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

1454 (Addiss and Dreyer, 2000). Expanded use of ultrasound also has
facilitated the identification of infected individuals who are microfilaria
negative on blood examination. These individuals also benefit
from DEC treatment. During acute episodes of lymphangitis,
treatment with DEC is not recommended until acute symptoms subside
(Addiss and Dreyer, 2000).
For mass treatment with the objective of reducing microfilaremia
to levels whereby transmission is interrupted, effective strategies
have included the introduction of DEC into table salt (0.2-0.4%
by weight of the base) (Gelband, 1994). DEC, given annually as a single
oral dose of 6 mg/kg, is most effective in reducing microfilaremia
when co-administered with either albendazole (400 mg) or ivermectin
(0.2-0.4 mg/kg) (Ottesen et al., 1999). Although the adverse reactions
to microfilarial destruction are greater after the oral therapy with DEC
tablets than when the mass drug administration is administered by
medicated table salt, therapy is usually well tolerated.
SECTION VII
CHEMOTHERAPY OF MICROBIAL DISEASES
O. volvulus and L. loa. DEC is contraindicated for the treatment of
onchocerciasis because it causes severe reactions related to microfilarial
destruction, including worsening ocular lesions. Thus use of DEC
for control is considered contraindicated in areas where onchocerciasis
is endemic (Molyneux et al., 2003). Such reactions are far less
severe in response to ivermectin, the preferred drug for this infection.
Despite its drawbacks, DEC remains the best available drug for therapy
of loiasis. Treatment is initiated with test doses of 50 mg (1 mg/kg
in children) daily for 2-3 days, escalating to maximally tolerated daily
doses of 9 mg/kg in three doses for a total of 2-3 weeks.
In patients with high-grade microfilaremia, low test doses are
used, often accompanied by pretreatment with glucocorticoids or
antihistamines, to minimize reactions to dying microfilariae. Such
reactions may manifest as severe allergic reactions, and occasionally
meningoencephalitis and coma likely caused by CNS effects of
dying microfilariae. Repeated courses of DEC treatment, separated
by 3-4 weeks, may be required to cure loiasis. Although ivermectin
is not a good alternative to DEC for treatment of loiasis, albendazole
may be useful in patients who either fail therapy with DEC or
who cannot tolerate the drug (Klion et al., 1999).
DEC is clinically effective against microfilariae and adult
worms of Dipetalonema streptocerca, but filariasis due to
Mansonella perstans, M. ozzardi, or Dirofilaria immitis responds
minimally to this agent. DEC is no longer recommended as a firstline
drug for the treatment of toxocariasis.
Toxicity and Side Effects. Below a daily dose of 8-10
mg/kg, direct toxic reactions to DEC are rarely severe and
usually disappear within a few days despite continuation
of therapy. These reactions include anorexia, nausea,
headache, and, at high doses, vomiting. Major adverse
effects result directly or indirectly from the host response
to destruction of parasites, primarily microfilariae.
encephalopathy. In patients with onchocerciasis, the Mazzotti reaction
typically occurs within a few hours after the first dose, and it
manifests as intense itching, a papular rash, enlargement and tenderness
of the lymph nodes, and sometimes fever, tachycardia, arthralgia,
and headache. This reaction persists for 3-7 days and then
subsides. Ocular complications include limbitis, punctate keratitis,
uveitis, and atrophy of the retinal pigment epithelium (Dominguez-
Vazquez et al., 1983). DEC appears to be safe for use during
pregnancy
Precautions and Contraindications. Population-based therapy with
DEC should be avoided where onchocerciasis or loiasis is endemic,
although the drug can be used to protect foreign travelers from these
infections. Pretreatment with glucocorticoids and antihistamines
often is undertaken to minimize indirect reactions to DEC that result
from release of antigen by dying microfilariae. Dosage reduction
may be appropriate for patients with impaired renal function or persistent
alkaline urine.
Doxycycline
The discovery that filarial parasites, including W. bancrofti and O.
volvulus, harbor bacterial symbionts of the genus Wolbachia led to studies
that have established the efficacy of courses of doxycycline of duration
≥6 weeks in bancroftian filariasis and onchocerciasis (Taylor and
Hoerauf, 2001). A 6-week regimen of doxycycline (100 mg daily), by
killing the Wolbachia, leads to sterility of adult female Onchocerca
worms (Hoerauf et al., 2000). Studies using shorter treatment courses
and alternative antibiotics including rifampicin are in progress. The
pharmacology of doxycycline is discussed in Chapter 55.
Ivermectin
History. In the mid-1970s, surveys of natural products revealed that
a fermentation broth of the soil actinomycete Streptomyces avermitilis
ameliorated infection with Nematospiroides dubius in mice.
Isolation of the anthelmintic components from cultures of this organism
led to discovery of the avermectins, a novel class of 16-
membered macrocyclic lactones (Campbell, 1989). Ivermectin
(MECTIZAN; STROMECTOL; 22,23-dihydroavermectin B 1a
) is a semisynthetic
analog of avermectin B 1a
(abamectin), an insecticide developed
for crop management. Ivermectin now is used extensively to
control and treat a broad spectrum of infections caused by parasitic
nematodes (roundworms) and arthropods (insects, ticks, and mites)
that plague livestock and domestic animals (Campbell, 1993).
Delayed reactions to dying adult worms may result in lymphangitis,
swelling, and lymphoid abscesses in bancroftian and brugian
filariasis, and small skin wheals in loiasis. Reactions typically
are most severe in patients heavily infected with O. volvulus, less
serious in B. malayi or L. loa infections, and mild in bancroftian
filariasis. As noted, the drug occasionally causes severe side effects
in heavy L. loa infections, including retinal hemorrhages and severe