Zoonotic Visceral Leishmaniasis: New Insights on Innate Immune Response by Blood Macrophages and Liver Kupffer Cells to Leishmania infantum Parasites

L. infantum is the aetiological agent of zoonotic visceral leishmaniasis (ZVL), a disease that affects humans and dogs. Leishmania parasites are well adapted to aggressive conditions inside the phagolysosome and can control the immune activation of macrophages (MØs). Although MØs are highly active phagocytic cells with the capacity to destroy pathogens, they additionally comprise the host cells for Leishmania infection, replication, and stable establishment in the mammal host. The present study compares, for the first time, the innate immune response to L. infantum infection of two different macrophage lineages: the blood macrophages and the liver macrophages (Kupffer cells, KC). Our findings showed that L. infantum takes advantage of the natural predisposition of blood-MØs to phagocyte pathogens. However, parasites rapidly subvert the mechanisms of MØs immune activation. On the other hand, KCs, which are primed for immune tolerance, are not extensively activated and can overcome the dormancy induced by the parasite, exhibiting a selection of immune mechanisms, such as extracellular trap formation. Altogether, KCs reveal a different pattern of response in contrast with blood-MØs when confronting L. infantum parasites. In addition, KCs response appears to be more efficient in managing parasite infection, thus contributing to the ability of the liver to naturally restrain Leishmania dissemination.

Enhanced attraction of sand fly vectors of Leishmania infantum to dogs infected with zoonotic visceral leishmaniasis

Background The sand fly Phlebotomus perniciosus is the main vector of Leishmania infantum, etiological agent of zoonotic visceral leishmaniasis in the Western Mediterranean basin. Dogs are the main reservoir host of this disease. The main objective of this study was to determine, under both laboratory and field conditions, if dogs infected with L. infantum, were more attractive to female P. perniciosus than uninfected dogs. Methodology/Principal findings We carried out a series of host choice experiments and found that infected dogs were significantly more attractive to P. perniciosus than uninfected dogs in the laboratory as well as in the field. Significantly more P. perniciosus fed on infected dogs than on uninfected dogs. However, the fecundity of P. perniciosus fed on infected dogs was adversely impacted compared to uninfected dogs by lowering the number of laid eggs. Phlebotomus perfiliewi, the second most abundant sand fly species in the field site and a competent vector of L. infantum had similar trends of attractivity as P. perniciosus toward infected dogs under field conditions. Conclusions The results strongly suggest that L. infantum causes physiological changes in the reservoir host which lead to the host becoming more attractive to both male and female P. perniciosus. These changes are likely to improve the chance of successful transmission because of increased contact with infected hosts and therefore, infected dogs should be particularly targeted in the control of zoonotic visceral leishmaniasis in North Africa.

Spatio-temporal clustering of Mountain-type Zoonotic Visceral Leishmaniasis in China between 2015 and 2019

With several decades of concerted control efforts, visceral leishmaniasis(VL) eradication had almost been achieved in China. However, VL cases continue to be detected in parts of western China recent years. Using data of reported cases, this study aimed to investigate the epidemiology and spatio⁃temporal distribution, of mountain-type zoonotic visceral leishmaniasis (MT-ZVL) in China between the years 2015 and 2019. Epidemiological data pertaining to patients with visceral leishmaniasis (VL) were collected in Gansu, Shaanxi, Sichuan, Shanxi, Henan and Hebei provinces between the years 2015 and 2019. Joinpoint regression analysis was performed to determine changes in the epidemic trend of MT-ZVL within the time period during which data was collected. Spatial autocorrelation of infection was examined using the Global Moran’s I statistic wand hotspot analysis was carried out using the Getis-Ord Gi* statistic. Spatio-temporal clustering analysis was conducted using the retrospective space-time permutation flexible spatial scanning statistics. A total of 529 cases of MT-ZVL were detected in the six provinces from which data were collected during the study time period, predominantly in Gansu (55.0%), Shanxi (21.7%), Shaanxi (12.5%) and Sichuan (8.9%) provinces. A decline in VL incidence in China was observed during the study period, whereas an increase in MT-ZVL incidence was observed in the six provinces from which data was obtained (t = 4.87, P < 0.05), with highest incidence in Shanxi province (t = 16.91, P < 0.05). Significant differences in the Moran’s I statistic were observed during study time period (P < 0.05), indicating spatial autocorrelation in the spatial distribution of MT-ZVL. Hotspot and spatial autocorrelation analysis revealed clustering of infection cases in the Shaanxi-Shanxi border areas and in east of Shanxi province, where transmission increased rapidly over the study duration, as well as in well know high transmission areas in the south of Gansu province and the north of the Sichuan province. It indicates resurgence of MT-ZVL transmission over the latter three years of the study. Spatial clustering of infection was observed in localized areas, as well as sporadic outbreaks of infection.

Emerging and Re-Emerging Leishmaniases in the Mediterranean Area: What Can Be Learned from a Retrospective Review Analysis of the Situation in Morocco during 1990 to 2010?

In Morocco, cutaneous and visceral leishmaniases represent a public health concern. In this opinion paper, we propose to highlight chosen elements that have governed the drastic increase in the incidence of leishmaniases recorded in Morocco during the period between 1990 to 2010 in order to guide the prediction of the expansion of diseases and epidemic events. We highlight that the dispersion of the zoonotic cutaneous leishmaniasis (ZCL) form, caused by the Leishmania major parasite, appears to be closely related to that of its arthropod vector density, which is sensitive to changes in climate. The dissemination of anthroponotic cutaneous leishmaniasis (ACL) was related to an increase in human travel and local tourism during the studied decades. These are linked to economic expansion and infrastructure development. Interestingly, the main ACL foci are spatially aligned with the highways, and their occurrence was synchronized with the building of transportation infrastructure. During the above-mentioned decades, the zoonotic visceral leishmaniasis (ZVL) caused by Leishmania infantum has expanded from its historical northern territories, dispersing outwards in all directions. This spread follows the emergence of hamlets and villages connecting with major cities.