Pro f. ZHILIANG GAO

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GENERAL PRICIPLES OF INFECTIOUS DISEASES

• Pro f. ZHILIANG GAO
• Department of Infectious Diseases
• Third hospital, Sun Yet-sen University

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SINGNIFECANCE AND IMPORTANCE OF STUDY
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History review

• In 14th century, Plague in European ,20 million
  people death
• In 1718th century, smallbox in European ,150
  million people death
• In 1918, flu in the worldwide,40 million people
  death?

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In 1905,Nobel gainer of physiology and medicine
award Robert Koch (Germany)
In 1882, Koch discovered tubculosis bacilii
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In 1945,Nobel gainer of physiology and medicine
award Alexander Fleming(Scotland)
In 1928?, Fleming Discorvered Penicillin Into
antibiotics era
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• 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?

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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.

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Re-emergence of old infectious disease

• ?(Tuberculosis)
• ?(Viral hepatitis)
• ?(Sexually transmitted diseases)
• ?others cholera?charcoal

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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

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Emerging infectious diseases

• WHO information
• near 30 years,
• about 30 kinds of infectious diseases
  discovered in the worldwide
• Emerging infectious diseases

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Emerging infectious diseases

• ? 40 million of HIV/AIDS cases 4000? worldwide
• ? HIV infection rates16000persons/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

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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

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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 emerging infectious diseases
  in 21 century

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Emerging infectious diseases
Avian influenza H5N1 virus
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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.

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Hospital infections

• Antibiotics resistance in hospitals
• Organ transplantation, prosthetic devices,
  artificial organs, indwelling pace makers, and
  neonatal and adult intensive care

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COMMUNICABLE DISEASES
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• CONCEPT OF COMMUNICABLE DISEASES
• Caused by pathogens virus?chlamydia?richettsia?pr
  ion?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.

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• The goal of studying infectious disease
• to study these disease occurrence, development,
  spreading and prevention inside or outside of host

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• Infection and immunity

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• ?. Concept of infection
• The course of struggle between pathogens and
  human or animal bodies (host).
• Absolutely necessary condition

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Kinds of infections

• Commensals
• opportunistic infection
• Primary infection
• Repeated infection
• Mixed infection
• Superinfection
• Secondary infection

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• Commensalism Pathogens live in the host
  but dont induce pathologic changes.
  Escherichia coli in the colon
  Epstein-Barr virus

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• Opportunistic infection Pathogens within
  the host can induce pathologic changes if host
  immunity is suppressed by some factors.
  Cryptococcus neoformans Cytomegalovirus
  Candida albicans

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• Primary infection measles, chicken box
• Repeated infection
• malaria, schistosomiasis, ancylostomiasis
• Mixed infection rare
• Superinfection HBV overlap HEV
• Secondary infection HBV following bacilli

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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

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• ? Elimination pathogens were excluded
  out by host nonspecific or specific immunity.
  Such as Candida albicans
  Hepatitis A virus

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• ? inapparent/sub-clinical infection
  most frequently occurs in healthy
  individuals. The outcomes will be
  A. Immunity acquired. HAV B. Carrier
  state healthy carriers. HBV

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• ? apparent/clinical infection infection
  The outcomes will be A. Recovery.
  Shigella B. Chronic carrier.
  Salmonella typhi

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• ? Carrier state Definition of different
  types of carriers . incubation carrier
  . acute carrier . convalescent carrier .
  chronic carrier

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? Latent infection After infection,
pathogens remain latent inside the body.
Develop clinical manifestations when the host
immunity has been impaired. Pathogens
usually will notbe excreted by the host during
period of latency. Herpes simplex
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• The infection status may change each other in
  some conditions.
• Latent infection
• Apparent
• Carrier status
• Inapparent
• eliminate

frequency/ratio
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?? Role of Pathogens in Infection Process?
Invasiveness 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
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?? The Role of Immune Response in Infection
Process Differentiation between protective
immunity and allergy. . Protective immunity
beneficial . Allergy(anaphylactic reaction)
harmful
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• ? 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 (a ß ?), cytokines

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• ? 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.

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• Pathogenic Mechanisms of Infectious Diseases
  
• Establishment and development of infection
  process can be divided into three stages

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• 1. Portal of entry Each pathogen has its
  specific portal of entry. Mycobacterium
  tuberculosis, Meningococcus
• ----via breath tract. Shigella--- via
  digestive tract.

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• 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.

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• 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.

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?? 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.
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• 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.

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• 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

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• 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

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?? Important Patho-physiologic Changes in
infection
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• 1. Fever (pyrexia) Exogenous and endogenous
  pyrogens.. Exogenous pyrogens virus etc. .
  Endogenous pyrogens IL-1, IL-6, TNF, interferon
  etc.

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• 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

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Epidemiological Process of Infectious
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• Diseases and Influencing Factors Epidemiological
  Process(course) include

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Sources of infection Definition. Human,
animal.? Patients acute, chronic typical,
atypical(mild, severe).? Subclinical infection
no symptoms. poliomyelitis.? Carriers
chronictyphoid, shigellosis.? Infected
animals(natural source) rabies, plague,
schistosomiasis.
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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.
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• ? Arthropods A. Biologic intermediate
  hosts, e.g. mosquitoes in malaria,
  chiggers in scrub typhus. B. Mechanical
  passive transfer. e.g. flies in amebiasis

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?Bloob,body liquid transmission

• Such as HBV,HIV
• ?Vertical transmission mother to baby
• ?Horizontal transmission others

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3.susceptibility

• Susceptible person

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?? Factors Influencing Epidemiological Process
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• 1. Natural factors . Climatic season, rain,
  humidity.. Geographic endemicity,
  schistosomiasis clonorchiasis sinensis fresh
  fish

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• 2. Social factors Social system,
  social-economic condition, cultural background

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Characteristics of Infectious Diseases
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• 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.

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2. Clinical Characteristics(1) Stages of
development A. Incubation period.B. Prodromal
period.C. Symptomatic period.D. Convalescent
period.E. Recrudescence, relapse.F. Sequelae.
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? 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. ?
prodromal period from onset of diseases to
apparent clinical features
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? Symptomatic period. Apparent of clinical
manifestations.? convalescent period
lighten and disappear clinical manifestations,Lab.
normal
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• 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.

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? sequela body function abnormal after
recovering of diseases
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Characteristic of infectious disease
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3. Common symptoms and signs. ? Fever(pyrexia)
A. Effervescence early stage. B. Fastigium
full-blown stage.C. Defervescence
improvement stage
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Fever formsA. Sustained fever Difference
of body temperature less than 1 degree
centigrade within 24 hours, over 39?.
e.g. Second week of typhoid
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sustained fever
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• B. Remittent fever Change of body
  temperature more than 1 degree
  centigrade within 24 hours, the base line
  higher than normal. e.g. Septicemia.

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remittent fever
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• C. Intermittent fever Fluctuation between
  normal temperature and high fever within 24
  hours. e.g. Malaria.

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intermittent fever
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• D. Relapsing fever Fever lasting 57 days
  with relapse after several days. e.g.
  Relapsing fever, brucellosis.

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relapsing fever
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• E. Irregular fever Curve of body
  temperature is irregular. e.g.
  Brucellosis, septicemia

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• E. Irregular fever Curve of body
  temperature is irregular. e.g.
  Brucellosis, septicemia

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? Skin rash or eruption Note appearance
type and day of the disease.
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• Eraption time
• first day chickenbox.
• second day scarlatina
• third day smallbox.
• forth day measles..
• Fifth day ship fever
• sixth day typhoid fever

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• 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.

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macula
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papule
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herpes
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pustule
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• d. Urticaria Seen in serum sickness,
  tetenus antitoxin (TAT) parasitic
  diseases, schistosomiasis drug
  hypersensitivity, piperacillin, etc.

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• (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.

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• B. Mononuclear-phagocyte system
  (Reticulo-endothelial system) reactions
  hepatomegaly, splenomegaly,
  lymphadenopathy.

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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).
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• 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

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• 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.gpost-viral fatigue
  syndrome

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Diagnosis of Infectious Diseases
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• 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.

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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

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• 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.

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?? Laboratory Examinations(1) Routine
examinations blood, urine, stool.
Leukocytosis, leukopenia, eosinopenia,
eosinophilia. Biochemical analysis of the
blood for liver functions and kidney
functions, etc.
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Leukocytosis

• Infection with virus
• epidemic hemorrhagic fever
• Japanese B encephalitis
• infectious mononucleosis
• rabies
• Infection with bacteria, etc.

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• (2) Detection and isolation of pathogens
  A. Adequate collection and transportation
  of specimens.

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• 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

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• C. Culture by artificialCulture of causative
  organism
• From blood typhoid, brucellosis, Gram-negative
  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

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• D. Animal inoculation
• Intraperitoneal inoculation Rickettsia
  tsutsugamushi.
• Intracerebral inoculation encephalitis
  virus.

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• 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

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• F. Molecular biologic assay Using isotope
  or non-isotope probes Polymerase chain
  reaction (PCR). Mycobacterium
  tuberculosis, hepatitis C virus, etc.

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• ? other examination
• X raylobar 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

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Treatment of Infectious Diseases
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• Principles of therapy
• 1. Aim of treatment . for alleviation of
  symptoms and signs
• . for isolation of patients
• . Comprehensive treatmentincludes drug
  therapy, nursing care and isolation. . Pay
  attention to both specific and symptomatic
  treatments.

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2. Therapeutic methods? General and supportive
treatment. ? Etiologic (specific)
treatment.? Symptomatic treatment.?
Rehabilitation therapy for sequelae.?
Traditional Chinese medicine and acupuncture.
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Prevention of Infectious Diseases
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1. Measures against the source of infection
? Report of cases According to the Law
for Controlling Infectious Diseases
issued by the central government.
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• Three kinds of case reportKind A plague,
  cholera, smallpox, SARS.
  lt6hs. Kind B AIDS, hepatitis, etc.
  lt12hs.Kind C influenza, mumps,
  etc. lt48hs.

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• ? Isolation of patients until the patient
  becomes non-infectious.

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3. Quarantine of contacts until the
incubation period of the infectious
disease is over.
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• ? Identification and treatment of carriers.
• ? Control of infected animals Eradication
  or therapy

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• 2. Interrupt the routes of transmission

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• ? General hygienic measures Clean drinking
  water supply, Food hygiene, Correct sewage
  disposal.

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• ? Disinfection and eradication of insect
  vectors.

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• ? Intervention of parasite life cycles.e.g.
  eradication of snails in endemic area of
  schistosomiasis.

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• 3. Protection of the susceptible persons

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• ? Immunological prophylaxis . Active
  (vaccination) intracutaneous inoculation
  with smallpox vaccine. subcutaneous
  inoculation with hepatitis B vaccine. .
  passive (immunoglobulins) intramuscular
  injection with antibodies against tetanus
  bacillus.

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• ? Protection from environmental factors
  e.g. mosquitoes bites, skin penetration by
  Leptospira and hookworm larvae.

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Thank you very much.