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

in the sand fly and in cultures 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 1.5-4 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 amastigote amastigote amastigote promastigote promastigote binary fission migrate to the pharynx and buccal cavity the female sandfly sucks blood of human or mammalian host amastigote promastigote promastigote Enter the mid gut binary fission Macrophage rupture, invade fresh cells the female sandfly bite human or mammalian host amastigote amastigote

man sandfly Life cycle of Leishmania

Summary: Infect stage: the promastigote form The vector: sandfly Methods of transmission : the bite of sandfly Host: humans , dogs, wild rodents ,

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, Thrombocytopenia Normal value 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

Pathogenesis Albumin(A) normal value ：40-50g/L Globulin(G) normal value ：20-30g/L A/G normal value ：1.5 -- 2.5:1 A/G reversal ： ①Amastigote forms destroy macrophages →hyperplasia → lead to hepatosplenomegaly. ②Bone marrow turns hyperplastic, and parasitized macrophages replace the normal hemopoietic tissue. 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.

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. 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

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 Differential diagnosis: 1. Visceral leishmaniasis （Kala-azar） 2. Cutaneous leishmaniasis 3. Mucocutaneous leishmaniasis Differential diagnosis:

Laboratory Studies 1. Direct evidence of infection: 2. Indirect evidence of infection 3. Supportive tests ①. Bone marrow aspiration: Positivity rates ranging from 54-86% 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 . Today, an estimated 12 million cases of leishmaniasis exist worldwide. A total of 350 million people are at risk. . an estimated 1.5 -2 million new cases occurring annually.

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

Summary2 1.Infect stage: the promastigote form 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 blood spead lymphatic spread 6. Reside site: the cells of the reticuloendothelial system (skin, liver, spleen, lymph node, bone marrow)

Summary3 Visceral leishmaniasis （Kala-azar） 2. Cutaneous leishmaniasis 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 .