Leishmania of the Viannia subgenus, including Leishmania Viannia guyanensis, is the agent responsible for cutaneous and mucocutaneous leishmaniasis (CL and MCL) in the Americas from the US to Argentina. 48,000 new cases of Cl and MCL are reported yearly, among which 1/10 are associated with L. V. guyanensis infection transmitted by female Lutzomyia sandflies during the blood meal. Inoculated metacyclic promastigotes, coupled with Leishmania exosomes, will infect various inflammatory cells at inoculation sites, where they rapidly transform into amastigotes. Parasites divide and progress in the intra-macrophage form, leading to an initial CL skin ulceration. Depending on the inoculation site and host health condition, parasites may metastasize to the nasopharyngeal tissues within a few months. L. V. guyanensis is occasionally infected with Leishmania RNA virus 1 (LRV1) that can be enveloped by exosomes and is believed to accelerate MCL development.