Anthelmintic

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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). 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 ruminants such as goats and sheep. [1]

Contents

Anthelmintic medication is also used in mass deworming campaigns of school-aged children in many developing countries. [2] [3] Anthelmintics are also used for mass deworming of livestock. The drugs of choice for soil-transmitted helminths are mebendazole and albendazole; [4] for schistosomiasis and tapeworms it is praziquantel. [5]

Types

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. [6] 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. [6] The modern broad-spectrum anthelmintics were developed by pharmaceutical companies that can afford the screening programs and testing systems that modern drug development involves. [6] [7]

Historically, there have been three main classes of broad-spectrum anthelmintics. [8] These are benzimidazoles, imidazothiazoles/tetrahydropyrimidines, and macrocyclic lactones.

Anthelmintic resistance

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. [12] 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. [12] Anthelmintic resistance in parasites is widespread; drug resistance exists in all livestock hosts and to all anthelmintic drug classes. [13] This is a major threat to the sustainability of modern ruminant livestock production, resulting in reduced productivity, compromised animal health and welfare, [12] and increased greenhouse gas emissions through increased parasitism and farm inputs. [14] 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%, macrocyclic lactones except moxidectin 52%, levamisole 48%, and moxidectin 21%. All major gastrointestinal 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 and Ostertagia survived treatment. [14] 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. [7] Unlike sheep, cattle can develop sufficient immunoprotection against such parasites. [15]

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 nematodes, 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.[ citation needed ]

Both in vitro (egg hatch assay, larval development test, larval motility test, polymerase chain reaction and in vivo methods (fecal egg count reduction test) can be used to detect anthelmintic resistance.[11]  

Treatment with an antihelminthic drug kills worms whose phenotype renders them susceptible to the drug, but resistant parasites survive and pass on their "resistance" genes. Resistant varieties accumulate, and treatment failure finally occurs. [16]

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. [13] 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. [1] Other methods include using a combination of multiple different anthelmintics, and the use of refugia based strategies. Refugia 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. [17]

See also

Related Research Articles

<span class="mw-page-title-main">Parasitology</span> Study of parasites, their hosts, and the relationship between them

Parasitology is the study of parasites, their hosts, and the relationship between them. As a biological discipline, the scope of parasitology is not determined by the organism or environment in question but by their way of life. This means it forms a synthesis of other disciplines, and draws on techniques from fields such as cell biology, bioinformatics, biochemistry, molecular biology, immunology, genetics, evolution and ecology.

<span class="mw-page-title-main">Praziquantel</span> Medication

Praziquantel (PZQ), sold under the brandname Biltricide among others, is a medication used to treat a number of types of parasitic worm infections in mammals, birds, amphibians, reptiles, and fish. In humans specifically, it is used to treat schistosomiasis, clonorchiasis, opisthorchiasis, tapeworm infections, cysticercosis, echinococcosis, paragonimiasis, fasciolopsiasis, and fasciolosis. It should not be used for worm infections of the eye. It is taken by mouth.

<span class="mw-page-title-main">Abamectin</span> Insecticide and anti-parasitic worm chemical

Abamectin (also called avermectin B1) is a widely used insecticide and anthelmintic. Abamectin, is a member of the avermectin family and is a natural fermentation product of soil dwelling actinomycete Streptomyces avermitilis. Abamectin differs from ivermectin, the popular member of the avermectin family, by a double bond between carbons 22 and 25. Fermentation of Streptomyces avermitilis yields eight closely related avermectin homologs, with the B1a and B1b forms comprising the majority of the fermentation. The non-proprietary name, abamectin, refers to a mixture of B1a (~80%) and B1b (~20%). Out of all the avermectins, abamectin is the only one that is used both in agriculture and pharmaceuticals.

<span class="mw-page-title-main">Helminthiasis</span> Any macroparasitic disease caused by helminths

Helminthiasis, also known as worm infection, is any macroparasitic disease of humans and other animals in which a part of the body is infected with parasitic worms, known as helminths. There are numerous species of these parasites, which are broadly classified into tapeworms, flukes, and roundworms. They often live in the gastrointestinal tract of their hosts, but they may also burrow into other organs, where they induce physiological damage.

<span class="mw-page-title-main">Ivermectin</span> Medication for parasite infestations

Ivermectin is an antiparasitic drug. After its discovery in 1975, its first uses were in veterinary medicine to prevent and treat heartworm and acariasis. Approved for human use in 1987, it is used to treat infestations including head lice, scabies, river blindness (onchocerciasis), strongyloidiasis, trichuriasis, ascariasis and lymphatic filariasis. It works through many mechanisms to kill the targeted parasites, and can be taken by mouth, or applied to the skin for external infestations. It belongs to the avermectin family of medications.

<i>Haemonchus contortus</i> Species of roundworm

Haemonchus contortus, also known as the barber's pole worm, is a very common parasite and one of the most pathogenic nematodes of ruminants. Adult worms attach to abomasal mucosa and feed on the blood. This parasite is responsible for anemia, oedema, and death of infected sheep and goats, mainly during summer in warm, humid climates.

<i>Ascaridia galli</i> Species of roundworm

Ascaridia galli is a parasitic roundworm belonging to the phylum Nematoda. Nematodes of the genus Ascaridia are essentially intestinal parasites of birds. A. galli is the most prevalent and pathogenic species, especially in domestic fowl, Gallus domesticus. It causes ascaridiasis, a disease of poultry due to heavy worm infection, particularly in chickens and turkeys. It inhabits the small intestine, and can be occasionally seen in commercial eggs.

Egg hatch assay (EHA), also called an egg hatch test (EHT), is a method used to determine a given parasite's resistance to extant drug therapy.

<span class="mw-page-title-main">Moxidectin</span> Chemical compound

Moxidectin is an anthelmintic drug used in animals to prevent or control parasitic worms (helminths), such as heartworm and intestinal worms, in dogs, cats, horses, cattle and sheep. Moxidectin kills some of the most common internal and external parasites by selectively binding to a parasite's glutamate-gated chloride ion channels. These channels are vital to the function of invertebrate nerve and muscle cells; when moxidectin binds to the channels, it disrupts neurotransmission, resulting in paralysis and death of the parasite.

<span class="mw-page-title-main">Deworming</span> Use of anthelmintic drugs

Deworming is the giving of an anthelmintic drug to a human or animals to rid them of helminths parasites, such as roundworm, flukes and tapeworm. Purge dewormers for use in livestock can be formulated as a feed supplement that is eaten, a paste or gel that is deposited at the back of the animal's mouth, a liquid drench given orally, an injectable, or as a pour-on which can be applied to the animal's topline. In dogs and cats, purge dewormers come in many forms including a granular form to be added to food, pill form, chew tablets, and liquid suspensions.

<span class="mw-page-title-main">Oxfendazole</span> Chemical compound

Oxfendazole is a broad spectrum benzimidazole anthelmintic. Its main use is for protecting livestock against roundworm, strongyles and pinworms. Oxfendazole is the sulfoxide metabolite of fenbendazole.

<i>Teladorsagia circumcincta</i> Species of roundworm

Teladorsagia circumcincta is a nematode that is one of the most important parasites of sheep and goats. It was previously known as Ostertagia circumcincta and is colloquially known as the brown stomach worm. It is common in cool, temperate areas, such as south-eastern and south-western Australia and the United Kingdom. There is considerable variation among lambs and kids in susceptibility to infection. Much of the variation is genetic and influences the immune response. The parasite induces a type I hypersensitivity response which is responsible for the relative protein deficiency which is characteristic of severely infected animals. There are mechanistic mathematical models which can predict the course of infection. There are a variety of ways to control the infection and a combination of control measures is likely to provide the most effective and sustainable control.

<i>Parascaris equorum</i> Species of roundworm

Parascaris equorum is a species of ascarid that is the equine roundworm. Amongst horse owners, the parasites are colloquially called "Ascarids". This is a host-specific helminth intestinal parasite that can infect horses, donkeys, and zebras. Horses up to six months of age are the most susceptible to infection. After this time, infection rates begin to decline and is extremely uncommon in horses over twelve months of age. It cannot infect humans or other animals. It is yellow-white in color, and females can become as large as 15 inches (38 cm) in length. Found worldwide, P. equorum is one of the most difficult equine parasites to kill, requiring larger doses of more powerful anthelmintic medications than are needed for other equine parasites.

<i>Cooperia oncophora</i> Species of roundworm

Cooperia oncophora is one of the most common intestinal parasitic nematodes in cattle in temperate regions. Infections with C. oncophora may result in mild clinical symptoms, but can lead to weight loss and damage of the small intestine, especially when co-infections with other nematodes such as O. ostertagi occur. Infections are usually treated with broad-spectrum anthelmintics such as benzimidazole, but resistance to these drugs has developed in the last decades and is now very common. C. oncophora has a direct life cycle. Infective larvae are ingested by the host. The larvae grow to adults, which reproduce in the small intestines. Eggs are shed onto the pasture with the faeces, which leads to new infections. Co-infections with other gastro-intestinal nematodes such as O. ostertagi and H. contortus are common.

Ostertagia ostertagi, commonly known as the medium stomach worm or brown stomach worm, is a parasitic nematode of cattle. O. ostertagi can also be found to a lesser extent in sheep, goats, wild ruminants, and horses. It causes ostertagiosis, which is potentially fatal in cattle. It is found worldwide and is economically important to cattle industries, particularly those found in temperate climates.

The fecal egg count reduction test was suggested in the World Association for the Advancement of Veterinary Parasitology guideline for estimating the reduction in fecal egg counts and its corresponding confidence interval. The results of this test can be used to determine the anthelmintic resistance status of the animals.

<i>Cooperia</i> (nematode) Genus of roundworms

Cooperia is a genus of nematode from the Cooperiidae family that is one of the most common intestinal parasitic nematodes in cattle in temperate regions. Infections with Cooperia may result in mild clinical symptoms, but can lead to weight loss and damage of the small intestine, especially when co-infections with other nematodes such as Ostertagia ostertagi occur. Infections are usually treated with broad-spectrum anthelmintics such as benzimidazole, but resistance to these drugs has developed in the last decades and is now very common. Cooperia has a direct life cycle. Infective larvae are ingested by the host. The larvae grow to adults, which reproduce in the small intestines. Eggs are shed onto the pasture with the faeces, which leads to new infections. Co-infections with other gastro-intestinal nematodes such as O. ostertagi and Haemonchus contortus are common.

Parascaris univalens is a parasitic ascaridoid nematode that infects the gastrointestinal tracts of equines.

<span class="mw-page-title-main">Carlos Lanusse</span> Argentinean pharmacology researcher

Carlos E. Lanusse is an Argentine scientist and a professor of Pharmacology. He is the Director of the Veterinary Research Center and the Science and Technology Center of the Argentina National Council of Research in Tandil.

<span class="mw-page-title-main">Bunamidine</span> Chemical compound

Bunamidine is an anthelmintic drug used in veterinary medicine to treat infections by tapeworm parasites of the genus Taenia; thus it is classified as a taeniacide.

References

  1. 1 2 Praslicka, J.; Várady, M.; Corba, J.; Veselý, L. (March 1994). "A survey of anthelmintic resistance in Slovakia". Veterinary Parasitology. 52 (1–2): 169–171. doi:10.1016/0304-4017(94)90048-5. ISSN   0304-4017. PMID   8030184.
  2. ↑ WHO (2006). Preventive chemotherapy in human helminthiasis: coordinated use of anthelminthic drugs in control interventions: a manual for health professionals and programme managers (PDF). WHO Press, World Health Organization, Geneva, Switzerland. pp. 1–61. ISBN   9241547103.
  3. ↑ Albonico, Marco; Allen, Henrietta; Chitsulo, Lester; Engels, Dirk; Gabrielli, Albis-Francesco; Savioli, Lorenzo; Brooker, Simon (2008). "Controlling Soil-Transmitted Helminthiasis in Pre-School-Age Children through Preventive Chemotherapy". PLOS Neglected Tropical Diseases. 2 (3): e126. doi: 10.1371/journal.pntd.0000126 . PMC   2274864 . PMID   18365031.
  4. ↑ Taylor-Robinson, David C.; Maayan, Nicola; Donegan, Sarah; Chaplin, Marty; Garner, Paul (11 September 2019). "Public health deworming programmes for soil-transmitted helminths in children living in endemic areas". The Cochrane Database of Systematic Reviews. 9 (11): CD000371. doi:10.1002/14651858.CD000371.pub7. ISSN   1469-493X. PMC   6737502 . PMID   31508807.
  5. ↑ "Helminth control in school-age children" (PDF). World Health Organization. 2011. Retrieved 28 July 2015.
  6. 1 2 3 Bennet-Jenkins, E.; Bryant, C. (1996). "Novel sources of anthelmintics". International Journal for Parasitology. 26 (8–9): 937–947. doi:10.1016/s0020-7519(96)80068-3. ISSN   0020-7519. PMID   8923141.
  7. 1 2 Williams, J. C. (November 1997b). "Anthelmintic treatment strategies: current status and future". Veterinary Parasitology. 72 (3–4): 461–470, discussion 470–477. doi:10.1016/s0304-4017(97)00111-8. ISSN   0304-4017. PMID   9460212.
  8. ↑ Gilleard, John Stuart (October 2006). "Understanding anthelmintic resistance: the need for genomics and genetics". International Journal for Parasitology. 36 (12): 1227–1239. doi:10.1016/j.ijpara.2006.06.010. ISSN   0020-7519. PMID   16889782.
  9. ↑ Hagel I, Giusti T (October 2010). "Ascaris lumbricoides: an overview of therapeutic targets". Infect Disord Drug Targets. 10 (5): 349–67. doi:10.2174/187152610793180876. PMID   20701574. 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.
  10. ↑ Shoff WH (5 October 2015). Chandrasekar PH, Talavera F, King JW (eds.). "Cyclospora Medication". Medscape. WebMD. Retrieved 11 January 2016. 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.
  11. ↑ Veterinary Parasitology
  12. 1 2 3 Wolstenholme, Adrian J.; Fairweather, Ian; Prichard, Roger; von Samson-Himmelstjerna, Georg; Sangster, Nicholas C. (October 2004). "Drug resistance in veterinary helminths". Trends in Parasitology. 20 (10): 469–476. doi:10.1016/j.pt.2004.07.010. ISSN   1471-4922. PMID   15363440.
  13. 1 2 Kaplan, Ray M. (October 2004). "Drug resistance in nematodes of veterinary importance: a status report". Trends in Parasitology. 20 (10): 477–481. doi:10.1016/j.pt.2004.08.001. ISSN   1471-4922. PMID   15363441.
  14. 1 2 Rose Vineer, Hannah; Morgan, Eric R.; Hertzberg, Hubertus; Bartley, David J.; Bosco, Antonio; Charlier, Johannes; Chartier, Christophe; Claerebout, Edwin; de Waal, Theo; Hendrickx, Guy; Hinney, Barbara; Höglund, Johan; Ježek, Jožica; Kašný, Martin; Keane, Orla M.; Martínez-Valladares, María; Mateus, Teresa Letra; McIntyre, Jennifer; Mickiewicz, Marcin; Munoz, Ana Maria; Phythian, Clare Joan; Ploeger, Harm W.; Rataj, Aleksandra Vergles; Skuce, Philip J.; Simin, Stanislav; Sotiraki, Smaragda; Spinu, Marina; Stuen, Snorre; Thamsborg, Stig Milan; Vadlejch, Jaroslav; Varady, Marian; von Samson-Himmelstjerna, Georg; Rinaldi, Laura (2020). "Increasing importance of anthelmintic resistance in European livestock: creation and meta-analysis of an open database". Parasite. 27: 69. doi: 10.1051/parasite/2020062 . ISSN   1776-1042. PMC   7718593 . PMID   33277891. Open Access logo PLoS transparent.svg
  15. ↑ Sager, Heinz; Hosking, Barry; Bapst, Béatrice; Stein, Philip; Vanhoff, Kathleen; Kaminsky, Ronald (2009-01-22). "Efficacy of the amino-acetonitrile derivative, monepantel, against experimental and natural adult stage gastro-intestinal nematode infections in sheep". Veterinary Parasitology. 159 (1): 49–54. doi:10.1016/j.vetpar.2008.10.006. ISSN   0304-4017. PMID   19019553.
  16. ↑ Blackhall, William J.; Prichard, Roger K.; Beech, Robin N. (2008-03-25). "P-glycoprotein selection in strains of Haemonchus contortus resistant to benzimidazoles". Veterinary Parasitology. 152 (1–2): 101–107. doi:10.1016/j.vetpar.2007.12.001. ISSN   0304-4017. PMID   18241994.
  17. ↑ Pomroy, W. E. (December 2006). "Anthelmintic resistance in New Zealand: a perspective on recent findings and options for the future". New Zealand Veterinary Journal. 54 (6): 265–270. doi:10.1080/00480169.2006.36709. ISSN   0048-0169. PMID   17151723.

[1] [2]

  1. ↑ Shalaby, Hatem A. (2013). "Anthelmintics Resistance; How to Overcome it?". Iranian Journal of Parasitology. 8 (1): 18–32. ISSN   1735-7020. PMC   3655236 . PMID   23682256.
  2. ↑ Fissiha, Workye; Kinde, Mebrie Zemene (2021-12-15). "Anthelmintic Resistance and Its Mechanism: A Review". Infection and Drug Resistance. 14: 5403–5410. doi: 10.2147/IDR.S332378 . ISSN   1178-6973. PMC   8687516 . PMID   34938088.
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