Chapter: Modern Pharmacology with Clinical Applications: Antiprotozoal Drugs

Protozoal Diseases

The protozoan Entamoeba histolytica causes amebiasis, an infection that is endemic in parts of the United States.



Amebiasis and Balantidial Dysentery


The protozoan Entamoeba histolytica causes amebiasis, an infection that is endemic in parts of the United States. The parasite can be present in the host as either an encysted or a trophozoite form. Initial ingestion of the cyst may result either in no symptoms or in severe amebic dysentery characterized by the frequent pas-sage of bloodstained stools. The latter symptom occurs after invasion of the intestinal mucosa by the actively motile and phagocytic trophozoite form of the proto-zoan.

Trophozoites may spread to the liver through the portal vein and produce acute amebic hepatitis, or more rarely, the trophozoites may encyst and produce an amebic liver abscess many years later. On rare occa-sions, amebic abscesses are found in other organs, such as the lungs or the brain.


Many patients continue to excrete cysts for several years after recovery from the acute disease and there-fore are a hazard to themselves and other persons; the public health risk is greatest when persons employed as food handlers are affected. More recently, it has been recognized that infection can be transmitted by sexual activities.


Balantidium coli is the largest of the protozoans that infect humans. The trophozoite form is covered with cilia, which impart mobility. Infection is acquired through the ingestion of cyst-contaminated soil, food, or water. The trophozoite causes superficial necrosis or deep ulceration in the mucosa and submucosa of the large intestine. Otherwise healthy persons commonly exhibit nausea, vomiting, abdominal pain, and diarrhea, whereas debilitated or nutritionally stressed patients may develop severe dysentery.


Trichomoniasis and Giardiasis


Trichomoniasis is a genital infection produced by the protozoan Trichomonas vaginalis. Infections frequently are asymptomatic in the male, whereas in the female vaginitis characterized by a frothy pale yellow discharge is common. Relapses occur if the infected person’s sex-ual partner is not treated simultaneously.


Giardiasis is caused by the protozoan Giardia lam-blia and is characterized by gastrointestinal symptoms ranging from an acute self-limiting watery diarrhea to a chronic condition associated with episodic diarrhea and occasional instances of malabsorption. The parasite is similar to E. histolytica in that it exists in two forms, an actively motile trophozoite (usually confined to the up-per small bowel) and a cyst (commonly excreted in the feces).



Leishmaniasis and Trypanosomiasis


The flagellate leishmania is transmitted to humans by the bite of the female sandfly of the genus Phlebotomus. Three principal diseases result from infection with Leishmania spp. L. donovani causes visceral leishmania-sis (kala-azar); L. tropica and L. major produce cuta-neous leishmaniasis, and L. braziliensis causes South American mucocutaneous leishmaniasis. In visceral leishmaniasis, the protozoan parasitizes the reticuloen-dothelial cells, and this results in an enlargement of the lymph nodes, liver, and spleen; the spleen can become massive. Cutaneous leishmaniasis remains localized to the site of inoculation, where it forms a raised disfiguring ulcerative lesion. South American leishmaniasis is vari-able in its presentation. It is characterized by ulceration of the mucous membranes of the nose, mouth, and phar-ynx; some disfiguring skin involvement also is possible.


African trypanosomiasis follows the bite of Glos-sina, a tsetse fly infected with the protozoan Trypano-soma brucei. The ensuing illness (sleeping sickness) is initially characterized by the hemolymphatic stage of fever, headache, and lymph node enlargement. These symptoms are followed by meningoencephalopathic in-volvement, with wasting, mental disturbances, and drowsiness as the disease progresses. This latter more serious stage requires different, more potentially toxic drugs than does the hemolymphatic stage. There are ge-ographical variations of the disease. Rhodesian sleeping sickness, acquired in the savannah and woodlands of East Africa from Glossina morsitans, is a much more acute and rapidly progressive disease than Gambian sleeping sickness, acquired in riverine areas of West Africa from Glossina palpalis, in which the incubation period can be more prolonged and the disease more protracted.


Chagas’ disease, the South American variety of try-panosomiasis, is caused by Trypanosoma cruzi. It is quite different from African trypanosomiasis in its clin-ical and pathological presentation and in its failure to respond to many agents effective in that disease. It has both an acute and chronic phase. The latter frequently results in gastrointestinal and myocardial disease that ends in death.


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