Antiprotozoal Drugs

Antiprotozoal drugs treat infections by single-celled parasites other than malaria, including amoebiasis, giardiasis, trichomoniasis, cryptosporidiosis, toxoplasmosis and the trypanosomiases and leishmaniases. They fall into a few functional groups, and several drugs act on more than one organism.

Mechanisms.

• Nitroimidazoles (metronidazole, tinidazole, secnidazole): reduced in anaerobic parasites to form radicals that damage DNA.
• Nitazoxanide: inhibits pyruvate-ferredoxin oxidoreductase.
• Paromomycin: aminoglycoside acting on the parasite ribosome; poorly absorbed, so it acts in the gut lumen.
• Diloxanide furoate: luminal amoebicide.
• Pyrimethamine with sulphadiazine: sequential folate synthesis blockade.
• Pentamidine, miltefosine, sodium stibogluconate, benznidazole and nifurtimox: used for leishmaniasis, trypanosomiasis and Chagas disease.

• Metronidazole: amoebiasis, giardiasis, trichomoniasis, bacterial vaginosis, anaerobic infection.
• Tinidazole: single-dose alternative with a longer half-life.
• Nitazoxanide: Cryptosporidium and Giardia, 500 mg twice daily for 3 days (adults).
• Paromomycin or diloxanide: clear gut cysts after invasive amoebiasis.
• Pyrimethamine with sulphadiazine and folinic acid: toxoplasmosis.

Amoebiasis. Invasive disease (colitis, liver abscess): metronidazole 500 to 800 mg three times daily for 5 to 10 days (adult), then a luminal agent: paromomycin 25 to 35 mg/kg daily in three doses for 7 days, or diloxanide furoate 500 mg three times daily for 10 days.

Giardiasis. Tinidazole 2 g single dose, or metronidazole 250 mg three times daily for 5 days, or nitazoxanide 500 mg twice daily for 3 days.

Trichomoniasis. Metronidazole 400 to 500 mg twice daily for 7 days, or 2 g single dose; treat partners.

Cryptosporidiosis. Nitazoxanide 500 mg twice daily for 3 days in immunocompetent patients. In HIV, antiretroviral therapy restores immunity and is the main treatment.

Toxoplasmosis (cerebral, HIV). Pyrimethamine 200 mg loading, then 50 mg daily (under 60 kg) or 75 mg daily (60 kg and over), with sulphadiazine 1 g four times daily (under 60 kg) or 1.5 g four times daily (60 kg and over) and folinic acid 10 to 25 mg daily, for at least 6 weeks; alternative co-trimoxazole. Then lower-dose maintenance.

Region. In East Africa, amoebiasis, giardiasis and cryptosporidiosis are common causes of diarrhoea, especially in children and people with advanced HIV. Cerebral toxoplasmosis is a frequent cause of focal brain lesions in advanced HIV.

Contraindications. Previous hypersensitivity to nitroimidazoles. Sulphadiazine with sulphonamide allergy and G6PD deficiency. Pyrimethamine in the first trimester when alternatives exist.

Serious adverse effects. Metronidazole: metallic taste, nausea, peripheral neuropathy and encephalopathy with prolonged use, seizures. Pyrimethamine: marrow suppression, so folinic acid is essential. Sulphadiazine: crystalluria, rash, Stevens-Johnson syndrome. Paromomycin: rare ototoxicity and nephrotoxicity if absorbed in colitis.

Interactions. Metronidazole raises warfarin and lithium levels; alcohol should be avoided during treatment and for 48 hours afterwards. Phenytoin and phenobarbital reduce metronidazole levels.

Monitoring. Full blood count weekly with pyrimethamine; fluid intake with sulphadiazine; neurological review for courses over 10 days.

Special groups.

• Pregnancy: metronidazole is used when indicated; avoid pyrimethamine in the first trimester when alternatives exist.
• Breastfeeding: after a single high dose of metronidazole, pause feeding for 12 to 24 hours; after tinidazole, pause for 3 days.
• Liver impairment: reduce metronidazole dose.
• Children: weight-based dosing.

Referral and escalation. Refer amoebic liver abscess not responding in 72 hours, cerebral toxoplasmosis, and persistent diarrhoea.