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.
Pills containing anthelmintics are used in mass deworming campaigns of school-aged children in many developing countries.[1][2] Anthelmintics are also used for mass deworming of livestock. The drugs of choice for soil-transmitted helminths are mebendazole and albendazole;[3] for schistosomiasis and tapeworms it is praziquantel.[4]
Types
Antiparasitics that specifically target worms of the genus Ascaris are called ascaricides.
- Benzimidazoles:
- Albendazole – effective against threadworms, roundworms, whipworms, tapeworms, hookworms
- Mebendazole – effective against various nematodes
- Thiabendazole – effective against various nematodes
- Fenbendazole – effective against various parasites
- Triclabendazole – effective against liver flukes
- Flubendazole – effective against most intestinal parasites
- Avermectins (including ivermectin) - effective against most common intestinal worms, except tapeworms, for which praziquantel is commonly used in conjunction for mass dewormings
- Diethylcarbamazine – effective against Wuchereria bancrofti, Brugia malayi, Brugia timori, and Loa loa
- Pyrantel pamoate – effective against most nematode infections residing within the intestines
- Levamisole
- Salicylanilide – mitochondrial un-couplers (used only for flatworm infections):
- Nitazoxanide – readily kills Ascaris lumbricoides,[5] and also possess antiprotozoal effects[6]
- Oxamniquine – effective against flatworms (e.g., tapeworms and schistosoma)
- Praziquantel – effective against flatworms (e.g., tapeworms and schistosoma)
- Octadepsipeptides (e.g. Emodepside) – effective against a variety of gastrointestinal helminths
- Monepantel (aminoacetonitrile class) - effective against a variety of nematodes including those resistant to other anthelmintic classes
- Spiroindoles (e.g. derquantel) - effective against a variety of nematodes including those resistant to other anthelmintic classes
- Artemisinin – shows anthelmintic activity[7]
Anthelmintic resistance
Anthelmintic resistance is when a parasite is no longer sensitive to an anthelmintic that it once was and it is passed from one generation to the next.[11] There are many different things that can contribute to anthelmintic resistance such as frequency of treatment, mass anthelmintic treatment, underdosing, treating with only one anthelmintic, and resistance being transmitted during transfer of animals. [10] Anthelmintic resistance in parasites is now widespread. It is a major threat to the sustainability of modern ruminant livestock production, resulting in reduced productivity, compromised animal health and welfare, 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%, macrocyclic lactones except moxidectin 52%, levamisole 48%, and moxidectin 21%. All major gastrointestinal nematodes 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. [8]
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.
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]
The resistance is measured by the "fecal egg count reduction" value which varies for different types of helminths.[9]
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.
The ways in which anthelmintics are used have contributed to a major anthelmintic resistance issue worldwide. 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 animal are not being underdosed, rotating the anthelmintics that are being used, using a combination of multiple different anthelmintics, and the use of refugia based strategies. In refugia strategies, a portion of the group is not treated with anthelmintics which allows for less development of parasites with resistant genes.
See also
- Dysphania ambrosioides, an herb native to Central and South America
- Santonin, a historical anthelmintic no longer in use
- 4-Hexylresorcinol
References
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ "Helminth control in school-age children" (PDF). World Health Organization. 2011. Retrieved 28 July 2015.
- ↑ 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.
- ↑ 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.
- ↑ Veterinary Parasitology
- ↑ 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.
- ↑ Levecke, Bruno; Montresor, Antonio; Albonico, Marco; Ame, Shaali M.; Behnke, Jerzy M.; Bethony, Jeffrey M.; Noumedem, Calvine D.; Engels, Dirk; Guillard, Bertrand; Kotze, Andrew C.; Krolewiecki, Alejandro J.; McCarthy, James S.; Mekonnen, Zeleke; Periago, Maria V.; Sopheak, Hem; Tchuem-Tchuenté, Louis-Albert; Duong, Tran Thanh; Huong, Nguyen Thu; Zeynudin, Ahmed; Vercruysse, Jozef; Olliaro, Piero L. (9 October 2014). "Assessment of Anthelmintic Efficacy of Mebendazole in School Children in Six Countries Where Soil-Transmitted Helminths Are Endemic". PLOS Neglected Tropical Diseases. 8 (10): e3204. doi:10.1371/journal.pntd.0003204. PMC 4191962. PMID 25299391.
External links
- Anthelmintics at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
- Holden-Dye, L. and Walker, R.J.Anthelmintic drugs (November 2, 2007), WormBook, ed. The C. elegans Research Community, WormBook, doi/10.1895/wormbook.1.143.1
- ↑ 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.
- ↑ 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.