US Pharm. 2012;37(8):HS2-HS6.
Parasitic infections, starvation, insufficient shelter,
and lack of clean water sources are the greatest barriers to health in
our world’s growing population. Several of the parasitic infections that
are very common throughout the world (e.g., ascariasis) frequently
occur with mild, obscure symptoms or none at all. It is common for a
host (especially of an intestinal parasite) to be asymptomatic, which is
technically more of a mutualistic coexistence than true parasitism. The
parasitic infections thought to be the most prevalent worldwide include
toxoplasmosis, ascariasis, hookworm disease, and trichomoniasis (sorted
by worldwide prevalence in TABLE 1).1
Some infections with low mortality rates may cause
extensive morbidity, including fetal/neonatal damage, nutritional
deficiencies, cutaneous nodules, skin eruptions or necrosis, and major
end-organ damage of the eyes, central nervous system (CNS), lungs,
heart, or liver.2-4 Although they are not the most prevalent
infections, malaria, amebiasis, leishmaniasis, schistosomiasis, and
trypanosomiasis are the leading causes of mortality worldwide due to
parasitic infections.5 The scope of this topic could be
immense, as there are hundreds of parasitic species that infect humans.
This article will address drug therapy (and sometimes prevention) for
the parasitic infections most relevant to pharmacy practice in the
Parasitic Infections in the U.S.
It is postulated that U.S. residents suffer less from
parasitic infections because of better provisions of food, shelter,
matters of hygiene, and clean water. The U.S. is also somewhat
geographically isolated from the rest of the world, and its climate,
particularly in the northern part of the country, is also likely
protective. When U.S. residents are affected, it is usually due to
travel to tropical areas, recent immigration to the U.S., or direct
contact with new immigrants. Occasionally, infections are caused by
indigenous parasites, particularly through improperly prepared food or
direct contact with household pets or farm animals.6
Antimalarial Agents: The most common
use of agents against parasites by U.S. residents is for malaria
prophylaxis. The same arsenal of drugs is used for both prevention and
treatment of malaria. TABLE 2 highlights the most important antimalarial drugs for U.S. pharmacists.7-9
To achieve therapeutic levels, it is generally necessary for travelers
to take 2 doses before entering a malaria-endemic area and to continue
for 4 weeks after returning. Atovaquone-proguanil is an exception and
only needs to be continued for 1 week after returning.10,11
Pharmacists should educate their patients that continuing
the doses (for 1-4 weeks) after returning home is vital for successful
Antimalarial drugs do
not prevent the acquisition of malaria nor do they sufficiently prevent
parasitic migration to or occupation of the liver. Instead, these drugs
treat the later blood stages that cause clinical malaria. Therefore,
when used for prophylaxis, these drugs must be continued for a time
after the traveler returns from the malaria-endemic area in case of
unknown acquisition of a Plasmodium species.
Pharmacists should also inform their patients that while
pharmacologic prophylaxis is important, the best way to prevent malaria
is to avoid the bite of the Anopheles mosquito, which is most
active in the early evening. Preventive methods include wearing
long-sleeved and long-legged clothing, applying strong insect
repellants, and using mosquito nets.10
Not all drugs approved for malaria treatment or prophylaxis are included in TABLE 2. For example, amodiaquine and hydroxychloroquine are infrequently used for monotherapy against Plasmodium falciparum today due to resistance (although they are occasionally effective against chloroquine-resistant strains).7,9
Similarly to quinine, they are infrequently used for prevention because
they require daily dosing and also have higher rates of toxicity (e.g.,
blood dyscrasias, liver toxicity).
Metronidazole and Tinidazole: Metronidazole,
or alternatively tinidazole, is the basis of therapy for giardiasis,
trichomoniasis, and amebiasis. Of these, amebiasis presents the greatest
challenge because metronidazole alone is often not sufficient to
eradicate this intestinal parasite.12 Drug therapy for
amebiasis should generally consist of a “luminal agent” that is capable
of eradicating the luminal (intestinal) infection. If the infection is
only luminal and the patient is asymptomatic, then a luminal agent may
be used alone.13 The luminal agents available for use in the U.S. are iodoquinol and paromomycin.12
However, if there are symptoms or the disease is extraintestinal, it is
imperative to use a systemic agent as well, such as metronidazole or
tinidazole. Metronidazole 750 mg is given orally three times daily or
500 mg intravenously every 6 hours for 10 days. Tetracycline (when
available) is the most commonly used alternative systemic agent for
mild-to-severe intestinal infection; another alternative, erythromycin,
can be considered for mild or moderate infection.
For a hepatic abscess or other extraintestinal disease,
metronidazole or tinidazole is still the preferred agent and may be
combined with chloroquine for added efficacy. For cases of resistance or
intolerance to metronidazole and tinidazole, rarely dehydroemetine or
emetine plus chloroquine for 21 to 23 days may have to be used.
Dehydroemetine and emetine must be given either subcutaneously or
intramuscularly and are not commercially available in the U.S.12
Treatment of giardiasis is simpler and can generally be
accomplished with a low-dose course of metronidazole (e.g., 250 mg three
times daily with meals for 5 days) or a single 2-g dose of tinidazole
with a meal. If metronidazole or tinidazole cannot be used or is
ineffective, nitazoxanide or paromomycin is also an option.12,14
Trichomoniasis, whether it is vaginal or urethral (most
common sites), is also easily treated, often with a single 2-g dose of
metronidazole. However, this large single dose frequently causes
dyspepsia, and alternatively metronidazole 500 mg twice daily over 7
days (or similar regimen) may be prescribed. Tinidazole may also be
substituted for metronidazole and is at least as effective. It is
important to note that intravaginal metronidazole is intended for
bacterial vaginosis, not Trichomonas vaginalis.12,15,16
Adverse effects occur frequently with metronidazole and
may include nausea, parageusia, dermatologic reactions (occasionally
severe), and vaginal candida infection. Some neurologic reactions are
common, like dizziness or headache, but severe neurologic reactions may
also occur, including peripheral neuropathy, seizure, and disorders of
special senses (optic or auditory nerve disorders). Other serious
adverse effects may include leukopenia, aseptic meningitis,
encephalopathy, and hemolytic uremic syndrome. Alcohol should be avoided
due to the risk of a disulfiram-like reaction.17
Ivermectin: Ivermectin is one of the
more frequently used antiparasitic drugs in the U.S., but not for the
most impactful parasitic infections mentioned above. While it is FDA
approved for systemic infections by Onchocerca volvulus (microfilariae, not adult) and intestinal strongyloidiasis, it is most frequently used in the U.S. off-label for scabies, lice, and enterobiasis (pinworms).18
Just south of the U.S. in southern Mexico and Guatemala, the
availability of ivermectin is particularly important in the effort to
eradicate onchocerciasis (“river blindness”).19
Like other agents, ivermectin paralyzes certain helminths,
but its molecular mechanism of action is different. Ivermectin
intensifies GABA-mediated transmission, which causes postsynaptic neuron
hyperpolarization in susceptible helminths.20 Enhancement of GABA activity may occur in humans as well, and ivermectin should not be coadministered with GABA-ergic drugs.21 Taking ivermectin with food (specifically, a high-fat meal) greatly increases bioavailability.17
Ivermectin is usually given as a single dose. However, when treating
filariasis, a single dose is effective in reducing symptoms for many
months but rarely induces remission. Repeat doses may be needed once or
twice yearly for several years until the infection eventually subsides.21
Adverse effects of ivermectin are infrequent but may
include fatigue, dizziness, abdominal pain, or rash. Reactions due to
microfilariae death may occur within the first 2 days of treatment and
include arthralgias, myalgias, hypotension, tachycardia, lymphadenitis,
lymphangitis, and peripheral edema.21
Pyrantel Pamoate: Pyrantel is available OTC and is primarily used for the treatment of enterobiasis, commonly called pinworms (Enterobius vermicularis). Enterobius
usually infects only the gastrointestinal (GI) tract, but can also
occasionally infect the female genitourinary system and may increase the
rates of bacterial urinary tract infections.22 Pyrantel
pamoate has some efficacy against ascariasis and has occasionally been
used as an alternative to mebendazole for hookworms.3,21 It
is not absorbed systemically and is thus only effective against
susceptible helminths within the intestinal tract. Therefore, adverse
effects are usually GI in nature, although dizziness, headache, or
somnolence may occur.
Albendazole: Albendazole is at least as efficacious as mebendazole for the treatment of many helminth infections.23,24 Albendazole is only FDA approved for the treatment of echinococcosis and neurocysticercosis.25
However, due to the recent unavailability of mebendazole, off-label use
of albendazole may be required for the treatment of certain roundworms
(i.e., ascariasis, hookworms, enterobiasis). Pyrantel pamoate, available
OTC for the treatment of pinworms (enterobiasis), may also be a
reasonable choice for ascariasis.26 Dosing recommendations are available in most drug references for off-label uses of albendazole.
There are some important pharmacokinetic properties to
consider. Albendazole may be taken with or without food, and the ideal
choice is based on the location of the parasitic infection. Because very
little is systemically absorbed, the dosing for intestinal infections
in children and adults is similar. It is important to understand that
food increases albendazole absorption, particularly a fatty meal.21
For luminal infections (e.g., ascariasis), the dose can be given on an
empty stomach to reduce absorption. For systemic or extraintestinal
infections, albendazole can be given with food to enhance absorption.
Occasionally, serious adverse effects can occur with
albendazole, especially during prolonged therapy or during certain
infections (ocular and CNS infections are discussed below). In any
extended treatment course (more than 1 or 2 single doses), and
especially in hydatid disease, liver enzymes and blood cell counts
should be monitored every 2 weeks and before each repeat treatment
course. Ongoing physical examinations are necessary and must include
monitoring for liver toxicity. Albendazole should be avoided or
discontinued if liver transaminases are elevated or if the white blood
cell count is depressed. The prescribing information includes a warning
not to use in pregnancy and to avoid pregnancy for 1 month after
discontinuation of albendazole. Fortunately, conclusive evidence
indicating severe teratogenicity is lacking and is based on animal
models; if it occurs, it is infrequent.27 Still, other agents
are preferred over albendazole in pregnancy if appropriate for the
clinical scenario (e.g., praziquantel for schistosomiasis).28
Adverse Effects of Antihelminthic Drugs
Memorizing a list of adverse effects for each
antihelminthic drug is impractical in real clinical practice. Adverse
effects that might be attributed to a drug are highly dependent on the
infection being treated and the duration of therapy. An interesting
example of the infection-specific adverse-effect profile of these
medications is the prevalence of liver enzyme elevation in albendazole
therapy for hydatid disease versus neurocysticercosis. In hydatid
disease, abnormal liver function tests are seen 15.6% of the time but
less than 1% of the time in patients with neurocysticercosis.25 Some adverse effects may be due to the effects of the dying helminths rather than the direct toxicity of the agents.
Special Considerations When Treating Ocular or CNS Infections
Patients with neurocysticercosis often present with
seizures. Interestingly, this infection is an increasingly emerging
infection within the U.S. In the U.S., seizures are the most common
first-onset symptom (66% of patients), and antiseizure drug therapy is
usually necessary, especially if antihelminthic pharmacotherapy is
chosen. Neurocysticercosis is the most common cause of symptomatic
Many drugs that would be effective in vitro for the
treatment of a particular parasite may not reach the site of action when
the infection is extraintestinal. GI absorption and distribution to the
site of action must be considered. As previously mentioned, treatment
of extraintestinal infections with albendazole may be enhanced by giving
the drug with food. The use of a glucocorticoid (e.g., prednisone) can
greatly reduce morbidity when treating certain CNS manifestations of
parasitic infections, particularly certain forms of
neurocysticercosis—cysticercal encephalitis, subarachnoid
neurocysticercosis, and spinal intramedullary cysticercosis.26
Additionally, combining a glucocorticoid with albendazole may increase
drug action and reduce damaging inflammation at the site of infection.21
Antiparasitic drug therapy is not always indicated for CNS
or intraocular infections because dying helminths may cause more damage
than live ones. Praziquantel in particular should be avoided when
treating ocular infections, and rarely is it indicated when there are
signs of CNS involvement. Use of praziquantel for infections in these
sensitive tissues is further complicated by drug interactions with
dexamethasone (and perhaps prednisone), as coadministration
significantly reduces plasma praziquantel levels.21 If there is ocular or CNS involvement, an ophthalmologist or neurologist should be consulted prior to drug therapy.
Availability of Antiparasitic Agents
Many of the most toxic agents used for parasitic
infections around the world are not available in the U.S. due to low
occurrence of infections here. Because of this low occurrence, there has
also been little financial incentive for the pharmaceutical industry in
the U.S. and Western Europe to develop more effective, less toxic
agents. If there is a need for agents not approved for use in the U.S.,
some may be procured directly from the CDC if there is an existing
Investigational New Drug (IND) application on file with the FDA.30
Role of the Pharmacist
In conclusion, pharmacists should be aware of the following when encountering parasitic infections in their practice:
• Although mebendazole is now unavailable in the U.S., it
is still the recommended therapy for many helminthic infections. There
is no clear single alternative, but the pharmacist can help guide the
prescriber and patient to the appropriate use and dosage of albendazole,
pyrantel pamoate, or other antihelminthic agent.
• When prescribing under protocol, pharmacists can be an
excellent clinical provider for travel consultations, a part of which is
prescribing appropriate antimalarial prophylaxis that depends on a
variety of patient factors/preferences and the travel destination(s).
• Pharmacists should recommend involvement of a specialist
in the treatment of neurologic or ocular infections and provide
information on use of anti-inflammatory drugs and their pharmacokinetic
and pharmacodynamic interactions with antiparasitic agents.
• Pharmacists Pharmacists should recognize pinworm
infection (enterobiasis) and recommend OTC therapy (pyrantel pamoate) as
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