Infectious Process Lecture Notes PDF

INFECTIOUS PROCESS  INFECTIOUS PROCESS = the ensemble of pathophysiological and clinical phenomena, arising from the conflict between the microorganism and the human body.  INFECTION = all biological changes which are triggered in the human body at the penetretion...

INFECTIOUS PROCESS  INFECTIOUS PROCESS = the ensemble of pathophysiological and clinical phenomena, arising from the conflict between the microorganism and the human body.  INFECTION = all biological changes which are triggered in the human body at the penetretion of the infectious agent.  An important character of infection is specific etiologically (a specific infectious agent causes a particular infectious disease).  THE BASIC MECHANISMS OF INFECTIOUS PROCESS  The infection is achieved by the antagonistic combined actions of two factors:  A. THE PATHOGENICITY FACTORS OF BACTERIA  B. THE RESISTANCE FACTORS OF THE INFECTED BODY  A. THE PATHOGENICITY FACTORS OF BACTERIA  Pathogenicity = the ability of bacteria to cause a disease.  It is expressed by: virulence and toxingenesys of bacteria.  A.1. VIRULENCE  Definition - The ability of bacteria to penetrate, to adapt, to multiply, to invade and to determines specific lesions to tissues on which has tropism (microbial invasion).  Virulence is achieved by:  - corpuscular factors,  - enzyme factors.  A.1.1. Corpuscular virulence factors  They are related to certain elements of bacterial cell structure; these elements confer to bacteria protection against the means of defense of the human body and favors penetration into tissues of bacteria.  A.1.1.1. Capsule  Has anti-phagocytic effect (the inhibition of bacteria incorporating by phagocytes), favoring invasion of the microbe in tissues.  Acts against local antibodies and other bactericidal substances.  Examples of encapsulated bacteria:  - Pneumococcus  - Klebsiella pneumoniae  - Some strains of staphylococci and streptococci  A.1.1.2. Components of the bacterial cell wall  They are located in the superficial layers of bacteria and, they have an anti- phagocytic role.  Examples:  - M protein - Streptococcus β-hemolytic group A  - parietal virulence factor - Staphylococcus aureus  - cord factor - Koch bacillus  - factor of attachment to the intestinal mucous - pathogenic E. coli and Shigella  - Vi antigen (coating antigen) - in some strains of Salmonella typhi.  A.1.1.3. Mobility  Mobile bacteria are more virulent than other non-mobile bacteria.  Mobility can be achieved by:  - Movements of corkscrew of the cell body: special mobility of leptospires (spirili) which enters in the body through intact skin and mucous.  - Cilia (flagella), an attribute of species.  A.1.1.4. Fimbriae  Fimbriae have a role in germs attachment on receptors of susceptible cell surface from the entrance gate.  They are:  I. common pili (adhesion pili) which allow high adhesion to epithelia cells:  - P fimbriae – strains of E. coli associated with pyelonephritis  - S fimbriae – strains of E. coli involved in meningitis  - K88 and K89 fimbriae – enterotoxigenic strains of E. coli that produce malignant diarrhea in new-born  II. Non-adhesions pili:  - Glycocalyx  - Microcapsule - It is a virulence factor (Neisseria gonorrhea).  - Some substances from the human body with property of adhesion to mucosal surfaces = fibronectin, a plasma glycoprotein found in extracellular space. Some bacteria that enter in the human body adhere to fibronectine and, through it, to the surface of epithelial cells. Such microorganism are: Streptococcus pyogenes, Staphylococcus aureus.  A.1.2. Enzymatic virulence factors (exoenzyme)  They are substances produced by infecting bacteria and removed outside, which determines:  - local tissue changes,  - dissemination of bacteria in the body, step by step,  - invasion of tissues beyond the gate.  A.1.2.1. Coagulase - secreted by pathogenic staphylococci.  A.1.2.2. Fibrinolysin – secreted by pathogenic staphylococci.  A.1.2.3. Hyaluronidases - secreted by Staphylococcus aureus, Streptococcus β-hemolytic group A  A.1.2.4. Hydrolytic enzymes - collagenases, lecitinases, neuramidases, lipases, proteases, nucleases.  A.1.2.5. Cytolytic enzymes - Hemolysins and leukocidins – Ex. β-hemolytic streptolysin of group A streptococcus (streptolysin O and streptolysin S).  A.2. Toxinogenesys  It is the ability of bacteria to develop toxins = soluble substances with toxic effects on infected body tissues.  These toxins are divided into: exotoxins and endotoxins.  I. EXOTOXINS  They are toxic substances released by bacteria (Gram positive) living in the environment of the germ, in culture medium or in the infected body.  1. Physico-chemical properties  - They are thermostabile holoproteins.  - They can transform by aging and under the action of formalin (4%0) in efficient vaccines, toxoids, anatoxins, which are non toxic products with preserved immunogenicity.  They are sensitive to radiation and pH variations.  A toxoid is a bacterial toxin (usually an exotoxin) whose toxicity has been inactivated or suppressed either by chemical (formalin) or heat treatment, while other properties, typically immunogenicity, are maintained.  2. Biological properties  Toxicity - Toxic effects:  - appear after a latency period  - the toxic power is high  - the minimum lethal dose is small.  Selective tropism for certain areas is clearly distinguishable:  - tropism for skin tissue: exotoxin of coal bacillus;  - tropism for the respiratory mucous: diphtheria toxin.  Antigenicity  - have a high antigenic specificity  - are highly immunogenic  - are neutralized by specific antibodies  II. ENDOTOXINS  They are toxic products present in Gram-negative bacilli, part of their structure and that are freed only after death (lysis) of these bacteria.  Endotoxin is lipopolysaccharide (LPS) of the outer membrane of the cell wall of these bacteria and plays an important role in the pathogenesis of infections caused by these microorganisms.  1. Physico-chemical properties  They are heteroproteins (complex proteins), most are carbohydrate- lipid-polypeptide complex.  They are soluble, but not broadcast in the environment of the germ (emitted at the same time of the bacterial cell lysis).  They:  - are thermostable;  - are resistant to treatment with alcohol;  - do not turn into toxoids under the action of formalin.  2. Biological properties  Toxicity - Endotoxin toxicity is lower compared with the exotoxins. - The minimum lethal dose is high. - The toxic effects appear without latency period.  They have a more diffuse tropism, toxic manifestations are varied:  - hemodynamic disorders – from the level of the capillaries and arterioles up to peripheral collapse;  - changes in white blood cell counts (leukopenia);  - hyperglycemic effect  - activation of B lymphocytes with increased production of antibodies.  Antigenicity  - are less immunogenic than exotoxins  - can not be neutralized by specific antibodies  B. THE HOST DEFENSE AGAINST INFECTION  The resistance in the infected organism is:  - Non specific, natural, innate resistance - is common to all individuals of a species;  - Specific, acquired (anti-infective immunity) resistance - develops throughout life, due to continuous contamination with different infectious agents.  B.1. NON SPECIFIC (NATURAL, INNATE) RESISTANCE  It is a resistance state to certain infectious agents with which all individuals of a species are equipped.  Each species is:  - Resistant to certain infections and  - Susceptible to other.  Thus, the human is the only species which naturally gets syphilis, scarlet fever, gonorrhea. Animals are naturally resistant (lack of specific cellular receptors for the infectious agent).  Non specific defense factors can be divided into:  - skin and mucosal barriers  - febrile reaction  - internal factors: humoral and cellular  B.1.1. SKIN AND MUCOSAL BARRIERS  They are effective in prevention of penetration microbes into the organism.  They are:  - Mechanical barriers  - Chemical barriers  - Biological barriers  B.1.1.1. Mechanical barriers  Skin and mucosal integrity are barriers.  Integrity is the most important barrier against bacterial penetration beyond the gate.  This integrity is ensured by:  - horny layers of epidermis  - epithelium cilia movement in upper airway, mechanical removal of bacteria by natural mucus secretions (saliva, sputum, nasopharyngeal secretions)  - intestinal peristalsis.  B.1.1.2. Chemical barriers  - the low pH of the skin surface (pH 5-6), provided by long molecule fatty acids from sebaceous secretion (group A streptococci, diphtheria bacilli);  - lysozyme, existing in saliva, tear secretion, nasopharyngeal secretion, cervical mucus, prostatic fluid; it is a protein with lysis effect on bacteria through carbohydrate components dissolution of bacterial cell wall;  - hydrochloric acid from the gastric juice (pH = 2) has strong bactericidal effect on all the germs which enter with food;  - the acidic pH of the vagina, resulting from glycogen metabolism by lactic bacilli, it is also an effective means of defense against microbes.  B.1.1.3. BIOLOGICAL BARRIERS  These are represented by the commensal flora on skin and mucous membranes.  The coexistence in the same ecosystem of different species, bacterial strains and variants, as association with other agents (fungi, parasites, viruses) is strongly marked by the relationship of bacterial antagonism, which provides effective biological protection, especially in the upper respiratory tract, intestine, skin, vagina.  Example: Lactobacillus species in the vagina, normally maintain an acid pH, unfavorable for development of other bacteria.  B.1.2. FEBRILE REACTION  It comes as a rule with a bacterial infection.  It involves a disturbance of the mechanisms of thermoregulation system (central and peripheral), with the predominance of thermogenesis.  Thermoregulating centres in the hypothalamus will be excited by different pyrogenic factors as:  Gram-negative bacteria endotoxins: lipopolysaccharide from the cell wall of these bacteria acts on macrophages that will secrete endogenous pyrogens: interleukin-1 (IL-1), tumour necrosis factor (TNF-alpha);  other "endogenous pyrogens" secreted by: macrophages, monocytes, granulocytes due to the action of other bacteria, viruses, hormones, steroids, T lymphocytes, circulating immune complexes.  Febrile reaction, in terms of nonspecific anti-infective defence, ensures mobilization of resources to fight by:  - metabolic activation  - activating blood circulation.  A temperature of 38.5°-39°C increase the destruction of infectious agents by increasing the production of immunoglobulin and phagocytosis activation.  But prolonged fever may be associated with unfavorable effects:  - increased cardiac activity in a patient with compromised cardiovascular function  - seizures  - metabolic changes can lead to dehydration and electrolyte loss  - increased susceptibility to the effects of microbial toxins  B.1.3. INTERNAL FACTORS OF NONSPECIFIC DEFENCE  If the pathogenic bacteria have overcome mucosal or skin barriers, their diffusion is normally prevented by intercellular conjunctive tissue.  Sometimes, however, it may be destroyed by certain proteolytic bacterial enzymes: proteinases, fibrinolizynes, collagenases, streptokinases.  Internal factors of nonspecific defence are classified into two categories:  - humoral factors,  - cellular factors.  B.1.3.1. HUMORAL FACTORS  Lysozyme – a mucopeptidase which hydrolyses the peptidoglycan links from the bacteria cell wall, making them sensitive to osmotic lysis.  Opsonins – they are substances that adhere to the surface of a microorganism making it accessible to phagocytosis.  There are:  - specific opsonins (IgG antibodies involved in acquired anti-infective defence)  - non-specific opsonins (C3b, fibronectin).  Complement system (C’)  Complement is a complex component of normal plasma.  It consists of about 25 plasma proteins (“components") which in turn activates one another in a given order (“cascading activation").  These components are produced:  - mostly by the liver  - the macrophages - are the second major producer.  A limited synthesis of some of these factors can be done in: intestinal cells and fibroblasts.  There are 2 ways to activate the complement, with different starting points, but converging to the same end products:  common (classical) pathway – is activated by complexes antibody- antigen  alternative pathway - is activated directly by bacteria and bacterial products  The biological role of complement  Cytolysis – cells that have fixed C9, and are physologically foreign to body cells (bacteria) are lysed by the action of membrane attack complex.  Opsonization - phagocytes have on the surface receptors for C3b, so the microbes phagocytosis will be done more efficiently.  Trrigering inflammation – activation of C9 determines onset of inflammatory reaction by the intermediate products resulted during activation.  ex. - C5a is a powerful chemotactic and chemokinetic factor for polymorphonuclears (PMN) that will bring in the outbreak of infection.  Interactions with other physiological processes: coagulation, fibrinolysis and kinin system.  B.1.3.2. CELLULAR FACTORS  They are represented by:  - Phagocytosis  - Inflammation  B.1.3.2.1. PHAGOCYTOSIS  Is the cellular defence response in the body.  It consist of a mechanism for removal of microorganisms and damaged cells by embedding them by certain cells in the human body (phagocytes) specialized for this function.  These cells migrate to the place of entrance of bacteria in the body. They include and destroy them, by phagolysosomes.  The location of infection is clinically manifested by symptoms of inflammation: rubor (redness), tumor (swelling), calor (heat), dolor (pain) and functio laesa (loss of function).  TYPES OF CELLS WITH PHAGOCYTIC PROPERTIES (PHAGOCYTES)  They are able to migrate directly to the place of foreign particles.  Their migration into tissues is favoured by chemotactic substances: C5a, C5b and other factors produced during inflammation.  They are called professional phagocytes, but there are also unprofessional phagocytes: fibroblast, endothelial and reticular cells.  In phagocytosis are involved two main categories of cells:  - microphages  - macrophages  I. MICROPHAGES  - neutrophil granulocytes - They are “kamikaze“ cells of anti-infective defense system because they arrive first at the place of the injury.  - eosinophil granulocytes – take part in anti-parasitic defense in special.  - basophil granulocytes  II. MACROPHAGES  They can be: - mobile – are present in blood (monocytes) - fixed, but easily movable – are part of reticular- endothelial system (the phagocyte mononuclear system)  Examples:  - macrophages in the spleen and lymph nodes;  - Kuppffer cells of liver;  - histiocytes of connective tissue;  - some neuroglial cells.  Note: Some microorganisms (Mycobacterium, Listeria, Brucella and Toxoplasmosis) survive and multiply in macrophages. In this case, macrophages protect these microorganisms, serving as a factor for dissemination of infection.  STEPS OF PHAGOCYTOSIS  These steps are:  - chemotaxis (the movement of microorganism in response to a chemical stimulus)  - adsorption of particles on the phagocyte  - particle ingestion in the phagocyte  - intracellular digestion  Chemotaxis  It is a unidirectional mobilization, produced by the polymorphonuclear cells (PMN) to the place where they release chemotactic factors.  These factors include:  - Factors of bacterial origin  - Factors of host organism, occurring during inflammation: - C5a, - Kallikreins produced by damaged tissues,  - Prostaglandins (E2, D2),  -Thromboxanes, - Leukotrienes (B4), - Vasoactive amines, - Fragments of collagen, - Fibrin.  Under the influence of these factors, chemotactic phagocytes leave capillaries by diapedesis (the passage through intact walls of the capillaries into the tissues).  Adsorption (attachment) of particles on the phagocyte surface  The phagocyte surface attachment may be:  - Random – depends on chance of collision between phagocytes and particles,  - Directed – phagocytes migrate towards bacteria or other particles due to chemotaxis.  Normally, to allow attachment to phagocyte, the bacterial cell surface should be amended and the preparation for phagocytosis is called OPSONIZATION.  Opsonization can be achieved by:  - Specific mechanisms – involving participation of antibodies resulting from a IgG immune-response that binds the phagocytes by Fc fragment, making a bridge between surface of antigens of bacteria (Fab) and the receiver from phagocyte.  - Nonspecific mechanisms : C reactive protein, C3b.  Ingestion (integrating) of particles in the phagocyte  After attachment, the particles are embedded in a vacuole, consisting of a cytoplasm membrane by issuing pseudopodia.  After embedding the particle, the phagocyte vesicle moves to the cell (ingestion) = phagosome.  Digestion  The vacuole formed (phagosome) will merge with lysosomes (grouped around the vacuole) resulting phagolysosomes.  Forming phagolysosomes is a process accompanied by the disappearance of intracytoplasm grains (degranulation).  The lysis of granules will determine the release of lysosomal enzymes – which are various substances with microbicidal action that will trigger digestion.  In the same time there is a strong activation of PMN oxidative metabolism.  Destruction of microbes will be produced through two mechanisms:  - O2 – dependent mechanisms  - O2 – independent mechanisms  - O2 - dependent mechanisms  Sudden intensification of metabolism (8respiratory burst9) leads to the formation of compounds such as: oxygen atoms (O¯ ), hydroxyl radicals, peroxide hydrogen – which have strong bactericidal effect.  - O2 – independent mechanisms involved in killing the microorganisms, are due to enzymes: hydrolytic enzymes, defensins, lysosome, lactoferrin.  In PMN the complete degradation of the microorganisms is produced.  In macrophages – phagocyte particle are partially and incomplete degraded, antigens being then presented to the immune system.  B.1.3.2.2. INFLAMMATION  It is a natural process of anti-infection defense.  It consists of an overall clinical and pathophysiological process of nonspecific cellular defense, triggered by different agents, especially infectious, but also irritants, like chemical substances, heat and mechanical damage.  The result is an accumulation of a large number of phagocyte cells at the inflammation place.  Inflammation is a fast anti-infectious defense mechanism, which tends to localize the infection and prevent its dissemination.  Clinical signs of inflammation are:  - erythema (rubor),  - heat (calor)  - edema (tumor)  - pain (dolor)  - functional impotence of the region (functio laesa).  Inflammation may progress towards:  - healing restitutio ad integrum (restoration to original condition) of the tissue  - healing with sequelae  The outcome of an inflammatory reaction depends on:  - the extension of the inflammatory process  - the microorganisms involved  - the host reactivity  STEPS OF INFLAMMATION (PHYSIOPATHOLOGY ASPECTS) - local capillary vasodilatation - leucocytes attraction (chemoattraction) - leukocyte diapedesis  a.Local capillary vasodilatation  Local blood vessel dilatation causes a decrease in blood flow, which is accompanied by a increase in local capillary permeability thus causing edema.  b. Leukocytes attraction (chemoattraction)  Chemoattraction is represented by the attraction between leukocytes and interstitial space.  The first cells which arrive in the damaged tissue are PMN (polymorphonuclear) due to their high capacity of migration; then the reticular-endothelial system cells and lymphocytes which have the main role in initiating the immune responses.  All these cells are endowed with a large capacity of reception of chemotactic stimuli, which are mainly represented by:  - chemotactic bacterial factors,  - factors produced from the activation of the C (complement),  - those resulting from degranulation of the mast cells.  The most important factors ensuring inflammation are:  - vasoactive amines (histamine type),  - serotonin,  - some proteolysis enzyme: lysosome enzymes,  - some fraction of the complement system (C3a, C5a) called anaphylatoxins,  - interleukin-1 (IL-1) and interleukin-8 (IL-8) = monokines secreted by macrophages.  Under the pressure of these factors, PMN will leave capillary by diapedesis and will go to the inflammatory outbreak.  c. Leucocyte diapedesis  It is the process by which phagocyte slip among vascular endothelial cells and pass into the interstitial space.  This movement of cells into the interstitial space is achieved by a multistage mechanism:  - rolling,  - marginalization – adhesion,  - crossing by issuing pseudopodia.  In the process of phagocytes crossing through the vascular endothelial cells, adhesion molecules get involved as part of three families:  - selectin (L,E,P)  - integrin  - immunoglobulin superfamily  Adhesion molecules are structures expressed on the surface of leukocytes and endothelial cells allowing, through mutual interactions, the attach of leukocytes on capillary endothelium with increasing force, facilitating finally diapedesis.   ORAL MICROFLORA  The oral cavity has many surfaces and every surface encompasses a wide diverse microflora.  Oral cavity being the entry gate for the gastrointestinal tract provides a habitat for various microbial species inside the oral cavity such as bacteria, fungi, protozoa and few viruses.  Bacteria being the most predominant species, is significant in causing diseases.  Members of this microflora are participants in common oral cavity diseases like caries and periodontitis.  Factors such as saliva, food intake, developing dentition and antibiotics also affect them.  There are certain locations in the oral cavity such as gingival crevice which provide habitat for anaerobic species to survive.  Factors which affects the growth of microorganisms in the oral cavity are:  - Temperature  - Anaerobiosis  - pH  - Nutrients  - Host defences  - Host genetics  - Antimicrobial agents and inhibitors  Classification of bacteria based on Gram’s staining  Gram positive:  - Cocci: Abiotrophia, Peptostreptococcus, Streptococcus, Stomatococcus  - Bacilli: Actinomyces, Bifidobacterium, Corynebacterium, Lactobacillus, Propionibacterium, Pseudoramibacter, Rothia  Gram negative:  - Cocci: Moraxella, Neisseria, Veillonella  - Bacilli: Campylobacter, Capnocytophaga, Desulfobacter, Desulfovibrio, Eubacterium, Eikenella, Fusobacterium, Haemophilus, Leptotrichia  Few examples of anaerobic bacteria that are present in the oral cavity are: Bifidobacterium, Lactobacillus, Actinomyces, Propionibacterium, Treponema, Veillonella, Arachnia, Bacteroides, Eubacterium, Fusobacterium, Leptotrichia, Peptococcus, Peptostreptococcus, Selenomonas species.  Streptococcus salivarius are the first group of bacterial species to colonize as soon as infants acquire new microflora, these microorganisms colonise on the tooth surface and gums followed by colonization of Streptococcus sanguinis and Streptococcus mutans. Species other than these adhere to the soft tissues, but not the teeth.  Sites where oral microbiota is in abundance are the interproximal areas and the gingival crevices.  Pits and fissures are sites of largest microbial communities.  These large number of microorganisms produce various metabolites which leads to dental diseases like dental caries, gingivitis and periodontitis if not prevented by oral hygiene practices such as tooth brushing and flossing.   MICROFLORA OF INFANTS  Infants have a sterile oral cavity, but later they are colonized with microbes through milk, saliva and external environment.  The oral cavity of infants is highly selective and only few microorganisms are in common with the microbes of adult flora.  As soon as microflora develops in the oral cavity of infants, lactobacilli and candida are first to colonise.  Predominant species in the infants are streptococci: S. mitis, S. oralis and S. salivarius. STAPHYLOCOCCUS  1. MORPHOLOGICAL CHARACTERS  Staphylococci are Gram positive cocci, spherical, arranged in clusters, as grape-like clusters, non-spore forming and some strains are capsulated.  2. CULTURAL CHARACTERS  On liquid medium we can see turbidity by growing of bacterium.  On blood agar the colonies are round, 1-3 mm in diameter, convex, smooth, opaque.  They are differently pigmented:  - Staphylococcus aureus - golden colonies, Staphylococcus albus  - Staphylococcus epidermidis (S. albus) - white colonies  - Staphylococcus citrinus (S. saprophyticus) - lemon yellow colonies. Staphylococcus citrinus  The colonies of pathogenic strains can have β-hemolysis on blood agar medium.  Staphylococcus aureus can produce a special type of hemolysis called warm-cold: at 37°C the hemolysis is α and after keeping the plate in the fridge at 4°C it turns into β-hemolysis.  3. METABOLIC CHARACTERS  Aerobic staphylococci are: - non-pretentious, with minimal nutritional needs for growing - producers of catalase - which can decompose the hydrogen peroxide (H2O2) into water and oxygen gas.  4. ANTIGENIC CHARACTERS  There are three types of staphylococcal antigens:  - A and B specific polysaccharides – they are antigens linked to the cell wall  - protein A - is a surface protein of Staphylococcus aureus which binds IgG molecules by their Fc region  - the capsular antigen – present in capsulated strains correlated with virulence (have anti-phagocytosis properties)  5. PATHOGENICITY CHARACTERS  I. VIRULENCE  - CORPUSCULAR FACTORS – the capsule of mucous strains with anti- phagocyte role  - EXOENZYMES  - coagulase  - fibrinolysin  - hyaluronidase  - nucleases (DN-ase and RN-ase)  - lipase  - beta-lactamase (penicillinase)  II. TOXINOGENESYS  Staphylococcal toxins are:  - hemolysins  - leukocidines  - enterotoxin  - exfoliatin  - 8toxic shock syndrome9 toxin  6. CLINICAL FEATURES  Suppurated skin lesions – over 95% of all skin infections:  - Furuncle – purulent collection with a single crater and carbuncle - aggregation of infected furuncles.  - impetigo – are suppurated superficial face injuries, especially in children, around mouth  - intertrigo - are suppurated lesions in the interdigital folds and they are facilitated by moisture.  - sycosis – is an inflammation of hair follicles, especially on the beard area in men.  - whitlow – purulent collection in the nail and phalanx  - hidradenitis suppurativa – are suppurated lesions most common on the underarms and groin zones.  - scalded skin syndrome – in new-borns and infants it is manifested by redness and secondary exfoliation scales of the superficial epidermis  - acne – infection localized on the face  - erythematous pultaceous angina – appearing as white dots on red background pharynx, tonsillitis, mucosa  - enteritis  - septicemia – appear usually on a low resistance medium, from a localized staphylococcal lesion.  - osteomyelitis – the infection appears in long bones (metaphysis).  STAPHYLOCOCCUS AUREUS is a presumed pathogen for many oral diseases, such as:  - oral mucositis (OM) – is painful inflammation and ulceration of the mucous membranes lining the digestive tract anywhere from mouth to rectum. OM manifests as erythema, inflammation, ulceration and hemorrhage in the mouth and throat.  - periodontitis - is a serious infection of the gums who actually are pulling away from teeth, bones are deteriorating, and teeth loosening and potentially falling out.  - peri-implantitis - is a destructive inflammatory process affecting the soft and hard tissues surrounding dental implants. STREPTOCOCCUS  1. MORPHOLOGICAL CHARACTERS  On Gram stained smears appear as Gram positive (purple) cocci, spherical, placed in chains, non-spore forming, capsulated.  2. CULTURAL CHARACTERS  - On liquid medium – turbidity and granular deposit at the bottom of the test tube.  Typically, the colonies of Streptococcus pyogenes after 18-24 hours incubation on blood agar are about 0.5 mm in diameter, convex, with a smooth surface and an entire edge; they are surrounded by a complete zone of beta hemolysis.  3. METABOLIC CHARACTERS  - they are aerobic germs, but today frequently strains of anaerobic streptococci are isolated (Peptostreptococcus)  - the aerobic ones do not contain catalases and oxidases  - β-hemolityc streptococci do not lyse in bile, do not ferment inulin – which are metabolic characters that allow differentiation from pneumococcus  4. ANTIGENIC CHARACTERS  Group A β-hemolytic streptococcus have many antigens like:  - carbohydrate antigen – gives group specificity,  - capsular antigen – is a virulence factor through the anti-phagocyte protection of the germ,  - M antigen (protein MAP – 8M-associated-protein9) – is the most important antigenic and pathogenic factor for group A β-hemolytic streptococcus and it is on fimbriae,  - T and R antigens – are not virulence factors,  - glycerol – teichoic antigen – located deeper in the cell wall,  - deep nucleoprotein antigen (P antigen) - located in the bacterial cell nucleotides.  5. PATHOGENICITY CHARACTERS  I. VIRULENCE  A. CORPUSCULAR FACTORS – both hyaluronic acid of 8mucous9 strains and M protein present in the virulent strains, have a strong anti-phagocytic action.  B. ENZYME FACTORS  - streptokinase (fibrinolysin)  - hyaluronidase  - diphosphopyridine nucleotidase  - DN-ase (streptodornase)  II. TOXIN PRODUCTION  - hemolysins – streptolysin O and S – are responsible for beta-hemolysis of streptococci.  - erythrogenic toxin (erythrotoxin) – produced by the strains which can lead to scarlet fever.  6. CLINICAL FEATURES  A. ACUTE INFECTIONS  A.1. SUPPURATIVE  - streptococcal pharyngitis (group A Streptococcus) = is an infection of the back of the throat including the tonsils ,  - conjunctivitis,  - meningitis,  - bacterial pneumonia,  - endocarditis.  A.2. NON SUPPURATIVE  - Scarlet fever - A disease caused by a strain of streptococcus which produces an erythrogenic toxin.  The signs and symptoms - sore throat, fever, headaches, swollen lymph nodes and a characteristic rash. The rash is red and feels like sandpaper and the tongue may be red and bumpy.  It most commonly affects children between five and fifteen years of age.  The rash is the most striking sign of scarlet fever. It usually appears first on the neck and the face (often leaving a clear, unaffected area around the mouth). It looks like a bad sunburn with tiny bumps and it may itch.  B. Post-streptococcal complications  Acute proliferative glomerulonephritis – appears after infection with strains of streptococcus and are evolving clinical with albuminuria and haematuria. It is a disorder of the glomeruli (glomerulonephritis) or the small blood vessels in the kidneys.  Rheumatic fever (acute rheumatic fever) - is a inflammatory disease that can involve the heart, joints, skin and brain.  The disease typically can develops after two or four weeks of a streptococcal throat infection.  Signs and symptoms: fever, multiple painful joints, involuntary muscle movements and occasionally a characteristic non-itchy rash known as erythema marginatum. STREPTOCOCCUS VIRIDANS  Viridans group streptococci (VGS) comprises streptococci that are normal human colonizers.  Rarely can cause infections in immunocompetent individuals, although they can be pathogenic in the right patient host.  The major groups of VGS are Streptococcus mutans, S. salivarius, S. anginosus, S. mitis, S. sanguinis and S. bovis.  Antimicrobial resistance can vary, with the S. mitis group harboring the highest resistance rates.  Viridans streptococci play an important role by inhibiting the colonization of many pathogens, including pyogenic streptococci. This is achieved by two different mechanisms:  - production of bacteriocins  - production of hydrogen peroxide (also responsible for α- hemolysis).  1. MORPHOLOGICAL CHARACTERS  Viridans streptococci are Gram-positive cocci, spherical, arranged in chains.  2. CULTURAL CHARACTERS  Viridans streptococci form small colonies (0.1-0.5 mm in diameter), convex, gray, usually alpha- hemolytic producing a green coloration on blood agar plates, occasionally non-hemolytic.  3. METABOLIC CHARACTERS  - They do not express catalase and so are catalase-negative.  - They are leucine aminopeptidase positive, pyrrolidonylarylamidase negative and do not grow in 6.5% NaCl and almost all species are negative for growth on bile esculin agar.  They differ from pneumococci in that they are optochin resistant and are not bile soluble.  4. CLINICAL FEATURES  Viridans streptococci are normal inhabitants of mucous membrane-lined cavities of the animals and humans.  They form part of the normal flora of the upper respiratory tract, all the regions of the gastrointestinal tract, the female genital tract and are most commonly found in the oral cavity.  Streptococcus mitis and S. salivarius are associated with the tongue;  S. mitis and S. sanguinis are associated with the buccal mucosa;  S. mutans is common in all dental structures;  S. sanguinis, S. mitis and S. oralis are associated with early dental plaque,  while S. gordonii is associated with mature dental plaque.  S. anginosus is found in subgingival plaque.  The role of S. mutans in dental caries has been firmly established.  Because these microorganisms colonize the mouth in such high numbers, implication as the cause of respiratory tract infection is confirmed only when isolated from percutaneously aspirated specimens.  Dental infections, including dental caries, abscesses and periodontal disease, often are due to viridans streptococci, most commonly S. mutans and the S. anginosus microorganisms. Infections usually are polymicrobial, but viridans streptococci sometimes are isolated as sole pathogens.  Viridans streptococci are a rare cause of meningitis.  Can cause pyogenic infections, including brain abscess and localized intra-abdominal infections, such as hepatic and subphrenic abscesses. Microorganisms of the S. anginosus group account for most such infections, reflecting their proclivity for causing localized pyogenic infections, frequently in association with other microorganisms.  Pneumonia, empyema, sinusitis and otitis media occasionally are ascribed to viridans streptococci.  Viridans streptococci cause 30–40% of all cases of endocarditis.  S. sanguinis, S. bovis, S. mutans and S. mitis are most associated with endocarditis.  This is made possible by the transient bacteremia resulting from dental extractions and dental procedures.  S. mitis and S. oralis are increasingly recognized as causes of often fatal septicemias in immunocompromised patients. ENTEROCOCCUS  1. MORPHOLOGICAL CHARACTERS  Enterococci cells are Gram-positive with an ovoid shape.  They usually occur in pairs or in chains of different lengths.  Enterococci form neither spores nor capsules, but some species may be capable of movement by the flagellum. These motile species are Enterococcus casseliflavus and Enterococcus gallinarum.  2. CULTURAL CHARACTERS  The colonies are milky white when grown on usual agar plates, but some species produce carotenoid pigments which color them yellow.  Among these yellow colored enterococci are E. sulfureus, E. casseliflavus and E. mundtii. The colonies of Enterococcus faecalis, blood agar, 24 hours cultivation, 37°C  3. METABOLIC CHARACTERS  A rapid biochemical test can rapidly identify colonies of enterococci within minutes based on the ability of almost all enterococcal species to hydrolyze pyrrolidonyl-beta- naphthylamide (PYR).  As all enterococci produce leucine aminopeptidase, this test is used on some rapid streptococcal identification panels.  Other older tests that are used less frequently include the bile- esculin test, growth on broth containing 6.5% NaCl and ability to grow at both 10⁰C and 45⁰C.  For identification of newer species of enterococci, a combination of conventional biochemical tests and evaluation of DNA content is needed.  4. CLINICAL FEATURES  Enterococci are part of the normal intestinal flora.  They used to be classified as group D streptococci but are now considered a separate genus.  There are > 17 species, but E. faecalis and E. faecium most commonly cause infections in humans. Enterococci typically cause:  URINARY TRACT INFECTIONS - are the most common infection caused by enterococci and are often associated with urinary catheters.  Lower urinary tract infections (such as cystitis, prostatitis, and epididymitis) are frequently seen in older men.  However, enterococci are exceedingly uncommon as a cause of uncomplicated cystitis in young women.  Enterococcal urinary tract infections are more likely to be acquired in hospital or long-term care settings, and thus, are more likely to be resistant to many antibiotics.  BACTEREMIA AND ENDOCARDITIS  In the last few years, the source of a bacteremia is usually the genitourinary tract, although a bacteremia also often arises from intra- abdominal or biliary sources, indwelling central lines, or soft tissue infections.  Enterococci are found as a component of polymicrobial bacteremia more often than other microorganisms.  Enterococci cause between 5 to 15% of cases of infectious endocarditis, and this rate has not changed over several decades.  Intra-abdominal and pelvic infections  Skin, soft tissue, and wound infections  Other infections less commonly or rarely seen due to enterococci include meningitis, hematogenous osteomyelitis, septic arthritis, and pneumonia. Streptococcus pneumoniae   1. MORPHOLOGICAL CHARACTERS  They are Gram positive cocci, shaped like a candle flame (elongated cocci), non-spore forming, in diplo with a single capsule, arranged in short chains.  They have a capsule (of polysaccharide nature) which appears in ordinary colorations as a colorless clear halo around the pair of cocci.  They are immobile.  2. CULTURAL CHARACTERS  - on liquid medium they have at the beginning, a high rate of growth and reproduction, causing so the turbidity of medium and after several hours we can see the germs autolysis.  - on blood agar (solid medium) – small colonies, round, shiny, with alpha hemolysis area around (large greenish area of incomplete hemolysis).  3. METABOLIC CHARACTERS  A. INULIN FERMENTATION  The pneumococci can do the fermentation of inulin, which is a sugar.  The medium containing inulin is inoculated with the pneumococcal culture.  In the positive reaction the medium will become yellow.  B. OPTOCHIN TEST  Pneumococci are sensitive to optochin, as opposed to viridans streptococci, which are resistant.  The test is performed by placing an optochin disk in the middle of the inoculated area.  The positive test means sensitivity to the compound and is viewed as a round inhibition area around the optochin disk (minimal diameter is 20 mm).  C. BILE SOLUBILITY TEST  Streptococcus pneumoniae is lysed by bile salts whereas all other alpha-hemolytic streptococci are resistant.  The bile solubility test is performed by adding 0.5 ml of 2% sodium deoxycholate (bile salts) in one tube with liquid culture of the suspect streptococci, keeping another tube as control.  4. ANTIGENIC CHARACTERS  Pneumococci can have capsular antigens and somatic antigens.  A. Capsular antigens (SSS – 8Specific Soluble Substance9) – they are polysaccharide linked to the bacterial capsule and are used for describe more than 80 pneumococcal serotypes, among which, for pneumococci isolated in humans, types 1,2,3 have the highest importance.  B. Somatic antigens – linked to the microbial body:  - M antigen  - R antigen  - Pneumococcal C antigen  5. PATHOGENICITY CHARACTERS  5.1. VIRULENCE  It was established that the virulence of pneumococci is directly correlated with the presence of capsular antigens, which have anti-phagocyte protective role, allowing microbial invasion in the body.  We can establish a close relationship between the size of the pneumococci capsule and the virulence of germs.  Ex. – type 3 of pneumococcus with a larger capsule diameter is more virulent in humans and mice.  5.2. TOXINOGENESYS  - pneumolysin – toxin with hemolytic effect.  - the purpura-producing principle – injected in rabbits causes bleeding into dermis and internal organs.  - leukocidines – destruction of leukocytes and anti-phagocyte effect.  - necrotising factors.  6. CLINICAL FEATURES  - Lobar pneumonia - is a form of pneumonia which affects a large and continuous area of the lobe of a lung. Onset is sudden with high fever, cough, general malaise. During this state, the patient can have - cough, dyspnea (hard to breath), rusty sputum. Recovery time is from a few days to 1 - 2 weeks.  - Bronchopneumonia – the lesion includes several areas of the lung. The disease appears in children, elderly or people with poor resistance state.  Other pneumococcal infections:  - sepsis  - meningitis  - sinusitis  - middle otitis  - septic arthritis  - osteomyelitis  - peritonitis  - endocarditis