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

1448 Diphyllobothrium latum. Diphyllobothrium latum, the
fish tapeworm, is found most commonly in rivers and
lakes of the Northern Hemisphere. In North America, the
pike is the most common second intermediate host. The
eating of inadequately cooked infested fish introduces
the larvae into the human intestine; the larvae can develop
into adult worms up to 25 m long. Most infected individuals
are asymptomatic. The most frequent manifestations
include abdominal symptoms and weight loss; megaloblastic
anemia develops due to a deficiency of vitamin
B 12
, which is taken up by the parasite.
SECTION VII
CHEMOTHERAPY OF MICROBIAL DISEASES
Therapy with praziquantel readily eliminates the worm and
ensures hematological remission.
Hymenolepis nana. Hymenolepis nana, the dwarf tapeworm,
is the smallest and most common tapeworm parasitizing
humans. Infection with this cestode is
cosmopolitan, more prevalent in tropical than temperate
climates, and most common among institutionalized
children, including those in the southern U.S. H. nana
is the only cestode that can develop from ovum to
mature adult in humans without an intermediate host.
Cysticerci develop in the villi of the intestine and then
regain access to the intestinal lumen where larvae
mature into adults. Treatment therefore must be adapted
to this cycle of autoinfection.
Praziquantel is effective against H. nana infections, but higher
doses than used for other tapeworm infections usually are required.
In addition, therapy may have to be repeated. Treatment failure
or reinfection is indicated by the appearance of eggs in the stool
~4 weeks after the last dose. Albendazole is partially efficacious
against H. nana; in 277 cases from 11 studies, 69.5% of patients were
cured by albendazole (400 mg daily for 3 days) (Horton, 2000).
Echinococcus Species. Humans serve as one of several
intermediate hosts for larval forms of Echinococcus
species that cause “cystic” (E. granulosus) and “alveolar”
(E. multilocularis and E. vogeli) hydatid disease.
Dogs and related canids are definitive hosts for these
tapeworms. Parasite eggs from canine stools are a major
worldwide cause of disease in associated livestock (e.g.,
sheep and goats). E. granulosus produces unilocular,
slowly growing cysts, most often in liver and lung,
whereas E. multilocularis creates multilocular invasive
cysts, predominantly in the same organs. Removal of
the cysts by surgery is the preferred treatment, but leakage
from ruptured cysts may spread disease to other
organs.
Prolonged regimens of albendazole, either alone or as an
adjunct to surgery, are reportedly of some benefit. However, some
patients are not cured despite multiple courses of therapy, especially
in alveolar echinococcosis where lifelong therapy with albendazole
may be required. Treatment of infected dogs with praziquantel eradicates
adult worms and interrupts transmission of these infections.
New treatment methods, such as percutaneous puncture, aspiration,
injection of scolicidal agents, and re-aspiration–based techniques,
have received much attention, and they yield rates of cure and relapse
equivalent to those following surgery. Benzimidazole treatment
should be administered in the perioperative period (Kern, 2003).
Trematodes (Flukes)
Schistosoma haematobium, Schistosoma mansoni,
Schistosoma japonicum. These are the main species of
blood flukes that cause human schistosomiasis; less
common species are Schistosoma intercalatum and
Schistosoma mekongi. The infection affects >200 million
people (Figure 51–1), and >700 million are at risk
(Steinmann et al., 2006). In the Americas, schistosomiasis
occurs in Brazil, Suriname, Venezuela and certain
Caribbean islands (S. mansoni), much of Africa and
the Arabian Peninsula (S. mansoni and S. haematobium),
and China, the Philippines, and Indonesia (S. japonicum).
More than 90% of the cases of schistosomiasis
occur in sub-Saharan Africa, with approximately twothirds
of the cases caused by S. haematobium and onethird
caused by S. mansoni. Infected freshwater snails
act as intermediate hosts for transmission of the infection,
which continues to spread as agriculture and water
resources increase. Like most helminth infections, the
clinical manifestations of schistosomiasis generally
correlate with the intensity of infection, with pathology
primarily involving the liver, spleen, and GI tract
(for S. mansoni and S. japonicum) or the urinary and
genital tracts (S. haematobium). Heavy infection with
S. haematobium predisposes to squamous cell carcinoma
of the bladder. Chronic infections can cause
porto-systemic shunting due to hepatic granuloma formation
and periportal fibrosis in the liver.
Praziquantel is the drug of choice for treatment of schistosomiasis.
The drug is safe and effective when given in single or divided
oral doses on the same day. These properties make praziquantel especially
suitable for population-based chemotherapy. Moreover,
repeated chemotherapy with praziquantel is thought to accelerate protective
immune responses by increasing exposure to antigens released
from dying worms that induce a T H
2 response (Mutapi et al., 1998).
In sub-Saharan Africa, praziquantel is typically administered in mass
drug administration campaigns for populations infected with schistosomiasis,
with the use of a height pole as a guide to drug dosage.
Sadly, even the modest cost of US $0.08 per tablet is beyond the
health budgets of many sub-Saharan African countries (Hotez, 2009).
Although not effective clinically against S. haematobium and S.
japonicum, oxamniquine is effective for treatment of S. mansoni
infections, particularly in South America, where the sensitivity of
most strains may permit single-dose therapy. However, resistance has