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

1444
SECTION VII
CHEMOTHERAPY OF MICROBIAL DISEASES
Trichinella
Strongyloides
Tapeworms
Schistosomes
Enterobius
Filarias
Trichuris
Hookworms
Ascaris
HELMINTH INFECTIONS
AND THEIR TREATMENT
Infections
(percentage of world population)
0 10 20 30
0
0.6 1.2 1.8
Number of Infections
(Billion)
Figure 51–1. Relative incidence of helminth infections worldwide.
Nematodes (Roundworms)
The major nematode parasites of humans include the
soil-transmitted helminths (STHs; sometimes referred
to as “geohelminths”) and the filarial nematodes.
The major STH infections (ascariasis [roundworm],
trichuriasis [whipworm], and hookworm infection)
are among the most prevalent infections in
developing countries. Because STH worm burdens are
higher in school-aged children than in any other single
group, the WHO and the PCD advocate schoolbased
administration of broad-spectrum anthelmintics
on a periodic and frequent basis. The agents most
widely employed for reducing morbidity are the benzimidazole
anthelmintics (BZ), either albendazole
(ALBENZA and ZENTEL) or mebendazole (VERMOX, others)
(Table 51–1, p. 1450).
Single dose therapy with a BZ reduces worm burden to a
varying degree, with greatest efficacy for ascariasis, followed by
whipworm and hookworm (Keiser and Utzinger, 2008) and subsequently
reduces morbidity attributable to the parasite. Treatment
improves host iron stores and hemoglobin levels, physical growth,
cognition, educational achievement, and school absenteeism, as well
as having a positive influence on the entire community by reducing
transmission (Bethony et al., 2006). In 2001, the World Health
Assembly adopted a resolution urging that by 2010 member states
should regularly administer anthelmintics to at least 75% of all
school-age children at risk for morbidity (WHO, 2002). Concerns
with this recommendation have included:
• The scope of the undertaking
• The high rate of post-treatment reinfection that occur in areas of
high transmission
• Documented drug failures against hookworm with mebendazole
• The possibility that widespread treatment will lead to the emergence
of BZ drug resistance
• The possibility that by focusing exclusively on school-aged children,
other groups and vulnerable populations, such as preschool
children and women of reproductive age, will be omitted
In addition to targeting STH infections among schoolaged
children, there are ongoing programs to eliminate lymphatic
filariasis (LF) and onchocerciasis (river blindness) over the next
10-20 years (Molyneux and Zagaria, 2002; Molyneux et al., 2003).
The term elimination, as opposed to eradication, refers to the reduction
of disease incidence to zero or close to zero, with a requirement
for ongoing control efforts (Hotez et al., 2004). The major goals for
the LF elimination program (and to some extent, the onchocerciasis
elimination programs) are to interrupt arthropod-borne transmission
by administering combination therapy with either diethylcarbamazine
(DEC; HETRAZAN; available from CDC in the U.S.) and
albendazole (in LF-endemic regions such as India and Egypt), or
ivermectin (STROMECTOL) and albendazole (in LF regions where
onchocerciasis and/or loiasis are co-endemic). For onchocerciasis,
ivermectin also reduces the microfilarial load in the skin, leading to
reductions in so-called troublesome itching and ultimately, in preventing
river blindness. DEC and ivermectin target the microfilarial
stages of the parasite, which circulate in blood and are taken up by
arthropod vectors where further parasite development takes place.
Both control programs rely heavily on the generosity of major drug
companies that donate ivermectin and albendazole, respectively
(Burnham and Mebrahtu, 2004; Molyneux et al., 2003).
Ascaris lumbricoides and Toxocara canis. Ascaris lumbricoides,
known as the “roundworm,” parasitizes a billion
or more people worldwide (de Silva et al., 2003;
Hotez et al, 2009). Ascariasis may affect from 70-90%
of persons in some tropical regions; it is also seen in
temperate climates. People become infected by ingesting
food or soil contaminated with embryonated A.
lumbricoides eggs. The highest ascaris worm burdens
occur in school-aged children in whom the parasite can
cause intestinal obstruction or hepatobiliary ascariasis
(Crompton, 2001).
Effective and safe anthelmintics have replaced the older
ascaricides. The preferred agents are the benzimidazoles (BZ),
mebendazole and albendazole, and the broad spectrum drug pyrantel
pamoate. Cure with any of these drugs can be achieved in nearly
100% of cases. Mebendazole and albendazole are preferred for
therapy of asymptomatic to moderate ascariasis, as well as for mass
drug administration campaigns because those agents have a broad
spectrum of activity against GI nematodes. Both compounds
should be used with caution to treat heavy Ascaris infections, alone