加藤 大智

Dogs are the main reservoir host of Leishmania infantum, etiological agent of zoonotic visceral leishmaniasis (ZVL). An effective vaccine against Canine Visceral Leishmaniasis (CVL) will help the control and elimination of ZVL. In this study, we evaluated in dogs the safety, immunogenicity, and efficacy of a live attenuated Leishmania major Centrin gene-deleted (LmCen-/-) as a vaccine. Two doses (106 or 107) of LmCen-/- vaccine were administered intradermally in a prime-boost regimen. Both vaccine doses induced equally high level of IgG anti-Leishmania and exhibited strong antigen-specific cellular responses with IFN-γ production by CD4 + T cells one-month post-immunization. A second cohort of dogs was vaccinated with 106 LmCen-/- parasites one month prior to their transfer to a CVL endemic focus in Northern Tunisia for exposure to sand fly bites during three successive transmission seasons. Dogs were exposed to bite from naturally infected sandflies for 3-5 months per year. Our results showed that only 1/11 vaccinated dogs became PCR positive for Leishmania and developed clinical signs of CVL. In contrast, 4/11 unvaccinated dogs were tested PCR positive for Leishmania and displayed oligosymptomatic CVL, demonstrating that immunization with LmCen-/- vaccine confers long-term protection with an efficacy of 82.5% against CVL in natural transmission settings.

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.