DƯỢC LÍ Goodman & Gilman's The Pharmacological Basis of Therapeutics 12th, 2010

or with hookworms. In rare instances, following chemotherapy
hyperactive ascarids may migrate to unusual loci and cause serious
complications such as appendicitis, occlusion of the common bile
duct, and intestinal obstruction and perforation with peritonitis.
For this reason, some clinicians recommend the use of pyrantel for
heavy Ascaris infections because this agent paralyzes the worms
prior to their expulsion. Surgery may be required to alleviate
obstructive complications. Pyrantel is considered safe for use during
pregnancy, whereas BZ should be avoided during the first
trimester. Albendazole is available off-label for treatment of ascariasis
in the U.S.
Toxocariasis, a zoonotic infection caused by the
canine ascarid Toxocara canis, is a common helminthiasis
in North America and Europe. Although precise
information is not available, toxocariasis may have displaced
pinworm as the most common helminth infection
in the U.S. (Hotez and Wilkins, 2009). In the U.S.,
the highest rates of infection are found within African
American and Hispanic American populations, with
some evidence to suggest that toxocariasis is the most
common neglected infection associated with poverty
(Hotez, 2008; Hotez and Wilkins, 2009).
Three major syndromes are caused by T. canis infection: visceral
larva migrans (VLM), ocular larva migrans (OLM), and covert
toxocariasis (CTox). CTox may represent an under-appreciated cause
of asthma and seizures (Sharghi et al., 2001). Specific treatment of
VLM is reserved for patients with severe, persistent, or progressive
symptoms (Bethany et al., 2006). Albendazole is the drug of choice.
In contrast, anthelmintic therapy for treatment of OLM and CT is
controversial. In the case of OLM, surgical management often is
indicated, sometimes accompanied by systemic or topical steroids
(Sabrosa and de Souza, 2001).
Hookworm
Necator americanus, Ancylostoma duodenale. These
closely related hookworm species infect ~1 billion people
in developing countries (Figure 51–1).
N. americanus is the predominant hookworm worldwide,
especially in the Americas, sub-Saharan Africa, South China, and
Southeast Asia, whereas A. duodenale is focally endemic in Egypt
and in parts of northern India and China. Infection also occurs farther
north in unusual but relatively warm settings such as mines
and large mountain tunnels, hence the terms miner’s disease and
tunnel disease. Hookworm larvae live in the soils and penetrate
exposed skin. After reaching the lungs, the larvae migrate to the
oral cavity and are swallowed. After attaching to the small intestinal
mucosa, the derived adult worms feed on host blood. There is
a general relationship between the number of hookworms (hookworm
burden) as determined by quantitative fecal egg counts and
fecal blood loss. In individuals with low iron reserves, the correlation
extends to hookworm burden and degree of iron-deficiency
anemia. Unlike heavy Ascaris and Trichuris infections, which
occur predominantly in children, heavy hookworm infections also
occur in adults, including women of reproductive age. In some
endemic areas, the heaviest hookworm burdens occur exclusively
in adult populations.
Although iron supplementation (and transfusion in severe
cases) often is helpful in individuals with severe iron-deficiency anemia,
the major goal of treatment is to remove blood-feeding adult
hookworms from the intestines. Albendazole is the agent of first
choice against both A. duodenale and N. americanus. This drug has
the advantage of activity against other GI nematodes (Hotez, 2009).
Mebendazole is also commonly used; however, especially when used
in a single dose, albendazole is considered far superior to mebendazole
at removing adult hookworms from the GI tract (Keiser and
Utzinger, 2008). Oral albendazole is the drug of choice for treating
cutaneous larva migrans, or “creeping eruption,” which is due most
commonly to skin migration by larvae of the dog hookworm, A.
braziliense. Oral ivermectin or topical thiabendazole also can be used.
Trichuris trichiura. Trichuris (whipworm) infection
occurs in ~1 billion people in developing countries
(Bethony et al., 2006; de Silva et al., 2003; Hotez et al,
2009). The infection is acquired by ingestion of embryonated
eggs. In children, heavy Trichuris worm burdens
can lead to colitis, Trichuris dysentery syndrome, and
rectal prolapse (Bundy and Cooper, 1989).
Mebendazole and albendazole are the most effective agents
for treatment of whipworm, either as a single agent or together with
Ascaris and hookworm infections. Both drugs provide significant
reductions in host worm burdens even when used in a single dose,
such as what might be used in mass drug administration campaigns
(Hotez, 2009). However, single-dose therapy with either drug is
often ineffective for achieving “cure” (i.e., total worm burden
removal), so that a 3-day course of therapy is typically required
(Keiser and Utzinger, 2008).
Strongyloides stercoralis. S. stercoralis, sometimes
called the threadworm or dwarf threadworm, is almost
unique among helminths in being able to complete its
life cycle within the human host. The organism infects
30-100 million people worldwide, most frequently in
the tropics and other hot, humid locales. In the U.S.,
strongyloidiasis is still endemic in the Appalachian
region and in parts of the American South (Hotez, 2008).
It also is found in institutionalized individuals living in
unsanitary conditions and in immigrants, travelers, and
military personnel who lived in endemic areas.
Infective larvae in fecally contaminated soil penetrate the
skin or mucous membranes, travel to the lungs, and ultimately
mature into adult worms in the small intestine, where they reside.
Many infected individuals are asymptomatic, but some experience
skin rashes, nonspecific GI symptoms, and cough. Life-threatening
disseminated disease, known as the hyperinfection syndrome, can
occur in immunosuppressed persons, even decades after the initial
infection when parasite replication in the small intestine is
unchecked by a competent immune response. Most deaths
caused by parasites in the U.S. probably are due to Strongyloides
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CHAPTER 51
CHEMOTHERAPY OF HELMINTH INFECTIONS