Cutaneous, Mucocutaneous

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1 Cutaneous, Mucocutaneous
Leishmaniasis Cutaneous, Mucocutaneous And Visceral

2 Genus: Leishmania Disease: Leishmaniasis
I- Cutaneous leishmaniasis II- Mucocutaneous leishmaniasis III- Visceral Leishmaniasis.

3 Genus: Leishmania Disease: Leishmaniasis
Leishmaniasis is classified according to its clinical picture & geographical distribution: I- Cutaneous leishmaniasis A- Old World Cutaneous leishmaniasis. B- New World Cutaneous leishmaniasis. II- Mucocutaneous leishmaniasis A- New World Mucocutaneous leishmaniasis. III- Visceral Leishmaniasis.

4 Epidemiology Leishmaniasis occurs in tropical and temperate regions, in the living areas of the sand fly vector (Phlebotomus spp. in Old world and Lutzomyia spp. in New world). It is endemic in areas on four continents including the Middle East region. ~1.5 million annual new cases of which 3/4 are cutaneous forms and 1/4 visceral form.

5 Morphology) Amastigotes (donovan bodies): In vertebrates hosts [Man – Dog]. Reticulo-Endothelial Cells (RECs) all body organs in VL and in skin macrophage in CL. intracellular in macrophages. Promasitogtes (flagellated form): Motile (with anterior flagellum) [Vector – culture]

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7 Life cycle of Leishmania species
The infective stage is transmitted by the bite of several species of blood-feeding female sand flies (Phlebotomus or Lutzomyia) which carries the promastigote in the anterior gut and pharynx. It gains access to macrophages & other phagocytic cells of the reticuloendothelial system where it transform into amastigotes (Leishmania forms) and divides until the infected cell ruptures. The released organisms infect other cells. The sand fly acquires the organisms during its meal, the amastigotes transform into flagellate promastigotes (Leptomonad forms) and multiply in the gut until the anterior gut and pharynx are packed. Salivary glands are not invaded. Dogs and rodents are common reservoir hosts.

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9 When the sand fly attempts a subsequent blood meal, some of the infective promastigotes are dislodged, regurgitated, and introduced into the skin bite by their motility.

10 Leishmania spp. life cycle

11 Cutaneous Leishmaniasis
Cutaneous & Mucocutaneous Leishmaniasis

12 Cutaneous Leishmaniasis
D.H. man R.H. dogs, rodents Vector (I.H.) Sand fly

13 Geographical distribution of Cutaneous Leishmaniasis

14 Cutaneous Leishmaniasis
Infective stage Promastigote or Amastigote. Transmission 1- Biological: Bite of infected female ♀ sand flies. (Infective stage >>> Promastigote form). 2- Mechanical: Direct contact & autoinfection. (Infective stage >>> Amastigote form).

15 Cutaneous leishmaniasis [CL]
Old World CL: caused by L. tropica complex (L. tropica, L. major & L. aethiopica). New World CL: caused by L. mexicana & L. braziliensis complexes. Classical lesion The lesion starts at the site of inoculation (bite) as a Papule >>> Nodule; due to multiplication of Leishmania form in skin macrophages & granulomatous reaction around them; then >>> ulcerates and the ulcer heals leaving a disfiguring scar.

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17 A- Old World Cutaneous Leishmaniasis L. tropica complex
[1] Leishmania tropica Chronic, dry or urban Cutaneous Leishmaniasis: (1) Painless ulcer or Oriental sore. [2] Leishmania major Acute, wet or rural Cutaneous Leishmaniasis. [3] Leishmania aethiopica a. Diffuse (Disseminated) Cutaneous Leishmaniasis.

18 [1] a- Chronic, Dry or Urban CL [caused by L. tropica].
Reservoir host: Dogs. Incubation period: 2-8 months. Distribution: Occurs in Mediterranean region, Middle East, parts of Africa & Asia (mainly in urban areas). Insect vector: Female Sand fly - Phlebotomus papatassi

19 (1) Dry ulcer or Oriental sore
The lesion starts as a single red pruritic papule on the exposed parts of the body. It is dry & painless. It increases in size, crusts & ulcerates after several months. The ulcer [Oriental sore] has sharp cut edges, raised indurated margin (volcano like), with scanty exudate Healing in about 1-2 years leaving depigmented flat, atrophic, disfiguring scar.

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22 Dry Oriental Sore.

23 [2] a- Acute, Wet or Rural CL [caused by L. major]
Reservoir host: Rodents. Incubation period: 2-6 weeks. Distribution: Occurs in the desert areas of Middle East, Asia, Africa [mainly in rural areas]. Lesions are multiple & more severe than the chronic, dry type of L. tropica

24 [2] a- Acute, wet or rural CL [Cont.]
The Lesions are painless, severely inflamed, moist with serous exudate and rapidly ulcerating. Healing takes place within months, leaving large disfiguring scars.

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26 [3] a- Diffuse; Disseminated; Cutaneous Leishmaniasis [Caused by Leishmania aethiopica]
Distribution: L. aethiopica occurs mainly in Ethiopia, Kenya & south Yemen. The parasite causes chronic disseminated nodules, NOT Ulcerate. [due to deficient cell-mediated immunity & Failure of Immune system] Diffuse Cutaneous Leishmaniasis similar to Lepromatous leprosy

27 B- New world cutaneous leishmaniasis
Parasite: L. braziliensis complex a. Espundia: b. Uta: Caused by L. peruviana; & L. mexicana complex. a. Chiclero’s ulcer b. Diffuse Cutaneous Leishmaniasis. Distribution: Occurs in Central & South America. Reservoir hosts: Forest rodents & dogs. Vector: ♀ sand fly, genus Lutzomyia.

28 II- Mucocutaneous Leishmaniasis or Espundia
L. braziliensis produces single or multiple lesions; that undergo extensive ulceration. lymphatic spread to mucous membranes of nose, mouth & ear may occur >>> causing hypertrophy, destruction, severe pain & great deformity .

29 Mucocutaneous Leishmaniasis or Espundia [Cont.]
Disfiguration is often extreme with complete destruction of the nasal septum, perforation of the palate and damage to the tissues of the lips and larynx. Oedema, tissue destruction, (Espundia). Death may develop from aspiration pneumonia, or septicemia.

30 L. mexicana Chiclero’s ulcer Chiclero’s ulcer
Occurs in forest workers [Chicle collectors]. It is a single painless lesion mainly affects the ear Causing destruction of cartilage & heal spontaneously within 6 months. Chiclero’s ulcer

31 Diagnosis of Cutaneous Leishmaniasis

32 1- Direct Laboratory Methods
1-a- Aspirated tissue juice, scraping or biopsy material from raised nodule or raised edge of the ulcer & from mucosal scraping in mucocutaneous type to detect the parasite after: preparing smears & staining with Giemsa or Leishman stains >>> Amastigote form. b- Inoculation in culture [NNN medium] >>> Promastigote form. c- Animal inoculation 2- Aspirate or biopsy >>> PCR to diagnose & type the species. Amastigote Promastigote

33 Aspiration and biopsy from the ulcer
Scrape or take biopsy Aspiration Leishmania amastigotes (Giemsa stained)

34 It is a delayed hypersensitivity skin test.
2- Indirect Laboratory Methods 2- Indirect methods: a- Intradermal skin test [Leishmanin or Montenegro's test]: It is a delayed hypersensitivity skin test. Positive test [˃ 95%] >>> induration more than 5 mm at site of injection after 48 hours. It is –ve in D.C.L. (since there is deficiency in cell mediated immunity).

35 Treatment 1) Local measures:
Surgical excision especially in single lesions. Scraping (curettage). Intra- lesional injection of pentavalent antimonial or 2% atebrine sulphate I.D. Heating of lesion to 50% with coned infra red rays & freezing therapy, using carbon dioxide snow. - Antibiotics: for 2nd bacterial infections 5- Local heat application: for 12 hours as leishmania do not grow above 33 ºC.

36 Treatment Pentostam is the drug of choice.
2) Systemic treatment: Pentostam is the drug of choice. - Metronidazol against Mexican cutaneous leishmaniasis gives impressive results. - Amphotricin B. 5- Local heat application: for 12 hours as leishmania do not grow above 33 ºC.

37 Prevention & control Treatment of cases, control of reservoir hosts.
Proper dressing of the ulcer Active immunization on concealed parts of body in endemic areas. Protection: by using wire screens, repellents & mosquito nets fine mesh screening (40 meshes/ inch2) Control of sand flies by destruction of their breeding grounds and by the use of residual chlorinated hydrocarbon as DDT. 2- to reduce 2nd infection, to reduce transmission to sandflies.

38 Leishmania species & Disease
Cutaneous Leishmaniasis Leishmania tropica * Leishmania major * Leishmania aethiopica Leishmania mexicana Mucocutaneous Leishmaniasis Leishmania braziliensis Visceral Leishmaniasis Leishmania donovani * Leishmania infantum * Leishmania chagasi

39 Visceral Leishmaniasis

40 1- Visceral Leishmaniasis (Kala azar, black fever or Dum-dum fever)
Causes: A- In old world : L. donovani complex that includes, L. donovani and L. infantum. B- In new world: L. chagasi and L. amazonensis.

41 Geographical distribution of Visceral Leishmaniasis

42 Geographical distribution
L. donovani: the disease is endemic in India, Pakistan, Indonesia Thailand, Central Africa & Sudan. L. infantum: Mediterranean area (North Africa) and southern Europe, as it affects principally infants and young children L. chagasi: in the Americas (central & south America).

43 Morphology : - In Reticulo-Endothelial Cells (RECs) all over the human body & reservoir hosts, it takes numerous amastigote (Leishmalial) forms, intracellular in macrophages In insect vector and culture, it takes the promastigote (Leptomonal) form.

44 Infective stage: Promastigotes in buccal
Life Cycle: Habitat: R.E.Cs of the viscera, especially of spleen, liver, bone marrow, intestinal mucosa & mesenteric lymph nodes. Definitive host: Man. Reservoir hosts: domestic dogs, rodents & desert gerbils. Insect vectors: are female Sand flies of the Genus Phlebotomus ,which in the Americas has been renamed Lutzomyia. Infective stage: Promastigotes in buccal cavity & proboscis of Sand fly. Mode of infection: 1) Bite of infected sand fly. 2) Blood transfusion. 3) Direct from man to man in epidemics by nasal secretions. 4) Congenital. 5) Accidental infection in laboratory.

45 Clinical Manifestations
The incubation period is long 1-3 months, but may be as short as 2 weeks. A primary lesion at the site of infection is rarely observed, minute papules (dermal leishmaniomas). The phagocytosed parasites are numerous in the R.E.Cs of the previously mentioned organs with marked hyperplasia.

46 Clinical Manifestations
The most important physical finding is fever with characteristic twice-daily elevation, +malaise, headache, sweating, weakness, hepatomegaly. Splenomegaly. Diarrhea and dysentery,

47 Clinical Manifestations
Bone marrow involvement ↓ production of reticulocytes (aneamia), ↓ platelets (thrombocytopenia), also ↓ WBCs (neutropenia) allows bacteria and other secondary invaders to attack tissues. Oedema of the skin, ematiation, bleeding tendancy Anaemia in Kala-azar may be: 1) Aplasatic anaemia due to extensive multiplication of parasites in bone marrow. 2) Microcytic anaemia in 5% due to lack of iron absorption from intestine. 3) Macrocytic anaemia due to hepatic damage & fatty infiltration deficient storage of vit. B12.

48 Clinical Manifestations
Hyperpigmentation of the skin may be noticed, the term Kala-azar is for black sickness. A butterfly distribution over the nose.

49 Post kala- azar dermal leishmanoid:
Clinical Manifestations Post kala- azar dermal leishmanoid: It is an outbreak of chronic, progressive, granulomatous hypopigmented cutaneous nodules (no ulceration). It may appear 6 months to 5 years after spontaneous or drug cure. The parasite will migrate to the skin mostly of the face resemble Lupromatous leprosy or disseminated cutaneous Leishmaniasis.

50 Diagnosis of Visceral Leishmaniasis

51 2) Laboratory diagnosis: [parasite or antibodies] A- Direct:
1) Clinical diagnosis: kala azar may be suspected in a patient with irregular or remittent fever (often a double daily peak), hepato- splenomegaly, pain from perisplenism, anaemia, leucopenia & ematiation. 2) Laboratory diagnosis: [parasite or antibodies] A- Direct: - Detection of the parasites (amastigote inside & outside macrophages) in blood films after staining with Leishman stain.

52 Diagnosis The parasite can be demonstrated in aspirates from LN, liver , bone marrow, or Splenic puncture or blood : examined directly, or inoculated in N.N.N. culture media showing promastigotes in the form of rosette grouping of parasites.

53 B- Indirect: Diagnosis 1- Montenegro (leishmanin) test
- - A delayed reaction develops in cured individuals. - The test is negative in early cases due to depression of cellular immunity by the parasites, but becomes positive 6-8 weeks after completion of treatment.

54 Diagnosis 6- ELISA, IFA or direct agglutination: (↑ IgG).
2- Aldehyde test (Formol gel or Napier's test): - formalin is added to serum of person. The test is positive if the serum solidified. - It depends upon ↑ of serum gamma globulins. 3- Antimony test (Chopra's or Urea-Stibamine test) :  formation of white ring at the interface indicates positive reaction. 4- Globulin opacity test or (Sia's test) : - distilled water. opaque in positive cases. 5- Fluorescent antibody test 6- ELISA, IFA or direct agglutination: (↑ IgG).

55 Diagnosis

56 Treatment 1- Supportive treatment includes : - Good nursing care. - Diet rich in vitamins, iron & antibiotics. - Blood transfusion, for patients with severe anaemia or bleeding problems. 2- Specific treatment : - Pentostame (Antimony sodium gluconates or Sodium stibogluconate). - Amphotricin B.

57 Prevention & control Treatment of cases [proper & complete].
Control of reservoir hosts. Screening of blood donors Protection: by using wire screens, repellents & mosquito nets fine mesh screening (40 meshes/ inch2) Control of sand flies by destruction of their breeding grounds and by the use of residual chlorinated hydrocarbon as DDT. 2- to reduce 2nd infection, to reduce transmission to sandflies.