Erysipelas.docx

Lecture: Erysipelas -

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Is a super ficial cutaneous disease -> to dermis Have lymphatic involvement Distinguished by other forms of skin inf by 2 features:  Elevation on level of surrounding skin  Have clear line of demarcation of uninvolved tissue > common in infants, young child, & older adult In our hospital (Moscow) ->older adult By β-hemolytic streptococci In most cases, inf agent is in group A β- hemolytic streptococci Can be also caused by group C & G Rarely group B & Staphylococcus aureus Was described involved the “ Butterfly area of face” Have in lower extremities ( > freq) In pt with facial erysipelas have history of streptococci sore throat & mode of its transmission to skin is still unknown. (ophthal & antrum) Incl. surgical incision, trauma / incision & kin dis / psoriasis & local fungal inf. (> freq) Cutaneous lesion has localized erythema & swelling with changed red margin that raised & well demarcated from a normal young zone. < yaziki flamani> - demarcation zone is not level Have marked edema often with _________ formation & erysipelas have swollen eyes Can demonstrated ___________ Cutaneous manifestation have chill, fever & intoxication

Basic clinical principles: -

From stable high case rate, charac. of all region of the country, tendency to go to clinical chronic course Evaluation of clinical course o disease with ↑ of dis. With hemorrhagic erysipelas with longer fever & slowdown of reparation in the locus of an inflame The special place with contagious__________, hereditary determinant reaction of organism of pt with streptococcus group A. Onset of ___________ intra & extracellular factor of virulence (will be late)

Provoking factors: 1. Disturbances of integrity of integument as fracture, lesion, change T’ ,sharp trauma etc 2. Emotional stress & insolation & ↓ T’ 3. Trauma of field / bruises with erysipelas ( Intercurrent dis angina, bronchitis etc.)

Contribution factors: 1. Concommitant diseases: - DM, obesity, chronic venous failure (varicose dis of veins), chronic failure of absorbent vessels (lymphostasis), eczema, psoriasis & other skin diseases (mycosis of the auto- podium) 2. Presence of the locuses of chronic streptococci inf contamination (tonsillitis, otitis, sinusitis, karies, paradontitis) -> lead to oftenly to erysipelas of the foot, osteomyelitis, trophic ulcer etc. 3. Profesion trauma (bone trauma) with increasing of contamination of integument with________ (sportsman,drivers etc) 4. Chronic somatopathy with immunodeficiency (in advance ages) 5. End stage of pathogeny of erysipelas

Clinical classification of Erysipelas (V.I Cherkasov; 1986) 1. On character of aboriginal exhibiting : -

Erythematic Erythematic – bullous Erythematic – hemorrhagic Bullous – hemorrhagic

2. On a degree of gravity : Mild (I), Moderate (II), Severe (III) 3. On frequency rate of course: -

Primary Repeated (arising in 2 years, other localization of process) Relapsing (at presence not less than 3 relapses of an erysipelas for a year expediently determining “often relasing erysipelas” )

4. On prevalence of aboriginal exhibiting: -

Localized erysipelas Abundance erysipelas Metastatic erysipelas with the advent of remote from each other the locuses of an inflammation

5. Complications of an erysipelas: a) Aboriginal (an abscess, phlegmon, necrosis,phlebitis,periadenitis etc.) b) Common (a sepsis, toxic shock,thomboemboli of pulmonary arteries etc.) 6. Consequences erysipelas: a) Resistant lymphostasis (lymphatic edema) b) Secondary elephantitis (fibredema)

Features of pathogens of dev of erysipelas: -

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Making up of the resistant locus of a streptococcal infection contamination in an organism of the patient ( L-form ):  A derma  Lymph nodes  Bone marrow (osteal brain) Depression of functional condition status of neutrophil Fluctuation of a level of cellular & humoral immunodefense The high level of an allergization (cell- mediated type IV hypersensitivity to group A β – hemolytic streptococci.

Localization of the locus of an inflammation : -

Lower extremities : 60 -80% Face : 15 -25% Upper extremities: 5 -8 % Other localization (perineum,trunk etc): 1 -3%

Pathogenesis of Erysipelas: -

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Introduction of a streptococcus in a skin as a result of its damage (at a primary erysipelas) or by a becoming infected from the locus of a dosing infection contamination can descend & is immediate from the locus of independent disease of a streptococcal etiology (a pharyngitis, sinusitis, otitis etc.) Breeding of streptococcus in lymphatic capillary vessel dermas Development bacteriemia, toxemias, that leads to originating symptoms to an intoxication (the acute beginning of disease from rise in temperature, a cold fit,delicacy etc) Development of the aboriginal locus of an infectious – allergic inflammation of a skin with participation of immune- complex process (are formed perivascular) the located cell – bound immune complexes containing C-3 fraction of a complement). Disturbance capillary flows of lymph in a skin & microcirculation with formation of a lymphostasis, possible formation of hemorrhages & bladders with serous & hemorrhagic contents. Formation of the locuses of a chronic streptococcal infection contamination in a skin & partial lymphonduses with presence of bacterial & L –forms of a streptococcu that leads at a part of patients in development of relapse of disease (chronic course of erysipelas) Elimination of bacterial forms of a streptococcus by means of an engulment & formation of cellbound immune complexes both other immune mechanism & convalescence of the patient.

Indications for obligatory hospitalization in infectious diseases hospitals (abjointings) are: -

Serious current of an erysipelas with sharply expressed intoxication or the widespread lesion of a skin (especially at bullous – hemorrhagic to the form of an erysipelas) Frequent relapses of an erysipelas, irrespective of a degree of an intoxication, character of aboriginal process Presence of serious general concomitant diseases Senile children’s age of patients

Incubation period:-

From several hour till 3 – 5 days. At patients with relapsing course of the erysipelas, development of the next attack of disease is preceded often with a frigorism, stress. At the depressing majority o patients disease begins was acutely.

The initial stage of disease:-

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Is characterized by fast development of signs of an intoxication which more than at half of patients (it is usual at localization of an erysipelas on the lower extremities) for the term of from several hours till 1 -2 daysadvance originating aboriginal exhibiting of disease. The headache, the general delicacy, a cold fit, muscular pains is marked, 25 – 30% of patients have nausea & a vomiting. At the 1st hourof disease the temperature increase upto 38 – 40 ‘ C. On fields of a skin in the field of the future local exhibiting at of some patients are felt parasthesia, sense strutting or burning sensations, not intensive. Quite often there are alo pains in the field of enlarged partial lymph nodes.

The height of disease:-

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Comes in terms from several hours till 1- 2 days after the first exhibiting disease. Reach the maximum general – toxic exhibiting & a fever. There are characteristic aboriginal exhibiting an erysipelas. More often inflammatory process is localized on the lower extremities (60 -70%), less often on the face (20 -30%) and the top extremities ( 4 -7%), is rare only on a trunk, in the field of mammary gland, perineum, outside of reproductive organs. From the beginning of the treatment and uncomplicated character of an erysipelas the fever usually does not exceed 5 day. At 10 -15% of patients the fever is keptover 7days that is observed usually at the widespread process & not enough a high grade causal treatment. The longest feverish period at bullous – hemorrhagic to the erysipelas. From above, 70% that sizk of erysipelas, it is marked a lymphadenitis educing at all forms of disease.

The period of reconvalescence:-

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Normalization of temperature & decreasing of intoxication are observed at an erysipelas earlier, than the previous ly shown Acute presentation of disease are kept till 5 -8 days at hemorrhagic forms till 12 -18 day and more. To the residual phenomena of an erysipelas kept during several weeks & months, concern pastose and xanthopathy, a stagnant hyperemia on a place of the quenched erythema, dense dry crusted on a place of bullas, a hydropic syndrome. The kept enlarged & morbid lymph nodes, infiltrates of a skin in the field of the quenched locus of an inflammation, subfebrile temperature have unfavourable prognostic value ( probability of development of early relapse). Prognostically unfavourable also long conservation of a lymphatic edema (lymphostasis) which should be surveyed as an early stage (lymphatic edema) a secondary elephantitis. The hyperpigmentation of fields of a skin on the lower extremities at the patients, who have tolerated bullous – hemorrhagic an erysipelas, can be kept for life.

Diagnostic criteria of an erysipelas: (are based only on a characteristic clinical pattern of disease, laboratory methods of diagnostics are not used) -

The acute beginning of disease with the expressed igns of an intoxication Primary localization aboriginal inflame process on the lower extremities and the face Development of typical aboriginal exhibiting with a characteristic erythema, possible aboriginal hemorrhagic syndrome Development partial a lymphadenitis Absence of the expressed pains in the locus of an inflammation in rest

*Infectious – allergic and immunocomplex mechanisms of the inflammation at the erysipelas cause its serous- hemorrhagic character. Apposition of a purulent inflame testifies to the complicated disease.

Differential diagnosis: -

erysipelas should be compared with more than with 5 -10 diseases, concerning clinical features of surgical, dermal and contagious and intrinsic diseases. First of all,we need t exclude abscess, phlegmon, supurative hematom, thrombophlebitis (phlebitis), dermatitis,eczema, surrounding erysipeloid, a nodulose erythema.

Treatment of an erysipelas: (I)

Etiological treatment:

Treatment in hospital ; - a preparation of choice – is Benzylpenicilin daily dose 6 -12 million U, IM for 10 days - reserve preparation is cephalosporin I generation (Cefazolinum etc.) – in a daily dose 1,2 – 2,4 g and more,IM) are appointed at the serious omplicated course of erysipelas - In the serious course of disease, development of complications (an abscess, phlegmon etc) the combination Benzylpenicillin (in the specified dosage) & gentamycin (240 mg – once daily,IM). - Penicillin (in the specified dosage) & ciprofloxacin (400 – 800 mg IV drip) - Penicillin & clindamycin (in specified dosages) - Purpose of the combined antibacterial therapy is justified & at bullous hemorrhage of erysipelas with an abundant exudates of fibrin. Treatment for out-patient; - Give one of the drugs(antibiotics) below perorally: o Spiramycin 3 million ME 2x/d for 10 days o Azithromycin- in 1st day 0,5 g, then within 4 days on 0,25g 1x/d for 0,5g for 5 days o Roxithromycin - 0,15 g 2x/day for 10 days o Ciprofloxacin – 0,5g 2-3x/day for 10 days o Cefaclor 0,5 g 3x/day for 10 days o Use new Quinolones (Levofloxacin, gatifloxacin, moxifloxacin) are also possible

(II) -

(III)

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(IV) -

Pathogenetic treatment: Disintoxication therapy (if necessary IV) , with use of diuretic & cardiovascular preparations Anti inflammatory therapy (Indomethacin, Butadionum, Aspirinum etc) – precaution to DM pt Desensitization therapy (under indication) – anti allergic (Suprastin etc)

Local therapy:

Apply bandages with 0,02% furosilinum / 0,1% solution of Rivanolum, shanging them sometimes within day (erythematic erysipelas carrying out of aboriginal therapy is not required)

Physiotherapy: Use ultraviolet radiation on range of the locus of an inflammation & an electric current of ultrahigh frequency on range regional lymph nodes Conservation in the period of a reconvalescence of an infiltration of a skin, hydropic syndrome, regional a lymphadenitis are appointed an ozocerite or a bandage with warm taftaleneum ointment (to the lower extremities), paraffin (on the face), electrophoresis of lydasum

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(especially in initial stages of formation of an elephantitis), sodium chloridum of calcium, radon baths, a magneto therapy Last year high efficacy low-energy laserotherapy in treatment of an thermal inflammatory syndrome is established at varius clinical forms of an erysipelas. Laser radiance,as in red, and in infra-red range is used.

Anti recurrent therapy: (I)

Consecutive 2- course antibioticotherapy

(It is desirable in a hospital at developing an acute episode of disease) 1st course: -

Benzylpenicillin daily 6 -12 million U, IM for 10 days Cephalosporin (I) generation (Cefazolin in a daily dose of 3 -6 g IM for 10 days

2nd course: -

Lincomycin (30% a solution -2,0 ml – 3x /day, IM) or 0,5g 3x/day perorally for 7 – 10 days

(II)

Bicillinum prophylaxis (outside of an acute episode of disease)

After the tolerated primary, recurring or repeated erysipelas -

Bicilinum 5 -1,5 million U or Benzathine benzylpenicillin (Retarpen, Extenvilline) 2,4 million U, in/m once in 2 -3 weeks( the drug is appointed after careful finding out of the anamnesis excluding had survivability of Peniccilinum)

Variant Continuous In season

Course

Indications Frequent (not less than 3 for last year) relapses of an erysipelas Distinctly expressed seasonal prevalence of relapses Preserving significant residual the phenomenon in the season of a reconvalescence at the patients which have tolerated a relapsing, repeated or primary erysipelas

Course Till 2nd year and more The beginning 1 month prior to a season of relapse, within 3 -4 months Within 3 -6 months after an extact frm hospital

Prophylaxis of relapse it is necessary (it is our patient or in specialized abjointings) 1. The well-timed and high grade antibiotic therapies of primary disease and relapses 2. Treatment of the expressed residual phenome (the erosion, kept puffiness in the field of the aboriginal focus), consequences of an arysipelas (a non perishable lymphostasis an elephantitis) 3. Treatment is long and persistently proceeding chronic diseases the skins leading disturbances of its trophicity and appearance of entrance hiluses for an infection contamination 4. Treatment of the locuses of a chronic streptococcal infection contamination (chronic tonsillitis, sinusitis, otitis etc) 5. Treatment of disturbances of a flow of lymph & a circulation in a skin as a result of primary and secondary lymphostasis and an elephantiasis, chronic diseases of peripheral vessels. 6. Treatment of an obesity, a diabetes mellitus (which frequent decompensation is observed in erysipelas)

Morphology of group Streptococci: -

Streptococci is a gram (+), catalae (-), non-motile, non-spore forming have in chains or in pairs of cells. Individual cells are round to avoid cocci; 0,6 – 1,0 micrometer in diameter. Streptococci divide in 1 plane and thus occur in pairs or (especially in liquid media or clinical material) in chains of varying lengths. The metabolism of Streptococci is fermentative Nutrition of bac needs complex media and it prefers supplemental blood for best grows. Homeofermentative lactic acid without production of gas at major end – product. Aerobic & anaerobic It doesn’t use oxygen metabolically

The classification of streptococci (The type of hemolytic reaction displayed on blood agar) 1. β –hemolytic Streptococci (assoc. with complete lysis of red cells surrounding the colony) 2. α – hemolytic Streptococci ( a partial or “green” hemolysis assoc. with ↓ of red cell Hb) 3. γ – hemolytic Streptococci (non-hemolytic colonies) -> no changes in blood agar - The cell wall of streptococci is composed of repeating unit of N – Acetylglucosamine (polysaccharide). Historically, the definitive identification f treptococci has rested on the serologic reactivity of . Polysaccharide antigens as originally described by Rebecca Lancefield (1930s). 20 groups- specific antigens (Lancefield goups) were established (A,B,C,D etc)

Classification of Streptococci Most commonly assoc woth human diseases Lance field group A (β –hemolytic)

Species Streptococcus pyogenes

B ( β & γ- hemolytic)

Streptococcus agalactiae

C (β- hemolytic)

Streptococcus equisimilis , dysgalactiae

Streptococcus bovis D (α & γ hemolytic)

G (α,β,γ hemolytic)

Streptococcus canis

Viridans streptococci (α,β,γ hemolytic)

Streptococcus pneumonia Streptococcus mutans, S. oralis, sanguis, gordonii, crista, salivarius, anginosus, vestibularis

Most common Human diseases Pharyngitis, skin infection, wound inf, pneumonia, post inf glomerulonephritis, rheumatic fever Neonatal septicaemia, meningitis, osteomyelitis, pneumonia Wound inf, puerperal septicaemia, cellulitis, endocarditis, epidemic pharyngitis, pyogenic arthritis Subacute endocarditis, bacteremia of hepatobiliary origin, malignant lesions of the colon Puerperal infection, skin &wound inf, endocarditis, pyogenic arthritis Pneumonia, otitis media, sinusitis, meningitis Endocarditis, septicaemia, dental infection inf (caries), intravascular catheter – related infection

Comparison of Early-Onset & Later-Onset Group B Streptococcal Infectious: Feature Age range Median age at onset Maternal obstrectic complications Frequency of gestation <37 weeks Usual clinical presentations

Common serotypes Mortality rate

Early onset < 7 days 1 hour Common

Late-onset 7 to 89 days 27 days Uncommon

Very late onset  3 months Unknown Varies

Frequency (30%)

Uncommon

Common

Septicaemia (35 - 55%) Meningitis (5-10%) Resp dis (pneumonia) (35-55%) I (Ia,Ib,Ia/c), II, III, V 5 – 70%

Meningitis (25 – 35%) Bacteremia without focus (40-60%) Osteoarhtitis (5%) III ( 75%) 2 -6 %

Bacteremia without focus (common) Bacteremia with a focus (occasional) Unknown Low

Streptococcus Group D infections 1. Echocardiography - Transthoracic / transesophageal (> sensitive), echocardiography frequently permits visualization of vegetations. 2. Liver ultrasonography & CT scanning - Usually liver US is performed 1st, followed by CT scanning 3. Barium enema (detecting malignant lesions in the colon) - Barium enema should be performed on patients with S. bovis bacteremia or endocarditis - The only alternative to a barium enema is a colonoscopy

Cell surface stucture of Streptococcus pyogenes & secreted products involved in virulence:

Group A Streptococcal M-Types ( >120) often associated ith nonsuppurative & toxin-mediated sequalae: Sequela Acute rheumatic fever Glomerulonephritis Postpharyngeal Postpyoderma Streptococcal toxic shock syndrome

M-Types 1, 3, 5,6, 18 1-4, 12, 15 49, 52, 55, 59, 60, 61 1, 3 predominantly; severa others

Mucosal immunity Against Group A Streptococci:

Factor of Virulence Group A streptococci (Streptococcus pyogenes) Components of a cellular wall A polysaccharide (group carbohydrate Ag or substance C) M- protein ( > 120)

Peptidoglycan

Lipoteichoic acid Hyaluronic acid capsule, fibronectin binding proteins Protein F1 Extracellular Products Streptococcal pyrogenic exotoxins (SpeA, SpeB, SpeC etc), SSA

Streptolysin O

Streptolysin S Hyaluronidase Streptokinase DNases A,B,C,D C5a / peptidase

Autoimmune reactions, formation of immune complexes, necrosis & a generation of collagenic fibres, a damage of lysosome macrophages Oppresion phagocytosis, autoimmune reactions (synovial membrane,skin, valve of heart, kidneys etc), formation of immune complexes factor of invasion, superantigen (invasion forms) Pyrogenic reactions, necrosis of tissue, activation of an internal way of hemostasis, activation kallikrein – kinin system Factors of adhesion, damage of platelets, erythrocytes Factors of adhesion Factors of invasion Pyrogenic reactions, superantigens (streptococcal toxic shock syndrome (Strep TSS), necrotizing fasciitis, and other severe infections), scarlatinal toxins (SpeA & SpeC) Autoimmune reactions damage the membranes of polymorphonuclear leukocytes, platelets, erythrocytes ad subcellular organelles, cardiotoxic action Cytotoxic action (polymorphonuclear leukocytes,platelets, erythrocytes) Damage of the basic substance of a connecting fabric, endothelium of vessels (spread thru tissues) Activation fibrinolysis, cytotoxic action (skin kidneys) Cytotoxic action Streptococcal inhibitor of complement (oppression pagocytosis, blocks migration of Polymorphonuclear leukocytes)

Summary of diseases caused by Streptococcus pyogenes:

1. Supurative conditions (active infections assoc with pus) occur in throat, skin and systemically Throat

Skin

Streptococcal pharyngitis is acquired by inhaling aerosols emitted by infected individuals. The symptoms reflect the inflammatory events at the ite of infection. A few (1- 3%) people develop rheumatic fever weeks after the infection has cleared Impetigo involves the infection of epidermal layer of skin. Pre-pubertal children are the most susceptible. Cellulitis occurs when the infection spreads subcutaneous tissues. Erysipelas is the infection of the dermis. About 5% of patients will develop more disseminated disease. Necrotizing fasciitis involves infection of the fascia &may proceed rapidly to underlying muscle.

2. Systemic Scarlet fever

Is caused by production of erythrogenic toxin by a few strains of the organism. 2 of the most severe, but least common, forms of invasive GAS disease are called “necrotizing fasciitis” and “streptococcal toxic shock syndrome” (STSS)

3. Non – supurative sequelae -

Some of the antibodies produced during the above infections cross-react with certain host tissues. These can indirectly damage host tissues even after the organisms have been cleared and cause non-supurative complications

Rheumatic fever Glomerulonephritis

M protein cross reacts with sarcolemma Antibodies cross reacts with heart tiua, fix complement and cause damage Antigen-Antibody complexes may be deposited in kidney, fix complement, and damage glomeruli. Only a few M-types are nephritogenic.

Impetigo: -

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Is an initially vesicular, later crusted, superficial inf of the skin.. Most cases occur in children. Histopathologically, impetigo consists of a superficial intra epidermal, unilocular vesicopustule. In epidemiological studies, group A streptococcal acquisition on normal skin antedates the appearances of impetigo by about 10 days. During that time,minor trauma (eg:insect bite,abrasion) predisposes to the development of infected lesions. Impetigo is most common during hot, humid summer weather. 2 -3 weeks after skin acquisition of streptococci, pharyngeal colonization by the same organism occurs in about 30% of children with skin lesions. The sporadic cases of the facial impetigo occur in colder climates probably result from contagious spread from an initial nasopharyngeal infection, and the serotypes involved are those commonly causing pharyngeal disease. In contrast, in the case of staphylococcal impetigo,(in case of only S. aureus is the pathogen), nasal colonization precedes that of the normal skin; skin lesions then occur after such colonization.

Classification of Bacterial superficial infections of the skin Type of lesion Impetigo Follicullitis Furuncles & carbuncles Paronychia Ecthyma

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Etiological agents Staphylococcus aureus, group A streptococci S. aureus, Candida, Pseudomonas aeruginosa, Pityrosporum ovale S. aureus S. aureus, group A streptococci, Candida, P. aeruginosa Group A streptococci

Erysipelas involves the more superficial layers of the skin & cutaneous lymphatic, whereas cellulitis extens more deeply into the subcutaneous tissues. This anatomical distinction is the basis for the clinical differentiation of the 2 entities. In typical erysipelas, the area of inflammation is raised above the surrounding skin, and there is a distinct demarcation between involved & normal skin. In cellulitis, neither of these clear distinction between infected nor not infected one is present.

Specific Anatomical Variant of Cellulitis & Cause Predispoition to the Condition Predisposing condition Periorbital cellulitis

Etiological agent Staphylococcus aureus, pneumococcus, group A streptococcus Bucal cellulitis Haemophilus influenza Perianal cellulitis Group A streptococcus Cellulitis complicating body piercing (ear, nose, S. aureus, group A streptococcus umbilicus) Mastectomy (with axillary – node dissection) for Non-group A hemolytic streptococcus breast cancer Harvest of saphenous vein for coronary bypass Group A or non- group A hemolytic streptococcus Liposuction (thigh, abdominal wall) Group A streptococcus, peptostreptococus Postoperative (very early) wound infection Group A streptococcus (abdomen, chest hip) Injection of drugs used (“skin popping”) – S. aureus, streptococci (groups A,C,F,G) extremities, neck Gas gangrene, crepitant cellulitis Clostridium perfringens and other clostridial species: Bacteroides,peptostreptococci, Klebsiella, E. coli

Necrotizing fasciitis: -

is an infection of the dermal of the dermal, fascial and subcutaneous layers of the skin it is characterized by microbial & leucocytic infiltrates leading to vasculitis, thrombosis and tissue necrosis the infection is commonly acute, fulminant process but may follow a subacute, progressive course. Necrosis may become widespread, with signs of systemic toxicity appearing unless the infection is treated in its earliest stages. Mortality rates upto 76% have been reported without early intervention.

Etiologic Agents of Necrotizing Fasciitis: Predisposing Condition None Diabetes mellitus

Prior surgery Immunosuppression & malignancy Arterioclerosis Odontogenic infection Varicella infection Streptococcal gangrene & necrotizing fasciitis

Etiological agent Group A streptococcus Bacteroides fragilis (other gram negative anaerobic bacilli), Enterobacteriaceae, Staphylococcus aureus, Streptococcus sp. Bacteroides sp. , Clostridium sp, Staphylococcus aureus, Group D streptococcus Pseudomonas aeruginosa, Enterobacteriaceae Streptococcus sp, Clostridium sp Prevotella sp, Porphyromonas sp, Fusobacterium sp Group A streptococcus Group A streptococci, mixed infections with Enterobacteriaceae & anaerobes

Definition of Streptococcal toxic shock-like syndrome: (I)

Isolation of GAS from:

A) a normally sterile site (eg: blood,CSF, pleural fluid or peritoneal fluid, tissue biopsy, surgical wound etc.) B) a non sterile site (eg: throat, sputum, vagina, superficial skin lesion etc)

(II)

Clinical signs of severity:

A) Hypotensive : systolic BP ≤ 90 mmHg in adult and <5% for children B) ≥ 2 of the following signs i) ii)

iii)

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v) vi)

Renal impairment: creatinine ≥ 177 µM for adults or ≥ 2 of the upper limit of normal age. N patients with pre-existing renal disease, in ≥ 2-fold elevation over the baseline level. Coagulopathy: platelets ≤ 100 x 109 /L or disseminated intravascular coagulation defined by prolonged clotting times, low fibrinogen level and the presence of fibrin degradation products Liver involvement: alanine aminotransferase, aspartate aminotransferase or total bilirubin levels ≥2 x the upper limit of normal age. In patients with preexisting liver disease, a ≥ 2-fold elevation over the baseline level Adult resp distress syndrome defined by acue onset of diffuse pulmonary infiltrates & hypoxemia in the absence of cardiac failure or evidence of diffuse capillary leak manifested by acute onset of generalized edema or pleural or peritoneal effusions with hypoalbuminemia A generalized erytematous macular rash that may desquamate Soft tissue necrosis, including necrotizing fasciitis or myositis or gangrene

An illness fulfilling criteria IA and II (A and B) is defined as definitive case. An illness fulfilling criteria IB and II (A and B) is defined as a probable case if no other etiology for the disease is identified.