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Journal ArticleDOI

Sero-epidemiological survey for alveolar echinococcosis (by Em2-ELISA) of blood donors in an endemic area of Switzerland

01 Nov 1987-Transactions of The Royal Society of Tropical Medicine and Hygiene (Oxford University Press)-Vol. 81, Iss: 6, pp 960-964

TL;DR: Sera from 17,166 blood donors living in 10 cantons of northern Switzerland in an area endemic for Echinococcus multilocularis were investigated by serological survey for alveolar echinococcosis, finding 2 asymptomatic clinical cases of AE within this population of blood donors.
Abstract: Sera from 17 166 blood donors living in 10 cantons of northern Switzerland in an area endemic for Echinococcus multilocularis were investigated by serological survey for alveolar echinococcosis (AE). A highly species-specific antigen (Em2) and a commonly used E. granulosus hydatid fluid antigen (EgHF) were compared for their suitability in seroepidemiology. EgHF showed a degree of nonspecificity which did not allow direct detection of AE cases. Antibody reaction with Em2 resulted in the detection of 2 asymptomatic clinical cases of AE (seroprevalence 0·01%) within this population of blood donors. A further 4 persons were positive in Em2-ELISA. These 4 persons had negative imaging studies and will be followed serologically and clinically.
Topics: Echinococcus multilocularis (56%), Seroprevalence (53%), Population (52%)

Summary (1 min read)

Introduction

  • DOI: https://doi.org/10.1016/0035-9203(87)90365-8.
  • Posted at the Zurich Open Repository and Archive, University of Zurich ZORA URL: https://doi.org/10.5167/uzh-153786.
  • Sero-epidemiological survey for alveolar echinococcosis (by Em2-ELISA) of blood donors in an endemic area of Switzerland.
  • Transactions of the Royal Society of Tropical Medicine and Hygiene, 81(6):960-964.
  • DOI: https://doi.org/10.1016/0035-9203(87)90365-8 960.

TRANSACTIONS OF TNE ROYAL SOCIETY OF TIIOPICAI. MEDICINE AND HYGIENE (1987) 81, 960.964

  • Sero-epidemiological survey for alveolar echinococcosis (by Em2-ELISA) of blood donors in an endemic area of Switzerland.

BRUNO GOTTSTEIN~, CHRISTIAN LENGELER', PIERRE BACHMANN~, PETER HAGEMANN~, PIERRE KOCHER~, MICHEL BROSSARD’, FELIX WITASSEK' AND JOHANNES ECKERT’

  • A highly species-specific antigen (Em2) and a commonly used E. granulosus hydatid fluid antigen (EgHF) were compared for their suitability in seroepidemiology.
  • Between 1956 and 1969 an annual average of 8.7 new cases of AE was diagnosed, amounting to 122 cases (DROLSHAMMER et al., 1973).
  • Further sera were obtained from 5166 healthy blood donors originating from 2 other cantons (Jura including Jura bernois, Neuchatel) of the endemic area (Fig. 1).
  • 4 persons had negative imaging studies and will be followed closely with periodic serology and US/CT studies.
  • Antibody concentrations in Em2-ELISA were 14%, 16%, 35% and 21%, respectively.

962 SEROEPIDEMIOLOGY OF ALVEOLAR ECHINOCOCCOSIS

  • @ Villages screened by mobile Bquipes for blood donation performances.
  • The use of Em2 for immunodiagnosis of AE has been assessed in a pilot study in Alaska (GOTTSTEIN et uE., 1985; SCHANTZ & GOTTSTEIN, 1986), which showed that lesions were detectable by Em2 which were not indicated by EgHF.
  • One patient (G.A.), although asymptomatic, unfortunately had already reached an advanced stage of the disease and was considered to be inoperable.
  • Such positive antibody responses in asymptomatic persons without liver lesions may be due to early or abortive E. multilocularis infections, or possibly to challenge with eggs which did not develop into metacestodes.
  • The total number of inhabitants of the age allowing.

964 SEROEPIDEMIOLOGY OF ALVEOLAR ECHINOCOCCOSIS

  • Blood donation in the whole area of the present survey was estimated to be about 1 million.
  • Serological screening with Em2-ELISA will detect all persons infected with E. muZtiZocuZaris, especially early asymptomatic AE cases, which, if not detected by serology in a preclinical stage, may develop into symptomatic clinical cases of AE.
  • Zeitschrift fiir Parasitenkunde, 69, 347-356.
  • An international study on the serological differential diagnosis of human and alveolar echinococcosis.
  • Sckweizeriscke Mediainiscke Wockenschrift, 116, 1088-1093.

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Year:1987
Sero-epidemiologicalsurveyforalveolarechinococcosis(byEm2-ELISA)of
blooddonorsinanendemicareaofSwitzerland
Gottstein,Bruno;Lengeler,Christian;Bachmann,Pierre;Hagemann,Peter;Kocher,Pierre;
Brossard,Michel;Witassek,Felix;Eckert,Johannes
Abstract:Serafrom17166blooddonorslivingin10cantonsofnorthernSwitzerlandinanareaendemic
forEchinococcusmultiloculariswereinvestigatedbyserologicalsurveyforalveolarechinococcosis(AE).
Ahighlyspecies-specicantigen(Em2)andacommonlyusedE.granulosushydatiduidantigen(EgHF)
werecomparedfortheirsuitabilityinseroepidemiology.EgHFshowedadegreeofnonspecicitywhich
didnotallowdirectdetectionofAEcases.AntibodyreactionwithEm2resultedinthedetectionof2
asymptomaticclinicalcasesofAE(seroprevalence0·01%)withinthispopulationofblooddonors.A
further4personswerepositiveinEm2-ELISA.These4personshadnegativeimagingstudiesandwillbe
followedserologicallyandclinically
DOI:https://doi.org/10.1016/0035-9203(87)90365-8
PostedattheZurichOpenRepositoryandArchive,UniversityofZurich
ZORAURL:https://doi.org/10.5167/uzh-153786
JournalArticle
PublishedVersion
Originallypublishedat:
Gottstein,Bruno;Lengeler,Christian;Bachmann,Pierre;Hagemann,Peter;Kocher,Pierre;Brossard,
Michel;Witassek,Felix;Eckert,Johannes(1987).Sero-epidemiologicalsurveyforalveolarechinococcosis
(byEm2-ELISA)ofblooddonorsinanendemicareaofSwitzerland. TransactionsoftheRoyalSociety
ofTropicalMedicineandHygiene,81(6):960-964.
DOI:https://doi.org/10.1016/0035-9203(87)90365-8

960
TRANSACTIONS OF TNE ROYAL SOCIETY OF TIIOPICAI. MEDICINE AND HYGIENE (1987)
81, 960.964
Sero-epidemiological survey for alveolar echinococcosis
(by Em2-ELISA) of blood donors in an endemic
area of Switzerland
BRUNO
GOTTSTEIN~, CHRISTIAN LENGELER',
PIERRE
BACHMANN~,
PETER HAGEMANN~, PIERRE KOCHER~,
MICHEL BROSSARD’, FELIX WITASSEK' AND JOHANNES
ECKERT’
‘Institute of Parasitology, University of Zurich, CH-8057 Zurich, Switzerland; ‘Institute of Zoology, University
of Neuchcitel, CH-2000 Neuchdtel, Switzerland; 3Central Laboratory, Blood Transfusion Service, Swiss Red
Cross, CH-3000 Bern, Switzerland; 4Central Laboratory, Kantonsspital, CH-8596 Miinsterlingen, Switzerland;
‘Blood Transfusion Centre of La-Chaux-de-For&, CH-2300 La Chaux-de-Fonds, Switzerland
Abstract
Sera from 17 166 blood donors living in 10 cantons of northern Switzerland in an area endemic for
Echinococcus multilocularis were investigated by serological survey for alveolar echinococcosis (AE). A
highly species-specific antigen (Em2) and a commonly used E. granulosus hydatid fluid antigen
(EgHF) were compared for their suitability in seroepidemiology. EgHF showed a degree of
nonspecificity which did not allow direct detection of AE cases. Antibody reaction with Em2 resulted
in the detection of 2 asymptomatic clinical cases of AE (seroprevalence 0.01%) within this population
of blood donors. A further 4 persons were positive in Em2-ELISA. These 4 persons had negative
imaging studies and will be followed serologically and clinically.
Introduction
Alveolar echinococcosis (AE) is a zoonotic disease
caused by the larval stage (metacestode) of Echinococ-
cus multilocularis. There is evidence that the infection
is acquired many years before clinical manifestation of
the disease. At the time when symptoms occur,
pathological lesions in the liver, and sometimes other
organs, have progressed so far that 42 to 74% of the
patients are inoperable
(SCHANTZ
et al., 1982;
SCHANTZ & GOTTSTEIN, 1986). In these cases, and
also after partial resection of liver lesions, the
prognosis is unfavourable. In patients not submitted
to specific chemotherapy lethality is very high,
reaching 94% within 10 years after diagnosis of the
disease (SCHICKER, 1976).
In Switzerland echinococcosis is well known as a
public health hazard. Between 1956 and 1969 an
annual average of 8.7 new cases of AE was diagnosed,
amounting to 122 cases (DROLSHAMMER et al., 1973).
The annual morbidity rate per 100 000 inhabitants
was 0.14. Most cases were of Swiss nationality and in
the aee arouo between 51 and 60 years. The highest
number-of cases was found in the northern pacts of
the countrv. Recentlv. for the neriod 1970 to 1983, an
annual average
of 16kew case’s of
AE,
with a total
of
145 cases, has been registered (Gloor, unpublished
observations).
In Switzerland the epidemiological situation is
comnlicated bv the fact that E. multiloculuris and E.
grunulosus occur sympatrically (ECKERT, 1970;
DROL-
SHAMMER et al., 1973).
The aim of the resent survey was to determine
the prevalence an
B
geographical distribution of AE
in a population of blood donors and to attempt
early diagnosis of the infection. Early diagnosis and
treatment may reduce mortality of the disease. The
epidemiological situation of low prevalence re-
quired a serological test system of high diagnostic
sensitivity and species-specificity for the detection
of infections with E. multilocularis.
The purification of a species-specific antigenic
polypeptide (Em2) from E. multilocularis
metacestodes b affinity chromatography and its
subsequent eva uation by enzyme-linked immuno-
P
sorbent assay (ELISA) demonstrated a high di-
agnostic sensitivity (93.6%) and specificity with
regard to cross-reactions due to nematode and
trematode infections (100%) and to cestode infec-
tions (95%)
(GOTTSTEIN
et al., 1983; 1986a; Gore-
STEIN,
1985).
This paper summarizes the results of 2
seroepidemiological studies on AE in northern
Switzerland carried out by 2 institutions, particularly
regarding the relative potential of EM2 and EgHF as
immunodiagnostic tools for sero-epidemiology of AE.
Materials and Methods
Sera from 12 000 healthy blood donors were obtained
between September 1984 and March 1985 from 9 cantons of
northern Switzerland (Aargau, 1495; Appenzell, 109; Basel,
2370; Bern, 279; Schaffhausen, 1158; Solothurn, 197; St
Gallen, 369; Thurgau, 4932; Zurich, 1091) which are
endemic areas of AE
(DROLSHAMMER
et
al., 1973) (Fig. 1).
The sera were collected by mobile teams of the Central
Laboratory of the Blood Transfusion Service (Swiss Red
Cross) and by local blood donation centres at Frauenfeld and
Munsterlingen. These sera were selected for direct testing
with Em2 by ELISA. Further sera were obtained from 5166
healthy blood donors originating from 2 other cantons (Jura
including Jura bernois, Neuchatel) of the endemic area (Fig.
1). These sera were collected by the regional blood
transfusion centre of La Chaux-de-Fonds and were pretested
with EgHF for comparative purposes. All sera were stored at
-80°C till required. The following information was obtained
concerning 9000 blood donors: 65% males and 35% females
aged between 20 and 75 years (mean age for both sexes, 40
years); 90% of all blood donors included in this study lived in
rural or semirural areas.

B. GOTT~TEIN et al.
961
The ELISA using Em2 was performed as described by
GOTTSTEIN (1985), using the criteria for interpretation of
seropositivity reported earlier (GOTTSTEIN et al., 1984).
Briefly, the results are expressed as percentages of the
maximum absorbence at 404nm of a positive reference serum
minus mean value (2) plus 3 standard deviations (SD) of sera
from healthy blood donors living in an area not endemic for
E. multiloculuris
(canton of Ticino). The ELISA using EgHF
(fertile hydatid fluid of bovine origin) was carried out
according to VOLLER et al. (1981) and positive sera were
tested in a second step with Em2 for specificity confirmation.
In both tests a result was considered “positive” (specific
antibodies detectable) if its corresponding absorbance value
was higher than % + 3 SD determined as described above.
In order to exclude any error during sampling and proces-
sing of the sera, a second blood sample was collected from all
blood donors demonstrating antibody activity to Em2.
The overall sensitivity (93.6%) and specificity (100%) of
the ELISA for Em2 has been reported earlier (GOTTSTEIN,
1985). For EgHF-ELISA, the sensitivity was 91% (GOTT-
STEIN et
al.,
1986b), and the specificity with regard to an
adult healthy Swiss population was 93.6% (ST~~RCHLER et
al., 1986). The predictive values of positive and negative
results were calculated for a hypothetical population of
10 000 with 0.01% infected persons, which corresponds
approximately to the clinical prevalence in the canton of
Thurgau (JAEGER et al., 1979), as follows.
Alveolar echinococcosis
present absent
Test result
+ a
Test result -
f;
where a = expected number of &es x sensitivity/lOO,
b =
expected number of healthy blood donors x (100 -
specificity)/lOO, c = expected number of AE cases x (100 -
sensitivity)/lOO, and d = expected number of healthy blood
donors X specificityi100. Then,, positive predictive
value = al(a +
b);
negative predictive value = d/(c + d).
Patients with a positive result in EmZ-ELISA were further
investigated by ultrasound (US) and/or computer assisted
tomography (CT) of the intra-abdominal and retroperitoneal
organs. Both methods are very sensitive in diagnosing liver
echinococcosis (HAERTEL et al., 1980; Orro et al., 1982).
US, however, is slightly inferior to CT when imaging lesions
of small size in the liver (OTTO et al., 1982).
Predictive values
Results
The predictive value of positive results in Em2-
ELISA was calculated to be >99%, based on specific-
ity, sensitivity and prevalence data listed above. For
EgHF-ELISA, the positive predictive value was only
0.14%. The predictive value of a negative result was
>99%
for both Em2-ELISA and EgHF-ELISA.
Sewepidemiology
The results of the present survey with sera directly
tested in Em2-ELISA are shown in Table 1. Sera
from 5 blood donors had antibodies reacting with
Em2. All these persons were submitted to imaging
studies with either US or CT, or both.
In 1 patient lesions were detected by imaging
studies (see case histories).
4
persons had negative
imaging studies and will be followed closely with
periodic serology and US/CT studies. None of these
4
persons’ serum showed arc-5 precipitation in im-
munoelectrophoresis. Antibody concentrations in
Em2-ELISA were 14%, 16%, 35% and 21%, respec-
tively. In contrast, antibodies were not detected by
ELISA using EgHF.
The results of sera pretested by EgHF-ELISA with
subsequent re-examination of the positive reactions
by Em2-ELISA are shown in Table 2. Serum
Table l-Prevalence of antibodies to species-specific polypeptide (Em2) antigen by ELISA in Swiss adult blood donors
(sampled between September 1984 and March 1985)
FoYP
:I
III
Serological result’
Positive
Positive
Negative
Clinical finding
AE confirmed clinically
No liver lesion detected by US/CT
No investigation made
Blood donors
No. %
1
0.01
0.03
1199: 99.96
Total
‘Positive: antibodies detected with EmZ-antigen.
12 000 100~00
Negative: no antibodies detected with EmZ-antigen.
Abbreviations. AE: alveolar echinococcosis, US: ultrasound examination, CT: computer assisted tomography.
Table 2-Prevalence of antibodies to
E.
grunulosus hydatid fluid (EgHF) antigen by ELISA in Swiss adult blood donors
(sampled between October 1984 and May 1985)
Group
No. Serological result’
Clinical finding
I
Positive (EgHF-antigen), No liver lesion detected by US/CT
negative (EmZ-antigen)
II
Positive (EgHF-antigen),
positive (EmZ-antigen)
AE confirmed clinically by US/CT
III
Negative (EgHF-antigen)
No investigation made
Total
‘Positive: antibodies detected with EgHF or Em2 antigen.
Negative: no antibodies detected with EgHF or Em2 antigen.
Abbreviations: see Table 1.
Blood donors
No. %
16 0.31
1
0.02
5149
99.67
5166
100~00

962
SEROEPIDEMIOLOGY OF ALVEOLAR ECHINOCOCCOSIS
Frauenfeld
La
Mtinsterlingen
#Home of AE patient W.C. + Home of AE patient G.A. 0 Homes of 4 persons positive in Em2-ELISA;
no liver lesion (US/CT), no sign of AE. @ Villages screened by mobile Bquipes for blood donation
performances. @b Regional blood donation centres.
Fig. 1. Map showing
blood
sampling areas and homes of EmZ-positive blood donors
and
patients with alveolar echinococcosis
detected
serologically.
antibodies from 17 persons reacted in EgHF-ELISA,
but only one serum was confirmed for specificity by
Em2-ELISA. This EmZ-positive serum was from a
22-year-old man (W.C.) with positive imaging studies
(see case histories). All 16 persons “positive” by
EgHF-ELISA but “negative” by Em2-ELBA
showed no clinical sign of the presence of AE and will
not be followed in this study. Fig. 1 shows the
geographical location of all villages and areas screened
in the present study, location of detected AE patients
and healthy persons with antibodies to Em2 but
negative imaging studies. Overall, the investigation of
17 166 blood donors’ sera resulted in 2 patients
positive by Em2-ELISA with clinically confirmed
AE, a seroprevalence of clinically confirmed AE of
0.01%. Furthermore, 4 persons were detected with
antibody to Em2 but without clinical evidence of AE
at the time of investigation, giving a total seropreva-
lence of 0.03%.
Case histories
Patient G.A.
(Table 1). A 41-year-old woman of
Austrian origin, but living in Switzerland for 19 years.
The ELISA revealed an antibody concentration of
69% using Em2 and 77% using EgHF. Furthermore,
arc-S was precipitated in immunoelectrophoresis. US
and CT imaging demonstrated a lesion involving both
lobes of the liver with a maximum diameter of about
10 cm, compatible with AE (Fig. 2). A second lesion
was found in the head of the pancreas. Due to the
localization and extent of the lesions the patient was
considered to be primarily inoperable and continuous
;Erbeitherapy with mebendazole (2.5 g/d) was
Patient
W.C. (Table 2). A 22-year-old Swiss man.
Antibody concentrations of 61% and 51% were
obtained by Em2-ELISA and EgHF-ELISA respec-
tively. No arc-5 was detectable by immunoelec-
trophoresis. US showed a lesion in the right lobe of
the liver with a maximum size of
6~ 7
cm (Fig. 3). In
this patient a complete resection of the parasite lesion
was performed by right side hemihepatectomy.
Pathological examination confirmed AE.
4 further persons, 3 men and a woman of Swiss
nationality aged between 20 and 43 years, showed
anti-Em2 antibody concentrations between 14% and
35%. Detection of arc-5 in immunoelectrophoresis
failed, one serum precipitating an arc which was not
arc-S. US, CT, or both, did not demonstrate liver
lesions. In order to ascertain whether the anti-Em2
antibodies are related to early AE, these persons will
be examined every 6 months by serology and every
year by US.
Discussion
Experience with AE in Switzerland points to a
fundamental need for a reliable method permitting an
early diagnosis during the preclinical stage. If an
organ lesion could be identified in an initial, small
stage and before infiltrating bile ducts or major
vessels, or before the formation of distant metastases,
the surgical resectability rates and the prognosis of the
disease should considerably improve.
The use of Em2 for immunodiagnosis of AE has
been assessed in a pilot study in Alaska
(GOTTSTEIN et
uE.,
1985;
SCHANTZ & GOTTSTEIN, 1986),
which
showed that lesions were detectable by Em2 which
were not indicated by EgHF. This Alaskan study was
designed for an area in which
E. multilocularis
is

B. G~T-I~TEIN
et al.
963
Fig. 2. (a) Ultrasound (US) and (b) computer-assisted tomography
(CT) findings in patient G.A. CT imaging clearly demonstrates the
irregular lesion in both lobes of the liver with a maximum diameter of
10 cm. In US the contour of the margin of the lesion appears mote
sharply. In the section shown the diameters of the lesion (marked
by + signs) were 6.6 cm and 7.9 cm, respectively.
hyperendemic. Based on these results, and on the
predictive values of Em2-ELISA, we designed the
present study for an area of moderate endemicity.
Despite the relatively low number of blood donors
included in this study, the survey resulted in the
detection of 2 asymptomatic, clinically confirmed
cases of AE. One patient (G.A.), although asymp-
tomatic, unfortunately had already reached an adv-
anced stage of the disease and was considered to be
inoperable. In the second patient (W.C.), however,
the parasite lesion was small and completely resect-
able.
4 persons had positive Em2-serology but showed
negative imaging studies (US and/or CT). Interesting-
ly, 3 of these 4 persons lived in the canton of
Thurgau, which has a slightly higher prevalence of
human cases than the other cantons investigated
(J~GER et
al.,
1979). Due to the high specificity of
Fig. 3. Ultrasound imaging in patient W.C. showed a lesion caused
by E. nulrilocularis in the right lobe of the liver. The extent of the
lesion (+) was 4.8 cm. In this patient radical surgery was performed.
Em2, false positive reactions due to heterologous
infections can be excluded with a high degree of
probability. Such positive antibody responses in
asymptomatic persons without liver lesions may be
due to early or abortive
E. multilocularis
infections, or
possibly to challenge with eggs which did not develop
into metacestodes. The lesions caused by the parasite
could also be located in tissues not examined by
routine imaging studies. This, however, is not very
likely because primary lesions of AE are located in the
liver in 98% to 100% of cases
(DROLSHAMMER
et al.,
1973). Studies in Alaska have already shown that
Em2-ELISA detected asymptomatic cases not de-
tected by other serological techniques (especially
using antigens derived from
E. granulosus),
in which
the larval cestode was of very small size and had died
out at an apparently early stage of infection
(BAUSCH
et al.,
1987). This was assessed through immunohis-
tochemical tests and by inoculation of parasite mate-
rial isolated from patients into susceptible rodents.
The spontaneous death of larval
E. multilocularis,
which is known to occur in animals with high natural
resistance against this parasite, like cattle and sheep
(LUKASHENKO,
1971), was also postulated for hu-
mans but has never yet been demonstrated. Such
spontaneous rejection of the infection may also have
occurred in the Swiss patients. These persons will be
followed carefully by clinical and serological means;
long-term studies on them will provide more informa-
tion about the possibilities listed above which may be
responsible for EmZ-seroconversion.
The comparison of the use of Em2 and EgHF in
ELISA for seroepidemiology clearly shows that, for
assessing an endemic area with a relative low preva-
lence of AE, there is an absolute need for a highly
specific antigen like Em2. The use of a non-specific
antigen like EgHF alone is of little value.
The detection of 2 cases of AE among 17 166 blood
donors implies a prevalence rate of 11.6 per 100 000.
The total number of inhabitants of the age allowing

Citations
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Journal ArticleDOI
Johannes Eckert1, Peter Deplazes1Institutions (1)
TL;DR: Various aspects of human echinococcosis are discussed in this review, including data on the infectivity of genetic variants of E. granulosus to humans, the increasing invasion of cities in Europe and Japan by red foxes, the main definitive hosts ofE.
Abstract: Echinococcosis in humans is a zoonotic infection caused by larval stages (metacestodes) of cestode species of the genus Echinococcus. Cystic echinococcosis (CE) is caused by Echinococcus granulosus, alveolar echinococcosis (AE) is caused by E. multilocularis, and polycystic forms are caused by either E. vogeli or E. oligarthrus. In untreated cases, AE has a high mortality rate. Although control is essentially feasible, CE remains a considerable health problem in many regions of the northern and southern hemispheres. AE is restricted to the northern hemisphere regions of North America and Eurasia. Recent studies have shown that E. multilocularis, the causative agent of AE, is more widely distributed than previously thought. There are also some hints of an increasing significance of polycystic forms of the disease, which are restricted to Central and South America. Various aspects of human echinococcosis are discussed in this review, including data on the infectivity of genetic variants of E. granulosus to humans, the increasing invasion of cities in Europe and Japan by red foxes, the main definitive hosts of E. multilocularis, and the first demonstration of urban cycles of the parasite. Examples of emergence or reemergence of CE are presented, and the question of potential spreading of E. multilocularis is critically assessed. Furthermore, information is presented on new and improved tools for diagnosing the infection in final hosts (dogs, foxes, and cats) by coproantigen or DNA detection and the application of molecular techniques to epidemiological studies. In the clinical field, the available methods for diagnosing human CE and AE are described and the treatment options are summarized. The development of new chemotherapeutic options for all forms of human echinococcosis remains an urgent requirement. A new option for the control of E. granulosus in the intermediate host population (mainly sheep and cattle) is vaccination. Attempts are made to reduce the prevalence of E. multilocualaris in fox populations by regular baiting with an anthelmintic (praziquantel). Recent data have shown that this control option may be used in restricted areas, for example in cities, with the aim of reducing the infection risk for humans.

1,417 citations


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  • ...Older data from Austria, Germany, France, and Switzerland have indicated that persons working in agriculture were at increased risk of infection (57, 110)....

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  • ...Biological, Epidemiological, and Clinical Aspects of Echinococcosis, a Zoonosis of Increasing Concern Johannes Eckert* and Peter Deplazes Institute of Parasitology, University of Zurich, CH-8057 Zurich, Switzerland INTRODUCTION .......................................................................................................................................................108 E. GRANULOSUS AND CYSTIC ECHINOCOCCOSIS........................................................................................108 The Parasite and Its Life Cycle ............................................................................................................................108 Cystic Echinococcosis in Humans ........................................................................................................................109 Course of infection..............................................................................................................................................109 Diagnosis..............................................................................................................................................................111 Treatment.............................................................................................................................................................112 (i) Surgery........................................................................................................................................................112 (ii) Puncture-aspiration-injection-reaspiration ..........................................................................................112 (iii) Percutaneous thermal ablation.............................................................................................................113 (iv) Chemotherapy ..........................................................................................................................................113 E. granulosus Infection in Animals .......................................................................................................................114 Defintive hosts .....................................................................................................................................................114 Intermediate hosts ..............................................................................................................................................114 Epidemiology ...........................................................................................................................................................114 Life cycle patterns...............................................................................................................................................114 Transmission dynamics......................................................................................................................................115 Infection risk for humans..................................................................................................................................115 Global distribution of E. granulosus and CE in humans ..............................................................................116 Factors associated with persistence, emergence, or reemergence................................................................117 Examples of emergence or reemergence ..........................................................................................................117 Control Options and Prevention ..........................................................................................................................117 E. MULTILOCULARIS AND ALVEOLAR ECHINOCOCCOSIS ........................................................................118 The Parasite and Its Life Cycle ............................................................................................................................118 Alveolar Echinococcosis in Humans ....................................................................................................................118 Course of infection..............................................................................................................................................118 Diagnosis..............................................................................................................................................................119 Treatment.............................................................................................................................................................120 (i) Surgery........................................................................................................................................................120 (ii) Chemotherapy...........................................................................................................................................120 E. multilocularis Infection in Animals ..................................................................................................................121 Defintive hosts .....................................................................................................................................................121 Intermediate and aberrant hosts......................................................................................................................121 Epidemiology ...........................................................................................................................................................121 Parasite-host assemblages .................................................................................................................................121 (i) Arctic region...............................................................................................................................................122 (ii) Sub-Arctic regions....................................................................................................................................122 Influences of landscape characters and rodent populations ........................................................................123 (i) Factors related to larger regions ............................................................................................................123 (ii) Factors related to macro- and microfoci ..............................................................................................123 Eggs in the environment ....................................................................................................................................123 Infection risk for humans..................................................................................................................................124 Global distribution in humans .........................................................................................................................124 Emergence and spread of E. multilocularis?....................................................................................................124 (i) Risk areas and spreading.........................................................................................................................124 (ii) AE in humans as a risk indicator .........................................................................................................125 (iii) Increasing fox populations and parasite prevalences........................................................................125 (iv) Invasion of urban areas by foxes ..........................................................................................................126 (v) Potential modes of spreading..................................................................................................................126 Control Options and Prevention ..........................................................................................................................126 Control in definitive hosts .................................................................................................................................126 * Corresponding author....

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  • ...For example, prevalences up to 21 and 39% have been recorded in two studies of water voles (Arvicola terrestris) in high-endemicity foci in Switzerland (89, 188) and prevalances of 12 to 14% have been recorded in Microtus arvalis in a focus in France (79)....

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  • ...In Zurich, Switzerland, high contamination with fox feces was found in the recreational area, and it was observed that foxes deposit their feces directly on ground systems of A. terrestris (38)....

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  • ...By the end of the 1980s, areas of endemic infection with E. multilocularis were known to exist in only four countries (Austria, France, Germany, and Switzerland), but by the end of 2001 the parasite was known to occur in red foxes in at least nine further central European countries (Belgium, Czech Republic, Denmark, Italy, Liechtenstein, Luxembourg, Poland, Slovak Republic, and The Netherlands) (references 51, 58, and 173 and references therein)....

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Book ChapterDOI
Philip S. Craig1, M.T. Rogan1, J C Allan1Institutions (1)
TL;DR: The chapter addresses the problem of neurocysticercosis and epilepsy in developing countries particularly Latin America and its public health consequences in the USA and elsewhere.
Abstract: Publisher Summary This chapter focuses on the public health importance of taeniid cestode zoonoses especially cystic echinococcosis, alveolar echinococcosis and T. solium cysticercosis. The chapter addresses the problem of neurocysticercosis and epilepsy in developing countries particularly Latin America and its public health consequences in the USA and elsewhere. E. multilocularis , which is the cause of one of the most pathogenic of all human parasitic infections, appears to be spreading in parts of western Europe, USA, and Japan. The remarkable development in the past 20 years or so of high resolution imaging technologies, such as computerized tomography (CT) scan and ultrasound have enabled precision detection of taeniid larval cystic infection in humans. Coupled with improvements in immunodiagnostic test sensitivity and antigen specificity, diagnosis of cestode zoonoses is now more accurate than ever before. Although further developments in immunodiagnosis are required, laboratory tests have provided improved capability for screening populations in both epidemiological and community studies. Parallel and recent development of genus specific coproantigen tests for human taeniasis and canine echinococcosis have also provided major new tools for epidemiological and surveillance programs.

211 citations


Journal ArticleDOI
01 Oct 2003-Parasitology
TL;DR: Improved diagnostic technology, as well as a real increase in the infection rate and an extension to new areas, can explain that more than 500 cases of alveolar echinococcosis have been reported for these 2 decades while less than 900 cases were published for the previous 7 decades.
Abstract: Human alveolar echinococcosis (AE), caused by the metacestode of the fox tapeworm Echinococcus multilocularis, is the most pathogenic zoonosis in temperate and arctic regions of the northern hemisphere. Prospective collection of human cases in some areas and mass screenings using ultrasound imaging and confirmation with serological techniques have markedly improved our knowledge of the epidemiology of the disease in humans during the past two decades. Transmission occurs when eggs of the tapeworm, excreted by the final hosts (usually foxes but also dogs, wolves and cats), are ingested accidentally by humans or during normal feeding by a variety of rodents and small lagomorphs. However, the species of host animals differ according to regional changes in mammalian fauna. This review mostly focuses on epidemiology of alveolar echinococcosis in those parts of the world where new and more accurate epidemiological data are now available, i.e. China and Europe, as well as on new epidemiological trends that can be suspected from recent case reports and/or from recent changes in animal epidemiology of E. multilocularis infection. The People's Republic of China (PRC) is a newly recognized focus on AE in Asia. Human AE cases were firstly recognized in Xinjiang Uygur Autonomous Region and Qinghai Provinces at the end of 1950s and infected animals were first reported from Ningxia in central China and northeast of Inner Mongolia in the 1980s. E. multilocularis (and human cases of AE) appears to occur in three areas: (1) Northeastern China (northeast focus): including Inner Mongolia Autonomous region and Heliongjiang Province (2) Central China (central focus): including Gansu Province, Ningxia Hui Autonomous Region, Sichuan Province, Qinghai Province and Tibet Autonomous Region and (3) Northwestern China: including Xinjiang Uygur Autonomous Region, bordered with Mongolia, Russia, Kazakhstan and Kyrgyzstan. The highest prevalence of the disease, up to 15 per cent of the population in some villages, is reached in China. In Europe, data from the European Echinococcosis Registry (EurEchinoReg: 1982-2000) show 53 autochthonous cases of AE in Austria, 3 in Belgium, 235 in France, 126 in Germany, 1 in Greece, and 112 in Switzerland, and 15 'imported' cases, especially from central Asia; 14 cases were collected in Poland, a country not previously considered endemic for AE. Improved diagnostic technology, as well as a real increase in the infection rate and an extension to new areas, can explain that more than 500 cases have been reported for these 2 decades while less than 900 cases were published for the previous 7 decades. New epidemiological trends are related to an unprecedented increase in the fox population in Europe, to the unexpected development of urban foxes in Japan and in Europe, and to changes in the environmental situation in many countries worldwide due to climatic or anthropic factors which might influence the host-predator relationship in the animal reservoir and/or the behavioural characteristics of the populations in the endemic areas.

188 citations


Cites background from "Sero-epidemiological survey for alv..."

  • ...Sero-epidemiological survey for alveolar echinococcosis (by Em2-ELISA) of blood donors in an endemic area of Switzerland....

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  • ...Between 1980 and 2000, autochthonous human cases of AE have been documented and published from several European countries, namely Austria, France, Germany, Switzerland and the European part of Turkey (see Bresson-Hadni et al. 1988, 1997, 2000; Stössel, 1989; Vuitton et al. 1990; Schantz et al. 1995; Ammann&Eckert, 1995; Eckert, 1997; Eckert & Deplazes, 1999; Eckert et al. 2001)....

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  • ...Mass screenings performed at the middle of the 1980s in the endemic areas of Franche-Comté (east of France at the border with Switzerland), which disclosed several cases within 5 years and more generally raised the awareness of the disease in this region, might explain the observed increase in the number of cases in France....

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  • ...A concomitant increase in fox populations has been observed in several countries of Europe since the beginning of the 1990s: regionally in Spain, Bulgaria, Sweden, France, Germany, Switzerland, Belgium and Czech Republic (Artois, 1997; Chautan, Pontier & Artois, 2000), a combination of rabies vaccination and modification in human-fox interactions (fox control, habitat changes) may account for higher survival and fertility (Chautan et al. 2000)....

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  • ...In fact, taking the population size in the two counties into account, the prevalence rate may be estimated to be 200 per 100000 inhabitants in comparison to 65 per 100 000 in St Lawrence (Alaska), 10 per 100 000 in Franche-Comté (eastern France) or in northern Switzerland (Schantz et al. 1995; Bresson-Hadni et al. 1997; Eckert, 1997)....

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Journal ArticleDOI
02 Nov 2000-Acta Tropica
TL;DR: Long-term transmission of Echinococcus multilocularis and risk of zoonotic infection of south Gansu farmers may be related ultimately to a process of deforestation driven by agriculture and subsequent development of a peri-domestic cycle involving dogs.
Abstract: Human alveolar echinococcosis (AE) is usually a rare, highly pathogenic zoonotic disease, transmitted across the northern hemisphere between fox and rodent hosts. In China the first cases were described in 1965; however very few epidemiological studies have been undertaken since. Following identification in 1991 of a serious focus of human AE in south Gansu province, detailed village-based community and ecological studies were carried out between 1994 and 1997. Hepatic ultrasound mass screening with serological testing (five tests) identified 84/2482 new AE cases (3%). An overall prevalence of 4.1% (135/3331) was recorded for the area when previous cases were also included. Based on a seropositive result only, without an ultrasound scan indication, no additional AE cases were identified. Of the evolutive AE cases, 96% were seropositive in at least one test, while up 15-20% of individuals who exhibited hepatic calcified lesions and 12-15% exhibiting hepatic nodular lesions were seropositive for specific Em2 or Em18 antibodies. Village (n=31) human AE prevalence rates varied from 0 to 15.8%. Questionnaire analysis indicated that total number of dogs owned over a period was a risk factor (P 0.6). Rodent ecology studies revealed an association between density indices of voles (Microtus limnophilus) and village AE prevalence rates, on the one hand, and village landscape characterised by a ratio of scrub/grassland to total area above 50% (P<0.005). Long-term transmission of Echinococcus multilocularis and risk of zoonotic infection of south Gansu farmers may be related ultimately to a process of deforestation driven by agriculture. This in turn probably results in creation of optimal peri-domestic habitats for rodents that serve as intermediate host species (such as M. limnophilus) and subsequent development of a peri-domestic cycle involving dogs.

181 citations


Journal ArticleDOI
03 Oct 1992-The Lancet
TL;DR: The high prevalence of human AE in this region of central China is most probably due to semi-domestic transmission of E multilocularis between wild rodents and dogs, together with the poverty and poor hygiene in these rural communities.
Abstract: Human alveolar echinococcosis (AE) is a rare and highly pathogenic helminthic zoonosis due to infection with the intermediate stage of the small fox tapeworm, Echinococcus multilocularis. Parasite transmission is restricted to northern latitudes, including central and north China, from where few clinical and no detailed community studies have been reported. In August, 1991, 65 (5%) of 1312 people residing in three rural communes of Zhang County, Gansu Province, China were diagnosed as having hepatic AE after mass ultrasound scanning with serological back-up. This represents one of the highest prevalence rates of AE ever recorded. It is also the first time that mass ultrasound scanning and serology have been used together in an AE endemic region. The region was selected one year earlier, when a preliminary serosurvey on 606 unselected people in the same locality resulted in an 8.8% serum antibody positive rate with a 76% rate of confirmation of hepatic AE in 37 individuals who could be followed up in 1991. Seropositivity rates varied for villages between 0 and 20.5%. Overall, females (7.8%) had a significantly greater risk of infection than males (2.5%), especially in the 31-50 age group, a difference which may be related to contact with dogs and dog faeces over many years. Age-specific prevalence of AE increased from 0% in the under 5-year group to 8.2% in those aged 31-50. The youngest case was 11 years and the mean age of diagnosis was 40 years. Adult tapeworms of E multilocularis were identified from the small intestines of 10% of domestic dogs. Sylvatic animal hosts of the parasite have not yet been identified. The high prevalence of human AE in this region of central China is most probably due to semi-domestic transmission of E multilocularis between wild rodents and dogs, together with the poverty and poor hygiene in these rural communities.

161 citations


References
More filters

Journal ArticleDOI
TL;DR: Treatment of human patients infected with E. granulosus is followed by subjective improvement in most, and evidence of regression of cysts in some; in other patients, cysts continue to grow or have been proven viable even after several months of high-dose mebendazole therapy.
Abstract: Mebendazole, its fluorine analogue flubendazole, and other benzimidazole derivatives are active against many gastrointestinal and tissue-stage helminths. This article reviews the published literature and proceedings of a workshop on the use of benzimidazoles against larval echinococcosis (hydatid disease). Orally administered high doses (30–50 mg/kg body weight) of mebendazole given daily for 20–90 days to rodents or sheep infected with larvalEchinococcus granulosus cause damage or destruction of the cyst wall, loss of cyst fluid, and death of protoscolices. Similar treatment of rodents infected withE. multilocularis with mebendazole, flubendazole, fenbendazole, and albendazole for 60–300 days leads to reduction of weight, inhibition of growth and of metastases formation ofE. multilocularis tissue, and to prolonged host survival time although the metacestodes are not killed. Mebendazole or flubendazole treatment of human patients infected withE. granulosus is followed by subjective improvement in most, and evidence of regression of cysts in some; in other patients, cysts continue to grow or have been proven viable even after several months of high-dose mebendazole therapy. In patients infected withE. multilocularis, the progressive course of the disease appeared to be arrested, but treatment apparently did not kill the parasite. Side effects in some patients have included allergic reactions, alopecia, and reversible neutropenia. Some possible reasons for differnet responses to treatment include inadequate plasma drug absorption from the gut and age, condition, and location of cysts. Many remaining questions concerning the risk versus benefits of mebendazole therapy can be answered only through controlled clinical trials.

143 citations


Journal ArticleDOI
TL;DR: The findings show that the Em2 ELISA may be positive in patients having lesions of AHD in which the etiologic agent is no longer viable, in agreement with the clinical impression that the cestode was dead.
Abstract: Nine cases of asymptomatic alveolar hydatid disease (AHD) of the liver were diagnosed in 1985 among Eskimos from the endemic region of western Alaska. The patients were identified by screening with the enzyme-linked immunosorbent assay, using purified Echinococcus multilocularis antigen (Em2 ELISA). Five patients, and one diagnosed earlier (1979), were found to have lesions in which the larval E. multilocularis had died spontaneously at an early stage of infection. Viability was assessed histologically; by the avidinbiotin immunohistochemical method; and in vivo through intraperitoneal inoculation of membranes of the larval cestode into red-backed voles, Clethrionomys rutilus. The results were in agreement with the clinical impression, based on findings by computerized tomography and ultrasound scanning, and on the macroscopic appearance of the lesions, that the cestode was dead. Spontaneous death of E. multilocularis in humans has not been previously reported. The findings show that the Em2 ELISA may be positive in patients having lesions of AHD in which the etiologic agent is no longer viable.

139 citations


Journal ArticleDOI
Bruno Gottstein1, Johannes Eckert1, Hans Fey2Institutions (2)
TL;DR: An enzyme-linked immunosorbent assay (ELISA) was adapted for the serological differential diagnosis of cystic or alveolar echinococcosis in man caused by Echinococcus granulosus or E. multilocularis respectively.
Abstract: An enzyme-linked immunosorbent assay (ELISA) was adapted for the serological differential diagnosis of cystic or alveolar echinococcosis in man caused by Echinococcus granulosus or E. multilocularis respectively. By affinity chromatography using rabbit anti hydatid fluid IgG coupled covalently to CNBr-Sepharose 4B a protein fraction (Em 1) containing shared antigens of both parasites could be isolated from an extract of E. multilocularis metacestode tissue. From the same source another antigen fraction (Em 2) with a high degree of specificity for E. multilocularis was prepared by immunosorption. Antigen Em 1 was equally sensitive for the detection of antibodies against E. granulosus and E. multilocularis, whereas antigen fraction Em 2 appeared to be more specific for E. multilocularis. A correct serological differential diagnosis was achieved in 95% of 57 confirmed cases of human cystic or alveolar echinococcosis by the simultaneous use of both antigen fractions in the ELISA and by comparison of their reactivities.

96 citations


Journal ArticleDOI
Bruno Gottstein1Institutions (1)
TL;DR: A polypeptide (Em2a) purified by affinity chromatography from the Echinococcus multilocularis metacestode showed a high degree of purity as assayed by SDS‐PAGE and analytical isoelectrical focusing and a minor contamination with host albumin was revealed.
Abstract: A polypeptide (Em2a) purified by affinity chromatography from the Echinococcus multilocularis metacestode showed a high degree of purity as assayed by SDS-PAGE and analytical isoelectrical focusing. A minor contamination with host albumin was revealed. Estimation of relative mol. mass gave a value of 54,000. The isoelectric point was found to be 4.8. Antigenic activity of the polypeptide was demonstrated by immunoprecipitation and western blotting. In these assays the protein was recognized only by homologous sera from patients infected with larval E. multilocularis. This antigen (Em2a) did not react in the ELISA with sera from patients infected with heterologous helminths; these sera were highly cross-reacting with antigen from E. granulosus hydatid fluid. Seventy-three (94%) from 78 investigated patients (alveolar echinococcosis) showed a seropositive reaction with the polypeptide Em2a.

88 citations


"Sero-epidemiological survey for alv..." refers background or methods in this paper

  • ...B. GOTT~TEIN et al. 961 The ELISA using Em2 was performed as described by GOTTSTEIN (1985), using the criteria for interpretation of seropositivity reported earlier (GOTTSTEIN et al., 1984)....

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  • ...%) of the ELISA for Em2 has been reported earlier (GOTTSTEIN, 1985)....

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Journal ArticleDOI
11 May 1985-The Lancet

40 citations