Introductory Chapter: Changes in Eco-System Change Echinococci - “One Health Concept” against Echinococci

1. Introduction

1.1 Historical perspective of echinococcosis

Echinococcosis or Hydatid disease has been “described” thousands of years ago [1]. The first implication of Echinococcosis dated back to Hippocrates (460–377 BC). He mentioned hydatids (clear fluid full of metacestods of Echinococcus granulosus) as “In those whose water stuffed liver opens into omentum, the belly is filled with water, and they die” [2]. Hydatid disease has been also mentioned by Galen (129–200 BC). Interestingly, Aretaeus (80–138 AD), ancient physician from Cappadocia, has stated his observation as “many small fluid-filled blisters may be present in some patients with ascites” (Neisser A. DieEchinococcen-Krankenheit. Verlag August Hirschwald Berlin 1877.) Thereafter, many observations have been reported, however, the animal nature of metacestodes and their parasitic character was first reported by Francesco Redi (1626–1697). Since then, there have been many observations and investigations that lead to our wide knowledge in 21st century [3].

1.2 Echinococcus spp and causative agent of echinococcosis

Echinococcus belongs to family of Taeniidea in the subclass of Cyclophillidea and the class of Cestoda in the phylum of Platyhelminthes. Although there have been more than 20 different species defined in Echinococcus (E.) spp., there are four species that are of health concern in humans; E. granulosus (Batsch, 1786), E. multilocularis (Leuckart, 1863), E. oligarthrus (Diesing, 1863) and E. vogeli (Rausch and Bernstein, 1972). The diseases in the human according to the types of Echinococci are “Cystic echinococcosis” by E. granulosus, “Alveolar echinococcosis” by E. multilocularis, “Polycystic echinococcosis” by E. oligarthrus and E. vogeli. There are two new species, namely E. shiquicus in small mammals from the Tibetan plateau and E. felidis in African lions, however the importance of these and the transmission from animals to humans are not known yet [4].

Adult forms of Echinococcus spp. are 1.2–6 mm in length and consist of a head (scolex), a neck (proliferation zone), and body (strobilia). The scolex contains four suckers and a rostellum with 25–50 hooks. The proglottids are formed from the Proliferation zone (the neck). There are 2–6 chains called proglottids in strobilia; the first is immature, the second is mature and the others are gravid proglottids. Mature proglottid has both male and female reproductive organs (hermaphrodite). Gravid proglottids have many eggs [5, 6, 7].

In humans, two forms of Echinococci are utmost important clinically; E. granulosus (causative agent of “Cystic echinococcosis”, CE) and E. multilocularis, (causative agent of “Alveolar echinococcosis”, AE). For E. granulosus, dogs and other members of “familie canidea” (carnivores) are definitive hosts and hold the adult forms, whereas “the familie ungunatae” (such as sheep, goats, pigs, horses etc.) (herbivores) are the intermediate hosts where the larval stage of Echinococci exist. There are other intermediate hosts such as hares, marsupials, rabbits, rodents. Humans do not play a role in transmission (dead-end), they called as “aberrant intermediate hosts” [8]. For E. multilocularis, definitive hosts are mainly foxes (especially red foxes), domestic dogs, wolves, and intermediate hosts are their preys mainly rodents.

The life cycle of Echinococci is similar in different forms. The adult forms of the parasite reside in the mucosal layer of the definitive hosts’ small intestines and release the eggs thru feces. The eggs are highly resistant to difficult environmental conditions. One example is that the eggs can survive 225 days at 6°C in water or wet sand [9]. When the embryonated eggs are ingested by the intermediate hosts, the egg shell is broken and the embryo (oncosphere) is released in the stomach. In the small intestines the oncospheres first attach to the mucosa and then penetrate it. Thereafter the oncospheres travel to various organs via blood steam and develop cysts. In the cysts, by enlarging, protoscolices and daughter cysts are being formed and fill the cysts. The life cycle is completed by ingestion of the cysts (via organs) by definitive hosts. Apart from consuming contaminated water of food, humans especially children may also take the eggs directly from the hair of infected dogs.

Although the life cycle of Echinococci is simple, the transmission pathways are complex due to involvement of different wild and domestic mammalian animals [10]. Due the changing climate and -in general- environment, both genotypic and phenotypic changes of the strains draw the curtain over the systems of transmission. Detailed data concerning the transmission according to geographic distribution would really be appreciable to provide a control in all over the world.

Until recently, the scientists tried to differentiate the types and subtypes. However, in recent years, holistic approach gained value as “One Health Concept”. This is more realistic to eradicate the disease and agents in all over the world because, whether for all hosts and intermediate hosts, either domestic or wild, all types and subtypes are in the same eco-system. “Cleverly”, the parasite can modify itself according to changing eco-system, thus escapes from the controls [11].

2. Control of echinococcosis

2.1 International organizations

Echinococcus spp. are important health causative agents in the World. The spread of the disease also causes economic losses. Infection with echinococci of the farm animals such as sheep and cattle leads to not only direct economic losses but also workload, treatment costs, risk of disease epidemics among organisms including humans. World Health Organization (WHO) accepted “echinococcosis” as one of the 17 neglected diseases for year 2050 and included this parasitic disease in “elimination program” [12]. Along with this program, the World Health Organization/Food and Agriculture Organization included Taenia solium, E. granulosus, and E. multilocularis in the food borne parasitic diseases [13]. Echinococcosis has a global distribution with an estimated 2–3 million people affected and 200,000 new cases diagnosed annually. Cystic echinococcosis can be seen with prevalence levels of up to 5–10% in Argentina, Peru, East Africa, Central Asia and parts of China (Figure 1) [15, 16, 17].

Figure 1.

The distribution of echinococcosis in the world [14].

This map shows the worldwide distribution of Echinococcus spp. It is defined in different colors, taking into account the rate of infection of definitive and intermediate hosts.

2.2 Local organizations

There are many researches and preventive investigations on echinococcosis especially in Europe and Asia. Changes in eco-system have important effects on Echinococcus spp., leading to biologic diversities [18, 19]. These changes may cause health problems in animals and humans [20].

According to WHO report on 2021, cystic echinococcosis has a worldwide distribution except Antarctica, whereas alveolar echinococcosis is confined to northern hemisphere especially north central region [21]. However, precise mapping is still difficult to achieve in whole geographic areas.

3. The field of research and development

3.1 Echinococcus species

Up until now, people have been rude to the nature for their own interests. We used all-natural resources for ourselves only. To produce more food source, livestock-feed was increased. To achieve this, genetic alterations were used. Meantime, pollution of soil and water by industrial products risked the right to live of all living things. In the end, global warming destroyed the eco-system in the World.

3.2 Animals

3.2.1 Domestic animals

Echinococcus spp. may reside in many farm animals in close similarity to humans. These intermediate hosts are sheep, buffalo, horse, cattle, camel, pig. The definitive hosts are dogs and other members of canidea [10, 14].

3.2.2 Wild animals

It is difficult to combat against echinococcosis in wild-nature. The definitive hosts and intermediate hosts especially for Echinococcus spp. are in the wild-nature. The definitive hosts are wild animals such as fox, cat, wolf, raccoon–dog (Nyctereutes procyonoides albus), American cervid strain (European or Fennoscandian cervid strain), pigs, lions (Panthera leo), jackals (Canis mesomelas and C. aureus) wild canids (eg. hunting dogs (Lycaon pictus), hyaenas (Crocuta crocuta).

The intermediate hosts in the wild are plains zebras (Equus quagga), giraffe (Giraffa camelopardalis), moose (Alces alces), Wapiti (or elk) (Cervus canadensis) Muskox (Ovibos moschatus), as small mammals; rodents, Soricidae, Talpidae, Sciuridae, Cricetidae and Dipodidae, and pikas (Ochotonidae) (meriones ungualitis, rattus norvegicus) [10, 14, 22, 23, 24, 25].

3.3 Humans

Humans are aberrant intermediate hosts (dead-ends). E. granulosus and then E. multilocularis are the top two most common in human echinococcosis.

3.4 Water

Echinococcus spp. eggs are highly resistant to tough conditions. Survival of the eggs mainly depends on humidity and temperature [26]. According to data, eggs protect their viability for 3 weeks at 30°C, 225 days at 6°C and even 32 days at 10-21°C in water and moist soil [27]. In waters from heavy rain and melting glaciers, Echinococcus spp eggs may stay long enough time until it is drunken by hosts [28]. Rain may also lead to increased vegetation and may also increase intermediate host [29].

4. Clinical characteristics

Echinococcosis may stay silent in human for many years. The liver is the most commonly involved organ in human. It may show itself by non-specific complaints such as loss of appetite, weight loss, hepatic enlargement (hepatomegaly), uneven and firm liver on palpation, sometimes ascites. The second most common involved organ is the lungs. There may be cough, chest and back pain, high fever, sputum, hemoptysis, dyspnea, allergic signs. Other exceptional signs may be due to cyst compression to the surrounding organs.

In laboratory analyses, hyperbilirubinemia, anemia, eosinophilia (>5%), lymphopenia, low prothrombin time may be present. In addition, high liver function tests (Gamma-glutamyl transferase (GGT), Aspartate aminotransferase (AST), Alanine aminotransferase (ALT)) may be high [14].

4.1 Diagnosis

4.1.1 Radiological diagnosis

According to clinical findings, ultrasound (US) [22]. and/or direct radiograms [30, 31] can be used. Additionally, radiological examinations via computed tomography (CT) scans [32], Magnetic Resonance Imaging (MRI) [33], Fluorodeoxyglucose Positron Emission Tomography (FDG-PET) [34],⁶⁷Ga Scintigraphy [35] can aid to diagnose “echinococcosis”. In recent years, radiological methods do not only aid in diagnosis but also give a chance to treatment. Puncture, aspiration, injection, re-aspiration (PAIR) technique are widely being used in type I and Type IICE in non-complicated locations [36, 37].

4.1.2 Serological and molecular diagnosis

Indirect fluorescent antibody (IFA), indirect hemagglutination (IHA), Enzyme-linked immunosorbent assay (ELISA), Western blotting (EmWB) (LD BIO Diagnostics, Lyon, France) [38], 70–90 Em WB [39] are the serological methods for the diagnose. Molecular methods in the diagnoses of echinococcosis are DNA detection, real time PCR [40, 41], quantitative and/or nested PCR assays nested PCR [42], LAMP-based assays [43, 44], cell-free DNA (cfDNA) [45].

4.2 Treatment

Treatment of echinococcosis is mainly surgical. As anti-infective medical treatment, Benzimidazole carbamates, Albendazole (ABZ) (10–15 mg/kg/day, continuously), or Mebendazole (4.5 g/day) are in use. However, ABZ and Mebendazole act as parasitostatic, thus they just stop the growth of larvae [46].

4.3 Prevention

The World Health Organization (WHO) has listed echinococcosis as one of the 17 neglected diseases targeted for control or elimination by 2050 [12].

One arm of prevention would be the prevention of dissemination of the disease from the hosts. This may be achieved first the diagnose by using stool antigen tests in dogs. The second arm would be “vaccination”. Although there is no vaccination against Echinococci for dogs, vaccination of sheep would be helpful. EG95 vaccine is a vaccine for E. granulosus and can be given as two doses monthly injection, thereafter as yearly booster [14, 47]. It is more difficult to find a way to control E. multilocularis, since the life cycle is tricky to break due to hosts in wild life, thus there is no vaccination [48]. The treatment of red foxes has been shown effective but sustainability of such method of prevention is difficult due to high cost [49].

4.4 Education

4.4.1 Training of educators

Multidisciplinary international meetings should be held to define strategies for action plans against echinococcosis.

4.4.2 Public education

Professions, those related to animals and animal products, especially farmers, shepherds, hunters, tanners, veterinarians and people in the endemic areas such as soldiers, climbers, athletes, scouts, hikers should be informed and educated periodically (Table 1) [62].

Species	New classification	Natural definitive host species (excluding humans)	Human public health importance	intermediate host	Geographic Distribution	References
1.E. granulosus
1.1.(G1) (sheep strain)	E. granulosus sensu stricto	carnivors (dogs, foxes, dingo, jackal, hyena)	High	Domestic (sheep, cattle, pigs, camels, and goats)	Australian mainland, Europe, USA, New Zealand, Africa, China, Middle East,South America and Russian Federation	[50, 51, 52, 53, 54]
1.2.E. granulosus (G2) (Tasmanian sheep strain)	Genotype G2 is no longer considered a valid genotype, but it is recognized as a microvariant of G3	carnivors (dogs, foxes)	High	Domestic (sheep, cattle)	Tasmania, Argentina	[10, 55]
1.3.E. granulosussensustricto (G3) (buffalo strain)	Manda	carnivors (dogs, foxes)	?		Asia	[5, 10]
1.4.E. granulosus (G4) (horse strain)	E. equinus	carnivors (dogs) lions (Panthera leo), black-backed jackals (Canis mesomelas)	No	Perissodactylids; (horses); Donkeys,; plains zebras (Equus quagga),; red ruffed lemur (Varecia rubra)	Europe, Middle East, South Africa, (New Zealand? USA?)	[23, 56]
1.5.E. granulosus (G5) (cattle strain)	E. ortleppi	Domestic Dogs	Yes (rarely)	Cattle, Goats, pigs, zebra, oryx antelopes (Oryx gazella), giraffe (Giraffa camelop ardalis)	Europe, South Africa, India, Sri Lanka, Russian Federation, South America?	[57, 58]
1.6.E. granulosus (G6) (camel strain)		Dogs	Yes	Camels,sheep,	Middle East, Africa, China, Argentina	[59]
1.7.E. granulosus (G7) (pig strain)	E. canadensis (G6/G7)	Pig-raising Domestic:Dogs; Wild: wolf; Camel-raising: domestic dogs and	Yes(moderate)	Pig-raising: Pigs other livestock (e.g., goats),; Wild: wild boar; Camel-raising: Camel, dromedaries house mouse (M. musculus)	Pig-raising regions of western; Eurasia and South/Central America Camel-raising regions (from eastern and northern Africa through the Middle East to central Asia)	[10]
1.8.E. granulosus (G8) (American cervid strain)	Echinococcus ortleppi	Wolf,; Dogs,	Yes	moose (Alces alces),; Wapiti or elk (Cervus canadensis) Muskox (Ovibos moschatus); Cervids	North America, Canada, northeastern United States, Eurasia	[10]
1.9.E. granulosus (G9)	Dog		pig strain; cervid	Humans	Polonya	[14]
1.10. E. granulosus (G10)	E. canadensis (European or Fennoscandian; cervid strain)	Domestic dog, wolf		Wild: moose, wapiti, caribou,; moose; Domesticated reindeer and moose; Pig, camel, cervids	Canada; Unitad States; Mongolia; Eurasia,	[10]
Lion strain	E. felidis	Lions (P. leo),; potted hyenas; (Crocuta crocuta),		Zebra, wildebeest, warthog, bushpig,; buffalo, various; Antelope, giraffe?; hippopotamus? red river hogs; (Potamochoerus porcus)	Africa	[10, 60]
Lagomorf (?)
2.E. multilocularis
2.1. European isolate		Fox, dog, cat, wolf, raccoon–dog	Yes	Rodents (Microtus. levis), domestic and wild pig, dog, monkey	Europe, China?	[10, 17]
2.2. Alaskan isolate		Wolves (C. lupus), dog, cat	Yes	Rodents Tundra voles (Microtus oeconomus) singing vole (Microtus; miurus)	Alaska	[10, 17]
North American isolate		Arctic foxes (Vulpes lagopus), dog, cat, coyote	Yes	Rodents	North America	[10, 17]
2.3. Hokkaido isolate		Fox, dog, cat, raccoon –dog	Yes	Rodents, pig, monkey, horse		[10, 17]
3. E. vogeli		Bush dog	Yes	Rodents (Paca)	Central and South America	[10, 17]
4.E. oligarthra		Wild felids	Yes	Rodents (Agouti)	Central and South America	[10, 17]
E. shiquicus		Tibetan fox		Pika	Tibetan plateau	[61]

Table 1.

Schematic phylogeny of interrelationships between members of the Echinococcus species, strains, isolates, genotypes, definitive host and intermediate host vertebrates.

5. Conclusion

• Echinococcosis is STILL an important “neglected disease”, and food borne parasitic diseases.

• Adaptive changes of Echinococcus spp. stemmed mainly from humans wrong attitude towards eco-system. To prevent this;

  • Global warming should be taken into consideration since endemic areas for Echinococci are also increased.

  • Dissemination of infected tissues to the environment and contamination should be prevented.

  • The spread of the disease causes economic losses.

• In this 21st century, new molecular-based and radiological methods should be investigated and developed.

• To increase the awareness of echinococcosis, national and international communication should be provided.

• To combat against the disease, cooperation among healthcare professionals, veterinarians, municipalities should be coordinated both in national and international levels. That is to say “One health concept” is important.