Antiprotozoal Drugs

Antiprotozoal Drugs

1. Definition, scope & general principles

• Antiprotozoal (non-malarial) drugs are agents used against the pathogenic protozoa of humans other than Plasmodium — chiefly Entamoeba histolytica (amoebiasis), Giardia intestinalis/lamblia (giardiasis), Trichomonas vaginalis (trichomoniasis), Leishmania spp. (leishmaniasis/kala-azar), Trypanosoma spp. (sleeping sickness, Chagas disease), and Toxoplasma gondii (toxoplasmosis) (G&G 14e Ch.67, pp.1309–12; KDT 8e Ch.62, p.893).
• Humans host protozoa transmitted by insect vectors (sandfly, tsetse fly, triatomid bug), from mammalian reservoirs (zoonoses), or person-to-person (faecal–oral, sexual) (G&G 14e Ch.67, p.1309).
• The immune system is pivotal — many protozoa cause opportunistic/severe disease chiefly in the immunosuppressed (infants, cancer, transplant, HIV/AIDS); leishmaniasis, cryptosporidiosis and toxoplasmosis are recognised AIDS-associated opportunistic infections (G&G 14e Ch.67, pp.1309, 1311–12).
• No effective vaccines exist, so chemotherapy is the only practical means to both treat individuals and reduce transmission (G&G 14e Ch.67, p.1309).
• Key therapeutic problem: many antiprotozoals are toxic at therapeutic doses, compounded by increasing drug resistance (e.g. antimonial-resistant kala-azar in India; metronidazole-resistant T. vaginalis; melarsoprol resistance) (G&G 14e Ch.67, p.1309; KDT 8e Ch.62, pp.902–04).
• Selective toxicity in this class most often arises from parasite-specific biochemistry: the amitochondriate/anaerobic energy metabolism (nitroimidazole activation via PFOR), the trypanosomatid-unique trypanothione redox system, parasite-specific transporters (TbAT6, TbAQP2), and the absence of a mammalian homologue of the type-1 nitroreductase (fexinidazole/nifurtimox) (G&G 14e Ch.67, pp.1312–13, 1316).