Transcript Infectivity

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.