1、1Human Parasitology Introduction II2Medical protozoa3Nematode (Round worm)4 Trematode5Cestode（Tapeworm) 6Medical arthropodology7Now U may be able to answer ! Morphology Life cycleHow many stages of the life cycle?Which stage is infective stage? And how?Which stage inhabit humans? And where?Which sta

2、ge is primary cause of the disease?Which stage was detected for diagnosis? Pathogenesis and clinical manifestation Diagnosis Epidemiology and control8傳染源傳播途徑易感人群Life cycle9Source of infection傳染源Humans source or reservoir from one infected man to another man called anthroponosis(人類傳染病). (e.g., taenia

3、sis, amoebiasis, etc) Animals From animals to humans -called parasitic zoonoses(人獸共患病) (e.g., hydatid disease). Reservoir host（保蟲宿主） Prevalence and control of parasitic diseases10Route of transmission傳播途徑 excrementsecretion food, water, finger, mouthblood direct or indirect contact skin or woundfocu

4、s of mucosainfection blood transfusion, injection, placenta intermediate host, insects sucking blood, congenital , touch soil, water, grassSusceptible people易感者 Prevalence and control of parasitic diseases11傳播途徑寄生蟲從傳染源排出、借助的某些傳播因素或媒介，侵入另一宿主的方式； 1）經(jīng)水傳播：血吸蟲，阿米巴 2）經(jīng)食物傳播：豬帶絳蟲，華支睪吸蟲 3）經(jīng)土壤傳播：蛔蟲，鉤蟲 4）經(jīng)空氣傳播

5、：蟯蟲 5）經(jīng)節(jié)肢動物傳播：瘧原蟲，絲蟲 6）經(jīng)人體直接接觸傳播：陰道毛滴蟲，疥螨 7）經(jīng)醫(yī)療行為傳播：瘧原蟲，錐蟲 12五大寄生蟲病(經(jīng)水、土壤、節(jié)肢動物傳播)Schistosomiasis血吸蟲病 water-borne disease Malaria瘧疾 arbo diseaseFilariasis絲蟲病 arbo diseaseKala-azar黑熱病 arbo diseaseHookworm diseases鉤蟲病 soil-borne disease 陰道毛滴蟲：經(jīng)人體直接接觸傳播肺孢子蟲 隱孢子蟲 弓形蟲：機(jī)會致病13經(jīng)口感染的寄生蟲病(病從口入) 包囊：溶組織阿米巴 藍(lán)氏賈第鞭

6、毛蟲 蟲卵：蛔蟲 鞭蟲 蟯蟲 包蟲病 肉類等食物：食源性寄生蟲病 food-borne parasitosis 食源性：因生食或半生食含有感染期寄生蟲寄生的食物而感染的寄生蟲病豬：豬帶絳蟲，旋毛蟲、肉孢子蟲、弓形蟲的重要宿主牛：牛帶絳蟲，肉孢子蟲和弓形蟲狗肉、羊肉：旋毛蟲、肉孢子蟲、弓形蟲青蛙蛇：是曼氏迭宮絳蟲及線中殖孔絳蟲、異形吸蟲、棘口吸蟲鼠：旋毛蟲、肉孢子蟲、弓形蟲，肺吸蟲、曼氏迭宮絳蟲淡水魚蝦：華支睪吸蟲、異形吸蟲、棘口吸蟲、棘顎口線蟲和腎膨結(jié)線蟲海魚或海里的軟體動物：異尖線蟲的中間宿主 螃蟹、蝲蛄（俗稱小龍蝦）：肺吸蟲（并殖吸蟲）水生植物：姜片吸蟲福壽螺： 廣州管圓線蟲14寄生蟲進(jìn)入

7、人體的常見感染途徑：病原體最初侵入宿主時的感染部位或方式經(jīng)口感染：溶組織內(nèi)阿米巴、蛔蟲、鞭蟲、蟯蟲、華支睪吸蟲、豬囊尾蚴經(jīng)皮膚感染：鉤蟲、血吸蟲（主動）；瘧原蟲，利什曼原蟲、絲蟲（被動，蚊蟲叮咬）等，疥螨（偶然因素）經(jīng)呼吸道感染：蟯蟲（吸入）、肺孢子蟲等經(jīng)自身感染：蟯蟲、豬帶絳蟲（體外），微小膜殼絳蟲、豬帶絳蟲（體內(nèi)）經(jīng)輸血感染：瘧原蟲，經(jīng)胎盤感染：弓形蟲、瘧原蟲、鉤蟲經(jīng)粘膜感染：陰道毛滴蟲15自然社會生物傳染源傳播途徑易感人群Factors of prevalence 16Factors of prevalence of parasitic diseasesThree factors res

8、trict the prevalence Natural自然因素: including weather, rain, sunshine time and geography Social社會因素: including the levels of economic, education, science, habits of lifeBiological生物因素: including vectors and intermediate hosts 17Epidemiological feature of parasitic diseaseEndemic epidemic地方性 Seasonal e

9、pidemic季節(jié)性 Natural focal epidemic自然疫源性 Parasitic zoonosis人獸共患寄生蟲病18傳染源傳播途徑易感人群The principles of parasitic diseases controlTreatment of the source of infectionThe blockade of the route of infectionThe protection of the susceptible population19PARASITE CONTROLPrevention of Environmental Contamination:

10、 Antiparasite drugs. Treated hosts should be protected from re-infection. Sanitation. Destruction of Free-Living Stages: Protozoan cysts, helminth eggs and infective larvae are often extremely resistant to toxic chemicals.Destruction of Intermediate Hosts and Vectors: chemicals to kill snails, insec

11、ticides. Altering the environmental conditions so the the target species do not find the suitable habitat for its survival. Does not rely on public cooperation.Destruction of Reservoir Hosts: dogs in leishmaniasis, cattle in schistosomiasisPrevention of Infection: Many infective stages gain entry in

12、 drinking water, Cryptosporidium, Giardia, etc. These can be controlled by safe water supplies. Meat inspection to prevent Taenia. Bednets prevents mosquito bites. Shoes stops hookworm larvae burrowing through the skin.Prevention of Parasite Maturation: chemoprophylaxis and vaccinationIntegrated Con

13、trol20 damage Parasite Host（human） resistance / elimination Relationship of host and parasiteParasitism21寄生蟲的數(shù)量/密度臨床表現(xiàn)的嚴(yán)重程度ParasitosisParasitic infectionthreshold22Relationship of host and parasiteThe damage of parasites to hostsInjury to the host may be brought about in many ways.1) Depriving the h

14、ost of nourishment 2) Mechanical effect of parasites on host tissues and organs3) Toxic effect 4) Immuno-pathological lesion (Asthma, Rashes, Shock)23蛔蟲在小腸寄生24蛔蟲性腸梗阻25鉤蟲引起的貧血26蚊咬所致嚴(yán)重過敏27血吸蟲病28larva migrans 幼蟲移行癥 Cutaneous larva migrans Visceral larva migrans非正常宿主，保持幼蟲階段，皮下或內(nèi)臟穿行ectopic parasitism 異位寄

15、生非常見寄生部位寄生Symptoms associated with parasitic disease processes29Neoplasms occur naturally in invertebrates but are not known to develop in tapeworms. We observed nests of monomorphic, undifferentiated cells in samples from lymph-node and lung biopsies in a man infected with the human immunodeficienc

16、y virus (HIV). The morphologic features and invasive behavior of the cells were characteristic of cancer, but their small size suggested a nonhuman origin. A polymerase-chain-reaction (PCR) assay targeting eukaryotes identified Hymenolepis nana DNA. Although the cells were unrecognizable as tapeworm

17、 tissue, immunohistochemical staining and probe hybridization labeled the cells in situ. Comparative deep sequencing identified H. nana structural genomic variants that are compatible with mutations described in cancer. Invasion of human tissue by abnormal, proliferating, genetically altered tapewor

18、m cells is a novel disease mechanism that links infection and cancer.Parasite and CancerIn January 2013, a 41-year-old man in Medelln, Colombia, presented with fatigue, fever, cough, and weight loss of several months duration. He had received a diagnosis of HIV infection in 2006 and was nonadherent

19、to therapy; the most recent CD4 cell count was 28 per cubic millimeter, and the viral load was 70,000 copies per milliliter. Stool examination revealed H. nana eggs and Blastocystis hominis cysts(人芽囊原蟲包囊).lung noduleslung noduleslymph nodesIrregular, crowded nests of small, atypical cellsSyncytia co

20、ntaining atypical nuclei were present at the periphery of the nestsSmall, atypical cells with scant cytoplasm and prominent nucleoliRibosome-rich cytoplasm with scattered mitochondria (arrowhead) and a nucleuswith a conspicuous central nucleolus (asterisk).immunohistochemical stainingin situ hybridi

21、zationMalignant transformation of H. nanaTissue invasion MetastasisContinued proliferationTumor cellsDelusional ParasitosisPeople with delusional parasitosis have an unshakable, false belief that they are infested with insects, worms, mites, lice, fleas, or other organisms. Some people also believe

22、the parasites have infested their home, surroundings, and clothing. They often provide vivid descriptions of how the organisms enter their bodies via their skin and other body openings and move around.41Delusional Parasitosis-symptomsSensations of itching, crawling, and irritation are very real to t

23、he patientsPatients may scratch, pick at, or mutilate their skin enough to cause sores or ulcers to try to ger rid of the delusional parasitesMay apply various chemicals and/or disinfectants to their skinBring samples of hair, skin, and debris, such as dried scabs, dust, and lint, to their doctor to

24、 prove the infestation is realDelusional parasitosis most often affects people over 50 and women but is very rarehave a disorder that causes them to excessively worry about their health(illness anxiety disorder)May be aware of some parasitic disorder (for example,scabies) from the media or may have

25、been in contact with a person infected by itmental disorder, such as schizophrenia, depression, anxiety, or obsessive-compulsive disorder, but most do notAfter abuse of certain drugs or withdrawal after prolonged use of alcohol42432. The resistance of hosts to the parasites Immune systemThe genetic

26、constitution of the host Duffy blood group-P. vivax The sickle cell trait-P. falciparumThe nutritional status of the host442. The resistance of hosts to the parasites Eliminate the parasites from the hostMaintain a balance between the impact of parasite and resistance of host No obvious signs of dis

27、easecarrier帶蟲者沒有明顯臨床癥狀，攜帶并傳播病原體suppressive infection 隱性感染chronic infection 慢性感染Opportunistic pathogenesis 機(jī)會致病45寄生蟲的數(shù)量/密度臨床表現(xiàn)的嚴(yán)重程度ParasitosisthresholdChronic AND suppressive infection 462. The resistance of hosts to the parasites Eliminate the parasites from the hostMaintain a balance between the im

28、pact of parasite and resistance of host (no obvious signs of disease)The resistance can not inhibit the parasites and the obvious signs and symptoms develop even host diedParasitic disease47HOST IMMUNITY 1. Types of immune responses2. Antigens of parasite3. Immune responses4. Hypersensitivity reacti

29、ons5. Immune evasionThe resistance of hosts to the parasites 48Immune system: ComponentsInnate:skin, mucosa: barriermacrophages: phagocytosiscomplement-mediated lysisNK cells: altered or missing MHCneutrophils, eosinophils, mast cellsAdaptive: T cells and B cells Dependent on innate to get activated

30、But are much more complex in part because of specificityToll-like receptor,TLRPAMP4950Innate immunity of parasite infection It is the inherited but non-immune type of the host defense against a parasite: Plasmodium falciparum: Haemoglobin-S thalasaemia（地中海貧血） and glucose- 6- phosphate dehydrogenase

31、（葡萄糖6-磷酸脫氫酶，G6PD）deficient erythrocytes（紅細(xì)胞） Plasmodium vivax: Duffy-negative genes（Duffy陰性基因）51Protective immune response 1) Sterilizing immunity complete immunity, complete elimination of the parasite from the host and life long resistance against subsequent infection. It occurs rarely in humans.

32、It occurs only in the cutaneous leishmaniasis.2) Incomplete immunity It is associate with the clinical recovery from the disease and the development of immunity to specific challenge with the parasite. The parasites always persist in the host, even though relatively at a low level. This incomplete i

33、mmunity also known as “premunition(帶蟲免疫)” typically is found in many protozoal infections(e.g., malaria), as “concomitant immunity(伴隨免疫)” typically is found in helminthic infection(schistosomiasis).3) Absence of an effective immunity It is seen after complete clinical cure from infections(e.g.,amoeb

34、iasis, visceral leishmaniasis, American trypanosomiasis).Adaptive immunity of parasite infection 52Adaptive immunity of parasite infectionHarmful immune responses:hypersensitivity reactions. Anaphylactic reaction(過敏反應(yīng)) type I reactionanaphylactic reaction of ruptured hydatid cyst invasion of the ski

35、n: hookworm, Schistosoma Cytoxic（細(xì)胞毒）type II reaction a) anaemia in malaria b) chronic myocarditis（心肌炎）and megacolon（巨結(jié)腸） in Chagasdisease c) quinine（奎寧） induced massive haemolysis（溶血）and haemoglobinuria（血蛋白尿） in malaria .53Adaptive immunity of parasite infection Immune complex mediated（免疫復(fù)合物介導(dǎo)） typ

36、e III reaction glomerulonephritis（腎小球腎炎） seen in malaria nephritis in leishmaniasis, trichinosis and schistosomiasis. Delayed hypersensitivity（遲發(fā)性變態(tài)反應(yīng)） type IV reaction a) Schistosoma species infectionsb) local lymphatic inflammation in filariasisc) inflammation of muscle tissue around Trichinella 5

37、4immune evasion 免疫逃避Immune evasion- Many parasites appear not to be eliminated or not to be affected by their hosts immune response, this phenomena was termed as “Immune Evasion”55Mechanism of immune evasion-Host遺傳決定的免疫無應(yīng)答或低應(yīng)答狀態(tài) 易感 高蟲荷新生兒的免疫無反應(yīng)性 免疫系統(tǒng)發(fā)育不全有關(guān)成熟宿主的免疫低反應(yīng)性 免疫力低下時期56Mechanism of immune eva

38、sion-Parasitesurface absorption of host materialsmolecular mimicry分子模擬與偽裝 loss of surface antigens表膜脫落與更新 antigenic variation抗原變異 anatomic seclusion解剖位置的隔離 57與寄生蟲有關(guān)的領(lǐng)域Drug Discovery & DevelopmentVector control Vaccine58Why Do We Need New Drugs?Control of insect vectors inadequateCurrent drugs are un

39、satisfactory Drug resistance Side effects Poor efficacy High cost Route of administration Availability No vaccines available yetAnopheles gambiaeIncidence of resistance to common antimalarial drugs591960/tdb/edb/pfdb/CQR.html196519781989Resistance to chloroquine60The Ideal Product ProfileSafe for us

40、e (men, women, children and foetus)Minimal toxicity (tolerable side effects)Few contraindications (drug-drug interactions; HIV or TB co-infections)Efficacious (treatment 14 days; 3 days malaria) No Resistance (low resistance potential)Orally active (avoid needles and hospitalization)Broad spectrum (

41、all disease species, including resistant lines)Stable (2 years shelf life at 40 C and 75% relative humidity)Affordable (diseases of the poor; $1 per patient, malaria)61Recommendations for vector controlGenetic manipulation of vectors: Transgenic mosquitos with impaired ability to transmit the parasi

42、te. This is attractive because is likely to be economically viable and relatively “l(fā)ow technology”. Vector immunity and vector-parasite interactions: Genome projects as the A. gambiae one would help identify novel targets in the mosquito gut and salivary glands that are involved in digestion of the

43、blood meal and host-parasite-vector interactions could be used to develop vaccines that block the transmission of parasites and mosquito immune regulators or smart sprays that disrupt the development of the parasite in the mosquito.Vector behavior and other approaches to vector control: Elucidating

44、the molecular basis of many mosquito behavior may be an expensive research investment, but the simple traps and repellant devises anticipated from this research could be easily adopted in malaria-endemic countries 62 Vaccines availableDiphtheria 白喉Tetanus 破傷風(fēng)Measles 麻疹Mumps 流行性腮腺炎Rubella 風(fēng)疹Polio 脊灰H

45、epatitis B 乙肝Vaccine success storiesEdward Jenner giving smallpax vaccine (1802)63What does a vaccine do ?Stimulates normal protective immune response of host to fight invading pathogen.What knowledge is needed to produce a vaccine ? 1. Understand lifecycle of parasite find best target stage. 2. Und

46、erstand immune mechanisms stimulated by parasite. humoral /cellular response ?PARASITE VACCINES64 Four life stages Many potential targets at each stageOver 5000 potential antigenic targets in totalAdapts to the immune systemWhy limited success in parasite vaccine development ?Parasites avoid, deflec

47、t & confuse host immune system.Right parasite antigens not identified yet: complicated life cycles. (maybe 20,000 proteins in nematodes).Protective host responses not understood in target species : multi-responses (most research in rodent models) Ten antigenic targets Of which only two induce protec

48、tive antibodies65Hill AVS (2006) Pre-erythrocytic malaria vaccines: towards greater efficacyNat Rev Immu 6: 2132 doi:10.1038/nri1746The Plasmodium falciparum malaria life cycle.66寄生蟲疫苗低毒野生型活疫苗減毒疫苗滅活疫苗基因工程疫苗基因工程亞單位疫苗(genetic engineering subunit vaccine)合成肽疫苗(synthetic peptide vaccine)基因工程載體疫苗(genetic engineering vectoring vaccine)抗獨特型疫苗(anti-idiotype vaccine)核酸疫苗(nucleic acid vaccine)目前尚無可應(yīng)用于人的寄生蟲疫苗！ No vaccines available yet單細(xì)胞或多細(xì)胞生活史復(fù)雜抗原成分復(fù)雜大量培養(yǎng)蟲體困難抗原變異免疫逃避What we believe is that a successful parasitic vaccine is in the near future！67類別寄生蟲感染階段感染方式感染途徑中