Eukaryotes Genomes - LEISHMANIA MAJOR
Leishmania major
causes Leishmaniasis
Members of the genus
Leishmania are sandfly-transmitted protozoan parasites that
cause
leishmaniasis in their vertebrate hosts. Within that
host,
Leishmania reside within phagocytic cells and induce
a spectrum of diseases ranging from mild cutaneous to lethal visceral
forms.
There
are several different types of
Leishmaniasis, but all are
transmitted by the bite of a sandfly. When an infected Phlebotomid
sand fly takes a blood meal it infects the vertebrate host with
promastigote metacyclic forms. There are two forms of the parasite,
the intracellular amastigote form found in the vertebrate host,
and the promastigote form predominately found in the insect vector.
Within a short time the promastigotes are taken up by macrophages,
the first line of defence of the immune system. During the process
of uptake by the macrophage, the promastigote loses its flagella
and transforms into the amastigote form. Once internalised in a
phagosome the macrophage lysosome fuses with the phagosome to from
a phagolysosome containing the parasite. Amastigotes are spherical
in shape, only about 2.5 to 5 m in diameter, and are contained
within a parasitophagus vacuole within a macrophage. There is a
prominent nucleus and kinetoplast, and the cytoplasm is vacuolated
and contains lysosomes. The outer membrane has a polysaccharide
component but there is no surface coat. The promastigote is similar
in structure, apart from the prominent flagella. The surface membrane
has binding site molecules such as glycoproteins, and manose receptors
have also been detected. These are important in the uptake of the
promastigotes by the macrophages. Antibodies in the host serum bind
to the promastigotes and facilitate uptake and entry into the macrophage.
Unlike
other intracellular protozoans, which either inhibit lysosomal fusion
with the phagosome (
Toxoplasma gondii), or escape the parasitophorous
vacuole (
T. cruzi),
Leishmania depend on their defence
mechanisms to survive.
There are
a large number of species and subspecies of
Leishmania and
they have been grouped according to their development within the
sandfly vector. The names given to the groupings refer to the promastigote
development in the digestive tract relative to the position of the
pylorus, the valve dividing the stomach from the ileum. The taxonomy
of this genus is complex and often confusing. In general species
differentiation is not based on the morphology of the organism but
on the pathology and symptoms of the disease, site of infection,
vector species and reservoir hosts. In addition biochemical and
serological factors are also used for characterization of the species
complex.
The disease
Leishmaniasis affects the populations of 88 countries worldwide
with L. Major being most prevalent in North Africa, the Middle East,
West India and Sudan.
Twenty
three species of
Leishmania cause disease in humans. Depending
upon the species and the reaction of the individual, several different
syndromes are seen, the commonest of which are visceral
leishmaniasis
(which is usually fatal if not treated), cutaneous
leishmaniasis
(which will usually self cure eventually, leaving unsightly scars)
and mucocutaneous
leishmaniasis (of Latin America; treatment
is frequently unsuccessful). Other clinical manifestations include
post kala-azar dermal
leishmaniasis; Sudanese oronasal
leishmaniasis
and disseminated anergic
leishmaniasis.
Diagnosis
of
Leishmania infection remains problematic; existing methods
are labour-intensive and have sensitivity and specificity issues;
current chemotherapeutic agents are unsuitable because of their
high toxicity and there are no approved vaccines.
Leishmaniasis obtained public notoriety during the Desert Storm campaign
as many soldiers became infected with the parasite after being bitten
by the sandfly vector and it is only seen in the United States in
people that travel outside the U.S.
Several
species of
Leishmania have been reported in dogs, however
L. major is not the major concern for canine infection.
References:
Proc. Natl. Acad. Sci. U.S.A. 96(6):2902-2906(1999).
Nucleic Acids Res. 31(14):4201-4210(2003).
http://www.sanger.ac.uk/Projects/L_major/
http://www.leishmania.co.uk/
http://martin.parasitology.mcgill.ca/jimspage/biol/leish.htm
http://www.who.int/mediacentre/factsheets/fs116/en/
http://www.leishmaniasis.info
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