Angiostrongylus, Opisthorchis, Schistosoma, and Others in Europe

Parasites where you least expect them: Angiostrongylus, Opisthorchis, Schistosoma, and others in Europe

Edoardo Pozio Istituto Superiore di Sanità ESCMIDRome, eLibrary Italy © by author Scenario of human parasites in Europe in the 21th century

• Cosmopolitan and autochthonous parasites • Parasite infections acquired outside Europe and development of the disease in Europe • Parasites recently discovered or rediscovered in Europe – imported by humans or animals (zoonosis) – always present but never investigated ESCMID– new epidemiological scenarios eLibrary © by author Parasites recently discovered in Europe: Schistosoma spp.

Distribution of human schistosomiasis in 2012 What we knew on the distribution of schistosomiasis, worldwide up to 2012

ESCMID eLibrary © by author Parasites recently discovered in Europe: Schistosoma spp.

• Knowledge on Schistosoma sp. in Europe before 2013 – S. bovis in cattle, sheep and goats of Portugal, Spain, Italy (Sardinia), and France (Corsica) – S. bovis strain circulating in Sardinia was unable to infect humans – intermediate host snail, Bulinus truncatus, is present in Portugal, Spain, Italy, France and Greece – S. haematobium foci were described in Algarve (Portugal) ESCMIDfrom 1921 to early 1970s eLibrary © by author Parasites recently discovered in Europe: Schistosoma spp. • more than 125 schistosomiasis infections were acquired in Corsica (France) from 2013 to 2015 • eggs excreted from patients in the urine were identified as – S. haematobium – S. bovis – S. haematobium/S. bovis hybrid

ESCMID eLibrary Outbreak of urogenital schistosomiasis in Corsica (France): an epidemiological case study Boissier et al. Lancet Infect Dis . 2016 Aug;16(8):971 ©-9. by author Parasites recently discovered in Europe: Schistosoma spp.

• What we known today – intermediate host snail, Bulinus truncatus, of Corsica can be vector of: – Zoonotic strain of S. bovis from Senegal – S. haematobium from Senegal – S. haematobium/S. bovis hybrids from Senegal – Non zoonotic livestock strain of S. bovis

• What we can argue today – human schistosomiasis can spread in the European regions bordering the Mediterranean basin, where populations of B. truncatus are present – Planorbis metidjensis had been also considered as vectorESCMID of S. haematobium and S. eLibrarybovis in the Iberian peninsula © by author Conclusions

• Schistosoma spp. have been introduced in Corsica from immigrants of Senegal • The Corsica focus tell us how easy Schistosoma spp. can spread even where good hygiene and sanitation practices are in place • Only contacts with infected freshwater is a prerequisite for humans to be infected – Systems involving primary and secondary sewage treatment without chlorination are highly successful for removing schistosoma eggs • The persistence of the parasite in humans is very high – Adult parasites can live several decades emitting eggs throughout their host's lifetime • Since a percentage of human cases are asymptomatic makes parasite detection problematic • It is difficult to support public health services in the control of this disease • We are far from being able to quantify the risk of schistosomiasis emergenceESCMID in Europe eLibrary © by author Parasites recently re-discovered in Europe: Opisthorchis felineus

• O. felineus was described in cats of Italy by Rivolta in 1884 • In the 20th century, it was described in humans of Eastern Europe (e.g., Belarus, Russia, and Ukraine) and Asia (Siberia) • In EU in the last fifty years, sporadic infections had been described in: – humans of Germany and Greece – domestic and wild animals (mammals and fish) • From 2003 to 2016, 213 persons acquired opisthorchiasis ESCMIDin Italy (9 outbreaks eLibrary and 5 single infections) © by author 2009 outbreak from the index case to the outbreak - 1

• Index case – a 46-year-old woman who organized gastronomic events presented with eosinophilia to the hospital, on March, 2010 • She had suffered fever, headache, muscle and abdomen pain, asthenia, and general malaise between late December 2009 and January 2010 • She was treated with mebendazole, but there was no reduction in the eosinophilia • Fecal and serum samples tested positive for O. felineus eggs and anti- Opisthorchis IgG

ESCMID eLibrary (egg size 22–32 µm × 10–22 µm) © by author 2009 outbreak from the index case to the outbreak - 2 • the woman reported the consumption of raw tench fillets during a gastronomic event in the town of Bomarzo (Central Italy) on December 8, 2009 • because the gastronomic event was only by invitation, it was possible to trace all the participants 4–5 months after the event (April to May, 2010) • 12/44 participants had had symptoms of unknown etiology in late December 2009 and early January 2010 • 31/44 serum samples tested positive for anti-Opisthorchis IgG (attack rate 70%) • 28/36 fecal samples tested positive by either microscopic analysis (N = 19) or PCR (N = 9) for Opisthorchis eggs identified as O. felineus by PCR

ESCMID eLibrary © by author 2010 outbreak from the index case to the outbreak - 1

• the index patient was hospitalized in the Aosta town, Northern Italy, on August 15 • 10 additional people were hospitalized from August 22 to 26 • due to eosinophilia, fecal and serum samples were tested and resulted to be positive for O. felineus • 49 additional cases were diagnosed between September and December, 2010 • All infected persons had attended a gastronomic event in a village of Valle d’Aosta region (Northern Italy) on July 24, 2010 • 60 infected persons /93 participants at the dinner (attack rate 64.5%)

ESCMID eLibrary © by author 2010 outbreak epidemiological investigation • organizers of the gastronomic event had used marinated fillets of tench purchased on the Bolzano market • The owner of the Bolzano market had purchased tenches on the Rovigo market • The Rovigo market was supplied by a Viterbo company, which fished tenches from the Bracciano Lake (Latium region, Central Italy) • According to the Italian regulation, wholesalers must label the boxes that contain tenches with a warning, that states that the ﬁsh should not be consumed raw if not previously ESCMID frozen eLibrary Unfortunately, labels were lost during transportation!!! © by author 2011 outbreak from the index case to the outbreak • The index patient was hospitalized at the Viterbo hospital on 24 August – 18 additional people were hospitalized from 25 to 31 August – Other 61 cases were diagnosed between September and October • 100 people were traced back, of which 81 were infected (attack rate 81%) – 57 symptomatic persons – 24 asymptomatic persons • All infected persons had a meal at a restaurant on the Bolsena lake shore, on July 22 • According to the receipt matrixes, about 500 people, had eaten raw marinated ﬁsh • whether the approximately 400 persons who were not traced back acquired the infection in an asymptomatic form or did not get infected, remains unknown ESCMID eLibrary © by author 2011 outbreak epidemiological investigation

• 45 infected persons were tourists from the Viterbo and Orvieto towns (about 35 km away) • 19 infected persons were tourists from 7 other Italian towns and cities • 2 infected persons were tourists from Austria • 5 infected persons were tourists from the Netherlands ESCMID eLibrary © by author O. felineus in final and intermediate hosts of central Italy lakes

Lakes Trasimeno Bolsena Vico Bracciano Snail (Bithynia sp.) n.t. 13.3% n.t. 1.2% Tench (Tinca tinca) 0% 74% 28% 95% Stray cats 0% 36.6% n.t. 73.3%

ESCMID eLibrary © by author Conclusions - 1

• Clinical signs and symptoms and laboratory features of opisthorchiasis are not pathognomonic • The incubation period could be of 2-3 weeks • The prepatent period could be longer than 5 weeks • In low infected non-treated people, eggs cannot be detected in feces after 5-6 months p.i. • The detection of O. felineus DNA in fecal samples by PCR is more sensitive than the microscope detection of the parasite eggs • No commercial kits are available on the EU market to detect anti- Opisthorchis IgG in humans • Opisthorchiasis can be suspected in persons: – with eosinophilia, increased liver enzymes and malaise – who had consumed raw freshwater fish • The albendazole treatment fails to kill the parasites in a percentage of patients • The praziquantel treatment is more effective than the albendazole treatment • About 1/3 of infected persons were asymptomatic (serious problems for chronic infections and risk of cholangiocarcinoma) • ESCMIDThere could be a number of persons eLibrary with cryptic and chronic infection in the EU © by author Conclusions - 2

• only freezers marked with 3-4 stars reach a temperature of −18 °C, which kill metacercariae in fish • marinating does not kill metacercariae present in fish fillets • fishermen and restaurant owners, should avoid to spread uncooked fish and fish scraps in the environment or in not controlled garbage • tenches and other cyprinidae fish intermediate hosts of O. felineus, should be market with caution and always consumers must be informed on the risk of infection • fresh tenches fished in the central Italian lakes can reach North Italian and European markets in few hours ESCMID eLibrary © by author A parasite recently discovered in Europe: Angiostrongylus cantonensis

• zoonotic nematode endemic in Asia, the Paciﬁc islands, Australasia, Africa, the Caribbean islands and the USA • humans acquire this infection by ingesting raw terrestrial snails and slugs infected with larvae or paratenic infected hosts • the most frequent clinical symptom is headache, followed by neck stiffness, paresthesia, vomiting, fever, nausea, and blurred vision of diplopia • clinical symptoms and signs are always joined with eosinophilic meningitis • never, this parasite had been documented in Europe ESCMID up to 2010 eLibrary © by authoradult female A parasite recently discovered in Europe: Angiostrongylus cantonensis

• In 2010, A. cantonensis was documented in rats (Rattus rattus) and intermediate slug hosts of two localities of Tenerife, adult female Canary Islands (Spain)

• The phylogenetic tree based on ITS-2 sequences shows that worms of Canary islands belong to the same aplotype of those of Philippines • Probably this parasite was introduced in the Tenerife island by rats which reached the Canary island by vessels adult female • Climatic conditions, such as the temperature and precipitation could be important factors determining the distribution of A. cantonensis in Tenerife • The changing climate conditions (e.g., increasing temperature) could favor the spread of this zoonotic nematode in Europe

• Baylisascaris procyonis is a zoonotic North American nematode imported into Europe with its host, the raccoon (Procyon lotor) • Humans acquire the infection ingesting embryonate eggs • This nematode is the etiological agent of neural, ocular and visceral larva migrans, causing eosinophilic meningoencephalitis and progressive neurological disease • As with Toxocara infections, young children of 1–4 years of age are at the greatest risk of heavy infection due to poor hygiene and pica • In the environment, eggs remain infective for years and ESCMID can survive freezing temperatures eLibrary of -15 °C © by author Parasites imported in Europe by humans or animals: Baylisascaris procyonis - 2

• Today, there are about 70,000 raccoons in Central Europe • Human infections have been diagnosed in Germany • Children who survive to this infection, often have profound neurological impairment, with partial paralysis, blindness, seizures and incontinence • Magnetic resonance imaging may reveal findings consistent with acute disseminated encephalomyelitis • Diagnosis is based on clinical signs and symptoms, and resological tests • Antigens for serology are available at CDC (Atlanta, USA) and at the National Reference Center for Parasitology ESCMID of Montreal (Canada) eLibrary © by author What do these examples teach us? • New pathogens can be introduced in Europe if intermediate and/or final hosts are present (e.g., Schistosoma spp.) • The global worming is favoring the development of parasites, which did not survive in the past during the winter time (e.g., Schistosoma spp.) • Foodborne parasites, which circulated for centuries in Europe without causing infections in humans, can suddenly cause hundreds of infections due to changing eating habits (e.g., O. felineus) • The introduction of alien animals as pet (e.g. the raccoon) in Europe can be the courier of new zoonotic parasites (e.g. Baylisascaris procionis) • International airports can be the gate of new pathogens due to the illegal introduction by personal buggage of thousand tons of meat and other food products per week • Zoonotic parasitic infections can be difficult to be diagnosed due to the lack of diagnostic kits and experienced physicians • ESCMIDMost of commercial kits on theeLibrary EU market to diagnose parasitic infections are not validated by an independent body, resulting in very low performance © by author Thank you for your attention