Understanding anthelmintic resistance: the need for genomics and genetics |url=https://pubmed.ncbi.nlm.nih.gov/16889782/ |journal=International Journal for Parasitology |volume=36 |issue=12 |pages=1227–1239 |doi=10.1016/j.ijpara.2006.06.010 |issn=0020-7519 |pmid=16889782}} These are benzimidazoles, [[imidazothiazoles]]/tetrahydropyrimidines, and macrocyclic lactones. [10] => [[File:Benzimidazole structure.png|thumb|The benzimidazole nucleus]] [11] => * [[Benzimidazoles]] disrupt parasitic worms' [[Microtubule|microtubules]], a critical part of their cells' [[Cytoskeleton|cytoskeletons]]. Drugs in this category include: [12] => ** [[Albendazole]] – effective against [[Strongyloides stercoralis|threadworms]], [[roundworms]], [[whipworms]], [[tapeworms]], [[hookworms]] [13] => ** [[Mebendazole]] – effective against various nematodes [14] => ** [[Thiabendazole]] – effective against various nematodes [15] => ** [[Fenbendazole]] – effective against various parasites [16] => ** [[Triclabendazole]] – effective against [[liver fluke]]s [17] => ** [[Flubendazole]] – effective against most intestinal parasites [18] => * Imidathiazoles/tetrahydropyrimidines are [[nicotinic acetylcholine receptor]] [[Agonist|agonists]], including: [19] => ** [[Levamisole]] [20] => ** [[Pyrantel pamoate]] – effective against most parasitic nematodes of the [[Gastrointestinal tract|GIT]] [21] => * Macrocyclic lactones are [[Glutamic acid|glutamate]]-gated [[chloride channel]] agonists, and include: [22] => ** [[Avermectins]] (including [[ivermectin]] and [[moxidectin]]) - effective against most common intestinal worms, except tapeworms, for which [[praziquantel]] is commonly used in conjunction for mass dewormings [23] => * Drugs not members of these three main categories include: [24] => ** [[Diethylcarbamazine]] – effective against ''[[Wuchereria bancrofti]]'', ''[[Brugia malayi]]'', ''[[Brugia timori]]'', and ''[[Loa loa]]'' [25] => ** [[Salicylanilide]] – mitochondrial un-couplers such as [[Niclosamide]] and [[Oxyclozanide]], and are used only for flatworm infections [26] => ** [[Nitazoxanide]] – readily kills ''[[Ascaris lumbricoides]]'',{{cite journal | vauthors = Hagel I, Giusti T | title = Ascaris lumbricoides: an overview of therapeutic targets | journal = Infect Disord Drug Targets | volume = 10 | issue = 5 | pages = 349–67 | date = October 2010 | pmid = 20701574 | doi = 10.2174/187152610793180876| quote = new anthelmintic alternatives such as tribendimidine and Nitazoxanide have proved to be safe and effective against A. lumbricoides and other soil-transmitted helminthiases in human trials.}} and also possesses antiprotozoal effects.{{cite web |vauthors=Shoff WH |veditors=Chandrasekar PH, Talavera F, King JW | title=Cyclospora Medication | url=http://emedicine.medscape.com/article/236105-medication | website=Medscape | publisher=WebMD | access-date=11 January 2016 | date=5 October 2015 | quote=Nitazoxanide, a 5-nitrothiazole derivative with broad-spectrum activity against helminths and protozoans, has been shown to be effective against C cayetanensis, with an efficacy 87% by the third dose (first, 71%; second 75%). Three percent of patients had minor side effects.}} This is also an [[ascaricides|ascaricide]]. [27] => ** [[Oxamniquine]] – effective against [[flatworms]] (e.g., tapeworms and [[schistosoma]]) [28] => ** [[Praziquantel]] – effective against [[flatworms]] (e.g., tapeworms and [[schistosoma]]) [29] => ** Octadepsipeptides (e.g. [[Emodepside]]) – effective against a variety of gastrointestinal helminths [30] => ** Monepantel (aminoacetonitrile class) - effective against a variety of nematodes including those resistant to other anthelmintic classes [31] => ** Spiroindoles (e.g. derquantel) - effective against a variety of nematodes including those resistant to other anthelmintic classes [32] => ** [[Artemisinin]] – shows anthelmintic activity[https://pubag.nal.usda.gov/pubag/downloadPDF.xhtml?id=48686&content=PDF Veterinary Parasitology] [33] => [34] => ==Anthelmintic resistance== [35] => Anthelmintic resistance occurs when a heritable genetic change occurs in the parasite's DNA, rendering it insensitive to a previously effective anthelmintic drug. This is a particularly serious problem in helminth parasites of small ruminant farm animals. There are many factors that contribute to anthelmintic resistance, such as frequent, mass anthelmintic treatment, underdosing, treating repeatedly with only one anthelmintic, and resistance being transmitted during transfer of animals. Anthelmintic resistance in parasites is widespread; drug resistance exists in all livestock hosts and to all anthelmintic drug classes.{{Cite journal |last=Kaplan |first=Ray M. |date=October 2004 |title=Drug resistance in nematodes of veterinary importance: a status report |url=https://pubmed.ncbi.nlm.nih.gov/15363441/ |journal=Trends in Parasitology |volume=20 |issue=10 |pages=477–481 |doi=10.1016/j.pt.2004.08.001 |issn=1471-4922 |pmid=15363441}} This is a major threat to the sustainability of modern ruminant livestock production, resulting in reduced productivity, compromised animal health and welfare,{{Cite journal |last=Wolstenholme |first=Adrian J. |last2=Fairweather |first2=Ian |last3=Prichard |first3=Roger |last4=von Samson-Himmelstjerna |first4=Georg |last5=Sangster |first5=Nicholas C. |date=October 2004 |title=Drug resistance in veterinary helminths |url=https://pubmed.ncbi.nlm.nih.gov/15363440/ |journal=Trends in Parasitology |volume=20 |issue=10 |pages=469–476 |doi=10.1016/j.pt.2004.07.010 |issn=1471-4922 |pmid=15363440}} and increased greenhouse gas emissions through increased parasitism and farm inputs. A database of published and unpublished European AR research on gastrointestinal [[nematodes]] was collated in 2020. A total of 197 publications were available for analysis, representing 535 studies in 22 countries and spanning the period 1980–2020. Results in sheep and goats since 2010 reveal an average prevalence of resistance to [[benzimidazoles]] of 86%, [[moxidectin]] 52%, and [[levamisole]] 48%. All major gastrointestinal [[nematodes|nematode]] genera survived treatment in various studies. In cattle, prevalence of anthelminthic resistance varied between anthelmintic classes from 0–100% (benzimidazoles and macrocyclic lactones), 0–17% (levamisole) and 0–73% (moxidectin), and both ''[[Cooperia (nematode)|Cooperia]]'' and ''[[Ostertagia]]'' survived treatment.{{cite journal|last1=Rose Vineer|first1=Hannah|last2=Morgan|first2=Eric R.|last3=Hertzberg|first3=Hubertus|last4=Bartley|first4=David J.|last5=Bosco|first5=Antonio|last6=Charlier|first6=Johannes|last7=Chartier|first7=Christophe|last8=Claerebout|first8=Edwin|last9=de Waal|first9=Theo|last10=Hendrickx|first10=Guy|last11=Hinney|first11=Barbara|last12=Höglund|first12=Johan|last13=Ježek|first13=Jožica|last14=Kašný|first14=Martin|last15=Keane|first15=Orla M.|last16=Martínez-Valladares|first16=María|last17=Mateus|first17=Teresa Letra|last18=McIntyre|first18=Jennifer|last19=Mickiewicz|first19=Marcin|last20=Munoz|first20=Ana Maria|last21=Phythian|first21=Clare Joan|last22=Ploeger|first22=Harm W.|last23=Rataj|first23=Aleksandra Vergles|last24=Skuce|first24=Philip J.|last25=Simin|first25=Stanislav|last26=Sotiraki|first26=Smaragda|last27=Spinu|first27=Marina|last28=Stuen|first28=Snorre|last29=Thamsborg|first29=Stig Milan|last30=Vadlejch|first30=Jaroslav|last31=Varady|first31=Marian|last32=von Samson-Himmelstjerna|first32=Georg|last33=Rinaldi|first33=Laura|title=Increasing importance of anthelmintic resistance in European livestock: creation and meta-analysis of an open database|journal=Parasite|volume=27|year=2020|pages=69|issn=1776-1042|doi=10.1051/parasite/2020062|pmid=33277891|pmc=7718593|doi-access=free}} {{open access}} However, resistance is not seen as often in the parasitic helminths that affect cattle, compared to sheep. Reasons for this include the fact that cattle receive anthelminthic drugs less frequently than sheep, and the different nature of their faecal pats that could leave different numbers of resistant infective larvae on the pasture. Unlike sheep, cattle can develop sufficient immunoprotection against such parasites.{{Cite journal |last=Sager |first=Heinz |last2=Hosking |first2=Barry |last3=Bapst |first3=Béatrice |last4=Stein |first4=Philip |last5=Vanhoff |first5=Kathleen |last6=Kaminsky |first6=Ronald |date=2009-01-22 |title=Efficacy of the amino-acetonitrile derivative, monepantel, against experimental and natural adult stage gastro-intestinal nematode infections in sheep |url=https://pubmed.ncbi.nlm.nih.gov/19019553/ |journal=Veterinary Parasitology |volume=159 |issue=1 |pages=49–54 |doi=10.1016/j.vetpar.2008.10.006 |issn=0304-4017 |pmid=19019553}} [36] => [37] => The ability of parasites to survive treatments that are generally effective at the recommended doses is a major threat to the future control of worm parasites in small ruminants and horses. This is especially true of [[nematode]]s, and has helped spur development of [[aminoacetonitrile]] derivatives for treatment against drug-resistant nematodes, as well as exploration of [[doxycycline]] to kill their endosymbiotic ''[[Wolbachia]]'' bacteria.{{cn|date=April 2023}} [38] => [39] => Both ''in vitro'' (egg hatch assay, larval development test, larval motility test, [[polymerase chain reaction]] and ''in vivo'' methods ([[Faecal egg count reduction test|fecal egg count reduction test]]) can be used to detect anthelmintic resistance.[11]   [40] => [41] => Treatment with an antihelminthic drug kills worms whose phenotype renders them susceptible to the drug, but [[drug resistance|resistant]] parasites survive and pass on their "resistance" genes. Resistant varieties accumulate, and treatment failure finally occurs.{{Cite journal |last=Blackhall |first=William J. |last2=Prichard |first2=Roger K. |last3=Beech |first3=Robin N. |date=2008-03-25 |title=P-glycoprotein selection in strains of Haemonchus contortus resistant to benzimidazoles |url=https://pubmed.ncbi.nlm.nih.gov/18241994/ |journal=Veterinary Parasitology |volume=152 |issue=1-2 |pages=101–107 |doi=10.1016/j.vetpar.2007.12.001 |issn=0304-4017 |pmid=18241994}} [42] => [43] => The ways in which anthelmintics are used have contributed to a major anthelmintic resistance issue worldwide. From the 1950s to the 1980s, new classes of effective and inexpensive anthelmintics were made available every decade, leading to excessive use throughout agriculture and disincentivizing alternative anti-nematodal strategies. Developing new anthelmintics is time consuming and expensive therefore, it is important to use the ones that currently exist in a way that will minimize or prevent the development of anthelmintic resistance.[11] Some of these methods are ensuring animals are not being underdosed, rotating the anthelmintics that are being used, and rotation of grazing land to reduce the parasite population.{{Cite journal |last=Praslicka |first=J. |last2=Várady |first2=M. |last3=Corba |first3=J. |last4=Veselý |first4=L. |date=March 1994 |title=A survey of anthelmintic resistance in Slovakia |url=https://pubmed.ncbi.nlm.nih.gov/8030184/ |journal=Veterinary Parasitology |volume=52 |issue=1-2 |pages=169–171 |doi=10.1016/0304-4017(94)90048-5 |issn=0304-4017 |pmid=8030184}} Other methods include using a combination of multiple different anthelmintics, and the use of ''refugia'' based strategies. R''efugia'' refers to the portion of the parasite population not being exposed to anthelmintics. This population is therefore not undergoing selection for resistance. Use of ''refugia'' helps to slow down the speed of evolution of resistance to anthelmintic drugs.{{Cite journal |last=Pomroy |first=W. E. |date=December 2006 |title=Anthelmintic resistance in New Zealand: a perspective on recent findings and options for the future |url=https://pubmed.ncbi.nlm.nih.gov/17151723/ |journal=New Zealand Veterinary Journal |volume=54 |issue=6 |pages=265–270 |doi=10.1080/00480169.2006.36709 |issn=0048-0169 |pmid=17151723}} Due to the problem of anthelmintic resistance, research into alternatives is continuing, including in the field of [[Drug design|rational drug design]].{{Cite thesis |title=An investigation into the interdomain region of Caenorhabditis elegans fatty acid synthase and its implications as a drug target |url=https://opal.latrobe.edu.au/articles/thesis/An_investigation_into_the_interdomain_region_of_Caenorhabditis_elegans_fatty_acid_synthase_and_its_implications_as_a_drug_target/21841695/1 |publisher=La Trobe |date=2009-01-01 |degree=thesis |language=en |first=Christopher David |last=Sgro}} [44] => [45] => == See also == [46] => * ''[[Dysphania ambrosioides]]'', an herb native to Central and South America [47] => * [[Santonin]], a historical anthelmintic no longer in use [48] => * [[4-Hexylresorcinol]] [49] => [50] => ==References== [51] => {{reflist|30em}}{{Cite journal |last=Shalaby |first=Hatem A. |date=2013 |title=Anthelmintics Resistance; How to Overcome it? |journal=Iranian Journal of Parasitology |volume=8 |issue=1 |pages=18–32 |issn=1735-7020 |pmc=3655236 |pmid=23682256}}{{Cite journal |last1=Fissiha |first1=Workye |last2=Kinde |first2=Mebrie Zemene |date=2021-12-15 |title=Anthelmintic Resistance and Its Mechanism: A Review |journal=Infection and Drug Resistance |volume=14 |pages=5403–5410 |doi=10.2147/IDR.S332378 |issn=1178-6973 |pmc=8687516 |pmid=34938088 |doi-access=free }} [52] => [53] => ==External links== [54] => * {{MeshName|Anthelmintics}} [55] => * Holden-Dye, L. and Walker, R.J.[http://www.wormbook.org/chapters/www_anthelminticdrugs/anthelminticdrugs.html Anthelmintic drugs] (November 2, 2007), WormBook, ed. The C. elegans Research Community, WormBook, doi/10.1895/wormbook.1.143.1 [56] => {{Major Drug Groups}} [57] => {{Anthelmintics}} [58] => [59] => {{Authority control}} [60] => [61] => [[Category:Anthelmintics|*]] [62] => [[Category:Articles containing video clips]] [] => )
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Anthelmintic

Anthelmintics or antihelminthics are a group of antiparasitic drugs that expel parasitic worms (helminths) and other internal parasites from the body by either stunning or killing them and without causing significant damage to the host. They may also be called vermifuges (those that stun) or vermicides (those that kill).

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