Transcript GENERAL PRINCIPLES

GENERAL PRINCIPLES OF
INFECTIOUS DISEASES
Department of Infectious Diseases,
the Third Affiliated Hospital
Li Gang (李刚）
2009.2
Introduction
· Definition of infectious
diseases and communicable
diseases.
· Distinction between
infectious diseases and
communicable diseases.
Definition:
1. Infectious disease: any infection
caused by microbes or parasites.
2. Communicable disease:
infection transmitted from persons
or animals to other persons.
The goal of studying infectious disease:
1. To study etiology, epidemiology,
pathogenesis, clinical manifestations,
treatment and prevention of
infectious diseases.
2. To control and eliminate these diseases.
(occurrence, spreading, prevention)
Infection and immunity
The concept of infection
The course of struggle
between pathogens and human
or animal bodies (host).
Pathogens:(microbes, parasites)
Prion; virus; chlamydia;
rickettsia; bacteria; fungus;
spirochete.
Protozoa; helminth.
Emerging pathogens and infectious diseases
1977
1977
1982
1983
1986
1988
1989
1992
1997
2003
Hantaan virus
Ebola virus
E coli O157：H7
HIV
CJD
HEV
HCV
Vibrio cholerae O139 strain
H5N1
SARS coronavirus
Three kinds of infection
⑴ Commensal infection:
Pathogens live in the host
but don’t induce pathologic
changes.
⑵ Opportunistic infection:
Pathogens within the host
can induce pathologic changes if
host immunity is suppressed by
some factors.
⑶ Pathogenic infection:
According to the severity
of the pathologic changes,
several degrees in clinical
manifestation from mild,
moderate to severe will occur.
Infection status:
Primary infection
re-infection
co-infection
super infection
secondary infection
Manifestations of Infection
Process
Entrance and colonization of
pathogens will lead to the
following results.
1. Elimination:
pathogens were excluded out
by host nonspecific or specific
immunity.
Such as Candida albicans
Escherichia coli
2. Covert (subclinical) infection:
￭ Most frequently occurs in
healthy individuals.
￭ The outcomes will be:
A. Immunity acquired.
B. Carrier state: healthy carriers.
3. Overt (clinical) infection:
The outcomes will be:
A. Recovery.
B. Chronic carrier.
4. Carrier state:
Definition of different types of
carriers:
. incubation carrier
. acute carrier
. convalescent carrier
. chronic carrier
5. 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.
The Role of Pathogens in the
Infection Process:
⑴ Invasiveness: adhesion, penetration
ability.
⑵ Virulence: toxins, enzymes, and
histolytic ability.
⑶ Infection dose: minimal dose that can
cause an infection.
⑷ Variability: change in structure of
the pathogen to evade from host
immunity.
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: macrophages,
monocytes, and granulocytes.
C. Humoral factors: complements,
interferons, lysozyme, 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) and their
functions.
Pathogenic Mechanisms
of Infectious Diseases
The occurrence and natural
course of infections can be
divided into three stages:
1. Portal of entry:
Each pathogen has its specific
portal of entry.
Such as:
Mycobacterium tuberculosis,
Meningococcus via breath tract.
Shigella via digestive tract.
2. Localization and Dissemination
in the host:
Specific for each pathogen.
Such as:
. 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. Such as:
. Hepatitis A in the stool.
. Hepatitis B in the blood.
. Measles virus in expiratory
air.
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, etc.
Mechanism of Tissue Damages
3. Immunopathogenesis:
Immunosuppression, T-cell
destruction, immune complexes,
antibody-mediated cytotoxicities.
Important Patho-physiologic
Changes in infection
1. Fever(pyrexia):
Exogenous and endogenous
pyrogens.
. Exogenous pyrogens: virus etc.
. Endogenous pyrogens: IL-1,
TNF, IL-6, interferon etc.
2. Metabolism changes:
(1) Protein:
higher proteins catabolism.
“acute” proteins (C-reactive protein,
sign of acute inflammation).
(2) Carbohydrate:
acceleration of glucolysis.
2. Metabolism changes:
(3) Water and electrolytes:
dehydration, hypokalemia.
(4) Endocrine disturbances:
higher anabolism, stress,
hyper-corticosteroidemia.
Epidemiological Process of
Infectious Diseases and
Influencing Factors
Epidemiological Process
(course):
Definition: case occur, spread.
The essential elements of
epidemiological process
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.
2. Routes of transmission
⑴ Air, droplets, dusts.
e.g. measles.
⑵ Water, food, flies(fecal-oral
infection).
e.g. typhoid.
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.
3. Population susceptibility:
Proportion of susceptibles.
Factors Influencing
Epidemiological Process
1. Natural factors:
Climatic and geographic
factors.
. Climatic: season, rain, humidity.
. Geographic: endemicity.
2. Social factors:
social system,
social-economic condition,
cultural background.
Characteristics of Infectious
Diseases
1. Basic characteristics:
(1) Pathogens.
(2) Infectivity.
(3) Epidemiological features:
age, sex, season; imported or
endemic; sporadic, epidemic,
pandemic, outbreaks.
(4) Post-infection immunity.
2. Clinical Characteristics:
(1) Development stage:
A. Incubation period.
B. Prodromal period.
C. Symptomatic period.
Apparent clinical manifestations.
D. Convalescent period.
E. Recrudescence or relapse.
F. Sequelae.
2. Common symptoms and
signs.
⑴ Fever(pyrexia) :
Courses:
A. Effervescence: early stage.
B. Fastigium: full-blown stage.
C. Defervescence: improvement
stage
Forms:
A. Sustained fever:
Difference of body temperature
less than 1℃ within 24 hours, over
39℃.
e.g. Second week of typhoid.
1 2 3 4 5 6 7
B. Remittent fever:
Change of body temperature
more than 1 ℃ within 24 hours,
the base line higher than normal.
e.g. Septicemia.
C. Intermittent fever:
Fluctuation between normal
temperature and high fever
within 24 hours.
e.g. Malaria.
D. Relapsing fever:
Fever lasting 5~7 days
with relapse after several
days.
e.g. Relapsing fever.
E. Undulent fever:
Fever lasting several
weeks with relapse after
several weeks.
e.g. brucellosis.
波状热
F. Irregular fever:
Curve of body temperature
is irregular.
e.g. Brucellosis, septicemia.
G. Saddle-type fever:
Fever for several days, then
with normal temperature for 1
day, and then relapse.
e.g. Dengue.
⑵ Skin rash or eruption:
Note appearance type, day
of the disease, and distribution.
A. Exanthem:
Rash on skin surface.
e.g. chickenpox.
B. Enanthem:
Rash on mucous membrane.
e.g. Koplik spots in measles.
a. Maculopapular rash:
e.g. Macula and papule
(Maculopapule) in measles;
rose spots in typhoid fever.
b. Petechiae:
subcutaneous hemorrhages
or ecchymosis.
e.g. septicemia, typhus,
hemorrhagic fever with
renal syndrome.
c. Vesiculo-pustule rash:
Vesicles and pustules in skin and
mucous membrane.
e.g. Varicella(chickenpox), herpes
zoster, smallpox.
d. Urticaria:
Seen in serum sickness,
parasitic diseases,
drug hypersensitivity, 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. 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).
Diagnosis of Infectious
Diseases
1. Clinical manifestations
(1) Mode of onset
(2) Type of fever
(3) Accompanying symptoms:
headache, myalgia, arthralgia etc.
(4) Signs:
Consciousness, jaundice, skin rash,
buccal membrane, Koplik spot,
eschar, subcutaneous hemorrhage,
liver, spleen, lymph nodes.
Pathognomonic signs
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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
Characteristic sign of scrub typhus
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.
3. 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.
• Infection with bacteria, etc.
(2) Detection and isolation of
pathogens:
A. Adequate collection and
transportation of
specimens.
B. Direct examination:
macroscopy: e.g. Ascaris
lumbricoides, hook worm,
Enterobius vermicularis, etc.
microscopy:e.g.Plasmodium,
Cryptococcus neoformans,
Mycobacterium tuberculosis
C. Culture by artificial
media or tissue culture.
Media culture:
Entamoeba histolytica,
Shigella, Salmonella, etc.
Tissue culture:
dengue virus, poliovirus, etc.
D. Animal inoculation.
Intraperitoneal inoculation:
Rickettsia tsutsugamushi.
Intracerebral inoculation:
encephalitis virus.
E. Specific antigen detection:
Methods: agglutination test,
ELISA, EIA, FAT, RIA, flow
cytometry, etc.
F. Molecular biologic assay:
Using isotope or non-isotope
probes;
Polymerase chain reaction
(PCR).
Mycobacterium tuberculosis,
hepatitis C virus, etc.
PCR technique
dNTPs、
Mg2+、Taq酶、
模板、引物
PCR体系
第一次循环
第二次循环
～30次后
106
(3) Detection of specific
antibodies:
By means of :
ELISA, RIA, etc.
IgM, IgG antibodies.
ELISA test
标 记 酶
无色底物
有色底物
抗原
抗体
(4) Others:
T-cell subset assay:
e.g. for AIDS.
Skin test:
e.g. for tuberculosis,
cysticercosis.
Fibro-optic endoscopy:
e.g. for esophageal varices.
Imaging (X-ray, ultrasound,
CT, MR):
e.g. for amebic liver abscess.
Biopsy:
e.g. for chronic hepatitis.
Treatment of Infectious
Diseases
Principles of therapy
1. Aim of treatment:
. Not only for alleviation of
symptoms and signs, but also for
isolation of patients to prevent
propagation of infection to the
community.
. 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. <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 (Block)
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
(Oncomelania) 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.
⑶ Chemo-prophylaxis:
artesunate against malaria
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