医学寄生虫学：利什曼原虫 LEISHMANIA

1、利什曼原虫 LEISHMANIA2015-12-22LeishmaniaAn obligate intro-macrophage & -DC cellsMore than 20 speciesTransmitted to human by 30 species of plebotomine sandflies.CONCEPTIONLeishmaniasis （利氏曼病）Spreading in 88 countries, 22 New World 66 Old WorldVector：Sandfly （白蛉）Occurring in several forms, visceral form ：

2、内脏型cutaneous form :皮肤型Mucocutaneous：粘膜皮肤型人兽共患病History dating back as far as the first century AD. Ecuador and Peru “skin lesions and facial deformities “, William Leishman, 1901, discovered ovoid bodies in the spleen of a British soldier Published as “dum-dum fever”Charles Donovan published his disc

3、overy symptoms in other kala-azar patients a few weeks after Leishman. in 1903. These amastigotes were known as Leishman-Donovan bodies and officially, this species became known as, L. Donovani. 3、19241926年外国学者Cash在中国调查发现：中国地鼠易感； 在昆虫白蛉体内无鞭毛体转变发育成前鞭毛体， 并大量繁殖 钟惠澜 (PUMC) ： 1942年经白蛉叮咬志愿受试者，感染成功 。History

4、Five Characteristics Invading and living in MacrophagesReside in phagolysosomes of the cell Appearing markedly different clinical manifestationsHuman host genetic makeup and/or nutritional state to the course of infection have yet been described completely. “Successful” drug treatment followed a qui

5、te different clinic manifestation such as post-kala-azar dermal leishmanoid. Leishman-Donovan bodiesMorphology of Leishmania amastigotes (无鞭毛体）Scanning electron micrograph of isolated L. amazonensis amastigotes （Membrane remnants of the PV are attached to the posterior pole of the parasite (white ar

6、rowhead).The white arrows indicate the entry of the flagellar pocket (anterior pole). Macrophages were incubated with amastigotes of L. mexicana. At 6 h (A) or 24 h (B)Post contact with purified amastigotes, Note the progressive enlargement of the PVs (white arrows) containing numerousamastigotes.Li

7、ght microscopic Morphology of Leishmania promastigote (前鞭毛体）Trypanosoma & Leishmania are the medically important and best studied genera in this groupTrypanosoma LeishmaniaLeishmania infects and thrives in macrophagesLife circle Leishmania infects and thrives in macrophagesMacrophages are important

8、“microbe killers”, however several pathogens have found ways to escape the killing phagocytosis or active invasion and escapes into the cytoplasm by the parasites：Trypanosoma cruzi ToxoplasmaLeishmaniaClinical syndromesCtaneous leishmaniasis （皮肤型） Diffuse cutaneous leishmaniasis (弥漫性皮肤型）Mucocutaniou

9、s leishmanisis (粘膜皮肤型)Visceral leshmaniasis (VL，kala-azar， 内脏型、黑热病)Three syndromes associated with Leishmania infection in humansCutaneous LeishmaniasisInfection remains restricted to the initial site of infection (the bite site)Cutaneous leishmaniasisOne or more ulcer(s) or nodule(s) in skinDiffere

10、nt species induce variable clinical presentations and prognoses;heal spontaneouslyLeave disfiguring scarsCutaneous leishmaniasisEspundia or mucocutaenous leishmaniasisCaused by L. braziliensis20% of infected patients develop ulcers of the oral and nasal mucosaMuco-cutanious leishmanisis (espundia)pr

11、ogressively destructive ulcerations of themucosa, extending from the nose and mouth to the pharynx and larynx.Not self-healingUsually seen months or years after a first episodeMostly caused by Leishmania braziliensis, responsible for most cases of muco-cutaneous leishmaniasis.Espundia鼻咽粘膜利什曼病 or muc

12、ocutaenous leishmaniasisProgression of the ulceration is slow but steady, ultimately destroying all soft parts of the nose, the lips, and the soft palateDeath can occurs through secondary bacterial infectionSkull damages by EspundiaVisceral Leishmaniasis or Kala-AzarSystemic infection of reticulo-en

13、tdothelial cells (mostly macrophages) throughout multiple internal organs and the bloodVisceral leshmaniasis (VL; kala-azar)systemic disease that is fatal if left untreatedcaused by the Leishmania donovani complex L. donovani sensu stricto in East Africa and the Indian subcontinent Leishmania infant

14、um in Europe, North Africa Latin AmericaThere are two types of VL, differ in their transmission characteristics:Zoonotic 动物源性 VLfrom animal (mainly dogs) to vector to human By L. infantum Anthroponotic 人源性VL:from human to vector to humanBy L. donovaniClinical presentation of VL patients Incubation p

15、eriod lasts between 2 and 6 monthsSymptoms and signs of persistent systemic infection: fever, fatigue, weakness, loss of appetite and weight loss；parasitic invasion of the blood and reticulo-endothelial system：enlarged lymph nodes, spleen and liver.Anaemia, bleedingThe ratio of incident asymptomatic

16、 infections to incident clinical cases varies Clinical syndromes of three leishmaniasis A variety of species and species complexes causes disease in humansVisceral LeishmaniasisLeishmania donovaniLeishmania infantumLeishmania chagasiCutaneous LeishmaniasisLeishmania tropicaLeishmania majorLeishmania

17、 aethiopicaMucocutaneous LeishmaniasisLeishmania brazieliensisLeishmania mexicanaLeishmania amazoniensisDiffuse cutaneous leishmaniasisCharacteristic diffusion of lesions, great abundance of parasites, anergy to skin tests with the specific antigen and resistance to treatment. Due, not to a differen

18、t type of parasite, but to an immunological defect of the human host, which makes him respond with these special clinical and parasitological manifestations.anergy Diagnosisvisceral leishmaniasis - taking a blood sample and/or taking a biopsy from the bone marrow to show the parasite. cutaneous leis

19、hmaniasis - small biopsy or scraping of the ulcer. mucocutaneous leishmaniasis - a biopsy of the affected tissues. Biopsy samples are examined by microscopy, culture and other methods to look for the parasite and identify the specific kind of Leishmania causing the ulcer. Some of these methods will

20、give results within a few days, but culture may take 2-4 weeks to demonstrate the parasite. DiagnosisNon-leishmanial tests.A reduction in the number of red and white blood cells and platelets，high titers of non-specific antibody Parasite detection.Amastigote by microscope in spleen bone marrow lymph

21、 nodesPCRAntibody-detection tests.always be used in combination with a standardized clinical case definition for VL diagnosisELISA， IFA，DAT (direct agglutination test)ICT(Rk39-based immunochromatograpphic test) PCRTreatment strategiesfirst-line treatment for VL in many areas for more than 70 years:A

22、ntimonials sodium stibogluconateMeglumine antimoniate 葡萄糖酸锑钠 戊脘脒 二脒替From 2002, miltefosine (hexadecylphosphocholine, 米替福新），orally administered drug cure 98% VL cases. Epidemiology Epidemiology of Leishmaniasis Threatens about 310 million peopleIn 88 countries around the world. During the past 10 yea

23、rs the disease has spread considerably. An estimated 1.3 million new cases and estimated 20,000 to 30,000 deaths occurs annually. Linked to environmental changes such as deforestation, building of dams, irrigation schemes and urbanization. Epidemiology of LeishmaniasisCurrently, leishmaniasis occurs

24、 in four continents, 72/88 countries are developing countries: 90% of all VL s cases occur in Bangladesh, Brazil, Ethiopia, India, South Sudan and Sudan; 1/3 of CL cases occur in Americas, the Mediterranean basin, and the Middle East and Central Asia. An astimated 0.7 to 1.3 million new cases occur

25、worldwide annually. 90% of mucocutaneous leishmaniasis are reported in Bolivia, Brazil and Peru; (WHO 2013)visceral leishmaniasis in the Old and New worldcutaneous and mucocutaneous leishmaniasis in the New Worldcutaneous leishmaniasis due to L. tropica and related species and L. aethiopicacutaneous

26、 leishmaniasis due to L. majorEcology of old world LeismaniasisIn urban environments infection is mostly human to humanIn rural areas Leishmaniasis can be a zoonosis Infection in dogs is quite frequent in the Mediterranean Ecology of new world leishmaniasisMost people get infected while working or h

27、unting in the forestWild animals provide a reservoir for the parasiteMore than a 1000 American soldiers contacted Leishmaniasis in Iraq !A REGION INFLAMED: Hundreds of U.S. Troops Infected by Parasite Borne by Sand Flies, Army SaysBy DONALD G. MCNEIL JR.Published: December 6, 2003Hundreds of America

28、n troops in Iraq have been infected with a parasite spread by biting sand flies, and the long-term consequences are still unknown, Army doctors said Friday 皮肤型利什曼病1.5 million/y; Afghanistan, Algeria, Iran, Iraq, Saudi Arabia, and Syria and in Brazil and Peru; 一个中国人从“沙特归来患上罕见利什曼病 ,表现为全身皮肤溃烂 ” 金陵晚报 20

29、10-12-07 08:52:27 国内流行情况人源型 平原地区 传播媒介家栖型中华白蛉和长管白蛉 青少年和壮年犬源型 丘陵山区 四川阿坝地区（5.39/10万） 传播媒介野栖型中华白蛉 婴幼儿自然疫源型 荒漠地区 (新疆喀什、和田地区 ) 传染源野生保虫宿主 传播媒介 吴氏白蛉和亚历山大白蛉 以 幼儿为主 ，成人为淋巴结型黑热病国内流行情况6省区始终存在新疆、甘肃、四川、 陕西、山西、内蒙古每年新感染患者200-300例（CDC IPD) （新疆南部喀什、和田地区3岁以下儿童发病数百例，症状与黑热病相似，死亡18例，其余均已康复。1-3月发病，70%血清rK39阳性 2007）我国黑热病的特

30、殊临床表现 皮肤型黑热病: 面部和颈部皮肤结节 （平原地区） 淋巴结型黑热病: 浅表淋巴结肿大 （荒漠地区）7 预后 （取决于早期特效治疗） 未经治疗死亡率高达70-90% 特效药治愈率较高 Vector control Shand fly(attached)(detached)Control strategiesControl strategiesReservoir controlSerological screening of dogs and killing of sero-positive animals.Vector control.Sandflies are susceptible to the sameinsecticidesInsecticide-impregnated materials. The use of insecticide-treated bednets (ITNs)Early diagnosis and treatmen