Antiparasitic

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Antiparasitics are a class of medications which are indicated for the treatment of parasitic diseases, such as those caused by helminths, [1] amoeba, [2] ectoparasites, parasitic fungi, [3] and protozoa, [1] among others. Antiparasitics target the parasitic agents of the infections by destroying them or inhibiting their growth; [4] they are usually effective against a limited number of parasites within a particular class. Antiparasitics are one of the antimicrobial drugs which include antibiotics that target bacteria, and antifungals that target fungi. They may be administered orally, intravenously or topically. [4] Overuse or misuse of antiparasitics can lead to the development of antimicrobial resistance.

Contents

Broad-Spectrum antiparasitics, analogous to broad-spectrum antibiotics for bacteria, are antiparasitic drugs with efficacy in treating a wide range of parasitic infections caused by parasites from different classes.

Types

Broad-spectrum

Antiprotozoals

Antihelminthic

Antinematodes

Ancylostoma caninum, a type of hookworm, attached to the intestinal mucosa. Hookworms.JPG
Ancylostoma caninum, a type of hookworm, attached to the intestinal mucosa.

Anticestodes

Antitrematodes

Antiamoebics

Antifungals

Medical uses

Antiparasitics treat parasitic diseases, which impact an estimated 2 billion people. [1]

Administration

Antiparastics may be given via a variety of routes depending on the specific medication, including oral, topical, and intravenous. [4]

Resistance to antiparasitics has been a growing concern, especially in veterinary medicine. The Egg hatch assay can be used to determine whether a parasite causing an infection has become resistant to standard drug treatments. [10]

Drug development history

Early antiparasitics were ineffective, frequently toxic to patients, and difficult to administer due to the difficulty in distinguishing between the host and the parasite. [4]

Between 1975 and 1999 only 13 of 1,300 new drugs were antiparasitics, which raised concerns that insufficient incentives existed to drive development of new treatments for diseases that disproportionately target low-income countries. This led to new public sector and public-private partnerships (PPPs), including investment by the Bill and Melinda Gates Foundation. Between 2000 and 2005, twenty new antiparasitic agents were developed or in development. [11] Metal-containing compounds are the subject of another avenue of approach. [12]

Research

In the last decades, triazolopyrimidines and their metal complexes have been looked at as an alternative drug to the existing commercial antimonials, searching for a decrease in side effects and the development of parasite drug resistance. [13]

See also

Related Research Articles

<span class="mw-page-title-main">Parasitic disease</span> Medical condition

A parasitic disease, also known as parasitosis, is an infectious disease caused by parasites. Parasites are organisms which derive sustenance from its host while causing it harm. The study of parasites and parasitic diseases is known as parasitology. Medical parasitology is concerned with three major groups of parasites: parasitic protozoa, helminths, and parasitic arthropods. Parasitic diseases are thus considered those diseases that are caused by pathogens belonging taxonomically to either the animal kingdom, or the protozoan kingdom.

<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">Giardiasis</span> Parasitic disease that results in diarrhea

Giardiasis is a parasitic disease caused by Giardia duodenalis. Infected individuals who experience symptoms may have diarrhoea, abdominal pain, and weight loss. Less common symptoms include vomiting and blood in the stool. Symptoms usually begin one to three weeks after exposure and, without treatment, may last two to six weeks or longer.

<i>Trichomonas vaginalis</i> Species of parasite that causes sexually transmitted infections

Trichomonas vaginalis is an anaerobic, flagellated protozoan parasite and the causative agent of a sexually transmitted disease called trichomoniasis. It is the most common pathogenic protozoan that infects humans in industrialized countries. Infection rates in men and women are similar but women are usually symptomatic, while infections in men are usually asymptomatic. Transmission usually occurs via direct, skin-to-skin contact with an infected individual, most often through vaginal intercourse. The WHO has estimated that 160 million cases of infection are acquired annually worldwide. The estimates for North America alone are between 5 and 8 million new infections each year, with an estimated rate of asymptomatic cases as high as 50%. Usually treatment consists of metronidazole and tinidazole.

<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">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, today 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.

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

Albendazole is a broad-spectrum anthelmintic and antiprotozoal agent of the benzimidazole type. It is used for the treatment of a variety of intestinal parasite infections, including ascariasis, pinworm infection, hookworm infection, trichuriasis, strongyloidiasis, taeniasis, clonorchiasis, opisthorchiasis, cutaneous larva migrans, giardiasis, and gnathostomiasis, among other diseases.

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

Fumagillin is a complex biomolecule and used as an antimicrobial agent. It was isolated in 1949 from the microbial organism Aspergillus fumigatus.

<span class="mw-page-title-main">Parasitic worm</span> Large type of parasitic organism

Parasitic worms, also known as helminths, are large macroparasites; adults can generally be seen with the naked eye. Many are intestinal worms that are soil-transmitted and infect the gastrointestinal tract. Other parasitic worms such as schistosomes reside in blood vessels.

Microsporidiosis is an opportunistic intestinal infection that causes diarrhea and wasting in immunocompromised individuals. It results from different species of microsporidia, a group of microbial (unicellular) fungi.

Antiprotozoal agents is a class of pharmaceuticals used in treatment of protozoan infection.

<span class="mw-page-title-main">Miltefosine</span> Phospholipid drug

Miltefosine, sold under the trade name Impavido among others, is a medication mainly used to treat leishmaniasis and free-living amoeba infections such as Naegleria fowleri and Balamuthia mandrillaris. This includes the three forms of leishmaniasis: cutaneous, visceral and mucosal. It may be used with liposomal amphotericin B or paromomycin. It is taken by mouth.

Diphyllobothriasis is the infection caused by tapeworms of the genus Diphyllobothrium.

<span class="mw-page-title-main">Nitazoxanide</span> Broad-spectrum antiparasitic and antiviral medication

Nitazoxanide, sold under the brand name Alinia among others, is a broad-spectrum antiparasitic and broad-spectrum antiviral medication that is used in medicine for the treatment of various helminthic, protozoal, and viral infections. It is indicated for the treatment of infection by Cryptosporidium parvum and Giardia lamblia in immunocompetent individuals and has been repurposed for the treatment of influenza. Nitazoxanide has also been shown to have in vitro antiparasitic activity and clinical treatment efficacy for infections caused by other protozoa and helminths; evidence as of 2014 suggested that it possesses efficacy in treating a number of viral infections as well.

<span class="mw-page-title-main">Pyruvate synthase</span> Class of enzymes

In enzymology, a pyruvate synthase is an enzyme that catalyzes the interconversion of pyruvate and acetyl-CoA. It is also called pyruvate:ferredoxin oxidoreductase (PFOR).

<span class="mw-page-title-main">Protozoan infection</span> Parasitic disease caused by a protozoan

Protozoan infections are parasitic diseases caused by organisms formerly classified in the kingdom Protozoa. They are usually contracted by either an insect vector or by contact with an infected substance or surface and include organisms that are now classified in the supergroups Excavata, Amoebozoa, SAR, and Archaeplastida.

<span class="mw-page-title-main">Anthelmintic</span> Antiparasitic drugs that expel parasitic worms (helminths) from the body

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 or vermicides. Anthelmintics are used to treat people who are infected by helminths, a condition called helminthiasis. These drugs are also used to treat infected animals.

Jean-François Rossignol is a French scientist, a medicinal chemist and a physician, born in France on September 5, 1943. He was educated at the University of Paris, later specializing in tropical medicine. He then pursued a career in academia and in the pharmaceutical industry discovering and developing new drugs for the treatment of parasitic diseases such as halofantrine in the treatment of multidrug resistant Falciparum malaria or albendazole and nitazoxanide for the treatment of intestinal protozoan and helminthic infections. In 1993, he co-created his own pharmaceutical company, Romark Laboratories, L.C., to develop his own invention nitazoxanide, the first of the thiazolides. At Romark, he is the Chairman of the Board of Directors of the company and its Chief Science Officer. Following the discovery of the antiviral activity of the thiazolides Rossignol went to Stanford University in California to study interferon stimulated gene pathways and chronic viral hepatitis under Prof. Emmet Keeffe and Prof. Jeffery Glenn. It was in the Glenn laboratory that the mechanism of antiviral activity of nitazoxanide against the hepatitis C virus was discovered.

<span class="mw-page-title-main">Soil-transmitted helminthiasis</span> Roundworm infection contracted from contaminated soil

Soil-transmitted helminthiasis is a type of worm infection (helminthiasis) caused by different species of roundworms. It is caused specifically by those worms which are transmitted through soil contaminated with faecal matter and are therefore called soil-transmitted helminths. Three types of soil-transmitted helminthiasis can be distinguished: ascariasis, hookworm infection and whipworm infection. These three types of infection are therefore caused by the large roundworm A. lumbricoides, the hookworms Necator americanus or Ancylostoma duodenale and by the whipworm Trichuris trichiura.

<span class="mw-page-title-main">GNF6702</span> Chemical compound

GNF6702 is the name for a broad-spectrum antiprotozoal drug invented by researchers working at the Genomics Institute of the Novartis Research Foundation in 2013, with activity against leishmaniasis, Chagas disease and sleeping sickness. These three diseases are caused by related kinetoplastid parasites, which share similar biology. GNF6702 acts as allosteric proteasome inhibitor which was effective against infection with any of the three protozoal diseases in mice, while having little evident toxicity to mammalian cells.

References

  1. 1 2 3 Kappagoda, Shanthi; Singh, Upinder; Blackburn, Brian G. (2011). "Antiparasitic Therapy". Mayo Clin. Proc. 86 (6): 561–583. doi:10.4065/mcp.2011.0203. PMC   3104918 . PMID   21628620.
  2. Kusrini E, Hashim F, Azmi WN, Amin NM, Estuningtyas A (2016). "A novel antiamoebic agent against Acanthamoeba sp. - A causative agent for eye keratitis infection". Spectrochimica Acta Part A: Molecular Spectroscopy. 153: 714–21. Bibcode:2016AcSpA.153..714K. doi:10.1016/j.saa.2015.09.021. PMID   26474244.
  3. 1 2 Molina JM, Tourneur M, Sarfati C, et al. (June 2002). "Fumagillin treatment of intestinal microsporidiosis". N. Engl. J. Med. 346 (25): 1963–9. doi: 10.1056/NEJMoa012924 . PMID   12075057.
  4. 1 2 3 4 "ANTIPARASITICS". Purdue University Cytology Laboratories. Purdue Research Foundation. Retrieved 2015-08-30.
  5. Di Santo N, Ehrisman J (2013). "Research perspective: potential role of nitazoxanide in ovarian cancer treatment. Old drug, new purpose?". Cancers (Basel). 5 (3): 1163–1176. doi: 10.3390/cancers5031163 . PMC   3795384 . PMID   24202339. Nitazoxanide [NTZ: 2-acetyloxy-N-(5-nitro-2-thiazolyl)benzamide] is a thiazolide antiparasitic agent with excellent activity against a wide variety of protozoa and helminths.  ... Nitazoxanide (NTZ) is a main compound of a class of broad-spectrum anti-parasitic compounds named thiazolides. It is composed of a nitrothiazole-ring and a salicylic acid moiety which are linked together by an amide bond ... NTZ is generally well tolerated, and no significant adverse events have been noted in human trials [13]. ... In vitro, NTZ and tizoxanide function against a wide range of organisms, including the protozoal species Blastocystis hominis, C. parvum, Entamoeba histolytica, G. lamblia and Trichomonas vaginalis [13]
  6. White CA (2004). "Nitazoxanide: a new broad spectrum antiparasitic agent". Expert Rev Anti Infect Ther. 2 (1): 43–9. doi:10.1586/14787210.2.1.43. PMID   15482170. S2CID   219184877.
  7. Hemphill A, Mueller J, Esposito M (2006). "Nitazoxanide, a broad-spectrum thiazolide anti-infective agent for the treatment of gastrointestinal infections". Expert Opin Pharmacother. 7 (7): 953–64. doi:10.1517/14656566.7.7.953. PMID   16634717. S2CID   13436814.
  8. Anderson, V. R.; Curran, M. P. (2007). "Nitazoxanide: A review of its use in the treatment of gastrointestinal infections". Drugs. 67 (13): 1947–1967. doi:10.2165/00003495-200767130-00015. PMID   17722965.
  9. Lanternier F, Boutboul D, Menotti J, et al. (February 2009). "Microsporidiosis in solid organ transplant recipients: two Enterocytozoon bieneusi cases and review". Transpl Infect Dis. 11 (1): 83–8. doi:10.1111/j.1399-3062.2008.00347.x. PMID   18803616. S2CID   205423324.
  10. Sargison, Neil (2009-01-26). Sheep Flock Health: A Planned Approach. John Wiley & Sons. ISBN   9781444302608.
  11. Pink, Richard; Hudson, Alan; Mouries, Marie-Annick; Bendig, Mary (September 2005). "Opportunities and Challenges in Antiparasitic Drug Discovery". Nature. 4 (9): 727–740. doi: 10.1038/nrd1824 . PMID   16138106. S2CID   19379800.
  12. Gambino, Dinorah; Otero, Lucia (2019). "Chapter 13. Metal Compounds in the Development of Antiparasitic Agents: Rational Design from Basic Chemistry to the Clinic". In Sigel, Astrid; Freisinger, Eva; Sigel, Roland K. O.; Carver, Peggy L. (Guest editor) (eds.). Essential Metals in Medicine:Therapeutic Use and Toxicity of Metal Ions in the Clinic. pp. 331–357. doi:10.1515/9783110527872-019. ISBN   978-3-11-052691-2. PMID   30855114. S2CID   73728129.{{cite book}}: |editor4-first= has generic name (help); |journal= ignored (help)
  13. Review (2017). "Leishmanicidal and Trypanocidal Activity of Metal Complexes with 1,2,4-Triazolo[1,5-a]pyrimidines: Insights on their Therapeutic Potential against Leishmaniasis and Chagas Disease". Curr. Med. Chem. 24 (25): 2796–2806. doi:10.2174/0929867324666170516122024. PMID   28521698.