A Microscopic Look at Parasitic Infections

Parasitic infections affect >3 billion people and are associated with significant morbidity and mortality worldwide. These infections are drawing the increasing attention of clinicians in the United States because of the increase in international travel, the high influx of immigrants from endemic areas, and the steady growth of the immunosuppressed population.¹

A parasite is an organism that must live on other organisms to survive. Parasites usually inflict some degree of injury to the host while utilizing the host's resources for their own growth needs. Parasitic diseases typically are classified by the type of organism causing the infection: protozoa, helminths (worms), or arthropods.

Pharmacologic therapy has an important role, not only in the treatment of parasitic infections, but also in decreasing human transmission of these diseases.² Agents utilized in the management of these diseases may be subdivided into 4 families: antimalarials, antiprotozoan drugs, anthelmintic drugs, and antiectoparasitic drugs. In this article, we will briefly review the most commonly utilized antimalarial, antiprotozoal, and anthelmintic agents and the role of the pharmacist in the management of the most commonly encountered parasitic diseases. Antiectoparasitic agents will not be discussed here.

Antimalarial Agents

Malaria affects ~100 million people each year and is associated with >2 million deaths annually.^1,3 Table 1 lists the pharmacologic agents and the usual treatment doses for these antimalarial agents.

Chloroquine phosphate is the first-line agent used to suppress and treat malaria attacks, but it is not effective for the prevention of relapse. Mefloquine, pyrimethamine, atovaquone-proguanil, and primaquine phosphate are reserved for the treatment of patients with chloroquine- resistant and multidrug-resistant Plasmodium spp. Pyrimethamine should not be used as monotherapy for the treatment of an acute attack of malaria but may be used alone or in combination with other agents for suppression and prevention of the disease. Quinine sulfate has fallen out of favor, primarily because of its toxicity profile.

The most common adverse effects of antimalarial agents include hypotension (from chloroquine), electrocardiogram changes (from chloroquine or quinine), and gastrointestinal (GI) disturbances such as nausea, vomiting, diarrhea, and abdominal pain. GI side effects may be minimized by administering these agents with meals. Infrequent but serious adverse effects include ocular effects, reduced hearing, neuropsychiatric effects, potentially serious hematologic effects, and dermatologic reactions.

Measures to prevent the transmission of malaria are recommended for all patients traveling to areas where the disease is endemic. Pharmacologic therapy with chloroquine or mefloquine should be initiated 1 to 2 weeks prior to the trip and continued for 4 to 6 weeks after returning. Selection of chloroquine versus mefloquine is dependent on the prevalence of chloroquine-resistant Plasmodium spp in the endemic area. This information is readily available from the Centers for Disease Control and Prevention (www.cdc.gov). If atovaquoneproguanil is utilized for prophylaxis, the regimen should be initiated 1 to 2 days before entering an endemic area and continued daily during the stay and for 7 days after returning. All of these agents should be taken at the same time each day or week, depending on the agent utilized. For patients unable to tolerate mefloquine who are traveling to endemic areas with a high prevalence of chloroquine resistance, doxycycline may be used as an alternative for the prevention of malaria transmission. Additional preventive measures include using insect repellent, wearing protective clothing, and using netting to decrease exposure to disease-bearing mosquitoes.

Antiprotozoan Drugs

Antiprotozoan drugs are used to treat parasitic infections such as amebiasis, giardiasis, trichomoniasis, and toxoplasmosis. Table 2 lists the pharmacologic agents falling into this category and the usual treatment doses.

Metronidazole is the prototype antiprotozoan agent and is utilized as firstline therapy in the management of most intestinal protozoan infections. Additional options for these patients include tinidazole, iodoquinol, paromomycin, furazolidone, and nitazoxanide.

The most common adverse effects associated with metronidazole are GI in nature (nausea, vomiting, anorexia, abdominal pain). Other side effects include central nervous system disturbances such as dizziness, lightheadedness, and headache, as well as the possibility of disulfiram reactions in patients who consume alcoholic beverages.

Patients receiving metronidazole must be instructed to avoid alcohol ingestion for 48 hours after completion of metronidazole therapy. Pharmacists should advise patients about the drug's potential to discolor the urine and that this discoloration is harmless. Patients taking metronidazole for trichomonas infections need to understand that their sexual partner must be treated at the same time. Metronidazole should be taken with meals to minimize GI upset.

Tinidazole is a nitroimidazole compound similar to metronidazole. Tinidazole has a similar efficacy profile and slightly better tolerability, compared with metronidazole. It should be taken with meals to minimize GI intolerance. An extemporaneous formulation consisting of crushed tinidazole tablets suspended in cherry syrup may be compounded for patients unable to swallow the tablets. This formulation is stable for 7 days at room temperature. Pharmacists should instruct patients to avoid alcohol ingestion while on tinidazole therapy and for 48 hours after completion, because tinidazole may precipitate a disulfiramlike reaction similar to that produced by metronidazole.⁴

Iodoquinol is an antiprotozoan agent utilized for the management of intestinal protozoan infections. Unlike metronidazole and tinidazole, iodoquinol is active only against parasites that are present in the lumen of the intestine. It has no efficacy against tissue parasites. Adverse effects include GI disturbances, skin disorders, discoloration of hair and nails, headache, and malaise. More serious effects include peripheral neuropathy, optic neuritis, and optic atrophy. Patients who are allergic to iodine should not receive iodoquinol.⁴

Paromomycin is an aminoglycoside antimicrobial agent with activity against intestinal protozoan infections and tapeworm infestations. Similar to iodoquinol, paromomycin's activity is limited to the lumen of the intestine. Because of the drug's poor absorption from the GI tract, systemic side effects are rare, and most adverse reactions are GI in nature, including anorexia, nausea, vomiting, abdominal cramps, and diarrhea.

Furazolidone is a second-line agent, due to its unfavorable safety and druginteraction profile, for the treatment of giardiasis. It may be used in patients intolerant to metronidazole. Patients taking furazolidone should be instructed to avoid tyramine-containing foods, such as aged cheese, aged wine, avocados, and soy sauce. Concomitant monoamine oxidase inhibitor use must be avoided as well to prevent hypertensive crisis. Furazolidone also interacts with selective serotonin reuptake inhibitors, resulting in potential serotonin syndrome.

The most common adverse effects of furazolidone include GI intolerance. Severe reactions with this agent include hemolytic anemia, erythema multiforme, and agranulocytosis. Patients should be instructed to take tablets with meals and to avoid alcohol while taking furazolidone because of the potential for a disulfiram- like reaction.³

Nitazoxanide has efficacy against metronidazole-resistant strains of giardiasis. This agent is well-tolerated with minimal toxicity. It should be taken with food to minimize GI side effects. The availability of an oral suspension makes this agent an attractive option for pediatric patients.⁴

Anthelmintic Agents

Helminth infections are known to affect >1/4 of the world's population and thus present a serious public health concern.³ The prototype and drug of choice for treating most of these infections is mebendazole. Table 3 lists additional treatment options for helmintic infections.

The most common adverse effects associated with mebendazole therapy are limited to the GI tract. Because the drug is poorly absorbed, systemic effects are rare and may include blood abnormalities, dermatologic reactions, hematuria, crystalluria, and liver enzyme elevation.

Patients treated with mebendazole should be instructed to take the medication with small, frequent meals to minimize GI upset. Taking the drug with fatty foods such as milk, cheese, or ice cream increases absorption.

Patients taking mebendazole also should be instructed to drink at least eight 8-oz glasses of fluid daily to decrease the risk of crystalluria. In addition, all family members and close patient contacts should be treated at the same time to avoid reinfection, and all clothing and bed linens should be washed at the time that the whole family is being treated to prevent reinfection.

Albendazole is the newest benzimidazole, with broad-spectrum anthelmintic activity. It is indicated for the treatment of infections caused by larval forms of beef and dog tapeworms. Adverse effects of albendazole include GI discomfort, skin reactions (rare), and blood dyscrasias (rare). Patients should be instructed to take albendazole with food to increase oral absorption.

Pyrantel pamoate, given as a single oral dose, is utilized in the treatment of pinworm infections. This agent is well-tolerated, and most adverse effects are mild and transient in nature. Some common adverse effects are nausea, vomiting, abdominal distention, anorexia, headache, and dizziness. Patients with myasthenia gravis must avoid pyrantel because of the potential for exacerbation of this disease.¹

Niclosamide is indicated for the treatment of tapeworm infestations. This agent is not absorbed orally and therefore is active only against intestinal nematodes (roundworms). Because of its very limited bioavailability, this agent is devoid of systemic adverse effects. Most complications are GI in nature and include nausea, vomiting, anorexia, abdominal pain, and diarrhea.

Pharmacists' Role in the Management of Parasitic Infections

Pharmacists play a key role in screening patient profiles for possible drug interactions and contraindications. They also should educate patients on the most common effects with the aim of minimizing these adverse effects, as well as potentially preventing some parasitic infections (eg, malaria).

Dr. Boris Nogid is the clinical pharmacy coordinator of pharmacotherapy at Brooklyn Hospital Center and a clinical assistant professor at Arnold & Marie Schwartz College of Pharmacy and Health Sciences, Long Island University. Dr. Anna Nogid is an assistant professor of pharmacy practice at Arnold & Marie Schwartz College of Pharmacy and Health Sciences, Long Island University, and a critical care pharmacist at Bellevue Hospital Center.

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