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I. IntroductionProtozoal infections are common among people in underdeveloped tropical and

subtropical countries, where sanitary conditions, hygienic practices, and control of thevectors of transmission are inadequate. However, with increased world travel, protozoadiseases, such as malaria, amebiasis, leishmaniasis, trypanosomiasis, trichomoniasis, andgiardiasis, are no longer confined to specific geographic locales. Because they areeukaryotes, the unicellular protozoal cells have metabolic processes closer to those of thehuman host than to prokaryotic bacterial pathogens. Protozoal diseases are thus lesseasily treated than bacterial infections, and many of the antiprotozoal drugs cause serioustoxic effects in the host, particularly on cells showing high metabolic activity, such asneuronal, renal tubular, intestinal, and bone marrow stem cells. Most antiprotozoal agentshave not proved to be safe for pregnant patients.

II. Anti-Protozoal Agents

ANTI-MALARIAL DRUGSMalaria is an acute infectious disease caused by four species of the protozoal genus

Plasmodium. The parasite is transmitted to humans through the bite of a femaleAnopheles mosquito, which thrives in humid, swampy areas. Plasmodium falciparum is themost dangerous species, causing an acute, rapidly fulminating disease that ischaracterized by persistent high fever, orthostatic hypotension, and massiveerythrocytosis (an abnormal elevation in the number of red blood cells accompanied byswollen and reddish condition of the limbs). P. falciparum infection can lead to capillaryobstruction and death if treatment is not instituted promptly. Plasmodium vivax causes amilder form of the disease. Plasmodium malariae is common to many tropical regions, butPlasmodium ovale is rarely encountered. Resistance acquired by the mosquito toinsecticides, and by the parasite to drugs, has led to new therapeutic challenges,particularly in the treatment of P. falciparum.

a. Examples

Artemisinin

Chloroquine Mefloquine

Primaquine

Pyrimethamine

Quinine/Quinidine

Amodiaquine

Proguanil

Doxycycline

Halofantrine

Atavoquone-proguanil (Malarone)

b. Mechanism of Action

c. Pharmacokinetics

d. Unwanted Effects

e. Resistance

OTHER ANTI-PROTOZOAL DRUGS

ANTI-AMEBIASIS

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Amebiasis (also called amebic dysentery) is an infection of the intestinal tractcaused by Entamoeba histolytica. The disease can be acute or chronic, with patientsshowing varying degrees of illness, from no symptoms to mild diarrhea to fulminatingdysentery. The diagnosis is established by isolating E. histolytica from fresh feces. Therapyis aimed not only at the acutely ill patient but also at those who are asymptomaticcarriers, because dormant E. histolytica may cause future infections in the carrier and be apotential source of infection for others.

a. Examples

Chloroquine

Dehydroemetine

Emetine

Iodoquinol

Metronidazole

Paramomycin

Tinidazole

Diloxanide furoate


c. Pharmacokinetics

d. Unwanted Effects

e. Resistance

ANTI-TRYPANOSOMIASISTrypanosomiasis refers to two chronic and, eventually, fatal diseases caused by

species of Trypanosoma: African sleeping sickness, and American sleeping sickness(Figure 36.13). In African sleeping sickness, the causative organisms, Trypanosoma bruce

gambiense and Trypanosoma brucei rhodiense, initially live and grow in the blood. Theparasite invades the CNS, causing an inflammation of the brain and spinal cord thatproduces the characteristic lethargy and, eventually, continuous sleep. Chagas' disease(American sleeping sickness) is caused by Trypanosoma cruzi and occurs in SouthAmerica.

a. Examples

Benznidazole

Melarsoprol

Nifurtimox

Pentamidine

Suramin

Eflornithine


c. Pharmacokinetics

d. Unwanted Effects

e. Resistance

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ANTI-LEISHMANIASISThere are three types of leishmaniasis: cutaneous, mucocutaneous, and visceral

[Note: In the visceral type (liver and spleen), the parasite is in the bloodstream and cancause very serious problems.] Leishmaniasis is transmitted from animals to humans (andbetween humans) by the bite of infected sandflies. The diagnosis is established bydemonstrating the parasite in biopsy material and skin lesions. The treatments ofleishmaniasis and trypanosomiasis are difficult, because the effective drugs are limited bytheir toxicities and failure rates. Pentavalent antimonials, such as sodium stibogluconate,are the conventional therapy used in the treatment of leishmaniasis, with pentamidine andamphotericin B as backup agents. Allopurinol has also been reported to be effective (it isconverted to a toxic metabolite by the amastigote form7 of the organism).

a. Examples

Sodium stibogluconate

Meglumine antimonate


c. Pharmacokinetics

d. Unwanted Effects

e. Resistance

ANTI- TOXOPLASMOSISOne of the most common infections in humans is caused by the protozoan

Toxoplasma gondii, which is transmitted to humans when they consume raw orinadequately cooked, infected meat.An infected pregnant woman can transmit theorganism to her fetus. Cats are the only animals that shed oocysts, which can infect otheranimals as well as humans. The treatment of choice for this condition is the antifolate drugpyrimethamine. A combination ofsulfadiazine andpyrimethamine is also efficacious.Leucovorin is often administered to protect against folate deficiency. Other inhibitors offolate biosynthesis, such as trimethoprim and sulfamethoxazole, are without therapeuticefficacy in toxoplasmosis.

a. Examples

Pyrimethamine


c. Pharmacokinetics

d. Unwanted Effects

e. Resistance

ANTI-GIARDIASIS

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Giardia lamblia is the most commonly diagnosed intestinal parasite in the UnitedStates.10 It has only two life-cycle stages: the binucleate trophozoite with four flagellae,and the drug-resistant, four-nucleate cyst. Ingestion, usually from contaminated drinkingwater, leads to infection. The trophozoites exist in the small intestine and divide by binaryfission. Occasionally, cysts are formed that pass out in the stool. Although some infectionsare asymptomatic, severe diarrhea can occur, which can be very serious in immune-suppressed patients. The treatment of choice is metronidazole for 5 days. One alternativeagent is tinidazole, which is equally effective as metronidazole in treatment of giardiasisbut with a much shorter course of treatment (2 g given once). Nitazoxanide, anitrothiazole derivative structurally similar to aspirin, was recently approved for treatmentof giardiasis. Nitazoxanide is also equally efficacious as metronidazole and, in comparison,has a 2 day shorter course of therapy.

a. Examples

Metronidazole

Nitazoxanide

Tinidazole


c. Pharmacokinetics

d. Unwanted Effects

e. Resistance

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