host-parasite interactions in the oral cavity: host-parasite interactions in the oral cavity: oral...

Host-parasite Interactions in the Host-parasite Interactions in the Oral Cavity:Oral Cavity:

Oral Microorganisms and Oral Microorganisms and Systemic DiseasesSystemic Diseases

enamel cariesenamel caries

dentinal cariesdentinal caries

infected pulpinfected pulp

cementumcementum

infected root canalinfected root canal

periapical osteitisperiapical osteitis

root surface cariesroot surface caries

periodontal pocketperiodontal pocket

lateral canallateral canal

adapted from Marsh, 1999adapted from Marsh, 1999

gingival crevicegingival crevice

Progression of infections affecting the tooth Progression of infections affecting the tooth and its supporting structureand its supporting structure

Puberty GingivitisPuberty Gingivitis

Pregnancy GingivitisPregnancy Gingivitis

Drug-induced Gingival OvergrowthDrug-induced Gingival Overgrowth

Necrotizing Ulcerative GingivitisNecrotizing Ulcerative Gingivitis

Prepubertal GingivitisPrepubertal Gingivitis

Juvenile PeriodontitisJuvenile Periodontitis

Rapidly Progressive PeriodontitisRapidly Progressive Periodontitis

Dental PlaqueDental Plaque

Base ProductionBase Production

CalculusCalculus

Acid ProductionAcid Production

CariesCaries

PulpitisPulpitis

““Inert”Inert”

GingivitisGingivitis

Adult PeriodontitisAdult Periodontitis

OsteomyelitisOsteomyelitisPeriodontal AbscessPeriodontal AbscessPeriapical LesionPeriapical Lesion AcuteAcute Chronic SuppuratingChronic Suppurating Chronic Non-suppuratingChronic Non-suppurating

OsteomyelitisOsteomyelitis CellulitisCellulitis Septic ThrombophlebitisSeptic Thrombophlebitis

This is This is where it where it

all all begins ??begins ??

Systemic DiseasesSystemic Diseases

The Diseases, and Casualties This Year The Diseases, and Casualties This Year Being 1632Being 1632

Abortive and StillbornAbortive and Stillborn 445445 Dropsie and SwellingDropsie and Swelling 267267 MurtheredMurthered 77

AfrightedAfrighted 11 DrownedDrowned 3434 Over-laid, and starved at Over-laid, and starved at nursenurse

77

AgedAged 628628 Executed, & prest to deathExecuted, & prest to death 1818 PalsiePalsie 2525

AgueAgue 4343 Falling SicknessFalling Sickness 77 PilesPiles 11

Apoplix, and MeagromApoplix, and Meagrom 1717 FeverFever 1,1081,108 PlaguePlague 88

Bit with a mad dogBit with a mad dog 11 FistulaFistula 1313 PlanetPlanet 1313

BleedingBleeding 33 Flox, and Small PoxFlox, and Small Pox 531531 Pleurisie, and SpleenPleurisie, and Spleen 3636

Bloody flux, Scowring, & FluxBloody flux, Scowring, & Flux 348348 French PoxFrench Pox 1212 Purples, and Spotted FeverPurples, and Spotted Fever 3838

Brused; Issues, Sores & UlcersBrused; Issues, Sores & Ulcers 2828 GangreneGangrene 55 QuinsieQuinsie 77

Burnt and ScaldedBurnt and Scalded 55 GowtGowt 44 Rising of the LightsRising of the Lights 9898

Burst, and RuptureBurst, and Rupture 99 GriefGrief 1111 SciaticaSciatica 11

Cancer, and WolfCancer, and Wolf 1010 JaundiesJaundies 4343 Scurvey, and ItchScurvey, and Itch 99

CankerCanker 11 JawfalnJawfaln 88 SuddenlySuddenly 6262

ChildbedChildbed 171171 ImpostumeImpostume 7474 SurfetSurfet 8686

Chrisomes, and InfantsChrisomes, and Infants 2,2682,268 Kil’d by Several AccidentKil’d by Several Accident 4646 Swine PoxSwine Pox 66

Cold, and CoughCold, and Cough 5555 King’s EvilKing’s Evil 3838 TeethTeeth 470470

Colick, Stone, and StranguryColick, Stone, and Strangury 5656 LethargieLethargie 22 Thrush, and Sore MouthThrush, and Sore Mouth 4040

ConsumptionConsumption 1,7971,797 LivergrownLivergrown 8787 TympanyTympany 1313

ConvulsionConvulsion 241241 LunatiqueLunatique 55 TissickTissick 3434

Cut of the StoneCut of the Stone 55 Made away themselvesMade away themselves 1515 VomitingVomiting 11

Dead in the street, and starvedDead in the street, and starved 66 MeaslesMeasles 8080 WormsWorms 2727

Christened: 9,584Christened: 9,584 Buried: 9,535Buried: 9,535 Whereof, of the Plague: 8Whereof, of the Plague: 8

Periodontal disease as a risk factor Periodontal disease as a risk factor for systemic diseasesfor systemic diseases

Infective endocarditisInfective endocarditis Bacterial pneumoniaBacterial pneumonia Cardiovascular disease and Cardiovascular disease and

atherosclerosisatherosclerosis Cerebral vascular accidents (strokes)Cerebral vascular accidents (strokes) Infections of prosthetic devicesInfections of prosthetic devices Diabetes mellitusDiabetes mellitus Adverse pregnancy outcomesAdverse pregnancy outcomes

Poor oral health may be an Poor oral health may be an independent contributor to CVD and independent contributor to CVD and

other systemic diseasesother systemic diseases

Dental decay and periodontal disease could lead to Dental decay and periodontal disease could lead to increased bacterial penetration of host.increased bacterial penetration of host.

Bacteria in gingival tissue could increase serum Bacteria in gingival tissue could increase serum cytokine and prostaglandin levels.cytokine and prostaglandin levels.

Bacteria in blood stream could increase white Bacteria in blood stream could increase white blood cell count and fibrinogen levels.blood cell count and fibrinogen levels.

THE PERIODONTAL-SYSTEMIC THE PERIODONTAL-SYSTEMIC CONNECTIONCONNECTION

A State-of-the-Science SymposiumA State-of-the-Science SymposiumApril 18-20, 2001 • Bethesda, Maryland • April 18-20, 2001 • Bethesda, Maryland •

AAP-NIDCRAAP-NIDCR

PurposePurpose To explore the emerging body of research linking To explore the emerging body of research linking

periodontal infections with chronic systemic diseases and periodontal infections with chronic systemic diseases and conditions in order to:conditions in order to:

advance the science by identifying the most promising areas advance the science by identifying the most promising areas for future research and targeting research funding prioritiesfor future research and targeting research funding priorities

foster collaborations in research and clinical practice that will foster collaborations in research and clinical practice that will optimize patient outcomesoptimize patient outcomes

inform healthcare professionals and industryinform healthcare professionals and industry

educate the publiceducate the public

Cardiovascular Disease Cardiovascular Disease (CVD)(CVD)

The relationship between infection, inflammation and CVD: The relationship between infection, inflammation and CVD: an overviewan overview

The association between periodontal diseases and CVDThe association between periodontal diseases and CVD

The role of coagulation and thrombosis in CVDThe role of coagulation and thrombosis in CVD

The role of inflammatory and immunomodulatory mediatorsThe role of inflammatory and immunomodulatory mediators

The role of microbial effects in cardiovascular diseasesThe role of microbial effects in cardiovascular diseases

The role of genetics in cardiovascular diseases: a potential The role of genetics in cardiovascular diseases: a potential mechanism linking PD & CVDmechanism linking PD & CVD

Dental plaque, platelets, and Dental plaque, platelets, and cardiovascular diseasecardiovascular disease

Dissemination of oral microbes @ periodontitisDissemination of oral microbes @ periodontitis Infection of vascular endotheliumInfection of vascular endothelium ?? Contribution to cardiovascular disease?? Contribution to cardiovascular disease

In vitroIn vitro: induction of platelet aggregation by : induction of platelet aggregation by S. S. sanguissanguis and and P. gingivalisP. gingivalis

In vivoIn vivo: ECG changes, increased heart rate and : ECG changes, increased heart rate and blood pressure, within 30 min of blood pressure, within 30 min of S. sanguisS. sanguis infectioninfection

Herzberg et al., various studiesHerzberg et al., various studies

Model of Dental-Associated EndocarditisModel of Dental-Associated Endocarditis

Heart valve deformityHeart valve deformity

Endothelial cell damage to valveEndothelial cell damage to valve

Platelet aggregation on on valvePlatelet aggregation on on valve

Non-bacterial thrombotic endocarditis?Non-bacterial thrombotic endocarditis?

Bacterial adherence to NBTEBacterial adherence to NBTE

Bacterial colonization of valveBacterial colonization of valve

Bacterial endocarditisBacterial endocarditis

Dental procedureDental procedure

Dental diseasesDental diseases

BacteremiaBacteremia

Blood flowBlood flowTurbulenceTurbulence

Hypercoagulability?Hypercoagulability?

Experimental transient bacteremia Experimental transient bacteremia due to tooth brushingdue to tooth brushing

Silver et al. 1977Silver et al. 1977

96 Subjects96 Subjects

Gingival indexGingival index Plaque indexPlaque index

0-0.750-0.75 0.76-1.50.76-1.5 1.51-2.251.51-2.25 2.26-3.002.26-3.00

# in group# in group 2525 // 4040 2424 / / 2626 2525 // 1616 2222 // 1414

# positive blood # positive blood cultureculture

44 // 1414 88 // 99 1414 / / 1010 1515 // 88

% positive blood % positive blood cultureculture

16%16% // 35%35% 33%33% // 35%35% 56%56% // 63%63% 68%68% // 57%57%

Experimental transient bacteremia Experimental transient bacteremia due to tooth brushingdue to tooth brushing

Silver et al. 1977Silver et al. 1977

# of species # of species of bacteria..of bacteria..

Gingival indexGingival index

0-0.750-0.75 0.76-1.500.76-1.50 1.51-2.251.51-2.25 2.26-3.002.26-3.00

00 2121 1616 1111 77

11 44 55 66 55

22 00 22 22 33

33 00 11 44 11

44 00 00 11 11

55 00 00 00 00

66 00 00 00 11

77 00 00 00 33

88 00 00 00 00

99 00 00 00 00

1010 00 00 00 11

Model of Dental-Associated EndocarditisModel of Dental-Associated Endocarditis








Dental procedureDental procedure

Dental diseasesDental diseases

BacteremiaBacteremia



A New Model of Dental-Associated A New Model of Dental-Associated EndocarditisEndocarditis

Gingivitis Gingivitis periodontitisperiodontitis

Dental plaqueDental plaque

‘‘Late’ bacteremiaLate’ bacteremia(minutes to hours)(minutes to hours)










‘‘Early’ bacteremiaEarly’ bacteremia(months to years)(months to years)

GingivitisGingivitis

PeriodontitisPeriodontitis

Dental extractions Dental extractions scalingscaling

Periapical diseasePeriapical disease

How could periodontal infections How could periodontal infections contribute to atherosclerosis ?contribute to atherosclerosis ?

Direct effects of infectious agents in Direct effects of infectious agents in atheroma formation.atheroma formation.

Indirect (host-mediated) effects triggered Indirect (host-mediated) effects triggered by infection.by infection.

Common genetic predisposition for Common genetic predisposition for periodontal disease and atherosclerosis.periodontal disease and atherosclerosis.

Common risk factors (such as lifestyle).Common risk factors (such as lifestyle).

Scannapieco and Genco, 1999Scannapieco and Genco, 1999

Direct effects of infectious agents Direct effects of infectious agents in atheroma formationin atheroma formation

Presence of Presence of P. gingivalisP. gingivalis in carotid and in carotid and coronary atheromas.coronary atheromas.

P. gingivalisP. gingivalis invades and may proliferate in invades and may proliferate in aortic and heart endothelial cells aortic and heart endothelial cells in vitroin vitro..

S. sanguisS. sanguis and and P. gingivalisP. gingivalis induce platelet induce platelet aggregation, which is thought to be associated aggregation, which is thought to be associated with thrombus formation.with thrombus formation.

P. gingivalisP. gingivalis proteases may contribute to proteases may contribute to remodeling of ECM of atheromatous plaquesremodeling of ECM of atheromatous plaques


Indirect (host-mediated) effects Indirect (host-mediated) effects triggered by infectiontriggered by infection

PD-induced inflammatory response elevates PD-induced inflammatory response elevates levels of C-reactive protein and fibrinogen, levels of C-reactive protein and fibrinogen, acute phase proteins that are risk factors for acute phase proteins that are risk factors for CAD.CAD.

Binding of autoantibodies induced by bacteriaBinding of autoantibodies induced by bacteria Antibodies to heat shock proteins (Hsp60, etc.).Antibodies to heat shock proteins (Hsp60, etc.). Mammalian and bacterial Hsp60’s share Mammalian and bacterial Hsp60’s share

approximately 60% homology.approximately 60% homology. Host Hsp’s may exposed in injured endotheliumHost Hsp’s may exposed in injured endothelium


Common genetic predisposition for Common genetic predisposition for periodontal disease and atherosclerosis ?periodontal disease and atherosclerosis ?

A hyper-inflammatory monocyte A hyper-inflammatory monocyte phenotype trait is proposed as a risk phenotype trait is proposed as a risk factor for both PD and CAD.factor for both PD and CAD. Periodontal flora provides lots of LPSPeriodontal flora provides lots of LPS Inflammatory cytokines (TxA2, IL-1Inflammatory cytokines (TxA2, IL-1, ,

PGE2, TNF-PGE2, TNF-))

Together, these may promote Together, these may promote atherogenesis and thrombogenesis.atherogenesis and thrombogenesis.


Common risk factors in PD and Common risk factors in PD and CAD (such as lifestyle)CAD (such as lifestyle)

““Coincidental” association between PD & CAD?Coincidental” association between PD & CAD? PD and poor oral hygiene may be an indicator PD and poor oral hygiene may be an indicator

of lifestyle and lack of overall health care.of lifestyle and lack of overall health care.

NOTENOTE:: many epidemiological studies were controlled many epidemiological studies were controlled for variety of lifestyle risk factors (such as smoking, for variety of lifestyle risk factors (such as smoking, diet, etc.), suggesting that PD-CAD relationship is diet, etc.), suggesting that PD-CAD relationship is not completely explained by lifestyle.not completely explained by lifestyle.


Dentate Individuals in the US Geriatric Dentate Individuals in the US Geriatric Population: Population: Relative and Absolute IncreasesRelative and Absolute Increases

YearYear % of % of PopulationPopulation

65 years65 years

Number of Number of Individuals Individuals

65 years65 years

Number with Number with TeethTeeth

EdentulousEdentulous

19001900 44 3,000,0003,000,000 1,200,0001,200,000 60 %60 %

19751975 1111 25,000,00025,000,000 15,000,00015,000,000 40 %40 %

20002000 1616 52,000,00052,000,000 39,000,00039,000,000 25 %25 %

IncreaseIncrease 4 - fold4 - fold 17 - fold17 - fold 32.5 - fold32.5 - fold

adapted from data in Hiikler and Wayne 1984, Miller et al., 1987, Winn et al, 1996adapted from data in Hiikler and Wayne 1984, Miller et al., 1987, Winn et al, 1996 WJLWJL

Prevalence and Extent of Attachment Loss and Prevalence and Extent of Attachment Loss and Periodontal Pocketing Among Older US ResidentsPeriodontal Pocketing Among Older US Residents

Periodontal ParametersPeriodontal Parameters AgeAgeAttachment LossAttachment Loss 45-5445-54 55-6455-64 > 65> 65

Prevalence (% of subjects)Prevalence (% of subjects)

one site ≥ 3 mmone site ≥ 3 mm 63%63% 74.1%74.1% 81.5%81.5%

one site ≥ 5 mmone site ≥ 5 mm 2727 35.135.1 41.241.2

Extent (% of sites / subject)Extent (% of sites / subject)

≥ ≥ 3 mm3 mm 1818 2626 3131

≥ ≥ 5 mm5 mm 66 88 9.69.6

Probing Pocket DeptthsProbing Pocket Deptths

Prevalence (% of subjects)Prevalence (% of subjects)

one site ≥ 4 mmone site ≥ 4 mm 32.732.7 37.237.2 3131

one site ≥ 6 mmone site ≥ 6 mm 7.37.3 7.97.9 6.66.6

Extent (% of sites / subject)Extent (% of sites / subject)

≥ ≥ 4 mm4 mm 5.15.1 5.65.6 4242

≥ ≥ 6 mm6 mm 1.81.8 1.51.5 1.51.5adapted from Brown et al., 1996 J. Dent. Res. 75(S):672-683adapted from Brown et al., 1996 J. Dent. Res. 75(S):672-683 WJLWJL

Dental/oral parameters and various Dental/oral parameters and various medical risk factors in CVDmedical risk factors in CVD

Potential Risk FactorPotential Risk FactorAll SubjectsAll Subjects Dentate SubjectsDentate Subjects

Odds RatioOdds Ratio 95% CL95% CL Odds RatioOdds Ratio 95% CL95% CL

S. sanguisS. sanguis 0.880.88 0.8-0.960.8-0.96 0.850.85 0.75-0.950.75-0.95

Complaint of xerostemiaComplaint of xerostemia 1.411.41 0.74-2.670.74-2.67 2.602.60 1.12-6.051.12-6.05

No. xerogenic meds.No. xerogenic meds. 1.181.18 1.1-1.271.1-1.27 1.481.48 1.14-1.431.14-1.43

Niid help feedingNiid help feeding 0.220.22 0.06-0.750.06-0.75 0.160.16 0.03-0.940.03-0.94

1-14 teeth1-14 teeth 2.412.41 1.11-5.201.11-5.20 2.792.79 1.22-6.391.22-6.39

15-28 teeth15-28 teeth 1.231.23 0.64-2.360.64-2.36

PB score 1.5-2.5PB score 1.5-2.5 3.753.75 1.09-12.931.09-12.93

PB score > 2.5PB score > 2.5 6.296.29 1.78-22.251.78-22.25

Quit smokingQuit smoking 1.441.44 0.62-3.250.62-3.25 1.821.82 0.70-4.750.70-4.75

CholesterolCholesterol 1.01.0 0.99-1.00.99-1.0 1.01.0 .099-1.00.099-1.00

AgeAge 1.021.02 0.96-1.080.96-1.08 1.021.02 .094-1.10.094-1.10

Diabetes-insulinDiabetes-insulin 1.091.09 0.51-2.350.51-2.35 2.142.14 0.78-5.860.78-5.86

Respiratory DiseaseRespiratory Disease

The relationship between infection and chronic respiratory The relationship between infection and chronic respiratory diseases: an overviewdiseases: an overview

Epidemiologic associations between periodontal diseases Epidemiologic associations between periodontal diseases and respiratory diseasesand respiratory diseases

The biology and biochemistry of respiratory diseasesThe biology and biochemistry of respiratory diseases

How could periodontal infections How could periodontal infections contribute to respiratory infection ?contribute to respiratory infection ?

Aspiration of oral pathogens into the lung.Aspiration of oral pathogens into the lung. Action of PD-associated enzymes in saliva on Action of PD-associated enzymes in saliva on

mucosal surfaces to promote adhesion and mucosal surfaces to promote adhesion and colonization of respiratory pathogens.colonization of respiratory pathogens.

PD-associated enzymes which may destroy PD-associated enzymes which may destroy protective salivary pellicles.protective salivary pellicles.

Cytokines originating from periodontal tissues may Cytokines originating from periodontal tissues may alter respiratory epithelium, thus promoting infection alter respiratory epithelium, thus promoting infection by respiratory pathogens.by respiratory pathogens.


Adverse Pregnancy OutcomesAdverse Pregnancy Outcomes

The relationship between infections and adverse pregnancy The relationship between infections and adverse pregnancy outcomes: an overviewoutcomes: an overview PLBW association w/ maternal infections during pregnancyPLBW association w/ maternal infections during pregnancy ? role of infections in modulation of cytokines & hormones related ? role of infections in modulation of cytokines & hormones related

to pregnancy outcomesto pregnancy outcomes Periodontal diseases and prematurity, low birth weight and Periodontal diseases and prematurity, low birth weight and

preeclampsiapreeclampsia PGE-2 and IL-1ß in GCFPGE-2 and IL-1ß in GCF

PGE-2 levels elevated ~2X in PLBWPGE-2 levels elevated ~2X in PLBW perio-pathogen levels (perio-pathogen levels (P.g., B.f., T.d., P.g., B.f., T.d., and and A.a.A.a.))

All @ increased levels in PLBW mothersAll @ increased levels in PLBW mothers

Implications for clinical practice and intervention strategiesImplications for clinical practice and intervention strategiesOffenbacher et al, 1998Offenbacher et al, 1998

Studies exploring molecular mechanisms of Studies exploring molecular mechanisms of association between oral organisms and association between oral organisms and

systemic diseasessystemic diseases

•Most studies to date have yielded data on Most studies to date have yielded data on associationsassociations between oral organisms and systemic between oral organisms and systemic diseases. diseases.

•Very few have examined specific Very few have examined specific mechanismsmechanisms or or identified potential bacterial virulence mechanisms identified potential bacterial virulence mechanisms that may be involved in these processes.that may be involved in these processes.

Experimental endocarditis in rats Experimental endocarditis in rats inoculated with oral streptococciinoculated with oral streptococci

Rats catheterized, then wait 24hRats catheterized, then wait 24h

Challenge with 10Challenge with 1077 StreptococcusStreptococcus strain of interest strain of interest

Sacrifice after 48hSacrifice after 48h

Development of endocarditis assayed by culture of Development of endocarditis assayed by culture of

streptococci from vegetations.streptococci from vegetations.

Curley et al., 1995Curley et al., 1995Viscount et al., 1997Viscount et al., 1997

P. gingivalisP. gingivalis interactions with cells interactions with cells of the cardiovascular systemof the cardiovascular system

Epidemiology indicates correlation between PD and CADEpidemiology indicates correlation between PD and CAD ?? Role of ?? Role of P.g.P.g. surface proteins in this process surface proteins in this process

proteases (3 major, plus ~6 “minor” proteases) proteases (3 major, plus ~6 “minor” proteases) hemagglutinins (encoded by at least 4 distinct genetic loci)hemagglutinins (encoded by at least 4 distinct genetic loci)

P. gingivalisP. gingivalis invades human coronary artery endothelial cells invades human coronary artery endothelial cells and human coronary artery smooth muscle cellsand human coronary artery smooth muscle cells

What effects do intracellular What effects do intracellular P. gingivalis P. gingivalis have on coronary have on coronary cells and tissue ??cells and tissue ??

How might How might P. gingivalis P. gingivalis influence CAD development ??influence CAD development ??

Progulske-Fox et al. 1999Progulske-Fox et al. 1999

Detection of DNA of periodontal Detection of DNA of periodontal organisms in atherosclerotic lesionsorganisms in atherosclerotic lesions

Detection of bacterial DNA in 88 archived samples Detection of bacterial DNA in 88 archived samples of atherosclerotic lesions from 15 individuals.of atherosclerotic lesions from 15 individuals.

PCR amplification of specific 16S rRNA sequences.PCR amplification of specific 16S rRNA sequences.

P. gingivalisP. gingivalis 12/8812/88 E. corrodensE. corrodens 12/8812/88 A. actinomycetemcomitans A. actinomycetemcomitans 43/8843/88 T. denticolaT. denticola 7/88 7/88

Van Poperin et al., IADR 2000Van Poperin et al., IADR 2000

Animal model of systemic Animal model of systemic manifestations of periodontitismanifestations of periodontitis

Systemic translocation of bacteria/products in PD ?Systemic translocation of bacteria/products in PD ?

Alterations in systemic inflammatory markers in PD ?Alterations in systemic inflammatory markers in PD ?

Relationship of PD to levels of lipids & lipoproteins ?Relationship of PD to levels of lipids & lipoproteins ?

Ebersole et al., 1999Ebersole et al., 1999

Animal model of systemic Animal model of systemic manifestations of periodontitismanifestations of periodontitis

Systemic translocation of bacteria/products in PD.Systemic translocation of bacteria/products in PD. Increased serum levels of LPS Increased serum levels of LPS (5/23 16/23)(5/23 16/23)

Alterations in systemic inflammatory markers in PD.Alterations in systemic inflammatory markers in PD. IncreasedIncreased acute phase inflammatory markers acute phase inflammatory markers CRPCRP, a1-antitrypsin, haptoglobin, , a1-antitrypsin, haptoglobin, fibrinogenfibrinogen, , IL-8IL-8

Relationship of PD to levels of serum lipids and Relationship of PD to levels of serum lipids and lipoproteins.lipoproteins. CholesterolCholesterol, , tri-glyceridestri-glycerides, HDL, , HDL, LDLLDL, apoA-I, apoA-I Changes exacerbated by high-fat content diet.Changes exacerbated by high-fat content diet.

Ebersole et al., 1999Ebersole et al., 1999

Periodontal disease as a risk factor Periodontal disease as a risk factor for systemic diseasesfor systemic diseases

Infective endocarditisInfective endocarditis Bacterial pneumoniaBacterial pneumonia Cardiovascular disease and atherosclerosisCardiovascular disease and atherosclerosis Cerebral vascular accidents (strokes)Cerebral vascular accidents (strokes) Infections of prosthetic devicesInfections of prosthetic devices Diabetes mellitusDiabetes mellitus Adverse pregnancy outcomesAdverse pregnancy outcomes

host-parasite interactions in the oral cavity: host-parasite interactions in the oral cavity: oral...

Documents

periodontal diseases

chronic systemic diseases

systemic diseasesthe

periodontal infections

cvdthe role of inflammatory

cvdthe role of coagulation

systemic diseasesdental

oral cavity