Anthelminthic therapies

INTRODUCTION — Helminths are multicellular parasites with complex life cycles within and outside of human hosts. The mechanisms of action for many anthelminthic agents remain incompletely understood.

Anthelminthic drugs are used for treatment of symptomatic disease and for mass drug treatment programs in regions with high prevalence of infection and disease [1-3]. In some endemic areas, deworming strategies have been associated with health benefits including improvements in hemoglobin levels, growth and physical fitness, cognitive performance, and nutritional status [4-6]. (See "Mass drug administration for control of parasitic infections".)

In the United States, some agents are available through the Centers for Disease Control and Prevention Drug Service (telephone 1-404-639-3670).

An overview of anthelminthic therapies will be presented here. Therapeutic and more detailed considerations for specific helminth infections are discussed separately. (See related topics.)

IVERMECTIN — Ivermectin is a semisynthetic derivative of avermectin, which is derived from the soil mold Streptomyces avermitilis. Ivermectin opens glutamate-sensitive chloride channel currents in helminths and this may be its mechanism of action [7].

Ivermectin is lipophilic. In individuals with higher body mass index, this can result in lower plasma levels; however, this can also result in a longer half-life and time to clearance [8-10]. The clinical impact of these effects on treatment efficacy is unknown; given the lipophilicity, we favor dosing based on actual body weight.

Ivermectin is the drug of choice for the treatment of onchocerciasis and for strongyloidiasis. (See "Onchocerciasis" and "Strongyloidiasis".)

Ivermectin has activity against other filarial worms including Wuchereria bancrofti, Brugia malayi, and Loa loa. It is not the drug of choice for these infections, though it may be useful in certain circumstances. (See related topics.)

Ivermectin is effective against several intestinal nematodes including ascariasis, trichuriasis, and enterobiasis [11]. Ivermectin is also used to treat cutaneous larva migrans and Mansonella ozzardi. Ivermectin is ineffective against human hookworms [11]. (See "Ascariasis" and "Enterobiasis (pinworm) and trichuriasis (whipworm)" and "Hookworm-related cutaneous larva migrans" and "Mansonella infections".)

Ivermectin is also effective for treatment of ectoparasitic infections including scabies and head lice. (See "Scabies: Epidemiology, clinical features, and diagnosis" and "Pediculosis capitis".)

Ivermectin should not be administered to pregnant or lactating women, and its safety in children <15 kg is not known. In areas of West Africa where loiasis is endemic, ivermectin should be used with caution; it should be avoided in those with high-grade microfilaremia who are susceptible to treatment-induced encephalopathy. (See "Loiasis (Loa loa infection)".)

BENZIMIDAZOLES — The benzimidazole class of antiparasitic agents includes four drugs: thiabendazole, mebendazole, albendazole, and triclabendazole.

Benzimidazoles exert their anthelminthic effect by binding to free beta-tubulin and thus inhibiting the polymerization of tubulin and microtubule-dependent glucose uptake [12].

Benzimidazoles should be avoided in pregnant women when possible. When used in mass drug treatment programs for soil-transmitted helminths, the World Health Organization indicates that mebendazole and albendazole may be administered to pregnant women in the second and third trimesters [2].

Albendazole — Albendazole has a broad range of activity against helminthic infections, including neurocysticercosis, echinococcosis, ascariasis, hookworm, and trichuriasis. (See related topics.)

Albendazole also has activity against a number of less common tissue nematode infections, including cutaneous larva migrans [13], visceral and ocular larva migrans [14], gnathostomiasis [15], intestinal capillariasis [16], clonorchiasis [17], Lagochilascaris minor [18], and human infections with the nematodes Trichinella pseudospiralis [19] and Oesophagostomum bifurcum [20]. (See related topics.)

Absorption of albendazole is enhanced by taking it with fatty meals [21]. Albendazole should be taken with fatty foods for treatment of invasive systemic parasitic infections; it should be taken with no food (eg, on an empty stomach) for treatment of intraluminal parasitic infections with no systemic involvement. Side effects of albendazole include abdominal pain, nausea, vomiting, and increased hepatic transaminases; these are generally transient and usually do not require discontinuation of the drug [22]. Neutropenia and, rarely, agranulocytosis can occur with longer-term treatments (as for echinococcosis or neurocysticercosis), so blood counts should be monitored. Alopecia can occur during prolonged treatments but resolves after albendazole treatment ends.

Mebendazole — Mebendazole is a benzimidazole derivative that is effective against a spectrum of intestinal and tissue nematode infections, including ascariasis, hookworm, enterobiasis, and trichuriasis, and as an investigational drug for Capillaria. Side effects of mebendazole include mild abdominal pain and diarrhea.

Triclabendazole — Triclabendazole is the drug of choice for treatment of liver fluke infections due to Fasciola hepatica [23,24]. Triclabendazole should be taken with food to enhance absorption [25]. (See "Liver flukes: Fascioliasis".)

In the United States, triclabendazole was approved by the US Food and Drug Administration in February 2019 for treatment of patients with fascioliasis ≥6 years of age [26]. Triclabendazole prolongs the QTc interval but otherwise is generally well tolerated.

Thiabendazole — Thiabendazole is an older benzimidazole derivative that is active against a variety of nematode parasites, but frequent and severe side effects have limited its use [27]. Adverse reactions include dizziness, nausea, vomiting, drowsiness, pruritus, headache, neuropsychiatric disturbances, hepatitis, and hypersensitivity reactions including Stevens-Johnson syndrome. A topical suspension of thiabendazole has been used for cutaneous larva migrans.

PRAZIQUANTEL — Praziquantel has activity against schistosomiasis, intestinal tapeworms, cysticercosis, and other flukes (exclusive of Fasciola hepatica). (See related topics.)

Its mechanism of action is unknown, but, in schistosomes, it causes paralysis and tegumental disruption. Side effects include headache, dizziness, drowsiness, nausea, and abdominal discomfort.

OTHER AGENTS — A number of other drugs are available for the treatment of specific helminthic infections.

Diethylcarbamazine — Diethylcarbamazine (DEC) is a piperazine derivative that has activity against lymphatic filariasis, loiasis, and visceral larva migrans. The mechanism of action is uncertain.

Side effects in filarial infections are generally proportional to the microfilarial burden and largely attributable to release of lipopolysaccharides and other constituents from endosymbiont Wolbachia [28,29]. Symptoms include fever, headache, dizziness, and transient exacerbation of lymphangitis. DEC induces the Mazzotti reaction when administered in the setting of onchocerciasis (eg, pruritus, ocular and constitutional symptoms). In areas of West Africa where loiasis is endemic, DEC should be used with caution; it should not be administered to individuals with high-grade microfilaremia who are susceptible to treatment-induced encephalopathy. (See "Loiasis (Loa loa infection)".)

In the United States, DEC is available from the Centers for Disease Control and Prevention Drug Service.

Pyrantel — Pyrantel is a well-tolerated pyrimidine derivative that acts against intestinal nematodes by inducing neuromuscular paralysis, allowing worms to be expelled. A single dose is usually curative for ascariasis, enterobiasis, and trichostrongyliasis; several doses are recommended for hookworm infection. It is not active against Trichuris trichiura. (See "Ascariasis" and "Enterobiasis (pinworm) and trichuriasis (whipworm)" and "Miscellaneous nematodes" and "Hookworm infection".)

Nitazoxanide — Nitazoxanide is a nitrothiazolyl-salicylamide derivative with an uncertain mechanism of action [3]. Nitazoxanide has US Food and Drug Administration approval for treatment of two protozoan enteric infections, giardiasis and cryptosporidiosis. (See "Giardiasis: Treatment and prevention" and "Cryptosporidiosis: Treatment and prevention".)

There is limited clinical experience with nitazoxanide for treatment of intestinal helminths including Ascaris, Trichuris, Enterobius, as well as the dwarf tapeworm, Hymenolepis nana, and Fasciola hepatica [1,3].

Oxamniquine — Oxamniquine is a tetrahydroquinolone derivative that is used as an alternative agent for the treatment of Schistosoma mansoni [1]. Higher doses are required in Egypt and South Africa for partially resistant strains; completely resistant strains have also been encountered. Oxamniquine is well tolerated, with occasional side effects of headache, dizziness, drowsiness, and gastrointestinal disturbances. Oxamniquine is contraindicated for use during pregnancy and is not available in the United States. (See "Schistosomiasis: Treatment and prevention".)

SUMMARY

●Helminths – Helminths are multicellular parasites with complex life cycles within and outside of human hosts. (See 'Introduction' above.)

●Ivermectin – (see 'Ivermectin' above):

•Ivermectin is the drug of choice for the treatment of onchocerciasis and for strongyloidiasis. Ivermectin is effective against several intestinal nematodes including ascariasis, trichuriasis, and enterobiasis. Ivermectin is also effective for treatment of ectoparasitic infestations including scabies and head lice.

•Ivermectin has activity against other filarial worms including Wuchereria bancrofti, Brugia malayi, and Loa loa; it is not the drug of choice for these infections, though it may be useful in certain circumstances.

●Benzimidazoles

•Albendazole – Albendazole has a broad range of activity against helminthic infections, including neurocysticercosis, echinococcosis, ascariasis, hookworm, and trichuriasis. Albendazole also has activity against a number of less common tissue nematode infections. (See 'Albendazole' above.)

•Mebendazole – Mebendazole is a benzimidazole derivative that is effective against a spectrum of intestinal and tissue nematode infections, including ascariasis, hookworm, enterobiasis, and trichuriasis.

•Triclabendazole – Triclabendazole is the drug of choice for treatment of liver fluke infections due to Fasciola hepatica. (See 'Triclabendazole' above.)

●Praziquantel – Praziquantel has activity against schistosomiasis, intestinal tapeworms, cysticercosis, and other flukes (exclusive of Fasciola hepatica). (See 'Praziquantel' above.)

●Diethylcarbamazine (DEC) – DEC has activity against lymphatic filariasis, loiasis, and visceral larva migrans. DEC induces the Mazzotti reaction when administered in the setting of onchocerciasis (eg, pruritus, ocular and constitutional symptoms). (See 'Diethylcarbamazine' above.)