Chapter 323. Antiparasitic Therapy

Melissa Held; Michael Cappello

Antiparasitic Therapy: Introduction

Parasitic diseases afflict more than 2 billion people worldwide and are among the leading causes of death and chronic morbidity in resource-limited countries. Because parasites collectively represent a wide array of species, effective therapy of infections caused by these evolutionarily distinct eukaryotes requires an equally diverse armamentarium of pharmacologic agents. The past decade has seen a renewed commitment to antiparasitic drug development, spearheaded by novel public-private partnerships and supported by international philanthropic organizations, a commitment that may ultimately yield new agents for these globally important diseases.1-3 Equally encouraging is the recent recognition that integrated control of multiple tropical diseases can be achieved through periodic administration of inexpensive, orally available medicines to at-risk individuals living in endemic communities.4,5

Table 323-1 lists the major parasitic species that cause disease in humans along with the currently recommended drugs and doses used for therapy or prevention.6 Antimalarial therapy is discussed in Chapter 352, and detailed in Tables 352-2, 352-3, and 352-4. Below are brief descriptions of these agents, including common side effects and toxicities. More specific information is available in the chapters on each pathogen.

Table 323-1. Antiparasitic Drug Therapy*

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Table 323-1. Antiparasitic Drug Therapy*

Drugs of Choice and Dosages

Nematodes

Intestinal nematodes

Ancylostoma duodenale, Ancylostoma caninum, Necator americanus (hookworm)

Albendazole 400 mg by mouth once or Pyrantel pamoate 11 mg/kg (max 1 g) by mouth 3 times a day or Mebendazole 100 mg by mouth twice a day for 3 days or 500 mg once

Ascaris lumbricoides

Albendazole 400 mg by mouth once or Mebendazole 100 mg twice a day by mouth for 3 days or 500 mg once or Ivermectin 150–200 μg/kg by mouth once

Trichuris trichiura

Mebendazole 100 mg by mouth twice a day for 3 days or 500 mg once

(Alternatives) Albendazole 400 mg by mouth for 3 days or Ivermectin 200 μg/kg by mouth daily for 3 days

Enterobius vermicularis (pinworm)

Pyrantal pamoate 11 mg/kg base by mouth once (max 1 g); repeat in 2 weeks or Albendazole 400 mg by mouth once; repeat in 2 weeks or Mebendazole 100 mg by mouth once; repeat in 2 weeks

Strongyloides stercoralis

Ivermectin 200 μg/kg/day by mouth for 2 days

(Alternative) Albendazole 400 mg by mouth twice a day for 7 days

Trichinella spiralis (Trichinosis)

Albendazole 400 mg by mouth twice a day for 8–14 days or Mebendazole 200–400 mg by mouth 3 times a day for 3 days, then 400–500 mg 3 times a day for 10 days plus steroids for severe symptoms

Blood and tissue nematodes

Wuchereria bancrofti, Brugia malayi, Loa loa (Filariasis)

Diethylcarbamzine 6 mg/kg/day by mouth in 3 doses for 12 days

Mansonella ozzardi

Ivermectin 200 μg/kg by mouth once

Mansonella perstans

Albendazole 400 mg by mouth twice a day for 10 days

(Alternative) Mebendazole 100 mg by mouth twice a day for 30 days

Mansonella streptocerca

Ivermectin 150 μg/kg by mouth once or Diethylcarbamazine 6 mg/kg/day by mouth for 12 day

Onchocerca volvulus (river blindness)

Ivermectin 150 μg/kg by mouth once, repeat every 6–12 months until asymptomatic

Capillaria philippinensis

Mebendazole 200 mg by mouth twice a day for 20 days

(Alternative) Albendazole 400 mg by mouth daily for 10 days

Ancylostoma braziliense, A caninum

Thiabendazole (topical) or (cutaneous larva migrans, creeping eruption) Albendazole 400 mg by mouth daily for 3 days or Ivermectin 200 μg/kg by mouth daily for 1–2 days

Toxocara canis, Toxocara cati (Visceral and ocular larva migrans)

Albendazole 400 mg by mouth twice a day for 5 days or Mebendazole 100–200 g by mouth twice a day for 5 days

Dracunculus medinensis (Guinea worm)

Slow extraction of worm combined with wound care.** Metronidazole decreases inflammation and facilitates removal of the worm. Mebendazole can kill worm directly.

Cestodes

Intestinal (adult) tapeworms

Diphyllobothrium latum, Taenia saginata, Taenia solium, Dipylidium caninum

Praziquantel 5–10 mg/kg by mouth once

(Alternative) Niclosamide 2 g by mouth once

Hymenolepis nana

Praziquantel 25 mg/kg by mouth once

(Alternative) Nitazoxanide 500 mg by mouth once daily for 3 days or twice a day for 3 days

Tissue (larval) tapeworms

Echinococcus granulosis, Echinococcus multilocularis

Albendazole 400 mg by mouth twice a day for 1–6 months (surgical excision for E multilocularis may be the only reliable treatment)

T solium (cysticercosis)

Initial treatment should focus on symptomatic treatment.

Albendazole 400 mg by mouth twice a day for 8–30 days; may repeat or Praziquantel 100 mg/kg/day by mouth in 3 doses for 1 day then 50 mg/kg/day in 3 doses for 29 days

T solium (Neurocysticercosis)

Albendazole (same dose as for cysticercosis) plus steroids plus antiseizure medication if live cysts or Praziquantel is 100 mg/kg/day in 3 doses for 1 day, followed by 50 mg/kg/day in 3 doses for 29 days

Trematodes

Schistosoma haematobium, Schistosoma mansoni

Praziquantel 40 mg/kg/day by mouth in 2 doses for 1 day

(Alternative drug for S mansoni is oxamniquine at 15 mg/kg by mouth once)

Schistosoma japonicum, Schistosoma mekongi

Praziquantel 60 mg/kg/day by mouth in 3 doses for 1 day

Clonorchis sinensis (Chinese liver fluke)

Praziquantel 75 mg/kg/ day by mouth in 3 doses for 1 day or 25 mg/kg 3 times for 2 days or single 40 mg/kg or Albendazole 10 mg/kg/day by mouth for 7 days

Fasciola hepatica (sheep liver fluke)

Triclabendazole 10 mg/kg by mouth once or twice

(Alternative) Bithionol (not available in United States) 30–50 mg/kg on alternate days for 10–15 doses or Nitazoxanide 500 mg by mouth twice a day for 7 days

Fasciolopsis buski, Heterophyes heterophyes

Praziquantel 25 mg/kg by mouth once

Metagonimus yokogawai (intestinal flukes)

Metorchis conjunctus

Nanophyetus salmincola

Praziquantel 60 mg/kg/day by mouth in 3 doses for 1 day

Opisthorchis viverrini

Praziquantel 75 mg/kg/day by mouth in 3 doses for 2 days

Paragonimus westermani (lung fluke)

Praziquantel 75 mg/kg/day by mouth in 3 doses for 2 days

(Alternative) Bithionol (not available in United States) 30–50 mg/kg on alternate days for 10–15 doses

Protozoa

Intestinal protozoa

Entamoeba histolytica (amebiasis)

Asymptomatic

Iodoquinol 650 mg by mouth 3 times a day for 20 days or Paromomycin 25–35 mg/kg/day by mouth in 3 doses for 7 days or diloxanide furoate 500 mg by mouth 3 times a day for 10 days

Mild to moderate disease or severe intestinal and extraintestinal

Metronidazole 500–750 mg by mouth 3 times a day for 7–10 days (or 35–50 mg/kg/day by mouth in 3 doses for 7–10 days) or Tinidazole 2 g once by mouth daily for 3 days (over 3 years of age use 50 mg/kg/day, max 2 g, by mouth in 1 dose for 3 days) either followed by Iodoquinol 650 mg by mouth 3 times a day for 20 days (or 30–40 mg/kg/day, max 2 g, by mouth in 3 doses for 20 days) or Paromomycin 25–35 mg/kg/day by mouth in 3 doses for 7 days

Entamoeba polecki

Metronidazole 500–750 mg by mouth 3 times a day for 7–10 days (or 35–50 mg/kg/day by mouth in 3 doses for 7–10 days)

Balantidium coli

Tetracycline 500 mg by mouth in 4 doses for 10 days (or 40 mg/kg/day, max 2 g, by mouth in 4 doses for 10 days)

(Alternative) Iodoquinol 650 mg by mouth 3 times a day for 20 days (or 30–40 mg/kg/day, max 2 g, by mouth in 3 doses for 20 days) or Metronidazole 750 mg by mouth 3 times a day for 5 day (or 35–50 mg/kg/day by mouth in 3 doses for 5 days)

Dientameba fragilis

Iodoquinol 650 mg by mouth 3 times a day for 20 days (or 30–40 mg/kg/day, max 2 g, by mouth in 3 doses for 20 days) or Paromomycin 25–35 mg/kg/day by mouth in 3 doses for 7 days or Tetracycline 500 mg by mouth in 4 doses for 10 days (or 40 mg/kg/day, max 2 g, by mouth in 4 doses for 10 days) or Metronidazole 500–750 mg by mouth 3 times a day for 10 days (or 35–50 mg/kg/day by mouth in 3 doses for 10 days)

Giardia duodenalis

Metronidazole 250 mg by mouth 3 times a day for 5–7 days (or 15 mg/kg/day by mouth in 3 doses for 5-7 days) or Nitazoxamide 500 mg by mouth twice a day for 3 days (if 1–3 years use 100 mg by mouth every 12 h for 3 days, if 4–11 years use 200 mg by mouth every 12 h for 3 days) or Tinidazole 2 g by mouth once (or 50 mg/kg by mouth once)

(Alternative) Paromomycin 25–35 mg/kg/day by mouth in 3 doses for 5–10 days or Quinacrine 100 mg by mouth 3 times a day for 5 days (or 2 mg/kg/day by mouth in 3 doses for 5 days) or Furazolidone 100 mg by mouth in 4 doses for 7–10 days (or 6 mg/kg/day by mouth in 4 doses for 7–10 days)

Cryptosporidium

Nitazoxanide 500 mg by mouth twice a day for 3 days (1–3 years 100 mg by mouth twice a day for 3 days; 3–11 years 200 mg by mouth twice a day for 3 days)

Microsporidiosis

Encephalitozoon intestinalis

Albendazole 400 mg by mouth twice a day for 21 days

Enterocytozoon bieneusi

Fumagillin 20 mg by mouth 3 times a day for 14 days

Ocular (Encephalitozoon hellum, Encephalitozoon cuniculi, Vittaforma corneae)

Albendazole 400 mg by mouth twice a day plus Fumagillin

Malaria (See Chapter 352 and Tables 352-2, 352-3, and 352-4.)

Other Blood and Tissue Protozoa

Naegleria species, Acanthamoeba species (amebic meningoencephalitis)

Amphotericin B 1.5 mg/kg/day IV in 2 doses for 3 days, then 1 mg/kg/day for 6 days plus 1.5 mg/day intrathecally for 2 days, then 1 mg/day every other day for 8 days

Babesia species (Babesiosis)

Clindamycin 1.2 g twice a day IV or 600 mg 3 times a day by mouth for 7–10 days plus Quinine 650 mg by mouth 3 times a day for 7–10 days or Atovaquone 750 mg by mouth twice a day for 7–10 days plus Azithromycin 600 mg by mouth daily for 7–10 days

Toxoplasma gondii (Toxoplasmosis)

Pyrimethamine 25–100 mg/day by mouth for 3–4 weeks plus Sulfadiazine 1–1.5 g by mouth 4 times a day for 3–4 weeks

Trypanosoma brucei gambiense

Hemolymphatic stage

Pentamidine isethionate 4 mg/kg/day IM for 7 days; (Alternative) Suramin

Late stage

Melarsoprol 2.2 mg/kg/day IV for 10 days or Eflornithine 400 mg/kg/day IV in 4 doses for 14 days

Trypanosoma brucei rhodesiense

Hemolytic stage

Suramin 100–200 mg (test dose) IV, then 1 g IV on days 1, 3, 7, 14, 21

Late stage

Melarsoprol 2–3.6 mg/kg/day IV for 3 days, after 7 days 3.6 mg/kg/day for 3 days; repeat after 7 days

Trypanosoma cruzi (American trypanosomiasis or Chagas disease)

Nifurtimox 8–10 mg/kg/day by mouth in 3–4 doses for 90–120 days (1–10 years use 15–20 mg/kg/day by mouth in 4 doses for 90–120 days; 11–16 years use 12.5–15 mg/kg/days in 4 doses for 90–120 days) or Benzimidazole 5–7 mg/kg/day by mouth in 2 doses for 30–90 days (< 12 years use 10 mg/kg/day by mouth in 2 doses for 30–90 days)

Leishmania mexicana, Leishmania major

Leishmania tropica, Leishmania braziliensis, Leishmania donovani, Leishmania infantum

Cutaneous

Sodium stibogluconate 20 mg Sb/kg/day IV or IM for 20 days or Meglumine antimonate 20 mg Sb/kg/day IV or IM for 20 days or Miltefosine 2.5 mg/kg/day by mouth (max 150 mg/day) for 28 days

(Alternative) Paromomycin topically twice a day for 10–20 days or Pentamidine 2–3 mg/kg IV or IM daily or every second day for 4–7 doses

Visceral

Sodium stibogluconate or liposomal Amphotericin B 3 mg/kg/day IV day 1–5, 14 and 21 or Miltefosine

(Alternative) Meglumine antimonate (above) or Amphotericin B 1 mg/kg IV daily for 15–20 days or every second day for up to 8 weeks or Paromomycin 15 mg/kg/day IM for 21 days

Mucosal

Sodium stibogluconate or Meglumine antimonate or Amphotericin B or Miltefosine (see treatments above)

Ectoparasites

Lice (Pediculus humanus, Pediculus humanus capitis,Phthirus pubis)

1% Permethrin or 0.5% Malathion (both topically)

(Alternative) Pyrethrins with piperonyl butoxide or Ivermectin 200 μg/kg by mouth

Scabies (Sarcoptes scabiei)

5% Permethrin (topically)

(Alternative) Ivermectin or 10% Crotamiton

*Adapted from: Drugs for parasitic infections. The Medical Letter. 2007; Suppl:1–15.

Drugs for the Treatment of Helminth Infections

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Nematodes

Mebendazole (Vermox) is a broad-spectrum anthelminthic with activity against many intestinal nematode species that infect humans. It is also effective against certain filarial worms, as well as adult and larval stages of Trichinella spiralis. Side effects may include mild abdominal pain, vomiting, and diarrhea.7 There is occasionally an immediate hypersensitivity response to the dying worms during treatment, termed the Jarisch-Herxheimer reaction. In the setting of severe symptoms caused by infection with T spiralis, steroids should be given concomitantly. For visceral larva migrans caused by Toxocara species, mebendazole should be given twice a day for 5 days.6,8

Albendazole (Albenza), also a benzimidazole, has replaced mebendazole as the drug of choice for intestinal nematode infections in most parts of the developing world. Its side effects and toxicity profile are much like mebendazole.8 Albendazole is administered as a single dose of 400 mg to treat infections with the following nematodes: Ancylostoma caninum (eosinophilic enteritis), Ascaris lumbricoides, Enterobius vermicularis, and hookworm. It is also used for treatment of pinworm (E vermicularis), Trichuris trichiura, Capillaria philippinensis, and for cutaneous larva migrans (caused by dog and cat hookworms) or visceral larva migrans (Toxocara).9

Although benzimidazoles are not approved by the Food and Drug Administration (FDA) for use in pregnancy, there is growing evidence to suggest that mebendazole and albendazole are safe when administered in the second trimester or beyond.10-12 However, recent concerns about benzimidazole resistance among intestinal nematodes suggests that these agents may become less effective in coming years, especially in those communities previously subjected to extensive deworming.13

Thiabendazole (Mintezole) is a systemically absorbed synthetic benzimidazole effective in the treatment of strongyloidiasis.9 However, because of its frequent side effects and toxicity, it has been replaced by ivermectin as the drug of choice for infection with Strongyloides stercoralis. The most common side effects of thiabendazole are gastrointestinal symptoms, although hepatotoxicity and central nervous system disorders have also been reported. The recommended dose of thiabendazole is 50 mg/kg/day divided in 2 doses (maximum dose 3 g/day) for 2 days.

Pyrantel pamoate (Antiminth), which causes neuromuscular blockade in parasites, is an effective anthelminthic agent for the treatment of the intestinal nematodes, including hookworms (Ancylostoma duodenale and Necator americanus), and is the drug of choice for E vermicularis.8 The most frequent side effects are gastrointestinal, although occasional central nervous system effects may be seen. The recommended dose is 11 mg/kg (maximum dose 1 g) given for 3 days. For pinworm, the dose is given once and should be repeated in 2 weeks.

Diethylcarbamazine (Hetrazan), a derivative of the anthelminthic piperazine, has activity against many filarial nematodes. It is the drug of choice for infections caused by Wuchereria bancrofti, Brugia malayi, and Loa loa. It is also recommended for treatment of tropical pulmonary eosinophilia. The major side effects include gastrointestinal symptoms, as well as headache and myalgias. Because of severe inflammatory reactions, termed the Mazzotti reaction, noted in patients infected with Onchocerca volvulus, diethylcarbamazine is no longer recommended for treatment of onchocerciasis.8 The recommended dosing for W bancrofti, B malayi, and L loa is 6 mg/kg in 3 doses for 12 days. For patients with microfilaremia, the following regimen is recommended: on day 1, 50 mg; day 2, 50 mg 3 times a day; day 3, 100 mg 3 times a day; days 4 to 14, 6 mg/kg in 3 doses (for L. loa days 4–14, 9 mg/kg in 3 doses). The dose for tropical pulmonary eosinophilia is 6 mg/kg/day in 3 doses for 12 to 21 days.

Ivermectin (Mectizan, Stromectin) is a broad-spectrum antiparasitic agent with activity against a variety of nematodes and ectoparasites. It has become the drug of choice for the treatment of onchocerciasis and strongyloidiasis. It is also highly effective in patients with cutaneous larva migrans and has activity against a number of intestinal nematode species. The side effects of ivermectin are primarily seen in patients treated for onchocerciasis who are also co-infected with Loa loa; such patients can develop toxic side effects, including encephalopathy. The recommended dose of ivermectin for onchocerciasis (river blindness) is 150 μg/kg once, repeated every 6 to 12 months until asymptomatic. The dose for strongyloidiasis is 200 μg/kg/day for 2 days. For cutaneous larva migrans, a single dose of 200 μg/kg daily for 1 to 2 days is recommended.

Cestode and Trematode Infections

Praziquantel and albendazole have become the drugs of choice for nearly all infections caused by flatworms. The exception is Fasciola hepatica (liver fluke), which is treated with triclabendazole, nitazoxanide, or bithionol. Praziquantel (Biltricide) is a heterocyclic prazino-isoquinolin that causes rapid paralysis of intestinal cestodes and damages the tegument of trematodes. Its use is associated with primarily central nervous system and gastrointestinal side effects, which are usually mild and resolve with cessation of therapy. The recommended dose for the adult tapeworms Diphyllobothrium latum, Taenia saginata, T solium, and Dipylidium caninum is 5 to 10 mg/kg given once. For infections with Hymenolepis nana, the dose is increased to 25 mg/kg. For the treatment of neurocysticercosis, the dose of praziquantel is 100 mg/kg/day in 3 doses for one day, followed by 50 mg/kg/day for 29 days, usually in conjunction with steroids. The dose of praziquantel recommended for the treatment of the flukes Clonorchis sinensis, Fasciolopsis buski, Heterophyes heterophyes, Metagonimus yokogawai, Metorchis conjunctus, and Opisthorchis viverrini is 75 mg/kg/day in 3 divided doses for 1 day. For infections with Paragonimus westermani, treatment should be administered for a total of 2 days. Nanophyetus salmincola infections are treated with praziquantel at a dose of 60 mg/kg/day in 3 doses for 1 day. Praziquantel is also the drug of choice for most infections with schistosomes. The dose for Schistosoma mansoni and Schistosoma haematobium infection is 40 mg/kg/day in 2 doses for one day, while for Schistosoma japonicum infection the dose is 60 mg/kg/day in 3 doses for one day. Alternatively, oxamniquine (Vansil) can be used to treat Schistosoma mansoni infections at a one dose of 15 mg/kg.

Albendazole (see nematode infections above) is also an effective therapeutic agent for the treatment of neurocysticercosis14 and echinococcosis. The dose is 15 mg/kg/day (maximum dose 800 mg/day) in 2 doses for 8 to 30 days for neurocysticercosis and 15 mg/kg/day (maximum dose 800 mg/day) in 2 doses for 1 to 6 months for echinococcosis.

Triclabendazole, which is available through the CDC, is used for treatment of infections with Fasciola hepatica. Bithionol is no longer a first-line drug. The dose of triclabendazole is 10 mg/kg PO once or twice.

Drugs for the Treatment of Protozoan Infections

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Intestinal Protozoa

Metronidazole (Flagyl) is a nitroimidazole frequently used in the treatment of infections caused by anaerobic bacteria but is also effective for treatment of parasites that use anaerobic metabolism. Most of the parasites that are sensitive to metronidazole are intestinal protozoa, including Entamoeba histolytica, Entamoeba polecki, Giardia lamblia, Blastocystis hominis, and Balantidium coli. Metronidazole is also the drug of choice for Trichomonas vaginalis infection. Metronidazole will kill the trophozoites of E histolytica in the intestine and tissue, but it will not eradicate the cyst form. Therefore, therapy for intestinal amebiasis usually is followed with a luminal agent.15 Side effects include nausea, vomiting, and a disulfiram-like reaction that precludes the use of alcohol while on therapy.

The recommended dose of metronidazole is 15 mg/kg/day (maximum dose 250 mg) divided 3 times a day for infection with G lamblia. A 5-day to 7-day course is recommended for giardiasis. For trichomoniasis, 2 g may be given once or 500 mg twice a day for 7 days. The pediatric dosing is 15 mg/kg/day divided into 3 doses for 7 days. The dose of tinidazole, a related nitroimidazole, for giardiasis is 50 mg/kg once, with a maximum dose of 2 g for adults. For amebiasis, as well as infections with E polecki and B hominis, the recommended dose is 50 mg/kg/day (maximum dose 2 g) in 1 dose for 3 days. Of note, tinidazole was recently approved by the FDA and appears to be as effective as and better tolerated than metronidazole.16 Nitazoxanide is also effective against intestinal protozoan infections and is approved by the FDA for use in children older than 2 years.17 Furazolidone (Furoxone) is an alternative drug for G lamblia infections in children and has activity against some bacterial pathogens. Side effects are mostly gastrointestinal, including nausea, vomiting, and a disulfiram-like reaction similar to that of metronidazole. The recommended dose for giardiasis is 6 mg/kg/day divided 4 times a day (maximum dose 100 mg) for 7 to 10 days.

Iodoquinol (Yodoxin) is an oxyquinolone with activity against the luminal stages of E histolytica, B hominis, B coli, and Dientamoeba fragilis. It is used primarily as adjunctive therapy in amebiasis with metronidazole in order to eradicate both the tissue stages (trophozoites) and intestinal cysts of the parasite. The dose is 30 to 40 mg/kg/day (maximum dose 2 g) divided 3 times a day for a total of 20 days. Side effects include nausea, diarrhea, abdominal cramps, and, less frequently, skin rash or acne.

Paromomycin (Humatin) is a poorly absorbed aminoglycoside antibiotic that is an alternative agent for the treatment of intestinal protozoa, including G lamblia, E histolytica, D fragilis, and Cryptosporidium species. In patients with underlying renal insufficiency, it may cause nephrotoxicity and ototoxicity. The recommended dose of paromomycin is 25 to 35 mg/kg/day in 3 divided doses for 7 to 10 days.

Albendazole (see nematode infections above) is the drug of choice for microsporidiosis, caused by intestinal infections with Encephalitozoon intestinalis, as well as tissue infections caused by E hellem, Encepalitozoon cuniculi, Trachipleistophora species, and Pleistophora species. The recommended dose is 400 mg twice a day, although the optimal duration of therapy is unknown.

Other Blood and Tissue Protozoa

Nifurtimox (Lampit) is used in the treatment of American trypanosomiasis (Chagas disease).23 The side effects of nifurtimox include anorexia, vomiting, and neurologic toxicities, including sleep disorders, parasthesias, tremors, and, rarely, seizures. Although benznidazole (Rochagan), a nitroimidazole agent, is considered the drug of choice for American trypanosomiasis, it is not available in the United States. Its side effects include gastrointestinal symptoms, neuropathy, psychiatric disturbances, and bone marrow suppression.

Melarsoprol (Arsobal) is effective against the central nervous system stages of African sleeping sickness caused by Trypanosoma brucei rhodesiense and Trypanosoma brucei gambiense. It is a trivalent antimonial compound. Frequent side effects or toxicities include myocardial damage, encephalopathy, hypertension, peripheral neuropathy, and gastrointestinal disturbance. In addition, both a Jarisch-Herxheimer reaction and severe hemolytic anemia have been described, the latter occurring in patients with glucose-6-phosphate dehydrogenase (G-6-PD) deficiency.

Eflornithine (difluoromethylornithine; Oridyl) is the treatment of choice for African sleeping sickness caused by T brucei gambiense. This drug inhibits parasite ornithine decarboxylase and is better tolerated than melarsoprol. Its use is associated with bone marrow suppression (anemia, leukopenia), occasional gastrointestinal symptoms, convulsions, and hallucinations. More recent studies report improved chemotherapeutic efficacy for African sleeping sickness using eflornithine in combination with nifurtimox.

Suramin sodium, which is only available through the Centers for Disease Control and Prevention (CDC), is recommended for the blood-borne stages of African trypanosomiasis, with limited efficacy in patients with advanced central nervous system disease. Its frequent side effects include gastrointestinal symptoms and hypersensitivity reactions. Long-term administration has been associated with ocular, renal, hepatic, and neurologic toxicity.

Sodium stibogluconate (Pentostam) is an antimonial compound used for the treatment of leishmaniasis. Meglumine antimonate (Glucantime), a closely related pentavalent antimonial, is frequently used outside the United States. Side effects of these two agents include gastrointestinal symptoms, myalgias, arthralgias, transaminitis, and occasionally electrocardiogram changes.

Amphotericin B deoxycholate, as well as the newer lipid-associated formulations, are alternative agents for the treatment of certain types of leishmaniasis. The lipid formulations are associated with substantially less nephrotoxicity than the deoxycholate preparation and can be used to treat both children and adults.24

Pentamidine isethionate (Pentam 300), a diamidine, is an alternative therapy for the treatment of African trypanosomiasis and leishmaniasis. It is usually well tolerated, but its use has been associated with hypotension and hypoglycemia.

The antibiotic clindamycin is used in conjunction with quinine sulfate for the treatment of infections caused by Babesia species.21 This combination is also an alternative regimen for the treatment of chloroquine-resistant malaria. The use of clindamycin has been associated with Clostridium difficile pseudomembranous colitis.

Pyrimethamine (Daraprim) (see antimalarials above), in combination with sulfadiazine, is the drug of choice for Toxoplasma gondii infections. The dose of pyrimethamine is 2 mg/kg/day for 2 days, followed by 1 mg/kg/day (maximum dose 25 mg/day) for 4 weeks. The dose of sulfadiazine is 100 to 200 mg/kg/day for 3 to 4 weeks. Leucovorin should be given with each dose of pyrimethamine. For congenital toxoplasmosis, a dose of pyrimethamine should be given every 2 or 3 days and a sulfonamide daily for up to a year. The CDC no longer recommends the use of sulfadoxine and pyrimethamine for the treatment of malaria due to the increasing resistance of Plasmodium falciparum.

Drugs for the Treatment of Ectoparasite Infestations

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Infestations with lice or scabies are both treated with topical permethrin (Nix, Elimite) (see Chapter 368).25,26 The use of this agent has been associated with pain, burning, or an erythematous rash. For lice (Pediculus humanus, Pediculus humanus capitis, and Phthirus pubis), the concentration of permethrin is 1%, whereas for scabies infestation (Sarcoptes scabiei) a 5% topical solution is recommended. Ivermectin is also effective in a single oral dose of 200 μg/kg for the treatment of scabies and should be repeated in 10 to 14 days.

References

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Chapter 323. Antiparasitic Therapy

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Antiparasitic Therapy: Introduction

Drugs for the Treatment of Helminth Infections

Nematodes

Cestode and Trematode Infections

Drugs for the Treatment of Protozoan Infections

Intestinal Protozoa

Other Blood and Tissue Protozoa

Drugs for the Treatment of Ectoparasite Infestations

References

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