Schistosomiasis in Europe

The purpose of this review is to provide an overview of the burden of schistosomiasis in the European continent. It discusses three subjects: the endemic forms of non-human schistosomiasis in Europe; the introduction of transmission of human schistosomiasis into Europe; and the occurrence of imported cases of human schistosomiasis. Europe is not endemic for human schistosomiasis; nevertheless, it is affected by the disease in multiple ways, although the magnitude of the burden remains elusive because of gaps in surveillance and reporting. Schistosomiasis is a global neglected disease prevalent in tropical and subtropical areas. As of 2022, it is estimated that 251 million people require preventive chemotherapy for schistosomiasis, 90% of whom live in Africa. In Europe, human schistosomiasis is frequently detected in migrants from endemic countries who reach the continent. Additionally, outbreaks due to local transmission can sporadically occur following the introduction of schistosomes in one of the many freshwater bodies in southern Europe where competent snail hosts are found. Finally, human cercarial dermatitis is frequently occurring in Europe, because of the presence of avian schistosomiasis in several countries across the continent. A stronger epidemiological surveillance and reporting system, coupled with more surveys on humans and snails, can contribute to better assess and characterize the burden of schistosomiasis in Europe.


Introduction
Schistosomiasis is a neglected tropical disease caused by blood flukes (trematode parasites) belonging to the genus Schistosoma. It is a vector-borne disease transmitted by several species of freshwater snails. Human infection is associated with two main clinical forms: intestinal schistosomiasis and urinary (or urogenital) schistosomiasis [1•].
The species responsible for intestinal schistosomiasis in humans are six: S. mansoni, transmitted by Biomphalaria spp. snails; S. japonicum, transmitted by Oncomelania spp. snails; S. mekongi, transmitted by Neotricula spp. snails; S. malayensis transmitted by Robertsiella spp.; and S. guineensis and the related S. intercalatum, transmitted by Bulinus spp. The only species responsible for urinary (or urogenital) schistosomiasis in humans is S. haematobium, transmitted by Bulinus spp. snails [1•].
More than 10 other schistosome species are parasites of animals, in which they cause forms of schistosomiasis that are endemic in several countries and may occasionally infect humans. Nevertheless, parasitic larvae rarely reach adult stage in the human host and are only responsible for mild and transient disease.
Schistosomiasis is a global disease mainly prevalent in tropical and subtropical areas. According to WHO, at global level, over 251 million people require preventive chemotherapy for schistosomiasis, with approximatively 90% of them living in Africa. Globally, 78 countries are considered endemic for schistosomiasis by WHO [2•]. Nevertheless, the actual number of endemic countries could be higher. For example, cases of schistosomiasis have been reported recently in Nepal [3,4], in Myanmar [5], as well as in Europe (please see further below).
This review focuses on schistosomiasis in Europe. It discusses three subjects: (2) The introduction of transmission of human schistosomiasis into Europe (3) The occurrence of imported cases of human schistosomiasis

Avian Schistosomiasis and Other Forms of Non-human Schistosomiasis
Although human schistosomiasis is not endemic in Europe, avian schistosomiasis is present in several European countries, including Czech Republic, Denmark, France, Germany, Iceland, Poland, Spain, and Switzerland [6, 7•]. Its distribution is in fact global and outside Europe, it has been documented in several countries including Argentina, Australia, Canada, Chile, Iran, Japan, the Netherlands, New Zealand, Saudi Arabia, South Africa, and the USA [6,[8][9][10]. Trichobilharzia spp., Ornithobilharzia spp., and Bilharziella spp. are the most common genera responsible for avian schistosomiasis in Europe, while the most common molluscan intermediate hosts belong to the pulmonate snail families Physidae (e.g., Physa spp.), Lymnaeidae (e.g., Radix spp.), and Planorbidae (e.g., Biomphalaria spp.) [6].
As the word "avian" indicates, the natural hosts are represented by several aquatic birds, such as ducks of the genera Anas, Aythya, Cairina, and Spatula; swans of the genus Cygnus; and geese of the genus Anser [11,12].
Avian schistosomes may be responsible for disease in their natural animal hosts; for example, the pathogenic effects of Trichobilharzia regenti on the central nervous system of Anas, Cairina, and Spatula are well-known and studied [13].
Adult schistosomes reside in the mesenteric veins of their animal host. Eggs reach the intestine, are passed in feces, and released in the environment. In contact with water, eggs hatch and liberate miracidia which in turn penetrate into a suitable snail intermediate host and develop into cercariae. Finally cercariae are released in water where they can infect animal hosts and occasionally human hosts (Fig. 1). Surface freshwaters are typically those where cercariae are found.
Besides avian schistosomes, a few genera of the family Schistosomatidae having mammals as natural hosts are known to be responsible for cercarial dermatitis. Among them, Orientobilharzia spp. has been found in Europe (Hungary, Russia), where Radix auricularia has been identified as the intermediate host; natural final hosts are ungulates such as cervids (e.g., deers) [14][15][16].
The distribution of mammal schistosomiasis in Europe and its relevance to human health are certainly less important than in the case of avian schistosomiasis. Nevertheless, it should be noted that S. bovis, a parasite causing intestinal schistosomiasis in ruminants, is present in several areas of Mediterranean Europe, where its intermediate hosts are Bulinus spp. and Planorbarius metidjensis [17]. Although S. bovis is not associated with infection in humans, it can hybridize with other Schistosoma species and produce infective offspring. Notably, S. haematobium/S. bovis hybrids have been found to be responsible for human infections in Corsica [18•] (see below).

Epidemiology
Humans can be accidental hosts of avian schistosomes, as their larval stages (cercariae) can penetrate human skin. However, when in the human body, avian cercariae die in the skin, being entrapped by the host's immune response; as such, they do not mature into adults and are not able to complete the life cycle within the human accidental host.
Nevertheless, cercariae are responsible for a cutaneous, localized inflammatory response associated with their penetration of the human skin. Human cercarial dermatitis, commonly referred to as swimmer's itch, is frequently reported from several European countries; it is often underreported because of its mild health impact and as such likely to occur in other countries in addition to those mentioned above.
The earliest known reports of human cercarial dermatitis ("koganbyo" or "lakeside disease") can be traced in the late nineteenth-century Japan, a country then endemic for human schistosomiasis due to S. japonicum [19]. In 1928, William W. Cort first described the occurrence of human cercarial dermatitis due to non-human schistosomes at Douglas Lake, Michigan, USA [19], while the first documented outbreak occurred at Clear Lake, Manitoba, Canada, in 1934, with over 50,000 people affected [19]. In Europe, the earliest reports of human cercarial dermatitis date back to the 1930s, when Brumpt described a case of "dermatite des nageurs" due to Cercaria ocellata in France [20]. Case reporting continued from other European countries over the following decades; in Denmark, for example, the first case of human cercarial dermatitis was reported in the 1950s, although avian schistosomiasis had already been documented in the 1930s [7 •]. While human cercarial dermatitis due to mammal schistosomes has not been reported from Europe, it cannot be excluded that human infections by cercariae of mammalian schistosomes can lead to similar pathologies as those caused by avian schistosome. In fact, human cercarial dermatitis from Orientobilharzia spp. has been reported from non-European countries such as Iran [21].
The burden of human cercarial dermatitis in Europe is not well known. The mildness of the disease entails its frequent under-reporting. Nevertheless, the condition is known to be widespread across the continent. It can be considered an occupational disease in people whose profession entails regular contact with water, as in the case of fishermen and people working on the docks [16].
Human cercarial dermatitis in Europe typically occurs during the summer (June to September), when bathing for recreational purposes is common as a mean to seek refreshment from warm temperatures.

Signs and Symptoms
Infection with avian schistosomes follows contact with infested water (lakes, ponds, or reservoirs; occasionally shallow marine waters too), usually for occupational or recreational purposes.
Symptoms of human cercarial dermatitis include reddening and itching of skin surfaces exposed to water; the most common locations are legs and feet. This is an indication of initial penetration of the cercariae.
The onset of symptoms usually occurs between a few minutes (when the person is still in the water or immediately after emerging) and a maximum of 24 h after exposure. Lesions are initially erythematous maculae (1-2 mm in diameter) due to local inflammation, but rapidly evolve into larger papulae (3-5 mm in diameter) and after a few additional hours may become vesicular (1-2 mm in diameter). Itching may be important and be associated with insomnia [16]. Signs and symptoms are usually self-limiting; they peak within 1-3 days after exposure, begin to resolve after 5-7 days, and may last 1-3 weeks. The resolution phase may be characterized by a reddish spot which gradually disappears; post-inflammatory hyperpigmentation (hypermelanosis) may persist for months or indefinitely [16].
The development of lesions is mediated by the human host's immune responses, indicating the occurrence of hypersensitization and the development of allergic-type, immunogenic reactions [7•]. The first exposure may not be associated with signs and symptoms but causes a sensitization, which triggers a more rapid and severe onset of signs and symptoms in people with a history of previous contact with cercariae, especially in the case of repeated exposure. Sensitization may persist for year even in absence of new exposures [16].
Infections with a large number of cercariae may also cause fever, limb swelling, nausea, and diarrhoea [16].
Scratching the affected areas may result in secondary bacterial infections, especially in the case of ruptured vesicles.
Recent studies in animal models have demonstrated that cercariae may occasionally survive in non-compatible hosts for days and weeks and reach other organs (including the central nervous system, heart, kidney, intestine, liver, and lungs) where they cause damage to host tissues. Such ectopic locations are more frequent in primary infections, as milder inflammatory reactions allow cercariae to escape from the skin and migrate further. Further investigations are required to assess the relevance of these findings to infection in humans [16].

Diagnosis and Treatment
The timeline, appearance, and distribution of the lesions body, as well as the history of exposure to a freshwater body should suggest the diagnosis of human cercarial dermatitis and enable a differentiation from similar skin lesions resulting from insect bites or contact dermatitis [16].
Most lesions resolve spontaneously and do not require any treatment; however, good hygiene to prevent itching and secondary infections is important.
Topical antipruritic agents, antihistamines, or corticosteroids can be used to relieve symptoms. Systemic antihistamines or corticosteroids may be required in case of severe clinical pictures [22•].
Praziquantel is the treatment of choice for all forms of human schistosomiasis [23 •]. However, it is not effective against the larval stages of Schistosoma spp. [24]; as such, its administration to patients suffering from human cercarial dermatitis is not recommended.

Introduction of Transmission of Human Schistosomiasis into Europe
Human schistosomiasis is not endemic in Europe. Nevertheless, foci of transmission have been occasionally documented as a result of the introduction of parasites into freshwater bodies populated by competent snail hosts.
In the course of the twentieth and twenty-first century, transmission of S. haematobium has been reported from three countries: Portugal, Spain, and France.
In Portugal, transmission was limited to one locality, Estoi, located in the southern Algarve province. Cases were first detected in the 1920s, and transmission was still reported in 1948. Nevertheless, it has been considered extinct since a survey was carried out in 1966 [25], while the last patient was cured in 1967 [26]. It is unclear how recent the establishment of transmission in Portugal could be considered; most probably, the parasite had been introduced by travelers from Angola (then a Portuguese colony), and autochthonous transmission could occur because of the presence of local strains of aquatic snails [ [31] has been developed in order to better delineate the potential areas of transmission.
The third documented outbreak due to autochthonous transmission of schistosomiasis in Europe occurred in Corsica, France, in 2011 [29,30]. Local transmission was confirmed in 2013, and more than 100 infected local cases and tourists from several European countries who had bathed in the natural pools along the Cavu river, near Sainte-Lucie-de-Porto-Vecchio, were identified [32]. Further investigations showed that a hybrid of S. haematobium and S. bovis is responsible for the transmission, while the intermediate host is B. truncatus. Although S. bovis is naturally present in Mediterranean Europe, it is considered more likely that hybridization may actually have taken place not in Corsica but elsewhere, likely in Senegal, from where hybrid parasites would have been introduced [18 •, 33,34]. Transmission is apparently still ongoing in Corsica, and a new focus different from the Cavu river [35, 36•], the Solenzara river, also located in the south-eastern part of the island, has been identified. The fact that a hybrid parasite is involved might explain why its transmission cycle remained active on the island; it may infect local livestock, which would act as reservoirs of the disease [34].
The risk of further introduction of transmission of urogenital schistosomiasis in Europe is significant in reason of the intensification of human travels (e.g., migration) and the widespread presence of Planorbidae strains susceptible to S. haematobium infection in several Mediterranean countries. The chance that infected people come into contact with freshwater bodies populated by susceptible snails is likely to increase in the future. Notably, presence of Bulinus spp. has been demonstrated in Cyprus, France, Greece, Italy, Spain, as well as Portugal [26,31,37,38], all countries subject to flows of migrants from endemic countries.
In addition, the area of distribution of snails can be further expanded by climate change [39,40], which can favor adaptation of snails to new environmental niches, as well as by transportation of snails via aquatic plant trade, or migrant birds.
Introduction of transmission of other species such as S. mansoni in Europe has not been documented so far. Nevertheless, Biomphalaria tenagophila, which is involved in transmission of S. mansoni in Brazil, has been identified in Romania [41]. In addition, some of the snails susceptible to this infection such as B. glabrata, B. traminea or B. tenagophila, as well as B. pfeifferi, an intermediate host of S. mansoni in South America, have proven their capacity to invade new continents [42].
In order to prevent the establishment of transmission of Schistosoma spp. in Europe, the following public health measures can be considered: -Regular malacological surveys including use of environmental DNA techniques in areas where competent snails can be found [43]. -Reinforcement of the epidemiological surveillance: screening of migrants reaching Europe and screening of tourists back from endemic countries [44].

Importation of Cases of Human Schistosomiasis into Europe
Every year, large numbers of people travel to European countries for different reasons and purposes. Without considering shorts stays for tourism, and limiting our analysis to European Union countries, between 2 and 3 million people settle in Europe every year. Approximately 90-95% are legal immigrants moving to Europe for work (45%), family (24%), education (12%) asylum (9%), or other reasons (10%). The remaining 5-10% reach Europe through irregular border crossings, including land border crossings and sea crossings [45]. Among those who are issued a first residence permit (legal immigrants), the most frequent countries of origin are Ukraine, Morocco, Belarus, India, Russia, Brazil, Turkey, China, Syria, and USA. Among such countries, only Brazil and China are still reporting autochthonous cases of schistosomiasis [45, 46•].
Among those reaching Europe through irregular border crossings, over 50% come from five countries that are either non-endemic or no-longer endemic for schistosomiasis: Syria (23.2%), Afghanistan (8.4%), Tunisia (8.3%), Morocco (8.2%), and Algeria (6.9%); the first endemic countries represented is Egypt, which however accounts for only 4.6% of the arrivals. Several African endemic countries follow with smaller proportions [45].
In general, it is therefore possible to conclude that the number of immigrants to Europe proceeding from countries endemic for schistosomiasis is quite small; consequently, the number of imported cases of schistosomiasis remains overall modest if compared to the global burden of disease attributable to schistosomiasis. We should also highlight that, irrespective of the numbers, a person with schistosomiasis living in Europe is unlikely to represent a public health problem for anyone, considering that it is almost impossible for Schistosoma spp. to find suitable environmental conditions in European countries to complete the transmission cycle and infect someone else, although exceptions exist (please see above).
Nevertheless, the proportion of immigrants from endemic countries that are diagnosed with schistosomiasis is not small, reflecting the high level of transmission as well as the limited access to diagnosis and treatment in countries of origin.
Most of the information on imported schistosomiasis comes from surveys published in scientific literature, with the limitations that this non-systematic method for collecting information often entails.
A study found that among African immigrants newly arrived to Spain from October 2004 to February 2017, the proportion of those infected with schistosomiasis was 12.3% [47]. Other published studies estimated the prevalence of infection among immigrants from sub-Saharan Africa to Italy to 17% [48], to 10% among immigrants from Mali and Senegal, and to 1% among the general immigrant population, when assessed by parasitology [49]. Another study found a seroprevalence of 10.2%, although only S. mansoni antigens were used [50]. Among 462 recently arrived asylum seekers screened in Italy between 2014 and 2015, 21.2% was positive to at least one test for schistosomiasis [51].
If we focus on studies carried out among people experiencing signs and symptoms of diseases, another study carried out in Italy found that among immigrants seeking care in nine infectious and tropical diseases sentinel centers across the country over a period of 7 years (2011-2017), 47.2% (1350/2858) was diagnosed with schistosomiasis [52].
Those infected are also usually found to suffer from advanced morbidity, indicating that management is often inappropriate in countries of origin, or screening implemented late upon arrival in Europe. For example, a survey [53] found that 47.6% of a group of immigrants to Italy aged 18-29 years infected with S. haematobium had bladder masses at ultrasound examination. Again from Italy, another survey [54] found that a high proportion of patients diagnosed with schistosomiasis, both asymptomatic and symptomatic, were screened or tested only several months after arrival in Italy and most of them presented with clinical apparent disease. A third survey [50] found that 68% of migrants to Italy suffering from urogenital schistosomiasis had urinary tract abnormalities when screened by ultrasonography. In France, Leblanc et al. (2017) [55] reported that 37/40 (93%) immigrant children with a diagnosis of 1 3 schistosomiasis had a chronic urinary form with hematuria. In Spain, Roure et al. (2017) [56] concluded that morbidity associated with chronic long-term schistosomiasis is frequent among African immigrants in non-endemic countries.
Some investigations were carried out among specific population groups, such as children or women.
In Paris, France, a survey conducted among both symptomatic and asymptomatic recently immigrated children estimated the prevalence of schistosomiasis at 24.3%, by using multiple tests [57].
A few studies have also focused on gender issues. For example, Roure et al. (2022) [58•] report on an assessment conducted among a migrant population coming from schistosomiasis-endemic countries and settled in metropolitan Barcelona, Spain. Serology for schistosomiasis among the whole sample was positive in 222/405 (54.8%). That proportion was slightly higher (58.8%) among the 51 women in that population (30/51). Positive women also showed a higher prevalence of gynecological signs and symptoms compared to the seronegative women (96.4% vs. 66.6%).
In addition to the more common infections with S. mansoni and S. haematobium, other rarer forms of imported schistosomiasis, such as the one caused by S. japonicum, have also been reported from Europe, as a recent review carried out in Italy has shown [59].
Few studies investigated the relative proportion of cases of schistosomiasis detected among non-European immigrants compared to the total number of cases detected in Europe. The European Network for Tropical Medicine and Travel Health conducted a sentinel surveillance study on 1465 cases of imported schistosomiasis between 1997 and 2010 [60]. The results show that 486 (33%) cases were identified among European travelers, 231 (16%) among long-term expatriates, and 748 (51%) among non-European immigrants.
A survey also tried to assess awareness of schistosomiasis among health professionals; an investigation including specific questions about the diagnosis and management of "tropical" urological diseases was carried among European urologists, showing limited knowledge of schistosomiasis and its associated morbidity [61].
In conclusion, it can be said that while the number of cases of schistosomiasis imported into Europe is overall relatively small, its proportion among people originating from endemic countries is quite high. Information available remains limited, however, for the reason that schistosomiasis is not a disease under surveillance in European Union or European Economic Area (EU/EEA) countries, and the relevant information, when available at country level, is not shared with institutions such as the European Centre for Disease Prevention and Control (ECDC) or WHO for compilation.
Most data available on schistosomiasis in Europe are consequently generated by surveys. Nevertheless, these are not likely to generate an accurate picture of prevalence and incidence of new cases. For example, they are implemented among selected population groups such as people experiencing symptoms of schistosomiasis or poor health in general, or those attending health facilities for any reason; in addition, they often employ different diagnostic techniques that may hamper a proper comparison and interpretation of information. Finally, a real appreciation of the burden of imported schistosomiasis in Europe is affected by the fact that most studies on this subject are available from a small number of European countries only, mainly those through which irregular immigrants from schistosomiasis-endemic countries (mainly African countries) enter the continent, that is, Italy and Spain. It should also be noted that in general, information on imported schistosomiasis in European countries not belonging to the EU/EEA is very limited.
In terms of normative directions, it should be noted that guidance published by the European Union advises that "serological screening and treatment (for those found to be positive) [should be offered] to all migrants from countries of high endemicity in sub-Saharan Africa, and focal areas of transmission in Asia, South America and North Africa," on the grounds that "it [is] likely to be effective and cost-effective to screen child, adolescent and adult migrants" [44,62].
Nevertheless, information on the actual implementation of this recommendation is not available. One of the reasons could be that there are no standard EU guidelines or standard operating procedures for the screening and treatment of schistosomiasis and consequently few examples of practice [44]. Ireland is reportedly the only EU/EEA country with a published general guidance for screening and treatment of schistosomiasis in asymptomatic migrants. The United Kingdom is the only other European country to have such guidance [44].

Conclusions
The burden of schistosomiasis in Europe is likely to be larger than currently reported or estimated [63]. Reasons include the underreporting of human cercarial dermatitis because of its mild associated morbidity, the scarcity and heterogeneity of data on schistosomiasis among people originating from schistosomiasis-endemic countries, and the possibility that small outbreaks of autochthonous transmission go unnoticed as probably associated with low intensity of infection and therefore mild symptoms.
A stronger involvement of health services in terms of epidemiological surveillance and reporting system, coupled with more surveys on humans and snails, can contribute to addressing the elusive burden of schistosomiasis in Europe.

Conflict of Interest
The authors declare no conflict of interest.

Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by either author.
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