INTERNATIONAL JOURNAL OF

Antimierobial
Agents
ELSEVIER International Journal of Antimicrobial Agents 4 (1994) 321-324

The efficacy of praziquantel for the treatment of cestode and metacestode

infections

S. Geerts

Institute of Tropical Medicine, Nationalestraat 155, 1t-2000 Antwerp 1, Belgium

Accepted 21 March 1994

Abstract
The activity of praziquantel against adult and larval cestode infections is reviewed. Praziquantel remains an excellent drug for
the treatment of taeniasis and hymenolepiasis. Neurocysticercosis, however, seems to respond better to a treatment with albendazole
than to praziquantel, especially when the anthelmintic treatment is combined with steroid drugs. Concerning the treatment of
hydatidosis and coenurosis, more research is needed to evaluate the efficacy of praziquantel.

Key words." Praziquantel; Cestodes; Metacestodes; Cysticercosis; Taenia solium; Taenia saginata; Hymenolepis nana

1. Adult cestode infections
Taeniasis
Until now the recommended treatment for Taenia sag-
inata and T. solium was a single dose of 5 to 10 mg/kg
ofpraziquantel (PZQ) [1,2]. During recent years the effi-
cacy of 10 mg/kg has been confirmed by different authors
[3,4]. PZQ was also very effective against the so-called
Taiwan Taenia, T. saginata taiwanensis [5]. Recently,
however, Pawlowski [6] showed that even a dose of 2.5
mg/kg was 100% effective in 124 patients infected with
T. saginata and carefully examined 4 months after treat-
ment. The same author advises 2.5 mg/kg as a safe and
more economical and probably still highly effective treat-
ment of T. solium, but admits that its efficacy remains to
be confirmed. Indeed, there are few data available on
T. solium. A dose rate of 5 mg/kg eliminated T. solium
in 33 (94.3%) out of 35 patients (Baranski; Rim cited by
Pawlowski [6]). A large-scale mass treatment trial in Ec-
uador confirmed that this dose is also quite safe, even in
a hyperendemic area for neurocysticercosis. After treat-
ment of 10 173 people with an average dose of 5.2 mg/kg
(3.4-8.7) only two serious complications were observed:
one patient with an epileptic attack and one with an
episode of dysentery [7]. Other reports on activation of
asymptomatic neurocysticercosis after treatment with
PZQ concerned doses of 20 mg/kg or higher [8,9].
It is too early to fully evaluate the efficacy of PZQ in
controlling the taeniasis--cysticercosis complex and espe-
cially neurocysticercosis by 'population oriented chemo-
therapy', but the first results in Ecuador and Mexico
were promising [7,10].
Hymenolepiasis and other cestodoses
Although several authors report excellent activity of
a single dose of 25 mg/kg PZQ against Hymenolepis nana
[1,3,5,11], the efficacy of this dose is sometimes less than
50% [12]. Therefore two doses of 25 mg/kg might be
necessary to obtain complete cure, as was already sug-
gested by Kumar et al. [13].
Concerning the efficacy of PZQ against Diphyllo-
bothriurn spp., no new data have become available, so
that the recommended treatment still remains a single
dose of 10 or 25 mg/kg respectively against D. pacificum
and D. latum [1]. A dose rate of about 10 mg/kg seems
also to be effective against Dipylidium caninum [14].
2. Metacestode infections
Cysticercosis
In the past many reports have been published which
did not allow an unequivocal evaluation of the efficacy
of PZQ for the treatment of neurocysticercosis due to the

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322 S. Geertsl International Journal of Antimicrobial Agents 4 (1994) 321~324
lack of control patients or the use of PZQ in combination
with other drugs, the possibility of spontaneous cure, etc.
[2,15,16]. Well designed studies including a sufficient
number of untreated control patients, however, have
provided clearcut answers on the efficacy of PZQ against
different types and different locations of cysticerci.
Treatment with 50 mg/kg PZQ per day for 15 days signif-
icantly decreased the number of cysts and also the fre-
quency of seizures in comparison with untreated patients
[17-19]. Vasquez and Sotelo [20] examined a large retro-
spective series of 240 patients (follow-up during 92 _+7
months) and showed very conclusively that treatment
with albendazole, PZQ or both caused an 82% reduction
in the mean number of brain cysts and a 95% reduction
in the mean frequency of seizures (from 11.3 to 0.6 per
year; 54% seizure-free after 3 years), whereas the un-
treated patients (without inflammation around the cysts)
averaged 10.9 seizures per year and none became seizure-
free. Spontaneous cure or satisfactory control of the dis-
ease without anthelmintic treatment, however, is possible
in patients with inflammation around the cysts and in
children. Actively inflamed acute lesions, which are very
common in the age group below 20 years, generally re-
solve completely in 2 to 9 months time [16,21-24].
There are strong indications that albendazole (15 mg/
kg per day for 30 days) is superior to PZQ (50 mg/kg per
day for 15 days) for the treatment of neurocysticercosis
patients. Up to now, however, prospective, double-blind,
placebo-controlled trials comparing both drugs are still
lacking. After the first report by Escobedo et al. [25], the
excellent activity of albendazole was confirmed by differ-
ent research groups in Mexico, Brazil and Ecuador
[19,20,26,27]. When few or no steroids are used simulta-
neously, the difference in the efficacy of PZQ and alben-
dazole is not very pronounced [27,28]. In combination
with prednisolone, however, albendazole gives a much
better overall improvement than PZQ: 84% against 62%
in a series of 50 patients treated with each of the drugs
[26]. Retrospective evaluation of a large number of pa-
tients, only 22% of whom were treated with dexa-
methasone, confirmed the better activity of albendazole,
resulting in 80% reduction of the total number of cysts
against only 65% reduction with PZQ [20]. These authors
also found a higher risk of persistent seizures after treat-
ment with PZQ than albendazole (odds ratio 2.3). The
improved activity of albendazole when combined with
steroids is due to an increase of the plasma level of the
drug by 50% [29], whereas just the opposite occurs when
PZQ is combined with steroids. In patients simultane-
ously treated with PZQ and dexamethasone PZQ plasma
levels were 50% lower than in those treated with PZQ
alone [30]. The bioavailability of PZQ, however, can be
increased by a factor of 2.5 through coadministration
with cimetidine, an inhibitor of the P450 cytochrome
metabolic pathway [31].
The current treatment schemes for cysticercosis using
albendazole or PZQ have been determined empirically
and only very few studies were set up to optimise these
schemes. Sotelo et al. [18] compared four treatment reg-
imens: 50 mg/kg PZQ for 15 or 8 days and 15 mg/kg
albendazole for 30 or 8 days. Surprisingly they found
that the short treatment scheme with albendazole was as
effective as the long one. It caused disappearance of the
lesions in 85% of the patients, whereas the short and the
long scheme with PZQ caused a reduction of only 48 and
60% respectively. The same authors recommend to start
treatment of neurocysticercosis with a short course using
albendazole. In patients showing a partial response to
albendazole after 3 months, the treatment can be contin-
ued with a 15-day course using PZQ. Indeed, some cysts
seem to respond better to PZQ, whereas others respond
better to albendazole. Several reports mention the disap-
pearance of cysticerci with albendazole after unsuccess-
ful treatment with PZQ [25,32,33].
Another treatment schedule was tried by Bittencourt
et al. [34]. They used 100 mg/kg PZQ for 10 days. Al-
though there was a disproportionally higher concentra-
tion of the drug in blood and CSF than with the usual
dose, these authors could not find any correlation be-
tween serum and CSF concentration of PZQ and disease
outcome [35].
Similarly, the optimal treatment schedule for muscular
and subcutaneous cysticercosis has not yet been deter-
mined. Usually 25 mg/kg PZQ is used for 3 to 4 days [2].
Gascon et al. [36], however, obtained good results using
three doses of 20 mg/kg PZQ at 4-h intervals. The advan-
tage of this schedule is that treatment of patients in rural
regions can be finished in one day. Further research is
absolutely necessary to identify minimum drug concen-
trations to kill cysticerci in vitro and to determine conse-
quently optimal treatment dosages in vivo.
Concerning the indications for treatment of neurocys-
ticercosis with either PZQ or albendazole, there is gen-
eral agreement that both drugs are most effective against
scattered living intraparenchymal, subcutaneous or mus-
cular cysts. They are less effective in patients with intra-
ventricular, spinal, racemose or disseminated cysts,
chronic meningitis and acute encephalitis and are even
contra-indicated for intraocular cysts [37-39].
Hydatidosis and coenurosis
In their recently published book, Morris and Richards
[40] review the activity of PZQ and conclude that 'the
drug has not been anything like as successful as in vitro
and animal experiments had suggested it would'. Indeed,
several authors proved PZQ to be a strong protoscol-
icidal agent in vitro both for Echinococcus granulosus
[41] and for E. multiloeularis [42]. PZQ, however, is less
effective in inhibiting cyst growth in laboratory animals
and sheep [40,43]. PZQ alone did not show very promis-
ing activity in the small number of patients with hydatid
disease treated up to now [44,45]. A combination of al-
 s. Geerts/ lnternational Journal of Antimicrobial Agents 4 (1994) 321-324
b e n d a z o l e (50 m g / k g p e r d a y ) a n d P Z Q (500 m g / k g p e r
d a y ) f o r 1 m o n t h , o n the o t h e r h a n d , was significantly
m o r e effective t h a n either d r u g a l o n e in a p r o p h y l a c t i c
t r e a t m e n t o f E. granulosus cysts in gerbils [46]. It m i g h t
be w o r t h w h i l e to f u r t h e r e x p l o r e c o m b i n a t i o n t h e r a p y .
P r o m i s i n g results were o b t a i n e d with a c o m b i n a t i o n o f
m e b e n d a z o l e a n d P Z Q in p a t i e n t s unsuccessfully t r e a t e d
with m e b e n d a z o l e [47].
M o n t h l y o r 6-weekly m a s s t r e a t m e n t s o f d o g s respec-
tively infected with E. multilocularis o r E. granulosus
using P Z Q are very effective in r e d u c i n g the risk o f
h u m a n h y d a t i d o s i s in h y p e r e n d e m i c areas. This was
nicely s h o w n b y R a u s c h et al. [48] in A l a s k a for E. mul-
tilocularis a n d in several E u r o p e a n c o u n t r i e s a n d in N e w
Z e a l a n d for E. granulosus [49].
T h e activity o f P Z Q a g a i n s t c e r e b r a l c o e n u r o s i s in
sheep at t o t a l d o s a g e s o f 100-500 m g / k g was recon-
firmed [50]. U p to n o w n o d a t a are a v a i l a b l e a b o u t treat-
m e n t o f h u m a n c o e n u r o s i s cases, b u t one r e p o r t m e n -
tions s o m e success o f P Z Q a g a i n s t a b d o m i n a l c o e n u r i in
a spectacled l a n g u r [51].
3. Conclusion
To s u m m a r i z e , it c a n be c o n c l u d e d t h a t P Z Q r e m a i n s
the d r u g o f choice to t r e a t a d u l t cestode infections. F o r
the t r e a t m e n t o f T. solium cysticerci in the b r a i n p a r e n -
c h y m a , a l b e n d a z o l e seems to be s u p e r i o r to P Z Q , cer-
t a i n l y when steroid d r u g s are used simultaneously. T h e
o p t i m a l schedules for the t r e a t m e n t o f n e u r o - c y s t i c e r c o -
sis a n d for m u s c u l a r cysticercosis using either P Z Q o r
a l b e n d a z o l e have still to be identified. C o n c e r n i n g the
use o f P Z Q f o r the t r e a t m e n t o f h u m a n h y d a t i d o s i s o r
coenurosis, the a v a i l a b l e d a t a are r a t h e r d i s a p p o i n t i n g .
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