加藤 大智

Leishmaniasis is a neglected tropical disease caused by protozoan parasites of the genus Leishmania. About 20 species of Leishmania are pathogenic to humans, with the specific infecting species playing a crucial role in determining clinical outcomes. There are three main forms of disease: cutaneous, mucocutaneous and visceral leishmaniasis. In addition to the infecting species, it has recently been suggested that parasite strains and genetic factors affect disease manifestation and response to treatment. This suggests that infecting parasites are a crucial risk factor for the pathology of leishmaniasis. These parasites are transmitted by sand flies, of which more than 1000 species have been recorded. However, only approximately 10 % of these species are responsible for transmitting Leishmania, with each sand fly species typically transmitting specific species of Leishmania. Most Leishmania species are zoonotically transmitted by sand flies, with reservoir animals playing a crucial role in disease transmission and endemicity. This aspect of the disease ecology highlights the importance of considering both vectors and reservoir animals in endemic areas as risk factors for leishmaniasis. Our epidemiological studies on leishmaniasis focus mainly on South American countries. This review describes the epidemiological aspects of leishmaniasis in Ecuador and Peru, with a focus on pathological and infectious risks.

Phlebotomine sand flies are very small hematophagous insects, and some species transmit human pathogens, such as Leishmania protozoa. Similar to other hematophagous insects, sand flies possess unique bioactive substances in their saliva to facilitate blood feeding. Active transcriptome and proteome analyses revealed that sand flies have unique molecules in their saliva that are structurally different from those of other arthropods. These components exert anticoagulant, antiplatelet, vasodilator, and anti-inflammatory effects on the host, and the unique bioactivities of each molecule are currently being characterized. Several bioactivities of salivary components have been associated with the exacerbation of Leishmania infection, and investigations on the molecular mechanisms responsible are underway. On the other hand, host immunity to some salivary components has been shown to confer protection against Leishmania infection, suggesting the potential of salivary components as vaccine candidates. Although some negative effects of protection by sand fly saliva have been reported, the identification of suitable immunogens and elucidation of appropriate protective immunity are expected for the development of a sand fly saliva vaccine against Leishmania infection.

Leishmaniasis is caused by an obligate intracellular protozoa of the genus Leishmania. Its clinical manifestations include cutaneous, mucocutaneous, and visceral forms. Sporotrichoid cutaneous leishmaniasis (SCL) is an atypical and rare form of cutaneous leishmaniasis (CL) reported mainly in the Old World. This case report describes SCL in a Japanese man infected with Leishmania (Viannia) peruviana in Peru. His lesions occurred on both feet, with the left foot lesion being a simple CL that resolved spontaneously. However, the lesion on the right foot did not cure by itself; instead, it progressed centrally along the lymph nodes, eventually forming an SCL. Amastigotes were detected in both feet and genetically identified as L. (V.) peruviana. The lesions gradually resolved after treatment with intravenous liposomal amphotericin B. Here, we report the first case of SCL caused by L. (V.) peruviana.

Tick saliva modulates host responses during a blood feeding process. We identified a novel chemokine binding protein 1-like (HLCBP1-like) gene from the salivary glands of the Asian longhorned tick, Haemaphysalis longicornis. The HLCBP1-like protein, lacking a well-defined conserved domain, showed structural similarity to evasin, a chemokine binding protein from the brown dog tick, Rhipicephalus sanguineus. A preliminary knockdown study of HLCBP1-like revealed that ticks with reduced expression of this gene, halted feeding in the early feeding phase, and did not fully-engorge, unlike the control dsRNA (malE) injected ticks. Also, knockdown ticks induced cellular immune responses in the host skin, similar to control dsmalE-injected ticks, but did not show hemorrhage. These findings suggest that HLCBP1-like may play a modulatory role in the slow feeding phase.

Phlebotomine sand flies are vectors of the protozoan parasite Leishmania spp. Although the intestinal microbiota is involved in a wide range of biological and physiological processes and has the potential to alter vector competence, little is known about the impact of host species and environment on the gut microbiome. To address this issue, a comparative analysis of the microbiota of sand fly vector populations of Leishmania major and L. tropica in a mixed focus of cutaneous leishmaniasis in Tunisia was performed. Bacterial 16S rRNA gene amplification and Illumina MiSeq sequencing were used to characterize and compare the overall bacterial and fungal composition of field-collected sand flies: Phlebotomus papatasi, Ph. perniciosus, Ph. riouxi, and Ph. sergenti. Thirty-eight bacterial genera belonging to five phyla were identified in 117 female specimens. The similarities and differences between the microbiome data from different samples collected from three collections were determined using principal coordinate analysis (PCoA). Substantial variations in the bacterial composition were found between geographically distinct populations of the same sand fly species, but not between different species at the same location, suggesting that the microbiota content was structured according to environmental factors rather than host species. These findings suggest that host phylogeny may play a minor role in determining the insect gut microbiota, and its potential to affect the transmission of the Leishmania parasite appear to be very low. These results highlight the need for further studies to decode sand fly Leishmania-microbiota interactions, as even the same bacterial species, such as Enterococcus faecalis, can exert completely opposite effects when confronted with different pathogens within various host insects and vice versa.