LeishmaniaLeishmania

.. protozoal disease of mammals, a zoonotic disease. protozoal disease of mammals, a zoonotic disease.

. . 2323+ + pathogenic species.pathogenic species.

.. transmitted by sandflies (Phlebotomus species). transmitted by sandflies (Phlebotomus species).

.. in the human host, Leishmania infect in the human host, Leishmania infect the mononuclear phagocytesthe mononuclear phagocytes. .

introductionintroduction

LeishmaniaLeishmania

☆ ☆ leishmania donovani leishmania donovani (complex)(complex)

☆☆ leishmania tropicaleishmania tropica

☆☆ leishmania majorleishmania major

☆☆ leishmania mexicana leishmania mexicana (complex)(complex)

☆☆ leishmania brazilliensis leishmania brazilliensis (complex)(complex)

☆☆ leishmania aethiopicaleishmania aethiopica

Species pathogenic in humans:Species pathogenic in humans:

LeishmaniasisLeishmaniasis

. . Visceral leishmaniasis (VL), also known as kala azar, is caused Visceral leishmaniasis (VL), also known as kala azar, is caused by L. donovani, is by L. donovani, is the most severe form of the diseasethe most severe form of the disease, which, if , which, if untreated, has a mortality rate of above 90%. untreated, has a mortality rate of above 90%.

.. Cutaneous leishmaniasis (CL) can produce large numbers of sk Cutaneous leishmaniasis (CL) can produce large numbers of skin ulcers. It is caused by L. tropica and L. mexicana. in ulcers. It is caused by L. tropica and L. mexicana.

. . Mucocutaneous leishmaniasis (MCL), or espundia, is caused bMucocutaneous leishmaniasis (MCL), or espundia, is caused by L. braziliensis, produces lesions of mucous membranes of the y L. braziliensis, produces lesions of mucous membranes of the nose, mouth and throat cavitiesnose, mouth and throat cavities..

introductionintroductionTo be categorized into 3 types, as follows: To be categorized into 3 types, as follows:

leishmania leishmania donovani donovani

1. Amastigote

2. Promastigote

MorphologyMorphology

living in the reticuloendothelial system (mononucleliving in the reticuloendothelial system (mononuclear cell / macrophage) of man and reservoir mammals. ar cell / macrophage) of man and reservoir mammals.

(liver, spleen, lymph node, bone marrow, skin)(liver, spleen, lymph node, bone marrow, skin)

(Leishman-Donovan body )(Leishman-Donovan body )

1. Amastigote

MorphologyMorphology

The ultrastructure of amastigote

1. Amastigote

2. Promastigote

MorphologyMorphology

in the sand fly and in the sand fly and in cultures in cultures

. Amastigote . Promastigote

MorphologyMorphology

.Mammalian stage .insect (sandfly).Mammalian stage .insect (sandfly)

.Non-motile .motile.Non-motile .motile

.Intracellular .midgut.Intracellular .midgut(macrophages)(macrophages)

The vector----- sandfly .Adult sandflies are only 1.5-.Adult sandflies are only 1.5-4 mm long, and yellow in color.4 mm long, and yellow in color.

.Hairy bodies. .Hairy bodies.

.Wings are held erect over th.Wings are held erect over the body.e body.

.Belonging to the genera Phl.Belonging to the genera Phlebotomus and Lutzomyia . ebotomus and Lutzomyia .

.Of 500 known phlebotomine .Of 500 known phlebotomine species, only about 30 of them species, only about 30 of them have been positively identified have been positively identified as vectors of the disease. as vectors of the disease.

Life cycleLife cycle

amastigoteamastigote promastigotepromastigote promastigotepromastigote

the female sandfly sucks blood the female sandfly sucks blood of human or mammalian host of human or mammalian host

Enter the mid gutEnter the mid gut

binary fission binary fission

migrate to the phmigrate to the pharynx and buccal arynx and buccal

cavitycavity

amastigoteamastigote amastigoteamastigote

the female sandfly bite humathe female sandfly bite human or mammalian hostn or mammalian host

binary fissionbinary fission

Macrophage Macrophage rupture, invade rupture, invade

fresh cells fresh cells

man

man

ss aan

dfly

nd

fly

Life cycle of Life cycle of LeishmaniaLeishmania

Life cycleLife cycle

amastigoteamastigote promastigotepromastigote promastigotepromastigote

the femalethe female sandfly sandfly sucks blood sucks blood of human or mammalian host of human or mammalian host

Enter the mid gutEnter the mid gut

binary fission binary fission

migrate to the migrate to the pharynx andpharynx andbuccalbuccal cavitycavity

amastigoteamastigote amastigoteamastigote

the femalethe female sandflysandfly bite bite human or mammalian hosthuman or mammalian host

binary fissionbinary fission

Macrophage Macrophage rupture, invade rupture, invade

fresh cells fresh cells

Summary:Summary:

1.1. Infect stage:Infect stage: the promastigote formthe promastigote form

2.2. The vector:The vector: sandflysandfly

3.3. Methods of transmission :Methods of transmission : the bite of sandflythe bite of sandfly

4.4. Host:Host: humans , dogs, wild rodentshumans , dogs, wild rodents ,,

Life cycleLife cycle

amastigoteamastigote promastigotepromastigote promastigotepromastigote

the femalethe female sandfly sandfly sucks blood sucks blood of human or mammalian host of human or mammalian host

Enter the mid gutEnter the mid gut

binary fission binary fission

migrate to the migrate to the pharynx andpharynx andbuccalbuccal cavitycavity

amastigoteamastigote amastigoteamastigote

the femalethe female sandflysandfly bite bite human or mammalian hosthuman or mammalian host

binary fissionbinary fission

Macrophage Macrophage rupture, invade rupture, invade

fresh cells fresh cells

Summary:Summary:

5. Parasite spread: 5. Parasite spread: macrophage lysismacrophage lysis→amastigote release.→amastigote release.

via blood speadvia blood spead

lymphatic spreadlymphatic spread

6. Reside site:6. Reside site: the cells of the reticuloendothelial systemthe cells of the reticuloendothelial system (skin, liver, spleen, lymph node, bone marrow)(skin, liver, spleen, lymph node, bone marrow)

PathogenesisPathogenesis①①Amastigote forms destroy macrophages Amastigote forms destroy macrophages →hyp→hyperplasiaerplasia →→ lead to hepatosplenomegaly. lead to hepatosplenomegaly.

②②Bone marrow turns hyperplastic, and parasitized Bone marrow turns hyperplastic, and parasitized macrophages replace the normal hemopoietic tissue.macrophages replace the normal hemopoietic tissue. pancytopenia .pancytopenia .

Oligocythemia of red blood cells,Oligocythemia of red blood cells,

Leucopenia, Leucopenia,

ThrombocytopeniaThrombocytopenia

Normal valueNormal value

RBCRBC ：： 3.5-5.03.5-5.0╳╳10101212/L, 4.0-5.5/L, 4.0-5.5╳╳10101212/L/LWBCWBC ：： 4,0-10 4,0-10 ╳╳101099/L /L Blood plateletsBlood platelets ：： 100-300 100-300 ╳╳101099/L/L

PathogenesisPathogenesis

②②Bone marrow turns hyperplastic, and parasitized macrophages replace Bone marrow turns hyperplastic, and parasitized macrophages replace the normal hemopoietic tissue.the normal hemopoietic tissue. pancytopenia .pancytopenia .

①①Amastigote forms destroy macrophages Amastigote forms destroy macrophages →hyperplasia→hyperplasia →→ lead to lead to hepatosplenomegaly.hepatosplenomegaly.

③③leishmanial antigens stimulate immune system an leishmanial antigens stimulate immune system an overproduction of both specific immunoglobulins and noverproduction of both specific immunoglobulins and nonspecific immunoglobulins also occurs a reversal onspecific immunoglobulins also occurs a reversal of the albumin-globulin ratio. of the albumin-globulin ratio.

Albumin(Albumin(AA) ) normal valuenormal value ：： 40-50g/L40-50g/L

Globulin(Globulin(GG)) normal valuenormal value ：： 20-30g/L20-30g/L

A/G A/G normal valuenormal value ：： 1.5 -- 2.5:11.5 -- 2.5:1

A/G reversal A/G reversal ：：

Clinical featuresClinical features1. Visceral leishmaniasis 1. Visceral leishmaniasis （（ Kala-azarKala-azar ））

③ ③Main symptomsMain symptoms ：： ..An insidious onset with irregular lowgrade fever.An insidious onset with irregular lowgrade fever.

. Hepatosplenomegaly.. Hepatosplenomegaly.

. Lymphadenopathy.. Lymphadenopathy.

. Anemia.. Anemia.

. The hemorrhagic tendency.. The hemorrhagic tendency.

. The skin on the hands, feet, abdomen and face may become dark. The skin on the hands, feet, abdomen and face may become darkened. ened.

. Pancytopenia.. Pancytopenia.

.A reversal of the albumin-globulin ratio..A reversal of the albumin-globulin ratio.

② ② The incubation period: The incubation period: 3-6 months (months or years). 3-6 months (months or years).

① ① is caused by L. donovani. is caused by L. donovani.

★ ★ Post–kala azar dermal leishmaniasisPost–kala azar dermal leishmaniasis

.Follows the treatment of visceral leishmaniasis, normal.Follows the treatment of visceral leishmaniasis, normally develops < 2 years after recovery.ly develops < 2 years after recovery.

. Restricted to skin.. . Restricted to skin..

. Dermal lesions are categorized into 3 types, as follo. Dermal lesions are categorized into 3 types, as follows: ws:

. . Depigmented macules Depigmented macules

. Erythematous patches . Erythematous patches

. Yellowish pink nodules. Yellowish pink nodules

ClinicalClinical1. Visceral leishmaniasis 1. Visceral leishmaniasis （（ Kala-azarKala-azar ））

③ ③Main symptomsMain symptoms ：： ② ② The incubation period: The incubation period: 3-6 months (months or years). 3-6 months (months or years).

① ① is caused by L. donovani. is caused by L. donovani.

④④Complications:Complications:

Bacterial pneumonia, septicemia, dysentery, tuberculosis, caBacterial pneumonia, septicemia, dysentery, tuberculosis, cancrum oris, and uncontrolled hemorrhage or its sequelae can ocncrum oris, and uncontrolled hemorrhage or its sequelae can occur as complications of leishmaniasis. cur as complications of leishmaniasis.

⑤⑤ Prognosis:Prognosis:

If untreated, death occurs within 2 years. If untreated, death occurs within 2 years.

. caused by mainly in 2 forms, L. tropica and L. mexic. caused by mainly in 2 forms, L. tropica and L. mexicana. L. tropica has two subspecies L. tropica and L. maana. L. tropica has two subspecies L. tropica and L. major. jor.

. the amastigote form resides in the large mononuclear . the amastigote form resides in the large mononuclear cells of the skin. cells of the skin.

. skin lesions mainly on the face, arms, and legs. . skin lesions mainly on the face, arms, and legs.

. often self-healing but can create serious disability an. often self-healing but can create serious disability and permanent scars. d permanent scars.

2. Cutaneous leishmaniasis2. Cutaneous leishmaniasis

ClinicalClinical

. The disease is also known as . The disease is also known as “oriental sore”. “oriental sore”.

. An ulcer of 1-3cm develops with . An ulcer of 1-3cm develops with a surrounding zone of inflammation a surrounding zone of inflammation (crater-like). (crater-like).

. Healing occurs in a few months . Healing occurs in a few months and there is a lasting immunity. and there is a lasting immunity.

2. Cutaneous leishmaniasis2. Cutaneous leishmaniasis

① ① caused by L. tropicacaused by L. tropica

ClinicalClinical

Typical lesions of cutaneous leishmaniasis caused by Typical lesions of cutaneous leishmaniasis caused by L. tropicL. tropicaa

After treatmentAfter treatment

Typical lesions of cutaneous leishmaniasis caused by Typical lesions of cutaneous leishmaniasis caused by L. tropicL. tropicaa

After treatmentAfter treatment

Typical lesions of cutaneous leishmaniasis caused by Typical lesions of cutaneous leishmaniasis caused by L. majorL. major

Typical lesions of cutaneous leishmaniasis caused by Typical lesions of cutaneous leishmaniasis caused by L. majorL. major

Typical lesions of cutaneous leishmaniasis caused by Typical lesions of cutaneous leishmaniasis caused by L. majorL. major

Typical lesions of cutaneous leishmaniasis caused by Typical lesions of cutaneous leishmaniasis caused by L. majorL. major

After treatmentAfter treatment

. The initial lesion in humans ulcerates and becomes cr. The initial lesion in humans ulcerates and becomes crater-like and inflamed (like oriental sore).ater-like and inflamed (like oriental sore).

. But it can cause “chiclero’s ulcer” which can involve . But it can cause “chiclero’s ulcer” which can involve almost total destruction of the external ear.almost total destruction of the external ear.

2. Cutaneous leishmaniasis2. Cutaneous leishmaniasis

②② caused by L. mexicanacaused by L. mexicana

ClinicalClinical

2. Cutaneous leishmaniasis2. Cutaneous leishmaniasis

▲ ▲ Diffuse cutaneous leishmaniasisDiffuse cutaneous leishmaniasis

.associated with a .associated with a deficient cell-mediated deficient cell-mediated immunity .immunity .

.enables the parasite .enables the parasite to disseminate in the to disseminate in the subcutaneous tissues.subcutaneous tissues.

. non-healing, life . non-healing, life long non-ulcerative long non-ulcerative infection infection

ClinicalClinical

. also called “espundia”. . also called “espundia”.

. caused by L. braziliensis .. caused by L. braziliensis .

. it destroys the mucous membranes of the nose, mouth, th. it destroys the mucous membranes of the nose, mouth, throat and even soft palate. roat and even soft palate.

3. Mucocutaneous leishmaniasis3. Mucocutaneous leishmaniasis

ClinicalClinical

ClinicalClinical1. Visceral leishmaniasis 1. Visceral leishmaniasis （（ Kala-azarKala-azar ））

2. Cutaneous leishmaniasis2. Cutaneous leishmaniasis

3. Mucocutaneous leishmaniasis3. Mucocutaneous leishmaniasis

Differential diagnosis: Differential diagnosis:

Laboratory StudiesLaboratory Studies

①①. Bone marrow aspiration: . Bone marrow aspiration: Positivity rates ranging from 5Positivity rates ranging from 54-86% 4-86%

②②. Splenic aspiration: . Splenic aspiration: Up to 98% positive results Up to 98% positive results

③③. Lymph node aspiration or biopsy: . Lymph node aspiration or biopsy: Positivity rates raPositivity rates ranging from 54-86% nging from 54-86%

④④. Culture:. Culture:

⑤⑤. Animal inoculation:. Animal inoculation:

⑥⑥.. cutaneous tissue biopsy or aspiration: cutaneous tissue biopsy or aspiration:

1. Direct evidence of infection:1. Direct evidence of infection:

2. Indirect evidence of infection2. Indirect evidence of infection

3. 3. Supportive testsSupportive tests

Laboratory StudiesLaboratory Studies

①①. Detection of hypergammaglobinemia:. Detection of hypergammaglobinemia:

.the aldehyde test .the aldehyde test

.the antimony test .the antimony test

②②. Immunological tests:. Immunological tests:

③③. Nonspecific tests:. Nonspecific tests:

. the direct agglutination test. the direct agglutination test

. immunofluorescent antibody test. immunofluorescent antibody test

.complement fixation .complement fixation

.counterimmunoelectrophoresis .counterimmunoelectrophoresis

. Leishmanin skin test (Montenegro test) . Leishmanin skin test (Montenegro test)

. Polymerase chain reaction (PCR) . Polymerase chain reaction (PCR)

1. Direct evidence of infection:1. Direct evidence of infection:

2. Indirect evidence of infection2. Indirect evidence of infection

Laboratory StudiesLaboratory Studies

①①. a normochromic normocytic anemia. a normochromic normocytic anemia

②②. leukopenia . leukopenia

③③. neutropenia . neutropenia

④④. thrombocytopenia. thrombocytopenia

⑤⑤. elevated gamma globulins . elevated gamma globulins

⑥⑥.. a reversal of the albumin-globulin ratio a reversal of the albumin-globulin ratio

1. Direct evidence of infection:1. Direct evidence of infection:

2. Indirect evidence of infection2. Indirect evidence of infection

3. 3. Supportive testsSupportive tests

EpidemiologyEpidemiology

Geographical Geographical

distribution distribution

EpidemiologyEpidemiology

. . Leishmaniases are considered to be endemic iLeishmaniases are considered to be endemic in 88 countries (16 developed countries, 72 develn 88 countries (16 developed countries, 72 developing countries) on 5 continents of Africa, Asia, oping countries) on 5 continents of Africa, Asia, Europe, North America, and South America. Europe, North America, and South America.

Geographical distribution Geographical distribution

EpidemiologyEpidemiology

.. Today, an estimated Today, an estimated 12 million12 million cases of leishmaniasis cases of leishmaniasis exist worldwide. A total of 350 million people are at risk. exist worldwide. A total of 350 million people are at risk.

.. an estimated an estimated 1.5 -2 million new cases1.5 -2 million new cases occurring a occurring annuallynnually. .

The number of casesThe number of cases

EpidemiologyEpidemiology

.. man-made environmental changes that increase human exposure man-made environmental changes that increase human exposure to the sandfly vector. to the sandfly vector.

.. the movement of susceptible populations into endemic areas, inc the movement of susceptible populations into endemic areas, including large-scale migration of populations for economic reasons. luding large-scale migration of populations for economic reasons.

.. The immune deficiency has lead to increased susceptibility to inf The immune deficiency has lead to increased susceptibility to infections, coexistence of leishmaniasis with HIV adds a serious dimeections, coexistence of leishmaniasis with HIV adds a serious dimension . nsion .

Today the number of cases of leishmaniToday the number of cases of leishmaniasis is increasing, Why? asis is increasing, Why?

PreventionPrevention

.. Treatment of active cases. Treatment of active cases.

.. Reservoir control. Reservoir control.

.. Sandfly control. Sandfly control.

.. Personal protection using repellants and nets is an Personal protection using repellants and nets is an important aspect. important aspect.

.. Education regarding preventing the bite of sandfly. Education regarding preventing the bite of sandfly.

TreatmentTreatment1. Visceral leishmaniasis 1. Visceral leishmaniasis （（ Kala-azarKala-azar ））

sodium antimony gluconate----- sodium antimony gluconate-----

upto 25% resistanceupto 25% resistance

Resistance to stibogluconate :Resistance to stibogluconate :

.should be treated with alternate agents, such as lip.should be treated with alternate agents, such as liposomal amphotericin, Pentamidine, aminosidine osomal amphotericin, Pentamidine, aminosidine

. combination of stibogluconate with drugs, such a. combination of stibogluconate with drugs, such as aminosidine and interferon gamma, s aminosidine and interferon gamma,

TreatmentTreatment2. Cutaneous leishmaniasis2. Cutaneous leishmaniasis

treatment essentially remains the same. treatment essentially remains the same. sosodium antimony gluconatedium antimony gluconate and pentamidine and pentamidine are the drugs of choice. are the drugs of choice.

3. Mucocutaneous leishmaniasis3. Mucocutaneous leishmaniasis

this responds to a 20-day course of this responds to a 20-day course of sodium sodium antimony gluconate antimony gluconate, with resistant cases bein, with resistant cases being treated with amphotericin.g treated with amphotericin.

TreatmentTreatment

. Good nursing and diet. Good nursing and diet

. Drug treatment. Drug treatment

☆ ☆ leishmania donovani leishmania donovani (complex)(complex)

☆☆ leishmania tropicaleishmania tropica

☆☆ leishmania majorleishmania major

☆☆ leishmania mexicana leishmania mexicana (complex)(complex)

☆☆ leishmania brazilliensis leishmania brazilliensis (complex)(complex)

☆☆ leishmania aethiopicaleishmania aethiopica

LeishmaniaLeishmania Species pathogenic in humans: Species pathogenic in humans:

Summary1Summary1

Life cycleLife cycle

amastigoteamastigote promastigotepromastigote promastigotepromastigote

the femalethe female sandfly sandfly sucks blood sucks blood of human or mammalian host of human or mammalian host

Enter the mid gutEnter the mid gut

binary fission binary fission

migrate to the migrate to the pharynx andpharynx andbuccalbuccal cavitycavity

amastigoteamastigote amastigoteamastigote

the femalethe female sandflysandfly bite bite human or mammalian hosthuman or mammalian host

binary fissionbinary fission

Macrophage Macrophage rupture, invade rupture, invade

fresh cells fresh cells 1.Infect stage:1.Infect stage: the promastigote formthe promastigote form

2.The vector:2.The vector: sandflysandfly

3.Methods of transmission :3.Methods of transmission : the bite of sandflythe bite of sandfly

4.Host:4.Host: humans , dogs, wild rodents ,humans , dogs, wild rodents ,

5. Parasite spread: 5. Parasite spread: macrophage lysis→amastigote release.macrophage lysis→amastigote release.

via blood speadvia blood spead

lymphatic spreadlymphatic spread

6. Reside site:6. Reside site: the cells of the reticuloendothelial systemthe cells of the reticuloendothelial system (skin, liver, spleen, lymph node, bone marrow)(skin, liver, spleen, lymph node, bone marrow)

Summary2Summary2

Summary3Summary31.1. Visceral leishmaniasis Visceral leishmaniasis （（ Kala-azarKala-azar ）） caused by L. donovani.caused by L. donovani.

2. Cutaneous leishmaniasis2. Cutaneous leishmaniasis

caused by mainly in 2 forms, L. tropica ancaused by mainly in 2 forms, L. tropica and L. mexicana. d L. mexicana.

3. Mucocutaneous leishmaniasis3. Mucocutaneous leishmaniasis

caused by L. braziliensis .caused by L. braziliensis .