Parasites are microorganisms that live on or inside another organism known as the host organism and benefit at the expense of their host organism. Parasites are responsible for billions of human infections, including malaria. Parasitic infections are especially prevalent in tropical areas, but they also occur in subtropical and temperate regions, where they tend to infect immigrants and travelers. While parasites can include a diverse array of microorganisms, including fungi and bacteria, medically-relevant parasites known to cause disease in humans are protozoa, helminths, and ectoparasites.
These unicellular organisms demonstrate a particularly high propensity to infect immunocompromised patients such as those with acquired immune deficiency syndrome (AIDS). Infections range in their presentation from asymptomatic to fatal. Protozoa further sub-categorized by phylum and subphylum based on its main mode of movement.
This term describes parasitic worms. They transmit via accidental ingestion, skin penetration, a vector bite, or consumption of the host as food. Transmission is highly dependent on climate, hygiene, and exposure to vectors. Helminths classify as follows:
These are organisms that live externally on the skin of hosts. They include mites, fleas, ticks, lice and bedbugs, and infest the skin and its appendages, causing symptoms such as intense pruritis. Diseases caused by ectoparasites include myiasis, pediculosis, scabies, and trombiculosis.
Antiparasitic drugs are used to manage infections caused by various protozoa, helminths, and ectoparasites. Treatment options vary, depending on the specific causative organism within each group.
The drug of choice to treat malaria is dependent on the Plasmodium species, the geographic region of the infecting species, and the severity of the patient’s infection. Chloroquine is the drug of choice to treat uncomplicated malaria caused by all Plasmodium species (P. vivax, P. malariae, P. ovale, and P. knowlesi) except P. falciparum, which has become increasingly resistant. Amodiaquine (discontinued in USA) can be used in combination with artesunate to treat chloroquine-resistant uncomplicated P. falciparum. An atovaquone-proguanil combination or an artemether-lumefantrine combination may also be a choice for first-line treatment for chloroquine-resistant P. falciparum. In pregnancy, oral quinine is indicated, and parenteral quinine(discontinued in USA) is useful for the treatment of severe malaria. Primaquine, mefloquine, atovaquone-proguanil, and doxycycline are indicated for chemoprophylaxis.
Babesiosis is similar to malaria, and the parasites Babesia divergens, and Babesia microti get transmitted via tick bite. Babesiosis management uses atovaquone and azithromycin or clindamycin plus quinine in severe disease.
Antiamoebic drugs are useful in the management of amoebiasis caused by Entamoeba histolytica. This infection may present asymptomatically, with amoebic colitis, or with extraintestinal manifestations. The presentation determines what antiamoebic therapy. Antiamoebic drugs can classify into luminal, tissue, systemic, or mixed amoebicides. Luminal amoebicides act on parasites in the lumen and include iodoquinol (discontinued in USA), paromomycin sulfate, and diloxanide furoate (discontinued in USA). Systemic amebicides like metronidazole, tinidazole, and emetine (discontinued in USA) have therapeutic use in managing extraintestinal diseases such as hepatic abscesses; chloroquine is an adjunct therapy to emetine for the management of hepatic abscesses. Metronidazole and tinidazole also serve as mixed amoebicides.
Giardia lamblia causes giardiasis and is managed using metronidazole. Alternative medications for giardiasis include tinidazole, furazolidone (discontinued in USA), and albendazole.
American trypanosomiasis, also called Chagas disease, is caused by the parasite Trypanosoma cruzi. Nifurtimox or benznidazole are used to manage the symptoms of Chagas disease. African trypanosomiasis (sleeping sickness) results from infection by the West African T. brucei gambiense and management is with pentamidine in the early stages of the disease, and eflornithine for central nervous system (CNS) manifestations. T. Rhodesiense is the East African parasite, which causes a more aggressive form of sleeping sickness, and suramin is the drug used for early-onset disease and melarsoprol for CNS involvement.
Leishmaniasis is among the neglected tropical diseases (NTD) and results from infection by Leishmania parasites. Infections manifest as visceral, cutaneous, or mucocutaneous leishmaniasis. Sodium stibogluconate is the agent of choice for the management of visceral and cutaneous leishmaniasis and other drugs such as meglumine antimoniate (not available in USA), pentamidine, or amphotericin B are acceptable alternatives. Paromomycin indications also include the treatment of visceral leishmaniasis.
Toxoplasma gondii causes congenital disease and central nervous system disease in immunocompromised patients. Sulfadiazine combined with pyrimethamine is the first-line therapy for the management of toxoplasmosis. Other alternative sulfonamides used in the treatment are sulfamethazine, and sulfamerazine which are not available in the USA.
Trichomoniasis results from Trichomonas vaginalis, and metronidazole is the drug of choice for its management.
Anthelminthic drugs act against parasitic worms as either vermicides or vermifuges. Vermicides act by killing the worms, whereas vermifuges help expel the worms, usually in their live state. The ideal anthelminthic drug would have a broad therapeutic index to ensure it is more toxic to the parasitic worm than the host. Antihelminthic drugs can be grouped based on the class of parasitic worms they act on and also based on the chemical structure of the drug.
Anticestodal drugs: Praziquantel is a broad-spectrum vermicide that is used to manage infection caused by cestodes (tapeworms) such as Taenia saginata, Diphyllobothrium latum, and Taenia solium. Alternatively, niclosamide (discontinued in USA) can be used to manage the above infections. Praziquantel is also effective in infections caused by Hymenolepis nana. Albendazole is another broad-spectrum anthelmintic drug and is the first choice for the management of hydatid disease and cysticercosis.
Antinematodal drugs: Praziquantel is also essential in managing infections caused by trematodes (flukes) and is the drug of choice for management for Schistosoma sp., Clonorchis sinensis, and Paragonimus westermani infections. Alternative medications include metrifonate, oxamniquine, and bithionol which are not available in the USA.
Antinematodal drugs: Albendazole is also used to manage most infections caused by nematodes (roundworms) and is the drug of choice for ascariasis, trichuriasis, trichinosis, cutaneous larva migrans, hookworm, and pinworm infections. Diethylcarbamazine (available thru CDC Drug Service) is the drug of choice for filariasis, loiasis, and tropical eosinophilia, and ivermectin is the drug of choice for onchocerciasis.
The most common human ectoparasites include head lice, pubic lice, and scabies mites.
Scabies is a highly contagious pruritic disease caused by Sarcoptes scabiei. Management of scabies is achieved using lindane, permethrin, benzyl benzoate (discontinued in USA), or ivermectin. Resistance to lindane and permethrin have increased over the years, and combination permethrin and oral ivermectin, topical ivermectin, and synergized pyrethrins have led to the highest cure rates.
Head lice caused by Pediculus humanus capitis is the most common human ectoparasitic infection. It is managed using permethrin and pyrethrins. With concerns for resistance rising, alternative management is achieved using malathion or ivermectin. Pediculosis pubis (pubic lice) is also managed using permethrins or pyrethrins, with malathion or ivermectin serving as alternatives.
Antibabesial agents :
Antigiardial agents :
Intestinal nematode infections
Tissue nematode infections
A discussion of the most common anthelminthic drugs is in this section.
Diethylcarbamazine (not available commercially in the USA - only from the CDC)
Benzyl Alcohol (discontinued in USA):
Chloroquine – Although generally well tolerated, some patients experience pruritis and gastrointestinal (GI) disturbances such as nausea, vomiting, anorexia, and abdominal pain with chloroquine. Rarely, glucose-6-phosphate dehydrogenase (G6PD) deficient patients experience hemolysis. Other rare side effects of chloroquine include agranulocytosis, hypotension, seizures, psychosis, blurring of vision, QRS widening, and T wave abnormalities. Long-term use may also lead to ototoxicity, peripheral neuropathy, and retinopathy.
Amodiaquine is related to chloroquine and may be used to replace chloroquine in resistant areas. It rarely has adverse effects, but some patients may experience agranulocytosis, hepatotoxicity, and aplastic anemia. This drug is not available in the USA but sees extensive usage in Africa.
Atovaquone has adverse effects such as headaches, insomnia, fever, rash, and GI disturbances such as nausea, vomiting, and diarrhea.
Artemisinins such as artemether are well tolerated but may cause symptoms such as nausea, diarrhea, and vomiting. Rarely, patients may exhibit neutropenia, hemolysis, and elevated liver enzymes. They are well tolerated in pregnancy.
Lumefantrine can be combined with artemether. The use of this combination can lead to GI disturbances, pruritis, dizziness, and headaches. It can also cause QTc interval prolongation on rare occasions.
Primaquine also has adverse effects of GI disturbances, including abdominal cramps, nausea, and epigastric pain. It can also cause hemolysis or methemoglobinemia especially in patients with G6PD deficiency.
Mefloquine may lead to adverse effects such as behavioral disturbances, insomnia, GI disturbances, rash, and dizziness. It can also lead to arrhythmias, bradycardia, and other cardiac conduction abnormalities.
Doxycycline also causes GI symptoms, and it also leads to photosensitivity and candida vaginitis.
Iodoquinol rarely may lead to adverse effects such as diarrhea, anorexia, nausea rash, and pruritis. Taking it with meals can prevent GI effects. Iodoquinol can also lead to an increase in serum iodine that is bound to proteins, leading to a decrease in measured I uptake.
Paromomycin leads to GI disturbances. It can accumulate in the kidneys of those with renal insufficiency and cause renal toxicity.
Metronidazole commonly leads to a metallic taste in the mouth, headache, nausea, and dry mouth. Other rare adverse effects of metronidazole include thrush, vertigo, neutropenia, pancreatitis, and toxicity in the central nervous system leading to seizures and encephalopathies. Tinidazole has a similar side effect profile to metronidazole but is better tolerated.
Albendazole causes GI disturbances, alopecia, an increase in liver enzymes, headaches, and pancytopenia. It is typically well-tolerated and usually has no significant side effects.
Benznidazole has adverse effects such as GI disturbances, myelosuppression, peripheral neuropathy, and rash.
Nifurtimox also has adverse effects, which include GI disturbances, rash, seizures, neuropathies, and insomnia.
Pentamidine is a very toxic drug that, when rapidly administered through IV, may cause hypotension, dyspnea, and tachycardia. If inhaled, it may cause bronchospasms and lead to difficulties in breathing. It leads to pancreatic toxicity and can cause hypoglycemia. It may also lead to renal insufficiency. Other side effects include an unpleasant taste in the mouth, gastrointestinal disturbances, hallucinations, and cardiac arrhythmias.
Eflornithine may cause GI disturbances as well as reversible thrombocytopenia, leukopenia, and seizures.
Suramin causes nausea, vomiting, and fatigue early on, and as time progresses can lead to severe signs and symptoms like agranulocytosis, hemolytic anemia, chronic diarrhea, neuropathies, and renal abnormalities amongst others. This agent is not FDA-approved for use in the USA.
Melarsoprol is a highly toxic drug and most commonly causes reactive encephalopathy, which manifests as seizures, coma, edema, and death. It also causes renal and cardiac diseases.
Sodium stibogluconate causes myalgias, arthralgias, and GI symptoms. T wave changes and QTc prolongation may also occur; thus, electrocardiographic (ECG) monitoring is recommended when a patient is on sodium stibogluconate. This agent is only available from the CDC and Military bases.
Amphotericin B can cause infusion reactions and can also lead to renal insufficiency. Acutely, it can lead to hypertension, hypotension, nausea, vomiting, and fever.
Pyrimethamine-sulfadoxine has cutaneous side effects such as Steven-Johnson syndrome, toxic epidermal necrolysis, and erythema multiforme. Because it contains a sulfonamide, this medication may also cause renal insufficiency, gastrointestinal disturbances, central nervous system disorders, and dermatologic disorders.
Trimethoprim-sulfamethoxazole (TMP-SMX) causes symptoms due to antifolate and sulfonamide activity. Antifolate side effects include megaloblastic anemia, granulocytopenia, and leukopenia, while symptoms due to sulfonamides include GI disturbances, central nervous disturbances, and renal toxicity.
Praziquantel causes symptoms, including GI disturbances, skin rashes, arthralgia, myalgia, and low-grade fever. In cases of neurocysticercosis, the damaging of the parasites may lead to CNS disturbances such as seizures, mental changes, meningismus, hyperthermia, intracranial hypertension, nausea, and vomiting. However, this is avoidable by the use of corticosteroids.
Pyrantel pamoate has GI side effects such as nausea, vomiting, abdominal cramps, and diarrhea. It is also associated with dizziness, rash, headaches, weakness, and drowsiness. It has been observed to cause a mild increase in liver enzymes. Therefore, patients with liver disease require close monitoring.
Permethrin causes side effects such as pruritis, burning, and stinging.
Lindane may lead to neurotoxicity and hematotoxicity; therefore, it should be avoided in pregnancy and children.
Chloroquine contraindications include patients with previous sensitivity to 4-aminoquinoline. Contraindications include patients with G6PD deficiency and those with porphyria or psoriasis. Additionally, it should be avoided in those with visual field defects or myopathies. It is, however, safe in pregnancy and for use in children.
Primaquine is contraindicated in patients with methemoglobinemia, granulocytopenia, or myelosuppression. It should be avoided in pregnancy and those with G6PD deficiency.
Mefloquine is contraindicated in patients with arrhythmias, cardiac conduction abnormalities, psychiatric disorders, and epilepsy. In the past, recommendations were to avoid its use in pilots or others with jobs that require fine motor skills.
Iodoquinol should be avoided in patients with renal or thyroid disease and om those who cannot tolerate iodine. It should also be discontinued in cases of iodine toxicity where symptoms such as fever, pruritis, and dermatitis persist.
Diloxanide furoate is typically not recommended in pregnancy.
Metronidazole causes a disulfiram-like reaction when taken with alcohol. Furthermore, it leads to lithium toxicity when taken with lithium and potentiates the effects of coumarin-type anticoagulants, e.g., warfarin. This drug should be avoided in pregnancy.
Emetine contraindications include patients with renal and cardiac disease and pregnancy.
Albendazole is contraindicated in patients with cirrhosis and those with previous hypersensitivity to benzimidazole drugs.
Amphotericin B causes renal insufficiency; therefore, concomitant use with nephrotoxic medications should be avoided.
Praziquantel should be avoided in ocular cysticercosis due to the damaging effects of the destruction of the parasites. Contraindications also include patients who need to stay alert for driving as it causes drowsiness. It should be avoided during pregnancy.
Lindane contraindications include patients with seizure disorders, and its use should be only as a second-line intervention in the elderly, young children, and patients weighing less than 50 kg, as they are more likely to present with these adverse effects.
Parasitic diseases constitute a large number of the 17 neglected tropical diseases identified by the World Health Organization (WHO). These diseases are of global importance as they affect over 1 billion people, including those who are very poor, cause debilitating disability, and often stigmatized. Enhancing healthcare outcomes for patients suffering from these diseases is multifaceted. Mass drug administration is key in the management of diseases such as onchocerciasis, lymphatic filariasis, and schistosomiasis. Community-directed treatment is recommended for the mass administration of drugs. Therefore, an interprofessional team approach consisting of the pharmacist needs to be aware that to attain better outcomes, the implementation of long term community programs is necessary for endemic regions. In many cases, the antiparasitic drugs have severe adverse reactions, and thus, adherence with medications is low. Therefore, direct observer therapy by the pharmacist is essential if one wants to improve outcomes.
Newer and safer drugs are necessary for the management of Chagas disease, leishmaniasis, and trypanosomiasis. Mebendazole is associated with high failure rates in treating hookworm infections, and single-dose albendazole is associated with a low rate of cure for trichuriasis. Therefore, there is a high demand for research and innovations in the management of neglected tropical diseases.
Antiparasitic drug therapy is usually a response to exotic and/or rare diseases. The clinician (MD, DO, NP, or PA) needs to be aware of the possible presenting signs and symptoms, and also perform a thorough history of travel that covers endemic areas for these diseases. Nursing staff will also have responsibility for taking this type of patient history and will document if present, as well as providing appropriate monitoring once therapy has started. The pharmacist will verify the clinician has chosen the suitable agent, verify dosing, and provide counsel to patients. Nurses and pharmacists must report any concerns encountered to the prescriber for corrective action.
An infectious disease specialist is almost mandatory in these cases. Coordination between the clinicians, nursing, and pharmacy is crucial, since many of the drugs used are uncommon, and dosing and potential interactions are critical. In the same vein, nursing must be made aware of the possible adverse effects from medication therapy, and report at the first sign of these appearing to the rest of the interprofessional healthcare team; this will permit the prescribing clinician to alter dosing or therapeutic agents, again in tandem with consult from the pharmacy. Only through this type of interprofessional collaboration can the healthcare team drive positive outcomes for patients with these infections. [Level V]
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