Transcript Leishmania

Leishmania
introduction
. protozoal disease of mammals, a zoonotic disease.
. 23+ pathogenic species.
. transmitted by sandflies (Phlebotomus species).
. in the human host, Leishmania infect the mononuclear phagocytes.
Leishmania
Species pathogenic in humans:
☆ leishmania
donovani (complex)
☆ leishmania
tropica
☆ leishmania
major
☆ leishmania
mexicana (complex)
☆ leishmania
brazilliensis (complex)
☆ leishmania
aethiopica
Leishmaniasis
introduction
To be categorized into 3 types, as follows:
. Visceral leishmaniasis (VL), also known as kala azar, is caused
by L. donovani, is the most severe form of the disease, which, if
untreated, has a mortality rate of above 90%.
. Cutaneous leishmaniasis (CL) can produce large numbers of
skin ulcers. It is caused by L. tropica and L. mexicana.
. Mucocutaneous leishmaniasis (MCL), or espundia, is caused
by L. braziliensis, produces lesions of mucous membranes of the
nose, mouth and throat cavities.
leishmania
donovani
Morphology
1. Amastigote
2. Promastigote
(Leishman-Donovan body )
living in the reticuloendothelial system
(mononuclear cell / macrophage) of man and reservoir
mammals.
(liver, spleen, lymph node, bone marrow, skin)
Morphology
1. Amastigote
The ultrastructure of amastigote
Morphology
1. Amastigote
2. Promastigote
in the sand fly and
in cultures
Morphology
. Amastigote
. Promastigote
.Mammalian stage
.insect (sandfly)
.Non-motile
.motile
.Intracellular
.midgut
(macrophages)
The vector----- sandfly
.Adult sandflies are only 1.54 mm long, and yellow in color.
.Hairy bodies.
.Wings are held erect over
the body.
.Belonging to the genera
Phlebotomus and Lutzomyia .
.Of 500 known phlebotomine
species, only about 30 of them
have been positively identified
as vectors of the disease.
Life cycle
binary fission
the female sandfly sucks blood
of human or mammalian host
amastigote
Enter the mid gut
binary fission
amastigote
Macrophage
rupture, invade
fresh cells
migrate to the
pharynx and
buccal cavity
promastigote
promastigote
the female sandfly bite
human or mammalian host
amastigote
man
sandfly
Life cycle of Leishmania
Life cycle
binary fission
the female sandfly sucks blood
of human or mammalian host
amastigote
Enter the mid gut
binary fission
amastigote
Macrophage
rupture, invade
fresh cells
migrate to the
pharynx and
buccal cavity
promastigote
promastigote
the female sandfly bite
human or mammalian host
amastigote
Summary:
1. Infect stage: the promastigote form
2. The vector: sandfly
3. Methods of transmission : the bite of sandfly
4. Host: humans , dogs, wild rodents ,
Life cycle
binary fission
the female sandfly sucks blood
of human or mammalian host
amastigote
Enter the mid gut
binary fission
amastigote
Macrophage
rupture, invade
fresh cells
migrate to the
pharynx and
buccal cavity
promastigote
promastigote
the female sandfly bite
human or mammalian host
amastigote
Summary:
5. Parasite spread: macrophage lysis→amastigote release.
via
blood spead
lymphatic spread
6. Reside site: the cells of the reticuloendothelial system
(skin, liver, spleen, lymph node, bone marrow)
Pathogenesis
①Amastigote forms destroy macrophages
→hyperplasia → lead to hepatosplenomegaly.
②Bone marrow turns hyperplastic, and parasitized
macrophages replace the normal hemopoietic tissue.
pancytopenia .
Oligocythemia of red blood cells,
Leucopenia,
Normal value
Thrombocytopenia
RBC：3.5-5.0╳1012/L, 4.0-5.5╳1012/L
WBC：4,0-10 ╳109/L
Blood platelets：100-300 ╳109/L
Albumin(A) normal value ：40-50g/L
Pathogenesis
Globulin(G) normal value ：20-30g/L
①Amastigote forms destroy macrophages →hyperplasia → lead to
hepatosplenomegaly.
A/G normal value ：1.5 -- 2.5:1
②Bone marrow turns hyperplastic, and parasitized macrophages replace
the normal hemopoietic tissue.
A/G reversal ：
pancytopenia .
③leishmanial antigens stimulate immune system
an
overproduction of both specific immunoglobulins and
nonspecific immunoglobulins also occurs
a
reversal of the albumin-globulin ratio.
Clinical features
1. Visceral leishmaniasis （Kala-azar）
① is caused by L. donovani.
② The incubation period: 3-6 months (months or years).
③Main symptoms：
.An insidious onset with irregular lowgrade fever.
. Hepatosplenomegaly.
. Lymphadenopathy.
. Anemia.
. The hemorrhagic tendency.
. The skin on the hands, feet, abdomen and face may become
darkened.
. Pancytopenia.
.A reversal of the albumin-globulin ratio.
★ Post–kala azar dermal leishmaniasis
.Follows the treatment of visceral leishmaniasis,
normally develops < 2 years after recovery.
. Restricted to skin..
. Dermal lesions are categorized into 3 types, as
follows:
. Depigmented macules
. Erythematous patches
. Yellowish pink nodules
Clinical
1. Visceral leishmaniasis （Kala-azar）
① is caused by L. donovani.
② The incubation period: 3-6 months (months or years).
③Main symptoms：
④Complications:
Bacterial pneumonia, septicemia, dysentery, tuberculosis,
cancrum oris, and uncontrolled hemorrhage or its sequelae can
occur as complications of leishmaniasis.
⑤ Prognosis:
If untreated, death occurs within 2 years.
Clinical
2. Cutaneous leishmaniasis
. caused by mainly in 2 forms, L. tropica and L.
mexicana. L. tropica has two subspecies L. tropica and
L. major.
. the amastigote form resides in the large mononuclear
cells of the skin.
. skin lesions mainly on the face, arms, and legs.
. often self-healing but can create serious disability
and permanent scars.
Clinical
2. Cutaneous leishmaniasis
① caused by L. tropica
. The disease is also known as
“oriental sore”.
. An ulcer of 1-3cm develops with
a surrounding zone of inflammation
(crater-like).
. Healing occurs in a few months
and there is a lasting immunity.
After treatment
Typical lesions of cutaneous leishmaniasis caused by L. tropica
After treatment
Typical lesions of cutaneous leishmaniasis caused by L. tropica
Typical lesions of cutaneous leishmaniasis caused by L. major
Typical lesions of cutaneous leishmaniasis caused by L. major
Typical lesions of cutaneous leishmaniasis caused by L. major
After treatment
Typical lesions of cutaneous leishmaniasis caused by L. major
Clinical
2. Cutaneous leishmaniasis
② caused by L. mexicana
. The initial lesion in humans ulcerates and becomes
crater-like and inflamed (like oriental sore).
. But it can cause “chiclero’s ulcer” which can involve
almost total destruction of the external ear.
Clinical
2. Cutaneous leishmaniasis
▲ Diffuse cutaneous leishmaniasis
.associated with a
deficient cell-mediated
immunity .
.enables the parasite
to disseminate in the
subcutaneous tissues.
. non-healing, life
long non-ulcerative
infection
Clinical
3. Mucocutaneous leishmaniasis
. also called “espundia”.
. caused by L. braziliensis .
. it destroys the mucous membranes of the nose, mouth,
throat and even soft palate.
Clinical
1. Visceral leishmaniasis （Kala-azar）
2. Cutaneous leishmaniasis
3. Mucocutaneous leishmaniasis
Differential diagnosis:
Laboratory Studies
1. Direct evidence of infection:
2.①.
Indirect
evidenceaspiration:
of infectionPositivity rates ranging from
Bone marrow
54-86%
3.
Supportive tests
②. Splenic aspiration: Up to 98% positive results
③. Lymph node aspiration or biopsy: Positivity rates
ranging from 54-86%
④. Culture:
⑤. Animal inoculation:
⑥. cutaneous tissue biopsy or aspiration:
Laboratory Studies
1. Direct evidence of infection:
2. Indirect evidence of infection
①. Detection of hypergammaglobinemia:
.the aldehyde test
.the antimony test
②. Immunological tests:
③. Nonspecific tests:
. the direct agglutination test
. immunofluorescent antibody test
.complement fixation
.counterimmunoelectrophoresis
. Leishmanin skin test (Montenegro test)
. Polymerase chain reaction (PCR)
Laboratory Studies
1. Direct evidence of infection:
2. Indirect evidence of infection
3. Supportive tests
①. a normochromic normocytic anemia
②. leukopenia
③. neutropenia
④. thrombocytopenia
⑤. elevated gamma globulins
⑥. a reversal of the albumin-globulin ratio
Epidemiology
Geographical
distribution
Epidemiology
Geographical distribution
Leishmaniases are considered to be endemic
in 88 countries (16 developed countries, 72
developing countries) on 5 continents of Africa,
Asia, Europe, North America, and South America.
.
Epidemiology
The number of cases
an estimated 12 million cases of leishmaniasis
exist worldwide. A total of 350 million people are at risk.
. Today,
estimated 1.5
annually.
. an
-2 million new cases occurring
Epidemiology
Today the number of cases of
leishmaniasis is increasing, Why?
. man-made environmental changes that increase human exposure
to the sandfly vector.
. the movement of susceptible populations into endemic areas,
including large-scale migration of populations for economic reasons.
. The immune deficiency has lead to increased susceptibility to
infections, coexistence of leishmaniasis with HIV adds a serious
dimension .
Prevention
. Treatment of active cases.
. Reservoir control.
. Sandfly control.
. Personal protection using repellants and nets is an
important aspect.
. Education regarding preventing the bite of sandfly.
Treatment
1. Visceral leishmaniasis （Kala-azar）
sodium antimony gluconate----upto 25% resistance
Resistance to stibogluconate :
.should be treated with alternate agents, such as
liposomal amphotericin, Pentamidine, aminosidine
. combination of stibogluconate with drugs, such
as aminosidine and interferon gamma,
Treatment
2. Cutaneous leishmaniasis
treatment essentially remains the same.
sodium antimony gluconate and
pentamidine are the drugs of choice.
3. Mucocutaneous leishmaniasis
this responds to a 20-day course of sodium
antimony gluconate, with resistant cases being
treated with amphotericin.
Treatment
. Drug treatment
. Good nursing and diet
Summary1
Leishmania Species pathogenic in humans:
☆ leishmania
donovani (complex)
☆ leishmania
tropica
☆ leishmania
major
☆ leishmania
mexicana (complex)
☆ leishmania
brazilliensis (complex)
☆ leishmania
aethiopica
Life cycle
binary fission
Summary2
the female sandfly sucks blood
of human or mammalian host
amastigote
Enter the mid gut
migrate to the
pharynx and
buccal cavity
promastigote
binary fission
1.Infect stage: the promastigote form
amastigote
Macrophage
rupture, invade
fresh cells
the female sandfly bite
human or mammalian host
amastigote
2.The vector: sandfly
3.Methods of transmission : the bite of sandfly
4.Host: humans , dogs, wild rodents ,
5. Parasite spread: macrophage lysis→amastigote release.
via
promastigote
blood spead
lymphatic spread
6. Reside site: the cells of the reticuloendothelial system
(skin, liver, spleen, lymph node, bone marrow)
Summary3
1. Visceral leishmaniasis （Kala-azar）
caused by L. donovani.
2. Cutaneous leishmaniasis
caused by mainly in 2 forms, L. tropica
and L. mexicana.
3. Mucocutaneous leishmaniasis
caused by L. braziliensis .