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

Chemotherapy of Helminth
Infections
James McCarthy, Alex Loukas,
and Peter J. Hotez
Infections with helminths, or parasitic worms, affect
more than two billion people worldwide. In regions of
rural poverty in the tropics, where prevalence is greatest,
simultaneous infection with more than one type of
helminth is common. The relative incidence of common
helminthic infections in humans worldwide is
illustrated in Figure 51–1.
Worms pathogenic for humans are Metazoa and
can be classified into roundworms (nematodes) and
two types of flatworms, flukes (trematodes) and tapeworms
(cestodes). These biologically diverse eukaryotes
vary with respect to life cycle, bodily structure,
development, physiology, localization within the host,
and susceptibility to chemotherapy. Immature forms
invade humans via the skin or GI tract and evolve into
well-differentiated adult worms with characteristic tissue
distributions. With few exceptions, such as
Strongyloides and Echinococcus, these organisms cannot
complete their life cycle and replicate within the
human host to produce mature offspring. Therefore,
the extent of exposure to these parasites dictates the
number of parasites infecting the host, a characteristic
recognized as infection intensity, which itself determines
the morbidity caused by infection. Secondly,
any reduction in the number of adult organisms by
chemotherapy is sustained unless reinfection occurs.
The burden of parasitic helminths within an infected
population is not uniformly distributed, and it typically
displays a negative binomial distribution whereby relatively
few persons carry the heaviest parasite burden,
resulting in increased morbidity in these individuals
who also contribute disproportionately to transmission.
Anthelmintics are drugs that act either locally
within the gut lumen to cause expulsion of worms from
the GI tract, or systemically against helminths residing
outside the GI tract. Safe and effective broad-spectrum
anthelmintics, initially developed for veterinary use, are
currently available for use in humans. However, therapy
for many tissue-dwelling helminths, such as filarial parasites,
is not fully effective. For many reasons, including
their long-lived and relatively complex life cycles,
acquired resistance to anthelmintics in humans has yet
to become a major clinical problem. However, with the
increasing deployment of mass drug therapy, and considering
the veterinary experience with resistance, the
potential for drug resistance among helminths in
humans requires monitoring.
Primarily as a result of stepped-up advocacy by
the World Health Organization (WHO), the World
Bank, the Global Network for Neglected Tropical
Diseases, and smaller nongovernmental organizations
such as the London-based Partnership for Child
Development (PCD), there is increasing appreciation
for the impact of helminth infections on the health and
education of school-aged children. These organizations
have promoted the periodic and frequent use of
anthelmintic drugs in schools as a means to control
morbidity caused by soil-transmitted helminths and
schistosomes in developing countries. In addition, interest
has grown in eliminating arthropod-borne helminth
infections by interrupting their transmission through the
widespread use of anthelmintics. Today, control programs
employing anthelmintics rank among the world’s
largest health efforts, and hundreds of millions of people
receive treatment annually (Hotez et al., 2009).
This chapter is divided into two main parts:
• clinical presentation and recommended chemotherapy
for common helminth infections in humans
• pharmacological properties of specific anthelmintics