Antiprotozoan Drugs

Abstract

Parasitic diseases caused by unicellular protozoa account for a huge burden of morbidity, mortality and economic deprivation across the globe. Current drugs for the treatment of such infections, particularly malaria, trypanosomiasis and leishmaniasis, are inadequate and new therapies are being sought. A review of currently available therapies for protozoal infections of medical importance is presented. Potential new treatments in the drug development pathway are also discussed. There are no registered vaccines available for any protozoal diseases, and only in the case of malaria are there candidate vaccines that have passed beyond Phase I clinical trials.

Key concepts

  • Understand the worldwide problem of parasitic protozoa and how they cause disease.

  • Understand the range of treatments available and which is best for a specific disease.

  • Understand the range of antimalarials available and their basic history.

  • Understand the limited treatment options available against other coccidian parasites such as Toxoplasma and Cryptosporidium.

  • Understand the therapies available for trypanosomiasis and leishmaniasis.

  • Understand the new therapies against parasitic protozoa currently under development.

  • Understand the various options available in the design and development of vaccines against malaria and other parasitic protozoa.

Keywords: malaria; trypanosomiasis; leishmaniasis; antimalarials; vaccines

Figure 1.

Antimalarials: (a) chloroquine, (b) quinine, (c) the quinoline derivatives piperaquine, (d) mefloquine, (e) amodiaquine, (f) halofantrine and (g) lumefantrine.

Figure 2.

Antiprotozoal naphthoquinones: (a) parvaquone, (b) buparvaquone and (c) atovaquone.

Figure 3.

Antifolates: (a) pyrimethamine, (b) proguanil and (c) cycloguanil.

Figure 4.

Antiprotozoal 8‐aminoquinolines: (a) primaquine, (b) tafenoquine and (c) sitamaquine.

Figure 5.

Antimalarials: (a) artemisinin and (b) its derivatives dihydroartemisinin, artemether and artesunate.

Figure 6.

Anticoccidial ionophores: (a) monensin, (b) lasalocid and (c) salinomycin.

Figure 7.

Antitrypanosomal diamidines: (a) pentamidine and (b) diminazene (berenil).

Figure 8.

Antiprotozoal organometallics: (a) melarsoprol and (b) meglumine antimoniate (Glucantime).

Figure 9.

Anticancer and antifungal drugs with antitrypanosomal and antileishmanial activity: (a) eflornithine, (b) miltefosine, (c) amphotericin B and (d) SCH‐56592.

Figure 10.

Antiprotozoal nitroheterocyclics: (a) nifurtimox, (b) benznidazole and (c) metronidazole.

Figure 11.

Candidate vaccine compartments at each stage of the Plasmodium life cycle, which proceeds clockwise. The names of parasite proteins considered possible vaccine targets are given around the periphery. AMA, apical membrane antigen; CSP, circumsporozoite surface protein; EBA, erythrocyte‐binding antigen; LSA, liver stage antigen; MSP, merozoite surface protein; PfEMP, Plasmodium falciparum erythrocyte membrane protein; Pfs, Plasmodium falciparum sexual (stage antigen).

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Carter R, Mendis KN, Miller LH, Molineaux L and Saul A (2000) Malaria transmission‐blocking vaccines – how can their development be supported? Nature Medicine 6: 241–244.

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Winstanley P and Ward S (2006) Malaria chemotherapy. Advances in Parasitology 61: 47–76.

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Fivelman, Quinton L, Yardley, Vanessa, and Sutherland, Colin J(Mar 2009) Antiprotozoan Drugs. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0001979.pub2]