Langenbecks Arch Surg (2003) 388:413–420

DOI 10.1007/s00423-003-0418-y OVERVIEW

Peter Kern
Echinococcus granulosus infection:
clinical presentation, medical treatment
and outcome

Received: 31 July 2003 Abstract Background: Chemothera- and re-aspiration (PAIR) or modified
Accepted: 5 August 2003 py of cystic echinococcosis became a PAIR-based techniques, have re-
Published online: 5 November 2003 treatment option 25 years ago, when ceived much attention, and in expe-

Springer-Verlag 2003 new anthelminthic drugs were intro- rienced hands these approaches yield
duced. Benzimidazole carbamates rates of cure and relapse equivalent to
were shown to kill the entire those following surgery. Adjunct
metacestode stage of the parasite, and treatment with benzimidazoles is the
praziquantel exhibited an effect on cornerstone of the interdisciplinary
protoscoleces. Continuous or inter- approach in cystic echinococcosis.
mittent treatment with albendazole is Conclusion: The recent ultrasound
recommended for a period of up to 6 WHO consensus classification of he-
months, and praziquantel may en- patic cysts is a major achievement,
hance the effect, in particular in the since on the basis of this classifica-
case of cyst spillage. Degenerative tion prospective clinical trials can be
changes in the cysts occur in ap- initiated. The results of such studies
proximately 75% of the patients by may provide the basis for a stage-
the end of the treatment period. specific appropriate medical, inter-
Benzimidazoles have to be applied in ventional or surgical therapy, or even
high daily doses, and adverse effects guide the clinicians to opt for ‘watch
P. Kern ()) are observed, such as leucopenia, and wait’ by close observation with-
Section of Infectious Diseases elevation of liver transaminases, and out specific treatment.
and Clinical Immunology, alopecia. Unfortunately, prospective
University Hospital and Medical Center, randomized trials on the efficacy of Keywords Cystic echinococcosis ·
Robert Kochstrasse 8, 89081 Ulm,
Germany chemotherapy versus surgery are not Echinococcus granulosus · Hydatid
e-mail: peter.kern@medizin.uni-ulm.de available. New treatment methods, disease · Clinical presentation ·
Tel.: +49-731-50024421 such as percutaneous puncture, aspi- Medical treatment · Benzimidazoles ·
Fax: +49-731-50024422 ration, injection of scolicidal agents Review

Introduction central countries but with medium or high prevalence in

southern, south-eastern and eastern regions. Prevalence
Human cystic echinococcosis is caused by the larval or rates of human cystic echinococcosis (CE) are largely
metacestode stage of the tapeworm Echinococcus gran- linked to the prevalence in livestock [1]. In Central
ulosus. The definitive hosts that harbour the adult stage of Europe, measures such as mandatory meat inspection
the parasite are dogs. Domestic ruminants (i.e. sheep, have interrupted the spread of the disease during the past
cattle, camels) serve as intermediate hosts for the 50 years. Thus, CE has to be considered as an imported
metacestode (hydatid) stage of the parasite. In Europe, infection in Germany, and autochthonous infections are
E. granulosus has an uneven geographic distribution, with rare exceptions. An understanding of the development
very low prevalence rates in some of the northern and and natural history of the metacestode in the infected
414

patient is a prerequisite for the development of an adapted tory host cells as well as for micro-organisms, allowing,
management of the disease. Advances in imaging tech- however, the access of nutritional factors for the parasite.
niques during the past 25 years have enabled us to The inner layer (‘germinative layer’) covers the inside of
visualize hydatid cysts in parenchymatous organs [2]. the cyst and consists of a monolayer of viable ‘pluripo-
Prior to that, clinical signs did not allow an early tent’ cells which proliferate and form large numbers of
detection of the hydatid cysts, and surgery was the only brood capsules filled with protoscoleces. These proto-
measure available to diagnose, and at the same time, treat, scoleces are the ‘anlagen’ of the heads of the future
hydatid disease. The recent proposal of a consensus WHO cestodes, showing the corona of hooks and four suckers in
classification by the WHO–Informal Working Group on an inverted form. In contrast, the ‘infertile’ endocyst
Echinococcosis (WHO-IWGE), the ‘WHO-IWGE classi- consists of the pluripotent germinative layer, but lacks
fication of ultrasound images of cystic echinococcosis brood capsules. Thus, the ‘viable’ metacestode can be
cysts’, is a major step forward; its wide application should ‘fertile’, which allows a macroscopic or parasitological
allow standardization of treatment indications and their diagnosis to be made, or ‘infertile’ when clear fluid is
evaluation in the future [3]. Since 1977, the introduction present, but protoscoleces cannot be detected. In both
of benzimidazole carbamates (albendazole or mebenda- situations the cysts expand slowly over a period of years
zole) has improved the treatment of echinococcosis, not [2, 5].
only as the sole treatment option for inoperable cases but
also as an adjunct to surgery [4]. The first part of this
review provides a general baseline for metacestode Organ preferences of the metacestode
growth and its morphology as well as for the resulting
clinical presentation. The focus of the second part covers Most patients (40% to 80%) have a single organ involved
the natural course of the metacestode within the human and harbour a solitary cyst. The primary organ affected is
host and the specific anthelminthic treatment. Alveolar the liver in approximately 70% of the patients; most
echinococcosis is caused by a different species of hepatic cysts are located in the right lobe. The second
Echinococcus, namely the fox tapeworm E. multilocula- most commonly affected organ is the lung, in about 20%
ris, which presents as a very different clinical entity and of the patients [6]. The frequencies of liver and lung
is, therefore, not covered in this review. location found in different case series may vary from
country to country and depend on the diagnostic tools, the
source of the statistical data, the age of the patient group
Development of the metacestode (hydatid) under study, etc. Of 459 cases with E. granulosus
infection from Switzerland, 68.8% had cysts in the liver,
After humans ingest the infective eggs, the first-stage 17.2% in the lung, 3.7% in the kidney, 3.3% in the spleen,
larva or oncosphere hatches in the stomach or in the small 2.2% in the muscles and skin, 2.0% in the abdominal and
intestine, penetrates the mucosal wall, enters the portal pelvic cavity, 1.1% in the mediastinum or heart, 0.9% in
circulation, and is carried to the liver. After passing the brain, 0.6% in the bones and <0.5% in the ovarium,
through the liver filter, or via lymphatic vessels, the eye, spinal cord, pancreas, testis, urinary bladder, etc. [2].
oncosphere reaches the right side of the heart and then the Thus, virtually every organ and tissue is suited to harbour
minor circulation. If the oncosphere again passes the lung the metacestode.
filter, it gets into the systemic circulation and can settle in
virtually all anatomical sites, especially in the organs of
greater vascularization. After an undefined incubation Morphology of the metacestode
period that depends largely on favourable environmental
conditions, the metacestode develops into a single, large, Primary and secondary cysts
fluid-filled cyst (‘hydatid’). The fluid resembles spring
water: It is clear, colourless, sterile, and contains highly The development of the metacestode from the oncosphere
antigenic material that is responsible for anaphylactic to a solitary cyst occurs in approximately 75% of patients
reactions that occur when the cyst ruptures. Within the [6]. In the remaining cases two or more cysts can initially
cyst large numbers of small ‘brood capsules’ are formed, be detected in the affected organ, which still covers the
which contain protoscoleces and usually float free in the definition of primary cysts, since it can be assumed that
cyst fluid (‘hydatid sand’). The cyst is surrounded by the every cyst has developed from a single oncosphere. Often,
periparasitic host tissue (pericyst) that encompasses the the metacestode is filled with smaller cysts, so called
endocyst of metacestode origin. The endocyst has a ‘daughter cysts’ or ‘secondary cysts’. The daughter cysts
cellular outer wall (‘multilaminated membrane’ or ‘chi- develop and detach from the germinal ‘pluripotent’ layer
tinous layer’) that is made up of a varying number of of the primary cyst. Floating freely within the primary
concentric layers of hyaline placed on top of each other. cyst they expand and become close to each other, which
While intact, it constitutes a perfect filter for inflamma- leads to a septate appearance of the cyst in diagnostic
 415

imaging procedures. Thus, multi-septate cysts contain Clinical presentation

daughter cysts inside or attached to the outer surface of
the primary endocyst. The imaging features are patho- The incubation period varies and may last months to years
gnomonic; they appear as ‘wheel-like’, ‘rosette-like’, or [6]. Occurrence is equally distributed between male and
‘honeycomb-like’ structures. The spread of an infection female victims, and all age groups are affected except
into the peritoneal cavity has been described as secondary children under 1 year of age. The clinical symptomatol-
echinococcosis, since it may have resulted from the ogy is highly variable and depends on (1) the organs
rupture of a primary liver cyst. The term is also used for involved, (2) the size of the cyst and its location, (3) the
new cysts developing after unintentional dissemination of interaction between the expanding cysts and the adjacent
the parasitic germinative layer into other organs during organs, (4) the complications related to cyst rupture,
interventional procedures or after trauma [7]. spread of protoscoleces and bacterial or fungal infection,
(5) systemic host reactions, such as urticaria, anaphylaxis
or nephropathy [2]. If cysts are small, well encapsulated,
Uncomplicated cysts degenerated or calcified, or localized in sites where they
do not induce significant pathological conditions, the
Fast-growing cysts exert pressure on the adjacent tissues infection may remain asymptomatic for a long time. The
and are, thus, active and symptomatic. However, in large metacestode may become symptomatic only if its size
parenchymatous organs, such as the liver, the develop- leads to a compression of adjacent tissue or if the host
ment of the metacestode may be completely asymptom- reaction towards the parasite induces other pathological
atic for a long time, until the space-occupying effect in events. In large case series it was shown that 38 to 60% of
the organ involved elicits symptoms. Inactive cysts the cases remained asymptomatic and diagnosis was made
represent a spectrum of pathology ranging from degen- accidentally [2]. The general availability of ultrasonog-
erating, partly viable to ‘dead’ cysts with solid matter raphy may shift the observed frequency of liver cysts
within the cyst, which may be, in addition, partially or when compared with that of lung cysts. Sudden symptoms
totally calcified. Regardless of the viability of the may occur after spontaneous or traumatic cyst rupture,
metacestode, active and inactive cysts can cause symp- which may be followed by secondary bacterial super-
toms, and appropriate treatment, medical or surgical, has infection of the empty cyst. Hepatomegaly may be
to be sought [2]. present, and, depending on the localization of the
metacestode, cholestasis with or without jaundice may
be a leading initial clinical feature. Of the cases with lung
Complicated cysts cysts, 75% are asymptomatic at initial presentation and
rarely experience chest pain or cough. However, a large
Ruptured E. granulosus cysts are classified into three pulmonary cyst eventually brings about disruption,
types: contained, communicating and direct. The con- stenosis, and occlusion of the neighbouring bronchi,
tained rupture occurs when only the endocyst ruptures but which can cause bronchopulmonary symptoms [8]. The
the pericyst remains intact, which usually precludes metacestode can also completely destroy the pulmonary
infection or allergic reactions. This rupture leads to a lobe. Of the cases diagnosed with pulmonary echinococ-
separation of the endocyst from the pericyst and is cosis, 25% reveal ruptured and infected cysts. Symptoms
frequently seen and clearly shown by imaging techniques, include chest pain, cough, haemoptysis, dyspnoea, aller-
i.e. the ‘water lily sign’. Endocyst rupture can occur gic reactions, and fever. The physical signs are not
spontaneously, during aging of the metacestode, or after characteristic. Rupture of the metacestode in the bronchus
trauma, during surgical or interventional treatment using is accompanied by a subfebrile state, haemoptysis and
disinfecting agents, and under anthelminthic chemother- coughing. The patient will usually complain of a feeling
apy. The communicating rupture occurs when the cyst that ‘something is tearing apart in the chest’. During
contents are released into the biliary or bronchial tree, coughing attacks, the patient will expel the cyst’s contents
which has severe clinical consequences. Direct rupture through the mouth. The fluid is clear, tastes salty, and
occurs when both the endocyst and the pericyst break, and contains remnants of the hyaline membrane of the
hydatid fluid, with daughter cysts, fragments of the metacestode [2, 6, 8]. More often, patients develop
germinal layer, brood capsules, and protoscoleces, spills complications associated with a severe inflammatory
into the neighbouring cavity or into the surrounding reaction and pneumonia. Eosinophilia is frequently pres-
tissues. Direct rupture is most frequently caused by ent in this instance, whereas it is rarely a presenting sign
trauma—including unintentional incision at surgery—and in asymptomatic and uncomplicated echinococcosis.
may cause various complications, i.e. anaphylactic shock, Routine laboratory findings are not of diagnostic rele-
secondary bacterial infection. The complete rupture vance. Presenting symptoms and signs for manifestation
reduces the turgor of the cyst, which then decreases in in other organs depend on the anatomical site where the
size or collapses [2]. metacestode grows and expands.
416

Fig. 1 WHO-IWGE classification of ultrasound images of cystic echinococcosis cysts (reproduced from [3] with the permission of WHO)

Imaging Immunodiagnosis
Ultrasonography, computed tomography and magnetic Serological examination is the second-line tool for the
resonance imaging are established and validated proce- diagnosis of CE [2, 11]. It should be noted that the
dures to visualize the characteristic structure and size of interpretation of serological results depends on various
hepatic cysts [9]. Hydatid cysts in other sites of the body factors, such as antigen quality, organ site involved,
are best identified by the organ-specific imaging method. single or multiple hydatid cysts, active or inactive cysts,
With the broad availability of these non-invasive imaging individual variability of immune responses, etc. With the
techniques, asymptomatic lesions in various sites have test systems available specific antibodies may not be
become detectable. Thus, the ultrasonographic description detectable in more than 20% of patients with hepatic cysts
and staging of echinococcal cysts has contributed tremen- or in more than 40% of patients with pulmonary cysts.
dously to our understanding of CE over the past years, The viable metacestode, fertile or infertile, is masked by
and a number of classification systems has been devel- the physical barrier of the acellular, multilaminated or
oped for diagnosis, staging and follow-up during therapy hyaline layer, which leads to a most effective sequestra-
[2, 10]. The recent consensus ultrasound classification tion from the host’s immune response. In addition, the
developed by the WHO-IWGE takes the spectrum of metacestode has probably evolved other strategies for
clinical pathology into account and provides the basis for evading the immune response [12]. If the structural
initiation of prospective trials [3]. The ‘cystic lesion’ (CL) integrity of the larva is disturbed, the adaptive immune
stage is unilocular with uniform anechoic content, not system can build up its response. The high rate of false
clearly delimited by a hyperechoic rim, may normally be negative reactions, especially in children, in patients with
round or oval, is variable in size but usually small, and, if ‘young’ hepatic cysts or in patients with extrahepatic
it represents an E. granulosus metacestode it is assigned cysts should be kept in mind, and for clinical practice,
as being an active, i.e. viable cyst. The classification negative serological results do not exclude the possibility
stages ‘cystic echinococcosis’ (CE 1 to 5) provide of metacestode development. On the other hand, serolog-
detailed descriptions of the most frequent pathological ical results are often positive after accidental puncture or
conditions: active cysts CE1 and CE 2, transitional cysts after any other invasive intervention.
CE3, and inactive cysts CE4 and CE5 (Fig. 1, reproduced
from [3] with the permission of WHO)
Case definition
The aggregation of case history and findings from
ultrasound, conventional X-ray and computed tomogra-
phy or magnetic resonance imaging, in conjunction with
 417

serological results, leads, in most cases, to a probable use in the animal-health industry. In general, benzimida-
diagnosis of CE [2]. The choice for the best imaging zoles dissolve poorly in water and, thus, their absorption
method depends on the organ involved and the particular in the small intestine is limited. They are safe for the host
site within this organ [9]. Serological examination may animal, are without drug toxicity, and are not retained in
not be satisfying in a considerable number of cases, the food chain. This is the greatest value of these drugs
despite the improvement of diagnostic tools [11]. Definite and a success story for the treatment of gastrointestinal
diagnosis can be made by macroscopic identification of E. roundworm infections in livestock [17]. Mebendazole,
granulosus cysts (structure and size) or microscopic and the newer benzimidazole carbamate, albendazole,
diagnosis in specimens (protoscoleces or hooks), obtained were further developed for the treatment of human
after surgery, and/or by histological examination of the intestinal helminthiases. The primary mode of action of
parasitic tissue [2]. Echinococcosis has been a notifiable these drugs is an interaction with the eukaryotic cyto-
disease in Germany since 2001. In 2001 and 2002, 26 and skeletal protein, b-tubulin, inhibiting its polymerization
22 cases, respectively, of CE were recorded [13]. into microtubules. As a secondary effect glucose uptake is
However, due to the recent notification pathway that reduced, leading to depletion of glycogen storage,
records serologically defined cases, not all new cases may degenerative alterations in the endoplasmic reticulum
have come to attention. and mitochondria of the germinal layer and, finally, to
cellular autolysis [18, 19]. Tubulin is a ubiquitous protein,
present in the mammalian host as well as the helminthic
Natural history of the metacestode parasite, but the benzimidazoles bind selectively to
parasite tubulin and, thus, have minor or no toxicity in
The maximum survival time of an Echinococcus cyst mammals [19]. The effect on tissue helminths, such as
observed in humans was 53 years [14]. In a small metacestodes of Echinococcus spp., was investigated in
longitudinal study it could be shown that asymptomatic various animal models in the 1970s [20, 21]. Promising
liver cysts remain symptom-free for over 10 years, results opened the field for the use of benzimidazoles in
regardless of the cyst size or type [15]. On the basis of human cystic and alveolar echinococcosis [22, 23, 24, 25,
these observations it is now generally accepted that many 26, 27].
cysts degenerate spontaneously over time, remaining Generally, benzimidazoles are highly effective in the
asymptomatic or oligosymptomatic. In addition, the treatment of intestinal helminths, owing to their poor
parasite may lose its biological potential over time, which absorption following oral administration. The treatment
can then be reflected in the clinical pathology, i.e. of tissue parasites, such as the metacestodes, requires high
calcifications, and presentation with stage CE 5 of the doses to be taken with fatty meals. Patients with CE and
WHO classification. Without any treatment, spontaneous- receiving 50 mg/kg per day of mebendazole orally had
ly degenerating cysts and active cysts may coexist within serum concentrations in the range of 10–37 ng/ml, but
the same organ. The rate of spontaneous regression of only approximately 1 ng/ml in the hydatid cyst fluid.
single cysts is largely unknown, as is the number of Mebendazole is excreted in the urine as the decarboxy-
‘aborted’ infections that are controlled by the immune lated derivative [2, 4, 19]. Albendazole is given at a
system early after establishment of the metacestode. In a dosage of 10–15 mg/kg body weight per day, in two
recent placebo-controlled prospective treatment study, divided, postprandial doses. Although albendazole is also
10% of hepatic cysts in the placebo group were classified poorly absorbed from the gut, it reaches plasma concen-
as being ‘improved’ after an observation period of 6 trations 15 to 49 times higher than those of mebendazole.
months. Those cysts showed changes similar to those in It is rapidly metabolized in the liver, and the primary
patients treated with albendazole in the verum group [16]. metabolite, albendazole sulphoxide, also has anthelmin-
Thus, carriers of liver cysts may be at low risk for thic activity. Adverse effects are seen for both benzim-
developing complications, so that it is difficult to idazoles at higher doses and for prolonged periods of
establish rules for their therapy, if any. application. Abnormalities in liver function, leucopenia
and alopecia have been reported. Albendazole has been
shown to be teratogenic in rats and rabbits and, therefore,
Anthelminthic drugs for chemotherapy should be avoided, if possible, during pregnancy and
lactation [2, 4, 18, 28, 29].
Benzimidazole carbamates (albendazole or mebendazole)

The introduction, in the 1960s, of benzimidazole deriva- Pyrazinoisoquinoline derivative (praziquantel)

tives as potent, broad-spectrum anthelminthics opened up
a new era in the control of parasitic diseases in veterinary The introduction of praziquantel in the early 1980s
medicine. Many benzimidazoles were screened, and some represents another major advance in the chemotherapy of
of them have been marketed and are now of widespread parasitic infections. Praziquantel has a broad spectrum of
418

anthelminthic action that includes schistosomes, her- 29]. In their reports they provided basic data on the safety
maphroditic flukes and cestodes. It is the drug of choice and efficacy of albendazole. Clinical outcome was
for the treatment of tapeworm infections of the adult stage classified as cure, improvement, no change, or worsening,
such as Taenia solium, T. saginata, Diphyllobothrium irrespective of the number of organs with cysts. Accord-
latum, and Hymenolepis nana [18, 30]. Praziquantel is ing to the compiled data approximately 30% of the
well tolerated and considerably less toxic and is better patients were cured and 30 to 50% improved; in 20 to
absorbed than albendazole. Activity against protoscoleces 40% of the patients no change (i.e. failure) was noted,
of E. granulosus was described in 1986 [31], but in vivo although it is unclear whether, in this group, the patients’
studies on secondary echinococcosis treatment have not status remained unchanged or worsened. Unfortunately,
been as conclusive [32]. Recently, the effect of praziqu- controlled clinical trials complying with the rules of good
antel in conjunction with benzimidazoles in animal clinical practice were not conducted during that period of
experiments demonstrated a substantial effect not only time [38].
on protoscoleces, but also on the germinative monolayer At present, evidence-based medical treatment of cystic
of E. granulosus [33]. A comparative clinical study has liver echinococcosis relies on few studies. A single-
shown that patients receiving combined treatment with centre, large, prospective, observational study [39, 40]
albendazole (10 mg/kg per day) and praziquantel (25 mg/ and two controlled trials involved a low number of
kg per day) for 1 month prior to surgery more frequently patients [16, 41]. In Spain, Gil-Grande et al. [41] studied
had non-viable protoscoleces than patients given the effect of albendazole on hepatic cysts and randomized
monotherapy with albendazole [34]. It is unclear whether 55 patients into three groups: 18 patients received no
praziquantel potentiates the drug level of albendazole. albendazole treatment, 18 patients received albendazole
Thus, further studies are needed to evaluate the efficacy for 1 month and 19 patients received albendazole for 3
of the combined treatment. Praziquantel might be useful months; all of them underwent surgery after having
in cases where cyst content is spilled during surgery, and medical treatment. The treatment was monitored by
has been proposed at a dosage of 40 mg/kg body weight ultrasonography, and parasite pathology results were
once a week concomitantly with benzimidazoles [4]. assessed (viability of protoscoleces by dye exclusion test,
intraperitoneal inoculation of surgical specimens in mice,
microscopy of membrane disruption of cysts). It was
Conservative treatment and outcome concluded from the study that initial medical treatment is
a suitable alternative to surgery in uncomplicated hydatid
Medical treatment of CE using mebendazole carbamate liver disease. Ultrasonographic improvement is highly
has a history of more than 25 years [2]. The first report on associated with the loss of cyst viability, and 3 months’
the successful treatment of four patients with hydatid liver treatment with albendazole has significantly greater
cysts appeared in 1977 [22]. Subsequently, reports on the efficacy than a course of 1 month. The straightforward
experiences in different clinical situations were published approach of this study is, at present, the basis for the
from Germany and Switzerland and confirmed activity of recommendation of treatment duration [4]. The time on
the compounds against human metacestode infections [23, drug was further addressed in two recent prospective
24]. All available data from that first period were placebo-controlled studies in Iran. Keshmiri et al. [16, 42]
compiled by Schantz et al. [25], who summarized the evaluated the effect of albendazole on hydatid liver and
first 6 years of chemotherapy and provided recommen- lung cysts. Treatment was given intermittently for a total
dations for future studies. In 1983, the newer and of 6 months. Despite the small number of patients with
promising benzimidazole derivative, albendazole, became liver cysts enrolled (29 patients with a total of 240 cysts),
available for the treatment of hydatid disease [26, 27]. the ultrasonographic findings demonstrated a significant
Multi-centre open clinical trials were initiated by effect of albendazole on hydatid cysts, with a cure rate of
WHO in the 1980s [35, 36]. However, comparative approximately 10%, size reduction of the metacestode of
efficacy studies were not performed; instead, a number of 60% and improvement in morphological appearance of
cohort studies and case reports addressing different 62%. Pulmonary cysts and abdominal cysts seem to
aspects of medical treatment of echinococcosis has since respond better to medical treatment than do liver cysts,
been published [2, 37]. It is generally accepted that the and the more heterogeneous and hyperechoic the cyst, the
choice of one or the other benzimidazole is not of major less the response to medical treatment. The authors
importance, since both mebendazole and albendazole, conclude that patients with an appropriate echographic
presumably, are equally effective [4]. Case definitions, cyst stage should receive a trial of medical treatment, and
diagnostic procedures and defined monitoring procedures surgery can be recommended in cases where there is no
for the long-term follow-up were not standardized [38]. response or where there is a significant complication. As
Horton et al. reviewed the clinical experience of open- noted above, at the end of the 6-month treatment period
labelled observational studies derived from published and degenerative changes were observed in 10% of the cysts
unpublished sources on the use of albendazole in CE [28,
 419

from patients who received placebo, but the further course the most appropriate treatment can be planned. Three
was not evaluated. major stages of the cysts will guide an appropriate
A long-term evaluation of patients was performed in a decision:
uni-centric observational study in Rome, Italy. Teggi et
al. [39] and Franchi et al. [40] treated an entire cohort of 1. Early cysts with fluid content, expanding when
patients with CE with benzimidazole carbamates exclu- measurements are taken successively. Percutaneous
sively. In total, 448 patients with 929 singly identifiable puncture, aspiration, injection of scolicidal agents, and
hydatid cysts received mebendazole or albendazole for 3 re-aspiration (PAIR) or surgery in conjunction with
to 6 months, continuously, and the long-term outcome prophylactic albendazole may be considered. In se-
was assessed. Ultrasonographic degenerative changes of lected cases medical treatment alone may be an option.
the cysts were observed in 74% at the end of the Praziquantel can be used peri-interventionally for a
treatment. This degenerative process continued in ap- few days so that the seeding of protoscoleces and
proximately 22% of the cysts treated. For the remaining initiation of secondary echinococcosis can be avoided.
cysts, degenerative changes, which had been observed 2. Transitional cysts with signs of progressive consoli-
after treatment, neither progressed nor regressed [40]. dation. These cysts degenerate, and part of the
Approximately 25% of the treated cysts relapsed. Liver metacestode is dying; however, within the lesion
cysts relapse more frequently than do cysts at other sites, viable parasitic material may still be present. The size
presumably because of greater proliferative potential of of the cyst and the pressure on the adjacent tissue will
the metacestode tissue remaining in the hepatic environ- guide the appropriate treatment approach. Medical
ment. Further cycles of benzimidazole treatment of treatment with benzimidazoles may be helpful to
patients with recurrences were again well tolerated and destroy the remaining viable metacestode tissue.
effective. It was suggested that the higher metabolic 3. Late cysts, which are completely solid and partially or
activity of relapsed cysts makes them more susceptible to totally calcified. These cysts can be regarded as
the action of benzimidazole carbamates [40]. inactive, and further regression can be anticipated.
Thus, medical treatment is not indicated, unless the
symptoms prevail.
Interdisciplinary management
of cystic echinococcosis Of major importance in the management of cystic
echinococcosis is long-term observation and longitudinal
The recent proposal of a unified classification of CE cysts monitoring [2]. As for other disease entities, prospective
(WHO-IWGE) serves as a basis for the standardization trials are definitely needed, and if data are available, an
and testing of stage-specific treatment options in prospec- evidence-based algorithm will guide the most appropriate
tive studies. Thus, each patient should be evaluated by an stage-specific management of cystic echinococcosis.
interdisciplinary team of physicians and surgeons so that

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