(1) The sandflies inject the infective stage, metacyclic promastigotes, during blood meals. (2) Metacyclic promastigotes in the puncture wound are phagocytized by macrophages, and (3) transform into amastigotes. (4) Amastigotes multiply in infected cells and affect different tissues, depending in part on the host, and in part on which Leishmania species is involved. These differing tissue specificities cause the differing clinical manifestations of the various forms of leishmaniasis. (5,6) Sandflies become infected during blood meals on infected hosts when they ingest macrophages infected with amastigotes. (7) In the sandflys midgut, the parasites differentiate into promastigotes, (8) which multiply, differentiate into metacyclic promastigotes, and migrate to the proboscis. The genomes of three Leishmania species (L. major, L. infantum, and L. braziliensis) have been sequenced, and this has provided much information about the biology of the parasite. For example, in Leishmania, protein-coding genes are understood to be organized as large polycistronic units in a head-to-head or tail-to-tail manner; RNA polymerase II transcribes long polycistronic messages in the absence of defined RNA pol II promoters, and Leishmania has unique features with respect to the regulation of gene expression in response to changes in the environment. The new knowledge from these studies may help identify new targets for urgently needed drugs and aid the development of vaccines. Vector
Although most of the literature mentions only one genus transmitting Leishmania to humans (Lutzomyia) in the New World, a 2003 study by Galati suggested a new classification for New World sand flies, elevating several subgenera to the genus level.
Chemistry
Sargramostim is a recombinant version of GM-CSF, which is a glycoprotein made of 127 amino acids; sargramostim is mixture of three versions of GM-CSF that have molecular weights of 19,500, 16,800 and 15,500 Daltons. It is manufactured in yeast. History
The sequence of human GM-CSF was first identified in 1985 and soon three recominbant human GM-CSFs were produced, one in bacteria, one in mammalian cells, and one in yeast; Immunex developed GM-CSF manufactured in yeast into Leukine. Clinical trials of sargramostim were initiated in 1987; in that same year it was administered to six people as part of a compassionate-use protocol for the victims of cesium irradiation from the Goiânia accident.It was approved by the FDA in March 1991 under the trade name Leukine for acceleration of white blood cell recovery following autologous bone marrow transplantation in patients with non-Hodgkins lymphoma, acute lymphocytic leukemia, or Hodgkins disease. In November 1996, the FDA also approved sargramostim for treatment of fungal infections and replenishment of  white blood cells following chemotherapy. A liquid formulation was approved in 1995. Immunex was acquired by Amgen in 2002. As part of the acquisition,  Leukine was spun off to Berlex, which became Bayer HealthCare in 2007.In January 2008, Bayer informed healthcare professionals of the market withdrawal of the current liquid formulation of sargramostim.