医学微生物学教学课件：STD-I

1、SEXUALLY TRANSMITTED DISEASESSTD的定义n性传播疾病(sexually transmitted diseases)是指主要通过性行为或类似性行为而传染的一组疾病，简称性病，过去民间称“花柳病”。n性病不仅仅发生在性器官上，也可侵犯附属淋巴器官及全身重要器官组织。Sexually Transmitted Diseases(STDs)Objectives: Know the type of causative agent, main symptoms, laboratory diagnosis, treatment, prevention1. Gonorrhea 2.

2、 Syphilis3. Soft chancre4. LGV: Chlamydia5.Genital Herpes6. AIDS7. condyloma acuminatum 8. nongonococcal urethritis Pathogens of STDsn BacterialuGonorrheauChlamydiauSyphilisn ViraluGenital Herpes Simplex (HSV-2)uPapillomavirus (HPV)uAIDS (HIV)n ProtozoaluTrichomoniasis流行概况及特征流行概况及特征n 2000年，WHO，感染 10

3、0万人/天，新增4亿/年n 其中u梅毒1200万u淋病6200万u衣原体感染8900万u滴虫病1.7亿u尖锐湿疣3000万u生殖器疱疹2000万 1995年不同地区年不同地区1549岁成人岁成人4种种STD的估计患病率（的估计患病率（%） 19812000年全国主要性病发病情况年全国主要性病发病情况 我国性病流行趋势我国性病流行趋势n 增长迅速u1980年全国仅报告48例, 至1988年全国各省市均有性病报告, 1981-1988年均增长124.31%. 1989-1997年均增长10%-25%. 1998年以来年均增长30%. n 梅毒增长幅度最大u 1998年全国梅毒报告数为53768例,

4、 是1993年的26.7倍. 在某些地区如福州和厦门市, 梅毒发病率超过150/10万人, 近年东北地区增长迅速n淋病一直为我国报告性病中的优势病种。u但有资料显示：天津, 广东, 广西和海南4个省市的NGU的报病数超过淋病, 居第一位。n性病报告存在大量的漏诊和漏报u专家估计, 实际性病数是报告数的6-10倍地区分布特点地区分布特点n 各省性病发病均呈上升趋势n 沿海开放省份高于内地, 经济发达地区高于经济落后地区n 城市高于农村, 90%以上的性病病人集中在城市, 尤其大中城市和经济发展较快, 交通便利的城市我国性病地区分布图我国性病地区分布图 人群分布的特点n 发病率不断上升，发病人群广

5、泛n 多数STD的发病率以男性为多，不同病种男女患者性别比例不同。n 近年女性病例逐年升高，男女比例差距逐渐减小，可能与女性主动就诊人数增加，诊断水平提高有关。 n 性活跃的人群为感染性病的危险人群。20-49岁青壮年占全部性病病例数的90%以上2000年我国人群年我国人群STD的年龄分布图的年龄分布图 STD的流行过程的流行过程 n 传染源传染源 -主要传染源：性病病人及病原携带者。 -感染和传播性病的“高危人群”：卖淫嫖娼者和吸毒人员 -嫖客等“桥梁人群”：STD向普通人群传播传播途径n性接触传播n血源性传播 n母婴传播 n医源性传播 n日常生活接触传播 易感人群n 人群对性病包括艾滋病普

6、遍易感，尚无有效的疫苗n 因此，可反复感染，也可久延不愈，时隐时现n 易感性与患者接触部位的状态（有无破损），感染病原体的种类和数量、感染的方式、次数以及自身非特异性免疫功能的高低等有关流行因素流行因素-1 n对外开放和经济发展导致价值观和道德观发生变化, 婚外性生活和多个性伴增多n贫富差距加大, 导致卖淫现象增加n人口流动增加流行因素-2n性教育薄弱n性病临床医疗服务水平低, 就诊环境差, 性病诊治不规范 n性病医疗市场混乱, 大量耐药病原体出现，如我国各地的耐青霉素淋菌株率高达52.5%-78%流行因素流行因素-3n艾滋病的出现, 非淋菌性尿道炎急剧增加, 性病性盆腔炎增多 n由于性行为方

7、式的多样化，病变的发生部位也成多样性，除生殖器外，肛门、直肠、口咽部等也可发病 STD的预防针对传播的三个环节，采取综合性措施(一)管理传染源性病患者早发现、早诊断、早隔离、早报告、早治疗。u加强性病知识宣传教育，使患病者及时、主动就医。u高危人群定期检查，入境人员卫生检疫。按中华人民共和国传染病法及时报告疫情，并对病人进行治疗。(二)切断传播途径1性接触传染(1) 性道德，洁身自爱，不性乱。遵守法律法规，杜绝卖淫嫖娼。(2)正确使用安全套，预防蔓延。2非性接触传染(1)公共环境，旅馆、游泳池、理发店、美容场所等设备与器械严格消毒。(2)个人自我保护，淋浴冲澡，不用浴盆；自带洁具(桶、盆等)3

8、血液传播(1) 严格控制血液制品(2)不以任何方式吸毒，尤其是不静脉吸毒。 (3)医疗单位一次性器械用品，强调一人一针一管。(4)理发店、美容院等器械严格消毒。(5)个人用品决不互用，牙刷、剃须刀等。4母婴传播性病及时治疗，一旦妊娠应及时终止。(三)保护易感人群无疫苗。生活方式，卫生习惯，体育锻炼，提高抗病能力。Neisseria gonorrhea Gonococcus内容要点n淋病奈瑟菌的生物学性状、致病物质及所致疾病Gonorrhean Leading cause of sterility in womenn Caused by bacteria Neisseria gonorrhoea

9、n One million cases/yrn Treated with antibioticsn May cause arthritis and endocarditis (inflammation of heart)n Diagnosed by a smear of the dischargeMorphologyn 0.8m, Gram negative, diplococci (pairs of cocci)n most in neutrophil cellsCultivationn CultureuObligatory aerobicugrow best on chocolate ag

10、ar, containing heated blood, brown in coloruThayer Martin Chocolate AgarA modified (selective) chocolate agarn Biological reactionsuGlucose fermentation onlyuCan not use other sugarsSurface AntigensnPiliuAdherence factor, weak antigenicnLPSnOut membrane protein (OP)uPI: major OP, 18 serotypes u base

11、d on PIuPII: adherence factorResistancenExtremely sensitive to environmental conditions, e.g., heat and coldnSensitive to penicillinnDrug resistance is quite commonuPenicillin doesnt work wellNew beta-lactam drugs are recommendeduR plasmidVirulent Substancesn PiliuInvolved in the initial adhesion of

12、 the organism to genital epitheliumn LPS (Endotoxin)n IgA1 proteinaseuExotoxins are not believed to be of importance in pathogenesisPathogenesisnThe only natural host is humannGonococci attack mucous membranes of the genitourinary tract, eye, and rectumuCause acute suppuration that lead to tissue in

13、vasionuFollowed by chronic inflammation and fibrosisnExclusive pathogenicuDiseases result from exogenous infectionDiseasesnAdultuGonorrheaSTD,The second most common venereal diseaseuSkin lesionsResults of gonococcal bacteremianNeonateuGonococcal Ophthalmia NeonatorumGonococcal conjunctivitisBlindnes

14、sGonorrhean Womenu80% of women asymptomatic carriersuMay cause Pelvic Inflammatory Disease (PID)n MenuDevelop a drip, pus exudate 3-8 days after exposureuPainful urinationn If newborn has contact with the bacteria during birth may cause blindnessuSilver nitrate is put into the newborns eyes to preve

15、nt blindness所致疾病n 淋病u人类是淋球菌唯一的天然宿主u成人淋病绝大多数通过性接触感染，是重要的性传播疾病（sexually transmitted disease，STD）n 新生儿淋球菌性结膜炎：经产道传播u“脓漏眼”Gonorrhea In Malesn Usually urethritis, with yellow, creamy pus and painful urination, but may be asymptomaticn As suppuration subsides in untreated infection, fibrosis occurs, somet

16、imes leading to urethral stricturesGonorrhea In FemalesnPrimary infection is in the endocervix and extends to the urethra and vagina, giving rise to mucopurulent dischargeuChronic gonococcal cervicitis is often asymptomaticnIt may progress to the uterine tubes, causing salpingitis, fibrosis of the t

17、ubesnInfertility occurs in 20% of women with gonococcal salpingitisGonococcal Ophthalmia NeonatorumnAlso, gonococcal conjunctivitisnAn infection of the eye of the newbornuacquired during passage through an infected birth canaluThe initial conjunctivitis rapidly progresses and, if untreated, results

18、in blindnessnTo prevent uInstillation of tetracycline, erythromycin, or silver nitrate into the conjunctival sac of the newborn is compulsory in most countriesGonococcal BacteremianA common feature of disseminated gonoccocal disease is arthritis uCommonly considered a form of septic arthritisuIn man

19、y cases gonococci cannot be isolated from the joint (i.e. they are reactive in nature)nDermatitis (skin lesion) is also commonImmunitynCan be infected repeatedlyudue to the variations of antigenecities of gonococci proteinsDiagnosisn SpecimensuPus and secretions taken from the urethra, cervix, rectu

20、m, conjunctivan Smear and microscopy examuA smear may show the presence of G- cocci present in polymorphonuclear cells n Cultivation and isolationuCulture is essential for definitive diagnosisuSpecial care is needed to keep the temperature and moisture to preserve the bacterian Bacterial antigen det

21、ectionn Nucleic acid detectionPrevention and TreatmentnThere is no vaccineusince strains are highly variable in their external antigens (both outer membrane and pili) nSocial management, surveillance, and prevention are more effective than drugnInstillation for neonatesAntibiotic Therapyn Penicillin

22、 therapy is still usually effectiven Because of the problems with antimicrobial resistance in N gonorrhoeae, it is recommends that uncomplicated genital infections be treated with ceftriaxone given intramuscularly as a single doseuAdditional therapy doxycycline orally twice a day for 7 days, is reco

23、mmended for the possible concomitant chlamydial infection Erythromycin base orally four times a day for 7 days, is substituted for doxycycline in pregnant womenn ceftriaxone uA beta-lactamase-resistant cephalosporin微生物学检查法n 标本 u保暖、保湿、立即送检n 直接涂片镜检 n 分离培养与鉴定 u巧克力色培养基及生化反应n 快速诊断法 u抗原检测：ELISA法、u核酸检测：杂交、

24、PCR技术Syphilis& Treponema pallidumn 8种性病发病率均在上升，但以梅毒为甚，有些地区呈现高速增长势头。n梅毒过去与麻风、结核并列称为世界三大慢性传染病。n梅毒危害严重，传染性大，症状多样，易误诊漏诊。特别是梅毒患者感染艾滋病的危险性比常人增加45倍，从而会促进艾滋病的传播。 19852006年全国梅毒发病流行趋势(说明 ：19912004年为全国性病病例报告系统数据，2005与2006年为全国网络报告数据) 2006年全国梅毒发病年龄与性别分布年全国梅毒发病年龄与性别分布2006年全国梅毒病例分期/类Syphilisn Caused by bacteria tr

25、eponema pallidumn Found in the remains of American natives 5000 years oldn AIDS of the 16th centuryuColumbus, Beethoven, Goya, Keats, James Joyce, Oscar Wilde, Peter the Great, Napoleon, and a few popes all had syphilisn Bacteria enters through the mucous membranes of mouth, genital tract, rectumSPI

26、ROCHETESnAxial filamentnTreponema pallidumnSyphilisnChancrengummanAnti-cardiolipin antibodiesGROWTH- T. pallidum can be cultured in rabbit testisSTRUCTUREnOuter sheath uglycosaminoglycannOuter membrane upeptidoglycannEndoflagella uaxial filamentsnCytoplasmic membranenProtoplasmic cylinderRESISTANCE

27、TO NATURAL AND CHEMICAL AGENTS n T. pallidum is rapidly killed by u dryingu heatu coldn T. pallidum survives in whole blood for at least 24 hours 4 !n be killed by a wide range of disinfectantsn sensitive to penicillins, can also be inhibited by low concentrations of tetracyclines and erythromycinPA

28、THOGENESIS & CLINICAL FINDINGSn Natural infection is limited in humann Usually transmitted by sexual contactuAcquired syphilisuCongenital syphilis n Primary syphilisn Secondary syphilisn Tertiary syphilisAcquired Syphilis- Primary stage nHard Chancreu2 to 10 weeks after contact, a chancre develops a

29、t the point of contactAcquired Syphilis- Secondary Stage n disseminated infection n A red maculopapular skin rash, condylomasurich in spirochetes!n Fever, headache, sore throat and enlarged lymph nodes develop n Complications in other organs: syphilis meningitis, hepatitis, nephritisAcquired Syphili

30、s- Tertiary Stage n Gummasugranulomatous lesions in almost any organ or tissuen Degenerative changes in CNSn Treponemes are very rareCongenital syphilis - vesicles on the face and palmsHutchinsons teeth - central notching, wide spacingCongenital SyphilisSaddle noseImmunitynThe immune response to syp

31、hilis is complexnTreponemal antibodies formed to protein antigens fix complement and immobilize the spirochetenOther antibodies are developed, termed non-treponemal antibodiesuReagin-react with cardiolipin in mammalian tissuesLaboratory DiagnosisnDarkfield and Flourescent antibody demonstration of s

32、pirochetesnSerologic tests: 1. Non treponemal cardiolipin tests VDRL ; RPR 2. Treponemal tests: FTA-Abs; TPHATreatment and ControlnPrompt and adequate treatment of all patientsnSafe sexnPenicillin is still effectiveMycoplasma & cell walldefective bacteriaMorphology and Physiologyn smallest & free-li

33、ving bacteria uPass through bacterial filter: 0.2-0.3umn lack of cell walluHighly pleomorphicuAntibiotic susceptibilityuOsmotic pressureuTriple-layeredCULTUREn the smallest genome size n Medium: serum, sterol, high osmotic pressuren Minute colonies in solid mediaufried egg colonies: round, with a gr

34、anular surface and a dark center typically buried in the agarPathogenic MycoplasmasnThe family Mycoplasmataceae contains two genera that infect humansuMycoplasma uUreaplasman M. pneumoniaeuUpper respiratory tract disease, tracheobronchitis, atypical pneumonian M. hominisuPostpartum fever & uterine t

35、ube infectionsn M. genitaliumunongonococcal urethritis n Ureaplasma urealyticumunongonococcal urethritisM. hominis and U. urealyticum nM. hominis : pelvic inflammatory disease and post-partum feversnU. urealyticum : non-gonococcal urethritis nEpidemiology uRates of colonization with M. hominis and U

36、. urealyticum are increased when individuals become sexually activeuopportunistic pathogens PATHOGENESISnAttachment & Adherence uP1 adhesinnToxic Metabolic Products nImmunopathogenesis Laboratory DiagnosisnMicroscopy - eliminating other possible pathogensnCulture - exudationnPCR-based testinguSensit

37、ivity and specificityuDetermination of speciesuFalse-positiveTreatment and PreventionnAntibioticsutetracycline (adults only) or erythromycinuPenicillin & cephalosporins?nNo vaccines are currently available Cell wall-defective bacterianWall-defective bacteria (L forms)nSimilar colonies on solid media

38、 to that of mycoplasmanNo genetic relationship between mycoplasma and L formsnCell wall-inhibiting drugs or lysozyme can produce L formsnChronic and persistent infectionMycoplasma and L-formMYCOPLASMAL-FORM BACTERIANo genetic relationship with bacteriaRelate to their parent bacteria ,sometimes can r

39、evertCholesterol for their cell membrane No cholesterol for their cell membraneStable in ordinary mediumNeed hyperosmotic solutionGrow slowly, colony small (diameter 0.1-0.3mm)Colony larger(diameter 0.5-1.0mm)Low turbidity in liquid mediumHigh turbidity in liquid medium ,may adhere to the wall or bo

40、ttom of the tubeCHLAMYDIAChlamydiancontains one medically important genus Chlamydiauobligate intracellular parasites of higher animals (mammals and birds)ugenerally parasitize epithelial cells and multiply in the cytoplasm of the host cellua unique development cycleMORPHOLOGYn roughly spherical n 0.

41、3 and 1.0 umn gram-negativen cell walls are similar to the cell walls of G-BuLPS +uPeptidoglycan -METABOLISMnlack of ATP-generating ability, need to obtain ATP from the host cellnThe cells can synthesize DNA, RNA and proteinGROWTH AND MULTIPLICATIONEB & RBn ELEMENTARY BODY (EB)n Size 0.3 umn Giemsa-

42、purplen RNA:DNA content = 1:1n Infectiousn Adapted for extracellular survivaln Metabolically inactiven RETICULATE BODY (RB)n Size 0.5 - 1.0 umn Giemsa-bluen RNA:DNA content = 3:1n Not infectiousn Adapted for intracellular growthn Metabolically activeEB & RBEach cell are two inclusionswith EBs (Giems

43、a stain)CLASSIFICATION AND DISEASESn C. trachomatisuOcular infection Trachoma Inclusion conjunctivitisuGenitourinary tract infection Nongonococcal urethritis Salpingitis Cervicitis Lymphogranuloma venereumuRespiratory infection Pneumoniae of infantsn C. pneumoniaeuRespiratory tract infectionn C. psi

44、ttaciuPsittacosis (ornithosis)CLASSIFICATION AND DISEASESTRANSMISSIONnChlamydia is spread byuSecretions uSexual contact uMother to childC. trachomatisnTrachomanInclusion conjunctivitisnPneumonia: infantsnLymphogranuloma venereum: STDnGenitourinary tract infectionsClassification of C. trachomatisnBio

45、logical characteristicsbiovarsuTrachoma biovaruLGV biovar nBiovars are subdivided into serovars according to Antigenic (MOMP):ALuCertain serovars are associated with particular diseasesTRACHOMAn Trachoma (serotypes A-C) is the single, greatest cause of blindness in underdeveloped countries uTransmis

46、sion - direct contactuChronic infection and reinfection are commonn Grow of chlamydiauconjunctival scarring and corneal vascularizationuEyelid deformitiesucorneal lesionsusecondary bacterial infectionsublindnessTRACHOMAEyelid deformitiesLABORATORY DIAGNOSISnCharacteristic cytoplasmic inclusion bodie

47、s: iodinenIsolation of the organism from conjunctival scrapingsuyolk sac of chick embryos uMcCoy human cellsnSerological diagnosisuimmunofluorescent tests is sensitive and specific DETECTION OF INCLUSION BODYnDetection of inclusion bodies with glycogen (C. trachomatis)-iodine stainCONTROLnSulfonamid

48、es, erythromycins, tetracyclinesnImprovement of hygienic standardsnSurgical correction of eyelid deformitiesnNo vaccines, reinfection is commonGENITAL INFECTIONn C. trachomatis D-K serovarsn Diseasesu80-90% of women, 10- 20% of men have no symptomsuNongonococcal urethritis in menuUrethritis, cervici

49、tis, salpingitis, PID (Pelvic Inflammatory Disease) in womenuInclusion conjunctivitis in newbornuLymphogranuloma venereum: LGV biovarn Additional infouRisk 3-5 times higher for contracting HIV if have ChlamydiauPID can lead to infertility, pelvic pain, ectopic pregnanciesGENITAL INFECTIONAdult inclu

50、sion conjunctivitis involving the tarsal conjunctivaLymphogranuloma venereum,Suppurative inguinal adenitis, sinus tractsGENITAL INFECTIONnLaboratory diagnosisuCultureuDetection of antigen: EIAuDetection of nucleic aciduSerologynTreatmentuTetracyclin, sulfonamidesuCombined topical and systemic use in inclusion conjunctivitisPelvic Inflammatory Disease