4. WHAT IS INFECTIOUS DISEASE??
It applies when an interaction with a microbe causes damage to host and
the associated damage or altered physiology results in clinical sign of
symptoms of host resulting from infection.
SIGNS AND SYMPTOMS??
Signs are objective changes such as rash or fever that a physician can
observe.
Symptoms are subjective changes in the body functions such as pain or loss
of appetite that are experienced by the patient.
.
5. TYPES OF HOST
OBLIGATE PRIMARY
SECONDARY TRANSPORT
HOST
Obligate Primary
Secondary Transport
HOST
6. CHAIN OF INFECTION
Portal of
entry
Susceptible
host
Infectious
agent
Reservoir
Portal of
exit
Mode of
transmission
8. EPIDEMOLOGICAL
BASIS OF
INFECTION
DESCRIPTION AND EXAMPLES
Epidemic infection Epizoonotic & Epornithic.
e.g - Cholera.
Endemic infection Hyper – endemic
Holo – endemic
(eg. Anthrax, Brucellosis, Tick typhus)
Pandemic infection E.g., Influenza pandemic of 1918 and 1957
Sporadic infection Irregular, haphazardly, and time to time
Exotic infection Imported to a country where it does not exist
9. Depending on the mode of transmission it can be,
Contagious disease – A disease that is transmitted through
physical contact. Examples - rabies, leprosy, trachoma, sexually
transmitted disease.
Communicable disease – It is an illness due to specific infectious
agents or its toxic products capable of being directly or indirectly
transmitted from man to man, animal to animal or from the
environment (through air, dust, soil, food, water etc) to man or
animal.
10. TRANSMISSION OF INFECTION
Three main components that play an important role in successful
transmission of microbial disease –
Reservoir
Mode of transmission
Susceptible host
The source of infection: It is defined as the person, animal, object or
substances from which an infectious agent passes or is disseminated from
the host.
It is of types:
SOURCE DESCRIPTION EXAMPLES
Exogeneous source The source of infection is from
outside host’s body.
Human, animals, insect, food, water
Endogeneous source The source of infection is the
normal flora present in the
human body.
E.Coli present as normal flora of the
intestine may cause urinary tract
infection in same host
11. RESERVOIR
Defined as any person, animal, arthopod, plant, soil or substances (or
combination of those) in which an infectious agent multiplies on which it
depends primarily for survival or it produces itself in such a manner that
it can be transmitted to susceptible host, i.e, reservoir is the natural
inhabitants in which organisms multiplies, replicates.
Reservoir can be – Human, Animal or Non living object (food, water)
Homologous – It is applied when another member of the same species is
victim.
Examples – Man – V.cholerae
Heterologous – When the infections is derived from a reservoir other than
man as for animal, bird infected with salmonella.
12. WHO IS CARRIER
A carrier is defined as an infected persons or animals that harbours a
specific infectious agent in the absence of discernible clinical disease and
serve as a potential source of infection for others
THE ELEMENTS IN CARRIER STATE:
The presence of disease agent in the body.
The absence of recognizable symptoms and signs of the disease.
The shredding of the disease agent in the discharge or excretion this
acting as a source of infection for other person.
Examples: Typhoid Mary is a classic examples of carrier.
13. CARRIER CAN BE CLASSIFIED IN
FOLLOWING WAYS
Based on type:
Incubatory carrier – Measles,
Polio, Pertussis and Influenza
Convalscent carrier - Typhoid
fever
Healthy carrier
Based on duration:
Temporary carriers – Incubatory,
Convalscent and healthy carriers
Chronic carriers – Tyhoid fever,
Dysentry, Cerebrospinal
meningitis and Gonorrhoea
14. ANIMAL RESERVOIR – ZOONOTIC INFECTIONS
Bacterial zoonoses Plague, Anthrax, Bovine tuberculosis
Viral zoonoses Rabies, Japanese encephalitis
Fungal zoonoses Dermatophytic infections
Parasitic zoonoses Toxoplasmosis, Cysticercosis
Insect vectors – Mosquitoes, Flies, Mites and Ticks
Mechanical vector Domestic flies carry enteric bacteria on their leg
Biological vector Biological vector ( e.g- rat fleas, female
anophales mosqitoes that transmit Plague, Malaria
respectively)
15. DIRECT MODE EXAMPLES
Direct contact. Common cold, Staphylococcal
infection, Syphilis, AIDS
Inhalation of droplet Tuberculosis, Pertussis.
Contact with soil Tetanus, Mycosis
Inoculation into skin or mucosa Rabies virus, HIV infection
Trans placental infection Treponema pallidum, Rubella,
Cytomegalo virus, Toxoplasma
gondii.
MODE OF TRANSMISSION
16. INDIRECT MODE EXAMPLES
Vehicle borne Typhoid fever, Cholera
Vector borne
Mechanical
Biological (Propagative,
Cyclopagative, Cyclo development)
Plague bacilli in rat fleas, Malaria
parasite in mosquito, Microfilarae in
mosquito.
Air borne (by droplet nuclei or dust) Tuberculosis, Coccidiomycosis, Q
fever.
Fomite borne Diphtheria, Typhoid fever.
Uncleaned hands and fingers Streptococci, Staphylococcal infection,
Typhoid fever, Dyssentery.
17. The pathogen can be transmitted either by vertical or
horizontal transmission.
Vertical transmission
Breast milk Passage through birth
canal
Transplacental
Ex: Group B Streptococci and Listeria monocytogenes cause neonatal sepsis,
Staphylococci cause skin and oral infection.
Horizontal infection
Person to person Contact with air, water,
food and Vectors
Ex:. Polio, Influenza, Typhoid
18. SUMMARY OF MODE OF TRANSMISSION OF
INFECTION
MODE OF
TRANSMISSION
DISEASE CAUSATIVE
ORGANISM
MECHANISM
HUMAN TO HUMAN
A. Direct contact
B. Indirect contact
C. Trans-placental
D. Blood borne
Gonnorrhea
Dyssentry
Congenital syphillis
Syphillis
N. gonorrhoea
Shigella dysenteriae
Treponema pallidum
Treponema pallidum
Intimate contact.
Fecal-oral route
Across placentra
Through transfused
Blood and intravenous
drug abuse
NONHUMAN TO
HUMAN
A. Animal source
B. Via insect vector
C. Through animal
excreta
Cat stratch fever
Lyme disease
Haemolytic uremetic
syndrome.
Bartonella lenselae
Borrelia burgdoferri
E.coli O.157
Bacteria enter in
catscratch
Bacteria enter in tick bite
Bacteria in cattle faeces
are ingested in
undercooked food
19. ROUTE OF ENTRY OF MICROBIAL PATHOGEN
PORTAL OF
ENTRY
BACTERIA VIRUS FUNGUS
Skin and mucous
membrane
Clostridium tetani
Leptospira
Hepatitis B virus,
HIV
Dermatophytes
Respiratory
tract
Streptococcus
pneumoniae,
Neisseria
meningitidis,
Mycobacterium
tuberculosis.
Rhinovirus,
Respiratory
syncytical virus,
Influenza virus
Cryptococcus
neoformans,
Histoplasma
capsulatum
Gastro-intestinal tract Shigella sp,
salmonella sp,Vibrio
sp.
Hepatiis A or E
virus, Polio virus
Candida albicans
Genital tract Neisseria
gonorrhoea,
Treponema pallidum .
HIV, Human
papilloma virus .
Candida albicans
23. VIRULENCE FACTORS
These are the molecules expressed and secreted by the bacteria
May be encoded on chromosomal, plasmid, transposon or temperate
bacteriophage DNA
Virulence factor genes - integrate into the bacterial chromosome.
24.
25. TYPES OF VIRULENCE FACTORS
Adherence factors.
Invasion factors.
Capsule.
Toxins.
Iron acquisition.
26. ADHERENCE OR COLONIZATION FACTORS
Pathogens and potentially pathogenic commensals adhere to the mucous
membrane surfaces with considerable selectivity
Fimbriae.
Slime layer.
Glyco-calyx.
Membrane protein.
Cell bound protein.
Bacterial biofilms.
27. TYPES OF ADHESION MECHANISM EXAMPLES
Pillus adhesion
Fimbriae
A) Mannose sensitive
fimbriae
B) Mannose-resistant
fimbriae
These are the main
mechanism by which
bacteria adhere to host cell.
These are the fibers that
extends from bacterial
surface, mediate attachment
of bacteria to specific
receptor on host cell
E.coli, Neisseria gonorrhoea,
Vibro cholerae.
TYPES OF NON-
PILLUS ADHESION
ORGANISMS INVOLVED
Haemaglutinin ( filament-
ous , mannose resistant,
fibrillar)
Bordetella pertusis, Helicobacter pylori, Salmonella
typhimureum
Biofilm CONS, Staphylococci, E.coli, Viridans group of streptococci
Curli (surface protein) E. coli, Salmonella, Shigella
Fibronectin Streptococcus pyogenes
Exopolysaccharide Streptococcus mutans
28. Bio-films are communities of microorganisms in a matrix that joins them together
and to living or inert substrates.
They are surface-attached communities of bacteria, encased in an extracellular
matrix of secreted proteins, carbohydrates, and/or DNA, that assume phenotypes
distinct from those of planktonic cells
BIO - FILMS
30. INVASION
Cell invasion refers to describe the entry of bacteria into host cells, ability
to avoid humoral host defense mechanisms and potentially provides a
niche rich in nutrients and devoid of comperition from another host.
Invasion of the tissue is enhanced by following factors:
(1) Invasin; (2) Enzymes; (3) Antiphagocyic factor; (4) Intra-cellular survival.
INVASIN: It is the bacterial surface protein that affect physical proportion
of tissue matrices , intracellular spaces, thereby promoting the spread of
pathogens.
31. Enzymes: Play an imporant role in-flammatory process.
ENZYMES ORGANISMS INVOLVED MECHANISM OF ACTION
1. Hyaluronidase Staphylococci; Group A, B,G
streptococci, Clostridium
perfringenes
Hydrolyse hyaluronic acid thereby
spreading bacteria to spread through
subcutaneous tissue
2.Collaginase Clostridium perfringenes Hydrolyse collaginase thereby
spreading bacteria to spread through
subcutaneous tissue
3.Coagulase Staphylococcus aureus It convert fibrinogen to fibrin clot,
thereby protect bacteria from
phagocytosis.
4.Streptokinase Group A, C, G streptococci. Bind to plasminogen and activate
the production of plasmin.
5.Staphylokinase Staphylococcus aureus Prevent formation of fibrin clot.
6. Lecithinase Clostridium perfringenes Hydrolyse lecithin.desrtoys the
integrity of the cytoplasmic
membrane of many cells
7.Phospholipase Staphylococcus aureus Lyse red blood cells
32. ENZYMES ORGANISMS INVOLVED EXAMPLES
8. IgG A1 proteae Staphylococcus aureus Cleaves IgA at specific pro-ser or pro-thr
bonds in he hinge region into Fab and Fc
fragments
9. Leukocidins Streptococcus pneumoniae,
Neisseria sp, Haemophilus
influenzae
These poreforming exotoxin cause
degranulation of lysosomes within leukocyte
10. Porins Staphylococci, Streptococci ,
pneumococci
Inhibit phagocyosis by activating adenylate
cyclase system.
11. Protein A Staphylococcus aureus Binds to IgA by its Fc end thereby preventing
complement from interacting with bound IgG
12. Dnase Staphylococci; Group A,
streptococci, Clostridium
perfringenes
Lowers viscosity of exudates, giving the
pathogen more mobility.
13. Hemolysins Staphylococci, streptococci,
E. coli
Lyse erythrocte, make iron available for
microbial growth
14. Pyogenic
exotoxin B
Group A streptococci degrades protein.
15. Elastin,
alkaline protease
Pseudomonas aeruginosa Cleaves laminin associated with basement
membrane.
33. INTRACELLULAR SURVIVAL
A few mechanisms that are suggested or the intra – cellular survival of
bacteria include – inhibition of phago – lysosome fusion, resisance to
action of lysosomal enzymes, adaption to cytoplasmic replication.
Mycobacterium tuberculosis interfere with the formation of phagolysome
in a phagocyte. They are able to grow intracellularly in alveolar
macrophages.
35. TOXINS – derived from Greek (Toxicon) – Bow poison
Components or products of microorganisms which, when
extracted and introduced into host animals, reproduces disease
symptoms normally associated with infection
Roux and Yersin – Diphtheria
Endotoxin
Exotoxin
36.
37. ENDOTOXIN (PFEIFFER – 1893)
Toxic lipopolysaccharide components – gram negative bacteria
Exhibit profound biologic effect on the host
Released mainly during the cell lysis and also during multiplication
Basic structure:
‘O’ side chain
oligosaccharide
Core
polysaccharide
Lipid A
Genus or Serotype antigens
Genus specific antigens
Toxic moiety
38. Biologic activities of lipid A component of endotoxin:
Mitogenic effects on B lymphocytes
Induction of gamma interferon production by T lymphocytes
Activation of the complement cascade with the formation of C3a and C5a
Induction of the formation of interleukin-1, Interleukin-2 and other
mediators.
40. Exotoxin
Neurotoxin Cytotoxin Enterotoxin
• Gram positive and gram negative species - Soluble protein toxins released
from viable bacteria during exponential growth phase
• Are excellent antigens that elicit specific antibodies called antitoxins
• Enter eukaryotic cells primarily through receptor mediated endocytosis
41. Damage of cell membrane
Enzymatic hydrolysis – α toxin of
C.perfringens
Pore formation – α toxin of S. aureus
Second messenger pathways
ADP – Ribosylation
Adenylate cyclase
Deamidation
Glucosyl transferase
Metallo – proteases
Tetanus toxin – Zinc
protease
Botulinum neurotoxin
Protein synthesis inhibition
Elongation factors – Exotoxin A –
C.diphtheria
Ribosomal RNA – Shiga toxin –
S.dysentriae
Immune system activation
Include pyrogenic superantigens
TSST – 1
Scarlet fever toxin
42. Bacterial exotoxin – AB structure – function properties
A domain – Catalytic domain
B domain – receptor binding domain
Fragment A Fragment B
Ex : Diphtheria toxin
43. ADP RIBOSYLATION
DIPHTHERIA TOXIN
Produced - infected with a
lysogenic tox+ ß phage
A holotoxin
3 functional regions
- Receptor binding region.
- Translocation region-B subunit.
-Catalytic region-A subunit.
EF-2 + NAD+ ADPR-EF2 + H+
1.Toxin binds to Heparin Binding
EGF-like molecule
2. Internalized into clathrin coated
pit
3.Uncoated pit – Endosome
4. pH in endosome ↓
5. Movement of catalytic A into
cytosol.
6. A subunit transfers ADP ribose
from NAD to amino acid
diphthamide on EF2 which is
required for translocation of
mRNA.
7.Protein synthesis inhibition and
cell death.
44. CHOLERA TOXIN
Bacteriophage CTXØ encodes -
ctx A and ctx B.
Phage binds to toxin co-regulated
pilus (tcp).
CTX gets integrated into Vibrio
cholerae genome.
1. B subunit binds to GM1
2. A subunit internalized.
3. A1 has ADP ribose transfer
activity.
4. ↑ intracellular cAMP
5. Activates cAMP dependent
protein kinase
6. Watery diarrhea.
45. SHIGA TOXIN
Produced by Shigella dysenteriae
type 1.
Inactivate ribosomal RNA.
Its an AB toxin.
Structure similar to Cholera toxin.
Enterohaemorrhagic E.coli,
O157:H7 E.coli, Citrobacter
freundii produce similar toxins
called Shiga-like toxins(formerly
called verotoxins).
1.B subunit pentamer binds to
Gb3.
2.Receptor mediated
endocytosis.
3.In cytosol splits into A1 and
A2.
4.A has N-glycosidase-cleaves
adenine from 28S
5.Protein inhibition
47. BOTULINUM TOXIN
Toxin produced by the bacterium
Clostridium botulinum
7 types of toxins (A to G)
– toxins A, B, E and F cause illness in
humans
The toxin is the most poisonous
substance known
High lethality
Toxin enters bloodstream from mucosal
surface or wound
Binds to peripheral cholinergic nerve
endings
Transported to PNS
(Stimulatory motor nerve endings)
Inhibits release of Ach
Muscle weakness and Flaccid Paralysis
occurs beginning with cranial nerves
and progressing downward
The Mode of action of the toxin is
synonymous to that of the
Tetanospasmin (Locked Jaw Syndrome)
49. CLOSTRIDIUM PERFRINGENS
TOXIN
Produces a wide array of exo-toxins
Gas gangrene
– Caused by α-toxin produced commonly in Type A strain of
Cl. perfringens
– Results from the contamination of wounds as in Tetanus
Food Poisoning
– Raw meat may contain spores of Cl. perfringens
– which when not sterilized and is subsequently kept in room temperature
for 2 hrs after cooking, Clostridia multiply
– Reaches enormous numbers in the intestine and begin to sporulate
– Enterotoxin is released during the sporulation
50. ANTHRAX TOXIN
Toxin produced by Bacillus anthracis
In humans - cutaneous, pulmonary and
intestinal anthrax
Toxin consists of three
thermolabile components
Factor 1
Edema factor
Factor 2
Edema factor
Factor 3
Lethal factor
They are non toxic individually but yield the following results in
combination:
PA+LF
Lethal activity
PA+EF
Edema
PA+LF+EF
Edema &
necrosis - Lethal
LF+EF
inactive
51.
52. TOXIC SHOCK SYNDROME TOXIN
Formerly called Pyrogenic
exotoxin.
Chromosomally encoded.
Massive immune activation and
pyrogenicity - Superantigens.
Similar mechanism-
– Scarlet fever toxin
– Staphylococcus enterotoxins
A-E,G,H
55. OTHER TOXINS
Bacillus cereus Produces two enterotoxins - Gastroenterites
Heat stable - causes the emetic form of the disease
Heat labile – Stimulates adenylate cyclase
- Increase in cAMP concentration
- Profuse watery diarrhea
Staphylococcal
enterotoxins
Preformed toxins
8 serologically distinct enterotoxins - A-E,G,I
3 subtypes of Enterotoxin C
Enterotoxin A is most commonly associated with disease
Enterotoxins C and D – found in contaminated milk
Enterotoxin B causes pseudomembranous enterocolitis
Inflammatory mediators - vomiting charecteristic of
Staphylococcal food poisoning.
Clostridium difficile 2 toxins A and B – structurally related
In vivo only Toxin A has enterotoxic activity
Toxin B is cytotoxic only in the presence of Toxin A
Alterations of target cell’s cytoskeleton
Commonest cause of pseudomembranous colitis
56. Regulation of virulence factor
• The signal (enviromental signal often called expression of the
virulence genes).
• Common signal include temperatue, iron availability,
osmolarity ,growth phase, pH, specific ions(Ca2+) or other
nutrient factors and quorum sensing.
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