(kat) bacterial pa tho genesis

8/3/2019 (Kat) Bacterial Pa Tho Genesis

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Kathleen Ross S. Caligagan, MD, FPSNM

PATHOGENESIS OF BACTERIALINFECTIONNORMAL HUMAN MICROBIOTA

PROPHYLAXIS



PATHOGENESIS OFBACTERIALINFECTION



PATHOGEN is a microorganism that isable to cause disease in a plant, animalor insect.

PATHOGENECITY is the ability toproduce disease in a host organism.- Microbes express their pathogenicity by means

of their VIRULENCE , a term which refers to the

quantitative ability of a microbe to cause adisease. It is determined by the genetic orbiochemical or structural features of the microbe.

BACTERIAL PATHOGENESISTERMINOLOGIES



KOCH’S POSTULATES • Bacillus anthracis is the first

microorganism to satisfy Koch’s postulatesin the late 19th century

• Exemptions:- cannot be grown in vitro but can infect

animals• Treponema pallidum (syphilis)• Mycobacterium leprae (leprosy)

- can be grown in vitro but cannot infect

animals•

BACTERIAL PATHOGENESISID BACTERIA THAT CAUSE DISEASE



Evidence for a potential pathogenbeing clinically significant

- Isolated in abundance

- Isolated in pure culture- Isolated on more than one occasion- Isolated from deep tissues-

Evidence of local inflammation- Evidence of immune response topathogen

- Fits with clinical picture

BACTERIAL PATHOGENESISID BACTERIA THAT CAUSE DISEASE



- Adherence factors- Invasins- Toxins

- Enzymes- Antiphagocytic factors- Intracellular pathogenecity

- Antigenic heterogeneity- Iron requirement- Bacterial biofilms

BACTERIAL PATHOGENESISVIRULENCE FACTORS



ADHERENCE FACTORS

• Bacterial adherence to mucosal surfacesrequires the participation of two factors:

1. RECEPTOR - a complementary macromolecular

binding site on a (eucaryotic) surfacethat binds specific adhesins or ligands

2. LIGAND, called ADHESIN- macromolecular component of the

bacterial cell surface which interactswith the host cell receptor.




Mechanisms of adherence to cell surfaces may involve

two steps:1. NONSPECIFIC ADHERENCE: - reversible attachment of the bacterium to the eucaryotic surface- sometimes called "docking"- involves nonspecific attractive forces which allow approach of the

bacterium to the eucaryotic cell surface.• hydrophobic interactions• electrostatic attractions• atomic and molecular vibrations resulting from fluctuating dipoles of

similar frequencies• Brownian movement

• recruitment and trapping by biofilm polymers interacting with the bacterialcapsule

2. SPECIFIC ADHERENCE:- reversible permanent attachment of the microorganism to the surface

- sometimes called "anchoring"- specific adherence involves permanent formation of many specific





COMPONENTS DESCRIPTION

FimbriaeFilamentous proteins on the surface of bacterial cells that maybehave as adhesins for specific adherence

Common pili Same as fimbriae

Sex pilus A specialized pilus that binds mating procaryotes together for thepurpose of DNA transfer

Type 1 fimbriae Fimbriae in Enterobacteriaceae which bind specifically to mannoseterminated glycoproteins on eucaryotic cell surfaces

Type 4 piliPili in certain Gram-positive and Gram-negative bacteria.In Pseudomonas, thought to play a role in adherence and biofilmformation

S-layerProteins that form the outermost cell envelope component of a broadspectrum of bacteria, enabling them to adhere to host cellmembranes and environmental surfaces in order to colonize.

Capsule A detectable layer of polysaccharide (rarely polypeptide) on thesurface of a bacterial cell which may mediate specific or nonspecificattachment

M protein A major virulence factor that acts as an antiphagocytic molecule

Lipopolysaccharide(LPS)

A distinct cell wall component of the outer membrane of Gram-negative bacteria with the potential structural diversity to mediate

specific adherence. Probably functions as an adhesinTeichoic acids Cell wall components of Gram-positive bacteria that may be involved




Bacterium Adhesin ReceptorAttachmentsite Disease

Streptococcus pyogenes

Protein FAminoterminus offibronectin

Pharyngealepithelium Sore throat

Streptococcus

mutans

Glycosyltransferase

Salivaryglycoprotein Pellicle of tooth Dental

caries

Streptococcus salivarius

Lipoteichoicacid Unknown

Buccalepithelium oftongue

None

Streptococcus

pneumoniae

Cell-bound

protein

N-acetylhexos-amine-

galactosedisaccharide

Mucosal

epitheliumpneumonia

Staphylococcus aureus

Cell-boundprotein

Aminoterminus offibronectin

Mucosalepithelium Various

Neisseria gonorrhoeae

Type IV pili (N-

methylphenyl-alanine pili)

Glucosamine-

galactosecarbohydrate

Urethral/

cervicalepithelium

Gonorrhea




Bacterium Adhesin ReceptorAttachmentsite Disease

UropathogenicE. coli

Type I fimbriae Complexcarbohydrate

Urethralepithelium Urethritis

UropathogenicE. coli

P-pili (pap)Globobioselinked to

ceramide lipid

Upper urinarytract

Pyelonephritis

Bordetella pertussis

Fimbriae("filamentoushemagglutinin")

Galactose onsulfatedglycolipids

Respiratoryepithelium

Whoopingcough

Vibrio cholerae N-methylphenyl-alanine pili

Fucose andmannose

carbohydrate

Intestinalepithelium Cholera

Treponema pallidum

Peptide in outermembrane (P1,P2, P3)

Surface protein(fibronectin)

Mucosalepithelium Syphilis

Mycoplasma Membraneprotein Sialic acid Respiratory

epithelium Pneumonia

Conjunctival or



INVASINS

• bacterial extracellular substances which act againstthe host by breaking down primary or secondarydefenses of the body.

• most are proteins (enzymes) that act locally todamage host cells and/or have the immediateeffect of facilitating the growth and spread of thepathogen.

• usually act at a short range and may not actually

kill cells as part of their range of activity (unlikeexotoxins which are cytotoxic, act at remote sites, and are





Invasin Bacteria Involved Activity

HyaluronidaseStreptococci,staphylococci andclostridia

Degrades hyaluronic acid ofconnective tissue

Collagenase Clostridium species Dissolves collagen framework ofmuscles

NeuraminidaseVibrio cholerae andShigella dysenteriae

Degrades neuraminic acid ofintestinal mucosa

Coagulase Staphylococcus aureus Converts fibrinogen to fibrinwhich causes clotting

KinasesStaphylococci andstreptococci

Converts plasminogen to plasminwhich digests fibrin

Leukocidin Staphylococcus aureusDisrupts neutrophil membranesand causes discharge oflysosomal granules




Invasin Bacteria Involved Activity

Streptolysin Streptococcuspyogenes

Repels phagocytes and disruptsphagocyte membrane andcauses discharge of lysosomalgranules

HemolysinsStreptococci,staphylococci andclostridia

Phospholipases or lecithinasesthat destroy red blood cells (andother cells) by lysis

Lecithinases Clostridium perfringens Destroy lecithin in cellmembranes

Phospholipases Clostridium perfringens

Destroy phospholipids in cellmembrane

Anthrax EF Bacillus anthracis

One component (EF) is anadenylate cyclase which causesincreased levels of intracellularcyclic AMP

One toxin component is anadenylate cyclase that acts



TOXINS• TWO TYPES OF TOXINS

1. EXOTOXIN- Proteins

- may be released into the extracellular environmentof pathogenic gram (-) and gram (+) bacteria- bears the name exotoxins, since they are

"released" from the bacteria and act on host cellsat a distance

2. ENDOTOXIN- Lipopolysaccharides- associated with the cell walls of Gram-negative

bacteria-





ENDOTOXIN Lipopolysaccharide

(mw = 10kDa)

Part of outer membrane

No (heat stable)Yes (weakly)

No

Relatively low (>100ug)

Low degree

No

Yes

CHEMICALNATURE

RELATIONSHIP TOCELL

DENATURED BY

BOILING ANTIGENIC

FORM TOXOID

POTENCY

SPECIFICITY

ENZYMATICACTIVITY

PYROGENICITY

EXOTOXIN Protein

(mw = 50-1000kDa)

Extracellular, diffusible

Usually (heat-labile)Yes (highly)

Yes

Relatively high (1 ug)

High degree

Usually

Occasionally



EXOTOXINS- are soluble proteins produced by both Gram-positive and Gram-negative bacteria duringexponential growth

- are the most potent poisons known and may showactivity at very high dilutions

- resemble enzymes in a number of ways:- are soluble proteins- are denatured by heat, acid, proteolytic enzymes- have a high biological activity (most act catalytically)- exhibit specificity of action (e.g. only Clostridium tetani

produces tetanus toxin; Corynebacterium diphtheriaeproduces the diphtheria toxin) or (terms such as


BACTERIAL PATHOGENESIS



EXOTOXINS- can be converted to toxoid since they are

inherently unstable, in time they lose their toxicproperties but retain their antigenic ones.

- TOXOIDS - are detoxified toxins which retain their antigenicity and their

immunizing capacity- use for artificial immunization against diseases caused by

pathogens where the primary determinant of bacterialvirulence is toxin production

- are the immunizing agents against diphtheria and tetanus

that are part of the DPT vaccine.





EXOTOXINS- COMPONENTS:

1. Subunit A- is responsible for the enzymatic activity of the

toxin- enzymatically active and but lack binding and

cell entry capability

2. Subunit B- is concerned with binding to a specific receptor

on the host cell membrane and transferring theenzyme across the membrane

- are nontoxic





EXOTOXINS- ARRANGEMENTS:

1. A-B or A-5B- indicates that subunits synthesized separately and

associated by noncovalent bonds2. A/B

- denotes subunit domains of a single protein thatmay be separated by proteolytic cleavage

3. A+B

- indicates separate protein subunits that interact atthe target cell surface4. 5B

- indicates that the binding domain is composed of 5identical subunits.




EXOTOXINS- ATTACHMENT AND MECHANISM OF ENTRY:

1. DIRECT ENTRY- the B subunit of the native toxin (A+B) binds to a specific

receptor on the target cell and induces the formation of apore in the membrane through which the A subunit istransferred into the cell cytoplasm.

2. RECEPTOR-MEDIATED ENDOCYTOSIS (RME) - the native toxin binds to the target cell and the A+B structure

is taken into the cell by endocytosis. The toxin is internalizedin the cell in a membrane-enclosed vesicle called anendosome. H+ ions enter the endosome lowering the internalpH which causes the A+B subunits to separate. Somehow,the B subunit affects the release of the A subunit from theendosome so that it will reach its target in the cell cytoplasm.The B subunit remains in the endosome and is recycled tothe cell surface.




the native toxin bindsto the target cell andthe A+B structure istaken into the cell by

endocytosis. The toxinis internalized in thecell in a membrane-enclosed vesiclecalled an endosome.H+ ions enter the

endosome loweringthe internal pH whichcauses the A+Bsubunits to separate.Somehow, the Bsubunit affects therelease of the Asubunit from theendosome so that itwill reach its target inthe cell cytoplasm.The B subunit remainsin the endosome and





NAME OF

TOXIN

BACTERIUM

INVOLVEDACTIVITY

Anthraxtoxin (EF)

Bacillusanthracis

Edema Factor (EF) is an adenylate cyclase that causesincreased levels in intracellular cyclic AMP in phagocytesand formation of ion-permeable pores in membranes(hemolysis)

Adenylate

cyclasetoxin

Bordetellapertussis

Acts locally to increase levels of cyclic AMP in

phagocytes and formation of ion-permeable pores inmembranes (hemolysis)

Choleraenterotoxin

Vibrio choleraeADP ribosylation of G proteins stimulates adenylatecyclase and increases cAMP in cells of the GI tract,causing secretion of water and electrolytes

E. coli LT

toxinEscherichia coli Similar to cholera toxin

Shiga toxinShigelladysenteriae

Enzymatically cleaves rRNA resulting in inhibition ofprotein synthesis in susceptible cells

Tetanustoxin

Clostridiumtetani

Zn++ dependent protease that inhibitsneurotransmission at inhibitory synapses resulting inspastic paralysis

Diphtheria Corynebacteriu ADP ribosylation of elongation factor 2 leads to inhibition





NAME OF TOXIN BACTERIUM

INVOLVEDACTIVITY

PYROGENIC EXOTOXINS or SUPERANTIGENS- represent a family of molecules with the ability to elicit massive activation of the immune

system.- hyperstimulate the immune system leading to shock- cause of toxic shock syndrome (TSST) by Staphylococcus aureus and Streptococcus

pyogenes- share the ability to stimulate T cell proliferation by interaction with Class II MHC

molecules on APCs and specific V beta chains of the T cell receptor.- the important feature of this interaction is the resultant production of IL-1, TNF, and other

lymphokines which are the principal mediators of disease processes associated withthese toxins .

Staphylococcusenterotoxins Staphylococcus aureus

Massive activation of the immune system,including lymphocytes and macrophages,leads to emesis (vomiting)

Toxic shock syndrometoxin (TSST-1)


Acts on the vascular system causinginflammation, fever and shock

Pyrogenic exotoxins(SPE) e.g.Erythrogenic toxin

Streptococcuspyogenes Causes localized erythematous reactions



ENDOTOXINS- always associated with Gram-negative bacteria as

part of the outer membrane of the cell wall (e.g. E.coli, Salmonella, Shigella, Pseudomonas, Neisseria,

Haemophilus)- Biological activity is associated with the

lipopolysaccharide. LPS activates complement bythe alternative (properdin) pathway:

• Lipid component (Lipid A) – responsible for toxicity• Core (R) polysaccharide components – responsible for

immunogenicity (antigenicity)• O polysaccharide (O antigens) – act as a determinant of

virulence in Gram-negative bacteria and responsible for theproperty of "smoothness" of bacterial cells, which may




teps in successful infection:

BACTERIAL PATHOGENESISSTEPS OF BACTERIAL PATHOGENICITY

S ex• comes beforedisease• acquire virulencegenes

S ense environment

S witch virulencegenes on and off

S wim to site ofinfection

S tick to site ofinfection

S cavenge fornutrients (Iron)

S urvive stress

S tealth• avoid immunesystem

S trike-back• damage hosttissues

S ubvert• host cellcytoskeletal andsignalling pathways

S pread throughcells and organs

S catter in theenvironment




1. Bacterial SEX

• Acquiring virulence genes• Bacteria have three ways of exchanging DNA

1. Transformation- cells directly take up naked DNA

2. Transduction- injection of foreign DNA by a bacteriophage into the host bacterium (phages carry

DNA)

2. Conjugation- transfer of genetic material between two bacterial cells in direct contact through

specialised appendages

• What are being transferred?1. Extrachromosomal Mobile Genetic Elements (MGE)2. Pathogenicity Islands

STEPS OF BACTERIAL PATHOGENICITY




1. Bacterial SEX• MOBILE GENETIC ELEMENTS

- transfer of these elements result in transfer of virulencefactor

1. Plasmids- eg) TTSSs in Shigella, Yersinia; toxins in

Salmonella, E. coli, anthrax

2. Bacteriophage- eg) botulinum toxins, diphtheria toxin, shiga-like

toxin, staphylococcal toxins, TTSS substrates inSalmonella

3. Transposons





1. Bacterial SEX• MOBILE GENETIC ELEMENTS

- transfer of these elements result in transfer of virulencefactor

1. Plasmids- eg) TTSSs in Shigella, Yersinia; toxins in

Salmonella, E. coli, anthrax

2. Bacteriophage- eg) botulinum toxins, diphtheria toxin, shiga-like

toxin, staphylococcal toxins, TTSS substrates inSalmonella

3. Transposons


VIRULENCE FACTOR & DISEASE

PLASMID ENCODEDEscherichia coli Heat-labile and heat stable enterotoxins that cause diarrhea

Escherichia coliHemolysin (cyotoxin) of invasive disease and urinary tractinfection

E. Coli, Shigella sp.Adherence factors and gene products involved in mucosalinvasion

Bacillus anthracis Capsule, edema factor, lethal factor, protective antigen

PHAGE ENCODEDClostridium botulinum Botulinum toxin that causes paralysis

Corynebactriumdiphtheria

Diphtheria toxin that inhibits human protein synthesis

Vibrio cholerae Cholera toxin that can cause a severe watery diarrhea




1. Bacterial SEX• PATHOGENICITY ISLANDS

- large organized group of genes located on the bacterialchromosomes

- concept originated from study of uropathogenic E. coli strains- Can encode for secretion system, adhesins, siderophores, toxins- MAJOR PROPERTIES:

- have one or more virulence genes- present in the genome of pathogenic members of a specie

but absent in the nonpathogenic members-

large, usually 10-200 kb- have different guanine plus cytosine content than the rest ofthe bacterial genome

- commonly associated with tRNA genes- found with parts of the genome associated with MGE

- have genetic instability (prone to deletion)- re resent mosaic structures with com onent ac uired at





1. Bacterial SEX• PATHOGENICITY ISLANDS

- large organized group of genes located on the bacterialchromosomes

- concept originated from study of uropathogenic E. coli strains- Can encode for secretion system, adhesins, siderophores, toxins- MAJOR PROPERTIES:

- have one or more virulence genes- present in the genome of pathogenic members of a specie

but absent in the nonpathogenic members-

large, usually 10-200 kb- have different guanine plus cytosine content than the rest ofthe bacterial genome

- commonly associated with tRNA genes- found with parts of the genome associated with MGE

- have genetic instability (prone to deletion)- re resent mosaic structures with com onent ac uired at


PAINAME VIRULENCE CHARACTERISTICS

Escherichia coli PAI I536

Alpha hemolysin, fimbriae, adhesions in UTIEscherichia coli PAI I J96 Alpha hemolysin, P-pilus in UTI

Escherichia coli(EHEC) O1#7

Macrophage toxin of enterohemorrhagic E. coli(EHEC)

Salmonellatyphimurium PAI-I Invasion and damage of host cell; diarrhea

Yersinia pestis HPI/pgm Genes that enhance iron uptake

Vibrio cholerae El TorO1 VPI-1 Neuraminidase, utilization of amino sugars

Staphylococcus aureus SCCmec

Methicillin and other antiobiotic resistance

Staphylococcus aureus SaPI1 Toxic shock syndrome toxin-1, enterotoxin




2. SENSE environment

- bacteria can sense changes in environment- Environmental signals often control the expression of the

virulence genes

- Temperature- Iron availability- Osmolality- Growth phase

- pH- Specific ions (eg Ca2+)- In simplest cases, change in intracellular concentration of

ion is linked directly to gene expression- eg) fall in intra-cellular iron levels triggers de-repression

of diphtheria toxin gene





3. SWITCH virulence factors on andoff

- Changes in DNA sequence- Gene amplification- Genetic rearrangements

- Transcriptional Regulation

- Translational Regulation- Post-translational Regulation





4. SWIM

- many bacterial pathogensare motile

- eg) Enterics,Campylobacter,Helicobacter,spirochaetes

- motility is crucial for

virulence in some cases- usual organelle of motility isthe flagellum

- Variants:- Twitching motility- Swarmin


Flagellum of Gram-negativeBacteria



5. STICK

- Colonization/Invasion,adherence and initialmultiplication

- to avoidphysical/immunologicalremoval, bacteria mustadhere to:

- cell surfaces andextracellular matrix (inrespiratory tract , GIT, GUT)

- solid surfaces (in teeth,heart valves, prostheticmaterial)

- Adherence factors and





6. SCAVENGE nutrients

- Iron is needed for bacterial growth making itsbioavailability an important factor in controlling infectionespecially those with aggressive virulence factors (suchas Diphtheria toxin, Shiga-like toxin, Pseudomonasaeruginosa exotoxin A)

- Bacteria require 0.4 – 4 umol of iron in order to grow

- Free iron levels very low in body fluids- Acute phase response causes further drop- Iron overload increases susceptibility to infection





6. SCAVENGE nutrients

- Siderophores (MW 500-1000):- small ligands secreted by some microorganism that

are specific for ferric iron- function to capture iron

- some bacteria without siderophores obtain and utilize ironby:

- using iron from hemin in the gut of the biting flea (Y.perstis)

- obtain iron from the host’s intracellular iron pools(Legionella, listeria, salmonella)


BACTERIAL PATHOGENESISS S O AC A A OG C



7. SURVIVE stress

- Nutrient-limitation stress- Acid stress within stomach

- Heat shock during fever- Oxidative stress within phagocytes





8. STEALTH - ability of the bacteria to bypass or overcome host defense

mechanism by:a. Avoiding contact with phagocytes thru production of

antiphagocytic substances on the bacterial surface- Polysaccharide capsules of S. pneumoniae, H. influenzae, T.

pallidum & K. pneumoniae- M protein and fimbriae of Group A streptococci- Surface slime (polysaccharide) produced by P. aeruginosa

- O antigen associated with LPS of E. coli- K antigen of E. coli or the analogous Vi antigen of S. typhi- Cell-bound or soluble Protein A produced by S. aureus

b. Evading complement- elastase enzyme inactivates components of complement by





8. STEALTH c. Avoiding host immunological responses

- production of IgA proteases (metalloproteases active againstIgA)

d. Immunological tolerance to a bacterial antigen- Tolerance is a property of the host in which there is an

immunologically-specific reduction in the immune response toa given Ag, which can arise in a number of ways such as:

- 1. Fetal exposure to Ag

- 2. High persistent doses of circulating Ag- 3. Molecular mimicry.

e. Antigenic mimicry- e.g. sialic acid capsule of group B meningococcus

f. Immunosuppression-





9. STRIKE-BACK - Toxigenesis- Damage host tissue thru production of endotoxin and

exotoxins

10. SUBVERT - inject proteins into host cells to subvert or weakens the

cytoskeleton and signal-transduction pathways





11. SPREAD- through cells and organs:

- within macrophages (eg: typhoid); through blood(need to be complement-resistant); within cells (eg:actin-based motility of Listeria monocyogenes,

depends on ActA protein)

12. SCATTER - Transmission, virulence and evolution- through biting arthopods, shedding into water, airborne,

etc.





CORRESPONDING INFECTION-DISEASE STAGES


INCUBATION STAGE• No signs and

symptoms

PRODROMAL STAGE• First signs and

symptoms• Pathogens

may be highlycommunicable

CLINICALSTAGE• Peak of

characteristic signs andsymptomsof infection

STAGE OFDECLINE• Condition of

hostdeterioratespossibly todeath; or

• Signs andsymptomsbegin to

subside ashostconditionimproves

CONVALENSCENT STAGE• Full recovery of

surviving host; or• Chronic infection

develops



NORMAL HUMANMICROBIOTA

NORMAL FLORADEFINITION



NORMAL/INDIGENEOUSFLORA

• is the mixture of microorganisms(bacteria and fungi) that are regularly foundat any anatomical site of human body like:- Skin- Conjunctiva- Respiratory tract- Oral Cavity- External ears- Urogenital tract- Gastrointestinal tract

DEFINITION

STERILE AREAS:BrainCSF

Amniotic fluidBonesHeartLiver

LungsMuscleBlood

Urinary bladder

Middle and innerear

NORMAL FLORANORMAL FLORA



Associations Between Humans and theNormal Flora:

1. MUTUALISTIC/SYMBIOTIC- both host and organism are thought to derive benefit

from each other2. PARASITIC

- the organism live at the expense of their host

3. COMMENSAL- no apparent benefit or harm to either organism or host

4. PATHOGENIC/OPPORTUNISTS- the organism is capable of producing disease when

host’s defense mechanism breaks down

NORMAL FLORA




COMPONENTS: • Mainly bacteria• Eukaryotic fungi

• Protists• Methanogenic Archaea

NORMAL FLORA



TWO GROUPS: 1. RESIDENT flora

- fixed types of microorganisms regularly found in agiven area at a given age

- if disturbed, it promptly reestablishes itself/ transientmicroorganisms may colonize, proliferate andproduce disease

- more important2. TRANSIENT flora

- non-pathogenic or potentially pathogenicmicroorganisms that inhabit the skin or mucousmembranes for hours, days, or weeks

- derived from the environment, does not producedisease

- does not establish itself permanently on the surface- little significance

NORMAL FLORA




RESIDENT FLORA - acquired rapidly during & after birth and changes

continuously through out life- Factors influencing composition of normal flora:

- genetics - nutrition- age - geographic location- stress - drug therapy- diet - hormonal changes- climate

- 90% is S. epidermidis; S. aureus, may be inmoist areas

NORMAL FLORA




BENEFICIAL EFFECTS - prevent colonization by pathogens by competing for

attachment sites or for essential nutrients. This isthought to be their most important beneficial effect

- synthesize and excrete vitamins in excess of their ownneeds, which can be absorbed as nutrients by their host- eg) enteric bacteria secrete Vitamin K and Vitamin

B12, and lactic acid bacteria produce certain B-vitamins

- may antagonize other bacteria through the production ofsubstances which inhibit or kill nonindigenous species.

- stimulate the development of certain tissues like thecaecum and Peyer's patches in the GI tract

- stimulate the production of natural antibodies. Low levelsof antibodies produced against components of the normalflora are known to cross react with certain relatedpathogens, and thereby prevent infection or invasion

NORMAL FLORA




HARMFUL EFFECTS- Bacterial synergism (cross-feeding) between a member

of the normal flora and a potential pathogen. This meansthat one organism is helping another to grow or survive

- Competition for nutrients. Normal flora in thegastrointestinal tract must absorb some of the host'snutrients for their own needs

- Induction of a low grade toxemia. Minute amounts ofbacterial toxins (e.g. endotoxin) may be found in thecirculation and these small amounts of bacterial antigenstimulate the formation of natural antibodies.

- May be agents of disease. Members of the normal floramay cause endogenous disease if they reach a site ortissue where they cannot be restricted or tolerated by thehost defenses

- Transfer to susceptible hosts. Some pathogens of

humans that are members of the normal flora may also

NORMAL FLORA




SKIN- majority of skin microorganisms

are found in the most superficiallayers of the epidermis and the

upper parts of the hair follicles.- Important bacteria:• Staphylococcus epidermidis• Staphylococcus aureus•

Micrococcus sp.• Propionibacterium acne• Mycobacterium smegmatis

- Non-bacteria: Pityrosporum(yeast), Demodex spp. (mites)

NORMAL FLORA




CONJUCTIVA

- Important bacteria:• Staphylococcus epidermidis

• Neisseria sp.• Corynebacterium sp.• Propoinibacterium acnes• Staphylococcus aureus• Viridans streptococci• Haemophilus influenza




EXTERNAL EAR

- Important bacteria:• Staphylococcus epidermidis

• Staphylococcus aureus• Corynebacterium sp




ORAL CAVITY - Important bacteria:

• Staphylococci epidermidis• Streptococcus sanguis (dental plaque)• Streptococcus mutans (dental plaque)• Streptococcus salivarius• Staphylococci aureus• Viridans streptococci• Lactobacilli• Corynebacterium sp.• Bacteroides sp.• Actinomyces sp.




RESPIRATORY TRACT:NARES (nostrils)

- Important bacteria:• Staphylococcus epidermidis• Staphylococcus aureus• Neisseria sp.

• Haemophilus sp• Corynebacteria• Streptococcus pneumoniae




RESPIRATORY TRACT:URT (nasopharynx)

- Important bacteria:• Staphylococcus epidermidis• Non-hemolytic streptococci• Alpha-hemolytic streptococci• Neisseria sp.• Streptococcus pneumoniae• Streptococcus pyogenes• Haemophilus influenzae• Neisseria meningitidis




RESPIRATORYTRACT: LRT (trachea, bronchi,

and pulmonary tissues): - usually sterile- individual may become

susceptible to infection by

pathogens descending fromthe nasopharynx like:• H. influenzae• S. pneumoniae




UROGENITAL TRACT:ANTERIOR URETHRA

- Important bacteria:• Staphylococcus epidermidis• Enterococcus faecalis• Apha-hemolytic streptococci.• Some enteric bacteria (e.g. E. coli, Proteus sp.)• Corynebacteria sp.• Acinetobacter sp.• Mycoplasma sp.• Candida sp.• Mycobacterium smegmatis




UROGENITAL TRACT:VAGINA

- Important bacteria:• Lactobacillus acidophilus• Staphylococci• Corynebacterium sp.• Nonpyogenic streptococci• Escherichia coli• Flavobacterium sp.• Clostridium sp.• Viridans streptococci• Other Enterobacteria




GASTROINTESTINAL TRACT:SMALL INTESTINE

- Important bacteria:• Lactobacilli• Enterococcus faecalis• Coliforms• Bacteroides

- At birth, the entire intestinal tract is sterile, but bacteriaenter with the first feed. The initial colonizing bacteriavary with the food source of the infant.




GASTROINTESTINAL TRACT:COLON

- Important bacteria:• Enterococci• Clostridia• Lactobacilli• Bacteroides• Bifidobacterium (account for >90% in breast-fed infants)• Escherichia coli• Methanogenic bacteria• Viridans streptococci• Staphylococcus sp.• Proteus sp.• Candida albicans (Yeast)• Mycoplama sp.

STAPHYLOCOCCI &



STAPHYLOCOCCI &CORYNEBACTERIA

occur at almost every site,skin, conjunctiva, nose,

pharynx, mouth, lower GIT,anterior urethra, vagina

STAPHYLOCOCCUSEPIDERMIDIS

is highly adapted to thediverse environments of itshuman host

STAPHYLOCOCCUS AUREUSis a potential pathogenit is a leading cause ofbacterial disease in humansit can be transmitted from thenasal membranes of anasymptomatic carrier to asusceptible host


Staphylococcus epidermidis

Many of the normal flora are



Many of the normal flora areeither pathogens oropportunistic pathogens. Thefollowing indicate members of

the normal flora that may beconsidered major pathogensof humans:STAPHYLOCOCCUSAUREUS

STREPTOCOCCUSMUTANSENTEROCOCCUSFAECALISSTREPTOCOCCUSPNEUMONIAESTREPTOCOCCUSPYOGENESNEISSERIA MENINGITIDISESCHERICHIA COLIPSEUDOMONASAERUGINOSA

STREPTOCOCCUS MUTANS



STREPTOCOCCUS MUTANSis the primary bacteriuminvolved in plaque formationand initiation of dental caries

viewed as an opportunisticinfection

ENTEROCOCCUS FAECALISwas formerly classified asStreptococcus faecalishas emerged as a significant,antibiotic-resistant,nosocomial pathogen.

Streptococcus mutans

Enterococcus faecalis

STREPTOCOCCUS



STREPTOCOCCUSPNEUMONIAE

is present in the upperrespiratory tract of about half

the populationif it invades the lowerrespiratory tract, it can causepneumoniacauses 95%of all bacterial

pneumonia

STREPTOCOCCUSPYOGENESrefers to the Group A, Beta-hemolytic streptococcicause tonsillitis (strep throat),pneumonia, endocarditissome can lead to rheumaticfever or nephritis which can

Streptococcus pneumoniae

Streptococcus pyogenes

NEISSERIA AND OTHER



GRAM-NEGATIVE COCCIare frequent inhabitants of theupper respiratory tract, mainly

the pharynxNeisseria meningitidis is animportant cause of bacterialmeningitis

PSEUDOMONASAERUGINOSAis the quintessentialopportunistic pathogen ofhumans that can invadevirtually any tissueit is a leading cause ofhospital-acquired(nosocomial) Gram-negativeinfections, but its source is

Neisseria sp

Pseudomonas aeroginosa

ESCHERICHIA COLI



is a consistent resident of thesmall intestineother enteric bacteria that may

reside in SI includesKlebsiella, Enterobacter andCitrobactersome strains of E. coli arepathogens that cause

intestinal infections, urinarytract infections and neonatalmeningitis.

HAEMOPHILUS INFLUENZAEis a frequent secondaryinvader to viral influenzathe leading cause ofmeningitis in infants andchildren until the recentdevelopment of the Hflu type

Escherichia coli

Haemophilus influenzae

BACTEROIDES



in the lower intestinal tractarethe Bacteroides, a group ofGram-negative, anaerobic,

non-sporeforming bacteriaThey have been implicated inthe initiation colitis and coloncancer

LACTOBACILLIcontribute to acid formation inthe oral cavity that leads todental caries

LACTOBACILLUSACIDOPHILUScolonizes the vaginal

epithelium during child-bearing years and establishesthe low pH that inhibits the

Bacteroides fragilis

Lactobacillus acidophilus

BIFIDOBACTERIA



are Gram (+), non-sporeforming, lactic acidbacteria. They have been

described as "friendly"bacteria in the intestine ofhumans

BIFIDOBACTERIUM BIFIDUM

is the predominant bacterialspecies in the intestine ofbreast-fed infants, where itpresumably preventscolonization by potentialpathogens. These bacteria aresometimes used in themanufacture of yogurts andare frequently incorporatedinto probiotics.

Bifidobacterium bifidum

CLOSTRIDIUM



PERFRINGENScolonize the bowelcommonly isolated from feces

CLOSTRIDIUM DIFFICILEmay colonize the bowel andcause "antibiotic-induceddiarrhea" or

pseudomembranous colitis

CLOSTRIDIUM TETANI"transiently associated" withhumans as a component ofthe normal floracan be isolated from feces in0 - 25 percent of thepopulationthe endospores are probablyingested with food and water,and the bacterium does not

Clostridium perfringens

Clostridium tetani

CORYNEBACTERIA, AND



CERTAIN RELATEDPROPIONIC ACID BACTERIA

are consistent skin flora

some have been implicated asa cause of acne

CORYNEBACTERIUMDIPHTHERIAEcausative agent of diphtheriaconsidered a member of thenormal flora before thewidespread use of thediphtheria toxoid, which isused to immunize against thedisease.

Propionibacterium acneCorynecbacterium

diphtheriae



PROPHYLAXIS

PROPHYLAXISDEFINITION



IMMUNIZATION• administration of an individual with

antibodies possessing power to destroy orinactivate the disease producing agent orneutralize its toxin

• ULTIMATE GOAL: eradication of the disease• IMMEDIATE GOAL: prevention of the

disease in an individual

PROPHYLAXISIMMUNIZATION



TWO TYPES OF IMMUNIZATION

1. ACTIVE IMMUNIZATION2.

PASSIVE IMMUNIZATION




ACTIVE IMMUNIZATION• involves the administration of all or part of a

microorganism (Ag) or a modified product ofthat microorganism to evoke an immunologicresponse that mimics the natural infection,but this infection usually presents with littleor no risk to the recipient.

• some immunizing agent may producelifelong protection and some only providepartial protection, thus, must be re-administered at regular intervals to maintainprotection.




PASSIVE IMMUNIZATION• administration of exogenously produced or

preformed antibody (Ig)

• provides temporary protection• Artificial Ig: tetanus, measles, chicken pox,

rabies, rubella• Natural Ig: through transplacentaltransmission of antibody to a fetus providing

protection against many infectious diseasesfor the first 3-6 months of the infant's life.




TYPES OF VACCINES

1. Inactivated or killed vaccines2. Attenuated or live vaccines3. Subunit vaccines4. Toxoids

5. Conjugate vaccines6. Recombinant vaccines7. DNA vaccines




1. INACTIVATED/KILLEDVACCINES

• these are usually inactivated or purified components

of virus and bacteria or those that are conjugatedchemically to be immunobiologically active proteins.• not capable of replicating in the host• must contain a sufficient antigenic mass to stimulate

a desired response• may require periodic administration of boosterdoses for maintenance of long lasting immunity

• immune response is mostly humoral or antibody-mediated




2. ATTENUATED/LIVEVACCINES

• this are attenuated or weakened form of the wild

virus or bacteria that induce an immunologicresponse simulating the response to naturalinfection.

• produces the active infection by viral replicationhowever, these produces little or no adversereaction to the host.

• these organisms multiply in the recipient until thedesired immune response occurs conferringlifelong protection with a single immunizing dose.




3. SUBUNIT VACCINE

• are fragment of inactivated or attenuatedmicroorganism to create an immune response

• eg) meningococcal, pneumococcal




4. CONJUGATE VACCINE

• combining or linking of the polysaccharide outercoats (which are poorly immunogenic) ofmicroorganism with proteins (like toxins) tobecome highly immunogenic.

• eg) Hib , pneumococcal (Prevnar)




5. RECOMBINANT VACCINE

• combining the physiology of one microorganismand the DNA of other microorganism

• eg) Hepatitis B, Human Papilloma (Gardasil,Cervarix)




6. TOXOID

• are chemically or thermally modified toxins torender them non-toxic but still immunogenic

• eg) diphtheria, tetanus




7. DNA VACCINE

• created from an infectious agents DNA• it works by insertion (and expressiom, triggering

immune system recognition) into human or animalcells, of viral or bacterial DNA

• still experimental

PROPHYLAXISSITE & ROUTE OF ADMINISTRATION



1. ORAL2. INTRAMUSCULAR

3. SUBCUTANEOUS4. INTRADERMAL

5. INTRANASAL




1. PER OREM• most common• eg) OPV, rotavirus

2. INTRAMUSCULAR• based on volume and size of the muscle• ANTEROLATERAL ASPECT of the THIGH: < 1

year of age

• DELTOID AREA: older children and adults• BUTTOCKS: rarely used• eg) DTP, Hepatitis B vaccines




3. SUBCUTANEOUS• 45˚ angle into the anterolateral aspect of thethigh or upper outer triceps• eg) Measles, MMR

4. INTRADERMAL• Volar aspect of the forearm• eg) Rabies (pre-exposure) and BCG

5. INTRANASAL• Upright position, 0.25 mL is sprayed into one

nostril, the 2nd half is administered to the othernostril.

• e Live attenuated influenza vaccine

PROPHYLAXISCONTRAINDICATIONS



ABSOLUTE RELATIVE NOT • Severe anaphylactic

reaction or allergicreaction to previousvaccine

• Encephalopathywithin 7 days ofadministration(Pertussis)

• Immunosuppressivetherapy

• Egg allergy

• Seizure within 3 daysof last dose (Pertussis)

• Shock within 48 hrs oflast dose

• Fever >/+ 40.5 Cwithin 48 hours of lastdose

• Mild illness with or withoutlow grade fever

• Current antibiotic therapy

• Recent infectious disease

• Positive PPD

• Prematurity, except in infantsstill hospitalized at 2 mos,

OPV should be delayed untildischarge. OR, if mother isHBsAg (-), Hep B vaccinedelayed until child >2000gm

PROPHYLAXISSCHEDULE



EXPANDED IMMUNIZATIONPROGRAM (EPI)Main Objectives:

To reduce the morbidity and mortality rates of

the seven EPI diseases which are: Poliomyelitis,Measles, Diphtheria, Pertussis, Tetanus,Tuberculosis, Hepatitis B

To reduce the incidence of neonatal tetanus byproviding pregnant women with tetanus toxoidimmunization

PROPHYLAXISEXPANDED IMMUNIZATION PROGRAM



VACCINE AGE INTERVAL AMOUNT SITE/ROUTE BOOSTER

BCG1 dose

At birth If >2 months-do PPD 1 st before givingBCG

NB: 0.05 ml>1mo: 0.1 ml

ID at deltoidarea

DPT3 doses

6 weeks 4 weeks 0.5ml IM atanterolateral

thigh

1 st- 1 yr after thelast dose

2nd

- 4-6 y/o OPV3 doses

6 weeks 4 weeks 0.5 ml mouth 1 st- 1 yr after thelast dose2nd- 4-6 y/o

HEPA B3 doses

At birth 1-2 monthsand 6-8 mos

0.5ml IM atanterolateralthigh

HEPA B3 doses

MEASLES1 dose

6 months / 9 months

0.5 ml SQ, thigh MMR 1 st-6 moafter measles2nd-4- 6 y/o or11-14 y/o

PROPHYLAXIS VACCINE



BACILLE CALMETTE GUERIN (BCG)

BCG vaccines are live vaccine from attenuated strains ofMycobacterium bovis

the WHO recommends that all children in countries with highincidence of TB infection should be immunized with a singledose of BCG at or soon after birth.does not prevent infection with pulmonary TB but preventsextra-pulmonary manifestations of tuberculosis (Military TB,TB meningitis)protection from PTB: 65%protection from Extra-pulmonary TB: 85%

PROPHYLAXIS VACCINE



BACILLE CALMETTE GUERIN (BCG)AGE/

INTERVAL AMOUNT SITE/ROUTE BOOSTER ADVERSE REACTION

single dose givenat birth:

<1month: 0.05cc

> 1 month:0.1cc

at 2nd month ofage: do PPD 1 st

newborn:0.05 ml

>1month:0.1 ml

intradermal at deltoidarea

none Koch’s phenomenon:accelerated BCGreaction

Indolent ulcers:ulceration of morethan 3 weekssubcutaneousabscess &lymphadenopathyosteomyelitis &muscle necrosisuncommonly (1-2%)result in local adversereactions

PROPHYLAXIS VACCINE



BACILLE CALMETTE GUERIN (BCG)NATURAL COURSE:

Wheal formation: disappears after 30 minutes of

injectionInduration: occurs after 2-3 weeks of injectionPustule formation: after 2-3 weeks of indurationUlceration: after 2-3 weeks of pustule formationScar formation: after 8-12 weeks after injection

PROPHYLAXIS VACCINE



DIPHTHERIA, PERTUSSIS &TETANUS (DPT)

is a combination vaccine composed of a diphtheria,

pertussis and tetanus components.

Inactivated vaccine

PROPHYLAXIS VACCINE



DIPHTHERIA, PERTUSSIS &TETANUS (DPT)

AGE/ INTERVAL

AMOUNT SITE/ROUTE

BOOSTER ADVERSE REACTION

3 doses given asearly as 6 weeksold at 4 weeksapart

0.5 cc IM 2 doses:1st:1 year afterthe last dose

2nd:4-6 yearsold

Local & febrile reactionsBacterial or sterileabscesses at the site ofinjectionAllergic reactionsSeizuresHypotonichyporesponsiveepisodes (HHE)“collapse” or “ shocklikestate”

Fever of 40.5°CIncessant crying

PROPHYLAXIS VACCINE



POLIO VACCINE (OPV/IPV)

The Live Oral Polio Vaccine (OPV)composed of an attenuated poliovirus types 1, 2 and 3derived from monkey kidney cell cultures

contains trace quantities of streptomycin & neomycin.3 doses confers a sustained, probably lifelong immunity.

The Inactivated Polio Vaccine (IPV)contains 3 types of poliovirus types 1, 2 and 3derived from monkey kidney or human diploid cellsinactivated with formaldehydehas trace amounts of streptomycin, neomycin & polymyxin B.lifelong immunity.inhibits pharyngeal acquisition of poliovirus & has a lesser extent ofintestinal acquisition of the virus.

PROPHYLAXIS VACCINE



POLIO VACCINE (OPV/IPV)

AGE/ INTERVAL

AMOUNT SITE/ROUTE


3 doses given asearly as 6 weeksold at 4 weeksapart

IPV:0.5 cc

OPV:2 drops

IPV:IM

OPV:PO

2 doses:1st:1 year afterthe last dose

2nd:4-6 yearsold

IPV:hypersensitivityreaction

OPV:vaccine-associatedparalytic polio(VAPP)



PROPHYLAXIS VACCINE



MEASLESAGE/

INTERVAL AMOUNT SITE/ROUT

E BOOSTER ADVERSE REACTION

3 doses:1st:6-12 months old

2nd:6 months afterthe first dose3rd:4-6 years old

0.5 cc SC none Fever after 5-7 daysfrom the time of injectionLocal swelling or pain

from site of injectionRashes

PASSIVE IMMUNIZATION with measles immunoglobulin ispreferred in susceptible and immuno-compromised patients

Give immunoglobulin within 6 days after exposureDose: 0.25cc/kg , IM or IVIG at a dose of 100-400 mg/kg

PROPHYLAXIS VACCINE



HEPATITIS B VACCINE

Killed/ inactivated vaccine

WHO recommendation that in any country whosecarrier rate is >2% should immunize their infantsagainst Hepa B at birth

Routine Pre-Exposure Immunization

All infants at or soon after birth (0-2 months)All children by 11-12 years of ageOlder persons in certain high-risk groups

PROPHYLAXIS VACCINE



HEPATITIS B VACCINE

AGE/ INTERVAL

AMOUNT SITE/ROUTE


3 doses: (0-1-6

mo)1st:at birth2nd:1 month after 1 st dose

3rd:6 months after1st dose

0.5 cc IM none Pain at the injection site

Fever (>37.7°C)Allergic reactions

PROPHYLAXIS VACCINE



HAEMOPHILUS INFLUENZAE TYPEB (Hib)Inactivated vaccine

The WHO now recommends that Hib vaccine shouldbe included as appropriate to national capacities andpriorities in routine infant immunization because

Haemophilus influenzae remains to be the mostcommon cause of meningitis in the first year of life.

PROPHYLAXIS VACCINE



HAEMOPHILUS INFLUENZAE TYPEB (Hib)AGE/



3 doses given asearly as 2months old, at 2months apart:

If first given at 6months old, 2doses is enough

If first given at 1year old, singledose is enough>5 years old, nolonger advisable

0.5 cc IM Singledose at 1year ofage

Pain at the injection site

PROPHYLAXIS VACCINE



VARICELLA VACCINE

The AAP and PPS recommends the universalimmunization for all healthy infants 12 months oldand susceptible older children and adolescents of

varicella vaccine

The recommendation for the post-exposureprophylaxis administration of varicella vaccine tosusceptible children is within 72 hours to 120 hoursafter exposure to prevent or significantly modify thedisease.

PROPHYLAXIS VACCINE



VARICELLA VACCINEAGE/



3 doses:1st:1 year old2nd:4-6 years old3rd:13 years old

If first given at>13 years old, 2doses is givenat 1 monthinterval

0.5 cc SC or IM none Pain at the injection site

PROPHYLAXIS VACCINE



TYPHOID VACCINE

The WHO recommends the administration of typhoidvaccine to those people living in endemic areas. Inthe Philippines the recommended age of

administration is 2 years old given intramuscularly.

AGE/ INTERVAL

AMOUNT SITE/ROUTE


single dose givenat 2 years ofage

0.5 cc IM single doseat 2-3 yearsof age

Pain at the injectionsite

PROPHYLAXIS VACCINE



PNEUMOCOCCAL VACCINE

Types:1. 23-Valent Polysaccharide vaccine which is given

in children 2 years and older2. 7- valent conjugate polysaccharide vaccine

which could be given in infants as early as 2months old.

These vaccines are associated with the reduction innasopharyngeal carriage with vaccine-typeorganisms but does not however, prevent theoccurrence of Otitis Media.



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