Epidemiologic Relationship between Toscana Virus Infection and Leishmania infantum Due to Common Exposure to Phlebotomus perniciosus Sandfly Vector

Sand flies are recognised vectors of parasites in the genus Leishmania and a number of arthropod-borne viruses, in particular viruses within the genus Phlebovirus, family Bunyaviridae. In southern France, Toscana phlebovirus (TOSV) is recognized as a prominent cause of summer meningitis. Since Leishmania and TOSV have a common vector (Phlebotomus perniciosus), an epidemiologic link has been assumed for a long time. However, there is no scientific evidence of such a link between human leishmaniosis and phleboviral infections. To identify a possible link, we investigated the presence and distribution of antibodies against these two microorganisms (i) in individuals and (ii) at a spatial level in the city of Marseille (south-eastern France). Five hundred sera were selected randomly in the biobank of the Department of Parasitology of the Public Hospitals of Marseille. All sera were previously tested for IgG against Leishmania by Western Blotting, and TOSV IgG were detected by indirect immunofluorescence. The seropositivity rates were 21.4% for TOSV and 28% for Leishmania. Statistical analysis demonstrated that seropositivity for one pathogen was significantly associated with seropositivity to the other pathogen. This result provided the first robust evidence for the existence of an epidemiological relationship between Leishmania infantum and TOSV. Addresses of tested patients were geolocalized and integrated into Geographical Information System software, in order to test spatial relationship between the two pathogens. Spatial analysis did not allow to identify (i) specific patterns for the spatial distribution of positive serological results for TOSV or Leishmania, and (ii) a spatial relationship between Leishmania and TOSV positive serological results. This may reflect the fact that the sample studied was not powerful enough to demonstrate either a spatial clustering or co-location, i.e. that the actual risk exposure area is smaller than the mean of distance between patients in our study (245 m).
Author Summary Sand flies are tiny insects widely distributed in peri-Mediterranean countries where they can transmit Leishmania parasite and Toscana virus (TOSV). Since those microorganisms have a common vector, an epidemiologic link has been assumed for a long time. However, there is no scientific evidence of such a link between human leishmaniosis and phleboviral infections. To identify a possible link, we investigated the presence and distribution of antibodies to both Leishmania and TOSV in 500 sera of individuals living in Marseille, France. Antibodies are markers of past infections and reflect the exposition of population to pathogens. Statistical analysis demonstrated that seropositivity to one of these pathogens was significantly associated with seropositivity to the other pathogen. This result provided first robust evidence for an epidemiological relationship between Leishmania infantum and TOSV. Home addresses of tested patients were geolocalized in order to test spatial relationship between the two pathogens. This spatial analysis did not allow identifying either a spatial clustering or co-location, most probably because the sample was not powerful enough. Risk-factors of infection by TOSV (or Leishmania) would be investigated in seropositive patients' neighbourhood, in a range inferior to the mean of distance between patients in our study (245 meters).