General Account
• Unicellular animal with full functions
• Distribute widely: water,soil, etc.
• Total species 65,000
– Free-living: majority
– Parasitic: about 10,000
Medical Protozoa
• Pathogenic protozoa
• Opportunistic parasite( 机会致病 )
– Not normally pathogens
– Become pathogenic due to impairment of host
resistance
– Clinical importance of the AIDS epidemic
Basic Structures• Plasma membrane: 侵袭致病 , 免疫反应• Cytoplasm
– Ectoplasm: locomotion , ingestion, etc– Endoplasm: metabolism
• Nuclear– Vesicular form( 泡状核 ) or compact form
• Locomotive organelle– Pseudopodium( 伪足 ), flagellum( 鞭毛 ), cilia
( 纤毛 )
Mode of Reproduction• Asexual reproduction
– Binary fission( 二分裂法 ): results in 2 daughter cells– Schizogony( 裂体增殖 ): multiple fission, results in mu
ltiple cells– Endodyogony( 内二芽增殖 ): by internal budding
results in 2 cells
• Sexual reproduction– Conjugation( 接合生殖 ): exchange of nuclear
materials of 2 – Gametogony( 配子生殖 ) : sexually differentiated cells
unit zygote
Life Cycle Patterns• One stage form( 简单型 )
– Trophozoite ( take food, be mobile, multiply)
• Two-stage form ( 简单型 )– Trophozoite & cyst (not mobile, with cyst wall)
• Two-host form– Mammals – mammals( 循环传播型 )– Mammals - insect vectors( 昆虫传播型 )
Characteristics of Protozoan in Infection
• Proliferation-parasitemia
• No larva and adult differentiation but stage differences
• May be intracellular lodgment
• Opportunistic & accidental infections (free-living)
MorphologyMorphology
• Trophozoite
– Size: 10-40 m
– Shape: ovoid with pseudopodium
– Basic structure: cytoplasm, vesicular nucleus (c
hromatin granules, nuclear membrane, karyoso
me)
• Cyst– Size: 10-20 m– Structure: cyst wall, 1-4 nuclei, chromatoid bod
y– Physiological function:
• The stage of discharge
• Resistant to external surroundings
• The infective stage
Main Points of Life Cycle
• Cycle: cyst—trophozoite—cyst
• Host: human being
• Lodgment: large intestine
• Infective stage: 4 nuclei cyst
• Infective route: mouth
Pathogenesis
• Pathogenic factor– Virulence– Species:
• E.histolytica (pathogenic species)
• E.dispar (non-pathogenic species)
– Immunity of host– Bacteria flora
• Mechanism: contact lysis
• Pathology: flask-like ulcer
• Clinical manifestation– Non symptomatic carriers– Intestinal amebiasis: dysentery, colitis– Extraintestinal amebiasis: liver abscess
Diagnosis
• Etiological diagnosis:– Stool examination of cyst or trophozoite– Sigmoidoscopy or aspiration– Immunological diagnosis
Epidemiology
• Cosmopolitan: 110 population
• China: 3%~10%; Rural area>urban
• Source of infection: carriers
• Transmit route: water contamination
• Insects: fly, cockroaches
Prevention and Control
• Patients and carriers: – Intestinal amoebiasis —metronidazole – Extra~ amoebiasis —diloxanide
• Water & nightsoil control
• Insect vector control
• Personal hygienic health education
Introduction
• Most important tropical disease
– 300 million cases with one million deaths world
wide in 1999;
– 30 million cases before liberation and 24000
cases reported with 39 death in 2000 in china;
• 4 species infecting human
– Plasmodium falciparum( 恶性疟原虫 )
– Plasmodium vivax( 间日疟原虫 )
– Plasmodium malariae( 三日疟原虫 )
– Plasmodium ovale( 卵形疟原虫 )
Life Cycle & Morphology
• Cycle in human (intermediate host)
– Exoerythrocytic stage( 红细胞外期 )
– Erythrocytic stage( 细胞内期 )
红细胞外期 ( 肝细胞内增殖 ) Exo-erythrocytic cycle
(速发型) 子孢子 红外裂殖体 裂殖子
sporozoite E-E Schizont Merozoite(迟发型 P.v. )
进入红细胞 P.v. 8d; P.f. 6d; P.m. 12d
红细胞内期 (RBC 内增殖 ) Erythrocytic cycle
•发育:环形滋养体 大滋养体 (Ring form) (Trophozoite)•增殖:早期裂殖体 (Immature schizont) RBC 内发育 成熟裂殖体 ( 子 ) 配子体形成 (Mature schizont) M 吞噬
Scanning electron micrograph of Plasmodium-infected red blood cells. One cell has burst open, releasing merozoites
蚊体内发育 ( 有性 ) Grouth in the mosequito 雌配子体 Gametocyte 雌雄配子 受精 雄配子体 (Gametogony) 动合子 Ookinete 合子 Zygote 卵囊 Oocyst (内含子孢子 Sporozoit
e )
疟原虫发育过程 Sporozoite Schizont 子 Ring form Trophozoite Oocyst 吞噬 merozoite Schiont
Ookinete Zygote Gamete Gametocyte(female/male)
( 动合子 ) ( 合子 ) ( 配子 ) ( 配子体 )
• Infective form: Sporozoite
• Period of one erythrocytic stage:– P.V 48h; P.M 72h; P.F 36-48h
• Resting stage of sporozoite of P.V & P.O:– Hypnozoite (brady sporozoite) in liver cell
Pathogenesis
• Primary attack
– Infected erythrocyte rupture products of schizont, stimulate the release of
cytokines (TNF) paroxysm (shiver, fever,
sweat)
Scanning electron micrograph of Plasmodium-infected red blood cells. One cell has burst open, releasing merozoites
• Relapse:
– It is a recurrence that taken place after complete
initial clearing of the erythrocytic infection and
implies reinvation of the blood stream by meroz
oites from activated hypnozoites in liver.
• Recrudescence
– It is a recurrence of symptoms in a patient
whose blood stream infection has previously
been at such a low level as not to be clinically
demonstrable or cause symptoms.
Complications
• Anemia– Hemolysis of infected erythrocytes– Hypersplenism– Autoimmunization of uninfected erythrocytes – TNF-
• Splenomegaly:• Malarious nephrosis• Cerebral malaria
Diagnosis
• Parasitological diagnosis:Parasite; Species; Density– Thin blood films (species identification)– Thick blood films
• 2. Immuno-diagnosis
– Specific antibody detection
past malaria
– Antigen detection
– Specific DNA or RNA detection
Immunity
• Congenital immunity– Duffy-negative erythrocytes are resistant to P.v
in West Africans
• Premunition– The protective immunity persists while the mal
aria parasites are still in the host.
• Evasion of immunity: An ability of malaria parasite to evade host immunity.
• Possible mechanism of evasion– 1) Antigenic variation– 2) Sequestration (avoiding exposure to immune effect
or mechanisms)– 3) Poor immunogenicity of its antigens (analogy exist
s between parasitic antigens and host molecules)
Treatment
• 1. Classes of antimalarial drugs– 1) Blood schizonticides (quinine; chloroquine; artem
isinin; mefloquine; sulfadoxin-pyrimethamine)
– Effect on erythrocytic stage, use for acute attack
P-aminobenoic acid(PABA)
+dihydropteridine
Dihydrofolate(folic acid)
Tetrahydrofolic acid(folinic acid)
Purines and Pyrimidines
Nucleinic acid
ANTI FOLIC ACIDANTI FOLIC ACIDSulfone
sulfanilamide
ANTI FOLINIC ACIDANTI FOLINIC ACIDdiguanides
diaminopyrimidines
inhibition
inhibition
– 2) Tissue schizonticides (Primaquine)
– Effect on the stages in liver (including hypnozoit
e), use for prevent relapse (radical cure) of P.v or
P.o malaria
• 2. Choice of drugs– 1) Treatment of vivax, malariae, ovale and chloroqui
ne-sensitive falciparum malaria: chloroquine– 2) Radical cure of vivax or ovale malaria: chloroquin
e + primaquine– 3) Treatment of chloriquine-resistant falciparum mala
ria: artemisinin or mefloquine or quinine
Transmission and Prevention
• 1. Factors of transmission– 1) Infected human (gametocyte-bearing)– 2) Suitable species of anopheles (60 species are
considered to be vectors of malaria, major vectors in China: A. sinensis, A. minimus)
– 3) Resistance of Anopheles to insecticides of re
sistance plasmodium to antimalarial drugs.
– 4) Susceptible population
– 5) Other transmission mode: by transfusion, syr
inge, congenital transmission
• 2. Prevention: breaking the human-mosquito-human cycle
– 1) Control of the source of infection by chemotherapy
– 2) Control of transmission route: • residual insecticides, avoidance of infected mosquitoes (b
ed nets impregnated with permethrin; mosquito repellents (diethyl-metatoluamide)
– 2) Chemoproplylaxis
taking suppressive drugs, beginning one week b
efore travel to endemic area and continuing unti
l 6 weeks after return
– 3) Malaria vaccines
General Introduction
• Zoonotic parasite
• One of the 5 major parasitic diseases
• Endemic northern to Yangtse river
• 0.5 million patients before 1949
• Basically eradicated in 1958
Morphology
• Amastigote (leishman-donovan body):– Human phase, reside in macrophage– Very, very minute elliptical body – No free flagellum– Nucleus: deep red, located at one side– Cytoplasm: blue (after right stain)– Kinetoplast: basal body; rhizoplast
• Promastigote:– Vector phase– Reside in the gut of sandfly– Spindle shaped with 1 free flagellum– Nucleus; cytoplasm; kinetoplast; basal body; rh
izoplast– Chrysanthemum-like in culture medium
Main Points of Life Cycle
• Host: man and sandfly
• No sexual development in the host
• Residing site: macrophage
• Infective stage: promastigote
• Infective route: inoculation of sandfly
• Reservoir host: dog
• Infection could also via transfusion
Clinical Feature
• Irregular, long term fever
• Skin pigmentation—Kala-azar (india)
• Very poor prognosis: die within 1-2 year without treatment
• Reason: lack of immunity after infection;
• But may gain sterilizing immunity after effectively cured
Clinical Manifestation
• Hepatosplenomegaly
• Pancytopenia (hypersplenofunction, immune lysis)
• Epistaxis (nosebleed)
• Nephrosis: albuminuria, hematuria
• Skin lesion: PKDL
• Enlargement of lymphaden
Laboratory Diagnosis
• Etiological diagnosis• Puncture smear
– Bone marrow: safe, of first choice
– Lymphaden: treatment evaluation
• Skin biopsy• Tissue cultivation• Animal inoculation• Probe test: DNA or McAb
• Plain type– Shangdon, dom. P.sinensis
• Hilly type– Qinghai, wild P.sinensis
• Desert type– Xinjiang, wild P.sinensis
Epidemic Links
• Source of infectin: patients and dogs
• Route of infection: phlebotomus spp.
• Susceptible population: all human beings ( but potent immunity developed after cure)
Control
• Treatment of patients: • Sodium stibogluconate• Kill infected dogs• Eradicate sandfly: weak points
– Limited flying capacity– Long breeding course– Short seasonal prevalence– Sensitive to insecticide
Reasons for a Successful Control in China
• Free charge of treatment
• Potent immunity after being cured
• Large production effective drug
• Weak points of sandfly
Morphology
• Trophozoite– Like badminton racket / “gost face”– 2 discs– 2 nuclei– 4 pairs of flagella– Axostyles
Main Points of Life Cycle
• Host: human being
• Residing site: small intestine
• Infective stage: 4 nuclei cyst
• Infective route: mouth
Epidemiology
• Cosmopolitan
• Source of infection: carriers and patients
• Transmission route: faeces----mouth
• Susceptible population: traveler, AIDS patients, homosexual population
Prevention and Control
• Patients and carriers: metronidazole
• Water & nightsoil control
• Insect vector control (fly, cockroach)
• Personal hygienic health education
Opportunistic Parasite
• Parasites which are not normally pathogens but become so due to impairment of host resistance.
• These are assuming increasing clinical importance in AIDS epidemic.
• Opportunistic protozoa – Toxoplasma gondii, Giadia lamblia, etc.
General Features
• A world wide distribution : 1/3 population
• Opportunistic parasite
• Intracellular parasite
• Zoonotic parasite
Life Cycle and Morphology
• Two host pattern with alternation of
generation
• Definitive host: cat (acts also as I.H.)
• Intermediate host: human being and other
animals (herbivores, carnivores, omnivores)
Development in Cat
• Intestinal phase (sexual and asexual stage)
Schizogony merozoites (schizont)
Gametogony: micro and macrogametocyte m
icro and macrogamete zygote oocyst
Sporogony: sporozoites (mature oocyst) (outsid
e of the cat)
Development in Man
• Extraintestinal phase (asexual)– Infective stage
• Oocyst
• Tachyzoite
• Cyst
• Infective route: mouth
• Residing site: tissue cells
Pathogenesis
• Acquired toxoplasmosis: eye lesion (uveitis,
choroiditis, choroidoretinitis); lymphadenop
athy
• Congenital toxoplamosis:
– Abortion;
– Still birth (abnormities): hydrocephalus, menta
l retardation
Pathogenesis
• Toxoplamosis in immunoincompetent hosts
– Encephalitis
– Pneumonitis
– Myocarditis
– Hepatitis, etc.
Diagnosis
• Immunological diagnosis of specific IgG or IgM (first choice), eg:DT, ELISA, IFA, IHA, etc
• Histological exams
• Animal inoculation
• PCR
Epidemiological Factors
• Consuming raw or undercooked meat contai
ning cyst
• Contact with cats ( oocyst consumption)