Streptococci -1 akram.ppt - Mymensingh Medical College file/Streptococci -1 akram.pdf · The...

StreptococciStreptococci

Professor Dr. Md. Akram HossainProfessor Dr. Md. Akram Hossain

July July 20092009

12/29/2013 1Prof. Muhammad Akram Hossain,

Streptococci

Review questions on StreptococciReview questions on Streptococci

1.1. What are salient features of streptococci? How they look like in Gram What are salient features of streptococci? How they look like in Gram stained smear and why?stained smear and why?

2.2. Compare Staphylococci and streptococci.Compare Staphylococci and streptococci.

3.3. How can you classify Streptococci.?How can you classify Streptococci.?

4.4. Clinical significance of S.pyogenes?Clinical significance of S.pyogenes?

5.5. Enumerate Toxins and enzymes of S. Pyogenes? Enumerate Toxins and enzymes of S. Pyogenes? 5.5. Enumerate Toxins and enzymes of S. Pyogenes? Enumerate Toxins and enzymes of S. Pyogenes?

6.6. Enumerate diseases caused by S. pyogenesEnumerate diseases caused by S. pyogenes

7.7. Write down pathogenesis of AGN & ARF? How can you prevent them? Write down pathogenesis of AGN & ARF? How can you prevent them? Role of penicillin?Role of penicillin?

8.8. Lab Diagnosis of ARF & AGNLab Diagnosis of ARF & AGN

9.9. What is ASO? Diagnostic significance .What is ASO? Diagnostic significance .

10.10. Clinical significance of Str Grr B G,Gr C& Gr D Clinical significance of Str Grr B G,Gr C& Gr D

11.11. Clinical significance of Str pneumoniae and Str viridiansClinical significance of Str pneumoniae and Str viridians


Streptococci

The StreptococciThe Streptococci

�� GramGram positive,positive, spherical,spherical, oror ovoid,ovoid,nonnon--motilemotile bacteriabacteria..

�� GrowGrow inin pairspairs oror chainschains ofof varyingvaryinglengthlength..lengthlength..

�� DivideDivide inin aa planeplane perpendicularperpendicular totothethe longlong axisaxis ofof thethe chainchain

�� OverOver 3030 identifiedidentified speciesspecies

�� MembersMembers ofof thisthis genusgenus causecause aa varietyvarietyofof diseasesdiseases butbut theythey areare alsoalso quitequitecommoncommon asas membersmembers ofof thethe normalnormalfloraflora..12/29/2013 3

Prof. Muhammad Akram Hossain, Streptococci

Each year …Each year …

� 610 million( 61 crores) cases of pharyngitis due to GAS

� 110 million cases of soft tissue infection � 110 million cases of soft tissue infection

� At least 18 million people suffer the consequences of serious GAS diseases

� At least 500,000 deaths


Streptococci

HistoryHistory

�� Hipocrates Hipocrates -- 55thth century BCcentury BC

�� Billroth 1874 Billroth 1874 –– Erysepalas and wound infectionErysepalas and wound infection

�� Pasteur Pasteur –– 1884 1884 –– puerperal sepsispuerperal sepsis

Rosenbach Rosenbach –– named itnamed it�� Rosenbach Rosenbach –– named itnamed it

�� 1919 1919 –– Brown Brown –– hemolysishemolysis

�� 19301930-- Rebeca lancefield Rebeca lancefield –– grouppinggroupping

�� 1935 1935 –– Griffith Griffith -- typingtyping


Streptococci


Streptococci

Classification Classification Classification is Complex. Following are some important classifications.Classification is Complex. Following are some important classifications.

�� Based on Oxygen requirement :Based on Oxygen requirement :

�� Obligate anaerobe : Obligate anaerobe : PeptostreptococcusPeptostreptococcus

�� Facultative anaerobe : Most of the streptococciFacultative anaerobe : Most of the streptococci

�� Based on Hemolysis in BA : (Brown Based on Hemolysis in BA : (Brown 19191919))

�� Beta hemolytic : Most pathogenic spp. eg. Beta hemolytic : Most pathogenic spp. eg. Str. pyogenesStr. pyogenes

Alpha hemolytic : Alpha hemolytic : Str. viridans, Str. pneumonaeStr. viridans, Str. pneumonae�� Alpha hemolytic : Alpha hemolytic : Str. viridans, Str. pneumonaeStr. viridans, Str. pneumonae

�� Gamma hemolytic : Gamma hemolytic : Str. fecalis, EnterococciStr. fecalis, Enterococci, etc., etc.

�� Based on Group and Type specific cell wall antigenBased on Group and Type specific cell wall antigen

�� Grouping based on cell wall CHO antigen : (Lancefield Grouping based on cell wall CHO antigen : (Lancefield 19331933) )

�� There There 19 19 Groups Groups –– A B C D E F G H K L M N O P Q R S T U V of which A B C D E F G H K L M N O P Q R S T U V of which

Group A, B, C, D, & G are human pathogensGroup A, B, C, D, & G are human pathogens

�� Typing based on cell wall M protein antigen : (Griffith )Typing based on cell wall M protein antigen : (Griffith )

�� Strains of Strains of Strep. Gr AStrep. Gr A are further typed into >are further typed into >80 80 serotypes, Some serotypes, Some

are rheumatogenic and some are nephrotigenic.are rheumatogenic and some are nephrotigenic.12/29/2013 7Prof. Muhammad Akram Hossain,

Streptococci

Classification based on Hemolysis on Blood Classification based on Hemolysis on Blood

AgarAgar

�� αα--HemolyticHemolytic:: PartialPartial hemolysishemolysiswhichwhich givesgives aa “greenish”“greenish”

appearanceappearance..

�� ExEx.. ViridansViridans StreptococciStreptococciExEx.. ViridansViridans StreptococciStreptococci

�� ββ--HemolyticHemolytic:: ClearClear zonezoneindicatingindicating lysislysis ofof redred bloodblood

cellscells..

�� ExEx.. StreptococcusStreptococcus pyogenespyogenes

�� γγ--HemolyticHemolytic:: NoNo hemolysishemolysis isisobservedobserved..


Streptococci

Alpha hemolytic streptococcusAlpha hemolytic streptococcus


Streptococci

Beta hemolysis by Beta hemolysis by Streptococcus Streptococcus pyogenespyogenes


Streptococci

Composition of Cell Wall Composition of Cell Wall

CarbohydratesCarbohydrates

Lancefield’s Grouping systemLancefield’s Grouping system

�� Differentiates streptococci into serogroups by Differentiates streptococci into serogroups by means of antigenic differences in cell wall means of antigenic differences in cell wall carbohydrates carbohydrates

�� 18 Groups: A18 Groups: A--H, KH, K--T T

�� Some species “nonSome species “non--typable”typable”

�� Streptococcus pneumoniaStreptococcus pneumonia, Viridans streptococci, Viridans streptococci


Streptococci

Lancefield ClassificationLancefield Classification

SerogroupSerogroup

�� A (A (Strep. pyogenesStrep. pyogenes))Usual Clinical FeaturesUsual Clinical Features

�� Pharyngitis, scarlet fever, Pharyngitis, scarlet fever,

rheumatic fever, cellulitis. rheumatic fever, cellulitis.

AGNAGN�� B (B (S. agalactiae)S. agalactiae)

AGNAGN

�� Neonatal sepsis and Neonatal sepsis and

meningitis, meningitis,

chorioamnionitischorioamnionitis


Streptococci

Lancefield ClassificationLancefield Classification

SerogroupSerogroup

�� C (C (S. equiS. equi))

Usual Clinical FeaturesUsual Clinical Features

�� Upper Respiratory InfectionsUpper Respiratory Infections

�� D (Enterococcus, D (Enterococcus, Strep Strep bovisbovis))

�� G G ((S. canis)S. canis)

Upper Respiratory InfectionsUpper Respiratory Infections

�� Genitourinary and wound Genitourinary and wound

infections, endocarditisinfections, endocarditis

�� Upper resp. infections, Upper resp. infections,

cellulitis, sepsiscellulitis, sepsis


Streptococci

Serology: Lanciefield ClassificationSerology: Lanciefield Classification

�� Streptococci classified into many groups from AStreptococci classified into many groups from A--K & HK & H--VV

One or more species per groupOne or more species per group

Streptococci

Group AS. pyogenes

Group BS. agalactiae

Group CS. equisimitis

Group DEnterococcus

Lanciefield classification

Other groups (E-U)

�� One or more species per groupOne or more species per group

�� Classification based on CClassification based on C-- carbohydrate antigen of cell wallcarbohydrate antigen of cell wall�� Groupable streptococciGroupable streptococci

�� A, B and D (more frequent)A, B and D (more frequent)

�� C, G and F (Less frequent)C, G and F (Less frequent)

�� NonNon--groupable streptococcigroupable streptococci

�� S. pneumoniaeS. pneumoniae (pneumonia)(pneumonia)

�� viridans streptococciviridans streptococci

�� e.g. e.g. S. mutansS. mutans

�� Causing dental carriesCausing dental carries12/29/2013 14

Prof. Muhammad Akram Hossain, Streptococci

Clinical Important StreptococciClinical Important Streptococci

�� S. pyogenesS. pyogenes

�� Group A Beta Hemolytic StrepGroup A Beta Hemolytic Strep

�� S. agalactiaeS. agalactiae

Group B StrepGroup B Strep�� Group B StrepGroup B Strep

�� EnterococciEnterococci

�� Viridens StreptococciViridens Streptococci

�� S. pneumoniaS. pneumonia


Streptococci


Streptococci

Streptoccus pyogenes Streptoccus pyogenes

�� Morphology / Culture / Biochemical properties Morphology / Culture / Biochemical properties

�� GPC in chains, Aerobic and FA, grow in BA GPC in chains, Aerobic and FA, grow in BA with clear zone of hemolysis, Catalase with clear zone of hemolysis, Catalase negative, Bacitracin sensitive.negative, Bacitracin sensitive.negative, Bacitracin sensitive.negative, Bacitracin sensitive.

�� FirstFirst describeddescribed inin 18791879 byby PasteurPasteur inin aasamplesample fromfrom patientpatient dyingdying ofof puerpuralpuerpural sepsissepsis


Streptococci

Streptococcus pyogenes:Streptococcus pyogenes:Microscopic appearance & colonial morphologyMicroscopic appearance & colonial morphology


Streptococci

Determinants of Pathogenecity Determinants of Pathogenecity

�� ToxinsToxins

�� EnzymesEnzymes

�� Other factorsOther factors


Streptococci

ToxinsToxins

�� StreptolysinStreptolysin ‘O’‘O’ –– OxygenOxygen labile,labile, hashasantigenicityantigenicity.. DestructsDestructs RBCs,RBCs, ASOASO risesrises followingfollowingstreptococcalstreptococcal soresore thorathora butbut notnot skinskin infectionsinfections..

�� StreptolysinStreptolysin ‘S’‘S’ –– OxygenOxygen stable,stable, NotNot antigenicantigenic..

�� PyrogenicPyrogenic toxintoxin (Erythogrnic(Erythogrnic toxin)toxin) AA ––�� PyrogenicPyrogenic toxintoxin (Erythogrnic(Erythogrnic toxin)toxin) AA ––

PresentPresent inin fewfew strainsstrains whichwhich areare lyosogeniclyosogenic andandresponsibleresponsible forfor scarletscarlet feverfever..

�� PyrogenicPyrogenic toxintoxin (Erythogrnic(Erythogrnic toxin)toxin) BB --RapidlyRapidly destroysdestroys tissuetissue andand responsibleresponsible forfor necrotizingnecrotizing

fascitisfascitis


Streptococci

EnzymesEnzymes

1.1. HyaluronidaseHyaluronidase (Spreading(Spreading factor)factor)-- BreaksBreaksdowndown proteoglycansproteoglycans ofof ConnectiveConnective tissuetissue..

2.2. StreptokinaseStreptokinase (Fibrinolysin)(Fibrinolysin) –– activatesactivatesplasminogenplasminogen toto plasminplasmin thatthat breaksbreaks fibrinfibrin clotclot..

3.3. DNaseDNase (Streptodornase)(Streptodornase) –– depolymerizesdepolymerizes3.3. DNaseDNase (Streptodornase)(Streptodornase) –– depolymerizesdepolymerizesDNADNA inin exudatesexudates oror necroticnecrotic tissuetissue.. AntigenicAntigenic..

4.4. CC55--aa peptidasepeptidase -- degrades complement component ofC5a, which attracts phagocytes to the sites of complementdeposition. Prevents chemotaxis of neutrophils andmononuclear phagocytes.


Streptococci

Other Other Virulence FactorsVirulence Factors

1.1. Capsule Capsule -- antiphagocyticantiphagocytic

2.2. Fc Binding Protein Fc Binding Protein -- antiphagocyticantiphagocytic

3.3. M Protein M Protein -- antiphagocytic, adhesionantiphagocytic, adhesion

4.4. Plasmin Binding ProteinPlasmin Binding Protein4.4. Plasmin Binding ProteinPlasmin Binding Protein


Streptococci

S. PyogenesS. Pyogenes –– Patterns of DiseasePatterns of Disease

1.1. Direct Bacterial InvasionDirect Bacterial Invasion

2.2. Toxin MediatedToxin Mediated•• Streptococcal Toxic Shock SyndromeStreptococcal Toxic Shock Syndrome

•• Scarlet FeverScarlet Fever•• Scarlet FeverScarlet Fever

3.3. Delayed Disease Caused by Host ResponseDelayed Disease Caused by Host Response•• Acute Rheumatic FeverAcute Rheumatic Fever

•• Acute GlomerulonephritisAcute Glomerulonephritis


Streptococci

Due to local invasionDue to local invasion

�� StreptococcalStreptococcal pharyngitis,pharyngitis, Tonsillitis,Tonsillitis, Sinusitis,Sinusitis,

Adenitis,Adenitis, OtitisOtitis mediamedia andand mastoiditismastoiditis..

�� SkinSkin infectionsinfections ––Folliculitis,Folliculitis, Cellulitis,Cellulitis, impetigoimpetigo

�� SepsisSepsis –– InfectionsInfections ofof wounds,wounds, burnsburns andand chronicchronic�� SepsisSepsis –– InfectionsInfections ofof wounds,wounds, burnsburns andand chronicchronic

skinskin lesionslesions

�� PulmonaryPulmonary abscess,abscess, empyemaempyema

�� Septicaemia,Septicaemia, acuteacute endocarditisendocarditis

�� PurperalPurperal sepsissepsis


Streptococci

Due to Exotoxin release Due to Exotoxin release

��Scarlet feverScarlet fever--

��Toxic shock syndrome Toxic shock syndrome ––

��Necrotizing fascitisNecrotizing fascitis��Necrotizing fascitisNecrotizing fascitis


Streptococci

Delayed antibody mediated Delayed antibody mediated

�� Rheumatic feverRheumatic fever

�� Following Pharyngitis due to type II hypersensitivityFollowing Pharyngitis due to type II hypersensitivity

�� Acute glomerulonephritisAcute glomerulonephritis

�� Following skin infections due to type III Following skin infections due to type III �� Following skin infections due to type III Following skin infections due to type III

hypersensitivityhypersensitivity


Streptococci

How common is invasive group A streptococcal How common is invasive group A streptococcal disease?disease?

�� AboutAbout 99,,400400 casescases ofof invasiveinvasive GASGAS diseasedisease occurredoccurred inin thethe

UnitedUnited StatesStates inin 19991999..

�� aboutabout 300300 werewere STSSSTSS andand 600600 werewere necrotizingnecrotizing fasciitisfasciitis..

InIn contrast,contrast, therethere areare severalseveral millionmillion casescases ofof strepstrep throatthroat andand�� InIn contrast,contrast, therethere areare severalseveral millionmillion casescases ofof strepstrep throatthroat andand

impetigoimpetigo eacheach yearyear..

�� AboutAbout 2020%% ofof patientspatients withwith necrotizingnecrotizing fasciitisfasciitis andand moremore thanthan

halfhalf withwith STSSSTSS diedie..

�� AboutAbout 1010%%--1515%% ofof patientspatients withwith otherother formsforms ofof invasiveinvasive groupgroup

AA streptococcalstreptococcal diseasedisease diedie..


Streptococci

Diagnosis Supporative infections Diagnosis Supporative infections

�� Specimen : Specimen : According to site of infection. eg. T/S, Pus, According to site of infection. eg. T/S, Pus,

SputumSputum

�� Microscopy : Microscopy : Gram positive cocci in chains Gram positive cocci in chains

�� Isolation and Identification : Isolation and Identification : Culture in BA, Small colonies Culture in BA, Small colonies

with clear zone of hemolysis which are confirmed by Catalase with clear zone of hemolysis which are confirmed by Catalase with clear zone of hemolysis which are confirmed by Catalase with clear zone of hemolysis which are confirmed by Catalase

and Bacitracin sensitivity test. and Bacitracin sensitivity test. Grouping Grouping andand TypingTyping is done is done

by serological test.by serological test.

�� Antigen Detection from T/S: Antigen Detection from T/S: ELISA and Agglutination ELISA and Agglutination

test are available.test are available.

�� Immunological test :Immunological test : Dick test for Scarlet fever.Dick test for Scarlet fever.


Streptococci

Poststreptococcal Sequelae: Poststreptococcal Sequelae: Acute Acute

Rheumatic FeverRheumatic Fever

�� Nonsuppurative inflammatory lesions involving the:Nonsuppurative inflammatory lesions involving the:

�� Heart Heart

�� JointsJoints

�� Subcutaneous TissuesSubcutaneous Tissues

Central Nervous SystemCentral Nervous System�� Central Nervous SystemCentral Nervous System

�� Usually follows an upper respiratory infection with Usually follows an upper respiratory infection with

Group A StrepGroup A Strep

�� Latency 1Latency 1--5 weeks (Average 19 days)5 weeks (Average 19 days)

�� Risk after untreated pharyngitis Risk after untreated pharyngitis �� <3%<3%

�� Cutaneous infections do not lead to ARFCutaneous infections do not lead to ARF


Streptococci


Rheumatic FeverRheumatic Fever�� Associated with Group A streptococci of Associated with Group A streptococci of

certain M protein serotypes certain M protein serotypes �� 1, 3, 5, 6, 14, 18, 19, 241, 3, 5, 6, 14, 18, 19, 24

�� Role of M protein in the pathogenesis is Role of M protein in the pathogenesis is �� Role of M protein in the pathogenesis is Role of M protein in the pathogenesis is unclear. Two hypothesis:unclear. Two hypothesis:

1.1. Due to structural features, M protein elicits the production Due to structural features, M protein elicits the production of of antibodies cross reactiveantibodies cross reactive with host myosinwith host myosin

2.2. Due to its Due to its superantigenicsuperantigenic properties, M protein elicit the properties, M protein elicit the

production of antibodies against host componentsproduction of antibodies against host components..


Streptococci

Diagnosis of Rheumatic Fever Diagnosis of Rheumatic Fever -- Jones CriteriaJones Criteria

�� Major CriteriaMajor Criteria�� Carditis (60%)Carditis (60%)

�� Endocardium, myocardium, pericardiumEndocardium, myocardium, pericardium

�� Tachycardia, mitral regurgitation, friction rubTachycardia, mitral regurgitation, friction rub

Polyarthritis (70%)Polyarthritis (70%)�� Polyarthritis (70%)Polyarthritis (70%)�� Migratory, large jointsMigratory, large joints

�� Chorea (10%)Chorea (10%)�� Emotional lability, weakness, involuntary movementsEmotional lability, weakness, involuntary movements

�� Erythema Marginatum (10%)Erythema Marginatum (10%)

�� Subcutaneous nodules (10%)Subcutaneous nodules (10%)


Streptococci

Rheumatic fever: Rheumatic fever: chronic valvar diseasechronic valvar disease

�� Repeated bouts of valve Repeated bouts of valve

inflammation may heal with:inflammation may heal with:

�� fibrosis of valve cuspsfibrosis of valve cusps

�� fusion between valve commissuresfusion between valve commissures�� fusion between valve commissuresfusion between valve commissures

�� Shortening, thickening of chordae Shortening, thickening of chordae

tendinae tendinae

�� Valves InvolvedValves Involved�� Mitral Mitral 7070% % �� Mitral + aortic Mitral + aortic 2525% % �� Tricuspid, Pulmonic rarelyTricuspid, Pulmonic rarely


Streptococci

Diagnosis of Rheumatic Fever Diagnosis of Rheumatic Fever -- Jones CriteriaJones Criteria

�� Minor CriteriaMinor Criteria�� ClinicalClinical

�� ArthralgiasArthralgias

�� FeverFever

�� Laboratory Laboratory

�� Elevated acuteElevated acute--phase reactantsphase reactants�� Elevated acuteElevated acute--phase reactantsphase reactants

�� Elevated erythrocyte sedimentation rateElevated erythrocyte sedimentation rate

�� Elevated CElevated C--reactive proteinreactive protein

�� Prolonged PR intervalProlonged PR interval

�� Supportive evidence of antecedent group A strep Supportive evidence of antecedent group A strep infectioninfection�� Positive throat culture or rapid streptococcal antigen testPositive throat culture or rapid streptococcal antigen test

�� Elevated or rising streptococcal antibody titer (ASO)Elevated or rising streptococcal antibody titer (ASO)


Streptococci

Prevention and Treatment of Acute Prevention and Treatment of Acute

Rheumatic FeverRheumatic Fever

�� Primary PreventionPrimary Prevention�� Adequate therapy of Strep. PharyngitisAdequate therapy of Strep. Pharyngitis

Ex. Penicllin for Ex. Penicllin for 10 10 daysdays

�� Treatment of ARFTreatment of ARF�� Treatment of ARFTreatment of ARF�� Penicllin to eradicate Strep.Penicllin to eradicate Strep.

�� AntiAnti--inflammatory drugsinflammatory drugs

�� Prevention of RelapsePrevention of Relapse�� Daily PCN Daily PCN > > 5 5 yearsyears


Streptococci


GlomerulonephritisGlomerulonephritis

�� Follows infection with a limited number of Follows infection with a limited number of Group A streptococci serotypesGroup A streptococci serotypes

�� More frequently associated with skin infectionsMore frequently associated with skin infections

�� M types 12, 4, 2, 49M types 12, 4, 2, 49�� M types 12, 4, 2, 49M types 12, 4, 2, 49

�� Incidence of nephritis:Incidence of nephritis:

�� Any Group A Strep infection Any Group A Strep infection �� <0.5%<0.5%

�� M type 49 M type 49 �� 23%23%


Streptococci

Poststreptococcal Sequelae: Acute GlomerulonephritisPoststreptococcal Sequelae: Acute Glomerulonephritis

�� Precise mechanism ????Precise mechanism ????�� Immune mediated Immune mediated

�� Antibodies elicited by nephritogenic streptococci react Antibodies elicited by nephritogenic streptococci react with renal tissues to produce glomerular injury with renal tissues to produce glomerular injury

�� M protein may be the streptococcal triggerM protein may be the streptococcal trigger

�� Light microscopy reveal a marked increase in glomerular Light microscopy reveal a marked increase in glomerular intracapillary cellularity (endothelial and mesangial intracapillary cellularity (endothelial and mesangial proliferation)proliferation)

�� Recurrences rareRecurrences rare�� Limited number of nephritogenic strains?Limited number of nephritogenic strains?

�� Acquisition of typeAcquisition of type--specific antibody?specific antibody?


Streptococci

Any Questions?Any Questions?


Streptococci

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