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HIV infectie - Itg

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Opportunistische <strong>infectie</strong>s<br />

Erika Vlieghe<br />

Instituut Tropische Geneeskunde - Universitair Ziekenhuis Antwerpen<br />

Cursus hiv en aids, de multi-disciplinaire<br />

aanpak<br />

Les 5 | 18 maart 2008<br />

www.itg.be - rubriek Onderwijs & Training


Wat zijn opportunistische <strong>infectie</strong>s?<br />

‣ OI is een <strong>infectie</strong> veroorzaakt door een<br />

micro-organisme organisme dat normaal geen ziekte<br />

veroorzaakt in een persoon met een<br />

normale immuniteit<br />

‣ Op het ogenblik van een verzwakking van<br />

het immuunsysteem wordt deze <strong>infectie</strong><br />

wel actief en levensbedreigend


30 year old teacher<br />

‣ Asymptomatic, during check up by the general<br />

practitioner found to be<br />

<strong>HIV</strong> seropositive<br />

‣ No medical follow up<br />

‣ …<br />

‣ 5 years later cough, temp 38°C<br />

‣ Chest physician: Chest X Ray normal<br />

‣ Cough syrup<br />

‣ 2 days later dyspnoea


Pneumocystis jiroveci


Op 28 AIDS aangiftes in 2005<br />

10<br />

9<br />

8<br />

7<br />

6<br />

5<br />

4<br />

3<br />

2<br />

1<br />

0<br />

PCP TB EC CMV ADC/PMLTOXO KS NHL MAC Fung<br />

Source: Erika Vlieghe (data: AIDS aangifte)


Opportunistische <strong>infectie</strong>s komen nog<br />

steeds voor ondanks HAART<br />

‣ Patiënten weten niet dat ze <strong>HIV</strong> positief<br />

zijn<br />

• Nooit laten of durven testen<br />

‣ Patiënten<br />

‘verdringen’ hun <strong>HIV</strong> diagnose<br />

• Komen laat, bij klachten<br />

‣ (Succes van HAART is 60-80%)<br />

• Therapie falen (non(<br />

non-adherence<br />

of resistentie)


<strong>HIV</strong> daling van de CD4 <br />

complicaties<br />

PREVENTIE?<br />

< 200 CD4 preventie door medicatie


Immunological staging<br />

Not significant immunosupression >500<br />

Mild immunosupression 350-499<br />

Advanced immunosup. 200-349<br />

Severe immunosup


WHO consultative meeting 1993<br />

Clinical staging of <strong>HIV</strong> in resource-<br />

limited settings, last version 2006<br />

WHO 1<br />

WHO 2<br />

WHO 3<br />

ADULTS<br />

WHO 4


Acute <strong>HIV</strong> infection (WHO stage I)


WHO stage 2


Seborrheic dermatitis


Herpes zoster<br />

(gordelroos)


Bacteriële<br />

pneumonie<br />

(klassieke<br />

longontsteking)


WHO stage 3


<strong>HIV</strong> and Tuberculosis


(Open) Long TBC


Type of TB in function of CD4 count<br />

500 CD4<br />

EARLY <strong>HIV</strong><br />

Typical Tuberculosis<br />

200 CD4<br />

50 CD4<br />

LATE <strong>HIV</strong><br />

Atypical<br />

PTB<br />

EPTB


Oral Thrush (orale(<br />

candida)<br />

Candida albicans is an<br />

endogenous yeast<br />

‣ 60% of patients per<br />

year with CD4 < 100<br />

‣ 10-20%<br />

Oesophageal<br />

candidiaisis


WHO stage IV


“Slim<br />

Disease”/Wasting


Causes of diarrhea<br />

‣ Infectious agents<br />

‣ Other causes<br />

AIDS enteropathy<br />

Kaposi’s sarcoma<br />

Lymphoma of the gut<br />

Medications<br />

Bacteria<br />

Protozoa<br />

Toxin induced<br />

Mycobacteria<br />

Helminthic<br />

Fungal<br />

Viral


‣ Typical chest X-rayX<br />

PCP, diagnosis<br />

• ‘Butterfly<br />

wings’ (25% normal!)<br />

‣ Sub-acute<br />

onset, , dry cough, , (fever(<br />

fever)<br />

‣ DYPNOEA (on(<br />

exertion)<br />

Diagnosis by<br />

clinical presentation,<br />

chest X-ray, , BAL


Casus<br />

‣ 58 jarige man<br />

‣ Bediende<br />

‣ Last om computer te bedienen<br />

‣ Hoofdpijn<br />

‣ Plotse hemi-paresis<br />

‣ Oppuntstelling CVA


Cerebral toxoplasmosis


Cerebral toxoplasmosis<br />

Cause : T. Gondii (oocysts<br />

in cat stools and<br />

undercooked meat)<br />

– invasion of lungs, heart, retinitis, brain<br />

SYMPTOMS:<br />

‣ Fever: 50%<br />

‣ Headache: 50-70%<br />

‣ Hemiparesis: : 50%<br />

‣ Seizures: 30%<br />

Diagnose : IgG, , scan, MRI (CSF normal)<br />

Response to empirical therapy


Casus 2<br />

‣ 38 jarige man<br />

‣ Homoseksueel<br />

‣ Hemiparese en abnormale beweging rechter<br />

arm<br />

‣ Traag denken<br />

‣ CT scan/MRI: multipele hypodense letsels in de<br />

witte stof van beide hemisferen<br />

‣ LP: PCR positief voor JC virus<br />

• PML: progressieve multifocale leuco-encephalopathie<br />

encephalopathie


Progressive multifocal<br />

leucoencephalopathy(PML)


Progressive Multifocal<br />

Leucoencephalopathy (PML)<br />

‣ JC virus<br />

‣ Sympt : insidious (no<br />

fever, no headache, no<br />

ICH)<br />

- Motor :Hemiparesis:<br />

Hemiparesis, hemiplegia<br />

- Visual : cortical blindness, hemianopsia dysarthria,<br />

- Cognitif : personality change, , dementia<br />

‣ Diagn: : CT Scan : multiple hypodense lesions<br />

of white matter, MRI, CSF: N (PCR: JC)<br />

‣ Prognosis : 6 M survival<br />

‣ Treatment = HAART<br />

‣ DD: lymphoma, toxo…


Casus 3<br />

‣ Homoseksuele man wordt door moeder<br />

binnengebracht op raadpleging<br />

‣ Geheugenstoornis sinds enkele maanden<br />

‣ Apathisch, komt niet meer buiten<br />

‣ Incontinent<br />

‣ Rolstoel


AIDS dementia complex


AIDS dementia Complex or <strong>HIV</strong><br />

Encephalopathy<br />

‣ Bijna 10% van de AIDS patiënten<br />

‣ Progressief over maanden<br />

‣ Gedragsstoornis<br />

‣ Motorische stoornissen<br />

‣ Geheugenstoornis<br />

‣ Exclusie diagnose<br />

‣ Normaal lumbaal vocht (JC negatief)


Cryptoccocal<br />

meningitis


AIDS related cancers<br />

‣ NHL/PCL/KS: veel frequenter in <strong>HIV</strong> + dan<br />

<strong>HIV</strong>- (60-200x)<br />

KS<br />

NHL<br />

PCL


Non-Hodgkin<br />

lymphoma


Cerebral lymphoma


Kaposi’s sarcoma


Kaposi’s sarcoma


NHL/PCL/KS<br />

‣ Geassocieerd met gamma-herpes<br />

virus<br />

(EBV, HHV-8)<br />

‣ na HAART: sterke daling in incidentie<br />

‣ maar: levensverwachting neemt toe life<br />

time risico verhoogt<br />

‣ Goede nieuws: betere overleving, met<br />

HAART, vergelijkbaar met <strong>HIV</strong> (-)(


Squamous cell carcinoma


Anal squamous carcinoma


Hoe deze OI te voorkomen?<br />

‣ Vaccinatie<br />

‣ Profylactisch antibiotica<br />

‣ Profylactisch INH<br />

‣ <strong>HIV</strong> diagnose tijdig stellen en…<br />

‣ HAART starten wanneer geindiceerd!


Incidence/year<br />

EUR/ US<br />

Cotrimoxazole<br />

> 10%<br />

PCP<br />

KS<br />

EC<br />

1-10%<br />


Incidence/year<br />

> 10%<br />

EUR/ US<br />

PCP<br />

KS<br />

EC<br />

1-10%<br />

Pneumovac<br />

Bacterial infections<br />

Chron Herpes simplex<br />

TB<br />

Toxoplasmosis<br />

cryptococcosis<br />

MAC<br />


Incidence/year<br />

EUR/ US<br />

> 10%<br />

PCP<br />

KS<br />

EC<br />

1-10%<br />


Incidence/year<br />

> 10%<br />

EUR/ US<br />

PCP<br />

KS<br />

EC<br />

1-10%<br />

INH<br />

Bacterial infections<br />

Chron Herpes simplex<br />

TB<br />

Toxoplasmosis<br />

cryptococcosis<br />

MAI<br />


Incidence/year<br />

> 10%<br />

1-10%<br />

INH<br />


Nieuwe AIDS gevallen in<br />

West- Europa<br />

30000<br />

25000<br />

20000<br />

15000<br />

10000<br />

5000<br />

0<br />

Aantal AIDS gevallen<br />

1986<br />

1987<br />

1988<br />

1989<br />

1990<br />

1991<br />

1992<br />

1993<br />

1994<br />

1995<br />

1996<br />

1997<br />

1998<br />

1999<br />

2000<br />

European Centre for the Epidemiological Monitoring of AIDS, France, 2001<br />

HAART


Syndroom van immuunreactivatie


Definition of IRIS<br />

Previously latent or incubating diseases<br />

which become symptomatic or worse<br />

after the introduction of HAART<br />

Paradoxical reaction: : worsening of<br />

symptoms of OI’s s which were already<br />

under treatment (TB, MAC, CMV),<br />

shortly after starting HAART


Susceptibility factors for IRD<br />

Antigens of opportunistic<br />

pathogens<br />

• Active infection<br />

• Subclin ical infection<br />

• Non-viable organisms<br />

IRD<br />

Disease susceptibility<br />

genes<br />

• Herpesvirus disease<br />

HLA-A2,-B44,-DR4<br />

IL12B-3’UTR*1<br />

• Mycobacterial disease<br />

TNFA-308*1<br />

IL6-174*G<br />

CD4 T-cells


En wat we verwachten is…<br />

HAART


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