Tuberculosis and the Immune Reconstitution Inflammatory Syndrome (IRIS) Bob Colebunders.
-
Upload
vanessa-zimmerman -
Category
Documents
-
view
226 -
download
2
Transcript of Tuberculosis and the Immune Reconstitution Inflammatory Syndrome (IRIS) Bob Colebunders.
![Page 1: Tuberculosis and the Immune Reconstitution Inflammatory Syndrome (IRIS) Bob Colebunders.](https://reader035.fdocuments.net/reader035/viewer/2022062404/55153a0355034685568b4bae/html5/thumbnails/1.jpg)
Tuberculosis and the Immune Reconstitution
Inflammatory Syndrome (IRIS)
Bob Colebunders
![Page 2: Tuberculosis and the Immune Reconstitution Inflammatory Syndrome (IRIS) Bob Colebunders.](https://reader035.fdocuments.net/reader035/viewer/2022062404/55153a0355034685568b4bae/html5/thumbnails/2.jpg)
Names
• Immune reconstitution inflammatory syndrome (IRIS)
• Immune restoration disease (IRD)
• Paradoxical reactions
![Page 3: Tuberculosis and the Immune Reconstitution Inflammatory Syndrome (IRIS) Bob Colebunders.](https://reader035.fdocuments.net/reader035/viewer/2022062404/55153a0355034685568b4bae/html5/thumbnails/3.jpg)
Pathogenesis
• Increased lymphoproliferative response to mycobacterium antigens in vitro
• Restoration of cutaneous response to Tuberculin
• Increased [Il-6], activation markers (CD38)
• Associated with TNFA-308*1, IL6-174*G
![Page 4: Tuberculosis and the Immune Reconstitution Inflammatory Syndrome (IRIS) Bob Colebunders.](https://reader035.fdocuments.net/reader035/viewer/2022062404/55153a0355034685568b4bae/html5/thumbnails/4.jpg)
Incidence TB/IRIS
Europe and USA– Narita et al 36% (Miami, 1998)– Wendel et al 11% (Baltimore 2001) – Breen et al 29% (London, 2004)– Breton et al 43% (Paris, 2004)
![Page 5: Tuberculosis and the Immune Reconstitution Inflammatory Syndrome (IRIS) Bob Colebunders.](https://reader035.fdocuments.net/reader035/viewer/2022062404/55153a0355034685568b4bae/html5/thumbnails/5.jpg)
Incidence TB/IRIS
Africa
– Breton et al: 41%
– No cases in TB/DOT study in South Africa (20 patients only)
India– Kumarasamy et al: IRIS of 15.2 cases per 100 patient-
years
– Patel et al: TB IRIS more often in patients with active TB at the start of HAART than in those without active TB at the start of HAART (11 [8.73] vs. 3 [2.32%], respectively; p = 0.0489).
![Page 6: Tuberculosis and the Immune Reconstitution Inflammatory Syndrome (IRIS) Bob Colebunders.](https://reader035.fdocuments.net/reader035/viewer/2022062404/55153a0355034685568b4bae/html5/thumbnails/6.jpg)
Risk factors for TB/IRIS
• Starting ARV’s within 6 weeks of TB treatment
• Disseminated, extra-pulmonary disease
• Low base line CD4 count
• Rise in CD4 %
• Fall in viral load
• High bacillary burden?
![Page 7: Tuberculosis and the Immune Reconstitution Inflammatory Syndrome (IRIS) Bob Colebunders.](https://reader035.fdocuments.net/reader035/viewer/2022062404/55153a0355034685568b4bae/html5/thumbnails/7.jpg)
Types of TB IRIS
• Patient unknown to have TB at the start of HAART
• Patient on TB treatment before or at the start of HAART
![Page 8: Tuberculosis and the Immune Reconstitution Inflammatory Syndrome (IRIS) Bob Colebunders.](https://reader035.fdocuments.net/reader035/viewer/2022062404/55153a0355034685568b4bae/html5/thumbnails/8.jpg)
Timing of IRIS
– Mean of 15 days after starting HAART
– Up to months (years)
– Syndrome lasts for 10-40+ days
![Page 9: Tuberculosis and the Immune Reconstitution Inflammatory Syndrome (IRIS) Bob Colebunders.](https://reader035.fdocuments.net/reader035/viewer/2022062404/55153a0355034685568b4bae/html5/thumbnails/9.jpg)
TB IRIS
![Page 10: Tuberculosis and the Immune Reconstitution Inflammatory Syndrome (IRIS) Bob Colebunders.](https://reader035.fdocuments.net/reader035/viewer/2022062404/55153a0355034685568b4bae/html5/thumbnails/10.jpg)
TB IRIS
![Page 11: Tuberculosis and the Immune Reconstitution Inflammatory Syndrome (IRIS) Bob Colebunders.](https://reader035.fdocuments.net/reader035/viewer/2022062404/55153a0355034685568b4bae/html5/thumbnails/11.jpg)
TB IRIS
![Page 12: Tuberculosis and the Immune Reconstitution Inflammatory Syndrome (IRIS) Bob Colebunders.](https://reader035.fdocuments.net/reader035/viewer/2022062404/55153a0355034685568b4bae/html5/thumbnails/12.jpg)
TB IRIS
![Page 13: Tuberculosis and the Immune Reconstitution Inflammatory Syndrome (IRIS) Bob Colebunders.](https://reader035.fdocuments.net/reader035/viewer/2022062404/55153a0355034685568b4bae/html5/thumbnails/13.jpg)
TB IRIS
![Page 14: Tuberculosis and the Immune Reconstitution Inflammatory Syndrome (IRIS) Bob Colebunders.](https://reader035.fdocuments.net/reader035/viewer/2022062404/55153a0355034685568b4bae/html5/thumbnails/14.jpg)
![Page 15: Tuberculosis and the Immune Reconstitution Inflammatory Syndrome (IRIS) Bob Colebunders.](https://reader035.fdocuments.net/reader035/viewer/2022062404/55153a0355034685568b4bae/html5/thumbnails/15.jpg)
![Page 16: Tuberculosis and the Immune Reconstitution Inflammatory Syndrome (IRIS) Bob Colebunders.](https://reader035.fdocuments.net/reader035/viewer/2022062404/55153a0355034685568b4bae/html5/thumbnails/16.jpg)
TB IRIS
![Page 17: Tuberculosis and the Immune Reconstitution Inflammatory Syndrome (IRIS) Bob Colebunders.](https://reader035.fdocuments.net/reader035/viewer/2022062404/55153a0355034685568b4bae/html5/thumbnails/17.jpg)
Prognosis– Breton et al: 16 cases of TB/IRIS: 5 ‘severe’
complications• Splenic rupture• Compressive lymphadenopathy• Ureteric obstruction
– Narita et al: The study found a 6-fold increased risk of subsequent TB relapse in patients who experienced IRIS during early TB treatment.
![Page 18: Tuberculosis and the Immune Reconstitution Inflammatory Syndrome (IRIS) Bob Colebunders.](https://reader035.fdocuments.net/reader035/viewer/2022062404/55153a0355034685568b4bae/html5/thumbnails/18.jpg)
MRI: TB abscess spinal cord
![Page 19: Tuberculosis and the Immune Reconstitution Inflammatory Syndrome (IRIS) Bob Colebunders.](https://reader035.fdocuments.net/reader035/viewer/2022062404/55153a0355034685568b4bae/html5/thumbnails/19.jpg)
Cryptococcal meningitis treated with HAART, bilateral blindness: fundoscopy: bilateral
papiloedema: IRIS?
![Page 20: Tuberculosis and the Immune Reconstitution Inflammatory Syndrome (IRIS) Bob Colebunders.](https://reader035.fdocuments.net/reader035/viewer/2022062404/55153a0355034685568b4bae/html5/thumbnails/20.jpg)
Differential diagnosis
• Side effects of the antiretroviral treatment
• Drug fever
• TB infection not responding to standard anti-TB treatment
• Other concomitant infection
• Failure of HAART (late IRIS)
![Page 21: Tuberculosis and the Immune Reconstitution Inflammatory Syndrome (IRIS) Bob Colebunders.](https://reader035.fdocuments.net/reader035/viewer/2022062404/55153a0355034685568b4bae/html5/thumbnails/21.jpg)
Proposed criteria for the diagnosis of IRIS in HIV patients on
antiretroviral therapyFrench et al
![Page 22: Tuberculosis and the Immune Reconstitution Inflammatory Syndrome (IRIS) Bob Colebunders.](https://reader035.fdocuments.net/reader035/viewer/2022062404/55153a0355034685568b4bae/html5/thumbnails/22.jpg)
Major criteria
• Atypical presentation of ‘opportunistic infections or tumours’ in patients responding to antiretroviral therapy
• Decrease in plasma HIV RNA level by 1log10 copies/mL
![Page 23: Tuberculosis and the Immune Reconstitution Inflammatory Syndrome (IRIS) Bob Colebunders.](https://reader035.fdocuments.net/reader035/viewer/2022062404/55153a0355034685568b4bae/html5/thumbnails/23.jpg)
Minor criteria
• Increased blood CD4 T-cell count after HAART• Increase in an immune response specific to the
relevant pathogen, e.g. DTH response to mycobacterial antigens
• Spontaneous resolution of disease without specific antimicrobial therapy or tumour chemotherapy with continuation of anti-retroviral therapy anti-retroviral therapy
![Page 24: Tuberculosis and the Immune Reconstitution Inflammatory Syndrome (IRIS) Bob Colebunders.](https://reader035.fdocuments.net/reader035/viewer/2022062404/55153a0355034685568b4bae/html5/thumbnails/24.jpg)
“Suspected TB IRIS”: a TB patient who after starting HAART develops either
• New persistent fevers (temperature >38.6°C) which last for more than 1 week without an identifiable source (e.g., urine and sputa testing, and other procedures when clinically indicated) or reason (e.g. an allergic reaction)
• or marked worsening or emergence of intrathoracic lymphadenopathy, pulmonary infiltrates
• or worsening or emergence of cervical adenopathies/abscesses, or worsening of other tuberculous lesions or manifestations, such as cutaneous peritoneal or central nervous system (CNS) inflammatory pathology.
![Page 25: Tuberculosis and the Immune Reconstitution Inflammatory Syndrome (IRIS) Bob Colebunders.](https://reader035.fdocuments.net/reader035/viewer/2022062404/55153a0355034685568b4bae/html5/thumbnails/25.jpg)
“Suspected TB IRIS”: a patient who after starting HAART develops TB characterised by
the formation of
• Large adenopathies
• Abscesses
• Miliary TB with large nodules
• Cavity formation
![Page 26: Tuberculosis and the Immune Reconstitution Inflammatory Syndrome (IRIS) Bob Colebunders.](https://reader035.fdocuments.net/reader035/viewer/2022062404/55153a0355034685568b4bae/html5/thumbnails/26.jpg)
“Confirmed” TB IRIS
Same definition as suspected TB IRIS but
• multi drug resistant TB excluded
and
• a satisfactory virological response to ART
![Page 27: Tuberculosis and the Immune Reconstitution Inflammatory Syndrome (IRIS) Bob Colebunders.](https://reader035.fdocuments.net/reader035/viewer/2022062404/55153a0355034685568b4bae/html5/thumbnails/27.jpg)
Diagnostic investigations
• AFB may be be present or absent
• Viable organisms despite TB treatment since > 2 months may suggest treatment failure
• Tuberculin skin testing– 88% of IRIS negative– 33% of non-IRIS negative
![Page 28: Tuberculosis and the Immune Reconstitution Inflammatory Syndrome (IRIS) Bob Colebunders.](https://reader035.fdocuments.net/reader035/viewer/2022062404/55153a0355034685568b4bae/html5/thumbnails/28.jpg)
![Page 29: Tuberculosis and the Immune Reconstitution Inflammatory Syndrome (IRIS) Bob Colebunders.](https://reader035.fdocuments.net/reader035/viewer/2022062404/55153a0355034685568b4bae/html5/thumbnails/29.jpg)
Recommendations to prevent TB IRIS
• Exclude TB before starting antiretroviral therapy
• Treat first the TB and start antiretroviral treatment only once the patient has clinically improved, is tolerating very well his TB treatment
• Increase awareness about TB IRIS
![Page 30: Tuberculosis and the Immune Reconstitution Inflammatory Syndrome (IRIS) Bob Colebunders.](https://reader035.fdocuments.net/reader035/viewer/2022062404/55153a0355034685568b4bae/html5/thumbnails/30.jpg)
Treatment recommendations
• TB treatment should be continued
• Exclude treatment failure– Ensure adequate treatment– Ensure adherence to ATT– Consider drug resistance
![Page 31: Tuberculosis and the Immune Reconstitution Inflammatory Syndrome (IRIS) Bob Colebunders.](https://reader035.fdocuments.net/reader035/viewer/2022062404/55153a0355034685568b4bae/html5/thumbnails/31.jpg)
Treatment recommendations
• Drainage
• Adding prednisolone/NSAIDS may be beneficial
• Continue HAART in most cases
• Consider stopping ARV’s if life threatening?
![Page 32: Tuberculosis and the Immune Reconstitution Inflammatory Syndrome (IRIS) Bob Colebunders.](https://reader035.fdocuments.net/reader035/viewer/2022062404/55153a0355034685568b4bae/html5/thumbnails/32.jpg)
Research questions?
• Propose definition of IRIS
• Validate clinical definition of IRIS
• Incidence of TB IRIS in different populations?
• Predictors/risk factors for IRIS?
• Morbidity and mortality (cause of early deaths?)
• What are the potential long term consequences?
![Page 33: Tuberculosis and the Immune Reconstitution Inflammatory Syndrome (IRIS) Bob Colebunders.](https://reader035.fdocuments.net/reader035/viewer/2022062404/55153a0355034685568b4bae/html5/thumbnails/33.jpg)
How to diagnose TB IRIS?
• What are the clinical manifestations of TB IRIS in adults and children?
• Are there immunological markers or other simple laboratory parameters that could help to diagnose TB IRIS?
• How useful is it to perform a tuberculin skin test prior to the start of ARVs and to repeat it when there is a suspicion of IRIS?
![Page 34: Tuberculosis and the Immune Reconstitution Inflammatory Syndrome (IRIS) Bob Colebunders.](https://reader035.fdocuments.net/reader035/viewer/2022062404/55153a0355034685568b4bae/html5/thumbnails/34.jpg)
What is the pathophysiology of TB IRIS (early and late forms of IRIS)?
![Page 35: Tuberculosis and the Immune Reconstitution Inflammatory Syndrome (IRIS) Bob Colebunders.](https://reader035.fdocuments.net/reader035/viewer/2022062404/55153a0355034685568b4bae/html5/thumbnails/35.jpg)
How to treat TB IRIS?
Corticosteroids (dose, duration)?, NSAIDs? thalidomide?…Aspiration of abscesses?
Should HAART be stopped? When?
Should the management of early and late TB IRIS be different?
![Page 36: Tuberculosis and the Immune Reconstitution Inflammatory Syndrome (IRIS) Bob Colebunders.](https://reader035.fdocuments.net/reader035/viewer/2022062404/55153a0355034685568b4bae/html5/thumbnails/36.jpg)
How to prevent/avoid IRIS?
• When is the optimal moment HAART should be started in a HIV/TB co infected patient?
• TB prophylaxis to avoid IRIS?
• Corticosteriod therapy able to prevent the development of TB IRIS?
![Page 37: Tuberculosis and the Immune Reconstitution Inflammatory Syndrome (IRIS) Bob Colebunders.](https://reader035.fdocuments.net/reader035/viewer/2022062404/55153a0355034685568b4bae/html5/thumbnails/37.jpg)
Operational issues
• How to diagnose TB IRIS clinically at the primary health level?
• When should a health care worker at the primary health care level refer a patient or call for advice?
![Page 38: Tuberculosis and the Immune Reconstitution Inflammatory Syndrome (IRIS) Bob Colebunders.](https://reader035.fdocuments.net/reader035/viewer/2022062404/55153a0355034685568b4bae/html5/thumbnails/38.jpg)
Research methods
• Cohort studies
• Randomised clinical trials