Category:Antiprotozoals

An antiprotozoal is a medicine used to treat infection by a parasitic protozoan organism. The category sits within the broader antiparasitics umbrella and covers the medicines for malaria (collected as a separate sub-category at antimalarials), for the intestinal and urogenital protozoa (Giardia lamblia, Entamoeba histolytica, Trichomonas vaginalis), for the blood and tissue protozoa (Leishmania species, Trypanosoma cruzi for Chagas disease, Trypanosoma brucei for African sleeping sickness, Toxoplasma gondii, Babesia microti), and for the opportunistic protozoa in immunocompromised patients (Cryptosporidium parvum, Cystoisospora belli, the microsporidia now reclassified as fungi).

The pharmacology of the protozoa is, in general, more difficult than that of the bacteria, for two reasons. The first is biological: protozoa are eukaryotes, sharing most of their cell biology with the human host, and selective toxicity must be obtained by exploiting parasite-specific organelles (the apicoplast of Plasmodium and Toxoplasma; the kinetoplast of the trypanosomatids; the hydrogenosome of Trichomonas), parasite-specific enzymes (dihydrofolate reductase variants, trypanothione reductase, pteridine reductase), or pharmacokinetic concentration at the parasite's life-cycle compartment. The second is epidemiological: most of the protozoan diseases occur predominantly in low-resource tropical settings, with limited commercial market for new medicines, and the contemporary antiprotozoal pipeline depends substantially on public-private partnerships and donation programmes.

The antimalarial story dominates the category. The cinchona bark, used by indigenous Peruvians and brought to Europe by Jesuit missionaries in the 1630s, contained quinine as its active alkaloid; quinine was isolated by Pelletier and Caventou in 1820 and remained the standard antimalarial for over a century. Synthetic 4-aminoquinolines followed in the 1930s (chloroquine at IG Farben, primaquine at the U.S. wartime research programme). Chloroquine resistance in Plasmodium falciparum emerged in southeast Asia in the 1950s and spread globally over the following three decades; mefloquine and the antifolate combinations sulfadoxine-pyrimethamine and proguanil filled the gap before they too lost efficacy to resistance. The artemisinin story, told under antiparasitics, gave the current first-line treatment: artemisinin-based combination therapies that pair a short-acting artemisinin derivative with a longer-acting partner agent (artemether-lumefantrine, artesunate-amodiaquine, artesunate-mefloquine, dihydroartemisinin-piperaquine) to reduce the selection pressure for resistance. The 8-aminoquinoline primaquine eliminates the hypnozoite liver stage of P. vivax and P. ovale and prevents relapse, with the important contraindication of G6PD deficiency. Tafenoquine, a single-dose primaquine alternative, was approved in 2018.

The intestinal protozoa are treated principally with the nitroimidazoles. Metronidazole, introduced by Rhône-Poulenc in 1959 for trichomoniasis, was found also to be active against Giardia lamblia and against the invasive trophozoite stages of Entamoeba histolytica;^[1] tinidazole (Pfizer, 1972) and secnidazole have similar mechanism and broader pharmacokinetics. Paromomycin and iodoquinol are luminal amebicides used as follow-up after metronidazole eradication of invasive disease, on the rationale that the nitroimidazoles do not reliably reach the colonic-lumen trophozoites. Nitazoxanide (Romark, 2002), a thiazolide developed for cryptosporidiosis in immunocompromised patients, has activity against a broad range of intestinal protozoa and is used for cryptosporidiosis and giardiasis.

The kinetoplastid protozoa, the trypanosomatids responsible for leishmaniasis and the two trypanosomiases, have produced some of the most difficult therapeutic problems in tropical medicine. The pentavalent antimonials (sodium stibogluconate, meglumine antimoniate) introduced in 1912 by Vianna and refined over decades have been the standard antileishmanial; the limitations include parenteral administration, substantial cardiotoxicity, and progressive resistance in Indian visceral leishmaniasis. Liposomal amphotericin B (AmBisome) is now first-line for visceral leishmaniasis in many areas. Miltefosine, an alkylphosphocholine originally developed as an antineoplastic, is the only oral medicine for visceral leishmaniasis and is used as part of WHO regimens. For African trypanosomiasis (sleeping sickness), suramin and pentamidine have been used for stage-1 disease since the early twentieth century; melarsoprol (an organoarsenical) for stage-2 disease has a substantial encephalopathy mortality and has been progressively replaced by the eflornithine-nifurtimox combination and by the more recent oral fexinidazole (DNDi-Sanofi, 2018) and acoziborole (in trial, single-dose oral). The American trypanosomiasis (Chagas disease) is treated with benznidazole (Roche, 1971) or nifurtimox; both are imperfect medicines with limited efficacy in the chronic phase and significant adverse-effect profiles.

The opportunistic protozoa in immunocompromised hosts complete the category. Toxoplasma is treated with pyrimethamine (Daraprim, the medicine whose 2015 price increase by Turing Pharmaceuticals brought it into political-headline territory) plus sulfadiazine, with folinic-acid rescue to limit the bone-marrow toxicity. Pneumocystis jirovecii, now classified as a fungus but historically treated as a parasite, responds to trimethoprim-sulfamethoxazole, dapsone, or atovaquone. Cryptosporidium parvum has no consistently effective treatment in the immunocompromised host beyond nitazoxanide and the restoration of immune function (antiretroviral therapy in HIV). Babesia microti is treated with atovaquone plus azithromycin in mild disease and with clindamycin plus quinine in severe disease.

By organism:

• Antimalarials (extensive sub-category): chloroquine, hydroxychloroquine, mefloquine, primaquine, tafenoquine, the artemisinin-based combination therapies, atovaquone-proguanil, quinine and quinidine, pyrimethamine and sulfadoxine
• Antiamoebic, antigiardial, antitrichomonal (anaerobic intestinal and urogenital protozoa): metronidazole, tinidazole, secnidazole, nitazoxanide, paromomycin, iodoquinol
• Antileishmanial: liposomal amphotericin B, sodium stibogluconate, meglumine antimoniate, miltefosine, paromomycin
• Antitrypanosomal:
  • African (sleeping sickness): suramin, pentamidine (stage 1); melarsoprol, eflornithine-nifurtimox combination, fexinidazole (stage 2)
  • American (Chagas disease): benznidazole, nifurtimox
• Antitoxoplasmal: pyrimethamine + sulfadiazine + folinic acid; trimethoprim-sulfamethoxazole alternative
• Anticryptosporidial / anti-cystoisosporiasis: nitazoxanide
• Antibabesial: atovaquone + azithromycin, clindamycin + quinine

The boundary of this category is "medicine used to treat infection by a parasitic protozoan." The antimalarials are collected as a sub-category for convenience, given the size and clinical importance of malaria; they are antiprotozoals in this category sense. The anthelmintic medicines (against the parasitic worms) are listed under antiparasitics separately. The medicines for Pneumocystis jirovecii are listed under antibacterials by their chemical class (trimethoprim-sulfamethoxazole, the older pentamidine, atovaquone) even though the organism is now reclassified as a fungus and was historically a protozoan; the contemporary listing follows the medicine chemistry. The medicines for the microsporidia (albendazole for Encephalitozoon and Enterocytozoon) are listed under the anthelmintic side of antiparasitics for the same chemical-class reason despite the recent reclassification of microsporidia as fungi.

This category page is an encyclopedia article about its subject. The actual index of medicines belonging to the category is generated automatically by the wiki engine, from category-membership declarations on the individual medicine pages, and appears at the foot of the page below the references.