Transcript Pathogenesis of Infectious Diseases

Pathogenesis of Infectious
Diseases
BY
Prof. DR. Zainalabideen A. Abdulla,
DTM&H., MRCPI, Ph.D., FRCPath. (U.K.)
Learning Objectives
Infection versus Infectious Diseases
• Patho from path = Disease
• Pathogenicity = Ability to cause a disease
• Pathogenesis = Steps/mechanisms involved
in development of a disease
• Infection = Colonization by a pathogen, but
NOT necessary to have infectious
disease (WHY?)
Why infection does not always occur
• Microbes are unable to multiply
e.g. respiratory microbes
on the skin
• Lack of a specific tissue receptor for microbes
• Antibacterial factors, e.g. Lysozymes
• Indigenous microbiota, e.g.
Bacteriocins
• Overall health status
• Immunity and vaccination
• Phagocytosis: In blood and tissues
Periods/Phases of infectious diseases
1. Incubation Period
Pathogen arrival
Symptoms Onset
2. Prodromal Period: Out of sort/No symptoms
3. Period of illness: Symptoms/Communicable
4. Convalescent: Recovery; may be long or
with tissue damage
Localized vs systemic infections
• Localized infections, e.g. boils, abscesses
• Systemic infection: Localized Spread by
blood, lymph or phagocytes (wondering)
e.g. Mycobacterium tuberculosis spread to
internal organs is called military tuberculosis
(disseminated)
Acute, Subacute, and Chronic diseases
Acute disease: Rapid onset; Rapid recovery
e.g. Measles, mumps
Chronic disease: Slow onset; Lasts a long time
e.g. Tuberculosis, Leprosy
Subacute disease: More sudden that chronic,
less than acute
e.g. Subacute endocarditis (SAE)
Symptoms vs Signs of a disease
Symptoms: Subjective evidence experienced or
perceived by patients, pain, itching, nausea, etc
Symptomatic disease: Clinical disease “with”
Asymptomatic disease: Subclinical “unaware”
Example: N. gonorrheae: Male: Symptomatic
Female: Asymptomatic
Trichomonas vaginalis: Reverse
Signs: Objective evidence of a disease detected
by clinicians, e.g. hepatomegaly, heart rate, etc
Latent infection
• Latent = Lie hidden
• Latent disease: Dormant (Not currently manifest)
Symptomatic
Asymptomatic
Symptomatic
Examples:
- Human Herpes Virus (HHV) type 1
Cold Sore or HHV type 2
Genital
- HHV type 3 (Chickenpox
Shingles)
- Syphilis (Spirochete: Treponema pallidum)
Primary vs Secondary Infections
• One infectious disease follows another
• First: Primary infection
Second: Secondary infection
• Example:
Primary: Mild viral respiratory infection
(damage respiratory ciliated epithelium)
Secondary: Pneumonia; due to inhaled:
• Streptococcus pneumonia
• Haemophilus influenzae
Steps in pathogenesis of infectious disease
1. Entry (different routes)
2. Attachment
3. Multiplication (Local or systemic)
4. Invasion or spread
5. Evasion (avoid) of host defenses
6. Damage to host tissue (s)
N.B.: Not always ALL steps involved
Virulence
• Synonym to Pathogenic (Virulent)
Disease
Nonpathogenic (Avirulent)
NOT
• Toxigenic (virulent), e.g. C. diphtheria
• Encapsulated (virulent), e.g. S. pneumoniae
• Some pathogens are more virulent than others
e.g. Shigella > Salmonella
• Strains more pathogenic than others of the
same pathogen, e.g. S. pyogenes producing
erythrogenic toxin (causes scarlet fever)
Virulence Factors
Attachment:
• Receptors (integrin) on tissues:
- Glycoprotein
- S. pyogenes: Adhesin (Protein F)
- HIV: CD4 receptor
• Adhesin (Ligand) on pathogens:
- HIV: Glycoprotein gp 120
CD4
Bacterial Fimbriae (Pili)
• Hairlike, flexible projections
• Proteins (Pilin)
• Attach to surfaces
• Example: N. gonorrheae: To Urethra
E.coli: Bladder
S. pyogenes M protein:
- Adhere to pharyngeal epithelium
- Anti-phagocytic
Obligate intracellular pathogens
• G- : Rickettsia (endothelial cells)
Chlamydia (Respiratory/genital epith.
Eye conjunctiva)
• Malaria: Plasmodium (RBC)
Facultative intracellular pathogens
• Extracellular and intracellular existance
e.g. in phagocytes & on culture media
Intracellular survival mechanisms
• Phagocytes: Macrophages & neutrophils
e.g. M. tuberculosis: Wax (protect m.o. from
destruction inside phagocytic cells); Table
Capsules
• Anti-phagocytic (unable to engulf)
e.g. Streptococcus pneumoniae
Haemophilus influenzae
Klebsiella pneumoniae
Flagella
• Motile bacteria: So invade aqueous areas
• Anti-phagocytic
Exoenzymes
• Necrotizing enzymes, coagulase, kinases,
hyaluronidase, collagenase, hemolysins
and lecithinase
• Some pathogens produce also toxins
e.g. S. pyogenes
Necrotizing enzymes
• Destroy tissues
- Clostridium perfringens causes gas gangrene
(myonecrosis) by proteases and lipases
- S. pyogenes (flesh-eating strain) causes
necrotizing fasciitis
Coagulase
• Staphylococcus aureus feature
• Binds prothrombin
Staphylothrombin
Clot plasma
Protect themselves
by fibrin coat against Ab and phagocytosis
Kinases
• Fibrinolysins (vs coagulase)
• Example: - Streptokinase of Streptococci
(used to treat coronary thrombosis)
- Staphylokinase of Staphylococci
Hyaluronidase
• Spreading factor
• Breaks hyaluronic acid of connective tissue
• Staphylococcus, Streptococcus, Clostridium
Collagenase
• Breaks collagen (tendon, cartilage, bones)
• Example: C. perfringens
Hemolysins
• Destroy RBC
Iron to pathogens
• Types of hemolysis (alpha, beta, gamma)
Lecithinase
• Breaks phospholipids (Lecithin) as of RBC
• Example: C. perfringens
Toxins
1. Endotoxin
2. Exotoxins
Endotoxin
• Septicemia (sepsis)
• G- cell wall (Lipid A of Lipopolysaccharides)
• Fever (caused by pyrogens)
•• Septic shock: Inadequate blood supply to
vital organs
Exotoxin
• Poisonous proteins
• Neurotoxins, enterotoxins, cytotoxins, exfoliative toxin, erythrogenic toxin, diphtheria toxin
cont./… exotoxins
Neurotoxins
• Affect CNS
• Clostridium tetani (Tetanospasmin effect:
spastic, rigid paralysis); Figure
Clostridium botulinum (generalized flaccid
paralysis)
Enterotoxins
• Cause diarrhea and vomiting
• E. coli, Shigella, Salmonella, C. perfringens
C. difficile (Toxin A and B)
Toxic Shock syndrome:
1. Staphylococcus aureus (common cause)
TSST-1 affects integrity of capillary wall
2. Streptococcus pyogenes (less common)
Exfoliative (epidermolytic) toxin
• S. aureus
Scaled Skin Syndrome
Erythrogenic toxin
• S. pyogenes
Scarlet fever
Leukocidin
• Destroy leukocytes (WBC)/the phagocytes
• Staphylococci, Streptococci, Clostridia
Diphtheria toxin
• Corynebacterium diphtheria
• Inhibits protein synthesis
Kills mucosal epithelial cells & phagocytes
Affects heart and nervous system
Coded for by bacteriophage gene (infected)