Epidemiology and control of echinococcosis

INTRODUCTION — Echinococcal disease is caused by infection with the tapeworm Echinococcus. Four species of Echinococcus cause infection in humans. E. granulosus and E. multilocularis are the most common, causing cystic echinococcosis and alveolar echinococcosis (AE), respectively. The two other species, E. vogeli and E. oligarthrus, cause polycystic echinococcosis and are less frequently associated with human infection (table 1) [1]. Two relatively new species have been identified: Echinococcus shiquicus in small mammals from the Tibetan plateau and Echinococcus felidis in African lions [2,3]; their transmission potential to humans is not known.

The geographic distribution and animal host species vary by Echinococcus species, and mixed infections involving more than one species have been reported. In addition, different strains within an Echinococcus species may have variable morphology, genetic characteristics, infectivity to humans, and pathogenicity [2,3].

The epidemiology and control of the echinococcal species will be reviewed here. The clinical manifestations, diagnosis, and treatment of cystic and AE are discussed separately. (See "Echinococcosis: Clinical manifestations and diagnosis" and "Echinococcosis: Treatment".)

ECHINOCOCCUS SPECIES

Echinococcus granulosus — E. granulosus causes cystic echinococcosis (CE).

Life cycle — The life cycle of echinococcus includes a definitive host (usually dogs or related species) and an intermediate host (such as sheep, goats, camels, cervids, horses, cattle, and swine) (figure 1). Humans are incidental hosts; they do not play a role in the transmission cycle. E. granulosus adult tapeworms are usually found in dogs or other canids.

The adult tapeworm inhabits the small intestine of the definitive host. The definitive host may be infected with thousands of worms. E. granulosus worms are usually 2 to 7 mm long and consist of a scolex with suckers and hooks as well as at least three proglottid segments. E. multilocularis worms are up to 4 mm long with two to six proglottic segments.

The tapeworm is composed of proglottid segments that have both male and female sexual organs and can produce parasite eggs 30 to 40 microm in size containing embryos (oncospheres). Each adult worm can produce thousands of eggs per day. The eggs are expelled in the stool of the definitive host and released to the environment, where they are infective to susceptible intermediate hosts and human incidental hosts. Eggs are highly resistant and can remain infective for a year in a moist environment at low temperature. For example, eggs of E. multilocularis can remain viable for 16 months in water at a temperature of 4°C (39.2°F) [4]. Eggs are sensitive to desiccation.

Following egg ingestion by the intermediate or incidental host, the oncospheres hatch from the eggs, penetrate the intestinal mucosa, enter the blood and/or lymphatic system, and migrate to the liver or other visceral organs. A few days later, a fluid-filled cyst begins to develop, with subsequent development of multiple layers to become a metacestode (hydatid cyst). The nature of the cyst is variable depending on the echinococcal species (table 2).

Subsequently, protoscolices develop within the hydatid cyst. In definitive hosts that ingest intermediate host visceral organs containing hydatid cysts composed of protoscolices, the protoscolices evaginate, attach to the intestinal mucosa, and develop into adult worms. Such development occurs over a period of four to seven weeks, completing the life cycle.

The highest rates of cystic echinococcal endemic disease tend to occur in areas where sheep are raised. Transmission frequently occurs in settings where dogs eat the viscera of slaughtered animals. The dogs then excrete infectious eggs in their stool, which are passed on to other animals or humans via fecal-oral transmission. This may occur via environmental contamination of water and cultivated vegetables or contact between infected domestic dogs and humans (often in children).

Human-to-human transmission of echinococcosis does not occur since two mammalian species are required for completion of the life cycle.

Epidemiology — Cystic echinococcosis is a significant public health problem in South America, the Middle East and eastern Mediterranean, some sub-Saharan African countries, western China, and the former Soviet Union [5-7]. The overall prevalence of echinococcal infection is underestimated in many series because systematic population surveys are not performed in all endemic areas. The number of recognized cases is increasing, however, which may be due in part to better diagnostic technology and surveillance programs.

In endemic rural areas, prevalence rates of 2 to 6 percent or higher have been recorded [8]. In the Peruvian Andes, observed prevalence in humans has ranged from 3 to 9 percent using portable ultrasonography and/or chest radiography [9-11]. Infection rates among canines and sheep were 32 and 38 percent, respectively [9]. Between 2019 and 2021, 9511 cases of human cystic echinococcosis were notified in Peru, Argentina, and Chile which accounted for 79, 12, and 9 percent of the cases, respectively; 16 percent involved children <15 years of age [12]. In a Chinese region endemic for both E. granulosus and E. multilocularis, village prevalence rates for CE and alveolar echinococcus (AE) were 6.8 and 6.2 percent, respectively [13]. The prevalence of CE ranged from 0 to 12 percent; prevalence of AE ranged from 0 to 14 percent. In northern Xinjian in China, 0.3 to 3 percent of the population had detectable CE cysts by ultrasound examination [14,15]. The highest prevalences (8.7 percent) have been observed among Mongolian and Kazak pastoralist communities [16]. These are among the highest rates recorded worldwide.

New echinococcal infections continue to occur throughout life, and the prevalence of liver and pulmonary hydatid cysts increases with age. One study in Uruguay noted an overall prevalence of 5.6 percent; the prevalence increased from 1 percent among patients 4 to 6 years of age to >11 percent among patients over 60 years of age [17].

In the United States, most cases occur among immigrants from endemic countries. Local transmission has been observed in California, Arizona, New Mexico, Utah, and Alaska [8,18].

Molecular studies have identified several distinct strains of E. granulosus with different geographic and host affinities (table 1). The presence of different strains of E. granulosus may have important implications for public health. For example, the shortened maturation time of the adult form of the parasite in the dog intestine (for E. granulosus strains G2, G5, and G6) suggests that the number of treatment doses per year may have to be increased in endemic areas for these strains [19].

Pathology — The hydatid cyst is usually filled with fluid (table 2). The inner layer is the germinative layer that gives rise to the hydatid fluid and small secondary cysts (brood capsules), which bud internally from this layer. Fragmentation of the germinative layer and brood capsules gives rise to daughter cysts. These may develop within the original cyst or separately.

After at least 10 to 12 months following infection, protoscolices are produced within the brood capsules. Cysts may contain liters of fluid and thousands of protoscolices. Cysts containing protoscolices are fertile and can produce daughter cysts, whereas cysts without protoscolices are sterile.

External to the germinative layer is an acellular, laminated membrane of variable thickness. A host granulomatous reaction occurs around this membrane; the resulting parenchyma and fibrous tissue reaction is known as the pericyst.

The pathology resulting from E. granulosus infection varies in different geographic regions and among different populations. Among patients in Turkana, Kenya, for example, many cysts are large, unilocular, and fertile [20]. In contrast, cysts among individuals in the northern hemisphere tend to be calcified, small, and infertile [1]. Such variations could depend upon a number of factors: the time between infection and diagnosis, intraspecies variation of the parasite, and host differences (immunologic, genetic, and/or nutritional) [1].

Immunity — Intermediate and incidental hosts mount both humoral and cellular immune responses to the organism. The initial immune response occurs against the oncospheres that penetrate the gastrointestinal mucosa. Subsequently, the host mounts an immune response against the metacestode (hydatid cyst). Metacestodes have developed highly effective mechanisms for evading host defenses. The membranes and host capsule surrounding the cyst protect the E. granulosus parasite from immune destruction [21].

Other less well-defined mechanisms, including parasite-derived modulating substances such as an anticomplement factor, may also dampen the host immune response [21]. Studies have suggested that Th1 cell activation is crucial for protective immunity, whereas Th2 cell activation is associated with susceptibility to progressive hydatid disease [22].

Echinococcus multilocularis — E. multilocularis causes alveolar echinococcosis (AE).

Life cycle — Rodents serve as intermediate hosts for E. multilocularis; humans are incidental hosts who acquire infection by ingesting eggs shed in stool by the definitive host, typically foxes [1]. The embryos or oncospheres hatch from the egg in the small intestine and are transported to the liver where they form multilocular hydatid cysts. In humans, the larval mass resembles a malignancy in appearance and behavior because it proliferates indefinitely by exogenous budding and invades the surrounding tissues. Unlike CE, protoscolices are rarely observed in human infection due to E. multilocularis. Fox and coyote populations have increasingly encroached upon suburban and urban areas of many regions and, as a result, domestic dogs or cats may become infected when they eat infected wild rodents [1].

Epidemiology — AE due to E. multilocularis has been reported in parts of central Europe, much of Russia, the Central Asian republics, northeastern, northwestern, and western China, the northwestern portion of Canada, and western Alaska [1]. A report suggests that European-like strains of E. multilocularis in animal hosts in Canada may be establishing in Canada and may result in the emergence of human AE in North America [23].

Foxes appear to play an important role in zoonotic transmission of E. multilocularis, as demonstrated by increases in the incidence of human AE in areas of Europe following an increase in the fox population. For example, in Switzerland, an increase in the incidence was observed from a mean of 0.10 per 100,000 (during 1993 to 2000) to a mean of 0.26 per 100,000 (during 2001 to 2005) [24,25]. In some eastern-central European countries previously considered to be free of AE, an increase in the number of human cases has been observed [26,27]. In some Baltic countries, a similar increase has been noted from 0.03 in 1997 to 2002 to 0.5 to 0.77 in 2009 to 2012 per 100,000 inhabitants [28]. The movement or relocation of foxes has also led to spread of the parasite from endemic to nonendemic areas in North America as well as on the north island of Hokkaido, Japan. Hunters, trappers, and others who work with fox fur are often exposed to alveolar hydatid disease. Hyperendemic areas have been described in parts of China with prevalences as high as 15 percent in some villages. In a 2020 report from Kyrgyzstan, the surgical incidence for cystic and alveolar echinococcosis was 13 per 100,000 and 3 per 100,000, respectively [7].

Human association with dogs that eat infected rodents can result in infection with the larval form of E. multilocularis. High prevalence rates have been reported among native peoples of Alaska and other Arctic regions, where local dogs feed on infected commensal rodents [29]. In hyperendemic foci in villages of the North American tundra, dogs prey on wild rodents, which live as commensals in and around dwellings. In central Europe, infected foxes expel eggs, which are then eaten by rodents inhabiting cultivated fields and gardens; these in turn can become a source of infection for dogs. Individuals who own dogs that kill game or dogs that roam outdoors unattended are at increased risk for E. multilocularis AE infection [30]. A higher risk of AE has also been observed among farmers. Foxes and rodents of the genera Microtus and Peromyscus are involved in the cycle in rural regions of central North America [31]. In western China and central Asia, coyote dogs and domestic dogs may play an important role in transmission of E. multilocularis [32,33].

Patients with immunosuppression are at increased risk for occurrence, delayed diagnosis, and progression of AE [34].

Pathology — E. multilocularis can cause severe infection in humans. The metacestode tissue behaves like a malignancy that invades and destroys tissue, extends beyond organ borders into adjacent structures, and can metastasize to distant sites [1,21,35]. In humans, disease spreads from primary infection in the liver to other organs, including the lungs and the brain, either by direct extension or hematogenous dissemination [1,21].

The lesions are composed of numerous irregular cysts of various sizes, with no sharp demarcation from surrounding organ tissue. Mixed solid and cystic lesions are common. The lack of limiting membrane allows exogenous budding, proliferation, and infiltration into adjacent tissues, resulting in necrosis of surrounding host tissue. Central necrosis of the lesions is frequent, and irregular calcifications are seen in up to 70 percent of cases. Microscopically, the cysts are composed of a thin laminated layer with minimal or no germinative layer. Brood capsules and protoscolices form in less than 10 percent of these cysts; instead, reproduction occurs by asexual lateral budding.

Metacestodes can die spontaneously, followed by degeneration [36].

Immunity — Most patients who become infected with E. multilocularis develop antibodies, although it is uncertain whether these antibodies play a role in controlling metacestode proliferation. T lymphocyte responses may be more important in controlling infection [37]. In addition, animal models suggest that the parasite may actively impair host immune responses. In vitro, E. multilocularis infection reduces interleukin (IL-) 2 receptor expression and IL-2 production but increases IL-5 secretion [37]. Certain human leukocyte antigens (HLAs) may also be involved in protection against or susceptibility to progressive infection. In patients with severe disease, for example, the frequency of HLA-DR 13 is increased five- to sixfold [38].

Echinococcus vogeli — E. vogeli occurs in central and northern South America. Human infections have been reported in Panama, Ecuador, Colombia, Venezuela, Costa Rica, Argentina, Peru, and Brazil. The definitive hosts are dogs and other canids; the principal intermediate hosts are pacas and other rodents [1]. A study found that as many as 11.7 percent of pacas in the Peruvian jungle were infected with E. vogeli cysts [39].

E. vogeli causes polycystic hydatid disease. Large cysts with multiple vesicles separated by septae often form and may spread to contiguous sites. Brood capsules bud internally from the germinative epithelium that lines the septa. Externally, the cyst is surrounded by fibrous tissue [1].

Polycystic echinococcosis (PE) is an emerging disease. In 1979, there were 12 cases in 4 countries, by 1997 there were 72 cases, and by 1998 there were 86 cases in 11 countries [40]. As of 2007, 172 human cases of PE were recorded from Central and South America [40]. Most cases of PE are due to E. vogeli. In one study including isolates from 72 human cases of PE in Central and South America in which species diagnosis was based on protoscolex hook morphology, 31 isolates were identified as E. vogeli and 3 were identified as E. oligarthrus; species identification was not possible in the remaining 38 isolates [41].

In general, the clinical disease is more severe than cystic disease but less severe than alveolar disease. The liver is involved in the majority of cases, and the lungs are involved in approximately 15 percent [21,40]. Progressive invasion of the liver and biliary tree may result in liver failure, portal hypertension, and biliary cirrhosis.

The diagnosis is made by imaging or serology. Most available serologic tests are not able to differentiate E. vogeli from other echinococcal species, particularly E. multilocularis [42]. However, the species may be differentiated by microscopic evaluation of the larvae.

Echinococcus oligarthrus — E. oligarthrus occurs from northern Mexico to southern Argentina. Three human cases of E. oligarthrus infection have been reported in Venezuela and Brazil [41]. The definitive hosts are wild felids such as the puma and the jaguar; the intermediate hosts include rodents and rabbits.

E. oligarthrus causes polycystic hydatid disease. Metacestodes tend to be localized in muscles or other extrahepatic sites. The human cases have affected the eye (two cases) and the heart (one case).

CONTROL OF ECHINOCOCCUS — The likelihood of cystic echinococcosis (CE) infection can be reduced by avoiding close contact with dogs. Careful washing of fresh produce can also reduce the likelihood of infection. The life cycle of the parasite can be disrupted by preventing dogs from consuming infected sheep viscera, which generally occurs in settings where dogs reside in close proximity to areas where sheep are slaughtered. Elimination of stray dogs has helped reduce infection in some endemic areas [43]. A traditional method for surveillance of E. granulosus among dogs consists of administering arecoline hydrobromide as a purging agent, with subsequent stool evaluation for worms or eggs. Stool antigen tests are a newer, safer, and effective surveillance technique [43]. Administration of praziquantel treatment to infected dogs has been shown to reduce the number of human cases in some countries (eg, Iceland, Australia, and New Zealand) [44]. Control programs are underway in Argentina, Chile, Portugal, China, and many Mediterranean countries.

Thus far, there is no available vaccine against the adult echinococcus infection in dogs [45]. Vaccination of sheep may also be useful for prevention of CE; intermediate hosts are capable of developing protective immunity [46]. A vaccine for E. granulosus, the EG95 vaccine, contains a purified recombinant protein of the parasite oncosphere as well as an adjuvant. Initially, two doses of the vaccine are administered one month apart, followed by a required annual booster [43,47-49]. In field trials of EG95 in Australia and Argentina, 86 percent of vaccinated sheep were found to be completely free of viable hydatid cysts one year after immunization (compared with unvaccinated control sheep that were experimentally challenged with E. granulosus eggs); the vaccination reduced the number of viable cysts by 99 percent [50]. Another trial found that EG95 afforded 90 percent protection to cattle, and a third dose boosted protection to 99 percent [51]. In a field trial of the EG95 vaccine against ovine CE, the prevalence of infection in older sheep was reduced from 56.3 percent before introduction of the vaccine to 21.6 percent eight years after its introduction [52].

Prevention of alveolar echinococcosis (AE) infection requires avoidance of contact with foxes and other potentially infected definitive hosts [53]. There are rare reports of cats acting as definitive hosts, but these are of uncertain significance [54,55]. Reducing contact between pets and rodent prey is also important for control; intermittent prophylactic treatment of canids with praziquantel can also be effective. Monthly praziquantel given to dogs in a 10-year field trial in Alaska was effective in reducing egg contamination [56]. A 10-year dog deworming program in Sichuan Province, China using praziquantel was very effective at reducing canine E. multilocularis infection as well as the prevalence of human AE [57]. Treatment of red fox populations using praziquantel baits in European and Japanese endemic areas has been shown to be effective at controlling transmission of E. multilocularis; however, the cost is high and sustainability is difficult [53,58]. No effective vaccine against E. multilocularis has been developed. Even if a vaccine became available, the primary cycle is almost always sylvatic, which makes a vaccination approach to control unlikely to be fully effective [59].

Delays in diagnosis of AE due to E. multilocularis can lead to progression of infection that cannot be managed with definitive surgery. Screening high-risk populations for earlier detection of alveolar hydatid disease might improve prognosis. (See "Echinococcosis: Treatment", section on 'Alveolar echinococcosis (E. multilocularis)'.)

SUMMARY

●Echinococcal disease is caused by infection due to the tapeworm Echinococcus. Four species of Echinococcus cause infection in humans. E. granulosus and E. multilocularis are the most common, causing cystic echinococcosis (CE) and alveolar echinococcosis (AE), respectively. The two other species, E. vogeli and E. oligarthrus, cause polycystic echinococcosis and are less frequently associated with human infection (table 1). Two additional species have been identified (Echinococcus shiquicus in small mammals from the Tibetan plateau and Echinococcus felidis in African lions), but their transmission potential to humans is not known. (See 'Introduction' above.)

●The life cycle of Echinococcus includes a definitive host (usually dogs or related species) and an intermediate host (such as sheep, goats, or swine). Humans are incidental hosts; they do not play a role in the transmission cycle. (See 'Life cycle' above.)

●The adult tapeworm inhabits the small intestine of the definitive host, which may be infected with thousands of worms. The tapeworm is composed of proglottid segments, which can produce parasite eggs containing embryos (oncospheres). The eggs are expelled in the feces of the definitive host and released to the environment, where they are infective to susceptible intermediate hosts and human incidental hosts. (See 'Life cycle' above.)

●Following egg ingestion by the intermediate or incidental host, the oncospheres hatch from the eggs, penetrate the intestinal mucosa, enter the blood and/or lymphatic system, and migrate to the liver or other visceral organs. A few days later, a fluid-filled cyst begins to develop, with subsequent development of multiple layers to become a metacestode (hydatid cyst). The nature of the cyst varies depending on the echinococcal species (table 2). (See 'Life cycle' above.)

●Protoscolices develop within the hydatid cyst. In intermediate and incidental hosts, protoscolices become daughter cysts (secondary cysts). In definitive hosts that ingest intermediate host visceral organs containing hydatid cysts composed of protoscolices, the protoscolices evaginate, attach to the intestinal mucosa, and develop into adult worms. (See 'Life cycle' above.)

●CE due to E. granulosus is a significant public health problem in South and Central America, the Middle East and eastern Mediterranean, some sub-Saharan African countries, western China, and the former Soviet Union. AE due to E. multilocularis occurs in the Northern hemisphere, in parts of central Europe, Russia, western China, areas of North America, and northern Africa; it accounts for less than 5 percent of all cases of hydatid liver disease. (See 'Echinococcus granulosus' above and 'Echinococcus multilocularis' above.)

●Control of echinococcosis infection requires avoidance of contact with dogs and other potentially infected definitive hosts. Careful washing of fresh produce can also reduce the likelihood of infection. Intermittent prophylactic treatment of canids with praziquantel can also be effective. Vaccination of sheep has been useful for prevention of CE in some areas. (See 'Control of Echinococcus' above.)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Dr. Karin Leder, who contributed to earlier versions of this topic review.