Properties of virulence emergence ofLeishmania infantumisolates fromPhlebotomus perniciosuscollected during the human leishmaniosis outbreak in Madrid, Spain. Hepatic histopathology and immunological parameters as virulence markers in the mouse model

Abstract

Recent anthropic activity related to the construction of the Bosquesur Green Park in a large urban setting in Madrid (Spain) has resulted in the largest reported community outbreak of human leishmaniosis in Europe. Previous phylogenetic and molecular-typing studies of parasite isolates have implicated the Leishmania infantum ITS-Lombardi genotype in this outbreak. In an unusual scenario, visceral leishmaniosis (VL) is affecting a significant number of individuals, suggesting that an increase in parasite virulence has occurred. In this work, using an in vivo BALB/c model of VL, we aimed to investigate the properties of emergent virulence of the L. infantum POL2FL7 and BOS1FL1 isolates obtained from Phlebotomus perniciosus collected in the outbreak area and compare them with those of the well-characterized strain BCN150 MON-1 isolated from a dog. The P. perniciosus specimens were collected during an entomological survey conducted in the transmission season of 2012. We observed a range of virulence phenotypes from moderately to highly aggressive after 5 weeks of infection. IV challenge of mice with outbreak isolates from sand flies induced higher splenic and liver parasite burdens, higher serological titres of specific anti-Leishmania antibodies and impaired capacities to control infection, as revealed by the arginine metabolism and low ratios of Th1/Th2 cytokine profiles analysed, compared with the corresponding measures evaluated in mice infected with the BCN150 strain. The BOS1FL1 isolate showed the highest degree of virulence among the isolates, superior to that of POL2FL7, as evidenced by the analysed biomarkers and the histopathological severity of liver lesions. These results provide insight into how L. infantum isolates from sand flies collected in the outbreak area have been able to affect not only immunosuppressed patients but also middle-aged people with normal immunocompetence in the largest human VL outbreak in Europe.

Transcriptomic Profile of Canine DH82 Macrophages Infected by Leishmania infantum Promastigotes with Different Virulence Behavior

“…In previous works, our group investigated the reasons behind the modifications in the ecoepidemiological features of the human leishmaniosis outbreak of Madrid, describing a higher virulence profile of the BOS1FL1 (IPER/ES/2012/BOS1FL1) L. infantum isolate obtained from the focus when compared with the well-characterized strain BCN150 (MCAN/ES/96/BCN150), first in vitro [17] and then using an in vivo murine model of visceral leishmaniosis (VL) [18]. This increase in the virulence of the outbreak isolate could be related to the high number of cases found in the human population, but it has not been reflected in an increase in canine leishmaniosis (CanL) prevalence.…”

Protective Efficacy in a Hamster Model of a Multivalent Vaccine for Human Visceral Leishmaniasis (MuLeVaClin) Consisting of the KMP11, LEISH-F3+, and LJL143 Antigens in Virosomes, Plus GLA-SE Adjuvant

“…A number of human, murine, and canine experimental VL models have established an association between the development and maturation of granulomas in the liver and spleen and resistance to infection [14,[50][51][52]. Immature granulomas are ineffective at controlling Leishmania infection; they can, however, develop into more successful mature and sterile granulomas, which ultimately eradicate the parasites before decreasing in number, thus resolving the hepatic inflammation caused [51].…”

“…Immature granulomas are ineffective at controlling Leishmania infection; they can, however, develop into more successful mature and sterile granulomas, which ultimately eradicate the parasites before decreasing in number, thus resolving the hepatic inflammation caused [51]. Importantly, the presence and number of sterile granulomas are strongly associated with the efficiency of the resolution of infection [50][51][52] and have been used to measure the effectiveness of VL vaccines in other animal models [14]. The percentage of mature and sterile granulomas in the present work may indicate the efficiency of the tested complete vaccine.…”

“…The efficiency of granuloma maturation and organization has been associated with the host capacity to resist infection in human, murine, and canine models [14,[50][51][52]. Moreover, the effectiveness of protozoan vaccines has been related to the capacity to induce sterile granulomas [14].…”

Feline Leishmaniosis: An Emerging Public Health Problem

“…Concretely, human leishmaniosis outbreak in Spain with high virulence seems to be related to wild hares and wild rabbit’s infection. Both species were found to be asymptomatic reservoirs for the parasite in an area with a low dog population density [ 26 , 27 ]. Early detection of infection in dogs and cats, together with its surveillance and treatments, are strategies to control and avoid human infection, following the “One Health” concept.…”