Antiprotozoal drugs II: miscellaneous agents

CHAPTER 99


Antiprotozoal drugs II: miscellaneous agents


For two reasons—increased world travel by Americans and increased immigration from regions where infectious protozoa are endemic (South America, Asia, Africa)—the incidence of protozoal infection in the United States is rising. The organisms encountered most frequently are Entamoeba histolytica, Trichomonas vaginalis, and Giardia lamblia (also known as G. duodenalis). Infections with most other protozoa (eg, Leishmania species, trypanosomes) are rare in North America. In approaching the antiprotozoal drugs, we begin with the diseases that protozoa produce, and then discuss the drugs used for treatment.




Protozoal infections


Our goal in this section is to describe the major protozoal infections, except for malaria, which is the subject of Chapter 98. Discussion focuses on causative organisms, sites of infection, symptoms, and preferred drug therapy. Causative organisms and drugs of choice are summarized in Table 99–1.








Amebiasis


Amebiasis is an infestation with Entamoeba histolytica. The disease affects between 1% and 4% of Americans and about 10% of people worldwide, causing 100,000 deaths each year. The principal site of infestation is the intestine. However, amebas may migrate to other tissues, most commonly the liver, where abscesses may form. Amebiasis is usually asymptomatic. When symptoms are present, the most characteristic are diarrhea, abdominal pain, and weight loss.


Drugs of choice are iodoquinol, paromomycin, metronidazole, and tinidazole. Iodoquinol and paromomycin are only active against amebas residing in the intestine. Metronidazole and tinidazole are active against amebas that inhabit the intestine, liver, and all other sites. For patients with asymptomatic intestinal infection, therapy with iodoquinol or paromomycin is sufficient. For patients with severe intestinal disease or with liver abscesses, metronidazole or tinidazole is given initially, followed by either iodoquinol or paromomycin.


Iodoquinol, metronidazole, and tinidazole are discussed below. Paromomycin is discussed in Chapter 87.



Cryptosporidiosis


Cryptosporidiosis is caused by Cryptosporidium parvum, a protozoan of the subclass Coccidia. Cryptosporidium parvum is an obligate intracellular parasite that can infect the intestinal tract of humans, cattle, and other mammals. Transmission is fecal-oral, often by ingesting water contaminated with livestock feces. The infection may also be acquired by animal-to-human contact, person-to-person contact, and ingestion of contaminated fruits or vegetables. Cryptosporidiosis is characterized by diarrhea, abdominal cramps, anorexia, low-grade fever, nausea, and vomiting. For immunocompetent patients, the disease is generally mild and self-limited. However, for those who are severely immunosuppressed (owing to HIV infection, cancer chemotherapy, or other causes), the disease can be prolonged and life threatening, with diarrhea volume up to 20 L/day. Nitazoxanide [Alinia] is the treatment of choice. The drug is very effective in immunocompetent patients, and much less effective in those who are immunosuppressed.



Giardiasis


Giardiasis is an infection with Giardia lamblia, also known as G. duodenalis. In the United States, giardiasis has a prevalence of 1 in 14,000. Infestation usually occurs by contact with contaminated objects or by drinking contaminated water. The primary habitat of G. lamblia is the upper small intestine. Occasionally, organisms migrate to the bile ducts and gallbladder. As many as 50% of affected individuals remain symptom free. However, symptoms that are both unpleasant and uncomfortable can develop. These include profound malaise; heartburn; vomiting; colicky pain after eating; and malodorous belching, flatulence, and diarrhea. The pain associated with giardiasis may mimic that of gallstones, appendicitis, peptic ulcers, or hiatal hernia. Drugs of choice are metronidazole, tinidazole, and nitazoxanide.



Leishmaniasis


The term leishmaniasis refers to infestation by certain protozoal species belonging to the genus Leishmania. Worldwide, the incidence of leishmaniasis is estimated at 12 million, with up to 2 million new cases each year. The disease is acquired through the bite of sand flies indigenous to tropical and subtropical regions. In the human host, the parasites take up residence inside cells of the reticuloendothelial system.


Leishmaniasis has three different forms: cutaneous, mucocutaneous, and visceral. The particular form is determined by the species of Leishmania involved. The forms of leishmaniasis vary greatly in severity, ranging from mild (cutaneous leishmaniasis) to potentially fatal (visceral leishmaniasis). In cutaneous leishmaniasis, a nodule forms at the site of inoculation; later, this nodule may evolve into an ulcer that is very slow to heal. Mucocutaneous leishmaniasis is characterized by ulceration in the mucosa of the mouth, nose, and pharynx. Symptoms of visceral leishmaniasis include fever, hepatosplenomegaly, liver dysfunction, hypoalbuminemia, pancytopenia, lymphadenopathy, and hemorrhage. Left untreated, visceral disease is frequently fatal. For all forms of leishmaniasis, sodium stibogluconate (given IM or IV) is the traditional treatment of choice. Liposomal amphotericin B (given IV) is an effective alternative. Miltefosine, an oral agent, is highly curative against visceral leishmaniasis, and probably against cutaneous disease. The drug appears reasonably safe and, owing to oral administration, is more convenient than stibogluconate or amphotericin B, both of which are given parenterally. Unfortunately, miltefosine is not available in the United States.




Trichomoniasis


Trichomoniasis is caused by Trichomonas vaginalis, a flagellated protozoan. Trichomoniasis is a common disease, affecting about 170 million people worldwide. In the United States, about 8 million new cases occur annually. The usual site of infestation is the genitourinary tract. Parasites may also inhabit the rectum. In females, infection results in vaginitis. In males, infection causes urethritis. The disease is usually transmitted by direct sexual contact but can also be acquired by contact with contaminated objects (eg, dildos). Metronidazole is the traditional drug of choice. However, tinidazole is just as effective and somewhat better tolerated, although much more expensive. Trichomoniasis is discussed further in Chapter 95 (Drug Therapy of Sexually Transmitted Diseases).



Trypanosomiasis


There are two major forms of trypanosomiasis: American trypanosomiasis and African trypanosomiasis. Both forms are caused by protozoal species in the genus Trypanosoma.



American trypanosomiasis (chagas’ disease).


Chagas’ disease is caused by infection with Trypanosoma cruzi, a flagellated protozoan. The disease is prevalent in South America and the Caribbean, where it affects some 10 million people. In the United States, about 300,000 are affected. The parasites are harbored in the digestive tract of certain blood-sucking bugs, and are transmitted as follows: The bug bites a sleeping person (usually on the face) and also defecates; the parasites, which are contained in the bug’s feces, are then forced into the bite wound by rubbing or scratching. An early sign of the disease is swelling and severe inflammation at the site of inoculation. Over time, parasites invade cardiac cells and neurons of the myenteric plexus. Destruction of these cells can cause cardiomyopathy, megaesophagus, and megacolon. Deaths have occurred, usually secondary to cardiac injury. In its early phase, Chagas’ disease can be treated with nifurtimox or benznidazole. Unfortunately, these drugs are less effective against chronic infection.



African trypanosomiasis (sleeping sickness).


African trypanosomiasis, transmitted by the bite of the tsetse fly, is caused by two subspecies of Trypanosoma brucei: T. brucei gambiense, which causes West African sleeping sickness, and T. brucei rhodesiense, which causes East African sleeping sickness. Disease caused by either subspecies has similar symptoms. Early symptoms, which involve the hemolymphatic system, include fever, lymphadenopathy, hepatosplenomegaly, dyspnea, and tachycardia. Late symptoms, which result from involvement of the central nervous system (CNS), include mental dullness, incoordination, and apathy. As CNS involvement advances, sleep becomes continuous and death may eventually follow. During the early (hemolymphatic) phase of African trypanosomiasis, pentamidine and suramin are the drugs of choice. (Pentamidine is preferred for disease caused by T. brucei gambiense, and suramin is preferred for disease caused by T. brucei rhodesiense.) During the late (CNS) stage, melarsoprol and eflornithine are drugs of choice. (Either drug can be used against T. brucei gambiense, but only melarsoprol is preferred for T. brucei rhodesiense.) All four drugs—pentamidine, suramin, eflornithine, and melarsoprol—can produce serious side effects. Treatment is difficult and frequently unsuccessful.




Drugs of choice for protozoal infections


Iodoquinol


Iodoquinol [Yodoxin] is a drug of choice for asymptomatic intestinal amebiasis. In addition, the drug is employed in conjunction with metronidazole to treat symptomatic intestinal infection and systemic amebiasis. In these last two cases, iodoquinol is administered to eliminate any surviving intestinal parasites after treatment with metronidazole. Very little iodoquinol is absorbed, and hence the drug is not active against systemic amebiasis.



Iodoquinol is generally well tolerated. Mild reactions occur occasionally. These include rash, acne, slight thyroid enlargement, and GI effects (nausea, vomiting, diarrhea, cramps, pruritus ani). Rarely, prolonged therapy at very high doses has caused optic atrophy with permanent loss of vision.


Iodoquinol [Yodoxin] is available in tablets (210 and 650 mg) and as a powder for oral administration, preferably after a meal. The usual adult dosage is 650 mg 3 times a day for 20 days. The dosage for children is 30 to 40 mg/kg/day (given in three divided doses) for 20 days.




Metronidazole


Metronidazole [Flagyl, Protostat, Metric 21], a drug in the nitroimidazole family, is active against several protozoal species, including E. histolytica, G. lamblia, and T. vaginalis. The drug is also active against anaerobic bacteria (see Chapter 91).




Therapeutic uses.

Metronidazole is a drug of choice for symptomatic intestinal amebiasis and systemic amebiasis. Because most of each dose is absorbed in the small intestine, metronidazole concentrations in the colon remain low, allowing amebas there to survive. To kill these survivors, metronidazole is followed by either iodoquinol or paromomycin, amebicidal drugs that achieve high concentrations in the colon.


Metronidazole is a drug of choice for giardiasis, and for trichomoniasis in males as well as females.


Many anaerobic bacteria are sensitive to metronidazole. Antibacterial applications are discussed in Chapter 91.

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Jul 24, 2016 | Posted by in NURSING | Comments Off on Antiprotozoal drugs II: miscellaneous agents

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