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1、1,Department of Infectious Diseases Third hospital, Sun Yet-sen University Pro.f Gao zhiliang,GENERAL PRICIPLES OF INFECTIOUS DISEASES,2,SINGNIFECANCE AND IMPORTANCE,3,History review,In 14th century, Plague in European ,20 million people death; In 1718th century, smallbox in European ,150 million pe

2、ople death; In 1918, flu in the worldwide,40 million people death。,4,In 1905,Nobel gainer of physiology and medicine award Robert Koch (Germany),Koch discovered tubculosis bacilii,5,In 1945,Nobel gainer of physiology and medicine award Alexander Fleming(Scotland),In 1928年, Fleming Discorvered Penici

3、llin Into antibiotics era,6,WHO reports: Among 52 million of death in the worldwide annually, 17 million(32%) of death from infectious diseases and parasite In developing country,a half of death by infectious diseases; About 15 million of death by infectious diseases per hour in the worldwide,most o

4、ccurred in developing country。,7,Pattern of Infection in Developed Countries,In 20th century, fall in the incidence of communicable diseases in developed countries due to factors such as : Immunization antimicrobial chemotherapy improved nutrition and better sanitation and housing.,8,Re-emergence of

5、 old infectious disease,(Tuberculosis) (Viral hepatitis) (Sexually transmitted diseases) others: cholera、charcoal,9,Re-emergence of old infectious disease,2 million death of TB in the worldwide annually 78 million infected by TB in the worldwide annually March 24,for World TB Day,10,Emerging infecti

6、ous diseases,WHO information near 30 years, about 30 kinds of infectious diseases discovered in the worldwide “Emerging infectious diseases”,11,Emerging infectious diseases,40 million of HIV/AIDS cases worldwide HIV infection rates: 11 cases/minute 16000persons/per day 6 million persons/annually。 95

7、% in developing country Maximal nation :Africa, infection rate about 10% Dec.1 for World AIDS Day,12,Emerging infectious diseases,SARS (SARSCoV) From 2002.11.16 to 2003.7,SARS spreaded 6 continent, 32 countries,cases of 8437,death of 916 In china, cases of 5327,death of 349 SARS: most serious emergi

8、ng infectious diseases in 21 century,13,Emerging infectious diseases,Avian influenza H5N1 virus H1N1 VIRUS,14,Antibiotics,Antibiotics, within the last 60 years, Resulted in the cure of many previously lethal infections Only several years , drug-resistant emerged. pathogenic staphylococci were found

9、to have the ability to produce enzymes (penicillinases) that destroyed penicillin, thus rendering the drug useless against these strains Overuse and misuse make them useless.,15,COMMUNICABLE DISEASES,16,CONCEPT OF COMMUNICABLE DISEASES Caused by pathogens: virus、chlamydia、richettsia、prion、bacteria、s

10、pirochete、fungus and parasite(helminth、protozoa)or medical insect Infectious disease: involve any organ or system of the body and thus embraces all medical disciplines. Communicability which differentiates infections from non-infectious diseases. Transmission of pathogenic organisms to other people,

11、 directly or indirectly, may lead to an epidemic.,17,Infection and immunity,18,一. Concept of infection The course of struggle between pathogens and human or animal bodies (host). Absolutely necessary condition,19,Commensals opportunistic infection Primary infection Repeated infection Mixed infection

12、 Superinfection Secondary infection,Kinds of infections,20,Commensalism Pathogens live in the host but dont induce pathologic changes. Escherichia coli in the colon Epstein-Barr virus,21,Opportunistic infection: Pathogens within the host can induce pathologic changes if host immunity is suppressed b

13、y some factors. Cryptococcus neoformans Cytomegalovirus Candida albicans,22,Primary infection: measles, chicken box Repeated infection: malaria, schistosomiasis, ancylostomiasis Mixed infection: rare Superinfection: HBV overlap HEV Secondary infection: HBV following bacilli,23,Eliminate pathogen ina

14、pparent/sub-clinical infection apparent/clinical infection Carrier status Latent infection,Infections status(infection spectrum) Entrance and colonization of pathogens will lead to the following results,24, Elimination: pathogens were excluded out by host nonspecific or specific immunity. Such as: C

15、andida albicans Hepatitis A virus,25, inapparent/sub-clinical infection: most frequently occurs in healthy individuals. The outcomes will be: A. Immunity acquired. HAV B. Carrier state: healthy carriers. HBV,26, apparent/clinical infection : The outcomes will be: A. Recovery. Shigella B. Chronic car

16、rier. Salmonella typhi,27, Carrier state: Definition of different types of carriers: . incubation carrier . acute carrier . convalescent carrier . chronic carrier,28, Latent infection: After infection, pathogens remain latent inside the body. Develop clinical manifestations when the host immunity ha

17、s been impaired. Pathogens usually will notbe excreted by the host during period of latency. Herpes simplex,29,The infection status may change each other in some conditions. Latent infection Apparent Carrier status Inapparent eliminate,frequency/ratio,30,三、 Role of Pathogens in Infection Process: In

18、vasiveness: adhesion, penetration ability. Shigella Virulence: toxins, enzymes, and histolytic ability. E. histolytica Infection dose: minimal dose that can cause an infection. S. typhi Variability: change in structure of the pathogen to evade from host immunity. Influenza virus,31,四、 The Role of Im

19、mune Response in Infection Process: Differentiation between protective immunity and allergy. . Protective immunity: beneficial . Allergy(anaphylactic reaction): harmful,32, Nonspecific immunity: A. Natural barriers: external (skin, mucous membrane, cilia), internal (blood-brain barrier).B. Phagocyto

20、sis: monocytes, macrophages, and granulocytes.C. Humoral factors: complements, lysozyme, interferons ( ), cytokines,33, Specific immunity: Immune respond to specific recognizable antigens. A. Cell-mediated immunity: Important in intracellular infections by viruses, fungi, protozoa and certain bacter

21、ia.B. Humoral immunity: Different kinds of antibodies (immune globulins, A D E G M) and their functions.,34,Pathogenic Mechanisms of Infectious Diseases,35,Establishment and development of infection process can be divided into three stages 1. Portal of entry: Each pathogen has its specific portal of

22、 entry. Mycobacterium tuberculosis, Meningococcus -via breath tract. Shigella- via digestive tract.,36,2. localization and Dissemination in the host: Specific for each pathogen. . Mumps virus in parotid gland. . Hepatitis C virus in the liver. . Shigella in the intestine.,37,3. Channels of excretion

23、: Important factor for host infectivity. As the source of infection. . Hepatitis A in the stool. . Hepatitis B in the blood. . Measles virus in expiratory air.,38,二、 Mechanism of Tissue Damages 1. Direct invasion: Cytolysis, tissue necrosis, inflammation.2.The actions of toxins and cytokines: Result

24、ing in septic shock, Disseminated intravascular coagulation, DIC etc.3. Immunopathogenesis: Immunosuppression, T-cell destruction, immune complexes induce cytotoxicities.,39,二、 Important Patho-physiologic Changes in infection,40,1. Fever (pyrexia): Exogenous and endogenous pyrogens. Exogenous pyroge

25、ns: virus etc. . Endogenous pyrogens: IL-1, IL-6, TNF, interferon etc.,41,2. Metabolism changes:(1) Protein metabolism: higher proteins catabolism.(2) Carbohydrate metabolism: acceleration of glucolysis.(3) Water and electrolytes metabolism: dehydration, hypokalemia. (4) Endocrine disturbances: high

26、er anabolism, hyper-corticosteroidemia,42,Epidemiological Process of Infectious,43,Epidemiological Process(course) include:1.Sources of infection: Human, animal. Patients: acute, chronic; typical, atypical(mild, severe). Subclinical infection: no symptoms. poliomyelitis. Carriers: chronic: typhoid,

27、shigellosis. Infected animals: (natural source) rabies, plague, schistosomiasis.,44,2. Routes of transmission Air, droplets, dusts: e.g. measles, diphtheria. Water, food, flies(fecal-oral infection): e.g. typhoid, cholera. Fingers, utensils (contact infection): e.g. shigellosis, influenza.,45, Arthr

28、opods: A. Biologic: intermediate hosts, e.g. mosquitoes in malaria, chiggers in scrub typhus. B. Mechanical: passive transfer. e.g. flies in amebiasis,46,Blood, body liquid transmission Such as HBV,HIV Vertical transmission: mother to baby Horizontal transmission: others,47,3.susceptibility,Suscepti

29、ble person,48,二、 Factors Influencing Epidemiological Process,49,Natural factors: . Climatic: season, rain, humidity. Geographic: endemicity, schistosomiasis clonorchiasis sinensis: fresh fish 2. Social factors: Social system, social-economic condition, cultural background,50,Characteristics of Infec

30、tious Diseases,51,1. Basic characteristics:(1) Presence of pathogens.(2) Infectivity: duration of infection, chronic carrier.(3) Epidemiological features: age, sex, season; imported or endemic; sporadic or epidemic and pandemic; epidemic outbreaks.(4) Post-infection immunity.,52,2. Clinical Characte

31、ristics: incubation period the period between the invasion of the tissues by pathogens and the appearance of clinical features prodromal period from onset of diseases to apparent clinical features,53, Symptomatic period. Apparent of clinical manifestations. convalescent period lighten and disappear

32、clinical manifestations,Lab. normal,54,relapse re-appear symptom after recovering of diseases. S. typhi recrudescence re-increasing and re-appear , when lighting of clinical symptom and decreasing of temperature. S. typhi.,55, sequela body function abnormal after recovering of diseases,56,Characteri

33、stic of infectious disease,57,3. Common symptoms and signs. Fever(pyrexia) :A. Effervescence: early stage. B. Fastigium: full-blown stage.C. Defervescence: improvement stage,58,Fever formsA. Sustained fever: Difference of body temperature less than 1 degree centigrade within 24 hours, over 39. e.g.

34、Second week of typhoid,59,sustained fever,60,B. Remittent fever: Change of body temperature more than 1 degree centigrade within 24 hours, the base line higher than normal. e.g. Septicemia.,61,remittent fever,62,C. Intermittent fever: Fluctuation between normal temperature and high fever within 24 h

35、ours. e.g. Malaria.,63,intermittent fever,64,D. Relapsing fever: Fever lasting 57 days with relapse after several days. e.g. Relapsing fever, brucellosis.,65,relapsing fever,66,E. Irregular fever: Curve of body temperature is irregular. e.g. Brucellosis, septicemia,67, Skin rash or eruption:,68,Note

36、 appearance type and day of the disease. Eraption time: first day: chickenbox. second day: scarlatina third day: smallbox. forth day: measles. Fifth day: ship fever sixth day: typhoid fever,69,A. Enanthem: Rash on mucous membrane (mucosa). e.g. Koplik spots in measles. B. Exanthem: Rash on skin surf

37、ace, e.g. chickenpox, smallpox. C. Maculopapular rash: e.g. Macula and papule (Maculopapule) in measles rose spots in typhoid fever.,70,macula,71,papule,72,herpes and pustule,73,d. Urticaria: Seen in: serum sickness, tetenus antitoxin (TAT) parasitic diseases, schistosomiasis drug hypersensitivity,

38、piperacillin, etc.,74,(3) Toxemic symptoms: A. General presentations: malaise; headache; anorexia pain in muscles, joints and bones disturbance in consciousness Meningeal irritation septic shock Liver and kidney failure, etc.,75,B. Mononuclear-phagocyte system (Reticulo-endothelial system)reactions:

39、 hepatomegaly, splenomegaly, lymphadenopathy.,76,4. Clinical forms:(1) development: Acute, subacute and chronic forms. (2) forms of clinical manifestation: mild, moderate (typical) or severe forms . ambulatory form in typhoid (without symptom and signs).,77,Acute Fever; anoxia, acute-phase protein r

40、esponse, albuminaemia, low serum iron, anemia, neutrophilia Inflammation: pain, dysfunction, tissue damage Convulsion; especially in children Shock Hemorrhage: hemolytic anemia, intravascular coagulation Organ failure: kidneys, liver, lung, heart, brain, necrosis of skin,78,Chronic Weight loss and m

41、uscle-wasting Malnutrition: especially associated with diarrhea Retardation of growth and intellect in children Anemia: iron sequestration Tissue destruction: e. g. lung in pneumonia or tuberculosis, liver in hepatitis B Post-infective syndromes: e.g:post-viral fatigue syndrome,79,Diagnosis of Infec

42、tious Diseases,80,Clinical manifestations(1) Mode of onset(2) Type of fever(3) Accompanying symptoms: headache, myalgia, arthalgia etc.(4) Signs: Consciousness, jaundice, skin rash, Koplik spot, eschar, subcutaneous hemorrhage, liver, spleen, lymph nodes.,81,Pathoghomonic signs,Measles: Koplik spots

43、 Mumps: swelling of parotid gland Scrub typhus: eschar Leptospirosis: myalgia, calf muscle Typhoid: rose spots Cysticercosis: subcutaneous nodules Hepatoencephalopathy: flapping tremor Shigellosis: mucus-pus-bloody stool Amebic dysentery: strawberry jam-like stool Rabies: hydrophobia,82,2. Epidemiol

44、ogical Data:(1) History of contact with similar cases.(2) Occupation, living environment and life style.(3) History of vaccination.(4) History of transfusion of blood or blood products.,83,三、 Laboratory Examinations:(1) Routine examinations: blood, urine, stool. Leukocytosis, leukopenia, eosinopenia

45、, eosinophilia. liver functions kidney functions, etc.,84,Leukocytosis:,Infection with virus: epidemic hemorrhagic fever Japanese B encephalitis infectious mononucleosis rabies Infection with bacteria, etc.,85,(2) Detection and isolation of pathogens:A. Direct examination: malaria in blood slides, c

46、holerae in stool, diphtheria in throat swab, Entamoeba in rectal scrape, schistosome ova in rectal snip, rickettsia in rash aspirate, fungi in skin scrapings, pneumococci in purulent sputum, leprosy bacilli in slit skin smear By electron microscopy: viruses in stool; herpes viruses from skin By hist

47、ology of biopsy specimen; acid fast bacilli in leprosy and tuberculosis, hepatitis B in liver, rabies virus in brain,86,B. Culture From blood: typhoid, brucellosis, Gram-negative speticaemia, pneumococcal pneumonia, HIV From bone marrow: tuberculosis, brucellosis, histoplasmosis From other body flui

48、ds, feces or tissues: urinary tract infection, bacillary dysentery, sputum in pneumonia,87,C. Animal inoculation Intraperitoneal inoculation: Rickettsia tsutsugamushi. Intracerebral inoculation: encephalitis virus.,88,D. Specific Immunological detection: Detection of microbial antigen (blood, cerebr

49、ospinal fluid, sputum, urine) Detection of antibody of IgM class e.g, hepatitis A Demonstration of antibody Rising titre: typhoid, brucellosis, HIV infection Skin testing: Tuberculosis, histoplasmosis, Nonspecific,89,F. Molecular biologic assay: Using isotope or non-isotope probes; Polymerase chain reaction(PCR). hepatitis C virus, etc.,90, other examination X ray: lobar pneumonia, renal tuberculosis, muscular cysticercosis Isotope: detection of abscess Ultrasound: abscess hydatid cyst Computed tomography (CT) or magnetic resonance imaging (MRI): intracranial infection, visceral

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