Update sul ruolo infettivo della saliva

Francesco Barchiesi

Istituto di Malattie Infettive e Medicina PubblicaUniversità Politecnica delle Marche

Roma, 19-21 ottobre 2006

MMBR 2002; 66: 486-505

modalità di trasmissione deimicrorganismi emessi con le secrezioni

respiratorie

FONTE

1 METRO

TRASMISSIONE DA DROPLET TRASMISSIONE AEREA

HIV HBV

HCV

Herpesviridae

Global HIV epidemic, 1990‒2005* HIV epidemic in sub-Saharan Africa, 1985‒2005*

Number of people living with HIV

% HIV prevalence, adult (15-49)

% HIV prevalence, adult (15‒49)

Number of peopleliving with HIV (millions)

0

10

20

30

40

50

1990 1995 2000 2005

0.0

1.0

2.0

3.0

4.0

5.0

1985 1990 1995 2000 2005

0

5

10

15

20

25

30

0.0

2.5

5.0

7.5

12.5

15.0

% HIV prevalence, adult (15‒49)

Number of peopleliving with HIV (millions)

Estimated number of people living with HIV and adult HIV prevalenceEstimated number of people living with HIV and adult HIV prevalence

This bar indicates the range around the estimate

*Even though the HIV prevalence rates have stabilized in sub-Saharan Africa, the actual number of people infected continues to grow because of population growth. Applying the same prevalence rate to a growing population will result in increasing numbers of people living with HIV.

10.0

2.2

A global view of HIV infectionA global view of HIV infection38.6 million people [33.4‒46.0 million] living with HIV, 2005

2.4

Casi di AIDS in Italia per semestre di diagnosi, corretti per ritardo di notifica e tasso annuale di incidenza al 30 giugno 2005

Distribuzione dei casi di AIDS in adulti per categoria di esposizione e per anno di diagnosi

Analysis of HIV-1 viral load in blood, semen and saliva: evidence for different viral compartments in a cross-sectional and

longitudinal studyAIDS 1996,10:F51-F56

1,E+00

1,E+01

1,E+02

1,E+03

1,E+04

1,E+05

1,E+06

0 1 2 3 4Plasma Semen Saliva

HIV

RN

A (

cop

ies/

ml)

HIV- inhibitory activity of different body fluids

78,5 72,5 68,9

51,2

38,8 36,7

13,6

0

20

40

60

80

%

Shugars et al., 2002, Oral Dis. 8(Suppl. 2):169-175

Factors HIV-inhibitory mechanismsAnti-HIV antibodies •Neutralize and inactivate the virus

•IgA inhibits interaction between gp120 and CD4

C1q of complement • In presence of fibronectin, virus binding and sedimentation

Cystatins • General antimicrobial activity

• Inhibit cysteine proteases

Defensins (, , ) •General antimicrobial activity

•Block virus penetration

Lactoferrin • Iron-mediated bacterial and viral replication

Lactoperoxidase • Virus inactivation by hypothiocyanite production

Lysozyme • Inhib. viral replication by destroying viral membranes

Campo et al., 2006, Oral Dis. 12:219-228

Factors HIV-inhibitory mechanismsRibonuclease •Inhibition of viral replication by destroying its genetic

material

Mucins • Sequester and aggregate viral particles

Secretory leucocyte proteaseInhibitor (SLPI)

• Interact with a cellular surface molecule to limit viral entry into target cells

Thrombospondin 1 (TSP-1) •Produces virus aggregation; during penatration by virus, blocks its interactions with lymphocytes

Proline-rich proteins (PRPs) • Bind of gp120 of the virus, preventing its penetration of lymphocytes

Salivary agglutinin (SAG) / Mucin MG2

• Bind and displace gp120 from virions

• Agglutinate HIV and dissociate viral envelope proteins

Hypotonic effect • Lyses HIV infected mononuclear leucocytes

Campo et al., 2006, Oral Dis. 12:219-228

Distribution of Acute Viral Hepatitis in Italy(SEIEVA 2000-2001)

54%34%

10% 2%

HAVHBVHCVnAnBnC

Total cases = 4071

Geographic distribution of chronic HBV infectionGeographic distribution of chronic HBV infection

National Immunization Programs (WHO)National Immunization Programs (WHO)

Incidence rate of acute HBV in ItalyIncidence rate of acute HBV in Italy

0

2

4

6

8

10

12

14

1985 1987 1989 1991 1993 1995 1997 1999 2001

Stroffolini et al., 2000ISS, 2003

Mass Hepatitis BMass Hepatitis B

Vaccination introducedVaccination introduced

Cas

es /

100

,000

Risk factors among hepatitis B cases in ItalyRisk factors among hepatitis B cases in Italy

0

5

10

15

20

25

30

35

40

45

1987 1988 1989 1990 1991 1992 1993 1994 1995 1996 1997

%

Blood Transf. IDU HBsAg + carrier >Sexual partner

Stroffolini et al., J. Hepatol., 2000

Paired measurements of quantitative hepatitis B virus DNA in saliva and serum of chronic hepatitis B patients: implications for

saliva as infectious agent J. Clin. Virol., 2004; 29:92-94

Serum

85%

15%

+-

Saliva

63%

37% +-

Transmission of hepatitis B by human bite—Confirmation by detection of virus in saliva and full genome sequencing

J. Clin. Virol., 2005; 33:254-256

Index patient

Resident A

WHO. Wkly Epidemiol Rec.

2000;75:18-19

Infezione da HCV: prevalenza globale

High serum hepatitis C virus RNA load predicts the presence of HCV RNA in saliva from individuals with chronic and acute

HCV infectionJID 2006; 193:672-6

Indicazioni per la gestione delle esposizioni a materiale biologico

Gestione post-esposizione occupazionale ad HIV, HBV ed HCV

Modalità di esposizione

Profilassi HIV Profilassi HBV Protocollo HCV

Ferita o puntura percutanea con ago o altro tagliente

RACCOMANDATA RACCOMANDATA RACCOMANDATO

Contaminazione congiuntivale

RACCOMANDATA RACCOMANDATA RACCOMANDATO

Contaminazione di cute lesa o mucose

CONSIDERATA RACCOMANDATA RACCOMANDATO

Ferita da morso umano (con soluzione di continuo della cute)

CONSIDERATA RACCOMANDATA CONSIDERATO

Contaminazione cute integra

SCONSIGLIATA SCONSIGLIATA NON APPLICABILE

Gestione post-esposizione occupazionale ad HIV, HBV ed HCV

Materiale biologico Profilassi HIV Profilassi HBV Protocollo HCV

Sangue o altro mat. biol. contenente sangue visibile

RACCOMANDATA RACCOMANDATA RACCOMANDATO

Liquido cerebro-spinale RACCOMANDATA RACCOMANDATA RACCOMANDATO

Liquido amniotico, sinoviale, pericardico, peritoneale

CONSIDERATA RACCOMANDATA CONSIDERATO

Tessuti, materiali di laboratorio

CONSIDERATA RACCOMANDATA CONSIDERATO

Sperma e secreazioni genitali femminili

CONSIDERATA RACCOMANDATA NON APPLICABILE

Urine, vomito, saliva, feci

SCONSIGLIATA SCONSIGLIATA NON APPLICABILE

Protocollo riassuntivo degli esami da effettuare nel soggetto esposto

Settimana 0 2 4 6 8 12 24

Prof. HIV

Anti HIV X X X X

ematochimici X X X X

CD4/CD8 X

Prof. HBV

Anti HBS X

Prot. HCV

Anti HCV X X X

HCV RNA qualit.

X

AST/ALT X X X X X X X

Profilassi post-esposizione (PPE) ad HIV

• Inizio il più presto possibile (entro 1-4 ore) dall’esposizione

• E’ sconsigliata se sono trascorse oltre 72 ore• Se dopo la somministrazione delle prima dose di PPE,

l’esposizione si rivela non a rischio la profilassi viene interrotta

• Regime a tre farmaci (es.: AZT + 3TC + IP)• Durata 4 settimane

Profilassi post-esposizione (PPE) ad HBV

Fonte HBsAg positivo Fonte HBsAg negativo Fonte HbsAg

Ignoto

Non vaccinato Anti HBs<10U/ml: HBIG x 2 + vaccino HBV 4 dosi

Vaccino HBV (3 dosi) Anti HBs<10U/ml: HBIG x 2 + vaccino HBV 4 dosi

Vaccinato responder Nulla Nulla Nulla

Vaccinato non responder a vaccinazione primaria

HBIG x 2 + Vaccino 4 dosi

Vaccino HBV (3 dosi) HBIG x 2 + Vaccino 4 dosi

Vaccinato non responder a vaccinazione 4 dosi o a 2 cicli completi

HBIG x 2 +

Possibile Vaccino alternativo

Possibile vaccino alternativo

HBIG x 2 +

Possibile Vaccino alternativo

Vaccinato in modo incompleto

Anti HBs<10U/ml: HBIG x 1 + vaccino HBV 4 dosi

Vaccino HBV (3 dosi) Anti HBs<10U/ml: HBIG x 1 + vaccino HBV 4 dosi

Herpesviridae

57

9

55

9

35

9

78

0

0

20

40

60

80

%

USA USA Greece Turkey

HSV-1

periodontitishealthy

79

27

64

18

78

17

44

13

72

6

89

46

81

19

49

15

0

20

40

60

80

100

%

USA USA Jamaica Greece Turkey Turkey China Japan

EBV

86

18

73

18

73

22

59

13

72

0

78

46

0

20

40

60

80

100

%

USA USA Jamaica Greece Turkey Turkey

CMV

Periodontology 2000, June 2005

Periodontitis lesions are a source of salivarycytomegalovirus and Epstein–Barr virus

CMV

1,E+00

1,E+03

1,E+06

pre post

cop

ies/

ml

Journal of Periodontal ResearchVolume 40 Page 187  - April 2005

EBV

1,E+00

1,E+03

1,E+06

1,E+09

pre post

cop

ies/

ml

High prevalence of multiple human herpesviruses in saliva from human immunodeficiency virus-infected persons in

the era of highly active antiretroviral therapy.

J. Clin. Microbiol.,2006; 44:2409-15

90

4857

2431

2

16

2

0

20

40

60

80

100

%

EBV HHV-8 CMV HSV-1

HIV posHIV neg

• Candida albicans Candida albicans 50%50%

• Candida tropicalis Candida tropicalis 15-30%15-30%

• Candida glabrata Candida glabrata 15-30%15-30%

• Candida parapsilosisCandida parapsilosis 15-30%15-30%

• Candida kruseiCandida krusei ~ 1%~ 1%

• Candida lusitaniaeCandida lusitaniae ~ 1%~ 1%

• Candida dubliniensisCandida dubliniensis < 1% < 1%

Genotyping and antifungal susceptibility of human subgingival Candida albicans isolates

Arch. Oral Biol., 2002; 3:189-196

Transmission of fluconazole-resistant Candida albicans between patients with AIDS and oropharyngeal candidiasis

documented by pulsed-field gel electrophoresis

Clin Infect Dis. 1995;21:561-4

A A A B A

MaleA 0.5 0.06A 4.0 1.0A >64 4.0

FemaleB 0.125 <0.03A >64 2.0

FLU MIC ITC MIC

g/ml g/ml

Grazie