1、11Spirochetes2Essential informationSelf-regulated learningA summary in Chinese Framework based learning (FBL)Classification:Morphology: Structure and chemical compositionEpidemiology : source of infection, transmission, susceptible populationPathogenesis: pathogenic elements& molecules responsible f

2、or tissue damage and clinical symptomsLaboratory diagnosis and clinical profile of infectionClinical management and infection preventionOthers33Live and learn 4TreponemaLeptospiraBorrelia Treponema pallidum Borrelia burgdoferi Family Treponemataceae 5Objectives Describe the general characteristics o

3、f the LeptospiraList clinical infections caused by Leptospira sppState the general characteristics of the genus Borrelia Compare the etiologic agents and the arthropod vectors of relapsing fever and Lyme disease. Describe the classic skin lesion of Lyme diseaseCompare the human pathogens of genus Tr

4、eponemaDiscuss the primary, secondary, and tertiary clinical manifestations of syphilisDiscuss the clinical manifestations of congenital syphilisDescribe and evaluate the diagnostic tests used to identify Treponema pallidum in the clinical laboratory6 Peptidoglycan cell wall, Axial fibrils Endoflage

5、lla（Motility ） Many are too thin and/or take stains poorly Dark-field demonstrates spirochetesMorphology and structure 7Cross-section of typical spirochete88Growth and classificationSpirochetes grow slowlyAerobic or anaerobic9Spirochaetaceae 9LeptonemaLeptospira Cristispira Spirochaeta Treponema Bor

6、relia Leptospiraceae Spirochetes Borrelia burgdorferiBorrelia hermsiiBorrelia recurrentis1010 Diagnosis OrganismMorphology Transmission Reservoir Microscopy Culture Serology Disease Treponema pallidumCorkscrew spiralsSexual, Transplacental TransfusionHumansDarkfield of chance or secondary lesionsNon

7、eVDRL, RPR, FTA-ABS, MHA-TPSyphilisLeptospira interrogansClose spirals, hooked endsIngestion of contaminated water Rodents, cattle, dogsNot recommended Rarely performedMATFever, meningitis, hepatitisBorrelia recurrentisLoose spiralsLice HumansGiemsa or wright stain of blood smearRarely performedNone

8、 Relapsing feverBorrelia hermsiiLoose spiralsTicks RodentsGiemsa or wright stain of blood smearRarely performedNoneRelapsing feverBorrelia burgdorferiLoose spiralsTicks White-footed mice, other rodents, (deer)Not recommended Rarely performedEIA+ western blotLyme diseaseFeatures of spirochetal diseas

9、es11Treponema pallidum11Christopher ColumbusOne night with Venus,a lifetime with Mercury水銀. 12Syphilis overview Tertiary syphilisCardiovascular Neurosyphilis Secondary syphilis通過淋巴和血液傳播形成 此時傳染性高 性伴侶易被感染 Primary syphilis 高傳染性Chancre 硬性下疳latent syphilis13History 13Believed to have astrological causes.

10、In 1494: European outbreak, first well-recordedBy 15461414 Morphology Cause of syphilis Slim (0.15m wide, 5 to15m long) Actively motile Darkfield microscopy Devoid of proteins in quantity15Growth and metabolismGrowth is limited and slow 15Histology: Treponema pallidum - testis infected rabbit Subcul

11、ture is difficult Sensitive to heat, drying, disinfectants16Epidemiology In most cases: acquired from direct sexual contactLess commonly: congenital先天的 contact with a lesion損害, sharing of needlesTransplacental transmission 16Transmission is exclusively by contact with mucosal surfaces or blood 17Wor

12、ldwide, with an estimated 12 million new cases annually. 17 Primary or secondary syphilis : 20% In china: reoccur in 1979 18Pathogenesis Spread from mucosal breaks to blood is rapidSlow multiplication: endarteritis, granuloma18Experimental systems are limited19 Ulcer heals spontaneously but spiroche

13、tes disseminate Latent periods : Minimal triggers for immune response but Injury is due to prolonged hypersensitivity responsesPathogenesis 20Immunity Immunity develops slowly and incompletely Antibodies to OMP reinfection resistanceCell-mediated immunity clears lesions 有效 Macrophages Variable T lym

14、phocyte suppression may link to relapses2021212323Signs and symptomsPrimary syphilisSecondary syphilisLatent syphilisTertiary syphilisTertiary stage Secondary stage Primary stage 2424Primary syphilisPainless, indurated ulcer starts the diseaseIncubation time: about 3 weeks Ulceration /inflammationPr

15、imary lesion-chancre(下疳) : Heal spontaneously2525Secondary syphilisDevelops 2 to 8 weeks after the appearance of the chancre.Symmetric mucocutaneous maculopapular rash 斑狀丘疹 Lymph node enlargement Fever, malaise不舒服26 Spirochetes are abundant and highly infectious Lesions resolve but disease resolve o

16、nly in one third of patientsSecondary syphilisCondylomata lata扁平濕疣2727Latent syphilis Definition: a stage in which there are no clinical manifestations but continuing infection is evidenced by serologic tests. Secondary relapses interrupt latency Blood-borne transmission risk continues2828Tertiary s

17、yphilis Occur several years later after infection Delayed hypersensitivity Rare, Low infectious (few organisms) Skin,bone,liver,etc Manifestations depend on the body sites involved29Tertiary syphilis Neurosyphilis Cardiovascular syphilis Aortitis leads to aneurysm主動脈炎導致動脈瘤 Chronic meningitis常見 degen

18、erative changes and psychosis Cortical degeneration記憶力減退 精神方面改變 產生幻覺 Demyelination（脫髓鞘） causes peripheral neuropathies： tabes dorsalis 脊髓癆 共濟失調 醉漢步態 Syphilitic paresis梅毒麻痹 has many signs 梅毒性癡呆 30gummasTertiary syphilis Gumma梅毒瘤Gummas are destructive, localized granulomas31Interstitial keratitis角膜炎Hu

19、tchinsons teeth Periostitis骨膜炎A variety of central nervous system anomalies31Congenital syphilis 胎盤或出生時獲得Rhinitis, rash, and bone changes are commonSerologic screening and treatment is preventative可以在懷孕的過程中避免感染 懷孕四個月之后，梅毒才會傳染給胎兒 screen to give 抗生素 高危女性懷孕最后四個月需要再次進行篩查 然后在生產時采取相應的措施3232Diagnosis Micro

20、scopic examination Serologic tests Nontreponemal tests:Rapid plasma regain (RPR)Venereal disease research laboratory (VDRL)Treponemal tests3333Infection Weeks Years Percent of patients with positive serologic test100500Primary Secondary Tertiary Treponemal testsNon-treponemal tests Treatment Syphili

21、s serology3434Treatment and prevention Penicillin is preferred35Treatment and prevention Safe sex blocks transmissionRoutine screening tests and treatment during gestation35Challenges Failure in screening for special populationsProgressive dementia四期Vaccines : difficult疫苗需要高的抗原性 而螺旋體的細胞壁蛋白較少 抗原較少363

22、737Leptospira interrogans Leptospira38Leptospira interrogans 38Loose spirals seen in dark-fieldMultiple serotypes Survives in waterHighly sensitive to drying & disinfectantsBacteriology 39Leptospirosis: general view Associated with water contamination Systemic， flu-like illness Begins with fever, na

23、usea, vomiting, headache, abdominal pain, and severe myalgia. In severe cases: impaired hepatic and renal function the CNS is often involved40Adult carrierWater,Soil, mudUrine Adult urinary sheddersAcute illnessAbortionCongenital infectionUrine Water, soil, mud Cattle Pigs, sheep, dogsHUMANSSEASONAL

24、 OCCUPATIONAL Epidemiology Animals are reservoirsWater is transmission route40Worldwide zoonosis Human is accidental 41Occupational exposure42Transmission42 Broken skin Conjunctiva結膜 Ingestion Upper alimentary tract mucosa.消化道Infected urine of Rodents Farm animalswaterLeptospira interrogans43Pathoge

25、nesis & Immunity 43 Enters through several routes Small mucosal breaks Blood and CNS spread is common Antibody may be a part of disease44 Clearing of the bacteremia : circulating antibody Antibody is also rising during the second phase: absence of response to antimicrobics Pathogenesis & Immunity 45

26、Factors involved in pathogenicity (key points)45Multiply in kidney and liver.Shed in the urine of infected animals life long 1 Entry 2 Spread 3 Exit3 Diseae :Meningitis HepatiisNephritisRash Damage to the capillary endothelium is the main cause4646Leptospirosis Incubation period: 7-13 days Initial d

27、isease is flu-like: bacteremia Second phase : Last 3 or more weeks: Meningitis and muscle aches Severe systemic disease: most severe form ( Weils disease) Manifestations Hemorrhagic rash出血性皮疹在皮膚上47Diagnosis47 The diagnosis of leptospirosis is primarily serologic (blood, urine, CSF): limited to refer

28、ence laboratories Dark field examination is not recommended Culture: difficult and rarely attempted 4848Treatmentmilder diseaseTetracyclines (eg. doxycycline) severe forms of leptospirosisPenicillin Ampicillin Erythromycin ? Third generation of cephalosporins & other antimicrobics :Prevention49 Anim

29、al and water control Vaccine : cattle and household petsDrainage of water known contaminatedCare on the subjects with occupational exposureAvoid ingestion or contaminationDoxycycline given once weekly4950Borrelia50Relapsing fever Lyme disease51Morphology51 Loose, irregular spirals taking common stai

30、ns long, slender, with 7-20 axial flagella Nutrients taken from external sources: amino acids, fatty acids, nucleic acids52 Abundant in outer membrane proteins and lipoproteins Surface proteins undergo antigenic variation eg. B. hermsii recombination between linear plasmids altered proteinMorphology

31、53EpidemiologyMay be caused by Borrelia recurrentis Body lice or ticks transmit the spirochete Tick reservoir feeds on rodents 嚙齒動物and small animals53Relapsing feverEpidemic (louse-borne) relapsing feverEndemic (tick -borne) relapsing fever54Nighttime夜間 painless tick bite transmits bacteriaBody lice

32、 infected from human bloodLice must be transferred from human to human54Outbreak: Northern Rim of the Grand Canyon55Pathogenesis & Immunity Spirochetes appear in blood Endotoxin -like featuresAltered OMPs occur with relapse. Immune responses develop slowly Antibody eventually controls disease when55

33、56Relaspsing fever: clinical aspectsManifestations Incubation period： 7 daysFever, headache and muscle pain last about 1 week Louse-borne is more severe56 3-4 relapses Higher Fatality57 Diagnosis Blood smears demonstrate borrelia Serologic tests are unhelpful. Treatment & Prevention Tetracycline and

34、 erythromycin Jarisch-Herxheimer reaction Attention to ticks and general hygieneRelaspsing fever: clinical aspects58Borrelia burgdorferiCause of Lyme disease581977, first found in Lyme, a town of southeast Connecticut, USA 1985: in china, the first case found in Hei Longjiang province 59Bacteriology

35、 At least 10 different subspecies Grows slowly in microaerophilic atmosphereOsps (outer surface proteins) differ at stages of infection59Wright stainGram stain60Lyme Disease:61EpidemiologyB.burgdorferi is transmitted in tick-mouse deer cycleEndemic In Connecticut, the majority of cases probably go u

36、nreported Adult and nymph stages can infect humans61Ticks must feed on humans in the woods.Ticks feed on mice and then deer No deer, no disease62PathogenesisSurface proteins bind to ECM (extracellular matrix fibronection H)Peptidoglycan causes inflammation 應該target此處62Tick (OspA)Host (OspC)4. Anti-O

37、spA antibody has autoimmune activities3. Immune functionChronicity 63Immunity Immune response develops slowly: IgM ,IgG Target of protective antibody is unclear Cell immunity: neutrophils , macrophages Metabolic burst64Manifestations 64Spreading lesion from bite site Acute disease: marked by Erythem

38、a migrans and febrile aches游走性紅斑Bulls eye erythema migrans65Manifestations Nerve palsies and cardiac findings appear laterRelapsing arthritis is the most persistent may become chronic. Manifestations are similar to Reiters syndrome Rheumatic feverResembles rheumatoid arthritis.6666Diagnosis Culture and PCR are not yet prac