INFECTIONS CAUSED BY NEMATODES
Nematodes are long,
cylindrical unsegmented worms that are tapered at both ends. Because of their
shape, they are commonly referred to as roundworms. Some intestinal nematodes
contain a mouth with three lips, and in some the mouth contains cutting plates.
Infection occurs after ingestion of embryonated eggs or tissues of another host
that contain larval forms of the nema-todes.
Some of the nematodes (filarial
worms and guinea worms) live in blood, lymphatics, and other tissues and are
referred to as blood and tissue nematodes. Others are found primarily in the
intestinal tract. One group, hookworms, undergoes a developmental cycle in
soil. The larvae penetrate the skin of humans, enter the venules, and are
carried to the lungs, where they enter the alveoli, sometimes causing
pneumonitis. The larvae then migrate up the trachea and are swallowed. In the
intestine, they attach to the mucosa, and using the cut-ting plates and a
muscular esophagus, feed on host blood and tissue fluid. This may result in
vague abdominal pains, diarrhea and, if many worms are present, anemia.
Strongyloides stercoralis infection is acquired, like hookworm, from filariform larvae in contaminated soil that
penetrate the skin. This parasite maintains itself for many decades in the
small intestine asymptomatically. Persons treated with immunosuppressive drugs
or who are debilitated by chronic illness may be at risk for widespread tissue
invasion or hyperinfection syndrome. Prompt treatment may be life saving in
Other intestinal nematodes
are acquired by inges-tion of eggs from soil. These groups lack cutting plates
and may not cause anemia. Still other nematodes, such as pinworms, migrate from
the anus to lay eggs, which are transmitted by fingers or through the air. The
eggs are ingested and the adult worm develops in the intes-tinal tract. In some
cases, the appendix may be invaded, resulting in symptoms of appendicitis. In
most cases, the symptoms are perianal pruritus and a restlessness asso-ciated
with the migration of the female worm through the anus to the perianal skin.
Other nematodes, such as Ascaris spp.,
are ingested in egg form but have a migra-tion similar to that of the hookworm.
The filarial worms differ
from other nematodes in that they are threadlike and are found in blood and
tis-sue. The infective larvae enter following the bite of an infected arthropod
(fly or mosquito). They then enter the lymphatics and lymph nodes. Fever,
lymphangitis, and lymphadenitis are associated with the early stage of the
disease. Chronic infections may be characterized by elephantiasis as a result
of lymphatic obstruction. Some species of filarial worms migrate in the
subcuta-neous tissues and produce nodules and blindness (on-chocerciasis).
Piperazine (Vermizine) contains a heterocyclic ring
that lacks a carboxyl group. It acts on the musculature of the helminths to
cause reversible flaccid paralysis mediated by chloride-dependent
hyperpolarization of the muscle membrane. This results in expulsion of the
worm. Piperazine acts as an agonist at gated chloride channels on the parasite
Piperazine has been used with
success to treat A. lumbricoides and E. vermicularis infections, although mebendazole is now the agent of choice. Piperazine is administered
orally and is readily absorbed from the in-testinal tract. Most of the drug is
excreted in the urine within 24 hours.
Piperazine is an appropriate
alternative to meben-dazole for the treatment of ascariasis, especially in the
presence of intestinal or biliary obstruction. Cure rates of more than 80% are
obtained following a 2-day reg-imen.
Side effects occasionally
include gastrointestinal dis-tress, urticaria, and dizziness. Neurological
symptoms of ataxia, hypotonia, visual disturbances, and exacerbations of
epilepsy can occur in patients with preexisting renal insufficiency. It should
not be used in pregnant women because of the formation of a potentially
car-cinogenic and teratogenic nitrosamine metabolite. Concomitant use of
piperazine and chlorpromazine or pyrantel should be avoided.
Diethylcarbamazine citrate (Hetrazan) is active against several
microfilaria and adult filarial worms. It inter-feres with the metabolism of
arachidonic acid and blocks the production of prostaglandins, resulting in
capillary vasoconstriction and impairment of the pas-sage of the microfilaria.
Diethylcarbamazine also in-creases the adherence of microfilariae to the
vascular wall, platelets, and granulocytes.
absorbed from the gastroin-testinal tract, and peak blood levels are obtained
in 4 hours; the drug disappears from the blood within 48 hours. The intact drug
and its metabolites are excreted in the urine.
Diethylcarbamazine is the
drug of choice for certain filarial infections, such as Wuchereria bancrofti, Brugia malayi
and Loa loa. Since
diethylcarbamazine is not universally
active against filarial infections, a specific di-agnosis based on blood
smears, biopsy samples, and a geographic history is important. Dosage should be
ad-justed in patients with renal impairment.
Caution is necessary when
using this agent, particu-larly when treating onchocerciasis. The sudden death
of the microfilariae can produce mild to severe reactions within hours of drug
administration. These are mani-fested by fever, lymphadenopathy, cutaneous
swelling, leukocytosis, and intensification of any preexisting eosinophilia,
edema, rashes, tachycardia, and headache. If microfilariae are present in the
eye, further ocular damage may result. Other side effects are relatively mild
and range from malaise, headache, and arthralgias to gastrointestinal symptoms.
Ivermectin (Mectizan) acts on parasite-specific
in-hibitory glutamate-gated chloride channels that are phylogenetically related
to vertebrate GABA-gated chloride channels. Ivermectin causes hyperpolarization
of the parasite cell membrane and muscle paralysis. At higher doses it can
potentiate GABA-gated chloride channels. It does not cross the blood-brain
barrier and therefore has no paralytic action in mammals, since GABA-regulated
transmission occurs only in the cen-tral nervous system (CNS). Ivermectin is
administered by the oral and subcutaneous routes. It is rapidly ab-sorbed. Most
of the drug is excreted unaltered in the fe-ces. The half-life is approximately
Ivermectin has broad-spectrum
activity in that it can affect nematodes, insects, and acarine parasites. It is
the drug of choice in onchocerciasis and is quite useful in the treatment of
other forms of filariasis, strongyloidia-sis, ascariasis, loiasis, and
cutaneous larva migrans. It is also highly active against various mites. It is
the drug of choice in treating humans infected with Onchocerca volvulus, acting
as a microfilaricidal drug against the skin-dwelling
larvae (microfilaria). Annual treatment can prevent blindness from ocular
onchocerciasis. Ivermectin is clearly more effective than diethylcarba-mazine
in bancroftian filariasis, and it reduces microfi-laremia to near zero levels.
In brugian filariasis diethyl-carbamazine-induced clearance may be superior. It
also is used to treat cutaneous larva migrans and dissemi-nated
strongyloidiasis. Its safe use in pregnancy has not been fully established.
The side effects are minimal,
with pruritus, fever, and tender lymph nodes occasionally seen. The side
ef-fects are considerably less than those associated with di-ethylcarbamazine
Suramin is widely used as a
macrofilaricide in human onchocerciasis, and its action on microfilariae also
is considerable. It also is useful in the treatment of the he-molymphatic stage
of African trypanosomiasis. Early treatment of the infection with suramin
clears try-panosomes from the blood and lymphatics within 30 minutes and keeps
them clear for approximately 3 months. Suramin inhibits a number of filarial
enzymes involved with carbohydrate metabolism as well as the production of
adenosine triphosphate (ATP). It is 35 times more inhibitory to the
dihydrofolate reductase of O. volvulus than
to the same enzyme in human tissue. It is
a potent inhibitor of reverse transcriptase, the DNA polymerase of
retroviruses, and also has some effects on the infective and cytopathic effects
of HIV. It is being evaluated as an anticancer drug, reducing pain and
de-laying progression in hormone-refractory prostate can-cer. Its most
significant toxicity has been the develop-ment of severe
Pyrantel pamoate (Antiminth) is a agonist at the
nico-tinic acetylcholine receptor, and its actions result in de-polarization
and spastic paralysis of the helminth mus-cle. Its selective toxicity occurs
primarily because the neuromuscular junction of helminth muscle is more
sensitive to the drug than is mammalian muscle. This drug is administered
orally, and because very little is ab-sorbed, high levels are achieved in the
intestinal tract. Less than 15% of the drug and its metabolites are ex-creted
Pyrantel pamoate is active
against several round-worms: A.
lumbricoides, Ancylostoma duodenale, Necator americanus, and E.
vermicularis. Pyrantel is an alterna-tive drug of choice in treating
infections with A. lumbri-coides, E.
vermicularis (pinworms), and hookworms
(N. americanus and A. duodenale). It is not recom-mended
for pregnant patients or for children under age 1 year.
Although most of the drug
remains in the intestinal lumen, enough can be absorbed systemically to cause
headache, dizziness, and drowsiness. No major adverse effects have been
reported on renal, hepatic, or hema-tological systems.