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Leishmaniasis. Different stages of Haemoflagellates.

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Presentation on theme: "Leishmaniasis. Different stages of Haemoflagellates."— Presentation transcript:

1 Leishmaniasis

2 Different stages of Haemoflagellates

3 Causative agent Leishmania genus parasitic protozoa transmitted to human by sandflies. Over 20 species and subspecies infect human, each causing a different spectrum of symptoms.

4 Promastigote Amasitgote Transformation Transformation Leishmania life cycle

5 Taxonomy Phylum: Sarcomastigophora Sub-phylum: Mastigophora Class: Zoomastigophora Order: Kinetoplastida Suborder: Trypanosomatina Family: Trypanosomatidae Genus: Leishmania –Subgenous Leishmania –Subgenous Viannia

6 Leishmania life cycle Amastigotes replicate in reticuloendothelial cells (mononuclear cells) including; –Monocytes –Macrophages in lymph nodes, spleen, and lung; –Kupffer cells in sinusoids of liver –Microglial cells in the central nervous system. –Dendritic cells Promastigotes reproduce in biting fly (Phlebotomus, Lutzomyia)

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8 Leishmania infects and thrives in macrophages Promastigotes attached to CR1 and CR3 receptors on the macrophages The parasite invades its host cell passively by phagocytosis (parasitophorous vacuole)

9 Ovoid small intracellular parasites in a bone marrow aspirate. The typical rod shaped kinetoplast is seen besides the nucleus. (Giemsa stain). Leishmania sp. amastigote stage

10 Leishmaniasis vectors There are over 600 species of sand flies divided into five genera. More than 30 species are proved vectors. Phlebotomus in the Old-world and Lutzomia in the New world are vectors of human leishmaniasis.

11 Procyclics and Metacyclic Promastigotes Amastigotes are released by digestion, transform into procyclic promastigotes and attach to the midgut epithelium Attached promastigotes divide rapidly Metacyclic (infective) promastigotes cease replication, detach and pass forward into the pharynx from where they are regurgitated into the bite site (attached) (detached)

12 subgenus Leishmania: develops in the sand fly’s midgut and foregut (suprapylorian) – Both Old world and New world visceral and cutaneous species subgenus Viannia: develops in the hindgut and midgut (peripylarian). –L. braziliensis complex, L. guyanensis complex. Two subgenera of Leishmania genus

13 Importance Leishmaniasis is a parasitic disease transmitted by the bite of sand flies. In at least 88 countries. 350 million people at risk. 12 million people are affected by leishmaniasis million new cases of cutaneous leishmaniasis estimated to occur annually new cases of VL which occur annually. 90% of CL cases were from Afghanistan, Algeria, Brazil, Iran, Peru, Saudi Arabia and Syria. 90% of VL cases were from Bangladesh, India, Nepal, Sudan and Brazil. 90% of mucocutaneous leishmaniasis occurs in Bolivia, Brazil and Peru.

14 Endemic areas for leishmaniasis Endemic areas for leishmaniasis

15 1.Cutaneous leishmaniasis (CL) 2. Visceral leishmaniasis (VL), (kala-azar) is the most severe form of the disease. Mortality rate 75-95% 3. Mucocutaneous leishmaniasis (MCL), or espundia, disfiguring, destruction of mucous membranes of the nose, mouth and throat cavities. Reconstructive surgery of deformities is an important part of therapy The disease main forms

16 Cutaneous Leishmaniasis

17 Skin ulcers on the exposed parts of the body such as the face, arms and legs. Old World: L. major, L. tropica, L. aethiopica (DCL) New World: L. mexicana, L. pifanoi, L. amazonensis, L. venezuelensis, L. granhami,

18 Cutaneous Leishmaniasis Characterized by one or more papules, nodules and sores on the skin Sore like a volcano with a raised edge and central crater. Two figures including urban (dry) and rural (wet) forms. Sores are usually painless but can become painful if secondarily infected chronic but self-limiting

19 The skin sores will heal by themselves, but this can take months or years. The sores can leave ugly scars. Swollen lymph nodes may be present near the sores (under the arm if the sores are on the arm or hand…)

20 Infection remains restricted to the initial site of infection (the bite site)

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22 Leishmania tropica Anthroponotic Cutaneous Leishmaniasis (ACL) Definitive Host: Humans (occasionally dog?) Intermediate Host: Phlebotomus sand flies –Main vector and also in Iran: P. Sergenti Dry or urban C.L. Face> hand, leg and… Incubation period: 2-8 months(usually 2-3 months) Lesion persist for several months (more than one year) then person is immune

23 Leishmania tropica Sores don’t heal very quickly –Often mistaken for leprosy or tuberculosis First sign: small papule nodule dry sore Itching Scar (if not treated)

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25 Rarely can cause visceral (viscerotropic) and diffuse cutaneous infections.

26 Leishmania major Wet or rural form Definitive Host: rodents (Rodentia: Gerbillidae) as reservoir host, Humans In Iran: Rhombomys opimus, Meriones libycus, M.hurrianae, Tatera indica Zoonotic Cutaneous leishmaniasis (ZCL) Intermediate Host: Phlebotomus sand flies. In Iran: P. papatasi. Incubation period: some weeks to 3 months ( usually 2 weeks) First sign: small papule nodule Wet sore (exudates) Itching Scar (if not treated) Disease period is usually short (2-8 months) More in hands and feet

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30 Sporotrichoid form: Dissemination of amastigotes via the lymphatics to the subcutaneous tissues. Regional lymphadenopathy with fever Different cases from Panama and Brazil. The main causative agents were L (V) panamensis and L (V) guyanensis. Old World CL is less commonly associated with sporotrichoid presentation but several cases have been reported from the Middle East. It is very rare in Europe and only a few cases have been reported in Italy.

31 Diffuse cutaneous leishmaniasis Recidivans leishmaniasis Sporotrichoid form

32 Cutaneous leishmaniasis differentials Fungal Bacterial Viral Inflammatory Neoplastic

33 Leprosy It is primarily a granulomatous disease of the peripheral nerves and mucosa of the upper respiratory tract.granulomatousperipheral nerves mucosaupper respiratory tract Skin lesions are the primary external sign. Left untreated, leprosy can be progressive, causing permanent damage to the skin, nerves, limbs and eyes.

34 Lupus volgaris (a sort of cutaneus TB) Persistent and progressive form of cutaneous TB. Small sharply defined reddish-brown lesions with a gelatinous consistency (called apple-jelly nodules). Lesions persist for years, leading to disfigurement and sometimes skin cancer

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36 New World cutaneous leishmaniasis L. mexicana (Chicleros Ulcer) –External ear L. pifanoi L. amazonensis –main cause of DCL –All four leishmaniasis forms L. (V.) peruviana (Uta) L. granhami L. venezuelensis

37 Visceral Leishmaniasis

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39 Systemic infection of reticulo-entdothelial cells (mostly macrophages) throughout multiple internal organs and the blood

40 Kala-azar, Visceral Leishmaniasis L. donovani complex –L. donovani (Asia, East Africa) Strain archibaldi –L. infantum (Medditeranian basin and Middle East, in children) –L. chagasi ( South & Central America) L. tropica (viscerotropic) L. amazonensis Weeks to months (2-6 months) incubation period

41 L. infantum, zoonosis, L. donovani,(archibaldi), zoonosis, L. donovani, anthroponotic L. chagasi, zoonotic

42 The most sever leishmaniasis form Mortality of untreated disease 75-95% Prolonged fever (usually dromedary but also continuous, reminant, interminnent) Splenomegaly, hepatomeglay, Weight loss (cachexia), Progressive anemia, pancytopenia, Hypergammaglobulinemia and hypoalbominemia Skin darkness ( around mounth, forehead, temple) Lymphadenopathy may be present Elevated liver enzymes, Nausea, vomiting. Pancytopenia: normochrome & normocytic anemia, trombocytopenia, but lymphocytosis

43 Visceral leishmaniasis should be considered in every case with chronic fever returning from an endemic area. Malaria, tropical splenomegaly, schistosomiasis, cirrhosis, portal hypertension, trypanosomiasis, milliary tuberculosis, brucellosis, typhoid fever, bacterial endocarditis, histoplasmosis, malnutrition, lymphoma, and leukemia (Singh, 2006). Apart from fly biting, other routes including; Placental, blood transfusion, mechanical, sexual routes. Visceral Leishmaniasis

44 Post kala-azar dermal leishmaniasis (PKDL) Sequel of VL which may manifest years after successful treatment and resolution of Kala-azar. Dermal lesions may contain parasites in great numbers. Post Kala-azar Dermal Leishmaniasis (PKDL) has been caused by L. donovani in East Africa and India Pigmentation, red or skin- colored macule, non-ulcerative nodules

45 Viscerotropic leishmaniasis L. tropica Oligoparasitic leishmaniasis Fever, fatigue, digestive tract problems First in desert storm operation in Iraq among American soldiers In Iran: One case from AIDS patient (Tehran), other case (Shiraz)

46 Epidemiology of visceral leishmaniasis in Iran Mediterranean Kala-azar: - Causative agent is L. infantum - Reservior host: involving canine such as Dog, Jackal, fox, wolf and other wild carnivorouses. - The probable main vector in Iran is Phlebotomus major (Fars), other vectors are P.keshishiani (Fars), P. Perfiliewi (Dashte-Moghan),P. kandelakii (Meshkinshahr). - Age distribution: the disease mainly occurs in children from 1 to 4 years of age.

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49 Mucocutaneous Leishmaniasis

50 Espundia or mucocutaenous leishmaniasis

51 May occur months to years after original skin lesion. Lesions can be very disfiguring and destroy all soft parts of the nose and the lips. Death can occurs through secondary bacterial infection. Occurs with Leishmania species from Central and South America Very rarely associated with L. tropica and L. major which are found in the Middle East Hard to confirm diagnosis as few parasites are in the lesion Espundia or mucocutaenous leishmaniasis (con.)

52 Three main agents: L. (V.) braziliensis (espundia=MCL) –MCL Main causative agent –Rodents, occasionally dog and hoarse –First self-healing cutaneous –After 6 months to years espundia (80% in nasopharynx and nose) L. (V.) panamensis (ulcer de bejuco) –MCL second rank agent –Sloth, rodent, monkey –Along lymphatic vein involves the nasopharynx L. (V.) guyanensis (painbois=CL) –Frequent relapse –Sloth, Myrmecophagidae –Like sporotrichosis (along lymphatic veins)

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55 Immunity TH1: –Macrophage produces IL12 –IL12 promote TH0 to TH1 –TH1 produces INF gama, IL2, TNF –Healing and resistance to disease TH2: –TH2 produces IL4, IL5, IL6, IL10, IL13 –Sensitivity to disease

56 Diagnosis

57 1. Clinical Diagnosis: –Patient history ( endemic region or travel), – Signs & symptoms Sores that will not heal, have to be referred for evaluation. Individuals with fevers, weight loss, gastrointestinal complaints, anemia, hypergammaglobulinemia, abnormal liver tests should be referred for evaluation

58 1. Cutaneous Leishmaniasis 1. Cutaneous Leishmaniasis Tissue sample (scraping, aspirate or punch biopsy) for smear and culture Take scrapings from the sore, put on slides, stain with Wright’s or Giemsa’s stains, and look for amastigotes. Culture (NNN & LIT, Evans, RPMI 1640), Laboratory animals inoculation (Souri andBalb/c mouse) only for L. major (no growth in L. tropica) Laboratory Diagnosis of leishmaniasis :

59 Cutaneous Leishmaniasis (con.) Leishmania skin test (Montenegro test) –0.1 ml (1,000,000 killed L. major promastigote), intradermal, –5mm< induration after 48-72h, DTH Isoenzyme profiles - ZymodemesIsoenzyme profiles - Zymodemes No serological approaches usually but monoclonal antibodies can be used.No serological approaches usually but monoclonal antibodies can be used. DNA hybridisation - PCRDNA hybridisation - PCR

60 2. Visceral Leishmaniasis 2. Visceral Leishmaniasis Finding Leishmania on biopsy of bone marrow (iliac, sternum, tibia (54-86% sensitivity)), liver (60%), enlarged lymph node (64%), or spleen (98%). Culture (NNN, Evans, LIT) Laboratory animals IP inoculation (Golden hamester) No LST for VL and PKDL diagnosis (Yes for VL and CL epidemiology and MCL and Lupoid diagnosis)

61 Visceral Leishmaniasis (con.) Serologic tests: –Antibody detection: DAT (sen %, spe 72-95%) IFA (sen 55-70, spe 70-89) ELISA,( sen % spe 84-95) Dipstick test (rk39, recombinant antigen 39kd, sen % spe %) DAT is easy, inexpensive, and with high specificity and sensitivity (most usage in Iran) –Antigen detection: KAtex (5-20 kd glycoprotein, membranous antigen, easy, field applicable, sen %, spe 100%, positive only in acute disease, useful for HIV/VL ) Formel gel, (Based on hyperimmunoglobulinemia)Formel gel, (Based on hyperimmunoglobulinemia) –Multiple myeloma, Schistosomiasis Isoenzyme profiles - ZymodemesIsoenzyme profiles - Zymodemes Monoclonal antibodiesMonoclonal antibodies DNA hybridisation – PCR (Schizodem)DNA hybridisation – PCR (Schizodem)

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64 3. Mucocutaneous Leishmaniasis diagnosis Early diagnosis and treatment is critical to avoid disfigurement Biopsies should be done but require special training to avoid further disfigurement. Biopsies would be evaluated by the same methods and special laboratories as for cutaneous lesion Because few parasites are present, PCR may be particularly useful

65 Cutaneous and mucocutaneous treatment Antimony components : Meglumine antimoniate (Glucantime) and Sodium stibogluconate (Pentostam) are drugs of choice. –20 mg/kg/d IV or IM for 20d -Pentamidine, Paromomycin are alternative drugs for CL -Amphotricine B for antimony resistant MCL Fluconazole may decrease healing time

66 Visceral leishmaniasis treatment Pentostam or Glucantime 20 mg /kg/d IV or IM for 28d Amphotricin B: mg/kg IV daily 15-20d Liposomal Amphotricin B (Ambisome): 3 mg/kg/d IV on days 1-5, day 14 and day 21 –Low toxicity and high stability, better delivery Alternative: Pentamidine ( 4mg/kg three times weekly, between 5-25 weeks ), Parmomycine

67 Visceral leishmaniasis treatment (con.) Miltefosine (Impavido) ( 2.5 mg/kg /d p.o. for 28 d ) –It was developed for cancer therapy at first –The only oral drug –safer and more tolerable drug (less toxicity for bone marrow and haematopoietic progenitor cells) –teratogenic

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69 Leishmaniasis control Vector control –insecticides –insecticide impregnated bed nets (IIB) Case finding treatment Aniaml reservoir control –Treatment or killing of seropositive dogs –Rodent killing Decrease of susceptibility: Childhood age, malnutrition and Immunosuppression are susceptibility factors for VL. –eliminating of childhood malnutrition –try to produce an efficient vaccine

70 0.1 ml in each week for 12 weeks

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79 روش نمونه برداری از ضایعات لیشمانیوز پوستی کناره های ملتهب و متورم ضایعات پوستی(لبه خارجی زخم) بیشترین میزان آمستیگوت را دارد. هر چه بافت بیشتر شانس یافتن آمستیگوت بیشتر تمیز کردن محل زخم با پنبه و الکل 70%، با توجه به عفونت باکتریایی و قارچی بر روی ضایعه سالک خشک شدن الکل قبل از نمونه برداری محل نمونه برداری توسط انگشت شصت و سبابه محکم گرفته شود. توسط تیغه اسکالپل نوک باریک و یا لانست استریل شکافی به عمق یک میلی متر در ناحیه ای که توسط دو انگشت گرفته شده ایجاد می شود. از عمق محل شکافته شده خراشهایی به سمت سطح و مرکز ضایعه جهت برداشت نمونه داده می شود.

80 ادامه روش نمونه برداری از ضایعات لیشمانیوز پوستی نوک تیغه اسکالپل را خارج و از مواد برداشت شده 3 اسمیر گرفته می شود و با قلم الماس شماره نمونه یا اسم بیمار بر روی لام شیشه ای ثبت شود. در صورت نیاز به کشت، در کنار شعله نمونه ( بر روی تیغه اسکالپل) به درون محیط کشت دایفازیک منتقل می شود.

81 رنگ آمیزی گیمسا محلول تجارتی غلیظ (و متفاوت) –پس از رقیق سازی بتواند گلبول سفید را به خوبی رنگ کند. اسلاید حاوی نمونه بدون شعله ودر دمای اتاق خشک شوند. متانول Methanol 70% متانول خشک شود (اصطلاحا بپرد) بسته به دستور تولید کننده مثلا 1 به 30 یا 1 به 50 رنگ رقیق شود. –آبی که جهت رقیق کردن استفاده می شود جهت7.2 pH تنظیم شده باشد. بسته به رقت و نوع آن مدت رنگ آمیزی دقیقه است که به طور تجربی بدست می آید. مشاهده با عدسی شیئی 10 و سپس 40 و سپس 100 (با روغن ایمرسیون) ومستقیما بدون لامل حداقل جستجوی 30 شان و یافتن ماکروفاژها در هر کدام از 3 لام –نبود ماکروفاژ و فراوانی گلبول قرمز نشانه نمونه نامناسب inadequate)) و ضرورت نمونه گیری مجدد

82 ایزولاسیون کشت در محیط NNN Novy, Macneal, Nicolle آگار 14 گرم NaCl 6 گرم آب مقطر cc 900 حرارت (جوشاندن) تا شفاف شدن ( ولی احتیاط جهت سر ریز نشدن) اتو کلاو و سپس سرد شدن تا حرارت درجه اضافه کردن گلوکز 30گرم در صد به میزان 5 درصد اضافه کردن خون خرگوش دفیبرینه درصد حجم محلول به صورت گرم، تقسیم در لوله های استریل درپیچ دار (3 میلی لیتر)، قرار دادن به شکل slant انتقال به یخچال پس از بستن آگار در هنگام استفاده، اضافه کردن 0.5 تا 1 سی سی PBS یا RPMI به عنوان فاز مایع

83 ادامه کشت نمونه بیوپسی پوستی، آسپیراسیون مغز استخوان و خون 2 میلی متر در عمق پایین ترین سطح شیب دار اینکوباسیون در درجه سانتیگراد انگل در فاز مایع رشد کرده و یافت خواهد شد. استریل کار کردن: باکتری و قارچ مانع رشد انگل هستند. بررسی کشت جهت جستجوی انگل: هفته ای یکبار و تا یکماه ( عدم رشد معادل منفی بودن است). –اگر انگل دیر رشد باشد زمان بیشتری را نیاز دارد.

84 Leishmaniasis Control WHO interest –African trypanosomiasis>Dengo>Leishm aniasis>Malaria>Schistosomiasis >Lymphatic filiriasis> Chagas Close contact of humans and their domestic animals can provide optimal conditions for sand flies and Leishmania transmission (stables provide good breeding ground for larvae) In urban environments infection is mostly human to human In rural areas Leishmaniasis can be a zoonosis Infection in dogs is quite frequent in the Mediterranean

85 Ecology of new world leishmaniasis In the new world most people get infected while working or hunting in the forest Here wild animals including rodents, monkeys and sloths provide a reservoir for the parasite A transmission pattern within a population of wild animals that result in occasional infection of humans is called sylvatic

86 In sand fly, amastigotes are surrounded by a peritrophic membrane (PM), a chitin lattice embedded in protein carbohydrate matrix secreted by the epithelium of midgut. Round amastigotes transform to short ellipsoid procyclic promastigotes (6- 8mm length). Procyclic promastigotes multiplicate within PM but gradually transform to nectomonad form when divide (in a more elongated form with μm body length). Nectomonades migrate from posterior midgut to anterior part and then into thoracic midgut and cardiac valve. After PM disintegration, some nectomonades attach to midgut epithelium particularly in the thoracic midgut in the vicinity of cardiac valve, inserting their flagella between the microvilli and then transform to haptomonad (5-8µm broad, shorter cells). From day five post feeding, metacyclic infective promastigotes can be observed in lumen (in a detached position). metacyclic promastigote are injected through the food channel in the sand fly proboscis.

87 Cutaneous Leishmaniasis in Birjand It is estimated that in recent years an endemic zone of CL has been emerged in Birjand area. In our study, among 80 Giemsa stained smears of CL patients in Birjand which identified by PCR methods, 8 (10%) had Leishmania major and 72 others infected by Leishmania tropica. So both Zoonotic and Anthroponotic cutaneous leishmaniais are endemic in this region.

88 Cutaneous Leishmaniasis is usually self-limiting A chronic but self-limiting dry ulceration at the site of the bite Parasites are not found outside the lesion Nearly absolute resistance to reinfection Inoculation to vaccinate has long been practiced in the middle east

89 Sporotrichoid form: dissemination of amastigotes via the lymphatics to the subcutaneous tissues. Regional lymphadenopathy with fever Different cases from Panama and Brazil. The main causative agents were L (V) panamensis and L (V) guyanensis (Herwaldt, 1999; Melby et al.1992). Old World cutaneous leishmaniasis is less commonly associated with sporotrichoid presentation but several cases have been reported from the Middle East (Kibbi et al. 1987; Ayattolahi, 2006). It is very rare in Europe and only a few cases have been reported in Italy.

90 Cutaneous leishmaniasis differentials Fungal – Paracoccidioidomycosis, chromoblastomycosis, sporotrichosis, blastomycosis Paracoccidioidomycosischromoblastomycosissporotrichosis blastomycosis Bacterial – Staphylococcal and streptococcal infections, pinta, yaws, syphilis, tuberculosis, leprosy, cutaneous diphtheria, tularemia, tropical pyoderma, and other mycobacteriosesstreptococcal infectionspintayawssyphilis tuberculosisleprosytularemia Viral - OrfOrf is an exanthemous disease caused by a parapox virus and occurring primarily in sheep and goats. It is also known as contagious pustular dermatitis, infectious labial dermatitis, ecthyma contagiosum, thistle disease [1] and scabby mouth. Orf virus is zoonotic - it can also infect humans. [1] Orfdiseaseparapox virussheepgoats [1]zoonotic [1] Inflammatory - Sarcoidosis, pyogenic granuloma, lupus Neoplastic - Cutaneous T-cell lymphoma, basal cell carcinoma, squamous cell carcinoma, metastases, Psoriasis, Keloids

91 peritrophic membrane (PM), a chitin lattice embedded in protein carbohydrate matrix secreted by the epithelium of midgut. Round amastigotes transform to short ellipsoid multiplicating procyclic promastigotes (6-8mm length). Procyclic promastigotes gradually transform to nectomonad form when divide (in a more elongated form with μm body length). Nectomonades migrate from posterior midgut to anterior part and then into thoracic midgut and cardiac valve. Nectomonades attach to midgut epithelium particularly in the thoracic midgut in the vicinity of cardiac valve, inserting their flagella between the microvilli and then transform to haptomonad (5-8µm broad, shorter cells). From day five post feeding, metacyclic infective promastigotes can be observed in lumen (in a detached position). metacyclic promastigote are injected through the food channel in the sand fly proboscis.

92 Zymodem Serodem Schizodem

93 Animal leishmania that occatinally transmitted to human L. inerity (guinapig): linear kinetoplast, large cytoplasmic vacule, metastatic property L. adlery, L. agame, L. gimnodactily (خزندگان L. turanica, L. gerbili, L, arabica (rodents) L. daini ( the biggest Leishmania amastigote), L. hertigi (خارپشت)

94 Rizhoplast Longitudinal binary fission Infective Metacyclic ( in stationary phase) Sandfly peptides in بزاق : increase severity, inhibit complement, vasodilant, anti- coagulant

95 L. tropica in world: –P. sergenti –P. cocasicus Iran: Bam, Shiraz, Kerman, Tehran, Mashhad, Sabzevar, Neishaboor In all seasons

96 L. major –In world: P. papatasi, P. lonipes, P. cocacicus, P. Ansari In Iran: Rhombomys opimus ( central;Isfahan, Fars, northeast: khorasan), Meriones libycus (Yazd), M.hurrianae (southest: sistan & Bloochestan), Tatera indica, Nosekia indica (west: khozestan) In last summer month and first fall

97 L. aethiopica –P. Pedifer –Hyrax –Due to immune deficecy in second signall (B71(CD80) and B72(CD86) in CMI –Anergy –No response to treatment LST is negative in: –DCL, VL, PKDL, early phase of urban CL LST is positive in: cured VL, MCL, last ACL phase (recidivans)

98 ZCL sorts Tardy exuicerating Acute necrotizing Abortive Erysipdoid Horn Exematoid Verueoid Tamral sprotrichoid

99 Aconitate hydratase diffrentiate leishmania subgenus from viannia

100 New World cutaneous leishmaniasis L. mexicana (Chicleros Ulcer) –External ear –Rodent, human –CL and DCL L. pifanoi (DCL) –DCL like L. aethiopica L. amazonensis –main cause of DCL –Not kealing DCL in AIDS –All four leishmaniasis forms –Rodent, Oposum, Fox L. (V.) peruviana (Uta) –Like L. tropica self-healing lesion –Probably originated from L. tropica but differe in zymodem. –Reservoir :Dog, and probably a redont L. granhami L. venezuelensis

101 American kala-azar: –L. chagasi (similar zymodem and schizodem pattern with L. infantum) –Dogs and fox –L. longipalpis Indian kala-azar –anthroponotic –P. argantipes –5-9 years –PKDL in 20% of cases 6 months after healing Loaded amastigotes A good source for sandfly Butterfly distribution on face (like lupus) No systematic manifestation such as fever and splenomegaly

102 Medditereanian kala-azar –Middle east and Meditteranian basin –1-4 years children –Canidea –P. major, P. longicuspis, P, chinensis, P. perfiliewi, P. kandelakii, P. ariasi, P. perniciosus

103 G6PD enzyme can differentiate L. guyanensis from L. panamensis L. laiensoi –Agoti L. colombiensis –sloth

104 Three main agents: L. (V.) braziliensis (Espundia=MCL) –MCL Main causative agent –Rodents, occasionally dog and hoarse –First self-healing cutaneous –After 6 months to years Espundia (80% in nasopharynx and nose) –Fastidious growth in culture –Reflecting bodies L. (V.) panamensis (Ulcer de bejuco) –MCL second rank agent –Sloth, rodent, monkey –Along lymphatic vein involves the nasopharynx –Sandfly: Luteromia, psycodopigus –Easily growthable in culture media L. (V.) guyanensis (Painbois=CL) –Frequent relapse –Metastatic –Sloth, مورچه خوار –Like sporotrichoid (along lymphatic veins)

105 GP63 Major surface protein, –metaloprotease (Zn) –Hb degradation and role in promastigote methabolism –Resistance against lysosome function in macrophage phagolyzozome –Role in attachment of parasite to macrophage receptors CR1 (CD35) and CR3 (CD11blCD18) –Degradation of collagen and fibronectin

106 LPG 25% of promastigote weight Role in attachment of parasite to macrophage receptors Proteinase C inhibition Phagosome-lysosome attachment inhibition Protection against tripsin enzyme in sandfly midgut Role in glycocalex production and protection against lysosome

107 Glycosyl phospatidyl inositol Glycocalyx conformation Resistance against lysosome in phagolysosome

108 Biohasic media –NNN –LIT –Evans Monophasic media –HOMEM –RPMI1640 –Graces –Schneider drosophila

109 Leishmania and Trypanosoma From the seven genera in the Trypanosomatidae family, only 2 genera, Leishmania and Trypanosoma, are important parasites of humans. Not all parasites in the family possess all the four morphological forms: Leishmania spp. - possesses only amastigote & promastigote forms Trypanosoma brucei - has only epimastigote & trypomastigote Trypanosoma cruzi - has all four forms

110 P.o. =per os= by oral route

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112 Cutaneous and mucocutaneous treatment Antimony components : Meglumine antimoniate (Glucantime) and Sodium stibogluconate (Pentostam) are drugs of choice. –20 mg per kg, daily IV or IM for 20d -Pentamidine, Paromomycin are alternative drugs for CL -Amphotricine B for antimony resistant MCL Fluconazole may decrease healing time in L. major infection

113 Leishmaniasis Control WHO interest –African trypanosomiasis>Dengo>Leishm aniasis>Malaria>Schistosomiasis >Lymphatic filiriasis> Chagas Close contact of humans and their domestic animals can provide optimal conditions for sand flies and Leishmania transmission (stables provide good breeding ground for larvae) In urban environments infection is mostly human to human In rural areas Leishmaniasis can be a zoonosis Infection in dogs is quite frequent in the Mediterranean

114 Ecology of new world leishmaniasis In the new world most people get infected while working or hunting in the forest Here wild animals including rodents, monkeys and sloths provide a reservoir for the parasite A transmission pattern within a population of wild animals that result in occasional infection of humans is called sylvatic

115 reaction is seen in people with previous contact to the antigen who have developed cellular immunity. Conversion occurs after several weeks in CL, and in VL usually only after treatment and cure (Peters and Killick- Kendrick, 1987). Present and past infections can not be differentiated. The Montenegro skin test is occasionally used in diagnosis of cutaneous disease (eg, in epidemiological surveys), because of its simple use and high sensitivity and specifi city;118 however, it fails to distinguish between past and present infections.


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