Flagellates 鞭毛蟲
Intestinal flagellates
Genital flagellates
Haemoflagellates
Intestinal and genital flagellates
Intestinal flagellates 腸道鞭毛蟲
• Enteromonas hominis; (non pathogenic) ( 人內滴蟲 )
恩特若姆那斯鞭毛蟲• Retortamonas intestinalis; 腸旋滴蟲 (non pathogenic)
• Chilomastix mesnili 脣形鞭毛蟲• Giardia lamlbia 梨形鞭毛蟲• Trichomonas hominis (large intestine) 腸道鞭毛滴蟲• Trichomonas tenax 口腔毛滴蟲 (mouth)
• Pentatrichomonas hominis 人毛滴蟲
Intestinal and genital flagellates
Genital flagellates 生殖道鞭毛蟲
* Trichomonas vaginalis 陰道鞭毛蟲
Chilomastix mesnili 麥氏唇形鞭毛蟲
Non-pathogenic
Large intestine
Life cycle Trophozoite: long cytostome 3 anterior flagella 1 cytostomal flagellum Cyst: single nucleus lemon-shape
p.30 fig.21
Giarida lamblis 梨形鞭毛蟲 (Syn. G. duodenalis)
Common infection in both tropic and sub-tropic area
Small intestine infection
Cystic infection, 10 cysts may produce infection
Infection via contaminated food and water
Excystation occurs in upper small intestine
活動體腹面觀
活動體背面觀
Ventral disc
Ventro lateral flange
Giarida lamblis
Life cycle
Trophozoite: symmetrical in shape (badminton racket)
2 oval nuclei;
4 pairs of flagella; moving as “falling leaf”
binding to tissue by striated disc (ventral surface) mechanical binding by host proteases activate the lectin of Giardia to promote attachment to enterocytes ( 腸細胞 ) multiple by binary fission
Giarida lamblis
Life cycle Cyst: oval to ellipsoid in shape (11-14 μm) 4 small oval nuclei distinct wall; shrunk cytoplasm produce a space under cyst wall
Giarida lamblis
Clinical aspects
Wide range of gastrointestinal symptoms (especial in children)
Vomiting 嘔吐 Flatulence 腸胃脹氣 ; Diarrhoea 痢疾 , 下痢 Malabsorption syndrome 吸收障礙 Cholecystitis 膽囊炎
Giarida lamblis
Clinical aspects
Histological aspects : mechanical & biochemical Shortening of villi Cellular infiltration of lamnia propria 黏膜固有層 of mucous membrane functional impairment of enterocytes
Abdominal cramps 腹部絞痛 痙攣
Induce motility disturbance
Giarida lamblis
Diagnosis
Stool examination for trophozoites or cysts diagnosis may concentrated by zinc sulphate flotation 硫酸鋅浮漂法
Duodenal aspiration
“Enterotest” capsule 腸內測試膠囊 a gelatin capsule containing a coiled thread for duodenal contents diagnosis
Giarida lamblis
Treatment
Mepacrine (quinacrine) hydrochloride( 鹽酸奎那克林 ) 5 mg/kg/day in divided doses thrice daily for 1 week
Nitroimidazoles Tinidazole 2 g single dose
Albendazole
Giarida lamblis
Prevention and control
Food hygieneFly control Sewage disposalProper water supply Identification and treatment of carriersChlorination of water can not kill the cystsIodination of water can kill the cysts (13 ml saturated solution of iodine per liter of water
Trichomonas spp 滴蟲
Life cycle
Trophozoite: ovoid or pyriform gliding motion 1 or 2 oval nuclei 4 flagella on anterior end 1 flagellum turns back and attach on undulating membrane axostyle 軸柱 projects out of body for attach to host tissues and cause irritation
divide by binary fission No cystic stage
Trichomonas hominis 人毛滴蟲
Parasite in large intestine
No medical significance
Trichomonas tenax 口腔毛滴蟲
Parasite in the mouth
No medical significance
Trichomonas vaginalis 陰道滴蟲
Urogenital infection
No cystic stage
Infected male acting as carrier
Trichomonas vaginalis
Life cycle
Trophozoite: ovoid or pyriform gliding motion single oval nuclei 4 flagella on anterior end 1 flagellum turns back and attach on undulating membrane axostyle projects out of body for attach to host tissues and cause irritation ingests food particles by cytostome Divide by binary fission
Trichomonas vaginalis
Clinical aspects
Vaginitis ( 陰道炎 )
resulting in a frothy and creamy white discharge
Inflame of vulva and cervix
Asymptomatic in males but some urethritis( 尿道炎 ) or (prostatitis) 前列腺炎
Trichomonas vaginalis
Diagnosis Vaginal secretion (woman) trophozoites
Semen or prostatic fluid examination (man)
Artificial culture
Trichomonas vaginalis
Treatment infected female and her male consort
Drug treatment Nitroimidazoles Metronidazole; 200 mg thrice daily orally for 1 week 2 g for single doses Tinidazole ; 2 g thrice daily orally Ornidazole;
Trichomonas vaginalis
Prevention and control
Normal sexual behavior
Fixed sexual partner
Safety sexual behavior
Haemoflagellates 血液性鞭毛蟲
Leishmania spp 利什曼原蟲 L. donovani complex; L. major L. tropica; L. aethiopica L. mexicana complex L. braziliensis complex; L. peruviana
Trypanosoma spp 錐蟲
T. rhodesiense; T. gambiense T. cruzi; T. rangeli
Leishmania spp infecting man
Geographical distribution
Visceral leishmaniasis (VL) 內臟利什曼原蟲症 India, Bangladesh, scattered areas in the Middle East Mediterranean region, parts of East Africa, South and Central America
Cutaneous leishmaniasis (CL) 皮下利什曼原蟲症 N. India, Pakistan, Middle East, Southern Europe Northern Africa all Mediterranean Coast, parts of East and West Africa, South and Central America
Muco-cutaneous leishmaniasis (MCL) 黏膜利什曼原蟲症 South and Central America
Leishmania spp infecting man
Taxonomic position is often confusing monoclonal antibody typing DNA probe hybidization RFLP karyotyping
L. donovani complex; L. major L. tropica; 熱帶利什曼原蟲 L. aethiopica L. mexicana complex L. braziliensis complex; L. peruviana
General Classification of Important Leishmaniasis in Relation to Clinical Manifestation
Clinical
Manifestation
Species Involved
Old world New world
VL L. donovani complex
L. donovani complex
MCL Rarely occurs L. braziliensis complex
CL L. tropica L. braziliensis complex
L. major L. mexicana complex
Leishmania spp
Morphology 4 types fig. 30
Trypomastigote 錐鞭毛體 kinetoplast is at posterior end, locomotory flagellum, long undulating membrane(supported by microtubules), Epimastigote 側鞭毛體 kinetoplast is anterior to the nucleus, short U membranePromastigote 前鞭毛體 kinetoplast is at anterior end, no U membraneAmastigote 無鞭毛體 (“Leishman-Donovan” body) ovoid, 2-3 μm, no flagellum binary fission, starts by division of the kinetoplast, following nucleus division, ending the outer membrane splits
Leishmania spp
Kinetoplast( 動基體 )
Single mitochondrian Extends along the whole length of the parasite
Reveals many cristae in the midgut of vector high degree of activity
Relatively less cristae in blood stream activity is suppressed
Distribution of morphological types in haemoflagellates
Trypo-mastigote
Epimas-tigote
Promas-tigote
Amas-tigote
Lesimania spp.
Animal host - - - +Vector - - + -
Trypanosoma spp. (Afican)
Animal host + - - -Vector + + - -
Trypanosoma cruzi
Animal host + + - +Vector + + - -
Life cycle
Vectors: Sandflies 白蛉
PhlebotomusLutzomyia Psychodopygus
Western hemisphere : Lutzomyia ; Psychodopygus
World wild: Phlebotomus
Female sandfly pool feeder ; biting by proboscis or mouth part
Host cell infection by promastigotes flagellar attachment or aflagellar poles phagocytosis by host cells
Macrophages Phagocytic cells
Become amastigotes inside a parasitophorou vacuoleBinary fission for multiplication
1.eliciting a small phagocytic oxidative response2.possessing membrane-associated acid phosphotase3. Possessing more catalase & glutathione peroxidase than promastigotes
Toxoplasma gondii : preventing phagosome-lysosome fusion
Leishmania spp infecting man
Clinical aspects Difference in virulence of various parasite species Difference in susceptible of various host Muco-cutaneous leishmaniasis (MCL) 黏膜利什曼原蟲症 Starts as a pustular swelling in mouth or on nostrils Lesion become ulcerative after many months Then extend into the naso-pharyngeal mucous membrane
2nd infection is very common with destruction of the nasal cartilage and the facial bone
Leishmaniasis 利什曼原蟲症
Leishmania spp
Visceral leishmaniasis (VL) 內臟利什曼原蟲症 : Kala-azar 黑熱病
Incubation period is 4 to 10 monthsEarly symptoms: low grade fever with malaise and sweatingLater stages: fever become intermittent hyperplasia of lymphoid-macrophage system liver and spleen become grossly enlarged no inflammatory changes lymphadenitis is common in Chinese form but not Indian form post Kala-azar dermal lieshmaniasis (PKDL) after 1 –2 years hypopigmented areas; nodular as lepromatous leprosy skin biopsy shows many parasites PKDL is of epidemiological significance vector transmission easily
Leishmania spp
Cutaneous leishmaniasis (CL) 皮下利什曼原蟲症
Starts as a painless papule( 丘疹 ) on exposed parts of body generally on the face Circular or oval ulcer produce Lesion ulcerates after few months dry type lesion: ulcer remains dry and heals readily wet type lesion: ulcer may spread with inflammatory zone around it, and heal slowly Diffuse cutaneous leishmaniasis (DCL) occur in parts of Africa Nodules and thickening of the skin without any ulceration Leishmaniasis recidivans (LR): chronic infection with very few parasites, not heal spontaneously
Leishmania spp
Diagnosis
Low WBC count Anaemia
Chronic symptom gama-globulin coagulation: formaldehyde
Immuno-assayBiopsy tissues: bone marrow, spleen; lymph gland
Culture
Leishmania spp
Treatment
Visceral & Muco-cutaneous leishmaniasis
Pentavalent antimony compounds sodium stibogluconate Diamidines pentamidine isethionate; hydroxystilbamidine
Cutaneous leishmaniasis sodium stibogluconate or mepacrine
Leishmania spp
Prevention and control Vector control Residual insecticides spread for control sandflies High susceptible to insecticide of sandflies
Reservoir animal control
Vaccination with promastigotes in cutaneous leishmaniasis U.S.S.R and Israel
Personal protection long sleeves and trousers; insect repellents; fine mesh nets impregnated with insecticides
Trypanosoma spp infecting man
Sleeping sickness 非洲睡眠病 : Africa Trypanosoma rhodesiense 羅德西亞錐蟲 Trypanosoma gambiense 甘比亞錐蟲
Chagas’ disease : America Trypanosoma cruzi 枯西式錐蟲
Non pathogenic : Central and South Africa Trypanosoma rangeli
African trypanosomes (sleeping sickness)
Pathogens: Trypanosoma rhodesiense 羅德西亞錐蟲 Trypanosoma gambiense 甘比亞錐蟲 (morphologically indistinguishable)
Vector: biting flies; tsetse fly 采采蠅 ; Glossina parasite undergoes a complex development in fly
Host: host in human blood with binary fission movement in the direction of flagellum pleomorphic; slender; intermediate; stumpy nucleus, kinetoplast, undulating membrane, flagellum can be recognised with stain
Geographical distribution
Trypanosoma rhodesiense 羅德西亞錐蟲
East Africa
Rhodesian form sleeping sickness; zoonosis
Trypanosoma gambiense 甘比亞錐蟲
Western and Central Africa
Gambian form sleeping sickness: human
Life cycle Page 46 fig. 36
Host : divided by binary fission slender; intermediate; stumpy
Vector : stumpy form initiated in midgut surrounded with PM (peritrophic membrane ) Change to elongated form (longer) Migrate to the space between PM and midgut, become a shorter elongated form Penetrate PM and forward movement to proboscis Turn back migrate to salivary gland, become a epimastigotes further develop to metacyclic form Infect host via biting injection with saliva may be penetrate into haemocoel via midgut
Antigenic variation 抗原變異作用 Fascination mechanism for escape host immunity
Avoid host immune responseProtecting the parasites from antibodies
Change and replacing outer variant surface glycoprotein (VSG)Weekly or 10-day cycle
Antigenically different Serotype; heterotype
Limitation : unlimitation ?
Clinical Aspects
Primary reaction 初始感染反應
Small sub-cutaneous nodule 皮下瘤結 occurs at the site of inoculation of Tyrpanosoma become a larger nodule, 25 to 100 mm in diameter persist about 2-3 weeks
Clinical Aspects
Systemic manifestation 系統性病變
Fever with headache
Winterbottom’s sign: T. gambiense lymph gland become enlarged (cervical & suboccipital) Fever becomes intermittent in later stages CNS involvement daytime sleeping; psychological changes; tremors 震顫 ; convulsions 全身痙欒 ; coma 昏迷 Death generally occurs from intercurrent infection 併發感染
Clinical Aspects
T. rhodesiense infection fast with CNS involvement occurring within a few months
Pathology of CNS leptomeningitis 軟腦膜炎 cellular infiltration 組織浸潤 : mononuclear cells perivascular cuffing 圍管現象 : around the blood vessels plasma cells and lymphocytes
Diagnosis
•Lymph gland puncture: T. gambiense
•Blood diagnosis: T. rhodesiense
•DEAE column separation: parasites concentration form blood
•Immuno-assay: CFT; complement fixation test
• FAT; fluorescence antibody test
•IgM level rise: blood & CNS (trypanosomiasis’ pathognomonic)
•Rats inoculation with T. rhodesiense : heavy parasitaemia
•Card agglutination trypanosomasis test (CATT)
•
Differences Between T. gambiense and T. rhodesiense
T. gambiense T. rhodesiense
VirulenceLess virulent to humans and laboratory animals
More virulent to humans and laboratory animals
Reservoir Mainly humans Mainly animals
VectorMainly Glossina palpalis
Mainly Gglossina morsitans
Geographical distribution
Mainly West Africa Mainly East Africa
Treatment
Depending on CNS condition
Early stage:
suramin (germanin)
0.2g intravenously injection for side reaction test 0.8g apply on day 2 1 g every 4th day until a total 10g is given
•Blood-brain barrier effect; BBB•Enphrotoxic (kidney failure patient avoid use)
Treatment
Late stage:
melarsoprol with dimercaprol (reduce toxicity) cells and protein levels higher than 40mg/100ml 20mg/kg; intravenously injection;3 course treatment each course 3 days; separated by 7 days rest Side effect: stop to rescue Encephalopathy : arsenical encephalopathy 砷腦病變 reactive encephlopathy 反應性腦病變
Eflornithine : early Gamabian trypanosomiasis
Prevention and control
Gambian form sleeping sickness: human
Riverine tsetse : for collecting water or for washing people
Rhodesian form sleeping sickness; zoonosis
Reservoir host reducing
Wild game destruction
Vector control : tsetse fly elimination
color attract: blue & black
residues application of insecticide
American trypanosomes (Chagas’ disease)
Geographical distribution
South America
Central America
Vectors
Reduviid bugs: Triatoma,
Panstrongylus. Rhodnius
Reservoir animal
Armadillos 犰狳 , opossums 小袋鼠 , cats, dogs, pigs
Life cycle of Trypanosoma cruzi
Metacyclic form is infectious formPass through the faeces of infected vectorParasites via skin damaged by the bite of assassin bug via the contamination mucous membranesPenetrate into tissue cells from blood stream mesenchymal origin 間質細胞 cardiac muscle mainly 心肌細胞Change into amastigote , epimastigote, trypomastigoteReplication only occur in amastigoteTrypomastigote emerge form muscle cells and enter blood stream Re-invasion : cardiac muscle cells circulate without division
Life cycle of Trypanosoma cruzi
Vector
Trypomastigote picked up by insectChange to epimastigotes Becoming metacyclic form after 8-10 days in the hindgut of vectorT. cruzi also transmissable by the congenital route or blood transfusion
Large kinetoplast and curved appearance distinguish with T. gambiense & T. rhodesiense
Congenitial route or blood transfusion infection
Life cycle of Trypanosoma cruzi
T. Cruzi survive in the cytoplasm of macrophages not in the parasitophorous vascuole of macrophages (Leishmania & Toxoplasma)
Clinical aspects
Chagoma as primary lesion: on the face near eyelids swelling of the eye; conjunctivitis; Romans’s sign
Chronic disease is cardiomyopathy mild case : extra systole 心收縮 slight tachycardia 心悸 , 心搏過速Severe case: heart block partially or completely cardiac failure
Some case: megaoesophagus 巨食管 ; dysphagia 吞嚥困難 megacolon 巨結腸
Diagnosis
Blood examination: isolation of T. cruzi from blood direct examination; centrifugation help parasites culture; NNN medium rats inoculation; 10 days: blood diagnosis 60 days: cardiac tissues examined (amastigotes)
Xenodiagnosis:uninfected laboratory-breed reduviid bugs動物接種診斷法 feeding on patient; 2 weeks inoculation examined for epimastigotes
Serological diagnosis: indirect haemagglutination test FAT
Amastigotes in the heart muscle
Pseudocyst
Epimastigote
Trypanosoma cruzi
Treatment
Effective chemotherapy is not available nitrofurans pyrimethamine primaquine nitroimidazoles allopurinol riboside
Symptomatic treatment for cardiac failure by standard drugs
Pace-maker implantation
Surgery in megaoesophagus and megacolon cases
Trypanosoma cruzi
Vector control successful in Brazil
Urbanization: vector habitat elimination
Gentian violet 龍膽紫 (1:4000) preventing blood (donor) transfusion infection
Prevention and control
Flagellates 鞭毛蟲Terms Used in Relation to Flagellates(Intestinal, Genital and Blood)
Flagellum 鞭毛 – roma An elongated, hair-like organelle used for locomotion. At the ultrastructural level, 1 pair of central tubules and 9 pairs of peripheral tubules are visible.Undulating membrane 波動膜 – A membranous structure which connects the flagellum to the body of the parasite. It is thrown into folds as the parasite moves, giving itan undulating appearance.Costa 肋– A cytoplasmic thickening seen at the base of the undulating membrane in some flagellates.Axostyle 軸柱 – A central supporting rod seen in some flagellates.
Amastigote 無鞭毛體– Also known as the leishmanial stage. It is round or oval in shape without any free flagella.Promastigote 前鞭毛體 – Also known as the leptomonad stage. It is elongated with kinetoplast anterior and distal to the nucleus. The flagellum emerges from the anterior end. There is no undulating membrane.Epimastigote 側鞭毛體 – Also known as the crithidial stage. It is elongated with the kinetoplast anterior and close to the nucleus. There is a short undulating membrane.Trypomastigote 錐鞭毛體 – Also known as the trypanosome stage. It is elongated with the kinetoplast posterior and distal to the nucleus. There is a long undulating membrane.
Axoneme 軸絲 – A delicate filament extending from the region of the kinetoplast to the cell membrane. It represents the cytoplasmic part of the flagellum.Kinetoplast 動基體– An oval or rod-shaped body seen in haemoflagellates. It stains with nuclear dyes and contains DNA. It is regarded as a modified part of the mitochondrium.Pleomorphic 多形性 – When a number of morphological types occur in one life cycle.Monomorphic 單形性 – When a single morphological type occurs in one life cycle.Metacyclic trypanosome – Infective forms of trypanosomes which develop in the vector.
Xenodiagnosis 病媒接種診斷 – A method of diagnosis in which a vector is fed on a suspected case and is later examined for the presence of the parasite.Peritrophic membrane 圍食膜 – A membrne which is secreted from the anterior end of the midgut in some blood- feeding arthropods. This membrane encloses the blood meal.Stercorian trypanosomes 糞內錐蟲 – Infective forms which develop in the faeces of the insect vector and enter the vertebrate host by contamination of the bite area. This is also known as the anterior station development.Salivarian trypanosomes 唾腺錐蟲 – Infective forms which develop in the mouth parts or salivary glands and enter the vertebrate host by inoculation during biting. This is also known as the anterior station development.
Volutin granules – Small inclusions seen in the cytoplasm of trypanosomes which stain red or purple with Romanovsky stains. They are probably lysosomes.Kissing bugs 錐鼻蟲 – Name given to biting bugs of the family Redurviidae which transmit Trypanosoma cruzi, become they frequently biet the face of sleeping people.Tsetse fly 采采蠅 – Name given to biting flies of the genus Glossina which transmit Trypanosoma gambiense and T . rhodesiense.Morula (mulberry) cells of Mott – These are altered plasma cells with cytoplasm filled with proteinaceous droplets. These are seen in brain tissues and characteristic of African trypanosomiasis.
Kerandel’s sign – Seen in African trypanosomiasis and in elicited by putting pressure on the palm of the hand. Severe pain occurs shortly after the pressure has been removed.Chiclero’s ulcer – A non-metastizing and long lasting skin lesion which is usually located on the ear. Caused by Leishmania mexicana.Espundia 鼻咽性 – A skin lesion which subsides spontaneously but later metastasizes to other areas. Caused by Leishmania braziliences.Uta – A skin lesion caused by Leishmania peruviana. It is usually mild and self healing. Oriental sore 東方瘡 – Cutaneous leishmaniasis of the old world cased Leishmania tropica and Leishmania major.Kala-azar 黑熱病 – Means black fever in Hindi (Indian). Refers to infection caused by Leishmania donovani.