Species of parasitic protist
Leishmania major
is a species of
parasite
found in the genus
Leishmania
, and is associated with the disease
zoonotic
cutaneous leishmaniasis
(also known as
Aleppo boil
,
Baghdad boil
,
Bay sore
,
Biskra button
,
Chiclero ulcer
,
Delhi boil
,
Kandahar sore
,
Lahore sore
,
Oriental sore
,
Pian bois
, and
Uta
).
[1]
L. major
is an
intracellular
pathogen
which infects the
macrophages
and
dendritic cells
of the
immune system
.
[2]
Though
Leishmania
species are found on every continent aside from
Antarctica
,
Leishmania major
is found only in the
Eastern Hemisphere
, specifically in Northern
Africa
,
[3]
the
Middle East
, Northwestern
China
, and Northwestern
India
.
[4]
[5]
Biology
[
edit
]
Life cycle
[
edit
]
As a
trypanosomatid
,
L. major
begins its lifecycle in
amastigote
form in the
midgut
of the main
vector
, female
sand flies
(
Phlebotomus spp.
).
[6]
Once in the gut of the sand fly, the parasites change from aflagelated
amastigotes
into
flagellated
promastigotes
for 1?2 weeks until they are fully developed, a which point they make their way to the
proboscis
.
[5]
Upon biting a
mammalian
host
,
promastigotes
are released into the
bloodstream
, where they are engulfed by
macrophages
.
[7]
Following engulfment,
promastigotes
differentiate into
amastigotes
.
[7]
Amastigotes
are oval or round, and have a
diameter
between 2-3
μm
.
[5]
Additionally, they contain a large, eccentrically placed
nucleus
along with a
kinetoplast
(which holds extracellular
DNA
).
[5]
Being equipped to survive the
acidic
environment inside the
phagosomes
of
macrophages
, the
amastigotes
reproduce through the process of
binary fission
.
[5]
At this point the
amastigotes
are released throughout the body, and can be ingested by female
sand flies
, thus completing the cycle.
[7]
L. major
has a sexual cycle, including a meiotic process.
[8]
Mating only occurs in the sand fly vector.
[9]
Hosts
[
edit
]
Meriones unguiculatus
, other
Meriones
and
jirds
, and other
rodents
are common hosts.
Dogs
,
[10]
[11]
: 2
Mustela nivalis
,
[10]
Atelerix algirus
,
[10]
and
Paraechinus aethiopicus
[10]
are rare hosts.
Mice
are natural hosts.
[12]
Transmission between mice is via
Phlebotomus papatasi
.
[12]
Infection
[
edit
]
Upon entering the
mammalian
bloodstream
,
L. major
meets the focal point of
infection
, the
macrophage
. As a result of two surface
molecules
, the
protease
gp63 and a
lipophosphoglycan
,
promastigotes
are able to bind to several
macrophage
receptors
.
[13]
[14]
Promastigote
attachment to
macrophages
is facilitated by a number of
receptors
, including
complement receptors
CR1
and
CR3
, and the
receptor for advanced glycosylation end products
.
[5]
Activation of complements occurs far from the
cell membrane
, and insertion of the
membrane attack complex
does not occur.
[5]
This action is what allows the
parasite
to avoid being
lysed
, and to persist within the
host's
macrophages
. In cattle
Th1
and
Th2
cells are an important part of the response.
[15]
Neither cell type expresses exclusively
IFNγ
or
IL-4
for
L. major
? Brown
et al.
1998 find they express both in cattle.
[15]
The
bovine myeloid antimicrobial peptide
BMAP-28
has leishmanicidal activity and may be usable
in vivo
in cattle infection.
[16]
Lynn
et al.
, 2011 obtain good results against two strains of the parasite, using two
isoforms
of BMAP-28, the retro-inverso and the D-amino acid.
[16]
Enzymatics
[
edit
]
Dimethylallyltranstransferase
is vital to
L. major
, making it an interesting target for leishmaniacidal substances.
[17]
Propenko
et al.
2014 present and validate several
dimethylallyltranstransferase inhibitors
.
[17]
Epidemiology
[
edit
]
The
incidence rate
of
cutaneous leishmaniasis
is estimated to be between 1?1.5 million cases a year.
[18]
However,
transmission
does not often occur
in utero
, during
blood transfusions
, or through interpersonal contact.
[5]
Thus, the main form of
transmission
is through the
sand fly
vector
.
Sand flies
do not fly long distances, and tend to complete their life cycles in areas with a diameter of less than 1 km.
[7]
Furthermore, because of the propensity of
sand flies
to seek out shelter in the
burrows
of small
rodents
,
[7]
where
L. major
is
endemic
, small
mammals
such as
gerbils
and birds serve as the main
reservoirs
.
[5]
Dogs
have also been documented as contracting cutaneous leishmaniasis in
Egypt
[19]
and
Saudi Arabia
.
[20]
This is rare however, and dogs are not important
hosts
for
L. major
.
L. major
and its cousin,
L. tropica
, are recognized as causing the majority of cases of
cutaneous leishmaniasis
across the
Middle East
, Northern
Africa
, and some areas of
China
and
India
(as mentioned above). Between 2002 and 2004, over 700 cases of the disease were reported among
United States
military personnel serving in
Iraq
.
[21]
Clinical manifestations
[
edit
]
Upon becoming infected, patients usually present with
lesions
at the site of the
sand fly
bite. The
infection
is
acute
, and usually has a duration of about 3?6 months.
[4]
As more and more
phagocytic
cells engulf
promastigotes
, prompting the production of
amastigotes
,
nodules
form on the
skin
.
[5]
These
nodules
then
ulcerate
, although due to the variable characteristics of the
lesions
, species specific identification of the
pathogen
is impossible.
[5]
Generally though,
lesions
appear moist and have raised outer borders, a granulating base, an overlying layer of white
purulent
exudate
, and have been described as "
pizza
-like."
[4]
[5]
Biopsies
of these
lesions
usually reveal a number of findings including numerous
macrophages
containing intracellular
amastigotes
as well as
lymphocytes
with observed
granuloma
formation and few
parasites
.
[22]
Diagnosis
[
edit
]
Leishmania major
should be considered in the
differential diagnosis
of
chronic
lesions of people who have spent time in areas where it is
endemic
. However, other
pathogens
can cause similar
lesions
and therefore paracoccidiodomycosis,
histoplasmosis
,
sporotrichosis
,
lobomycosis
,
lupus vulgaris
,
Mycobacterium ulcerans
,
syphilis
,
cutaneous sarcoidosis
, and
leprosy
should all be considered as well.
[5]
The most common ways of diagnosing
leishmaniasis
are to identify
amastigotes
in a
Wright-Giemsa-stained
touch preparation or through isolation of the
parasites
in cultures.
[5]
Treatment
[
edit
]
Because the
host's
immune system
tends to resolve
infection
after 3?6 months, treatment of the
lesions
generally focuses on limiting
tissue
damage and
necrosis
.
[4]
[5]
A number of different treatments have yielded results of varying effectiveness in the treatment of
L. major
caused
cutaneous leishmaniasis
.
- Fluconazole
given in 200 mg doses over the course of 6 weeks resulted in 90% cure rate versus 60% in those given a
placebo
.
[23]
- Topical application of 15%
paromomycin
and 12%
methylbenzethonium
has been used successfully to treat patients in
Israel
.
[24]
- Intralesional
injections
of 0.5?2.0 mL of 100 mg/ML
antimony
has also been shown to be effective when injected around the sides of
lesions
. When 10 such injections were given to patients in
Egypt
, 85% were cured within 3 months.
[5]
Prevention
[
edit
]
The spread of
leishmaniasis
can be prevented by interrupting the
sand fly
life cycle or removing or treating
pathogen
reservoirs
. Avoiding
sand fly
bites is an effective means of avoiding disease for short term visitors to areas where
L. major
is
endemic
. This can be accomplished through the use of
DEET
containing insect repellent, application of
insecticides
to clothes and bedding, as well as using
mosquito nets
to cover beds.
[5]
Sand flies
usually bite between
dusk
and
dawn
, so preventative measures should be taken during these times.
[7]
Though a
vaccine
does not yet exist that can prevent
cutaneous leishmaniasis
, it is speculated that one will be developed in the near future.
[5]
Patients who have recovered from
L. major
infections develop high- level immunity to the
pathogen
.
[5]
In
Russia
and
Israel
, soldiers were "immunized" against
L. major
through the injection of live
promastigotes
into the
buttocks
; however, this form of treatment was discontinued in
Israel
due to the occasional formation of large or slow-healing
lesions
.
[5]
References
[
edit
]
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Leishmania major
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