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

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.