1. The Leishmaniases in the WHO European Region: Epidemiology, Geographical Distribution and Burden Luigi Gradoni Head, Unit of Vector-borne Diseases and International Health Department of Infectious Diseases Istituto Superiore di Sanità (National Institute of Health) Rome, Italy luigi.gradoni@iss.it WHO-EURO Training Course on Case Management and Surveillance of the Leishmaniases Tbilisi, Georgia 30 January – 01 February 2017

2. LEISHMANIA LIFE CYCLE

3. Presence and density of competent Phlebotomus species are associated with endemic Leishmania transmission Leishmania species/genotype and mammal host factors are associated with clinical manifestations of leishmaniases

4. Clinical manifestations of human leishmaniases are caused by some 20 Leishmania species/subspecies worldwide Leishmaniases can roughly be grouped into two main clinical forms: - Visceral leishmaniasis, a severe condition resulting from the dissemination of Leishmania in macrophage-rich organs - Cutaneous leishmaniasis, a benign but disfiguring condition resulting from the multiplication of Leishmania in skin macrophages

5. Leishmaniases are endemic in over 98 countries with more than 350 million people at risk It is estimated that 1.3 million new cases of leishmaniasis (0.3 million of VL and 1.0 million of CL) occur every year (= the 9 th largest disease burden among infectious diseases) With other neglected ‘tropical’ diseases, leishmaniasis shares the characteristics of being not: - recognized and prioritized politically - visible according to its burden - having national strategies for its control Accurate information on its extent and distribution is often missing because of insufficient surveillance systems Practical tools for case management are often lacking

6. The Leishmaniases in the WHO European Region The diseases are caused by three distinct Leishmania species adapted to various hosts and transmitted by different phlebotomine vectors, which determine their prevalent/exclusive zoonotic or anthroponotic nature. Both VL and CL are endemic and widespread in the WHO European Region.

7. Leishmaniases caused by Leishmania infantum Leishmania infantum is the sole agent of autochthonous VL throughout the European Region This parasite also causes sporadic CL in the same geographic range Leishmania infantum has domestic dogs as the main reservoir host (= zoonotic VL and CL) Several phlebotomine species of the subgenus Phlebotomus (Larroussius) are the main proven vectors P. ariasi, P. perniciosus, P. neglectus, P. perfiliewi, P. tobbi, P. kandelakii, P. transcaucasicus P. (Adlerius) balcanicus P. (Adlerius) longiductus

8. The coevolution of Leishmania infantum and the subgenus Phlebotomus (Larroussius) P.ariasi P.perniciosus P.neglectus P.tobbi P.syriacus P.kandelakii

9. Leishmaniasis caused by Leishmania major Leishmania major is an agent of autochthonous CL in the eastern European Region. It is a natural parasite of wild rodents, mainly from the Gerbillinae subfamily (= zoonotic CL) The only proven phlebotomine vector is Phlebotomus papatasi P. papatasi R. opimus P. obesus

10. Leishmaniasis caused by Leishmania tropica Leishmania tropica is an agent of autochthonous CL in the eastern European Region. The parasite is assumed to have humans as the main natural host (= anthroponotic CL) The only proven phlebotomine vector is Phlebotomus sergenti P. sergenti

11. Imported (non-autochthonous) Leishmaniasis Localized CL is the most common clinical form of imported leishmaniasis caused by non-autochthonous Leishmania species in returning travelers or migrants. Limited information is available about the incidence of CL importation, which involves both non-endemic and endemic countries of the European Region. Recent reports show an increase in incidence The main competent vector of imported Leishmania

12. Leishmaniasis Burden in the WHO European Region The leishmaniases are neglected and poorly reported diseases with underestimated or undetermined incidence in most countries of the WHO European Region. In general, the regional incidence of leishmaniasis is estimated at less than 2 per cent of the global burden as per recent WHO estimates. Visceral leishmaniasis burden Underreporting is considered mild to moderate. The estimated annual incidence is around 1100 to 1900 cases. Spain, Italy, Albania, Turkey, Georgia, Azerbaijan and Tajikistan are the most affected countries. The incidence of VL has been declining where living standards have improved. VL associated with HIV infection has also been declining in Europe, thanks to the antiretroviral therapies.

13. Although stable or declining in burden, VL outbreaks or epidemic trends were recently reported from southern Europe Leishmaniasis outbreak in Fuenlabrada, Spain Multi-annual epidemic trend, Italy

14. Cutaneous leishmaniasis burden The Region is heterogeneous as regards geographical distribution of agents and estimates of disease incidence. Underreporting is considered moderate to severe in most countries. The estimated annual incidence is around 10,000 to 17,000 cases. Turkey, Israel, Turkmenistan, Uzbekistan and Tajikistan are the most affected countries. In southern European Union and in Balkan countries, sporadic CL is caused mostly by L. infantum, although cases of L. tropica also occur in Greece. In Turkey, the causative agents are L. tropica in southeastern Anatolia, L. tropica or L. infantum in eastern Mediterranean, and L. infantum in the Aegean coast. Recent cases of L. major CL have been identified. In Uzbekistan and Turkmenistan, at present, only zoonotic CL caused by L. major is recorded.