pro f. zhiliang gao department of infectious diseases third hospital, sun yet-sen university general...
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Pro f. ZHILIANG GAODepartment of Infectious Diseases
Third hospital, Sun Yet-sen University
GENERAL PRICIPLES
OF INFECTIOUS DISEASES
SINGNIFECANCE AND SINGNIFECANCE AND IMPORTANCE OF STUDYIMPORTANCE OF STUDY
History review• In 14In 14thth century, Plague in European ,20 century, Plague in European ,20
million people deathmillion people death ;;• In 17~18In 17~18thth century, smallbox century, smallbox in in
European European ,, 150 million people death150 million people death ; ;
In 1918, flu in the worldwideIn 1918, flu in the worldwide ,, 40 40 million people deathmillion 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 PenicillinInto 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 2 million death of TB in the
worldwide annuallyworldwide annually
• 77 ~~ 8 million infected by TB in the 8 million infected by TB in the
worldwide annuallyworldwide annually
• March 24,forMarch 24,for World TB DayWorld 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 forDec.1 for World AIDS DayWorld AIDS Day
Emerging infectious diseases
• In 1985,First case of AIDS in china, it In 1985,First case of AIDS in china, it
is american tourer to china is american tourer to china 。 。 • To 2003,about 840 thousands HIV in To 2003,about 840 thousands HIV in
chinachina ,, 80 thousands of AIDS cases80 thousands of AIDS cases
• HIV increase 30% annually in china 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 INFECTION AND
IMMUNITY
PATHOGENESIS
EPIDEMIOLOGY
DIAGLOSIS
TREATMENT
PROVENTION
PROFILE
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 infectionThe course of struggle between
pathogens and human or animal bodies (host).
• Absolutely necessary condition
• Commensals
• opportunistic infection
• Primary infection
• Repeated infection
• Mixed infection
• Superinfection
• Secondary infection
Kinds of infections Kinds of infections
• 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
• Eliminate pathogen
• inapparent/sub-clinical
infection
• apparent/clinical
infection
• Carrier status
• Latent infection
Infections statusInfections status (( infection spectru
m ) ) Entrance and colonization of pathogens
will lead to the following results
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
frequencyfrequency//ratioratio
三、 Role of Pathogens in Infection Process:
Invasiveness: adhesion,⑴
penetration ability. Shigella
Virulence: toxins, enzymes, and⑵
histolytic ability. E. histolytica
Infection dose: minimal dose⑶
that can cause an infection. S. typhi
Variability: change in structure⑷
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.
Patients: acute, chronic;⑴
typical, atypical(mild, severe).
Subclinical infection:⑵
no symptoms. poliomyelitis.
Carriers: ⑶
chronic:typhoid, shigellosis.
Infected animals:(natural source)⑷
rabies, plague, schistosomiasis.
2. Routes of transmission
Air, droplets, dusts: ⑴ e.g. measles, diphtheria.
Water, food, flies(fecal-oral⑵ infection):
e.g. typhoid, cholera.
Fingers, utensils (contact⑶ 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,HIV⑹Vertical transmission: mother to
baby⑺Horizontal 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.
Fever(pyrexia) :⑴A. Effervescence: early stage.
B. Fastigium: full-blown stage.
C. Defervescence:
improvement stage
Fever formsA. 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 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
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 treatmentincludes drug therapy, nursing care and isolation. . Pay attention to both specific and symptomatic treatments.
2. Therapeutic methods:
General and supportive⑴ treatment.
Etiologic (specific) treatment.⑵ Symptomatic treatment.⑶ Rehabilitation therapy for⑷
sequelae.
Traditional Chinese medicine⑸ and acupuncture.
Prevention of Infectious Diseases
1. Measures against the
source of infection
Report of cases: ⑴
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.