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GENERAL PRICIPLES OF INFECTIOUS DISEASES Pro f. ZHILIANG GAO Department of Infectious Diseases Third hospital, Sun Yet-sen University SINGNIFECANCE AND IMPORTANCE OF STUDY History review • In 14th century, Plague in European ,20 million people death; • In 17~18th century, smallbox in European ,150 million people death; In 1918, flu in the worldwide,40 million people death。 In 1905,Nobel gainer of physiology and medicine award Robert Koch (Germany) In 1882, Koch discovered tubculosis bacilii In 1945,Nobel gainer of physiology and medicine award Alexander Fleming(Scotland) In 1928年, Fleming Discorvered Penicillin Into antibiotics era 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 occurred in developing country。 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. Re-emergence of old infectious disease ◆(Tuberculosis) ◆(Viral hepatitis) ◆(Sexually transmitted diseases) ◆others: cholera、charcoal Re-emergence of old infectious disease • 2 million death of TB in the worldwide annually • 7~8 million infected by TB in the worldwide annually • March 24,for World TB Day Emerging infectious diseases WHO information near 30 years, about 30 kinds of infectious diseases discovered in the worldwide “Emerging infectious diseases” Emerging infectious diseases ★ 40 million of HIV/AIDS cases 4000万 worldwide ★ HIV infection rates:16000persons/per day,6 million persons/annually,11 cases/minute。 ★ 95% in developing country ★ Maximal nation :Africa,infection rate about 10% ★ Dec.1 for World AIDS Day Emerging infectious diseases • In 1985,First case of AIDS in china, it is american tourer to china 。 • To 2003,about 840 thousands HIV in china,80 thousands of AIDS cases • HIV increase 30% annually in china Emerging infectious diseases • SARS (SARS—CoV) • 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 emerging infectious diseases in 21 century Emerging infectious diseases Avian influenza H5N1 virus Antibiotics • Antibiotics, within the last 60 years, • Resulted in the cure of many previously lethal infections, “wonder drugs.” • Only several years , drug-resistant emerged. pathogenic staphylococci were found to have the ability to produce enzymes (penicillinases) that destroyed penicillin, thus rendering the drug useless against these strains • Overuse and misuse of these, “wonder drugs” will eventually reder them useless. Hospital infections • Antibiotics resistance in hospitals • Organ transplantation, prosthetic devices, artificial organs, indwelling pace makers, and neonatal and adult intensive care COMMUNICABLE DISEASES PROFILE INFECTION AND IMMUNITY PATHOGENESIS EPIDEMIOLOGY DIAGLOSIS TREATMENT PROVENTION CONCEPT OF COMMUNICABLE DISEASES • Caused by pathogens: virus、chlamydia、richettsia、 prion、bacteria、spirochete、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 is another factor which differentiates infections from non-infectious diseases. Transmission of pathogenic organisms to other people, directly or indirectly, may lead to an epidemic. The goal of studying infectious disease: to study these disease occurrence, development, spreading and prevention inside or outside of host Infection and immunity • 一. Concept of infection The course of struggle between pathogens and human or animal bodies (host). • Absolutely necessary condition Kinds of infections • Commensals • opportunistic infection • Primary infection • Repeated infection • Mixed infection • Superinfection • Secondary infection • Commensalism Pathogens live in the host but don’t induce pathologic changes. Escherichia coli in the colon Epstein-Barr virus • Opportunistic infection: Pathogens within the host can induce pathologic changes if host immunity is suppressed by some factors. Cryptococcus neoformans Cytomegalovirus Candida albicans • Primary infection: measles, chicken box • Repeated infection: malaria, schistosomiasis, ancylostomiasis • Mixed infection: rare • Superinfection: HBV overlap HEV • Secondary infection: HBV following bacilli Infections status(infection spectrum) Entrance and colonization of pathogens will lead to the following results • Eliminate pathogen • inapparent/sub-clinical infection • apparent/clinical infection • Carrier status • Latent infection ㈠ Elimination: pathogens were excluded out by host nonspecific or specific immunity. Such as: Candida albicans Hepatitis A virus ㈡ inapparent/sub-clinical infection: most frequently occurs in healthy individuals. The outcomes will be: A. Immunity acquired. HAV B. Carrier state: healthy carriers. HBV ㈢ apparent/clinical infection infection: The outcomes will be: A. Recovery. Shigella B. Chronic carrier. Salmonella typhi ㈣ Carrier state: Definition of different types of carriers: . incubation carrier . acute carrier . convalescent carrier . chronic carrier ㈤ Latent infection: After infection, pathogens remain latent inside the body. Develop clinical manifestations when the host immunity has been impaired. Pathogens usually will not be excreted by the host during period of latency. Herpes simplex • The infection status may change each other in some conditions. Latent infection Apparent Carrier status Inapparent eliminate frequency/ratio 三、 Role of Pathogens in Infection Process: ⑴ Invasiveness: adhesion, penetration ability. Shigella ⑵ Virulence: toxins, enzymes, and histolytic ability. E. histolytica ⑶ Infection dose: minimal dose that can cause an infection. S. typhi ⑷ Variability: change in structure of the pathogen to evade from host immunity. Influenza virus 四、 The Role of Immune Response in Infection Process: Differentiation between protective immunity and allergy. . Protective immunity: beneficial . Allergy(anaphylactic reaction): harmful • ⑴ Nonspecific immunity: A. Natural barriers: external (skin, mucous membrane, cilia), internal (blood-brain barrier). B. Phagocytosis: monocytes, macrophages, and granulocytes. C. Humoral factors: complements, lysozyme, interferons (α β γ), cytokines ⑵ Specific immunity: Immune respond to specific recognizable antigens. A. Cell-mediated immunity: Important in intracellular infections by viruses, fungi, protozoa and certain bacteria. B. Humoral immunity: Different kinds of antibodies (immune globulins, A D E G M) and their functions. Pathogenic Mechanisms of Infectious Diseases Establishment and development of infection process can be divided into three stages 1. Portal of entry: Each pathogen has its specific portal of entry. Mycobacterium tuberculosis, Meningococcus ----via breath tract. Shigella--- via digestive tract. 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. 3. Channels of excretion: 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. 二、 Mechanism of Tissue Damages 1. Direct invasion: Cytolysis, tissue necrosis, inflammation. 2.The actions of toxins and cytokines: Resulting in septic shock, Disseminated intravascular coagulation, DIC etc. 3. Immunopathogenesis: Immunosuppression, T-cell destruction, immune complexes induce cytotoxicities. • Shock is a special problem in severe infections. • Endotoxin from Gram-negative bacteria caused by other cell wall components and by lipoteichoic acid • Several mediators including kinins, components, histamines, cytokines, and endogeneous opiate • Results from reduced systemic vascular resistance brought about by dilated small vessels and leaky capillaries • The cycle of shock, tissue anoxia, and organ failure is difficult to break and may kill the patient within hours. Bacteramia and Septicaemia • Bacteraemia, the presence of living organisms in the blood, can occur in healthy people without causing symptoms • Unless there is a focus on which they can settle and multiply, e. g. an abnormal heart valve, these organisms are normally cleared very rapidly from the blood. • Other organisms invading the blood stream, such as staphylococcus aureus and Escherichia coli. , are less likely to be dealt with by the immune system and more likely to cause disease; Septicaemia • Caused by Gram-positive, Gram-negative, or fungal organisms. • Complicated by septic lesions in organs or tissues. • Such as: pneumococcal pneumonia and meningococcal meningitis. • Cirulatory failure, the septic shock syndrome, is the most dangerous complication • Blood cultures are the most important initial investigation 二、 Important Patho- physiologic Changes in infection 1. Fever (pyrexia): Exogenous and endogenous pyrogens. . Exogenous pyrogens: virus etc. . Endogenous pyrogens: IL-1, IL-6, TNF, interferon etc. 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: higher anabolism, hyper-corticosteroidemia Epidemiological Process of Infectious Diseases and Influencing Factors Epidemiological Process(course) include: 1. Sources of infection: Definition. Human, animal. ⑴ Patients: acute, chronic; typical, atypical(mild, severe). ⑵ Subclinical infection: no symptoms. poliomyelitis. ⑶ Carriers: chronic:typhoid, shigellosis. ⑷ Infected animals:(natural source) rabies, plague, schistosomiasis. 2. Routes of transmission ⑴ Air, droplets, dusts: e.g. measles, diphtheria. ⑵ Water, food, flies(fecal-oral infection): e.g. typhoid, cholera. ⑶ Fingers, utensils (contact infection): e.g. shigellosis, influenza. ⑷ Arthropods: A. Biologic: intermediate hosts, e.g. mosquitoes in malaria, chiggers in scrub typhus. B. Mechanical: passive transfer. e.g. flies in amebiasis ⑸Bloob,body liquid transmission • Such as HBV,HIV ⑹Vertical transmission: mother to baby ⑺Horizontal transmission: others 3.susceptibility • Susceptible person 二、 Factors Influencing Epidemiological Process 1. Natural factors: . Climatic: season, rain, humidity. . Geographic: endemicity, schistosomiasis clonorchiasis sinensis: fresh fish 2. Social factors: Social system, social-economic condition, cultural background Characteristics of Infectious Diseases 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. 2. Clinical Characteristics: (1) Stages of development: A. Incubation period. B. Prodromal period. C. Symptomatic period. D. Convalescent period. E. Recrudescence, relapse. F. Sequelae. ⒈ incubation period Incubation period is the period between the invasion of the tissues by pathogens and the appearance of clinical features of infection. infectivity to others. ⒉ prodromal period from onset of diseases to apparent clinical features ⒊ Symptomatic period. Apparent of clinical manifestations. ⒋ convalescent period lighten and disappear clinical manifestations,Lab. normal 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. ⒍ sequela body function abnormal after recovering of diseases Characteristic of infectious disease 3. Common symptoms and signs. ⑴ Fever(pyrexia) : A. Effervescence: early stage. B. Fastigium: full-blown stage. C. Defervescence: improvement stage Fever forms A. Sustained fever: Difference of body temperature less than 1 degree centigrade within 24 hours, over 39℃. e.g. Second week of typhoid sustained fever • B. Remittent fever: Change of body temperature more than 1 degree centigrade within 24 hours, the base line higher than normal. e.g. Septicemia. remittent fever C. Intermittent fever: Fluctuation between normal temperature and high fever within 24 hours. e.g. Malaria. intermittent fever • D. Relapsing fever: Fever lasting 5~7 days with relapse after several days. e.g. Relapsing fever, brucellosis. relapsing fever • E. Irregular fever: Curve of body temperature is irregular. e.g. Brucellosis, septicemia • E. Irregular fever: Curve of body temperature is irregular. e.g. Brucellosis, septicemia ⒉ Skin rash or eruption: Note 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 A. Enanthem: Rash on mucous membrane (mucosa). e.g. Koplik spots in measles. B. Exanthem: Rash on skin surface, e.g. chickenpox, smallpox. C. Maculopapular rash: e.g. Macula and papule (Maculopapule) in measles rose spots in typhoid fever. macula papule herpes pustule d. Urticaria: Seen in serum sickness, tetenus antitoxin (TAT) parasitic diseases, schistosomiasis drug hypersensitivity, piperacillin, etc. (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. B. Mononuclear-phagocyte system (Reticulo-endothelial system) reactions: hepatomegaly, splenomegaly, lymphadenopathy. 4. Clinical forms: (1) development: Acute, subacute and chronic forms. (2) forms of clinical manifestation: mild, moderate (typical) or severe forms of the disease. ambulatory form in typhoid (without symptom and signs). Acute • Fever; anoxia, protein catabolism, negative nitrogen balance, acute-phase protein response, 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 Chronic • Weight loss and muscle-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 Diagnosis of Infectious Diseases 1. 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. Pathognomonic signs • • • • • • • • • • • Measles: Koplik spots Mumps: swelling of parotid gland Scrub typhus: eschar Leptospirosis: myalgia, calf muscle Typhoid: rose spots Cysticercosis: subcutaneous nodules Hepatoencephalopathy: flapping tremor Schistosomiasis: urticaria Shigellosis: mucus-pus-bloody stool Amebic dysentery: strawberry jam-like stool Rabies: hydrophobia 2. Epidemiological 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. 三、 Laboratory Examinations: (1) Routine examinations: blood, urine, stool. Leukocytosis, leukopenia, eosinopenia, eosinophilia. Biochemical analysis of the blood for liver functions and kidney functions, etc. Leukocytosis: • Infection with virus: • epidemic hemorrhagic fever • Japanese B encephalitis • infectious mononucleosis • rabies • Infection with bacteria, etc. (2) Detection and isolation of pathogens: A. Adequate collection and transportation of specimens. B. Direct examination: Recognition of causative agent – malaria in blood slides, Vibrio cholerae in stool, diphtheria in throat swab, bacilli in urine – Entamoeba in rectal scrape, schistosome ova in rectal snip, rickettsia in rash aspirate, fungi in skin scrapings, pneumococci in purulent sputum, leprosy bacilli and leishmania in slit skin smear – By electron microscopy: viruses in stool; herpes viruses from skin – By histology of biopsy specimen; acid fast bacilli in leprosy and tuberculosis, hepatitis B in liver, rabies virus in brain C. Culture by artificial Culture of causative organism – – – From blood: typhoid, brucellosis, Gramnegative speticaemia, pneumococcal pneumonia, HIV From bone marrow: tuberculosis, brucellosis, leishmaniasis, histoplasmosis From other body fluids, feces or tissues: urinary tract infection, bacillary dysentery, sputum in pneumonia, liver in tuberculosis D. Animal inoculation • Intraperitoneal inoculation: Rickettsia tsutsugamushi. • Intracerebral inoculation: encephalitis virus. E. Specific Immunological detection: • Detection of microbial antigen Meingococcal and pneumococcal disease (blood, cerebrospinal fluid, sputum, urine) • Detection of antibody of IgM class Toxoplasmosis, hepatitis A • Demonstration of antibody Rising titre: typhoid, brucellosis, HIV infection Closely linked to clinical syndrome: amoebic abscess, visceral leishmaniasis Screening for latent disease: schistosomiasis, • Skin testing: Tuberculosis, histoplasmosis, leishmaniasis Nonspecific F. Molecular biologic assay: Using isotope or non-isotope probes; Polymerase chain reaction (PCR). Mycobacterium tuberculosis, hepatitis C virus, etc. ㈢ 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 abscesses, mediastinal lymph node enlargement Treatment of Infectious Diseases Principles of therapy 1. Aim of treatment: . for alleviation of symptoms and signs . for isolation of patients . Comprehensive treatment includes drug therapy, nursing care and isolation. . Pay attention to both specific and symptomatic treatments. 2. Therapeutic methods: ⑴ General and supportive treatment. ⑵ Etiologic (specific) treatment. ⑶ Symptomatic treatment. ⑷ Rehabilitation therapy for sequelae. ⑸ Traditional Chinese medicine and acupuncture. Prevention of Infectious Diseases 1. Measures against the source of infection ⑴ Report of cases: According to the Law for Controlling Infectious Diseases issued by the central government. Three kinds of case report: Kind A: plague, cholera, smallpox, SARS. <6hs. Kind B: AIDS, hepatitis, etc. <12hs. Kind C: influenza, mumps, etc. <48hs. ⑵ Isolation of patients: until the patient becomes non-infectious. 3. Quarantine of contacts: until the incubation period of the infectious disease is over. ⑷ Identification and treatment of carriers. ⑸ Control of infected animals: Eradication or therapy 2. Interrupt the routes of transmission ⑴ General hygienic measures: Clean drinking water supply, Food hygiene, Correct sewage disposal. ⑵ Disinfection and eradication of insect vectors. ⑶ Intervention of parasite life cycles. e.g. eradication of snails in endemic area of schistosomiasis. 3. Protection of the susceptible persons: ⑴ Immunological prophylaxis: . Active (vaccination): intracutaneous inoculation with smallpox vaccine. subcutaneous inoculation with hepatitis B vaccine. . passive (immunoglobulins): intramuscular injection with antibodies against tetanus bacillus. ⑵ Protection from environmental factors: e.g. mosquitoes bites, skin penetration by Leptospira and hookworm larvae. Thank you very much.