**Molecular and Epidemiology Data on Cystic Echinococcosis in Tunisia**

Myriam Oudni-M'rad, Selim M'rad and Hamouda Babba

Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/60891

#### **Abstract**

Cystic echinococcosis (CE) or hydatidosis is a widespread zoonose in the world. In Tunisia, despite the deployed prevention program, CE remains a serious public health problem. With a human surgical annual incidence averaging 12.6/100000 inhabitants, Tunisia is one of the most endemic areas amongst the Mediterranean countries. Three Echinococcus species have been described: *E. granulosus sensu stricto* (G1 and G3 genotypes), *E. canadensis*, and *E. equinus*. CE, which commonly starts during child‐ hood and described as a young adult disease, may be observed at any age. The liver and the lungs are the most commonly involved organs but the cyst can occur almost anywhere in the body. In production animals, the prevalence of CE is ranged from 16.42% to 40.42% in sheep, 8.56% in cattle, 6% in dromedaries, 2.9% in goats, and 8.48% in donkeys. The elevated number of stray and semi-stray dogs and their frequent contamination by *E. granulosus* infected viscera is the major cause of the CE spread. A high prevalence of *E. granulosus* infection has been reported in Tunisian dogs ranging from 3.75% to 27.1%, depending on the regions. Thus, the sanitary education concerning hydatidosis should be reinforced and efforts should be made to implement a targeted educational program.

**Keywords:** Cystic echinococcosis, Tunisia, molecular characterization, epidemiolo‐ gy, public health

© 2015 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

#### **1. Introduction**

Cystic echinococcosis (CE) or hydatidosis, caused by *Echinococcus granulosus*, is a widespread zoonosis in the world, especially in North African countries such as Libya, Algeria, Morocco, and Tunisia [1, 2]. Alveolar echinococcosis (AE), caused by the larval stage of *E. multilocula‐ ris* is extremely rare in Maghreb and only three autochthonous cases of human AE were reported in Tunisia and Morocco [3–5]. CE is of veterinary and medical importance because infection with metacestode may cause severe illness and significant socio-economic repercus‐ sions. With an annual surgical incidence (SI) averaging 12.6/100000 inhabitants [6] and approximately US\$ 10–19 million losses annually in both humans and animals [7], Tunisia is one of the most endemic areas amongst the Mediterranean countries. Neighboring countries such as Italy (SI*=*1.6), Algeria (SI=3.6–4.6), Morocco (SI*=*4.6), Libya (SI*=*4.2), Spain (SI*=*0.3), and France (SI=0.1) presented lower surgical incidence [1, 8, 9]. In the *E. granulosus* vital cycle the adult tapeworm lives in the intestine of some carnivores (definitive hosts), and the larval stage develops in the herbivores (intermediate hosts) and humans, essentially in the liver and lungs.

#### **2.** *Echinococcus granulosus* **genotyping**

*E. granulosus* is a complex in which four or five cryptic species are intermixed: *E. granulosus sensu stricto* (genotypes G1 to G3), *E. equinus* (genotype G4), *E. ortleppi* (genotype G5), *E. canadensis* (genotypes G6 to G10), and *Echinococcus felidis* (lion strain) [10–12]. The characteri‐ zation of the species/genotypes responsible for human and animal hydatidosis is important in order to adapt the measures of control and prevention against this parasitic disease. Indeed, it is known that the genotype influences the life cycle patterns, the host specificity, and the pathology. Four genotypes (G1, G3, G4, and G6) have been described in Tunisia using molecular techniques such as PCR-RFLP analysis of the ribosomal DNA ITS1 fragment and mitochondrial cytochrome C oxidase (Cox1) or elongation factor 1-alpha (ef1a) gene sequenc‐ ing (Table 1). The G1 genotype was identified in humans, sheep, cattle, and dromedaries [13– 16], the G3 genotype in cattle and human isolates [17], the G6 genotype in one human case and in the Southern dromedaries [13, 16], and the G4 genotype in donkeys [16]. Recently, it has been demonstrated that donkeys can be infected by two different species, *E. granulosus s.s* (G1 genotype) and *E equinus,* occurring in sympatry [16].



**Table 1.** Molecular epidemiology of cystic echinococcosis in human and production animals in Tunisia.

**1. Introduction**

56 Current Topics in Echinococcosis

**2.** *Echinococcus granulosus* **genotyping**

genotype) and *E equinus,* occurring in sympatry [16].

**Sheep**

**Cattle**

Cystic echinococcosis (CE) or hydatidosis, caused by *Echinococcus granulosus*, is a widespread zoonosis in the world, especially in North African countries such as Libya, Algeria, Morocco, and Tunisia [1, 2]. Alveolar echinococcosis (AE), caused by the larval stage of *E. multilocula‐ ris* is extremely rare in Maghreb and only three autochthonous cases of human AE were reported in Tunisia and Morocco [3–5]. CE is of veterinary and medical importance because infection with metacestode may cause severe illness and significant socio-economic repercus‐ sions. With an annual surgical incidence (SI) averaging 12.6/100000 inhabitants [6] and approximately US\$ 10–19 million losses annually in both humans and animals [7], Tunisia is one of the most endemic areas amongst the Mediterranean countries. Neighboring countries such as Italy (SI*=*1.6), Algeria (SI=3.6–4.6), Morocco (SI*=*4.6), Libya (SI*=*4.2), Spain (SI*=*0.3), and France (SI=0.1) presented lower surgical incidence [1, 8, 9]. In the *E. granulosus* vital cycle the adult tapeworm lives in the intestine of some carnivores (definitive hosts), and the larval stage develops in the herbivores (intermediate hosts) and humans, essentially in the liver and lungs.

*E. granulosus* is a complex in which four or five cryptic species are intermixed: *E. granulosus sensu stricto* (genotypes G1 to G3), *E. equinus* (genotype G4), *E. ortleppi* (genotype G5), *E. canadensis* (genotypes G6 to G10), and *Echinococcus felidis* (lion strain) [10–12]. The characteri‐ zation of the species/genotypes responsible for human and animal hydatidosis is important in order to adapt the measures of control and prevention against this parasitic disease. Indeed, it is known that the genotype influences the life cycle patterns, the host specificity, and the pathology. Four genotypes (G1, G3, G4, and G6) have been described in Tunisia using molecular techniques such as PCR-RFLP analysis of the ribosomal DNA ITS1 fragment and mitochondrial cytochrome C oxidase (Cox1) or elongation factor 1-alpha (ef1a) gene sequenc‐ ing (Table 1). The G1 genotype was identified in humans, sheep, cattle, and dromedaries [13– 16], the G3 genotype in cattle and human isolates [17], the G6 genotype in one human case and in the Southern dromedaries [13, 16], and the G4 genotype in donkeys [16]. Recently, it has been demonstrated that donkeys can be infected by two different species, *E. granulosus s.s* (G1

**Origin No. of cysts Gene markers Genotype frequency (%) Reference**

 ITS1 and cox1 G1 (100%) [13] 12s rRNA G1 (100%) [18] Cox1 G1 (100%) [17] Cox1 and ef1a G1 (100%) [16]

79 ITS1 and cox1 G1 (100%) [13] 4 12sRNA G1 (100%) [18] The Tunisian situation is grossly the same as other Maghreb countries (Algeria and Libya) where the G1 and the G6 genotypes were reported in livestock and camels [19–22].

In Tunisia, the most frequent genotype associated with CE is the G1 genotype (*E. granulosus sensu stricto*) [13–16]. Currently, at least 43 different haplotypes were described for the Cox1 gene by molecular analysis in humans and different intermediate hosts (Genbank accession numbers: U50464, AY679144, AY679145, AY679146, KM014606-KM014644, Table 2) [13, 16]. The existence of genetic and phenotypic variants inside this genotype has been previously shown by using isoelectric-focusing techniques [23, 24]. Regarding the host origin, it has been demonstrated that there is a slight difference of the G1 genotype in parasite populations between sheep, human, and cattle (Fst values from 0.05 to 0.15) [16, 23]. The cysts originating from human (lung or liver) are intermediary between sheep and cattle origins as considering the genetic variability, whereas cattle and sheep isolates are slightly different [25].


**Table 2.** Molecular epidemiology and G1 genotype genetic diversity observed in Tunisia.

slightly different [25].

**GenBank accession** 

**numbers Mutation**

#### **3. Human disease with special focus on pediatric hydatidosis** AY679145 G312A None Human Lung [13]

**CO1 protein mutation**

The *E. granulosus* adult stage infects the Canidae that releases the parasite eggs in the envi‐ ronment through their feces. Humans are a dead-end host that do not play a role in the natural cycle of the parasite. They are contaminated by an accidental consumption of the eggs, resulting from the contact with an infected dog or through the ingestion of contaminated vegetables. Eggs result in the development of one or several unilocular hydatid cysts (Figure 1) that could grow up to 20 cm in diameter [15, 26, 27]. Because of the slow rate of cyst growth, clinical symptoms do not usually arise until several years after infection. The liver and the lungs are the most commonly involved organs but the cyst can occur almost anywhere in the body. KM014606 to KM014644 - - Camels, cattle, goat sheep, human, jackals, donkey, wild boar - [16] Table 2. Molecular epidemiology and G1 genotype genetic diversity observed in Tunisia. **3-Human disease with special focus on pediatric hydatidosis** The *E. granulosus* adult stage infects the Canidae that releases the parasite eggs in the environment through their feces. Humans are a dead-end host that do not play a role in the natural cycle of the parasite. They are contaminated by an accidental consumption of the eggs, resulting from the contact with an infected dog or through the ingestion of contaminated vegetables. Eggs result in the development of one or several unilocular hydatid cysts (Figure 1) that could grow up to 20 cm in diameter [15, 26, 27]. Because of the slow rate of cyst growth, clinical symptoms do not usually arise until several years after infection. The liver and the lungs are the most commonly involved organs but the cyst can occur almost anywhere in the body.

populations between sheep, human, and cattle (Fst values from 0.05 to 0.15) [16, 23]. The cysts originating from human (lung or liver) are intermediary between sheep and cattle origins as considering the genetic variability, whereas cattle and sheep isolates are

U50464 C56T A27V Human, Sheep , Cattle Lung and Liver [13]

AY679144 T123C None Sheep Liver [13]

AY679146 T204G None Cattle Lung [13]

**Host Cyst localisation Reference**

**Figure 1.** Hydatid cysts from Tunisian children operated at F. Bourguiba Monastir teaching hospital. A: Pulmonary cyst from an eight-year-old child. B: Hepatic cyst from a six-year-old child. Photograph: LP3M: Laboratory of Medical and Molecular Parasitology-Mycology, Faculty of Pharmacy, University of Monastir, Tunisia.

3 Figure 1. Hydatid cysts from Tunisian children operated at F. Bourguiba Monastir teaching hospital. A: Pulmonary cyst from an eight-year-old child. B: Hepatic cyst from a six-year-old child. Photograph: LP3M: Laboratory of Medical and Molecular Parasitology-Mycology, Faculty of Pharmacy, University of Monastir, Tunisia. CE remains an important public health problem in Tunisia and despite the deployed preven‐ tion program, a slight reduction in the mean annual surgical incidence rate (SI) from 15 to 12.6 cases/100,000 inhabitants was observed during the last 20 years [6, 28]. The endemic status differs from one region to another, based on the SI, and some areas have been defined as hyperendemic (SI>22.6), holoendemic (15 < SI <22.6), mesoendemic (7.5< SI <15), and hypoen‐ demic regions (SI < 7.5) [6]. The geographical repartition of different endemic regions was shown in Figure 2. Hydatidosis is known to be more important in rural areas where the definitive hosts (domestic and wild Canid) and herbivore intermediate hosts are in close contact, but an extension in the urban zones was noted during the past decade.

In Tunisia, several human studies were focusing on pediatric hydatidosis [15, 27, 29–31]. Cystic echinococcosis, which commonly starts during childhood or adolescence and described as a young adult disease, may be observed at any age. Two studies on children hydatid cysts (161 and 241 cysts) were carried out between 1999 and 2009 and assessed that the greatest number of cases was observed in the age groups of 4–9 years [15, 31]. Another retrospective study conducted between 1985 and 2009 and based exclusively on 757 pulmonary cysts of young Molecular and Epidemiology Data on Cystic Echinococcosis in Tunisia http://dx.doi.org/10.5772/60891 59

**3. Human disease with special focus on pediatric hydatidosis**

**CO1 protein mutation**

body.

**A**

slightly different [25].

**GenBank accession** 

58 Current Topics in Echinococcosis

KM014606 to

**numbers Mutation**

KM014644 - -

**3-Human disease with special focus on pediatric hydatidosis**

Table 2. Molecular epidemiology and G1 genotype genetic diversity observed in Tunisia.

most commonly involved organs but the cyst can occur almost anywhere in the body.

Parasitology-Mycology, Faculty of Pharmacy, University of Monastir, Tunisia.

The *E. granulosus* adult stage infects the Canidae that releases the parasite eggs in the envi‐ ronment through their feces. Humans are a dead-end host that do not play a role in the natural cycle of the parasite. They are contaminated by an accidental consumption of the eggs, resulting from the contact with an infected dog or through the ingestion of contaminated vegetables. Eggs result in the development of one or several unilocular hydatid cysts (Figure 1) that could grow up to 20 cm in diameter [15, 26, 27]. Because of the slow rate of cyst growth, clinical symptoms do not usually arise until several years after infection. The liver and the lungs are the most commonly involved organs but the cyst can occur almost anywhere in the

Camels, cattle, goat sheep, human, jackals, donkey, wild boar

**B**

populations between sheep, human, and cattle (Fst values from 0.05 to 0.15) [16, 23]. The cysts originating from human (lung or liver) are intermediary between sheep and cattle origins as considering the genetic variability, whereas cattle and sheep isolates are

U50464 C56T A27V Human, Sheep , Cattle Lung and Liver [13]

AY679144 T123C None Sheep Liver [13]

AY679145 G312A None Human Lung [13]

AY679146 T204G None Cattle Lung [13]

The *E. granulosus* adult stage infects the Canidae that releases the parasite eggs in the environment through their feces. Humans are a dead-end host that do not play a role in the natural cycle of the parasite. They are contaminated by an accidental consumption of the eggs, resulting from the contact with an infected dog or through the ingestion of contaminated vegetables. Eggs result in the development of one or several unilocular hydatid cysts (Figure 1) that could grow up to 20 cm in diameter [15, 26, 27]. Because of the slow rate of cyst growth, clinical symptoms do not usually arise until several years after infection. The liver and the lungs are the

Figure 1. Hydatid cysts from Tunisian children operated at F. Bourguiba Monastir teaching hospital. A: Pulmonary cyst from an eight-year-old child. B: Hepatic cyst from a six-year-old child. Photograph: LP3M: Laboratory of Medical and Molecular

CE remains an important public health problem in Tunisia and despite the deployed preven‐ tion program, a slight reduction in the mean annual surgical incidence rate (SI) from 15 to 12.6 cases/100,000 inhabitants was observed during the last 20 years [6, 28]. The endemic status differs from one region to another, based on the SI, and some areas have been defined as hyperendemic (SI>22.6), holoendemic (15 < SI <22.6), mesoendemic (7.5< SI <15), and hypoen‐ demic regions (SI < 7.5) [6]. The geographical repartition of different endemic regions was shown in Figure 2. Hydatidosis is known to be more important in rural areas where the definitive hosts (domestic and wild Canid) and herbivore intermediate hosts are in close

In Tunisia, several human studies were focusing on pediatric hydatidosis [15, 27, 29–31]. Cystic echinococcosis, which commonly starts during childhood or adolescence and described as a young adult disease, may be observed at any age. Two studies on children hydatid cysts (161 and 241 cysts) were carried out between 1999 and 2009 and assessed that the greatest number of cases was observed in the age groups of 4–9 years [15, 31]. Another retrospective study conducted between 1985 and 2009 and based exclusively on 757 pulmonary cysts of young

and Molecular Parasitology-Mycology, Faculty of Pharmacy, University of Monastir, Tunisia.

contact, but an extension in the urban zones was noted during the past decade.

**Figure 1.** Hydatid cysts from Tunisian children operated at F. Bourguiba Monastir teaching hospital. A: Pulmonary cyst from an eight-year-old child. B: Hepatic cyst from a six-year-old child. Photograph: LP3M: Laboratory of Medical

**Host Cyst localisation Reference**


3

**Figure 2.** Hydatidosis endemic status based on mean human annual surgical incidence (SI) published by [6]. (The maps of Africa and Tunisia come from http://d-maps.com/).

Figure 2. Hydatidosis endemic status based on mean human annual surgical incidence (SI) published by [6]. (The maps of Africa and

children (3–7 years) and older children (8–15 years) demonstrated a mean age of 5.7 and 12 years old, respectively [27]. This early infestation has already been described in Turkey [32], Palestine [33], and Jordan [34]. 5 Tunisia come from http://d-maps.com/).

In children, the lungs are the most common sites for hydatid cysts followed by the liver (Table 3) [15, 27, 31]. This could be explained by noisier and earlier symptoms in children where cough, chest pain, and hemoptysis are the most frequently encountered signs [27, 30]. Some exceptional cyst localizations (central nervous system, orbit, spleen, kidney, and heart) were also described [15, 35, 36]. Several organs may be contaminated simultaneously and about 20% of cases reported in literature were involved in multiple cysts with essentially liver associated with lung [15, 27]. The growth of the hydatid is independent of children's age since cysts of high diameter (15 cm) were found in children of 4 years old [15, 31].


**Table 3.** CE prevalence, cyst fertility, and protoscoleces viability in Tunisian children.

Numerous pediatric studies have noted a slight male predominance compared to girls with a sex ratio of 1.2 to 1.8 [15, 27, 28, 31]. This observation was although reported in Algeria [37], Iran [38], Bulgaria [39], and Jordan [34]. The higher infestation of boys compared to girls in endemic countries is explained by the fact that school-age boys have more external activities than girls, with a greater promiscuity with dogs. In adults, in contrast to what is observed in children, women are more commonly affected than men [28, 40, 41]. This difference is due to their role in the home activities and that in rural areas, the women are more often at home and care very often for dogs and cattle, which increases the risk of contamination. In addition, the adult females have more regular medical follow-up (e.g., during pregnancy) that results in fortuitous cyst discoveries on ultrasound examinations.

The direct examination of the cyst allows studying its fertility (presence or absence of proto‐ scoleces) and the protoscolex viability. The cyst fertility was analyzed by light microscopic observation. Protoscolex viability was determined using vital eosin 0.2% coloration (Figure 3). The fertility of the cyst is independent of its location and its size and no relation with the age of infected children was noticed (Table 3) [15, 27, 42]. The cyst fertility and protoscoleces viability in humans are not involved in the maintenance of the parasite life cycle because human is a dead-end host but they are parameters attesting of the perfect adaptation of the parasite to humans.

As mentioned before in the genotyping section, the most frequent species associated with human hydatidosis is the *E. granulosus sensu stricto* (G1 genotype). Nevertheless, for two children, the *E. granulosus sensu stricto* (G3 genotype) and the *E. canadensis* species were observed. The fact that humans could be infected by different species/genotypes is an epide‐ miological feature to be taken into account in CE control measures.

Figure 3. Determination of protoscolex viability by using 0.2% eosin coloration: Alive (A) and dead (B) protoscolex. Photograph: LP3M: Laboratory of Medical and Molecular Parasitology-Mycology, Faculty of Pharmacy, University of Monastir, Tunisia. **Figure 3.** Determination of protoscolex viability by using 0.2% eosin coloration: Alive (A) and dead (B) protoscolex. Photograph: LP3M: Laboratory of Medical and Molecular Parasitology-Mycology, Faculty of Pharmacy, University of Monastir, Tunisia.

extensive sheep farming. Livestock are ubiquitous all over Tunisia, especially in rural areas and about 4 million sheep female unit

#### Livestock echinococcosis leads to economic repercussions because of animal liver and lung condemnations, decrease of the carcass weight, animal fertility, and milk production [43]. In Tunisia, breeding remains mainly traditional and the population practices **4. Cystic echinococcosis in production animals**

**4-Cystic echinococcosis in production animals**

(Figure 6).

exceptional cyst localizations (central nervous system, orbit, spleen, kidney, and heart) were also described [15, 35, 36]. Several organs may be contaminated simultaneously and about 20% of cases reported in literature were involved in multiple cysts with essentially liver associated with lung [15, 27]. The growth of the hydatid is independent of children's age since cysts of

**No. of patients No. of cysts Cyst localization Frequency (%) Fertility (%) Viability (%) Reference**

Liver 34.8 68.5

Other 3.4 71

Lung 59.5 70

Other 4.5 71

Numerous pediatric studies have noted a slight male predominance compared to girls with a sex ratio of 1.2 to 1.8 [15, 27, 28, 31]. This observation was although reported in Algeria [37], Iran [38], Bulgaria [39], and Jordan [34]. The higher infestation of boys compared to girls in endemic countries is explained by the fact that school-age boys have more external activities than girls, with a greater promiscuity with dogs. In adults, in contrast to what is observed in children, women are more commonly affected than men [28, 40, 41]. This difference is due to their role in the home activities and that in rural areas, the women are more often at home and care very often for dogs and cattle, which increases the risk of contamination. In addition, the adult females have more regular medical follow-up (e.g., during pregnancy) that results in

The direct examination of the cyst allows studying its fertility (presence or absence of proto‐ scoleces) and the protoscolex viability. The cyst fertility was analyzed by light microscopic observation. Protoscolex viability was determined using vital eosin 0.2% coloration (Figure 3). The fertility of the cyst is independent of its location and its size and no relation with the age of infected children was noticed (Table 3) [15, 27, 42]. The cyst fertility and protoscoleces viability in humans are not involved in the maintenance of the parasite life cycle because human is a dead-end host but they are parameters attesting of the perfect adaptation of the

As mentioned before in the genotyping section, the most frequent species associated with human hydatidosis is the *E. granulosus sensu stricto* (G1 genotype). Nevertheless, for two children, the *E. granulosus sensu stricto* (G3 genotype) and the *E. canadensis* species were observed. The fact that humans could be infected by different species/genotypes is an epide‐

Lung 61.8 83 77 [15]

Liver 36 81.5 79 [31]

high diameter (15 cm) were found in children of 4 years old [15, 31].

**Table 3.** CE prevalence, cyst fertility, and protoscoleces viability in Tunisian children.

fortuitous cyst discoveries on ultrasound examinations.

miological feature to be taken into account in CE control measures.

195 241

60 Current Topics in Echinococcosis

121 161

parasite to humans.

(FU), 700,000 goat FU, 420,000 cattle FU, and 17,000 camel FU are recorded [44]. The CE prevalence in food animals depends on the presence of the intermediate host of the parasite and their close contact with the final host (stray and semi-stray dogs). These intermediate hosts differ from one region to another in function of climatic factors and/or breeding or alimentary practices. Thus, dromedary breeding is essentially located in Southern Tunisia (desertic climate) where camels are most consumed, whereas sheep and cattle breedings are practiced throughout the country. Herbivores acquire the infection through ingestion of echinococcus eggs excreted by the dog feces. The breeding of small animals is practiced by farmers, but also commonly practiced by households in rural and urban areas (Figures 4 and 5). The importance of pastoral animal husbandry constitutes a significant risk factor for echinococcosis transmission because of the close contact of production animals with dogs. Thus, the infected livestock that died on the pastures are not buried and dogs or other carnivores are able to access these cadavers and lead to complete the transmission cycle Livestock echinococcosis leads to economic repercussions because of animal liver and lung condemnations, decrease of the carcass weight, animal fertility, and milk production [43]. In Tunisia, breeding remains mainly traditional and the population practices extensive sheep farming. Livestock are ubiquitous all over Tunisia, especially in rural areas and about 4 million sheep female unit (FU), 700,000 goat FU, 420,000 cattle FU, and 17,000 camel FU are recorded [44]. The CE prevalence in food animals depends on the presence of the intermediate host of the parasite and their close contact with the final host (stray and semistray dogs). These intermediate hosts differ from one region to another in function of climatic factors and/or breeding or alimentary practices. Thus, dromedary breeding is essentially located in Southern Tunisia (desertic climate) where camels are most con‐ sumed, whereas sheep and cattle breedings are practiced throughout the country. Herbi‐ vores acquire the infection through ingestion of *echinococcus* eggs excreted by the dog feces. The breeding of small animals is practiced by farmers, but also commonly practiced by households in rural and urban areas (Figures 4 and 5). The importance of pastoral animal husbandry constitutes a significant risk factor for echinococcosis transmission because of the close contact of production animals with dogs. Thus, the infected livestock that died on the pastures are not buried and dogs or other carnivores are able to access these cadavers and lead to complete the transmission cycle (Figure 6).

7

**Figure 4.** Pastoral sheep breeding in rural areas where sheep are in close contact with dogs. Photograph: LP3M: Labo‐ ratory of Medical and Molecular Parasitology-Mycology, Faculty of Pharmacy, University of Monastir, Tunisia.

Figure 4. Pastoral sheep breeding in rural areas where sheep are in close contact with dogs. Photograph: LP3M: Laboratory of

Medical and Molecular Parasitology-Mycology, Faculty of Pharmacy, University of Monastir, Tunisia.

Figure 5. Sheep breeding in urban areas where sheep are in close contact with dogs. Photograph: LP3M: Laboratory of Medical and Molecular Parasitology-Mycology, Faculty of Pharmacy, University of Monastir, Tunisia. **Figure 5.** Sheep breeding in urban areas where sheep are in close contact with dogs. Photograph: LP3M: Laboratory of Medical and Molecular Parasitology-Mycology, Faculty of Pharmacy, University of Monastir, Tunisia.

Figure 6. Carcass of dead cattle abandoned on the pasture and accessible to stray dogs. Photograph: LP3M: Laboratory of Medical

and Molecular Parasitology-Mycology, Faculty of Pharmacy, University of Monastir, Tunisia.

8

**Figure 6.** Carcass of dead cattle abandoned on the pasture and accessible to stray dogs. Photograph: LP3M: Laboratory of Medical and Molecular Parasitology-Mycology, Faculty of Pharmacy, University of Monastir, Tunisia.

**Figure 4.** Pastoral sheep breeding in rural areas where sheep are in close contact with dogs. Photograph: LP3M: Labo‐ ratory of Medical and Molecular Parasitology-Mycology, Faculty of Pharmacy, University of Monastir, Tunisia.

Figure 4. Pastoral sheep breeding in rural areas where sheep are in close contact with dogs. Photograph: LP3M: Laboratory of

Figure 5. Sheep breeding in urban areas where sheep are in close contact with dogs. Photograph: LP3M: Laboratory of Medical and

Medical and Molecular Parasitology-Mycology, Faculty of Pharmacy, University of Monastir, Tunisia.

**Figure 5.** Sheep breeding in urban areas where sheep are in close contact with dogs. Photograph: LP3M: Laboratory of

Figure 6. Carcass of dead cattle abandoned on the pasture and accessible to stray dogs. Photograph: LP3M: Laboratory of Medical

Molecular Parasitology-Mycology, Faculty of Pharmacy, University of Monastir, Tunisia.

and Molecular Parasitology-Mycology, Faculty of Pharmacy, University of Monastir, Tunisia.

Medical and Molecular Parasitology-Mycology, Faculty of Pharmacy, University of Monastir, Tunisia.

62 Current Topics in Echinococcosis

8

CE prevalence in production animals was estimated by post-mortem examination of slaugh‐ tered animals at abattoirs. A series of studies carried out in Tunisia assessed that the prevalence of *E. granulosus* infection ranged from 16.42% to 40.42% in sheep, 8.56% in cattle, 6% in Dromedaries, 2.9% in goats, and 8.48% in donkeys [14, 45–47] (Table 4). The highest prevalence was observed in sheep, as is the case in Libya (20%) and Italy (11.5%) [21, 48], while the lowest prevalence was noted in goats. In Morocco and Algeria, the cattle (23%) and the camels (25%), respectively, are the most infected animals whereas husbandry and slaughtering practices are grossly the same as in Tunisia [19, 49, 50]. It has been accepted that variations in animal CE prevalence rates can be related to the species/genotype involved in the infection [51]. Never‐ theless, in Tunisia, the G1 genotype is predominant in all intermediate hosts with high fertility rates [13] and only some infection cases by others genotypes are reported (see genotyping section). Moreover, a study conducted in Tunisia has demonstrated that the sheep over 8 years old are more often contaminated than sheep of 1-2 years and sheep of 4 years (60% vs. 20% and 40%, respectively) [46]. Consequently, in Tunisia, the difference in prevalence rate is more related to the age of slaughtered herbivores than to the species/genotype implied in the infection. In camels, the prevalence varies largely according to the region because of the difference in camel slaughtering practices. Thus, camels are slaughtered at an older age in South of Tunisia, whereas they are slaughtered at an earlier age (before 3 years) in Center of Tunisia. It has been demonstrated, in opposition to other intermediate hosts, that the camel cysts do not or seldom develop before the age of three [14, 52]. Therefore, it can be assumed that only old camels are implied in the parasite life cycle dog-camel.

Liver and lung are the only organs observed to be infected in production animals. The prevalence of the liver localization of the cyst was higher than that of pulmonary cysts except for the dromadaries where the pulmonary cysts are predominant (Table 4) [14, 45, 46, 53]. The co-infection of both organs in the same host is frequently observed and, contrary to what is usually described in humans, several cysts (up to 50 cysts) may develop in the same organ (Figure 7).


**Table 4.** CE prevalence and epidemiological data in Tunisian production animals.

However, available CE prevalence in livestock species does not reflect the real endemic situation since it is not considered private or illegal slaughtering. Uncontrolled home slaugh‐ tering during religious or local festivities is very common in Tunisia and the infected viscera Molecular and Epidemiology Data on Cystic Echinococcosis in Tunisia http://dx.doi.org/10.5772/60891 65

cysts do not or seldom develop before the age of three [14, 52]. Therefore, it can be assumed

Liver and lung are the only organs observed to be infected in production animals. The prevalence of the liver localization of the cyst was higher than that of pulmonary cysts except for the dromadaries where the pulmonary cysts are predominant (Table 4) [14, 45, 46, 53]. The co-infection of both organs in the same host is frequently observed and, contrary to what is usually described in humans, several cysts (up to 50 cysts) may develop in the same organ

**of cysts Frequency (%) Fertility**

1039 40.42 liver 40.42 - - 2001-2004 [45]

**Protoscolex viability**

Liver 54.97 19.24 74.94 2003-2010 [45] Lung 45.02 11.01 66.49 2003-2010 [45]

Liver 62.58 0.55 67.9 2003-2010 [45] Lung 37.41 0.40 89 2003-2010 [45]

Liver 67.82 15.57 25.63 2003-2010 [45] Lung 32.14 14.75 14.8 2003-2010 [45]

Liver 86.27 22.22 65.86 2003-2010 [45] Lung 13.72 22.22 13.72 2003-2010 [45]

Liver 7.69 - - - [14] Lung 92.30 - - - [14]

2006-2007 and

2006-2007 and

<sup>2009</sup> [47]

<sup>2009</sup> [47]

8 - - - 100 100 2000-2005 [53]

Liver 89.9 3.58 35.80

Lung 10.09 15.38 32.96

However, available CE prevalence in livestock species does not reflect the real endemic situation since it is not considered private or illegal slaughtering. Uncontrolled home slaugh‐ tering during religious or local festivities is very common in Tunisia and the infected viscera

**Table 4.** CE prevalence and epidemiological data in Tunisian production animals.



**Period Reference**

that only old camels are implied in the parasite life cycle dog-camel.

**Location**

(Figure 7).

**Hosts**

Sheep

Cattle

Dromedaries

**No. of animals**

64 Current Topics in Echinococcosis

248

203

Goat 3779 2.88

Donkey 2040 8.48

**Prevalence (%)**

2722 16.42

3913 8.56

404 5.94

291 6.5

Figure 7. Multiple hydatid cysts in the liver (A) and lungs (B) of a bovine. Photograph: LP3M: Laboratory of Medical and Molecular Parasitology-Mycology, Faculty of Pharmacy, University of Monastir, Tunisia. **Figure 7.** Multiple hydatid cysts in the liver (A) and lungs (B) of a bovine. Photograph: LP3M: Laboratory of Medical and Molecular Parasitology-Mycology, Faculty of Pharmacy, University of Monastir, Tunisia.

unsuitable for consumption are rejected and eaten by dogs. The knowledge of the parasite cycle and its transmission modalities are weak, in spite of a perception of the risk notably in rural areas. For example, a study conducted in 2007 (76 patients, 90 and 100 humans from urban and rural areas, respectively), has demonstrated that 40% of topics interrogated have the false notion that the humans' contamination is consecutive to the consumption of viscera containing hydatic cysts, whereas only 25.8% among them incriminate the dog [54]. The livestock trade in Tunisia is mainly based on weekly markets and exchange of animals all over the country. Thus, the lack of information on the exact geographical origin of livestock makes very difficult the identification of grazing areas at risk and the targeting of prophylactic measures. However, available CE prevalence in livestock species does not reflect the real endemic situation since it is not considered private or illegal slaughtering. Uncontrolled home slaughtering during religious or local festivities is very common in Tunisia and the infected viscera unsuitable for consumption are rejected and eaten by dogs. The knowledge of the parasite cycle and its transmission modalities are weak, in spite of a perception of the risk notably in rural areas. For example, a study conducted in 2007 (76 patients, 90 and 100 humans from urban and rural areas, respectively), has demonstrated that 40% of topics interrogated have the false notion that the humans' contamination is consecutive to the consumption of viscera containing hydatic cysts, whereas only 25.8% among them incriminate the dog [54]. The livestock trade in Tunisia is mainly based on weekly markets and exchange of animals all over the country. Thus, the lack of information on the exact geographical origin of livestock makes very difficult the identification of grazing areas at risk and the targeting of prophylactic measures. Molecular analyses have demonstrated that *E. granulosus* species circulating in Tunisia are *E. granulosus sensu stricto* (G1 and G3 genotypes), *E. canadensis* (G6 genotype), and *E. equinus* (G4 genotype) [13, 16, 17] (see Table 1 in genotyping section). The cyst fertility and the viability of protoscoleces are the main factors that allow the maintenance of the cycle between intermediate and definitive host and leads to the existence of particular life cycles. Cyst fertility varied amongst livestock host populations with average rates of 44.8% (range: 11–86%) in sheep, 15% in goats, 27.13% (range: 0.4–76.5%) in cattle, 48.5% (range: 22.22–100%) in camels, and 4.77% in donkeys [13, 14, 45, 47, 53] (Table 4). Contrary to what was observed in European countries [48], G1 genotype has a significant fertility rate (46%) in the cattle host in Tunisia [13] and Algeria (from 52% to 70%) [19]. In general, a significant fertility rate, as far as cattle was concerned, was due to the *E. ortleppi* species (G5 genotype) and rarely to *E. granulosus sensu stricto*

Molecular analyses have demonstrated that *E. granulosus* species circulating in Tunisia are *E. granulosus sensu stricto* (G1 and G3 genotypes), *E. canadensis*(G6 genotype), and *E. equinus* (G4 genotype) [13, 16, 17] (see Table 1 in genotyping section). The cyst fertility and the viability of protoscoleces are the main factors that allow the maintenance of the cycle between intermedi‐ ate and definitive host and leads to the existence of particular life cycles. Cyst fertility varied amongst livestock host populations with average rates of 44.8% (range: 11–86%) in sheep, 15% 10 (G1 genotype) [55, 56]. The findings of fertile hydatid cysts and viable protoscoleces in cattle, suggest that Tunisian and Algerian cattle can act as suitable hosts for the G1 genotype. The perfect adaptation of this genotype to bovine host is a significant parameter risk for human contamination via infected dogs and proved that cattle has more importance in the transmission cycle than previously believed.

in goats, 27.13% (range: 0.4–76.5%) in cattle, 48.5% (range: 22.22–100%) in camels, and 4.77% in donkeys [13, 14, 45, 47, 53] (Table 4). Contrary to what was observed in European countries [48], G1 genotype has a significant fertility rate (46%) in the cattle host in Tunisia [13] and Algeria (from 52% to 70%) [19]. In general, a significant fertility rate, as far as cattle was concerned, was due to the *E. ortleppi* species (G5 genotype) and rarely to *E. granulosus sensu stricto* (G1 genotype) [55, 56]. The findings of fertile hydatid cysts and viable protoscoleces in cattle, suggest that Tunisian and Algerian cattle can act as suitable hosts for the G1 genotype. The perfect adaptation of this genotype to bovine host is a significant parameter risk for human contamination via infected dogs and proved that cattle has more importance in the transmis‐ sion cycle than previously believed.

#### **5.** *Echinococcus* **in dogs**

The CE is highly endemic in many North African countries and very high infection rates have been reported in dogs (55–58% in Morocco [49], 20–25.8% in Libya [57] and 19–42% in Algeria [58]). In Tunisia, although a sylvatic life cycle involving wild carnivores (golden jackals and red foxes) as definitive hosts was described [59], the *E. granulosus* transmission is typically through a synathropic cycle between dogs and livestock (essentially sheep, cattle, and camels). In Tunisia, the dogs are used primarily to guard livestock and property. The canine population is estimated at 800,000 dogs and composed essentially of feral and semi-feral (free-roaming dogs that are fed by an owner) dogs that rarely receive deworming treatment (Figure 8) [60].

In rural, urban, and semi-urban areas, the canine density is one dog per 3.0 to 5.5 inhabitants, one dog per 16 inhabitants and one dog per 46 inhabitants, respectively. In urban regions, less than 20% of households own a dog, whereas in rural regions there are 7–30 dogs per km², and more than 80% of households own at least one dog [61].

The prevalence of *E. granulosus* in dogs is estimated by several techniques including the detection of worms at necropsy, worm antigen in feces (coproantigen), or direct examination of eggs in dog feces. The prevalence of *E. granulosus* infection in Tunisian dogs ranges from 3.75% to 27.1% depending on the regions [59, 62, 63] (Table 5).


n: mean number of parasites per infected dog

**Table 5.** Prevalence and molecular epidemiology of *E. granulosus* dog infection in Tunisia.

The study of the vital areas of stray dogs, based on 52 to 285 locations in a semi-urban area of Tunisia, has identified an area ranging between 0.06 and 8.53 km² [61]. Thus, considering that antigen in feces (coproantigen), or direct examination of eggs in dog feces. The prevalence of *E. granulosus* infection in Tunisian dogs ranges from 3.75% to 27.1% depending on the regions [59, 62, 63] (Table 5). Molecular and Epidemiology Data on Cystic Echinococcosis in Tunisia http://dx.doi.org/10.5772/60891 67

The CE is highly endemic in many North African countries and very high infection rates have been reported in dogs (55–58% in Morocco [49], 20–25.8% in Libya [57] and 19–42% in Algeria [58]). In Tunisia, although a sylvatic life cycle involving wild carnivores (golden jackals and red foxes) as definitive hosts was described [59], the *E. granulosus* transmission is typically through a synathropic cycle between dogs and livestock (essentially sheep, cattle, and camels). In Tunisia, the dogs are used primarily to guard livestock and property. The canine population is estimated at 800,000 dogs and composed essentially of feral and semi-feral (free-

In rural, urban, and semi-urban areas, the canine density is one dog per 3.0 to 5.5 inhabitants, one dog per 16 inhabitants and one dog per 46 inhabitants, respectively. In urban regions, less than 20% of households own a dog, whereas in rural regions there are 7–30

The prevalence of *E. granulosus* in dogs is estimated by several techniques including the detection of worms at necropsy, worm

roaming dogs that are fed by an owner) dogs that rarely receive deworming treatment (Figure 8) [60].

dogs per km², and more than 80% of households own at least one dog [61].

Figure 8. Stray and semi-stray dogs in rural area of Gafsa governorate (South of Tunisia). Photograph: LP3M: Laboratory of Medical **Figure 8.** Stray and semi-stray dogs in rural area of Gafsa governorate (South of Tunisia). Photograph: LP3M: Labora‐ tory of Medical and Molecular Parasitology-Mycology, Faculty of Pharmacy, University of Monastir, Tunisia.

the average number of worms per dog is estimated at several thousands [59] and more than 8,000 *Echinococcus* eggs were shed per day [64], dogs cause massive environmental contami‐ nation. Using direct examination of dog feces, the overall contamination index of dog feces by *E. granulosus* was estimated to 25.3% and was ranged between 8.3% to 41.3% depending on the regions [65]. Nevertheless, the canine echinococcosis is not necessarily correlated to human CE since transmission of echinococcus is influenced by human activities and behavior [65, 66]. As in many African countries, dog contamination is essentially due to the consumption of uninspected meat during familial or religious slaughtering, improper disposal of offal or carcasses unsuitable for consumption that are eaten by numerous stray and semi-stray dogs, and lack of knowledge about the transmission of the disease [50, 60, 67]. Thus, 38.4% and 44% of butchers and population, respectively, have an inappropriate behavior concerning the management of infected offal. They throw them directly into the trash or bury them superfi‐ cially leaving them easily accessible to dogs [67]*.* 11 and Molecular Parasitology-Mycology, Faculty of Pharmacy, University of Monastir, Tunisia.

#### **6. Conclusion**

**5-Echinococcus in dogs**

in goats, 27.13% (range: 0.4–76.5%) in cattle, 48.5% (range: 22.22–100%) in camels, and 4.77% in donkeys [13, 14, 45, 47, 53] (Table 4). Contrary to what was observed in European countries [48], G1 genotype has a significant fertility rate (46%) in the cattle host in Tunisia [13] and Algeria (from 52% to 70%) [19]. In general, a significant fertility rate, as far as cattle was concerned, was due to the *E. ortleppi* species (G5 genotype) and rarely to *E. granulosus sensu stricto* (G1 genotype) [55, 56]. The findings of fertile hydatid cysts and viable protoscoleces in cattle, suggest that Tunisian and Algerian cattle can act as suitable hosts for the G1 genotype. The perfect adaptation of this genotype to bovine host is a significant parameter risk for human contamination via infected dogs and proved that cattle has more importance in the transmis‐

The CE is highly endemic in many North African countries and very high infection rates have been reported in dogs (55–58% in Morocco [49], 20–25.8% in Libya [57] and 19–42% in Algeria [58]). In Tunisia, although a sylvatic life cycle involving wild carnivores (golden jackals and red foxes) as definitive hosts was described [59], the *E. granulosus* transmission is typically through a synathropic cycle between dogs and livestock (essentially sheep, cattle, and camels). In Tunisia, the dogs are used primarily to guard livestock and property. The canine population is estimated at 800,000 dogs and composed essentially of feral and semi-feral (free-roaming dogs that are fed by an owner) dogs that rarely receive deworming treatment (Figure 8) [60]. In rural, urban, and semi-urban areas, the canine density is one dog per 3.0 to 5.5 inhabitants, one dog per 16 inhabitants and one dog per 46 inhabitants, respectively. In urban regions, less than 20% of households own a dog, whereas in rural regions there are 7–30 dogs per km², and

The prevalence of *E. granulosus* in dogs is estimated by several techniques including the detection of worms at necropsy, worm antigen in feces (coproantigen), or direct examination of eggs in dog feces. The prevalence of *E. granulosus* infection in Tunisian dogs ranges from

**No. of dogs Prevalence (%) Worm burden (n) Diagnostic procedure Period Reference** 18.4 848 Necropsy 2007 [59] 3.75 - Purgation 2002-2003 [62] 6.9-27.1 2534 Necropsy 1998-1999 [63]

The study of the vital areas of stray dogs, based on 52 to 285 locations in a semi-urban area of Tunisia, has identified an area ranging between 0.06 and 8.53 km² [61]. Thus, considering that

sion cycle than previously believed.

more than 80% of households own at least one dog [61].

n: mean number of parasites per infected dog

3.75% to 27.1% depending on the regions [59, 62, 63] (Table 5).

**Table 5.** Prevalence and molecular epidemiology of *E. granulosus* dog infection in Tunisia.

**5.** *Echinococcus* **in dogs**

66 Current Topics in Echinococcosis

Despite the control programs, essentially based on the systematic condemnation of infected offal in slaughterhouses, cystic echinococcosis remains a major public health in Tunisia. The endemic status differs from one region to another, and some areas have been defined as hyperendemic, holoendemic, mesoendemic, and hypoendemic regions. Hydatidosis is important in rural areas but an extension in the urban zones was noted during the past decade. The characterization of the species responsible for echinococcosis in Tunisia is a significant point that has to be taken into consideration in order to focus and to adapt the control measures. Three *Echinococcus* species (*E. granulosus sensu stricto*, *E. canadensis* and *E. equinus*) have been described in different intermediate hosts but *E. granulosus sensu stricto* G1 genotype remains predominant. The continuing presence of CE in Tunisia depends on a variety of factors and human behavior plays an important role in the perpetuation of the cystic echinococcosis. The importance of pastoral animal husbandry, the elevated number of unrestrained dogs, and their frequent contamination by *E. granulosus* infected viscera are the major causes of the CE spread. The inadequate deworming treatment, the close contact of untreated dogs with humans, and animals particularly in rural areas, the hygiene level, the poor public awareness about the disease, and the favorable ecological and climatic conditions for the survival of *Echinococcus* eggs in the environment constitute ideal conditions for the transmission of the infection to dogs, humans, and animals. Thus, the sanitary education concerning hydatidosis should be reinforced and efforts should be made to implement a targeted educational program. Aware‐ ness should be created for the animal attendants, farmers, customers, slaughterhouse workers, and butchers regarding the CE public health significance.

#### **Acknowledgements**

The authors thank Imen Hizem-Attig for her assistance with the linguistic part of this paper.

#### **Author details**

Myriam Oudni-M'rad1\*, Selim M'rad1 and Hamouda Babba1,2

\*Address all correspondence to: myriam.mrad@gnet.tn

1 LP3M: Laboratory of Medical and Molecular Parasitology-Mycology, LR12ES08, Faculty of Pharmacy, University of Monastir, Monastir, Tunisia

2 Laboratory of Parasitology, teaching hospital F. Bourguiba, Monastir, Tunisia

#### **References**

[1] Dakkak A. Echinococcosis/hydatidosis: A severe threat in Mediterranean countries. Veterinary Parasitology 2010;174:2–11.

[2] Sadjjadi SM. Present situation of echinococcosis in the Middle East and Arabic North Africa. Parasitology International 2006;55:197–220.

endemic status differs from one region to another, and some areas have been defined as hyperendemic, holoendemic, mesoendemic, and hypoendemic regions. Hydatidosis is important in rural areas but an extension in the urban zones was noted during the past decade. The characterization of the species responsible for echinococcosis in Tunisia is a significant point that has to be taken into consideration in order to focus and to adapt the control measures. Three *Echinococcus* species (*E. granulosus sensu stricto*, *E. canadensis* and *E. equinus*) have been described in different intermediate hosts but *E. granulosus sensu stricto* G1 genotype remains predominant. The continuing presence of CE in Tunisia depends on a variety of factors and human behavior plays an important role in the perpetuation of the cystic echinococcosis. The importance of pastoral animal husbandry, the elevated number of unrestrained dogs, and their frequent contamination by *E. granulosus* infected viscera are the major causes of the CE spread. The inadequate deworming treatment, the close contact of untreated dogs with humans, and animals particularly in rural areas, the hygiene level, the poor public awareness about the disease, and the favorable ecological and climatic conditions for the survival of *Echinococcus* eggs in the environment constitute ideal conditions for the transmission of the infection to dogs, humans, and animals. Thus, the sanitary education concerning hydatidosis should be reinforced and efforts should be made to implement a targeted educational program. Aware‐ ness should be created for the animal attendants, farmers, customers, slaughterhouse workers,

The authors thank Imen Hizem-Attig for her assistance with the linguistic part of this paper.

and Hamouda Babba1,2

1 LP3M: Laboratory of Medical and Molecular Parasitology-Mycology, LR12ES08, Faculty of

[1] Dakkak A. Echinococcosis/hydatidosis: A severe threat in Mediterranean countries.

2 Laboratory of Parasitology, teaching hospital F. Bourguiba, Monastir, Tunisia

and butchers regarding the CE public health significance.

\*Address all correspondence to: myriam.mrad@gnet.tn

Pharmacy, University of Monastir, Monastir, Tunisia

Veterinary Parasitology 2010;174:2–11.

**Acknowledgements**

68 Current Topics in Echinococcosis

**Author details**

**References**

Myriam Oudni-M'rad1\*, Selim M'rad1


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74 Current Topics in Echinococcosis

#### **Chapter 4**

## *Echinococcus shiquicus* **and** *Echinococcus felidis*

#### Adel Spotin

Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/60819

#### **Abstract**

Currently, ten genotypes (G1-G10) of *Echinococcus* Sensu Lato have been explicitly identified on the basis of taxonomic criteria. These include morphometric keys, host specificity, geographical distribution, phylogenetic analysis and genome mapping. However, a few emergent species of genus *Echinococcus* have been indigenously confirmed in some autonomous regions of Tibet plateau and Africa where there is little known about their biological aspects and potential pathogenicity in intermediate and definitive hosts. This chapter is focused on the parasite history, life cycle, phenotypic aspects, epidemiology, zoonotic potential and phylogeny relationship of two enigmatic parasites namely: *Echinococcus shiquicus* and *Echinococcus felidis*. This aims to provide a better understanding of their taxonomic status, public health problems and biological features in the mentioned regions.

**Keywords:** *Echinococcus shiquicus*, *Echinococcus felidis*, Biological Aspects, Phyloge‐ netic traits

#### **1. Introduction**

Currently, ten genotypes (G1-G10) of *Echinococcus* Sensu Lato have been explicitly identified on the basis of taxonomic criteria. These include morphometric keys, host specificity, geo‐ graphical distribution, phylogenetic analysis and genome mapping. However, a few emergent species of genus *Echinococcus* have been indigenously confirmed in some autonomous regions of Tibet plateau and Africa where there is little known about their biological aspects and potential pathogenicity in intermediate and definitive hosts. This chapter is focused on the parasite history, life cycle, phenotypic aspects, epidemiology, zoonotic potential and phylog‐

© 2015 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

eny relationship of two enigmatic parasites namely: *Echinococcus shiquicus* and *Echinococcus felidis.* This aims to provide a better understanding of their taxonomic status, public health problems and biological features in the mentioned regions.

#### **2.** *Echinococcus shiquicus*

#### **2.1. History, morphology and biology**

In ~2005, *Echinococcus shiquicus* was first described by Xiao, from the Tibetan fox in Shiqu county of the Qinghai–Tibet plateau, China called the ''Roof of the World'' [1]. Earlier than molecular analysis, the *E. shiquicus* isolated from Tibetan fox; *Vulpes ferrilata* was considered as a morphological strain of *E. multilocularis*, whilst it is metacestode from the plateau pika; *Ochotona curzoniae*, was then recognized as *E. granulosus* because of its unilocular cystic characteristics [2].

**Figure 1.** The life cycle of *Echinococcus shiquicus*. Credit: Image courtesy of Seyyed Ali Shariatzadeh.

Afterward, based on taxonomic criteria including morphology, host specificity, molecular characters and geographical distribution was considered as a new species of *Echinococcus* [1].

eny relationship of two enigmatic parasites namely: *Echinococcus shiquicus* and *Echinococcus felidis.* This aims to provide a better understanding of their taxonomic status, public health

In ~2005, *Echinococcus shiquicus* was first described by Xiao, from the Tibetan fox in Shiqu county of the Qinghai–Tibet plateau, China called the ''Roof of the World'' [1]. Earlier than molecular analysis, the *E. shiquicus* isolated from Tibetan fox; *Vulpes ferrilata* was considered as a morphological strain of *E. multilocularis*, whilst it is metacestode from the plateau pika; *Ochotona curzoniae*, was then recognized as *E. granulosus* because of its unilocular cystic

**Figure 1.** The life cycle of *Echinococcus shiquicus*. Credit: Image courtesy of Seyyed Ali Shariatzadeh.

problems and biological features in the mentioned regions.

**2.** *Echinococcus shiquicus*

78 Current Topics in Echinococcosis

characteristics [2].

**2.1. History, morphology and biology**

The sylvatic cycle of *E. shiquicus* is supported by the Tibetan fox and the plateau pika as the definitive and intermediate hosts, respectively, which are indigenous to the highlands of Tibet (Figure 1) [1]. However, *E. shiquicus* using copro-PCR and sequencing strategies has been naturally reported in dogs from eastern Qinghai–Tibet plateau region, China [3].

The adult worms of *E. shiquicus* are observed into two types. The majority of the samples included pre-mature and gravid proglottid which testes and ovary are placed in the premature segment while the genital pore is closed (Figure 2A) [1]. The second type consisted of immature, mature and gravid proglottid (Figure 2B). The number of segments in an adult worm is limited to three. *E. shiquicus* is readily discriminated from *E. granulosus* by its shorter length, length of hooks on the rostellum, branchless gravid uterus and anterior position of genital pore in the gravid proglottid. Also, the upper position of genital pore in the mature segment, smaller rostellar hooks and the fewer eggs in gravid segment of *E. shiquicus* (less than 100) are useful for differentiation of *E. shiquicus* in compared to *E. multilocularis*.

**Figure 2.** Different adult types (A and B) of *Echinococcus shiquicus* in a naturally infected Tibetan fox.

The metacestode stage of *E. shiquicus* is characterized by presence of unilocular minicyst containing developed brood capsules with no daughter cysts. The morphometric aspects of *E. shiquicus*, *E. multilocularis* and *E. granulosus* are shown in Table 1.

The concomitant (dual) infections of *E. shiquicus* with *E. multilocularis* have been recently identified in *O. curzoniae* and Tibetan foxes [4]. The zoonotic potential of *E. shiquicus* is still


**Table 1.** Comparison of the morphological aspects of *Echinococcu*s spp.

unknown; although recently, some cases with unilocular and alveolar echinococcosis inclusive atypical ultrasound images have been characterized in Tibetans [5].

Although, no human infection of *E. shiquicus* has been reported yet, nevertheless the public health problems of *E. shiquicus* should not be neglected in control programs such as followup, monitoring and surveillance in an at risk population.

Therefore, additional studies are required to survey the possibility of human infections which can be employed in animal's models by serial passages using diagnostic antigens. The biological aspects of *E. shiquicus* including definitive host, intermediate hosts, genetic similarity and *etc*. are shown in Table 2.


**Table 2.** A list of *Echinococcus felidis* and *Echinococcus shiquicus* features.

#### **2.2. The evolutionary markers and molecular approaches in identifying** *Echinococcus* **spp.**

The evolution in *Echinococcus* spp. can be considered as a combination of three major mecha‐ nisms that separately affect the composition of the genome of each species: mutation, selection and genetic drift [6].

Mutations occurred in the non-synonymous sites (called replacement sites because mutations at these sites lead to a change in the protein sequence) and the synonymous sites (called silent sites because mutations there do not lead to a change in the protein sequence) [6, 7].

It is worth noting that the nucleotide substitutions (Transition/Tranversion models) and/or indels (insertion or deletion) in the first and second positions of codons usually lead to create a new species/strain, which directly affect the frame shift of amino acids in case of any amino acid shifting or changing protein functionality while, changing in third position of codons (wobble site) is frequently leaded to creating novel haplotypes [8–11].

To date, the status of *Echinococcus* spp. is identified evidently by sequencing of nuclear DNA [12] and mitochondrial genome (mitogenome) accompanied by employing phylogenetic analysis on the basis of cladistics methods (Maximum Likelihood and Maximum Parsimony or Bayesian statistics and uses allele frequencies to study the nature and extent of genetic variation within and between populations) [13]. Although recently, a diagnostic pattern has been reported based on RFLP technique in differentiation of *Echinococcus* spp. using noncoding conserved gene [14].

It is important that the employing extra nuclear (mitochondrial) markers with low copy numbers and high variation characteristics are able to identify the unknown species/strains even haplotypes in exceptional regions where several intermediate hosts are circulating unequivocally [15].

#### **2.3. Phylogenetic findings**

unknown; although recently, some cases with unilocular and alveolar echinococcosis inclusive

**Features** *E. shiquicus E. granulosus E. multilocularis*

Body Length (mm) 1.3 -1.7 2.0–11.0 1.2– 4.5 Number of segments 2–3 2– 7 2–6

Number of testicles 12–20 25– 80 16– 35

Although, no human infection of *E. shiquicus* has been reported yet, nevertheless the public health problems of *E. shiquicus* should not be neglected in control programs such as follow-

Therefore, additional studies are required to survey the possibility of human infections which can be employed in animal's models by serial passages using diagnostic antigens. The biological aspects of *E. shiquicus* including definitive host, intermediate hosts, genetic similarity

> Tibetan plateau

**2.2. The evolutionary markers and molecular approaches in identifying** *Echinococcus* **spp.**

The evolution in *Echinococcus* spp. can be considered as a combination of three major mecha‐ nisms that separately affect the composition of the genome of each species: mutation, selection

Mutations occurred in the non-synonymous sites (called replacement sites because mutations at these sites lead to a change in the protein sequence) and the synonymous sites (called silent

sites because mutations there do not lead to a change in the protein sequence) [6, 7].

**Distribution Intermediate host**

Africa Warthog (possibly

giraffe, hippopotamus)

zebra, wildebeest, bush pig, buffalo, various antelope,

**Definitive host**

20.0– 23.0 25.0– 49.0 24.9– 34.0

16.0–17.0 17.0– 31.0 20.4– 31.0

Pika Tibetan fox *Echinococcus*

**Species**

*shiquicus*

Lion *Echinococcus felidis*

atypical ultrasound images have been characterized in Tibetans [5].

up, monitoring and surveillance in an at risk population.

**Table 1.** Comparison of the morphological aspects of *Echinococcu*s spp.

**Genetic similarity**

*multilocularis*

*granulosus*

**Table 2.** A list of *Echinococcus felidis* and *Echinococcus shiquicus* features.

and *etc*. are shown in Table 2.

large hook on the rostellum (microns)

80 Current Topics in Echinococcosis

small hook on the rostellum (microns)

**Infectivity to humans**

Unilocular Uncertain *Echinococcus*

Unknown Uncertain *Echinococcus*

and genetic drift [6].

**Hydatid characters**

Length of

Length of

Sequencing, phylogenetic and bioinformatics' analyses of mtDNA [16] and nuclear DNA [12] revealed that *E. shiquicus* and *E. multilocularis* are sister species with identical branch lengths in a specific clade and bootstrapping value of 99%.


**Figure 3.** Nucleotide sequence alignments of *C*ox1 gene in *Echinococcus* spp.

The molecular characterization of *Echinococcus* spp. in the Tibetan plateau has demonstrated that the richness of genetic diversity indices of *E. shiquicus* is higher than those of *E. granulosus s.s* and *E. multilocularis* (Figure 3).

*E. shiquicus*, however, is placed with *E. multilocularis* in a common clade of ancestor with bootstrap value >70% (Figures 4 and 5).

This heterogeneity can be elucidated by description of three assumptions. First: presence of two turnover mechanisms, namely; unequal crossing over/transposition and slippage in the sequence length of parasite [17]. Second: lack of any bottleneck effects after its ancestor had been isolated on the Tibetan Plateau by colonizing alpine mammals (genetic drift or founder effect) [18]. And third: the long term geographic segregation into the plateau.

In a study, three polymerase chain reaction (PCR) assays based on the amplification of a fragment within the NADH dehydrogenase subunit 1 (ND1) mitochondrial gene have been optimized for the detection of *E. shiquicus*, *E. granulosus* and *E. multilocularis* in co-endemic regions of Qinghai-Tibet plateau, China [19].

#### **3.** *Echinococcus felidis*

#### **3.1. Introduction**

In *Echinococcus* species position, *E. granulosus* Sensu Lato has been categorized into *E. granu‐ losus* Sensu Stricto (G1–G3), *E. equinus* (horse strain; genotype G4), *E. ortleppi* (cattle strain; genotype G5) and *E. canadensis* (genotypes G6–G10).

However, the taxonomic position, human infection, intermediate hosts and DNA profile of enigmatic 'lion strain' from Africa [20] has been unknown due to unavailability of suitable isolates.

#### **3.2. History and biology**

In 1937, *Echinococcus felidis* (Cestoda: Taeniidae) was first described by Ortlepp, from the lion *Panthera leo*, in South Africa [21]. Then, Rausch and Nelson (1963) declared that the taxonomic status of *E. felidis* remained to be uncertain from other *Echinococcus* spp. owing to existence of the host specificity and its rostellar hooks [22]. Verster (1965) re-checked the morphological features of *E. felidis* proglottids and proposed as a sub-specific rank of *E. granulosus felidis* [23]. Afterward, Rausch (1967) invalidated the sub-specific/strain status regarding *E. felidis* as an *E. granulosus* synonym because of lack of a valid evidence for it being a geographically isolated sylvatic cycle [24].

Many records of this parasite remained unidentified from a large variety of African mammals, due to the lack of diagnostic criteria, mainly genetic characterization and the misdiagnosis with the sympatric *Echinococcus* spp. [25] (Figure 6).

Echinococcosis is a high public health priority in the endemic areas of the world especially Africa, where more than one species of intermediate host is present and there is the possibility of interaction between cycles of transmission. Therefore the concomitant infections of *E. felidis* with other *Echinococcus* spp. may be sympatrically overlapped in under studied regions where it can be neglected.

The explicit status of *E. felidis* had not been determined until recent times. Huttner et al. (2008) presented its validity based on genetic classification and phylogenetic position [20].

The felids act as definitive hosts for enigmatic 'lion strain' however, It is still unclear which of the sympatric wild ungulates serve as intermediate hosts in life cycle of *E. felidis*. The different features of *E. felidis* are shown in Table 2. Like *E. shiquicus*, there is not enough data about human infection, hydatid feature and intermediate hosts. Therefore the zoonotic potential and public health concern among circulating isolates particularly those concomitant infections should be noticed absolutely.

#### **3.3. Phylogenetic findings in** *E. felidis*

The molecular characterization of *Echinococcus* spp. in the Tibetan plateau has demonstrated that the richness of genetic diversity indices of *E. shiquicus* is higher than those of *E. granulosus*

*E. shiquicus*, however, is placed with *E. multilocularis* in a common clade of ancestor with

This heterogeneity can be elucidated by description of three assumptions. First: presence of two turnover mechanisms, namely; unequal crossing over/transposition and slippage in the sequence length of parasite [17]. Second: lack of any bottleneck effects after its ancestor had been isolated on the Tibetan Plateau by colonizing alpine mammals (genetic drift or founder

In a study, three polymerase chain reaction (PCR) assays based on the amplification of a fragment within the NADH dehydrogenase subunit 1 (ND1) mitochondrial gene have been optimized for the detection of *E. shiquicus*, *E. granulosus* and *E. multilocularis* in co-endemic

In *Echinococcus* species position, *E. granulosus* Sensu Lato has been categorized into *E. granu‐ losus* Sensu Stricto (G1–G3), *E. equinus* (horse strain; genotype G4), *E. ortleppi* (cattle strain;

However, the taxonomic position, human infection, intermediate hosts and DNA profile of enigmatic 'lion strain' from Africa [20] has been unknown due to unavailability of suitable

In 1937, *Echinococcus felidis* (Cestoda: Taeniidae) was first described by Ortlepp, from the lion *Panthera leo*, in South Africa [21]. Then, Rausch and Nelson (1963) declared that the taxonomic status of *E. felidis* remained to be uncertain from other *Echinococcus* spp. owing to existence of the host specificity and its rostellar hooks [22]. Verster (1965) re-checked the morphological features of *E. felidis* proglottids and proposed as a sub-specific rank of *E. granulosus felidis* [23]. Afterward, Rausch (1967) invalidated the sub-specific/strain status regarding *E. felidis* as an *E. granulosus* synonym because of lack of a valid evidence for it being a geographically isolated

Many records of this parasite remained unidentified from a large variety of African mammals, due to the lack of diagnostic criteria, mainly genetic characterization and the misdiagnosis

Echinococcosis is a high public health priority in the endemic areas of the world especially Africa, where more than one species of intermediate host is present and there is the possibility

effect) [18]. And third: the long term geographic segregation into the plateau.

*s.s* and *E. multilocularis* (Figure 3).

82 Current Topics in Echinococcosis

bootstrap value >70% (Figures 4 and 5).

regions of Qinghai-Tibet plateau, China [19].

genotype G5) and *E. canadensis* (genotypes G6–G10).

with the sympatric *Echinococcus* spp. [25] (Figure 6).

**3.** *Echinococcus felidis*

**3.2. History and biology**

sylvatic cycle [24].

**3.1. Introduction**

isolates.

Based on sequences of mitochondrial genes for cytochrome c oxidase subunit 1 (cox1), NADH dehydrogenase subunit 1 (nad1), cytochrome b (cob), rRNA (rrn), and nuclear genes for elongation factor 1 alpha (ef1a), ezrin-radixin-moesin (ERM)-like protein (elp) and

**Figure 4.** Phylogenetic tree of *Echinococcus* spp. inferred from nuclear protein-coding genes.

Internal transcribed spacer (ITS), *E. felidis* and *E. granulosus* Sensu Stricto are presumed to have a common ancestor from Asian Felidae [20, 26].

Considering the assumption, ancestral lineage of *Panthera leo* in Asia is refereed to late Pliocene [10], which had been invaded to Africa in the early Pleistocene [27]. Phylogenetic trees of *Echinococcus* spp. inferred from mitogenome and nuclear protein-coding genes shown that both *E. felidis* and *E. granulosus* have placed in *E. granulosus* Sensu Stricto complex (genotypes G1, G2 and G3; Figures 4 and 5). In Figure 4 the *E. felidis* and *E. granulosus* are characterized with different branch lengths in a common clade and bootstrapping value of 97%.

**Figure 5.** NeighborNet graph according to the Kimura-2 parameter model and concatenated sequences of *Cox1* gene (mitogenome) of *Echinococcus* spp. *Echinococcus felidis* and *Echinococcus shiquicus* have characterized by asterisk (\*) and red underline in *E. granulosus* and *E. canadensis* complexes respectively

The tree was reconstructed by the maximum likelihood method and Kimura-2 parameter model. *Echinococcus felidis* and *Echinococcus shiquicus* have characterized by asterisk (\*) and red underline.

At this time, there are no valid data on the pathogenicity of *E. felidis* to humans and livestock although its close relationship with *E. granulosus* s.s proposed a zoonotic potential [28].

On the other hand, information about intermediate hosts of this parasite is still unknown, even though a hydatid cyst was identified as *E. felidis* from warthog in Queen Elizabeth National Park, Uganda [29].

**Figure 6.** The life cycle of *Echinococcus felidis*. Credit: Image courtesy of Seyyed Ali Shariatzadeh.

#### **4. Conclusion**

Considering the assumption, ancestral lineage of *Panthera leo* in Asia is refereed to late Pliocene [10], which had been invaded to Africa in the early Pleistocene [27]. Phylogenetic trees of *Echinococcus* spp. inferred from mitogenome and nuclear protein-coding genes shown that both *E. felidis* and *E. granulosus* have placed in *E. granulosus* Sensu Stricto complex (genotypes G1, G2 and G3; Figures 4 and 5). In Figure 4 the *E. felidis* and *E. granulosus* are characterized

**Figure 5.** NeighborNet graph according to the Kimura-2 parameter model and concatenated sequences of *Cox1* gene (mitogenome) of *Echinococcus* spp. *Echinococcus felidis* and *Echinococcus shiquicus* have characterized by asterisk (\*) and

The tree was reconstructed by the maximum likelihood method and Kimura-2 parameter model. *Echinococcus felidis* and *Echinococcus shiquicus* have characterized by asterisk (\*) and red

At this time, there are no valid data on the pathogenicity of *E. felidis* to humans and livestock although its close relationship with *E. granulosus* s.s proposed a zoonotic potential [28].

On the other hand, information about intermediate hosts of this parasite is still unknown, even though a hydatid cyst was identified as *E. felidis* from warthog in Queen Elizabeth National

red underline in *E. granulosus* and *E. canadensis* complexes respectively

underline.

Park, Uganda [29].

84 Current Topics in Echinococcosis

with different branch lengths in a common clade and bootstrapping value of 97%.

In the past decade, *E. shiquicus* and *E. felidis* have been indigenously confirmed in some sympatric regions of Tibet plateau and Africa, however, there is no more known about their zoonotic potential, human infection and public health problems. The contents of this chapter can be useful in the parasite history, biology, morphometric aspects, epidemiology, zoonotic potential and phylogeny relationship of mentioned *Echinococcus* which is provided a better understanding of their taxonomic position, public health priority and biological aspects in the regions.

#### **Author details**

#### Adel Spotin

Address all correspondence to: Espotina@tbzmed.ac.ir ; Adelespotin@gmail.com

Department of Parasitology and Mycology, Tabriz University of Medical Sciences, Tabriz, Iran

#### **References**


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#### **Chapter 5**

## **Brain Hydatid Cyst**

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88 Current Topics in Echinococcosis

Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/60820

#### **Abstract**

Brain echinococcosis is the most common brain parasitic infection in the world. It happens in a very rare location, representing 1% to 2% all cases with hydatid disease. It is more common by approximately 50–70% in pediatric population and young adultswith a male predominance. The definite hosts of echinococcus are various carnivores; man is an accidental host. The growth of hydatid cysts is usually slow and asymptomatic, and clinical manifestations are caused by compression of the involved organ. CT provides definitive results of diagnosis. It shows hydatid cyst as a spherical, well defined, thin walled, homogeneous and non-enhancing cystic lesion without peripheral oedema. Dowling technic is the most commonly done procedure designed to give birth to the intact cyst by irrigating saline between cyst wall-brain interfaces. Medical treatment can be indicated in multiple locations and in cases with peropera‐ tive rupture. Prognosis is often good, but same complications can occur after surgery and depend on the location, the size, the number of cysts and the technique used.

**Keywords:** Brain hydatid cyst, Echinococcosis, CT, Dowling technic

#### **1. Introduction**

Echinococcosis, also referred to as hydatid disease, is a general term used to define zoonosis caused by Echinococcus tapeworms, or cestodes. There are four types of Echinococci, the most common seen worldwide is Echinococcus granulosis whose adult form parasite the dog's small intestine and the larval form that develops in humans, and alveolar echinococcosis, caused by *Echinococcus multilocularis* and restricted to the northern hemisphere (12). Echinococcosis of the central nervous system is the most common brain parasitic infection in the world. It is a

© 2015 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

cosmopolitan anthropozoonosis and represents a significant public health problem. Humans are the accidental intermediate host in the life cycle of this genus. Intracranial pressure, seizure and focal deficit are common signs. CT scan and MRI are the choice exams. Surgery is the radical treatment.

#### **2. Epidemiology**

Hydatid disease is endemic in Mediterranean countries, Middle East, South America, North Africa and Australia (14). The achievement pulmonary pleura is the second frequency (15– 40%) after the liver and associated to brain localization in 30% (7). Intracranial hydatid disease is rare, with reported incidence of 1–2% of all cases with hydatid disease (1,5). There are less than 5 cases per year in our practice (15). Cerebral hydatid disease is more common in pediatric population and young adults approximately 50–70%, with a male predominance. Sixty percent of our patients were males (9,15). Patients with cerebral hydatid cysts may have hydatid cysts in other organs in 10% to 28% of the cases, especially hepatic, pulmonary abut other organs. In general abdominal ultrasound and chest X-ray are sufficient to determine those locations.

#### **3. Pathophysiology**

Hydatid disease is due to the larval form of Taenia dog. The definite hosts of echinococcus are various carnivores, the common being the dog, which develop the adult worm in the gut following ingestion of the larvae that are present in the tissues of the intermediate host (typically sheep and goats and occasionally, humans) and then go on to develop in the visceral tissue, particularly in the liver and lungs. Man is an accidental host. He gets infected through the faeco-oral route by ingestion of food contaminated by dog faeces containing ova of the parasite or by direct contact with dogs. The embryos pass through the wall of the gut into the portal system and are carried to the liver where most larvae get entrapped and encysted. Some may reach the lungs and occasionally, some may pass through the capillary filter of the liver and lungs and get entry into the systemic circulation, to the brain or bone (6). The cerebral hydatid cysts are slow growing and present late when they increase in size and become large. There is no consensus on the growth rate of the hydatid cysts of the brain and has been variably reported between 1.5 and 10 cm/year (5). Intracranial hydatid cyst may also be classified as primary or secondary. The primary cysts are formed as a result of direct infestation of the larvae in the brain without demonstrable involvement of other organs. In the human host, a hydatid cyst can lead to life-threatening complications, such as cyst rupture, with the spread of new cysts, and bacterial infection.

There are some risk factors. Rural origin of adult patients was reported in over 70% of cases (1). Exposure may be the result of contact with dogs from breeders, farmers, butchers, veterinarians, or during recreational activities (hunting). Comorbidity is observed in some adults patients such as hypertension, diabetes, chronic lung disease or hepatitis.

#### **4. Pathology**

cosmopolitan anthropozoonosis and represents a significant public health problem. Humans are the accidental intermediate host in the life cycle of this genus. Intracranial pressure, seizure and focal deficit are common signs. CT scan and MRI are the choice exams. Surgery is the

Hydatid disease is endemic in Mediterranean countries, Middle East, South America, North Africa and Australia (14). The achievement pulmonary pleura is the second frequency (15– 40%) after the liver and associated to brain localization in 30% (7). Intracranial hydatid disease is rare, with reported incidence of 1–2% of all cases with hydatid disease (1,5). There are less than 5 cases per year in our practice (15). Cerebral hydatid disease is more common in pediatric population and young adults approximately 50–70%, with a male predominance. Sixty percent of our patients were males (9,15). Patients with cerebral hydatid cysts may have hydatid cysts in other organs in 10% to 28% of the cases, especially hepatic, pulmonary abut other organs. In general abdominal ultrasound and chest X-ray are sufficient to determine those locations.

Hydatid disease is due to the larval form of Taenia dog. The definite hosts of echinococcus are various carnivores, the common being the dog, which develop the adult worm in the gut following ingestion of the larvae that are present in the tissues of the intermediate host (typically sheep and goats and occasionally, humans) and then go on to develop in the visceral tissue, particularly in the liver and lungs. Man is an accidental host. He gets infected through the faeco-oral route by ingestion of food contaminated by dog faeces containing ova of the parasite or by direct contact with dogs. The embryos pass through the wall of the gut into the portal system and are carried to the liver where most larvae get entrapped and encysted. Some may reach the lungs and occasionally, some may pass through the capillary filter of the liver and lungs and get entry into the systemic circulation, to the brain or bone (6). The cerebral hydatid cysts are slow growing and present late when they increase in size and become large. There is no consensus on the growth rate of the hydatid cysts of the brain and has been variably reported between 1.5 and 10 cm/year (5). Intracranial hydatid cyst may also be classified as primary or secondary. The primary cysts are formed as a result of direct infestation of the larvae in the brain without demonstrable involvement of other organs. In the human host, a hydatid cyst can lead to life-threatening complications, such as cyst rupture, with the spread

There are some risk factors. Rural origin of adult patients was reported in over 70% of cases (1). Exposure may be the result of contact with dogs from breeders, farmers, butchers, veterinarians, or during recreational activities (hunting). Comorbidity is observed in some

adults patients such as hypertension, diabetes, chronic lung disease or hepatitis.

radical treatment.

90 Current Topics in Echinococcosis

**2. Epidemiology**

**3. Pathophysiology**

of new cysts, and bacterial infection.

Hydatid cyst is formed by two membranes. First is an outer circular membrane made of concentric layers acidophilic, soft and acellular, milky characteristic appearance. And another is an internal germinal membrane, thin, grainy and nucleate. The cyst contains a liquid compound NaCl, carbohydrate, protein and lipid. This liquid has a spring water appearance if the cyst is healthy, opalescent or purulent if infected. Daughter vesicles fertile cyst containing 10 to 100 scolex, born of the germinal membrane and bathed in liquid hydatid. This explains the interest to evacuate the block cyst to avoid dissemination. Between brain tissue and cyst volume increase, forms a third membrane or adventitious, easy peel and helps to better remove the cyst fluid (3).

#### **5. Clinical presentation**

The growth of hydatid cysts is usually slow and asymptomatic, and clinical manifestations are caused by compression of the involved organ. The average time before diagnosis is 7 months (15 days to 3 years). The patients with intracranial hydatid cysts usually present with features of raised intracranial pressure may be complicated by blindness or loss consciousness; focal neurological deficit and seizure. Papilloedema is usually present in patients with intracranial hydatid cysts at the time of diagnosis.

#### **6. Diagnosis**

#### **6.1. Imagery**

CT provides definitive results of diagnosis. The exact location, size and number of hydatid cysts in the brain can be determined with a CT scan. However, MR is becoming more and more widely used as a diagnostic tool as it can show details that cannot be seen on CT (18). CT scan and MRI characteristically show hydatid cyst as a spherical, well defined, thin walled, homogeneous and non-enhancing cystic lesion without peripheral oedema. The fluid density is generally equal to that of CSF. The cyst wall usually show a rim of low signal intensity on both T1- and T2-weighted images (Figures 1 and 2). The presence of daughter cysts is consid‐ ered pathognomonic but has been rarely reported (18). Compression of the midline structures and ventricles are seen in most of the cases, however surrounding oedema is usually absent in uncomplicated cases.

Intracranial hydatid can occur anywhere within the brain, but are more frequently located in the supratentorial compartment, especially in the middle cerebral artery territory. The parietal lobe is the most common site with 69% (11). Cerebellar location (Figure 3) is rare and serious with the risk of cerebral herniation and very rarely in the ventricles (18).

**Figure 1.** CT scan of solitary cerebral hydatid cyst.

**Figure 2.** MRI T1 weighted image of multiple cerebral hydatid cyst.

**Figure 3.** CT scan of double cerebellar hydatid cyst.

Exceptionally the skull can be reached after meningeal invasion (10). Cysts may be single or multiple (Figure 4), uni-or multiloculated. Intracranial hydatid cysts are commonly solitary in 93% (11). Multiple intracranial cysts are rare (18). We have reported 3.4% of each multiple and multiloculated hydatid cysts (15). They result from spontaneous, traumatic or surgical rupture of a solitary primary cyst or as a consequence of a cyst rupture elsewhere and embolization of hydatids to the brain. In those cases it necessary to search a cardiac location (2). A few cases of calcified or infected cyst were reported in the literature as in our series (10,11). The differ‐ ential diagnosis of intracerebral hydatid cysts includes cystic lesions such as arachnoid cyst, cystic tumor of the brain and pyogenic abscess. In contrast to hydatid cysts, arachnoid cysts are not spherical in shape and not surrounded entirely by brain substance. Arachnoid cysts are extra-axial masses that may deform adjacent brain. Cystic tumors of the brain could be differentiated by the enhancement of the mural nodule. When a pyogenic abscess shows a cystlike central necrotic area, peripheral oedema is almost always present and the rim enhances intensely following contrast administration (18). Proton MR spectroscopy and diffusionweighted MR imaging have been used to distinguish between cerebral abscess and cystic or necrotic brain tumor. Shukla-Dave et al. (16) reported three cases of hydatid cysts demon‐ strated an increase in lactate, acetate and succinate.

#### **6.2. Biology**

**Figure 1.** CT scan of solitary cerebral hydatid cyst.

92 Current Topics in Echinococcosis

**Figure 2.** MRI T1 weighted image of multiple cerebral hydatid cyst.

The definitive diagnosis is by physical imaging methods – CT and MRI. Immunodiagnosis can also play an important complementary role. It is useful not only for primary diagnosis but also for follow-up of patients after surgical or pharmacological treatment. The enzyme-linked

**Figure 4.** MRI T2 weighted image of multiple cerebral hydatid cyst.

immunosorbent assay (ELISA), the indirect immunofluorescence antibody test, immunoelec‐ trophoresis, and immunoblotting are the hydatid serological testing in laboratory application (12,17). ELISA for specific anti-echinococcus IgG and IgE titer detection is frequently used in cystic echinococcosis serological diagnosis and screening, as it requires a short preparation time, and shows a sensitivity and specificity of 95%. (11). But in primary brain location, it is rarely positive. It was positive in less than 4% in our series. Hyper-eosinophilia can be observed in cases with other visceral location bone. In the literature, cystic echinococcosis diagnosis and follow-up eosinophil cell counts have usually been considered of limited value because it is significantly high in no more than half of CE affected patients (6). Sedimentation rate is normal in healthy cyst, and can be accelerated if infected.

#### **7. Treatment**

The treatment of hydatid cyst is surgical and the aim of surgery is to excise the cyst in toto without rupture to prevent recurrence and anaphylactic reaction.

#### **7.1. Surgery**

The most commonly done procedure designed to give birth to the intact cyst by irrigating saline between cyst wall-brain interfaces (Figure 5). This technique, reported by Dowling and improved by Arana-Iniguez, is possible because of minimal adhesions around the cyst wall (4). Aspiration of the cystic contents through puncturing during the surgery for deep-seated cyst or cysts which located in critical areas is an alternative method, especially as multiple hydatid cysts resulting from the rupture of a primary cyst are infertile and have no broad capsule witch permits the use of Dowling technique. Scolicide product use, as hypertonique saline serum, is essential to protect the brain parenchyma and the risk of dessiminisation in cases of intraoperative ruptured. For multiple and bilateral hydatid cysts the surgery must be done in several times.

**Figure 5.** Dowling technique of solitary cerebral hydatid cyst.

#### **7.2. Medical treatment**

immunosorbent assay (ELISA), the indirect immunofluorescence antibody test, immunoelec‐ trophoresis, and immunoblotting are the hydatid serological testing in laboratory application (12,17). ELISA for specific anti-echinococcus IgG and IgE titer detection is frequently used in cystic echinococcosis serological diagnosis and screening, as it requires a short preparation time, and shows a sensitivity and specificity of 95%. (11). But in primary brain location, it is rarely positive. It was positive in less than 4% in our series. Hyper-eosinophilia can be observed in cases with other visceral location bone. In the literature, cystic echinococcosis diagnosis and follow-up eosinophil cell counts have usually been considered of limited value because it is significantly high in no more than half of CE affected patients (6). Sedimentation rate is normal

The treatment of hydatid cyst is surgical and the aim of surgery is to excise the cyst in toto

in healthy cyst, and can be accelerated if infected.

**Figure 4.** MRI T2 weighted image of multiple cerebral hydatid cyst.

without rupture to prevent recurrence and anaphylactic reaction.

**7. Treatment**

94 Current Topics in Echinococcosis

Only a few reports are available mentioning the efficacy of drug therapy. Albendazole therapy in a daily dose of 10 mg/kg, taken for four months, is a broad spectrum oral antihelminthic drug, which act by blocking glucose uptake of the larvae and the adult worm. The glycogen storage is depleted and thereby decreasing the ATP formation resulting in the death of the parasite (8). We think that medical treatment can be indicated in multiple locations and in cases with peroperative rupture.

#### **8. Post-operative complications**

Same complications can occur after surgery and depend on the location, the size, the number of cysts and the technique used. Hyperthermia within non meningitis or superinfection of the residual cavity, can be related to the translational phenomenon of brainstem during the evacuation of the cyst. It can be avoided by keeping the head turned to the opposite side of the lesion.

#### **9. Evolution**

Total recovery of the neurological deficit occurs in the majority of cases "90% in our practice". The risk of recurrence is about 19% and is correlated with the rate of intraoperative rupture of the cyst (6). The mortality is about 9% and is not negligible. Morbidity associated to hydatid cyst boils down a focal deficit or seizure (13).

#### **10. Conclusion**

Cerebral hydatid cyst is a rare disease that occurs in children with a history of contact with dogs. The definite hosts of echinococcus are various carnivores – man is an accidental host. It is most often manifested by intracranial hypertension, seizures and focal neurological deficit. The diagnosis is strongly suspected to brain CT scan. It show hydatid cyst as a spherical, well defined, thin walled, homogeneous and non-enhancing cystic lesion without peripheral oedema. MRI is especially useful in cases of hydatid cyst revamped to make the differential diagnosis with other cystic intracranial process. The positive hydatid serology is only sugges‐ tive. The treatment of choice is surgery with total removal without rupture, using Dowling technic, except in deep location. Medical treatment can be indicated in multiple locations and in cases with peroperative rupture. The prognosis is usually good if early diagnosis and out of multiple brain locations that pose a serious therapeutic problem.

#### **Author details**

Said Hilmani\*

Address all correspondence to: hilmani.said@yahoo.fr

Neurosurgical Department, Hassan II University, Casablanca, Morocco

#### **References**


**9. Evolution**

96 Current Topics in Echinococcosis

**10. Conclusion**

**Author details**

Said Hilmani\*

**References**

cyst boils down a focal deficit or seizure (13).

Total recovery of the neurological deficit occurs in the majority of cases "90% in our practice". The risk of recurrence is about 19% and is correlated with the rate of intraoperative rupture of the cyst (6). The mortality is about 9% and is not negligible. Morbidity associated to hydatid

Cerebral hydatid cyst is a rare disease that occurs in children with a history of contact with dogs. The definite hosts of echinococcus are various carnivores – man is an accidental host. It is most often manifested by intracranial hypertension, seizures and focal neurological deficit. The diagnosis is strongly suspected to brain CT scan. It show hydatid cyst as a spherical, well defined, thin walled, homogeneous and non-enhancing cystic lesion without peripheral oedema. MRI is especially useful in cases of hydatid cyst revamped to make the differential diagnosis with other cystic intracranial process. The positive hydatid serology is only sugges‐ tive. The treatment of choice is surgery with total removal without rupture, using Dowling technic, except in deep location. Medical treatment can be indicated in multiple locations and in cases with peroperative rupture. The prognosis is usually good if early diagnosis and out

of multiple brain locations that pose a serious therapeutic problem.

Neurosurgical Department, Hassan II University, Casablanca, Morocco

[1] Abbassioun K, Amirjamshidi A. Diagnosis and management of hydatid cyst of the central nervous system: Part 2 : hydatid cysts of the skull, orbit and spine. Neurosur‐

[2] Ait Ben Ali S, Hilmani S, Choukri M, Sami A, El Azhari A, Achouri M, Ouboukhlik A, El Kamar A, Boucetta M. Multiple cerebral hydatid cysts of cardiac origin. Neuro‐

Address all correspondence to: hilmani.said@yahoo.fr

gery, Vol. 11, March 2001: 10–16.

chirurgie. 1999 Dec;45(5):426–429.


#### **Chapter 6**

## **Genitourinary Hydatid Disease**

Santosh Kumar and Shivanshu Singh

Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/60904

#### **Abstract**

Genitourinary echinococcosis is an uncommon cyclo-zoonotic disease. It is caused by Echinococcus species. Kidneys are the common target organs in the genitourinary tract. Clinical presentation is usually non-specific. Pre-operative diagnosis requires a high index of suspicion. It should be considered in differential diagnosis of cystic mass of genitourinary tract, especially in endemic regions. Computed tomography, ultrasonography, and antibody testing aid in diagnosing and classifying the stage of the cyst. Although a number of operative techniques have been described, complete removal of germinal layer with daughter cysts without spillage of viable cyst contents with perioperative medical therapy provides an optimum chance of cure with minimal morbidity. Considering the benign nature of the disease, organ preservation is feasible in majority of the cases. The conventional open surgical treatment has evolved into minimally invasive laparoscopic, endoscopic, and even robotic techni‐ ques with concomitant improvement in postoperative and cosmetic outcome. Given the rarity of the disease, no randomized control trial comparing the treatment modalities for genitourinary hydatid exists. Moreover, long-term follow up in many cases is unavailable. Overall, the incidence of local and systemic recurrence is low.

**Keywords:** Genitourinary hydatid, echinococcosis, laparoscopic management

#### **1. Introduction**

Echinococcosis or hydatid disease in humans is caused by larval forms of cestode *Echinococcus granulosus* and rarely by *E. multilocularis* [1]. It's a cyclozoonotic parasitic infection with the liver (45%–75%) and the lung (10%–50%) being the most commonly involved organs [2]. The

© 2015 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

disease is endemic in Middle East Asia, South America, Australia, New Zealand, and Alaska where sheep and cattle rearing are common [3]. Genitourinary tract infestation is rare, with kidneys being the most common target. Renal involvement accounts for 1%–5% of all cases [4]. Cases of adrenal, prostatic, vesicle, retro-vesicle, and even testicular hydatid cyst have been reported in the literature. Imaging plays a key role in the diagnosis and staging of hydatid disease [5, 6]. Definitive therapeutic options include surgical excision or cyst aspiration with instillation of scolicidal agents. Laparoscopy and image guided percutaneous techniques have decreased the morbidity associated with open surgical excision. Medical therapy is commonly used as an adjunct in the perioperative period and as a primary modality in disseminated disease or in patients with poor surgical risk [7].

### **2. Etiopathogenesis and clinical presentation**

Echinococcosis is a zoonotic disease. Definitive hosts are carnivores such as dogs, wolves, and foxes [8]. The adult worms mature in the small intestine of definitive hosts and shed proglottids in their feces. Upon ingestion of these eggs by intermediate hosts (herbivores such as sheep, horses, cattle, pigs, goats, camel, and humans), the oncosphere larva is released in the small intestine and penetrates the mucosa to enter the lamina propria. From there, passive transport occurs to target organs by hematogenous or lymphaticroute, disseminating primarily to the liver, secondarily to the lung, and finally to other organs where it forms the hydatid cyst. The triple layered cyst consists of an inner germinal layer that gives rise to protoscoleces, a middle acellular laminated layer and an outer host-tissue derived fibrous layer. As life cycle depends on carnivores eating infected intermediate hosts, humans are usually a dead end for the parasite.

#### **2.1. Clinical presentation of renal echinococcosis**

Hydatid cysts are typically slow growing and clinical presentation seldom suggests diagnosis [9]. Renal echinococcosis usually presents between the third and fifth decades of life and accounts for 2%–3% of all cases [10]. Renal involvement can occur by hematogenous route or larval migration through retroperitoneal lymphatics [3]. Due to the slow-growing nature of the cyst, the renal echinococcosis remains asymptomatic for years. Most common symptoms are palpable mass, flank pain, hematuria, malaise, and fever [11]. Secondary infection can cause high-grade fever, rigors, malaise, and pain [12]. The only hallmark sign of genitourinary echinococcosis is the presence of hydaturia (presence of daughter vesicles in urine), but this is found in 10%–20% of the cases [13]. Reports suggest that left renal involvement is more common than right probably due to the smaller renal artery [4]. Renal lesions are usually found in the cortex and can be uni- or multilocular [9].

#### **2.2. Clinical presentation of adrenal echinococcosis**

Adrenal involvement is rare and accounts for less than 1% of the cases [14]. It accounts for 6%– 7% of all adrenal cysts [15, 16]. Mostly they are diagnosed incidentally, however, patients may present with vague non-specific dull aching pain in flank. Adrenal hydatid may cause hypertension, known as Goldblatt phenomenon, due to irritation of the functional tissue of the adrenal by the growing cyst [17]. Many authors believe that adrenal involvement is usually secondary and part of a generalized echinococcosis [14, 18].

#### **2.3. Clinical presentation of pelvic echinococcosis**

disease is endemic in Middle East Asia, South America, Australia, New Zealand, and Alaska where sheep and cattle rearing are common [3]. Genitourinary tract infestation is rare, with kidneys being the most common target. Renal involvement accounts for 1%–5% of all cases [4]. Cases of adrenal, prostatic, vesicle, retro-vesicle, and even testicular hydatid cyst have been reported in the literature. Imaging plays a key role in the diagnosis and staging of hydatid disease [5, 6]. Definitive therapeutic options include surgical excision or cyst aspiration with instillation of scolicidal agents. Laparoscopy and image guided percutaneous techniques have decreased the morbidity associated with open surgical excision. Medical therapy is commonly used as an adjunct in the perioperative period and as a primary modality in disseminated

Echinococcosis is a zoonotic disease. Definitive hosts are carnivores such as dogs, wolves, and foxes [8]. The adult worms mature in the small intestine of definitive hosts and shed proglottids in their feces. Upon ingestion of these eggs by intermediate hosts (herbivores such as sheep, horses, cattle, pigs, goats, camel, and humans), the oncosphere larva is released in the small intestine and penetrates the mucosa to enter the lamina propria. From there, passive transport occurs to target organs by hematogenous or lymphaticroute, disseminating primarily to the liver, secondarily to the lung, and finally to other organs where it forms the hydatid cyst. The triple layered cyst consists of an inner germinal layer that gives rise to protoscoleces, a middle acellular laminated layer and an outer host-tissue derived fibrous layer. As life cycle depends on carnivores eating infected intermediate hosts, humans are usually a dead end for the

Hydatid cysts are typically slow growing and clinical presentation seldom suggests diagnosis [9]. Renal echinococcosis usually presents between the third and fifth decades of life and accounts for 2%–3% of all cases [10]. Renal involvement can occur by hematogenous route or larval migration through retroperitoneal lymphatics [3]. Due to the slow-growing nature of the cyst, the renal echinococcosis remains asymptomatic for years. Most common symptoms are palpable mass, flank pain, hematuria, malaise, and fever [11]. Secondary infection can cause high-grade fever, rigors, malaise, and pain [12]. The only hallmark sign of genitourinary echinococcosis is the presence of hydaturia (presence of daughter vesicles in urine), but this is found in 10%–20% of the cases [13]. Reports suggest that left renal involvement is more common than right probably due to the smaller renal artery [4]. Renal lesions are usually found

Adrenal involvement is rare and accounts for less than 1% of the cases [14]. It accounts for 6%– 7% of all adrenal cysts [15, 16]. Mostly they are diagnosed incidentally, however, patients may

disease or in patients with poor surgical risk [7].

100 Current Topics in Echinococcosis

**2.1. Clinical presentation of renal echinococcosis**

in the cortex and can be uni- or multilocular [9].

**2.2. Clinical presentation of adrenal echinococcosis**

parasite.

**2. Etiopathogenesis and clinical presentation**

Primary pelvic hydatid cyst is rare with an incidence of 0.2%–2.25% [19]. Among the pelvic organs, ovaries are most commonly involved [20]. Symptomatology of pelvic echinococcosis is non-specific and can include abdominal pain, menstruation irregularities, infertility, and urinary disturbances [21]. Ovarian echinococcosis can mimic polycystic disease or malignancy [22]. Ovarian echinococcosis can also mimic endometriosis [23]. Although ovarian cysts are usually uni-locular, multilocular cysts have also been described [24]. Uterine echinococcosis can present with menorrhagia, and may be misdiagnosed as molar pregnancy [25]. Due to their large size, they can cause prolonged and obstructed labour requiring caesarean section [26]. Primary hydatid cyst of the broad ligament is extremely rare and may be misdiagnosed as pedunculated fibroid or a paraovarian cyst [27]. In one study of echinococcosis in an endemic region, the incidence of broad ligament echinococcosis was 0.37% among all cases of hydatid cyst [28].

Bladder hydatid cysts are characterized by clinical latency. Acute urinary retention is a commonly reported symptom [29] apart from frequency, urgency, and nocturia. Hydaturia, although specific, is uncommonly reported. Pelvic retrovesicle hydatidosis occurs by perito‐ neal dissemination, hematogenous or lymphatic seeding or spread from rectal mucosa to the perivesicle and pelvic venous plexus [30]. This site is unusual, even in endemic regions [31], accounting for 2% of all genitourinary echinococcosis [32]. They may present with pelvic pain, dysuria, membranuria, lower urinary tract symptoms, and hematospermia or may mimic ovarian cysts in females [32, 33]. Larger cysts may lead to urinary retention, ureteric compres‐ sion with renal atrophy [34], renal failure, constipation. and even obstructed labour [35] or may develop fistulous communication with the rectum and bladder [36].

Prostatic cysts can be classified in to six categories: 1) isolated medial cysts; 2) cysts of the ejaculatory duct; 3) simple or multiple cysts of the parenchyma; 4) complicated infectious or hemorrhagic cysts; 5) cystic tumors; and 6) cysts secondary to a parasitic disease. Hydatid cyst of the prostate is a rare differential diagnosis of prostatic cyst [37]. Prostatic involvement occurs by hematogenous dissemination with cyst development within the prostatic stroma. They can clinically present as intraprostatic cystic mass. Growing cyst may rupture into the urethra causing hydaturia. Intracystic stone formation can occur due to urinary stagnation.

#### **2.4. Other genitourinary sites of involvement**

Rare case reports of scrotal, testicular, epididymal, and seminal vesicle hydatid cysts exist in literature [38-41]. Blood-testis barrier may account for testicular resistance to echinococcosis [42]. It mimics testicular mass, with diagnosis being proven on final histopathology of orchidectomy specimen. Testicular infestation can be primary or secondary to rupture of an intra-abdominal hydatid cyst [43]. Testicular echinococcosis, although rare, should be remem‐ bered as a differential diagnosis of testicular mass. Seminal vesicle hydatid cysts may present with lower urinary tract symptoms [44].

#### **3. Diagnostic investigation**

Imaging plays a central role in the diagnosis of echinococcosis. Various serological tests have evolved over time and contribute to diagnosis making, although they have low sensitivity [45]. Insensitive and nonspecific tests such as Casoni intradermal test, complement fixation test, indirect hemagglutination, and latex agglutination tests are now replaced by ELISA, immu‐ noelectrophoresis, indirect immunofluorescence antibody test, and immunoblotting in routine laboratory testing [46, 47]. ELISA has positive titers in up to 80% of the cases [9]. Dipstick assays have been developed with nearly 100% sensitivity and approximately 91% specificity [48]. Newer immunodiagnostic tests are based on detection of echinococcal antigens in hydatid fluid fraction. These include *E.granulosus* antigen B (AgB), *E. granulosus* antigen 5 and EpC1. AgB8/2 antigen has provided the highest diagnostic sensitivity (84%–93.1%) and specificity (98%–99.5%) [49, 50]. Serology has a definite role in the follow up of cases, as the titer should fall after definitive treatment [51]. Eosinophilia occurs in 20%–50% of the cases [12].

Ultrasound is the key imaging tool to clinch the diagnosis. It demonstrates the floating membranes, daughter cysts, and hydatid sand apart from demonstrating the site, size, and number of cysts. The WHO/IWG-E classification for diagnosis and treatment is based on ultrasound imaging characteristics. It classifies the cyst into six subtypes (CL, CE1 to CE5) and three relevant groups: active (CE1 and 2), transitional (CE3), and inactive (CE4 and 5) [4]. "CL" is a univesicular, cystic lesion with uniform echoes, clear boundary, and thin visible wall. If it is a hydatid cyst, it is active. "CE1" is a univesicular anechoic cyst with presence of hydatid sand, double wall, and snowflake sign. The disease is active. "CE2" includes multi-vesicular, multi-septated cysts. Cyst septations produce ''wheel-like'' structures, and the presence of daughter cysts is indicated by ''rosette-like'' structure. "CE3a" is the detachment of laminated membrane from the cyst wall, visible as a ''big snake sign'' or as a ''water-lily sign''. The disease status is transitional. "CE3b" shows an intracystic shadow of the daughter vesicles and solid septation, manifested as complex cyst shadow. The parasite is dying. "CE4" has heterogenous, hypoechoic, or hyperechoic contents in the cyst. "CE5" is intracystic solid degeneration and calcification of the cystic wall. The parasite is inactive. Transrectal ultrasound is helpful in evaluating pelvic cystic lesions.

On CT scan, unilocular or multilocular cystic lesions are identified with frequently calcified walls, debris, small daughter cysts, and increased tissue density of hydatid membrane that enhances on intravenous contrast administration [7]. CT scan provides information regarding the number of cysts, the organ of origin, residual parenchyma in the affected organ, and relationship of the cyst with the adjacent structures [Figure 1–4]. This preoperative assessment is essential for planning the approach and type of surgery. Retrograde pyelography may not demonstrate communication with the pelvicalyceal system because of high intracystic pressures [52]. Communication may be demonstrated soon after cyst decompression. CTguided diagnostic needle aspiration is not indicated when echinococcal cyst is suspected due to risk of dissemination and anaphylactic reaction. Magnetic resonance imaging provides better tissue delineation especially in cases of pelvic hydatid cysts. In one study, the preoper‐ ative diagnostic accuracy for serological test was 73.3%, while it was 74% and 87.5% for ultrasound and CT scan respectively [4].

Hydatid cysts should be considered in the differential diagnosis of cystic masses of the genitourinary tract as they can radiologically and clinically mimic tumors, benign and malignant, and other cystic lesions of genitourinary tract.

**Legend:** Contrast-enhanced CT scan of the abdomen (coronal view) showing a multiloculated, exophytic, cystic lesion arising from lower pole of the right kidney with calcification of the cyst wall *(Courtesy: Kumar et al. J Endourol. 2008;22:1709–1713.)*

**Figure 1.** CT imaging of Renal Hydatid.

intra-abdominal hydatid cyst [43]. Testicular echinococcosis, although rare, should be remem‐ bered as a differential diagnosis of testicular mass. Seminal vesicle hydatid cysts may present

Imaging plays a central role in the diagnosis of echinococcosis. Various serological tests have evolved over time and contribute to diagnosis making, although they have low sensitivity [45]. Insensitive and nonspecific tests such as Casoni intradermal test, complement fixation test, indirect hemagglutination, and latex agglutination tests are now replaced by ELISA, immu‐ noelectrophoresis, indirect immunofluorescence antibody test, and immunoblotting in routine laboratory testing [46, 47]. ELISA has positive titers in up to 80% of the cases [9]. Dipstick assays have been developed with nearly 100% sensitivity and approximately 91% specificity [48]. Newer immunodiagnostic tests are based on detection of echinococcal antigens in hydatid fluid fraction. These include *E.granulosus* antigen B (AgB), *E. granulosus* antigen 5 and EpC1. AgB8/2 antigen has provided the highest diagnostic sensitivity (84%–93.1%) and specificity (98%–99.5%) [49, 50]. Serology has a definite role in the follow up of cases, as the titer should

fall after definitive treatment [51]. Eosinophilia occurs in 20%–50% of the cases [12].

Ultrasound is the key imaging tool to clinch the diagnosis. It demonstrates the floating membranes, daughter cysts, and hydatid sand apart from demonstrating the site, size, and number of cysts. The WHO/IWG-E classification for diagnosis and treatment is based on ultrasound imaging characteristics. It classifies the cyst into six subtypes (CL, CE1 to CE5) and three relevant groups: active (CE1 and 2), transitional (CE3), and inactive (CE4 and 5) [4]. "CL" is a univesicular, cystic lesion with uniform echoes, clear boundary, and thin visible wall. If it is a hydatid cyst, it is active. "CE1" is a univesicular anechoic cyst with presence of hydatid sand, double wall, and snowflake sign. The disease is active. "CE2" includes multi-vesicular, multi-septated cysts. Cyst septations produce ''wheel-like'' structures, and the presence of daughter cysts is indicated by ''rosette-like'' structure. "CE3a" is the detachment of laminated membrane from the cyst wall, visible as a ''big snake sign'' or as a ''water-lily sign''. The disease status is transitional. "CE3b" shows an intracystic shadow of the daughter vesicles and solid septation, manifested as complex cyst shadow. The parasite is dying. "CE4" has heterogenous, hypoechoic, or hyperechoic contents in the cyst. "CE5" is intracystic solid degeneration and calcification of the cystic wall. The parasite is inactive. Transrectal ultrasound is helpful in

On CT scan, unilocular or multilocular cystic lesions are identified with frequently calcified walls, debris, small daughter cysts, and increased tissue density of hydatid membrane that enhances on intravenous contrast administration [7]. CT scan provides information regarding the number of cysts, the organ of origin, residual parenchyma in the affected organ, and relationship of the cyst with the adjacent structures [Figure 1–4]. This preoperative assessment is essential for planning the approach and type of surgery. Retrograde pyelography may not demonstrate communication with the pelvicalyceal system because of high intracystic

with lower urinary tract symptoms [44].

**3. Diagnostic investigation**

102 Current Topics in Echinococcosis

evaluating pelvic cystic lesions.

**Legend:** Abdominal MRI revealing a multiloculated hydatid cyst of a kidney with a cyst-in-cyst appearance. *(Courtsey: Kumar et al. Asian J Endosc Surg. 2013;6:342–345.)*

**Figure 2.** MRI of renal hydatid cyst.

**Legend:** Contrast-enhanced computed tomography scan showing a cystic lesion involving the left adrenal gland with‐ out sepatations or daughter cyst. *(Courtesy: Kumar et al. Korean J Urol. 2014;55:493–495.)*

**Figure 3.** CT scan of adrenal hydatid cyst.

**Legend:** Contrast-enhanced CT of the abdomen (sagittal view) showing a retrovesical cyst with left hydroureteroneph‐ rosis. *(Courtesy: Kumar et al. J Endourol. 2008;22:1709–1713.)*

**Figure 4.** CT scan of retrovesicle hydatid cyst.

#### **4. Management**

**Legend:** Abdominal MRI revealing a multiloculated hydatid cyst of a kidney with a cyst-in-cyst appearance. *(Courtsey:*

**Legend:** Contrast-enhanced computed tomography scan showing a cystic lesion involving the left adrenal gland with‐

out sepatations or daughter cyst. *(Courtesy: Kumar et al. Korean J Urol. 2014;55:493–495.)*

*Kumar et al. Asian J Endosc Surg. 2013;6:342–345.)*

**Figure 2.** MRI of renal hydatid cyst.

104 Current Topics in Echinococcosis

**Figure 3.** CT scan of adrenal hydatid cyst.

Treatment depends on disease activity and symptom status. Actively growing or symptomatic cysts need to be treated. Treatment modalities include medical therapy, percutaneous inter‐ vention, and open and minimally invasive surgery. Surgical excision provides the best chance of cure. Medical therapy is used either as an adjunct to surgical excision or as a primary mode of treatment in poor surgical candidates, cases of disseminated hydatidosis, or cases of brain or bony hydatidosis [7]. Preoperative therapy with albendazole (10–15 mg/kg per day) with or without praziquantel (50 mg/kg) for 4 weeks before surgery may kill the scolices, decrease cyst material antigenicity, make the cyst inactive, reduce cyst wall tension thereby reducing risk of spillage [15]. In a study by Arif et al. on liver echinococcosis, patients who received preoperative Albendazole had a recurrence rate of 4.16%, while it was 18.75% in those who did not receive Albendazole [53]. One of the limitations of medical therapy is the serious drugrelated adverse effect such as hepatotoxicity, leukopenia, allergic reactions, and alopecia [54] and the limited amount of literature available on its use in genito-urinary echinococcosis.

Percutaneous puncture, aspiration, instillation of scolicidal agent, and re-aspiration techniques (PAIR) under ultrasound guidance have been devised in an attempt to reduce the morbidity associated with open surgical procedures in cases of unilocular cysts not communicating with the pelvicalyceal system. However, it carries the risk of dissemination of daughter cysts and lethal anaphylaxis has been reported in 0.03%–0.04% of percutaneous procedures [55].

The surgical treatment planning for renal hydatid is based on residual renal function, hydatid cyst size, location, number, and degree of renal involvement. With the advent of minimally invasive surgery, the morbidity associated with open surgery has reduced. Smaller incisions result in reduced wound-related complications, early ambulation, and early return to work. Surgical treatment options for renal echinococcosis include cysto-pericystectomy, cyst deroofing with endocyst evacuation, and partial or total nephrectomy. Laparoscopic manage‐ ment of renal hydatid cyst dates back to 1991 and includes laparoscopic cystopericystectomy, laparoscopic partial nephrectomy, laparoscopic aspiration, instillation of scolicidal agent, and suction [52]. Superficial hydatid cysts involving little renal parenchyma can be managed by pericystectomy while larger, deep seated cysts may require partial cystectomy or de-roofing withomentopexy,partial ortotalnephrectomy.Inmost cases,nephrectomy canbe avoidedand kidneycanbepreservedconsideringthebenignnatureofthedisease andthe factthatinhydatid cyst, the renal parenchyma is compressed and not invaded. Ex-vivo surgery with orthotopic replantation of the kidney for a centrally located hydatid cyst has been performed with good short-term outcome [56]. Partial nephrectomy may be necessary forthickened or calcified cysts with doubtful diagnosis [7]. Nephron-sparing surgeries are possible in 75% of the cases [57]. Nephrectomy may be needed in cases where the entire kidney is replaced by a hydatid cyst or in cases of poorly functioning kidney, cyst hemorrhage, cyst infection, or communicating cyst [7]. Techniques of controlled evacuation are used to prevent spillage and dissemination of daughter cysts. In controlled evacuation, one third of the cyst content is aspirated, followed by instillation of scolicidal agents such as 30% sodium chloride, 10% povidone iodine, 0.5% silver nitrate, or 95% ethanol [12, 15]. Moreover, during surgery, the cysts should be packed on all sideswithgauze soakedinscolicidal solutions including20%normal saline solution, 1%iodine, 10% cetrimide, 10% povidone-iodine, or 0.5% silver nitrate [58].

The laparoscopic approach for hydatid cyst management is safe and feasible with better postoperative recovery. The smaller incision, as compared to conventional open surgery leads to less postoperative pain, and wound-related complications. During surgery for hydatid cyst, the anesthetist should be ready with epinephrine injections, should severe anaphylactic reaction occur [58]. Both transperitoneal and retroperitoneal laparoscopic approaches have been described [59]. Transperitoneal approach provides a larger working space outside the Gerota fascia and prevents inadvertent cyst rupture [60]. Two of the main challenges in minimal invasive surgery for hydatid disease are the risk of intraperitoneal spillage and the difficult evacuation of particulate cyst contents including the daughter cyst and laminated membranes. However, even giant multilocular renal hydatid cysts have been successfully treated by percutaneous nephroscopic aspiration, instillation, and re-aspiration through single-incision laparoscopic approach—the Santosh-PGI technique (Figure 5) [52]. In this technique following pneumoperitoneum, three conventional laparoscopic trocars with cannula (one 10 mm and two 5 mm) are inserted through a single periumbilical incision. After medial mobilization of the colon, the cyst is punctured with a 18-gauge 20 cm puncture needle introduced through the right lumbar region. 10% povidone-iodine solution is instilled for 10 minutes, followed by the passage of a 0.8128 mm Terumo guidewire through the puncture needle. The tract is dilated with Amplatz dilators to accommodate 30 French instruments. Two separate camera monitors are used: one for laparoscopy and the other for hydatid cystoscopy. A suction catheter is placed through the 5-Fr periumbilical port to help suck out small amount of fluid that may spill during the process of tract dilatation. Following dilatation of tract with Amplatz dilator, a 24-French caliber 25-degree nephroscope is introduced into the cyst and the contents are aspirated under vision followed by the removal of the laminated membrane with grasping forceps. This is an attractive technique because of its acceptable success rate and reduced morbidity. It highlights the feasibility of successful laparoscopic treatment even in cases of a giant hydatid cyst. Laparoscopic guidance for cysts puncture avoids inadvertent colonic injury. The use of conventional laparoscopic instruments through a single periumbil‐ ical incision not only reduces operative costs but also provides excellent cosmesis.

did not receive Albendazole [53]. One of the limitations of medical therapy is the serious drugrelated adverse effect such as hepatotoxicity, leukopenia, allergic reactions, and alopecia [54] and the limited amount of literature available on its use in genito-urinary echinococcosis.

106 Current Topics in Echinococcosis

Percutaneous puncture, aspiration, instillation of scolicidal agent, and re-aspiration techniques (PAIR) under ultrasound guidance have been devised in an attempt to reduce the morbidity associated with open surgical procedures in cases of unilocular cysts not communicating with the pelvicalyceal system. However, it carries the risk of dissemination of daughter cysts and lethal anaphylaxis has been reported in 0.03%–0.04% of percutaneous procedures [55].

The surgical treatment planning for renal hydatid is based on residual renal function, hydatid cyst size, location, number, and degree of renal involvement. With the advent of minimally invasive surgery, the morbidity associated with open surgery has reduced. Smaller incisions result in reduced wound-related complications, early ambulation, and early return to work. Surgical treatment options for renal echinococcosis include cysto-pericystectomy, cyst deroofing with endocyst evacuation, and partial or total nephrectomy. Laparoscopic manage‐ ment of renal hydatid cyst dates back to 1991 and includes laparoscopic cystopericystectomy, laparoscopic partial nephrectomy, laparoscopic aspiration, instillation of scolicidal agent, and suction [52]. Superficial hydatid cysts involving little renal parenchyma can be managed by pericystectomy while larger, deep seated cysts may require partial cystectomy or de-roofing withomentopexy,partial ortotalnephrectomy.Inmost cases,nephrectomy canbe avoidedand kidneycanbepreservedconsideringthebenignnatureofthedisease andthe factthatinhydatid cyst, the renal parenchyma is compressed and not invaded. Ex-vivo surgery with orthotopic replantation of the kidney for a centrally located hydatid cyst has been performed with good short-term outcome [56]. Partial nephrectomy may be necessary forthickened or calcified cysts with doubtful diagnosis [7]. Nephron-sparing surgeries are possible in 75% of the cases [57]. Nephrectomy may be needed in cases where the entire kidney is replaced by a hydatid cyst or in cases of poorly functioning kidney, cyst hemorrhage, cyst infection, or communicating cyst [7]. Techniques of controlled evacuation are used to prevent spillage and dissemination of daughter cysts. In controlled evacuation, one third of the cyst content is aspirated, followed by instillation of scolicidal agents such as 30% sodium chloride, 10% povidone iodine, 0.5% silver nitrate, or 95% ethanol [12, 15]. Moreover, during surgery, the cysts should be packed on all sideswithgauze soakedinscolicidal solutions including20%normal saline solution, 1%iodine,

The laparoscopic approach for hydatid cyst management is safe and feasible with better postoperative recovery. The smaller incision, as compared to conventional open surgery leads to less postoperative pain, and wound-related complications. During surgery for hydatid cyst, the anesthetist should be ready with epinephrine injections, should severe anaphylactic reaction occur [58]. Both transperitoneal and retroperitoneal laparoscopic approaches have been described [59]. Transperitoneal approach provides a larger working space outside the Gerota fascia and prevents inadvertent cyst rupture [60]. Two of the main challenges in minimal invasive surgery for hydatid disease are the risk of intraperitoneal spillage and the difficult evacuation of particulate cyst contents including the daughter cyst and laminated membranes. However, even giant multilocular renal hydatid cysts have been successfully

10% cetrimide, 10% povidone-iodine, or 0.5% silver nitrate [58].

**Legend:** Surgical procedure. (a) Three conventional laparoscopic trocars, one 10 mm and two 5 mm, were inserted through the umbilical incision. (b) Laparoscopic guidance was used to puncture the cyst. (c) Tract dilatation with Am‐ platz dilators. (d,e) With the help of a nephroscope, all the cyst contents were aspirated until the clear cyst wall could be seen all around. (f) Injection of 10% povidone-iodine solution. (g) Cyst removal with grasping forceps through the nephroscope. (h) Deroofing the cyst. (i) Placement of the Portex drain into cyst cavity. (j) Closed port site. (k) Removed cyst contents. *(Courtesy: Kumar et al. Asian J Endosc Surg. 2013;6:342–345.)*

**Figure 5.** Percutaneous nephroscopic management of an isolated giant renal hydatid cyst guided by single-incision laparoscopy using conventional instruments: The Santosh-PGI technique.

The Palanivelu Hydatid System (PHS) helps in the controlled evacuation of the cyst contents, laparoscopically minimizing the fear of intraperitoneal spillage [61]. It consists of a 12 mm trocar and cannula assembly along with 5 mm and 8 mm reducers. The pyramidal tip of the trocar has fenestrations and the shaft is hollow to accommodate suction cannula. The 26 cm long cannula has 12 mm inner diameter with suction and irrigation channels [Figure 6]. This unique architecture of trocar and cannula allows for easy suction of scolices, as well as avoids spillage of contents. Following aspiration, the same cannula can be used for visualization of intracystic architecture and rule out its communication with the collecting system. Following the aspiration of the scolicidal agent after 10 minutes of contact time, the residual cyst can be marsupialized or excised depending on the location. The specimen is retrieved through a specimen retrieval bag.

**Legend:** Palanivelu hydatid system showing the long trocar and cannula with two side channels for suction and irriga‐ tion.

**Figure 6.** The Palanivelu Hydatid System (PHS).

Retroperitoneoscopic approach further minimizes the risk of intraperitoneal spillage of cyst contents. With the increasing experience in retroperitoneoscopy, reports of retroperitoneo‐ scopic hydatid cyst excision are emerging [62]. The technique involves standard three-port (5 mm, 10 mm, 10 mm) retroperitoneal access under the vision of a 30-degree telescope at 90 degree flank position, with the help of balloon dilatation. The cyst wall is packed with gauze soaked in scolicidal agent. In the technique described by Ozden and colleagues, a purse-string suture was placed on the cyst wall followed by cyst perforation with hook dissector. The fluid content was aspirated, followed by the instillation of scolicidal agent. Cystopericystectomy was performed and the intact cyst could be removed. The authors emphasize the technical feasibility of this approach, along with the advantage of limited risk of intraperitoneal spillage. Surgical management of adrenal hydatid cyst involves partial or complete excision of the cyst by laparoscopic or open techniques. In a series of nine cases by Ackay and collea‐ gues, adrenalectomy was performed in all cases with no recurrence at a median followup of 16 months (range: 6–64 months)[14]. Due to the limited amount of available data, it is difficult to say whether complete excision of adrenal is mandatory. Kumar and collea‐ gues did transperitoneal laparoscopic aspiration with instillation of scolicidal agent with partial cystectomy for adrenal hydatid cyst. The area around the cyst was packed with Betadine-soaked gauze pieces. The cyst was aspirated during the procedure followed by the instillation of the scolicidal agent and maintained for 10 minutes. An appropriate plane between the cyst and adrenal gland could not be made. A 10 mm trocar was introduced inside the cyst and the cyst contents were sucked out, including the germinal layer. Partial excision of the cyst wall was done as it was adherent to renal vessels. Patient had no recurrence at sixth-month follow up. Total adrenalectomy may not be essential and may be required only when there is complete destruction of the gland [63]. Complete evacua‐ tion of the cyst contents, along with the prevention of intraperitoneal spillage of viable scolices, is the key principle in managing the adrenal hydatid cyst.

The Palanivelu Hydatid System (PHS) helps in the controlled evacuation of the cyst contents, laparoscopically minimizing the fear of intraperitoneal spillage [61]. It consists of a 12 mm trocar and cannula assembly along with 5 mm and 8 mm reducers. The pyramidal tip of the trocar has fenestrations and the shaft is hollow to accommodate suction cannula. The 26 cm long cannula has 12 mm inner diameter with suction and irrigation channels [Figure 6]. This unique architecture of trocar and cannula allows for easy suction of scolices, as well as avoids spillage of contents. Following aspiration, the same cannula can be used for visualization of intracystic architecture and rule out its communication with the collecting system. Following the aspiration of the scolicidal agent after 10 minutes of contact time, the residual cyst can be marsupialized or excised depending on the location. The specimen is retrieved through a

**Legend:** Palanivelu hydatid system showing the long trocar and cannula with two side channels for suction and irriga‐

Retroperitoneoscopic approach further minimizes the risk of intraperitoneal spillage of cyst contents. With the increasing experience in retroperitoneoscopy, reports of retroperitoneo‐ scopic hydatid cyst excision are emerging [62]. The technique involves standard three-port (5 mm, 10 mm, 10 mm) retroperitoneal access under the vision of a 30-degree telescope at 90 degree flank position, with the help of balloon dilatation. The cyst wall is packed with gauze soaked in scolicidal agent. In the technique described by Ozden and colleagues, a purse-string suture was placed on the cyst wall followed by cyst perforation with hook dissector. The fluid content was aspirated, followed by the instillation of scolicidal agent. Cystopericystectomy was performed and the intact cyst could be removed. The authors emphasize the technical feasibility of this approach, along with the advantage of limited risk of intraperitoneal spillage.

specimen retrieval bag.

108 Current Topics in Echinococcosis

tion.

**Figure 6.** The Palanivelu Hydatid System (PHS).

Retrovesicle hydatid cyst contains small bowel, sigmoid colon, rectum, ureter, urinary bladder, pelvic vessels, or internal genitelia of females as part of the pericyst. Although complete cyst excision has been described in few reports [64], it carries a high risk of inadvertent pelvic visceral injury. The narrow pelvic space along with dense adhesions to the surrounding structures may render difficulties in complete excision of pelvic hydatid cysts. Few case reports exist in literature regarding their management. In cases of pelvic or peri-vesical hydatid, where the cyst is large and adherent to adjacent vital organs, partial excision of hydatid cyst with adequate drainage is an acceptable alternative [7]. Laparoscopic cyst aspiration with instilla‐ tion of scolicidal agent (LAIS) and suction has been successfully employed in the perivesical hydatid cyst (Figure 7) [7]. In this technique, pneumoperitoneum is created using Verres' needle in the epigastrium. Four ports are placed: a 12 mm camera port in the midline above the umbilicus; two 12 mm lateral working ports in the lower abdomen at lateral border of rectus; and an additional 5 mm port can be placed in the iliac fossa to help in retraction. Laparoscopy guided percutaneous puncture of the cyst with an 18 G needle is performed, followed by aspiration with instillation of scolicidal agent. The procedure is repeated to ensure the instillation of the scolicidal agent into the entire cyst. The ectocyst is opened and the lateral port is negotiated into the cyst for complete cyst evacuation using a wide-bore suction cannula followed by visual inspection of the cyst lumen to ensure the complete removal of scolices. Complete ectocyst excision is difficult with associated risk of inadvertent bladder-bowel injury. However, even in cases with partial or no excision of ectocyst, complete evacuation of daughter cysts, germinal layer, and lamellated membrane combined with medical therapy results in an acceptable short-term outcome. Even partial cystectomy can be difficult and may lead to inadvertent adjacent visceral injury [7]. However, on table recognition of such com‐ plication and primary repair reduces post-operative morbidity. With the advances in laparo‐ scopic techniques, such visceral injuries can be managed laparoscopically.

**Legend:** (a) Laparoscopic-guided percutaneous cyst puncture, aspiration, and instillation of 10% povidone iodine solu‐ tion. (b) Cyst contents and laminated membrane being sucked out through the port using a wide-bore suction cannula. (c) Excision of part of the ectocyst led to iatrogenic bladder injury, which was repaired by intra-corporeal suturing. *(Courtesy: Kumar et al. J Endourol. 2008;22:1709–1713.)*

**Figure 7.** LAIS for retrovesicle hydatid cyst.

The PHS system has also been successfully used for managing pelvic echinococcal cysts [65]. Ports include a 12 mm midline supra-umbilical port, two para-rectal lower abdominal ports (12 mm and 5 mm) and an accessory port in iliac fossa. After dissecting the ectocyst from adjacent viscera, Betadine-soaked gauzes are placed around the cyst. The puncture and aspiration technique is similar to the one described for renal echinococcosis. Complex retro‐ vesicle echinococcal cysts may communicate with the bladder or rectum [36]. Their manage‐ ment is a challenge. Retrovesicle cysts communicating with the bladder have been managed with intravesicle instillation of scolicidal agents with good outcome [66]. Pelvic retroperitoneal cysts can also be evacuated by transvaginal route [67].

Nowadays even robot-assissted surgical excision of the pelvic hydatid cyst has been performed [68]. Patient position is same as for robotic radical prostatectomy. Superior magnification, 3D vision, and endowrist technology help in the accurate dissection with minimal collateral damage thereby, helping in complete cyst excision. Robot assisted laparoscopic surgery is a safe and feasible option in the management of pelvic hydatid cyst.

Prostatic hydatid cysts are rarely reported with only few case reports discussing their man‐ agement. Sallami et al. described endoscopic management of prostatic hydatid cyst [69]. Surgery was performed under spinal anesthesia. Cystoscopy revealed a bulge in the posterior urethral wall. The posterior wall of the urethra was incised with a cold knife, taking care not to injure the bladder neck and verumontanum. Scolicidal agent was injected, followed by the aspiration of the cyst fluid. The cyst wall was opened, followed by the immediate suction of the cyst contents including the daughter cyst. The germinal layer was completely removed, followed by the re-instillation of the scolicidal agent. Post-procedure, a Foley catheter was placed for four days. Laparoscopic excision of the prostatic hydatid cyst is also safe and feasible [70]. Therapeutic principles are the same.

Preoperative diagnosis of testicular echinococcosis is difficult. In the cases reported, diagnosis was made based on histopathological examination of the orchidectomy specimen. The indications for orchidectomy were either suspicion of testicular malignancy or tuberculosis [39]. Ovarian echinococcal cysts have been rarely reported [22]. Although ovarian cystectomy shall be the ideal treatment, cyst marsupialization with evacuation of daughter cysts also has acceptable results [22].

#### **5. Outcome**

**Legend:** (a) Laparoscopic-guided percutaneous cyst puncture, aspiration, and instillation of 10% povidone iodine solu‐ tion. (b) Cyst contents and laminated membrane being sucked out through the port using a wide-bore suction cannula. (c) Excision of part of the ectocyst led to iatrogenic bladder injury, which was repaired by intra-corporeal suturing.

The PHS system has also been successfully used for managing pelvic echinococcal cysts [65]. Ports include a 12 mm midline supra-umbilical port, two para-rectal lower abdominal ports (12 mm and 5 mm) and an accessory port in iliac fossa. After dissecting the ectocyst from adjacent viscera, Betadine-soaked gauzes are placed around the cyst. The puncture and aspiration technique is similar to the one described for renal echinococcosis. Complex retro‐ vesicle echinococcal cysts may communicate with the bladder or rectum [36]. Their manage‐ ment is a challenge. Retrovesicle cysts communicating with the bladder have been managed with intravesicle instillation of scolicidal agents with good outcome [66]. Pelvic retroperitoneal

Nowadays even robot-assissted surgical excision of the pelvic hydatid cyst has been performed [68]. Patient position is same as for robotic radical prostatectomy. Superior magnification, 3D vision, and endowrist technology help in the accurate dissection with minimal collateral damage thereby, helping in complete cyst excision. Robot assisted laparoscopic surgery is a

*(Courtesy: Kumar et al. J Endourol. 2008;22:1709–1713.)*

cysts can also be evacuated by transvaginal route [67].

safe and feasible option in the management of pelvic hydatid cyst.

**Figure 7.** LAIS for retrovesicle hydatid cyst.

110 Current Topics in Echinococcosis

Majority of the literature available on genitourinary echinococcosis include case series and case reports. Many of the therapeutic principles are extrapolation of the experience with the hepatic hydatid cyst. Given the rarity of the disease, no randomized control trial comparing the treatment modalities for genitourinary hydatid exist. Moreover, long-term follow up in many cases is unavailable. Overall, the incidence of local and systemic recurrence is low. In a series of 30 cases of renal echinococcosis, only one patient had local recurrence, while extrarenal recurrence occurred in three more cases [4]. Risk factors for recurrence includes spillage of viable daughter cysts and scolices, incomplete removal of germinal layer, undetected cyst at other location, and return to endemic area.

#### **6. Conclusion**

Genitourinary echinococcosis is an uncommon disease. Preoperative diagnosis requires a high index of suspicion. It should be considered in differential diagnosis of cystic mass of genito‐ urinary tract, especially in endemic regions. Computed tomography, ultrasonography, and antibody testing aid in diagnosing and classifying the stage of the cyst. Although a number of operative techniques have been described, complete removal of germinal layer with daughter cysts without spillage of viable cyst contents with perioperative medical therapy provide an optimum chance of cure with minimal morbidity. Considering the benign nature of the disease, organ preservation is feasible in majority of the cases. The conventional open surgical treat‐ ment has evolved into minimally invasive laparoscopic, endoscopic, and even robotic techni‐ ques with concomitant improvement in wound-related morbidity and cosmetic outcome.

#### **Author details**

Santosh Kumar\* and Shivanshu Singh

\*Address all correspondence to: santoshsp1967jaimatadi@yahoo.co.in ; santoshsp1967@ya‐ hoo.co.in

Advanced Urology Center, Department of Urology, Postgraduate Institute of Medical Edu‐ cation and Research. Chandigarh, India

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[61] Chipde SS, Yadav A, Ranjan P, Prakash A, Kapoor R. Total laparoscopic manage‐ ment of a large renal hydatid cyst by using hydatid trocar cannula system. Journal of Surgical Technique and Case Report. 2012;4:32–35. DOI:10.4103/2006-8808.100351 [62] Ozden E, Bostanci Y, Mercimek MN, Yakupoglu YK, Yilmaz AF, Sarıkaya S. Renal hydatid cyst treatment: Retroperitoneoscopic "closed cyst" pericystectomy. Interna‐ tional Journal of Urology. 2011;18:237–239. DOI: 10.1111/j.1442-2042.2010.02703.x [63] Kumar S, Nanjappa B, Gowda KK. Laparoscopic management of a hydatid cyst of

[64] Turan T, Tuncay L, Kayik S, Atahan O, Aybek Z. Retrovesical hydatid cyst. J Urol.

[65] Subramaniam B, Abrol N, Kumar R. Laparoscopic Palanivelu-hydatid-system aided management of retrovesical hydatid cyst. Indian Journal of Urology: IJU: Journal of

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116 Current Topics in Echinococcosis

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## **Echinococcosis — Rare Locations and Uncommon Clinical Manifestations**

Antonio Di Cataldo#, Giuseppe Petrillo#, Claudia Trombatore#, Stefano Palmucci#, Antonella Agodi#, Martina Barchitta, Annalisa Quattrocchi, Nunzio Crimi, Silvia Fichera, Stefano Puleo, Amy Giarrizzo, Martina Calabrini, Rosalia Latino and Rosanna Portale

Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/61126

#### **Abstract**

Echinococcosis is a zoonotic infection caused by tiny tapeworms of the genus Echinocococcus. Cystic Echinococcosis, also known as hydatid disease, is caused by Echinococcus granulosus and rarely by Echinococcus multilocularis.

Although the worldwide incidence and prevalence of Echinococcosis dramatically decreased in the last decades, it remains a major public health issue in several countries, where the infection is currently considered an endemic disease.

The disease is characterized by cystic lesions especially in the liver and lungs. If the parasites go beyond the lung filter, it can spread to other locations that are classified as rare, very rare, or extremely rare locations.

In these rare locations, the disease is often asymptomatic and is frequently incidentally diagnosed.

Usually, there are mechanical clinical features that will be different according to the organ where the cyst is located. Serological tests, ultrasound, and imaging radiological studies are generally used in order to make the correct diagnosis.

**Keywords:** Echinococcosis, surgical procedures, operative, diagnostic imaging, par‐ asitic diseases, infection

© 2015 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

#### **1. Introduction**

Hydatid disease is a parasitic infection that is endemic in Mediterranean countries, but it is worldwide present in consequence of the migratory phenomena. The disease is characterized by cystic lesions especially located in the liver and in the lungs. If the parasite goes beyond the pulmonary filter, it can spread to other localizations that are classified rare, very rare, or extremely rare locations [1].

#### **2. Epidemiology of Echinococcosis**

Hydatid disease is known since the ancient times and Hippocrates first described it as being located in the liver. *Echinococcosis* is a major parasitic zoonosis, of public health importance worldwide, that in humans occurs in two main forms depending on the causative species: cystic *Echinococcosis* (CE, also known as hydatidosis) and alveolar *Echinococcosis* (AE), caused by the tapeworms *Echinococcus granulosus* and *E. multilocularis*, respectively. Both diseases can cause serious morbidity and death [2, 3] if the management is not correct, and both can be regarded as emerging or re-emerging diseases [4].

CE is globally distributed, with highly endemic areas mostly found in the eastern part of the Mediterranean region, northern Africa, southern and Eastern Europe, at the southern tip of South America, in Central Asia, Siberia, and western China. AE is confined to the northern hemisphere, in particular to regions of western and northern China, the Russian Federation, most countries of continental Europe, and northern countries of North America [3]. CE occurs commonly in Bulgaria, Poland, Slovenia, and in Spain and elsewhere in Eastern and Central Europe, it is considered a serious public health problem in Turkey. AE has also emerged in Central and Eastern Europe in association with increases in fox populations. The infection has been reported in Germany, Lithuania, Slovakia, Slovenia, and Switzerland [5].

CE has a renewed importance in Europe, as reemerging cases have been documented [6]. Furthermore, CE is reported in immigrants or persons with a history of travel to endemic areas [7]. Several national surveillance systems for CE and AE exist in European countries based on voluntary data entry or on compulsory notification [8].

The recent Annual epidemiological report on food and waterborne diseases and zoonoses of the European Centre for Disease Prevention and Control (ECDC) [8] relates that in 2012 the case rate of *Echinococcosis* was 0.19 cases per 100,000 population in the European Union and European Economic Area (EEA) countries. The rate of *Echinococcosis* has been fairly stable in the last years and the number of cases reported with AE has increased, most likely reflecting the increasing spatial distribution of the parasite in animals. The highest population-based risk was noted in Bulgaria, where the notification rate in 2012 was 23 times higher than the overall EU/EEA case rate (4.37 cases per 100,000 population; 39% of the reported number of cases in Europe). No significant differences were found in *Echinococcosis* rates by gender (male-tofemale ratio: 0.98:1 in 2012). The highest case rate was in males aged 65 years old and over (0.22 per 100,000) followed by females aged 65 years old and over (0.17 per 100,000). Rates were generally higher in males than in females for cases aged 25 years and older. Notably, the higher rates observed in the elderly can be explained by the extensive incubation period of several years. Furthermore, no seasonality has been observed for *Echinococcosis*, as expected for a disease with a very long incubation period. The most frequently isolated species was *E. granulosus* (81%), followed by *E. multilocularis* (18%), and by other *Echinococcus* species (1%). Over the last five years, an increasing number of cases infected with *E. multilocularis* (AE) was observed and this is an important issue since untreated disease is often fatal. Notably, as highlighted by the ECDC [8], most European surveillance systems capture only a proportion of the cases occurring in their countries and some cases of disease remain undiagnosed or are diagnosed but not reported to public health authorities. Furthermore, the direct comparison of *Echinococcosis* rates between countries should be undertaken with caution. In fact, in most cases, differences in case rates reflect not only differences in the occurrence of the disease, but also in systematic differences in health and surveillance systems [8].

**1. Introduction**

120 Current Topics in Echinococcosis

extremely rare locations [1].

**2. Epidemiology of Echinococcosis**

regarded as emerging or re-emerging diseases [4].

voluntary data entry or on compulsory notification [8].

Hydatid disease is a parasitic infection that is endemic in Mediterranean countries, but it is worldwide present in consequence of the migratory phenomena. The disease is characterized by cystic lesions especially located in the liver and in the lungs. If the parasite goes beyond the pulmonary filter, it can spread to other localizations that are classified rare, very rare, or

Hydatid disease is known since the ancient times and Hippocrates first described it as being located in the liver. *Echinococcosis* is a major parasitic zoonosis, of public health importance worldwide, that in humans occurs in two main forms depending on the causative species: cystic *Echinococcosis* (CE, also known as hydatidosis) and alveolar *Echinococcosis* (AE), caused by the tapeworms *Echinococcus granulosus* and *E. multilocularis*, respectively. Both diseases can cause serious morbidity and death [2, 3] if the management is not correct, and both can be

CE is globally distributed, with highly endemic areas mostly found in the eastern part of the Mediterranean region, northern Africa, southern and Eastern Europe, at the southern tip of South America, in Central Asia, Siberia, and western China. AE is confined to the northern hemisphere, in particular to regions of western and northern China, the Russian Federation, most countries of continental Europe, and northern countries of North America [3]. CE occurs commonly in Bulgaria, Poland, Slovenia, and in Spain and elsewhere in Eastern and Central Europe, it is considered a serious public health problem in Turkey. AE has also emerged in Central and Eastern Europe in association with increases in fox populations. The infection has

CE has a renewed importance in Europe, as reemerging cases have been documented [6]. Furthermore, CE is reported in immigrants or persons with a history of travel to endemic areas [7]. Several national surveillance systems for CE and AE exist in European countries based on

The recent Annual epidemiological report on food and waterborne diseases and zoonoses of the European Centre for Disease Prevention and Control (ECDC) [8] relates that in 2012 the case rate of *Echinococcosis* was 0.19 cases per 100,000 population in the European Union and European Economic Area (EEA) countries. The rate of *Echinococcosis* has been fairly stable in the last years and the number of cases reported with AE has increased, most likely reflecting the increasing spatial distribution of the parasite in animals. The highest population-based risk was noted in Bulgaria, where the notification rate in 2012 was 23 times higher than the overall EU/EEA case rate (4.37 cases per 100,000 population; 39% of the reported number of cases in Europe). No significant differences were found in *Echinococcosis* rates by gender (male-tofemale ratio: 0.98:1 in 2012). The highest case rate was in males aged 65 years old and over (0.22

been reported in Germany, Lithuania, Slovakia, Slovenia, and Switzerland [5].

Mandatory notification of CE to the Italian Ministry of Health has been discontinued since 1991 (D. Min. San. 15.12.1991), and thus, the data on CE occurrence have only produced by the regional cases summaries. Therefore, information on CE distribution in Italy is still incomplete and insufficient and no data has been submitted for the European surveillance. However, an Italian Registry of CE was established by the Istituto Superiore della Sanità (http://www.iss.it/ riec/). In Italy, the prevalence of the CE is high on the islands and medium in the central and southern regions of Italy [9–10] where farming and raising sheep are frequent activities, confirming that the disease is often an occupational one, and farming and raising sheep seem to be risk factors [11–12]. Data from the Italia registry reports that up to 75% of sheep and goats can be infected and up to 14 cases per 100,000 inhabitants (1,400 cases/year estimated) (http:// www.iss.it/riec/).

As suggested, compulsory notification of *Echinococcosis* and harmonization of the data entry system are essential instruments for the surveillance of human diseases in order to make both clinical and epidemiological data accessible to clinicians, epidemiologists, and policymakers [12]. In fact, surveillance data are useful to assist policymakers and health leaders in making evidence-based decisions to plan and improve programs, services, and interventions for preventing, managing, and treating these diseases [8].

In 2013, the EchinoWorld website (www.echinoworld.org), sponsored by the International Association of Hydatidology, was developed. It provides a feasible and effective platform for professionals and scholars around world in the field of hydatid disease, with the aim to help prevention, diagnosis, and treatment especially in endemic countries and globally.

CE can be prevented by periodic deworming of dogs; improved hygiene in the slaughtering of livestock, including proper destruction of infected offal; and public education campaigns. Vaccination of livestock offers encouraging prospects for prevention and control. The World Health Organization reports that a program combining vaccination of lambs, deworming of dogs, and culling of older sheep could lead to the elimination of human cystic *Echinococcosis* in less than 10 years [3]. Because of the unique sylvatic nature of AE, it is one of the few helminth infections in Europe that is not linked to poverty and inadequate sanitation [1–5]. Prevention and control of AE is particularly complex as the cycle involves wild animal species as both definitive and intermediate hosts. Regular deworming of domestic carnivores that have access to wild rodents should help to reduce the risk of infection to humans. However, sustainability and cost–benefit effectiveness of such campaigns are controversial [3].

#### **3. Unusual locations of echinococcosis**

About 90% of the hydatid cysts occur in the liver (65%–75%) and lungs (15%–20%), organs that can be affected simultaneously in about 5%–13% of the cases. If the cyst goes beyond the hepatic and pulmonary filters, it can spread to other organs. A possible dissemination through lymphatic channels could explain the presence of the cysts in uncommon sites [13].

The diameter of the parasite is about 25 microns–35 microns, and it can pass through the hepatic sinusoids (10 microns–100 microns), depending on the biophysical and structural features of the parasite, which has ameboid movements and different dimensions in the different stages of its biological cycle. It is as an emulsoid that adapts itself to the different diameters of the anatomic structures. Other factors such as pH, surface tension, and the presence of the colloids are also involved in explaining the passage of the parasite through the hepatic sinusoids. However, it is also possible that the parasite reaches the peripheral locations by passing the hepatic sinusoids through the presence of arteriovenous anastomoses or through anastomoses between the portal and hepatic veins. Furthermore, we should believe that the parasite is able to bypass the pulmonary capillary vessels in a similar way, otherwise, the incidence of the parasite in the lungs should be higher than in the liver [14].

In 1964, Grassi classified the peripheral locations of the hydatid disease into three groups:


The percentage of site involvement varies and the exact incidence in unusual locations is about 8%–10%, but it is difficult to ascertain, as they are only reported as case reports [4].

Previous data reported that incidence of CE involving the spleen, kidney, peritoneal cavity, skin, and muscles was about 2-3% each and incidence of the heart, brain, vertebral column, ovaries, pancreas, gall bladder, thyroid gland, bones, and breast involvement was about 1% or less, each [15]. Figure 1 summarizes updated data on frequencies of unusual locations of CE as reported in different scientific articles.

A recent meta-analysis conducted in Iran where *Echinococcosis* is endemic, focused on the unusual locations (i.e., other than the liver and lung) diagnosed in the last 20 years (1990– 2011). About 463 cases of the hydatid cyst located in different parts of the body, exclud‐ ing the liver and lung, have been published from Iran. The most common locations were

\* Only five case reports of testicular location

and control of AE is particularly complex as the cycle involves wild animal species as both definitive and intermediate hosts. Regular deworming of domestic carnivores that have access to wild rodents should help to reduce the risk of infection to humans. However, sustainability

About 90% of the hydatid cysts occur in the liver (65%–75%) and lungs (15%–20%), organs that can be affected simultaneously in about 5%–13% of the cases. If the cyst goes beyond the hepatic and pulmonary filters, it can spread to other organs. A possible dissemination through

The diameter of the parasite is about 25 microns–35 microns, and it can pass through the hepatic sinusoids (10 microns–100 microns), depending on the biophysical and structural features of the parasite, which has ameboid movements and different dimensions in the different stages of its biological cycle. It is as an emulsoid that adapts itself to the different diameters of the anatomic structures. Other factors such as pH, surface tension, and the presence of the colloids are also involved in explaining the passage of the parasite through the hepatic sinusoids. However, it is also possible that the parasite reaches the peripheral locations by passing the hepatic sinusoids through the presence of arteriovenous anastomoses or through anastomoses between the portal and hepatic veins. Furthermore, we should believe that the parasite is able to bypass the pulmonary capillary vessels in a similar way, otherwise, the incidence of the

In 1964, Grassi classified the peripheral locations of the hydatid disease into three groups:

**b.** very rare locations: diaphragm, pancreas, thyroid, brain, salivary glands, subcutaneous

**c.** extremely rare locations: thymus, lymphatic nodes, adrenal gland, hypophysis, tonsils [1]. The percentage of site involvement varies and the exact incidence in unusual locations is about

Previous data reported that incidence of CE involving the spleen, kidney, peritoneal cavity, skin, and muscles was about 2-3% each and incidence of the heart, brain, vertebral column, ovaries, pancreas, gall bladder, thyroid gland, bones, and breast involvement was about 1% or less, each [15]. Figure 1 summarizes updated data on frequencies of unusual locations of

A recent meta-analysis conducted in Iran where *Echinococcosis* is endemic, focused on the unusual locations (i.e., other than the liver and lung) diagnosed in the last 20 years (1990– 2011). About 463 cases of the hydatid cyst located in different parts of the body, exclud‐ ing the liver and lung, have been published from Iran. The most common locations were

8%–10%, but it is difficult to ascertain, as they are only reported as case reports [4].

lymphatic channels could explain the presence of the cysts in uncommon sites [13].

and cost–benefit effectiveness of such campaigns are controversial [3].

**3. Unusual locations of echinococcosis**

122 Current Topics in Echinococcosis

parasite in the lungs should be higher than in the liver [14].

**a.** rare locations: spleen, kidney, bone, muscle;

CE as reported in different scientific articles.

tissue;

(Adrenal gland: Akcay et al., 2004 [42]; Bones and spine: Drimousis et al., 2006 [43]; Brain: Greenberg SM, 2001 [44]; Altas et al., 2010 [45]; Breast: McManus et al., 2003 [15]; Gall Bladder: Raza et al., 2003 [46]; Mushtaque et al., 2011 [47]; Heart: McManus et al., 2003 [15]; Kidney: Gogus et al., 2003 [48]; Muscle: Verasaci et al., 2005 [49]; Arora et al., 2011 [50]; Pancreas: Palaivelu C, 2007 [51]; Moosavi et al., 2007 [52]; Seminal vesicle: Vasileios et al., 2002 [53]; Safioleas et al., 2006 [54]; Skin and subcutaneous tissue: Zulfikaroglu et al., 2005 [55]; Dirican et al., 2008 [56]; Spleen: Polat et al., 2003 [57]; Testes: Tlili et al., 2014 [58]. Thyroid: McManus et al., 2003 [15]; Uterus and ovaries: Arora et al., 2005 [59]; Palaivelu C, 2007 [59])

**Figure 1.** Frequencies of unusual locations of cystic *Echinococcosis* as reported in different scientific articles.

the central nervous system (brain, spinal cord, and orbit), musculoskeletal system, heart, and kidney, whereas some less common locations were the spleen, pancreas, appendix, thyroid, salivary gland, adrenal gland, breast, ovary, retroperitoneum, and mediastinum [16].

With the advent of modern DNA-based methods, the genetic variability of *E. granulosus* was confirmed and a number of genotypes were recognized (named G1–G10). *E. granulosus* comprises several intraspecific variants or strains that have substantial variation at the genetic level. By contrast, there seems to be very limited genetic variation within *E. multilocularis* [17]. A recent study has reported results of analyses conducted on agents responsible for causing 10 cases of cerebral hydatid disease. Strain differentiation was possible for eight cases and all were found to be of the G6 genotype, suggesting that this genotype may have a propensity for infecting the brain [18]. Further genetic investigations in unusual localizations are recom‐ mended to evaluate a possible cluster of genotypes and or subtypes by different location in order to support differential diagnosis of *Echinococcosis* for any cystic mass found in patients, especially from endemic areas [4].

#### **4. Diagnostic serological tests**

Immunodiagnosis is an important tool for diagnosis of hydatid infection. The increase in serum IgE is characteristic for helminthic disease and is stimulated by the synthesis of IL-4 from Th2 lymphocites [19]. Different serological tests were developed and applied. Usually, they detect anti-Echinococcus IgG, but there are also methods for examination of IgE in serum such as RAST (RIA), ELISA, and Western blot. The sensitivity of the ImmunoCAP system, in some studies, is significantly lower than the sensitivity of both the ELISA and Western blot. In contrast, the ImmunoCAP system demonstrated increased specificity and decreased crossreactivity compared with the ELISA. Western blot remains the principle method for the detection of CE because of its significantly higher sensitivity. The lower sensitivity of the ImmunoCAP system for detecting anti-Echinococcus IgE compared with the tests for specific IgG can be explained by the stronger IgG response in CE. Comparison of anti-Echinococcus IgE in hepatic and pulmonary CE showed significant differences in the immune response that were not only qualitative (more often positive in hepatic CE) but also quantitative (lower antibody levels in pulmonary CE). While there was a detectable difference in anti-Echinococ‐ cus IgG by ELISA and Western blot, the discrepancy was not significant. In rare locations of the disease, that are often peripheric locations, serological tests have shown a lower sensitivity. In conclusion, detection of anti-Echinococcus IgE could be applied as an additional confirma‐ tory method when false-positive results are suspected from other immunological tests [20].

#### **5. Imaging features**

Radiological signs of *Echinococcosis* are usually non-specific, and the serologic tests are necessary to confirm the diagnosis [21]. The liver (75%) and lungs (15%) are the most commonly involved organs, but the disease can be seen anywhere in the body (10%) [21–22]. Most typical imaging findings of the hydatid disease are cystic lesions in the affected organs; namely, imaging features vary according to the stage of cyst development [23]. In the early stage, the cysts usually show as a simple cyst, with a homogeneous fluid content with both CT attenu‐ ation values and MRI signal similar than water. Cystic content is generally hypointense on T1 weighted images, and homogeneously hyperintense on T2-weighted sequences. Then, imaging appearance may be slightly different due to the presence of intracystic debris, hydatid sand, and inflammatory cells. During the natural evolution of the hydatid cyst, a ring-like calcification of the cystic wall can be seen and this sign is more common in the liver, spleen, and kidney. However, calcification of the pericyst does not necessarily indicate death of parasite. It is, instead, highly likely when the cyst is completely calcified [24]. The endocyst may detach partially or completely from the pericyst causing "floating membranes" inside the cavity, a finding that is highly specific for hydatid disease. When there are daughter cysts inside the hydatid cyst, it appears multi-vesicular with a "honeycomb pattern" [22] (Figure 2); daughter vesicles are located peripherally and they usually contain fluid with a lower attenuation than that of the fluid in the mother cyst [24].

59. Arora V, Nijjar IS, Gill KS, Singh G: Case report: Primary hydatid cyst of muscle—A rare

In addition to the liver and lungs, echinoccosis could be also found in different other organs; in these cases, the diagnosis could be difficult, and differential diagnosis is generally required.

site. Indian J Radiol Imaging 16: 239–241, 2006.

Figure 2. Typical hydatid cyst of the liver, with some peripheral daughter cysts (arrow). **Figure 2.** Typical hydatid cyst of the liver, with some peripheral daughter cysts (arrow).

60. 61.

**4. Diagnostic serological tests**

124 Current Topics in Echinococcosis

**5. Imaging features**

attenuation than that of the fluid in the mother cyst [24].

Immunodiagnosis is an important tool for diagnosis of hydatid infection. The increase in serum IgE is characteristic for helminthic disease and is stimulated by the synthesis of IL-4 from Th2 lymphocites [19]. Different serological tests were developed and applied. Usually, they detect anti-Echinococcus IgG, but there are also methods for examination of IgE in serum such as RAST (RIA), ELISA, and Western blot. The sensitivity of the ImmunoCAP system, in some studies, is significantly lower than the sensitivity of both the ELISA and Western blot. In contrast, the ImmunoCAP system demonstrated increased specificity and decreased crossreactivity compared with the ELISA. Western blot remains the principle method for the detection of CE because of its significantly higher sensitivity. The lower sensitivity of the ImmunoCAP system for detecting anti-Echinococcus IgE compared with the tests for specific IgG can be explained by the stronger IgG response in CE. Comparison of anti-Echinococcus IgE in hepatic and pulmonary CE showed significant differences in the immune response that were not only qualitative (more often positive in hepatic CE) but also quantitative (lower antibody levels in pulmonary CE). While there was a detectable difference in anti-Echinococ‐ cus IgG by ELISA and Western blot, the discrepancy was not significant. In rare locations of the disease, that are often peripheric locations, serological tests have shown a lower sensitivity. In conclusion, detection of anti-Echinococcus IgE could be applied as an additional confirma‐ tory method when false-positive results are suspected from other immunological tests [20].

Radiological signs of *Echinococcosis* are usually non-specific, and the serologic tests are necessary to confirm the diagnosis [21]. The liver (75%) and lungs (15%) are the most commonly involved organs, but the disease can be seen anywhere in the body (10%) [21–22]. Most typical imaging findings of the hydatid disease are cystic lesions in the affected organs; namely, imaging features vary according to the stage of cyst development [23]. In the early stage, the cysts usually show as a simple cyst, with a homogeneous fluid content with both CT attenu‐ ation values and MRI signal similar than water. Cystic content is generally hypointense on T1 weighted images, and homogeneously hyperintense on T2-weighted sequences. Then, imaging appearance may be slightly different due to the presence of intracystic debris, hydatid sand, and inflammatory cells. During the natural evolution of the hydatid cyst, a ring-like calcification of the cystic wall can be seen and this sign is more common in the liver, spleen, and kidney. However, calcification of the pericyst does not necessarily indicate death of parasite. It is, instead, highly likely when the cyst is completely calcified [24]. The endocyst may detach partially or completely from the pericyst causing "floating membranes" inside the cavity, a finding that is highly specific for hydatid disease. When there are daughter cysts inside the hydatid cyst, it appears multi-vesicular with a "honeycomb pattern" [22] (Figure 2); daughter vesicles are located peripherally and they usually contain fluid with a lower Uncommon locations are briefly discussed, emphasizing imaging features.

*Spleen* is the most common affected organ after the liver and lungs and its involvement ranges from 0.9% to 8%. Primary splenic hydatidos is rare (less than 2%) [22].

Figure 3. Echinococcosis of the left kidney [60]. Splenic cysts are commonly solitary and often develop secondary to systemic dissemination or intraperitoneal spread from ruptured liver hydatid cysts. Differential diagnosis includes epidermoid cyst, pseudocyts, abscess, or hematoma; also cystic neoplasms should be differ‐ entiated from hydatid splenic disease [21].

b Figure 3. Echinococcosis of the left kidney [60]. *Pancreas* is involved very rarely (0.25% of the cases). Patients could aspecific symptoms as abdominal discomfort, nausea, and vomiting. In a case report described by Szanto et al., an hydatic pancreatic cyst was found on the tail of the pancreas, causing portal hypertension and splenic veins congestion [25]. In cases of pancreatic locations, lesions show typical imaging findings: cystic appearance, sometimes with wall calcifications and daughter cysts. Clear fluid content is generally represented hypodense on CT images. Additionally, signs of vascular compression could be detected on CT and MR imaging. Differential diagnosis from other pancreatic cystic lesions (pseudocyst, serous cystadenoma, and mucinous cystic neoplasm) may be difficult; it is based on the presence of a more thickened and laminated cystic wall, often with thin calcifications.

*Kidney* is a rare location of Echinoccosis. Symptoms are often nonspecific and, when the cysts are intact and the antigenic stimulation is too low, imaging is crucial for a correct diagnosis [26]. Renal cysts are usually unilateral and located in the cortex of the upper or lower pole; they appear unilocular or multilocular if there are daughter cysts inside the parental cyst. Three types of cysts have been described by Ishimitsu [27]:

**•** type 1: unilocular cysts (initial stage of parasite development)

60. 61.

**•** type 2: multiple daughter cysts within the mother cyst (intermediate stage of parasitic development)

disease: Report of a case. Ups J Med Sci 110:167–171, 2005.

disease from head to toe. Radiographics 23: 475–494, 2003.

miming a testicular tumor. J Case Reports 4: 151–154, 2014.

site. Indian J Radiol Imaging 16: 239–241, 2006.

the palm and the thigh: Two case reports. J Med Case Rep 2: 273, 2008.

55. Zulfikaroglu B, Koc M, Ozalp N, Ozmen MM: A rare primary location of echinococcal

56. Dirican A, Unal B, Kayaalp C, Kirimlioglu V: Subcutaneous hydatid cysts occurring in

57. Polat P, Kantarci M, Alper F, Suma S, Koruyucu MB, Okur A: Hydatid

58. Tlili G, Bouassida K, Slama A , Tlili T, Ziadi S, Taher MA: Hydatid cyst of the scrotum

59. Arora V, Nijjar IS, Gill KS, Singh G: Case report: Primary hydatid cyst of muscle—A rare

**•** type 3: completely calcified cysts (death of the parasite)

In type 1 and type 2 cysts, the cyst wall may be thick or calcified (Figure 3), and both the wall and the internal septa may show enhancement after e.v. administration of the contrast agent. In up to 18% of cases, the cyst may rupture into the collecting system and at imaging several round filling defects may be seen due to the migration of daughter cysts within calices and renal pelvis [24]. Differential diagnosis of renal hydatidosis includes simple or infected renal cyst, abscess, and cystic or necrotic neoplasms [22].

Figure 3. Echinococcosis of the left kidney [60]. **Figure 3.** Unilocular hydatid cyst of the left kidney with internal calcifications that move (arrows) changing patient's decubit: supine (a) and on the right flank (b).

Hydatid cysts of the *adrenal gland* are very rare, with an incidence at autopsy of 0.06%–0.18%. They are usually secondary to a systemic *Echinococcosis* beyond the hepatic and the pulmonary filters.

*Organs of female genital tract* are rarely involved; first articles have been reported more than 50 years ago. It is generally associated to the developing of other parasitic cysts in the pelvis after the rupture of a primary lesion located in an abdominal organ (Figure 4). Ovaries are more affected than the uterus; differential diagnosis includes all the other ovarian cystic lesions.

Involvement of the *peritoneum* represents about the 13% of all abdominal hydatidosis [22]. Primary peritoneal disease is extremely rare. Peritoneal cysts generally develop as a conse‐ quence of seeding from either spontaneous rupture or prior surgery of hepatic, splenic, or mesenteric cysts [28]. Peritoneal cysts may be multiple and located anywhere in the peritoneal cavity [24]; they can enlarge and cause abdominal distension or obstruction [21]. Isolated retroperitoneal hydatid cysts of *retroperitoneum* are rare; they usually are secondary to the involvement of the liver [22]. The invasion of the *abdominal wall* by liver hydatid cysts has already been reported in literature. A cyst usually passes through a small orifice and develops within the abdominal wall, keeping communication with its hepatic component and showing a typical "hourglass" configuration.

**\***

**Figure 4.** Pelvic hydatid cyst above the uterus (arrow), formed after the rupture of a liver cyst (open arrow). Asterisk shows another cyst at the hepatic dome.

Primary *soft-tissue* involvement is extremely rare and represents 0.5%–4.7% of patients. Clinical manifestation often consists of a palpable mass. Imaging findings are nonspecific and may include unilocular or multilocular cysts and complex solid lesions if some inflammatory changes overlap.

*Diaphragmatic* localization has an incidence of 1% and is often associated with liver disease. It is believed that the lack of peritoneum in the bare area of the liver is usually the weak point, which favors the transdiaphragmatic migration of a liver hydatid cyst. Diaphragma may appear thickened and lobulated with unilocular or multilocular cysts. When the chest is reached, possible complications may be represented by a rupture into the pleural cavity, seeding in the pulmonary parenchyma and chronic bronchial fistula.

#### **6. Clinical presentation**

**•** type 2: multiple daughter cysts within the mother cyst (intermediate stage of parasitic

disease: Report of a case. Ups J Med Sci 110:167–171, 2005.

disease from head to toe. Radiographics 23: 475–494, 2003.

miming a testicular tumor. J Case Reports 4: 151–154, 2014.

site. Indian J Radiol Imaging 16: 239–241, 2006.

the palm and the thigh: Two case reports. J Med Case Rep 2: 273, 2008.

55. Zulfikaroglu B, Koc M, Ozalp N, Ozmen MM: A rare primary location of echinococcal

56. Dirican A, Unal B, Kayaalp C, Kirimlioglu V: Subcutaneous hydatid cysts occurring in

57. Polat P, Kantarci M, Alper F, Suma S, Koruyucu MB, Okur A: Hydatid

58. Tlili G, Bouassida K, Slama A , Tlili T, Ziadi S, Taher MA: Hydatid cyst of the scrotum

59. Arora V, Nijjar IS, Gill KS, Singh G: Case report: Primary hydatid cyst of muscle—A rare

b

Figure 3. Echinococcosis of the left kidney [60].

In type 1 and type 2 cysts, the cyst wall may be thick or calcified (Figure 3), and both the wall and the internal septa may show enhancement after e.v. administration of the contrast agent. In up to 18% of cases, the cyst may rupture into the collecting system and at imaging several round filling defects may be seen due to the migration of daughter cysts within calices and renal pelvis [24]. Differential diagnosis of renal hydatidosis includes simple or infected renal

Figure 3. Echinococcosis of the left kidney [60]. **Figure 3.** Unilocular hydatid cyst of the left kidney with internal calcifications that move (arrows) changing patient's

Hydatid cysts of the *adrenal gland* are very rare, with an incidence at autopsy of 0.06%–0.18%. They are usually secondary to a systemic *Echinococcosis* beyond the hepatic and the pulmonary

*Organs of female genital tract* are rarely involved; first articles have been reported more than 50 years ago. It is generally associated to the developing of other parasitic cysts in the pelvis after the rupture of a primary lesion located in an abdominal organ (Figure 4). Ovaries are more affected than the uterus; differential diagnosis includes all the other ovarian cystic lesions. Involvement of the *peritoneum* represents about the 13% of all abdominal hydatidosis [22]. Primary peritoneal disease is extremely rare. Peritoneal cysts generally develop as a conse‐ quence of seeding from either spontaneous rupture or prior surgery of hepatic, splenic, or mesenteric cysts [28]. Peritoneal cysts may be multiple and located anywhere in the peritoneal cavity [24]; they can enlarge and cause abdominal distension or obstruction [21]. Isolated retroperitoneal hydatid cysts of *retroperitoneum* are rare; they usually are secondary to the involvement of the liver [22]. The invasion of the *abdominal wall* by liver hydatid cysts has already been reported in literature. A cyst usually passes through a small orifice and develops within the abdominal wall, keeping communication with its hepatic component and showing

**•** type 3: completely calcified cysts (death of the parasite)

cyst, abscess, and cystic or necrotic neoplasms [22].

development)

126 Current Topics in Echinococcosis

60. 61.

**Figures**

decubit: supine (a) and on the right flank (b).

a typical "hourglass" configuration.

filters.

The unusual anatomic locations may cause difficulties in making the differential diagnosis, as *E. granulosus* is usually not suspected in some locations of the body [29]; signs and symptoms may be easily confused with those of other illnesses [30]. In these peripheral locations the clinical picture is extremely variable and depends upon the involved organs. Mechanical symptoms on adjacent structures are often present, in other cases complications arise, due to secondary infection or rupture with unforeseeable anaphylactic reactions [3].

It is not easy, neither simple, to describe the clinical manifestations of a hydatid cyst located in a peripheric organ, very often each case presents different clinical features, as it appears from our series. In the rare localizations the hydatid disease in the beginning is almost always asymptomatic, due to the slow growth of the cyst, and frequently is incidentally diagnosed. While the clinical signs of the hepatic cysts depend on its size and location inside the liver, when it is located in the peripheric organs, after an initial period during which the cyst is asymptomatic, clinical signs appear only when the diameter of the cyst increases and deter‐ mines "mechanical" clinical features, which will be different according to the organ where the cyst is located. Splenic hydatid disease is mainly produced by systemic dissemination or intraperitoneal spread from a ruptured liver cyst [24].

The clinical manifestations include abdominal pain, enlarged spleen, and fever [21]. In renal hydatid disease, patients may be asymptomatic or refer non-specific clinical manifestation (flank mass, renal colic, persistent fever, hematuria, dysuria, pyuria, or hypertension) [21].

In *Echinococcosis* of the adrenal gland, when symptoms are present, they are related to local visceral compression. In the patient present in our personal series, abdominal pain and dispeptic symptoms were present [14].

#### **6.1. Personal series**

In the Department of General Surgery of the University of Catania, Italy, from 1974 to 2014, 434 patients underwent surgical treatment for hydatid disease: in 319 cases (73.50%) the cyst was located in the liver, while in 79 cases (18.20%) it was located in the lungs. The remaining 36 patients (8.29%) presented a rare localization of the disease: in 3 patients (0.69%) the cyst was in the mediastinum, in 3 patients (0.69%) in the diaphragm, in one case (0.23%) in the dorsal muscle, and in 1 case (0.23%) in the subcutaneous tissue of the right lumbar region. In 28 cases (6.45%) the rare localization of the hydatid cyst was in the abdominal cavity: 11 cysts (2.53%) were in the peritoneal serosa, 9 (2.07%) in the spleen, 6 (1.38%) in the kidney, 1 (0.23%) in the adrenal gland, and 1 (0.23%) in the retroperitoneal region.

In the patients in whom the cyst was located in the peritoneal serosa, pain was present in 6 cases, a palpable mass in 4 cases, while in the other cases the cyst was incidentally diagnosed in an asymptomatic phase. Nine patients had a splenic localization and in 3 of them a hepatic cyst was also present. In 4 patients, a palpable mass in the left hypochondrium was present, 3 patients complained of a painful clinical picture, while 2 patients were asymptomatic. The patient with a cyst in the retroperitoneal space complained of a continuous pain in the right gluteal region with diffusion to the iliac bone and the omolateral thigh. A palpable mass was present in the mesogastrium. The patient with an adrenal cyst had perceived abdominal pain and dyspeptic symptoms with nausea [14]. The patient with the localization in the dorsal muscle was a woman who had noticed a mass in the lower lateral part of the axilla, which had increased until it reached a diameter of 12 cm.

#### **6.2. Atypical manifestations**

Absolutely unexplainable was the growth pattern of the cyst located in the subcutaneous tissue of the lumbar region in a 77-year-old woman that we observed in 2007. The diameter of the mass was about 8 cm, and clinical examination revealed that the mass had a smooth surface with distinct margins (Figure 5a). Absolutely unusual, the report of CT that displayed the Figure 3. Echinococcosis of the left kidney [60].

atypical behaviour of the cyst that seemed to originate from the liver through a little peduncle and then went into the muscle layer and reached the subcutaneous tissue of the lumbar region (Figure 5b) [31]. These data were confirmed at surgery but a clear explanation of this atypical case has not been obtained. If a hydatid cyst develops into the liver, usually it grows inside the liver and outside it towards the peritoneal cavity, it can reach a great dimension but does not go over the abdominal wall muscles as an infiltrating tumor. A similar growth pattern may occur in cysts located in the liver cupola when, in consequence of an inflammatory process, go into the diaphragm and open to the bronchial tubes. However, in our case, infective processes were not present and so this case remains unexplainable. Figure 3. Echinococcosis of the left kidney [60].

Figure 5. Clinical (a), radiological (b) and surgical (c) appearance of a rare hydatid cyst of the subcutaneous tissue of the lumbar region, correlated to the liver through a little peduncle [31]. **Figure 5.** Clinical (a), radiological (b) and surgical (c) appearance of a rare hydatid cyst of the subcutaneous tissue of the lumbar region, correlated to the liver through a little peduncle [31].

#### **6.3. Diagnostic evaluation and surgical treatment**

asymptomatic, due to the slow growth of the cyst, and frequently is incidentally diagnosed. While the clinical signs of the hepatic cysts depend on its size and location inside the liver, when it is located in the peripheric organs, after an initial period during which the cyst is asymptomatic, clinical signs appear only when the diameter of the cyst increases and deter‐ mines "mechanical" clinical features, which will be different according to the organ where the cyst is located. Splenic hydatid disease is mainly produced by systemic dissemination or

The clinical manifestations include abdominal pain, enlarged spleen, and fever [21]. In renal hydatid disease, patients may be asymptomatic or refer non-specific clinical manifestation (flank mass, renal colic, persistent fever, hematuria, dysuria, pyuria, or hypertension) [21].

In *Echinococcosis* of the adrenal gland, when symptoms are present, they are related to local visceral compression. In the patient present in our personal series, abdominal pain and

In the Department of General Surgery of the University of Catania, Italy, from 1974 to 2014, 434 patients underwent surgical treatment for hydatid disease: in 319 cases (73.50%) the cyst was located in the liver, while in 79 cases (18.20%) it was located in the lungs. The remaining 36 patients (8.29%) presented a rare localization of the disease: in 3 patients (0.69%) the cyst was in the mediastinum, in 3 patients (0.69%) in the diaphragm, in one case (0.23%) in the dorsal muscle, and in 1 case (0.23%) in the subcutaneous tissue of the right lumbar region. In 28 cases (6.45%) the rare localization of the hydatid cyst was in the abdominal cavity: 11 cysts (2.53%) were in the peritoneal serosa, 9 (2.07%) in the spleen, 6 (1.38%) in the kidney, 1 (0.23%)

In the patients in whom the cyst was located in the peritoneal serosa, pain was present in 6 cases, a palpable mass in 4 cases, while in the other cases the cyst was incidentally diagnosed in an asymptomatic phase. Nine patients had a splenic localization and in 3 of them a hepatic cyst was also present. In 4 patients, a palpable mass in the left hypochondrium was present, 3 patients complained of a painful clinical picture, while 2 patients were asymptomatic. The patient with a cyst in the retroperitoneal space complained of a continuous pain in the right gluteal region with diffusion to the iliac bone and the omolateral thigh. A palpable mass was present in the mesogastrium. The patient with an adrenal cyst had perceived abdominal pain and dyspeptic symptoms with nausea [14]. The patient with the localization in the dorsal muscle was a woman who had noticed a mass in the lower lateral part of the axilla, which had

Absolutely unexplainable was the growth pattern of the cyst located in the subcutaneous tissue of the lumbar region in a 77-year-old woman that we observed in 2007. The diameter of the mass was about 8 cm, and clinical examination revealed that the mass had a smooth surface with distinct margins (Figure 5a). Absolutely unusual, the report of CT that displayed the

intraperitoneal spread from a ruptured liver cyst [24].

in the adrenal gland, and 1 (0.23%) in the retroperitoneal region.

increased until it reached a diameter of 12 cm.

**6.2. Atypical manifestations**

dispeptic symptoms were present [14].

**6.1. Personal series**

128 Current Topics in Echinococcosis

a In our experience, immunological tests have been very useful when the hydatid cyst was located in the liver, but have not showed the same diagnostic profit in patients affected by rare locations of the disease. In these cases, globally considered, echinotest has been positive in about one third of the cases. Diagnostic tools that have been essential to obtain the diagnosis were ultrasound and CT. The surgical treatment of the hydatid cysts peripherically located is not standardized, usually they are cases sporadically reported and the same great experience gained in the surgical treatment of the hepatic cysts is lacking. In hepatic cysts, a considerable reduction of the conservative surgical approaches has been reported and nowadays an increase in radical surgery is the preferred treatment.

In peripheric locations, the radical surgical removal without spreading the disease due to spillage of cystic fluid has been the treatment of choice, and this method has been applied to the cysts located in the peritoneum. In the splenic localization, splenectomy has always been performed and the patients underwent the standardized protocols to avoid the consequences of the overwhelming postsplenectomy infection [32]. In the renal localizations it has been possible to avoid nephrectomy and realize a partial pericystectomy and no recurrences have been observed. The cyst located in the adrenal gland was treated by surrenectomy and the cysts located in the dorsal muscle and in the subcutaneous tissue of the lumbar region (Figure 5c) were easily removed.

#### **7. Echinococcosis and allergy — Anaphylaxis**

*Echinococcus granulosus* and *E. multilocularis* are involved in parasitic disease in humans: cystic *Echinococcosis* (CE) ("hydatid diseas") and alveolar *Echinococcosis* (AE), respectively. Both diseases and parasites have tight links with allergy because of the immunological character‐ istics that contribute to maintaining the larva in its human host, as well as their potential in inducing clinical anaphylactic reactions in some patients [19].

Allergic reactions and anaphylaxis are well-known features of CE. Elevated total IgE, as well as occurrence of specific IgE against Echinococcus antigens in the serum of patients with CE are also key biological features of the disease [33–34]. IgE-dependent immune reactions were long neglected in AE; obviously, anaphylactic reactions are far less frequent than in CE. However, specific IgE antibodies against *E. Multilocularis* antigens may be found in patients with AE [19]. Anaphylactic reactions have been reported in cystic *Echinococcosis* for several decades and are usually observed in case of overt or unapparent rupture of the parasitic cyst [19]. A variety of allergic symptoms has been described in patients with CE. They include urticaria that may be only mild or present as chronic and apparently "idiopathic" urticaria, or as giant urticaria associated with systemic signs and symptoms. Respiratory symptoms may also be observed; asthma may be the first manifestation of hepatic hydatidosis and acute bronchospasm may occur when the cyst is manipulated at surgery. Anaphylactic shock is the most impressive and severe clinical presentation of IgE-dependent allergic reactions in CE. It may occur spontaneously and precede any other symptoms. Recurrent life-threatening anaphylactic shocks, with or without laryngospasm, may be due to small, incomplete rupture of the cyst [35–36]. Overt rupture of the cyst, however, is a much more frequent cause of anaphylaxis; it may be observed after trauma, even trivial, such as that derived from a sport (football) accident. Sometimes, however, intraperitoneal perforation of a hepatic hydatid cyst can happen without anaphylactic reaction, confirming the inaccurate knowledge of the mechanisms that control the allergic phenomena produced by the parasite [37]. The most usual circumstance is surgery, however, even in the immediate postoperative period, or laparoscopy. As for other etiologies of anaphylactic shock, tryptase measurement is of help for diagnosis [19]. In AE, the low rate of anaphylactic symptoms could be related to a more "masked" form of Echinococcus antigens in patients with AE than in those with CE: the extremely fibrotic lesions of AE cannot rupture, and the echinococcal fluid may never be in contact with mast cell-bound IgE [38].

#### **8. Medical treatment**

In peripheric locations, the radical surgical removal without spreading the disease due to spillage of cystic fluid has been the treatment of choice, and this method has been applied to the cysts located in the peritoneum. In the splenic localization, splenectomy has always been performed and the patients underwent the standardized protocols to avoid the consequences of the overwhelming postsplenectomy infection [32]. In the renal localizations it has been possible to avoid nephrectomy and realize a partial pericystectomy and no recurrences have been observed. The cyst located in the adrenal gland was treated by surrenectomy and the cysts located in the dorsal muscle and in the subcutaneous tissue of the lumbar region (Figure

*Echinococcus granulosus* and *E. multilocularis* are involved in parasitic disease in humans: cystic *Echinococcosis* (CE) ("hydatid diseas") and alveolar *Echinococcosis* (AE), respectively. Both diseases and parasites have tight links with allergy because of the immunological character‐ istics that contribute to maintaining the larva in its human host, as well as their potential in

Allergic reactions and anaphylaxis are well-known features of CE. Elevated total IgE, as well as occurrence of specific IgE against Echinococcus antigens in the serum of patients with CE are also key biological features of the disease [33–34]. IgE-dependent immune reactions were long neglected in AE; obviously, anaphylactic reactions are far less frequent than in CE. However, specific IgE antibodies against *E. Multilocularis* antigens may be found in patients with AE [19]. Anaphylactic reactions have been reported in cystic *Echinococcosis* for several decades and are usually observed in case of overt or unapparent rupture of the parasitic cyst [19]. A variety of allergic symptoms has been described in patients with CE. They include urticaria that may be only mild or present as chronic and apparently "idiopathic" urticaria, or as giant urticaria associated with systemic signs and symptoms. Respiratory symptoms may also be observed; asthma may be the first manifestation of hepatic hydatidosis and acute bronchospasm may occur when the cyst is manipulated at surgery. Anaphylactic shock is the most impressive and severe clinical presentation of IgE-dependent allergic reactions in CE. It may occur spontaneously and precede any other symptoms. Recurrent life-threatening anaphylactic shocks, with or without laryngospasm, may be due to small, incomplete rupture of the cyst [35–36]. Overt rupture of the cyst, however, is a much more frequent cause of anaphylaxis; it may be observed after trauma, even trivial, such as that derived from a sport (football) accident. Sometimes, however, intraperitoneal perforation of a hepatic hydatid cyst can happen without anaphylactic reaction, confirming the inaccurate knowledge of the mechanisms that control the allergic phenomena produced by the parasite [37]. The most usual circumstance is surgery, however, even in the immediate postoperative period, or laparoscopy. As for other etiologies of anaphylactic shock, tryptase measurement is of help for diagnosis [19]. In AE, the low rate of anaphylactic symptoms could be related to a more "masked" form of Echinococcus antigens in patients with AE than in those with CE: the extremely fibrotic lesions of AE cannot rupture, and the echinococcal fluid may never be in contact with mast

5c) were easily removed.

130 Current Topics in Echinococcosis

cell-bound IgE [38].

**7. Echinococcosis and allergy — Anaphylaxis**

inducing clinical anaphylactic reactions in some patients [19].

In patients treated for liver and/or lung hydatid cysts, the possibility of secondary *Echinococ‐ cosis* can be minimized by concurrent treatment with benzimidazoles [39].

Mebendazole (MBZ) and albendazole (ABZ) are the benzimidazole (BMZ) agents used for the treatment of hepatic CE. They interfere with the absorption of glucose through the wall of the parasite, causing glycogen depletion, and degenerative changes in echinococcal mitochondria and endoplasmic reticulum. BMZ may be favorably used alone for the treatment of small (<5 cm) CE liver cysts or for inoperable patients; BMZ is also usually associated with PAIR or surgery to prevent secondary CE. BMZ is not indicated for the treatment of inactive or calcified asymptomatic cysts, unless they are complicated lesions. Both ABZ and MBZ are effective, but ABZ is considered the drug of choice. The usual dose of orally administered ABZ is 10–15 mg/kg/day in two divided doses; if using MBZ, the daily dose is 40–50 mg/kg in three divided doses. Treatment with BMZ should be admin‐ istered continuously for 3–6 month. Praziquantel has been used (40 mg/kg once a week) with ABZ for combined treatment of CE; this therapeutic association seems to be more effective than ABZ alone [40–41]. Usual adverse effects include nausea, hepatotoxicity, neutropenia, and occasionally alopecia [39]. In patients treated for rare peripheric loca‐ tions, in our opinion, treatment with BMZ should be especially recommended. In these patients, hepatic and pulmonary filters have been bypassed, so the disease should be considered systemic and chemotherapy should be promising in preventing further recurrences.

#### **9. Conclusions**

Although the incidence of *Echinococcosis* has dramatically reduced in recent decades, many cases can still be found in daily medical practice. The surgeon must keep in mind that this parasitosis can occur even in uncommon locations and therefore it should be regarded as a potentially systemic disease. In these cases the diagnosis is challenging and can be achieved only through a complete interdisciplinary evaluation of clinical, laboratory, and radiological data.

#### **Acknowledgements**

Part of the text of paragraph 6.2. "Atypical manifestations" and Figure 5 are used with kind permission of the publisher for World Journal of Gastroent erology. The Authors wish to thank Bench srl for the technical support. Main Authors (Antonio Di Cataldo, Giuseppe Petrillo, Claudia Trombatore, Stefano Palmucci, Antonella Agodi) did study conception, acquisition and interpretation of data, wrote the manuscript and performed the final critical revision. Other Authors cooperated in the writing the manuscript, according to their competence and specific knowledge.

### **Author details**

Antonio Di Cataldo1 \* #, Giuseppe Petrillo2 #, Claudia Trombatore2 #, Stefano Palmucci2 #, Antonella Agodi1 #, Martina Barchitta1 , Annalisa Quattrocchi1 , Nunzio Crimi3 , Silvia Fichera3 , Stefano Puleo1 , Amy Giarrizzo1 , Martina Calabrini1 , Rosalia Latino1 and Rosanna Portale1

\*Address all correspondence to: dicataldoa@tiscali.it

1 Department of Medical and Surgical Sciences, Advanced Technologies GF Ingrassia, University of Catania, Italy

2 Radiodiagnostic and Radiotherapy Unit, University Hospital Policlinico-Vittorio Emanuele, Catania, Italy

3 Department of Respiratory Diseases and Allergology, University of Catania, Italy
