PPT Rizzardini "HAART, sostenibilità di un miracolo"StopTb Italia
This document discusses the sustainability of highly active antiretroviral therapy (HAART) for HIV/AIDS treatment. It begins by recounting the history of HAART from initial hope to "miracle" outcomes. However, it notes the global economic crisis challenges sustainability of healthcare systems. Charts show rising healthcare costs as a percentage of GDP in many nations by 2030 and 2050. Italy faces a large national debt and rising healthcare spending. The document questions if the HAART miracle can continue given these economic pressures and need to control costs.
PPT Rusconi "Le multiresistenze dell'HIV/AIDS"StopTb Italia
This document discusses HIV drug resistance and multiresistance. It notes that the emergence of resistance is an inevitable consequence of incomplete viral suppression by antiretroviral drugs. Resistance can develop through the selection of pre-existing mutations under drug pressure or the generation of new mutations over time. The level of resistance depends on factors like the genetic barrier of the drugs. Long-term failing treatment can lead to the accumulation of multiple resistance mutations. Data is presented on increasing resistance prevalence correlated with higher viral loads. Resistance testing is important to identify mutations and guide treatment choices.
PPT Rizzardini "HAART, sostenibilità di un miracolo"StopTb Italia
This document discusses the sustainability of highly active antiretroviral therapy (HAART) for HIV/AIDS treatment. It begins by recounting the history of HAART from initial hope to "miracle" outcomes. However, it notes the global economic crisis challenges sustainability of healthcare systems. Charts show rising healthcare costs as a percentage of GDP in many nations by 2030 and 2050. Italy faces a large national debt and rising healthcare spending. The document questions if the HAART miracle can continue given these economic pressures and need to control costs.
PPT Rusconi "Le multiresistenze dell'HIV/AIDS"StopTb Italia
This document discusses HIV drug resistance and multiresistance. It notes that the emergence of resistance is an inevitable consequence of incomplete viral suppression by antiretroviral drugs. Resistance can develop through the selection of pre-existing mutations under drug pressure or the generation of new mutations over time. The level of resistance depends on factors like the genetic barrier of the drugs. Long-term failing treatment can lead to the accumulation of multiple resistance mutations. Data is presented on increasing resistance prevalence correlated with higher viral loads. Resistance testing is important to identify mutations and guide treatment choices.
PPT Concia "Localizzazioni extrapolmonari nella coinfezione"StopTb Italia
This document discusses various sites of extrapulmonary tuberculosis. It begins by listing common sites of extrapulmonary TB, with percentages of extrapulmonary cases that occur at each site. The most common sites are pleura (20-25%), lymphatics (20-40%), and genitourinary (5-18%). It then discusses specific forms of extrapulmonary TB including tuberculosis of the central nervous system, bones/joints, skin, and other organ systems. Risk factors for developing extrapulmonary TB are also mentioned.
PPT Bonora "Clinica e terapia dell'HIV"StopTb Italia
The document discusses the clinical management of HIV infection and lessons from anti-tuberculosis therapy. It notes that combination antiretroviral therapy is effective at suppressing HIV due to its ability to prevent the selection of drug-resistant strains, in contrast to less effective single-drug regimens. Over time, combination therapy has resulted in more HIV-infected individuals achieving sufficient immune recovery to approach the life expectancy of the general population. However, non-AIDS comorbidities have become more prevalent as the HIV-infected population ages.
This document summarizes a presentation on immunological testing for tuberculosis (TB) and HIV co-infection. It discusses the clinical utility of interferon gamma release assays (IGRAs) for detecting latent TB infection (LTBI) in HIV-infected individuals. While IGRAs perform similarly to the tuberculin skin test (TST) in identifying those who could benefit from LTBI treatment, important questions remain about their use in HIV-positive populations with different CD4 counts. The document also examines the diagnostic value of IGRAs for active TB, finding no evidence they are more sensitive than the TST, especially in low- and middle-income countries.
PPT Castelli "Dall'HIV all'AIDS fino alla coinfezione: una diagnosi difficile?"StopTb Italia
This document discusses the challenges of diagnosing HIV, AIDS, and co-infections. It notes that distinguishing between HIV infection, AIDS, and co-infections can be difficult. Point-of-care rapid tests have helped increase HIV testing, though they cannot identify acute HIV infections. The document emphasizes the importance of confirming positive rapid HIV tests with supplemental tests due to the potential for false positives in low prevalence populations.
PPT Bocchino "Diagnosi dell'infezione tubercolare"StopTb Italia
This document summarizes guidelines for diagnosing tuberculosis infection. It discusses the characteristics and performance of interferon gamma release assays (IGRAs) like QFT-IT and T-SPOT compared to the tuberculin skin test (TST). While IGRAs generally have higher specificity than TST, their sensitivity can be reduced in high prevalence settings. Factors like BCG vaccination, repeated exposures, and immunocompromise can affect test performance. Guidelines provide recommendations on using IGRAs and TST depending on the clinical setting and population. Further research is still needed to optimize IGRA testing methods and better predict which individuals will develop active tuberculosis.
PPT Angarano "Storia naturale dell'HIV"StopTb Italia
The document summarizes the natural history of HIV/AIDS, beginning with its identification and description in 1981. It describes how HIV attacks and destroys CD4+ T cells, ultimately overwhelming the immune system. As the immune system is compromised, victims develop secondary infections and diseases that they are no longer able to fight off, leading to AIDS and death if left untreated. The introduction of antiretroviral therapy in the 1990s was able to control viral replication and boost CD4+ counts, reducing AIDS-related illnesses and death rates dramatically. However, even with treatment, chronic inflammation persists and contributes to accelerated aging effects and non-AIDS comorbidities over time.
The document discusses the genetic epidemiology of tuberculosis. It summarizes that analysis of TB epidemics in Europe from the 18th-19th centuries found mortality rates of up to 2% per year without chemotherapy. There was an initial spike in cases over the first 50-100 years, followed by a slow decline over the next 200-250 years. This supports the hypothesis that the initial phase eliminated the most susceptible 20% of the population.
The document summarizes epidemiological data on tuberculosis (TB) in Italy and globally. It notes that the TB notification rate in Italy decreased by 7.7% from 2007 to 2012. In 2012, 58.3% of Italian TB cases were in foreign-born individuals and the rate of multi-drug resistant TB was 3%. Globally in 2012, there were an estimated 8.6 million incident TB cases and 1.3 million deaths, with South-East Asia and Africa accounting for most cases and deaths. Major ongoing challenges include TB/HIV co-infection, multi-drug resistant TB, and improving detection of "missing" TB cases.
TB situation in 2011:Findings from the ECDC and WHO/EURO joint TB surveillanc...StopTb Italia
The document summarizes tuberculosis (TB) data from 2011 in the European Union and European Economic Area (EU/EEA). Some key findings include:
- 72,334 TB cases were reported in the EU/EEA in 2011, with notification rates ranging widely between countries.
- Overall notification rates have declined steadily between 2007-2011.
- Laboratory confirmation of TB cases varied between countries, from 28-95% of cases.
- Foreign-born individuals accounted for 25.8% of TB cases on average across EU/EEA countries.
PPT Raviglione "Stop TB in my lifetime -Giornata Mondiale della Tubercolosi"StopTb Italia
This document summarizes the global burden of tuberculosis (TB) in 2011. Some key points:
- There were an estimated 8.7 million new TB cases and 1.4 million TB deaths in 2011. The majority of cases and deaths occurred in Asia and Africa.
- TB is a leading cause of death among people living with HIV, with 1.1 million new HIV-associated TB cases in 2011. 80% of the global TB/HIV burden is in Africa.
- There were an estimated 630,000 multi-drug resistant TB cases in 2011, with over 60% occurring in China, India, Russia and other countries.
- Women and children also face a large burden,
PPT Concia "Localizzazioni extrapolmonari nella coinfezione"StopTb Italia
This document discusses various sites of extrapulmonary tuberculosis. It begins by listing common sites of extrapulmonary TB, with percentages of extrapulmonary cases that occur at each site. The most common sites are pleura (20-25%), lymphatics (20-40%), and genitourinary (5-18%). It then discusses specific forms of extrapulmonary TB including tuberculosis of the central nervous system, bones/joints, skin, and other organ systems. Risk factors for developing extrapulmonary TB are also mentioned.
PPT Bonora "Clinica e terapia dell'HIV"StopTb Italia
The document discusses the clinical management of HIV infection and lessons from anti-tuberculosis therapy. It notes that combination antiretroviral therapy is effective at suppressing HIV due to its ability to prevent the selection of drug-resistant strains, in contrast to less effective single-drug regimens. Over time, combination therapy has resulted in more HIV-infected individuals achieving sufficient immune recovery to approach the life expectancy of the general population. However, non-AIDS comorbidities have become more prevalent as the HIV-infected population ages.
This document summarizes a presentation on immunological testing for tuberculosis (TB) and HIV co-infection. It discusses the clinical utility of interferon gamma release assays (IGRAs) for detecting latent TB infection (LTBI) in HIV-infected individuals. While IGRAs perform similarly to the tuberculin skin test (TST) in identifying those who could benefit from LTBI treatment, important questions remain about their use in HIV-positive populations with different CD4 counts. The document also examines the diagnostic value of IGRAs for active TB, finding no evidence they are more sensitive than the TST, especially in low- and middle-income countries.
PPT Castelli "Dall'HIV all'AIDS fino alla coinfezione: una diagnosi difficile?"StopTb Italia
This document discusses the challenges of diagnosing HIV, AIDS, and co-infections. It notes that distinguishing between HIV infection, AIDS, and co-infections can be difficult. Point-of-care rapid tests have helped increase HIV testing, though they cannot identify acute HIV infections. The document emphasizes the importance of confirming positive rapid HIV tests with supplemental tests due to the potential for false positives in low prevalence populations.
PPT Bocchino "Diagnosi dell'infezione tubercolare"StopTb Italia
This document summarizes guidelines for diagnosing tuberculosis infection. It discusses the characteristics and performance of interferon gamma release assays (IGRAs) like QFT-IT and T-SPOT compared to the tuberculin skin test (TST). While IGRAs generally have higher specificity than TST, their sensitivity can be reduced in high prevalence settings. Factors like BCG vaccination, repeated exposures, and immunocompromise can affect test performance. Guidelines provide recommendations on using IGRAs and TST depending on the clinical setting and population. Further research is still needed to optimize IGRA testing methods and better predict which individuals will develop active tuberculosis.
PPT Angarano "Storia naturale dell'HIV"StopTb Italia
The document summarizes the natural history of HIV/AIDS, beginning with its identification and description in 1981. It describes how HIV attacks and destroys CD4+ T cells, ultimately overwhelming the immune system. As the immune system is compromised, victims develop secondary infections and diseases that they are no longer able to fight off, leading to AIDS and death if left untreated. The introduction of antiretroviral therapy in the 1990s was able to control viral replication and boost CD4+ counts, reducing AIDS-related illnesses and death rates dramatically. However, even with treatment, chronic inflammation persists and contributes to accelerated aging effects and non-AIDS comorbidities over time.
The document discusses the genetic epidemiology of tuberculosis. It summarizes that analysis of TB epidemics in Europe from the 18th-19th centuries found mortality rates of up to 2% per year without chemotherapy. There was an initial spike in cases over the first 50-100 years, followed by a slow decline over the next 200-250 years. This supports the hypothesis that the initial phase eliminated the most susceptible 20% of the population.
The document summarizes epidemiological data on tuberculosis (TB) in Italy and globally. It notes that the TB notification rate in Italy decreased by 7.7% from 2007 to 2012. In 2012, 58.3% of Italian TB cases were in foreign-born individuals and the rate of multi-drug resistant TB was 3%. Globally in 2012, there were an estimated 8.6 million incident TB cases and 1.3 million deaths, with South-East Asia and Africa accounting for most cases and deaths. Major ongoing challenges include TB/HIV co-infection, multi-drug resistant TB, and improving detection of "missing" TB cases.
TB situation in 2011:Findings from the ECDC and WHO/EURO joint TB surveillanc...StopTb Italia
The document summarizes tuberculosis (TB) data from 2011 in the European Union and European Economic Area (EU/EEA). Some key findings include:
- 72,334 TB cases were reported in the EU/EEA in 2011, with notification rates ranging widely between countries.
- Overall notification rates have declined steadily between 2007-2011.
- Laboratory confirmation of TB cases varied between countries, from 28-95% of cases.
- Foreign-born individuals accounted for 25.8% of TB cases on average across EU/EEA countries.
PPT Raviglione "Stop TB in my lifetime -Giornata Mondiale della Tubercolosi"StopTb Italia
This document summarizes the global burden of tuberculosis (TB) in 2011. Some key points:
- There were an estimated 8.7 million new TB cases and 1.4 million TB deaths in 2011. The majority of cases and deaths occurred in Asia and Africa.
- TB is a leading cause of death among people living with HIV, with 1.1 million new HIV-associated TB cases in 2011. 80% of the global TB/HIV burden is in Africa.
- There were an estimated 630,000 multi-drug resistant TB cases in 2011, with over 60% occurring in China, India, Russia and other countries.
- Women and children also face a large burden,
5. • Prevalence of infectious cases
• Duration of illness
• Intensity, frequency and duration of
contact Largely
endogenous
Largely exogenous Innate resistance
Form and site of TB
• Particles/volume x exposure time Performance of cell-
Age
• Production of infectious droplets mediated immunity
Patient’s susceptibility
• Clearance of air
Delay in diagnosis
• Extent of exposure Re-infection
Strain virulence
RF
RF
RF RF Infectious
Tuberculosis
Subclinical
Exposure Infection Death
Non-infectious
Tuberculosis
Modello epidemiologico
TB
6. PRIMA DI VON PIRQUET
Jenner
Pasteur
Koch 1890
• Cavie venute a contatto con MT viventi o morti acquisivano
resistenza a nuova infezione (fenomeno di Koch)
• Uso di filtrato sterile di coltura di MT (vecchia tubercolina -OT)
• Immunità ritardata
• USO A SCOPO TERAPEUTICO
Eber, Pearson1890 : uso di OT nel bestiame
• identifica infezione TB non clinicamente evidente
10. USO DIAGNOSTICO
1907 Clemens von Pirquet
comparsa precoce del nodulo nel fenomeno di Koch
allergia batterica
( ipersensibilità ai componenti del MT)
prima prova diagnostica della tubercolosi
Clemens Freiherr von Pirquet, Klinische Studien über Vakzination und vakzinale Allergie.
Leipzig–Wien : F. Deuticke, 1907
^ "Kutane und konjunktivale Tuberkulinreaktionen". In: Handbuch d. Technik und Method. der
Immunitätsforschung, 1st supplementary volume, Jena 1911
11. REAZIONE DI VON PIRQUET
Reazione cutanea ritardata
caratterizzata dall'insorgenza di
un'area arrossata e in rilievo che
segue, a distanza di 24-48 ore,
l'applicazione di una goccia di
soluzione della vecchia tubercolina
sulla pelle lievemente scarificata
13. METODI DI SOMMINISTRAZIONE
Patch test
Test percutaneo
Test congiuntivale
Test sottocutaneo
1908 Mantoux : Intradermoreazione
• Dose certa
• Lettura quantitativa (mm)
14. MIGLIORARE IL TEST
………
Sostanza (Siebert (1934)
Tuberculin is an extract of tubercle bacilli
• Molta ricerca fino agli anni 50 dedicata agli effetti terapeutici
• PPD-s (purified protein derivative)
• Maggiore specificità
• Assenza di capacità sensibilizzante
DOSE
• Da 1 a 250 TU
CUT-OFF diagnostico
• 5, 10, 15 mm
15. DOSI
Cumulative Percentage of Children Reacting to Increasing Doses
of Tuberculin, Among Healthy Children and Tuberculosis Patients
5 TU PPD-S
100
Tuberculosis patients
Per cent reacting
80
60
Healthy children
40
20
0
10 -9 10 -8 10 -7 10 -6 10 -5 10 -4 10 -3 10 -2 10 -1 10 0
Dose of tuberculin (mg)
Furcolow ML, et al. Public Health Rep 1941;56:1082-1100
16. DISTRIBUZIONE DELLE RISPOSTE
Distribution of Reaction Sizes to 5 TU Tuberculin PPD-S
in 5,544 Tuberculosis Patients, United States
20
Per cent reacting
15
10
5
0
0 5 10 15 20 25 30
Induration (mm)
Edwards LB, et al. Am Rev Respir Dis 1969;99(4, part 2 of 2):1-132
17. SPECIFICITA’
Tuberculin Skin Test Reaction Size Distribution
in Two Tuberculin Surveys, Korea 1965 and 1995
0.06 1965
Fraction reacting
0.04
0.02
0.00
0 5 10 15 20 25 30
0.06
1995
Fraction reacting
0.04
0.02
0.00
0 5 10 15 20 25 30
Induration (mm)
Korean Institute of Tuberculosis 1966:1-181
Korean National Tuberculosis Institute 1996:1-180
18. IL CUT-OFF
Frequency Distributions of Tuberculin Skin Test
Reaction Sizes in Surveys in Tanzania and Djibouti
0.10
Tanzania
0.08
0.06
Fraction reacting
0.04
0.02
0.00
0 5 10 15 20 25 30 35
0.10
0.08 Djibouti
0.06
0.04
0.02
0.00
0 5 10 15 20 25 30 35
Induration (mm)
Styblo K. TSRU Progress Report 1998;1:31-66
Data courtesy Djibouti: Trébucq A, IUATLD, 1995
19. VACCINAZIONE CON BCG
Distribution of Tuberculin Skin Test Reactions 2 1/2 Months to
4 to 5 Years After BCG Vaccination in Madras and in Puerto Rico
30 At 2 1/2 months
Chingleput
At 4
20 years
Per cent reacting
10
0
0 5 10 15 20 25 30
20
Induration (mm) to 5 years
At 4
Puerto Rico
10
0
0 5 10 15 20 25 30
Induration (mm)
Tuberculosis Prevention Trial, Madras. Indian J Med Res 1980;72(suppl):1-74
Comstock GW, et al. Am J Public Health 1974;64:283-91
20. EFFETTO DEL TEMPO DI LETTURA
0 150
100%
90%
Spec
80% Sens
70%
24 48 72 96 120
Ore dall’inoculo
24 vs 48 ore (GS)
71% sensibilità; 81% specificità
Menzies chp. 12 in Reichman 2000
21. CORRELAZIONE TRA REAZIONE CUTANEA AL
PPD E RISCHIO DI SVILUPPARE TB ATTIVA
20
N. casi di TB nel follow-up
18
16
14
12
10
8
6
4
2
0
5 10 15 20 25
Reazione PPD (mm)
23. USO LONGITUDINALE
Variazioni somministrazione, lettura, casuali
• 2/3 mm (5 mm =1.96 sd)
Boosting (Richiamo di immunità in assenza di nuova infezione)
• Rischio TB < 0,05%
• Fino a 2 anni dal I test
• 1-10% (dipende da NTM e BCG)
• 90% < 10 mm
Conversione (nuova infezione)
• Rischio TB > 5% anno
• Incremento di 10 mm (5 mm in CT) se il
precedente <10 mm
25. LIMITI DEL TST (MANTOUX TEST)
Somministrazione e LETTURA
• Personale addestrato
• Ritorno del testato
• Non ritorni >30%. Chaisson et al 1996, Serwint et al 1997, Malotte et al 1999, Tanke et al 1994
Soggettività e variabilità
• Interpretazione stratificata per livello di rischio (5,10, 15 mm).
• NTM e BCG. Huebner et al 1993, Lalvani et al 2001, Delgado et al 2002
• Cross reactività con BCG
• >10% falsi + per BCG; 10% NTM +, di cui 30% con TST +. Margileth 1994,
Huebner et al 1993, Von Reyn et al 2001
• Variazione PPD tra produttori e batch
• Villarino et al 2000, Chaparas et al 1985
Riproducibilità scarsa
• Kendig et al 1998
Boosting–
• Test ripetuti danno falsi positivi (Conversioni)(BCG)
Poco sensibile in TB attiva
• 20 to 40% of active TB patients are TST negative.Pathan et al 2000, Fietta et al 1985, ATS/CDC
Diagnostic guidelines
Anergia & HIV
• > 50% di coinfettati TB/HIV sono TST -
26. MODERNE MISURE DIAGNOSTICHE
PER TB: IFN- Γ IN VITRO
Purified lymphocyte techniques
• PBMC culture
• Flow cytometry
• Elispot
Whole blood culture
• QuantiFERON
• Diluted whole blood
27. IN VIVO AND IN VITRO
DIAGNOSTIC TESTS
IFN-γ"
Presentation of"
mycobacterial antigens" TNF-α" IL-8, etc."
IFN-γ"
Antigen" Memory"
TNF-α" IL-8, etc."
presenting" T-cell"
cell"
Andersen P, et al. Lancet 2000;356:1099"
29. SPECIE SPECIFICITÀ
DI ESAT-6 E CFP-10 (TB7.7 IN TUBE)
TB Complex Antigens Environmental Antigens
strains ESAT CFP
ESAT CFP
M abcessus - -
M avium - -
M tuberculosis + +
M branderi - -
M africanum + + M celatum - -
M bovis + + M chelonae - -
BCG substrain M fortuitum - -
M gordonii - -
gothenburg - -
M intracellulare - -
moreau - - M kansasii + +
tice - - M malmoense - -
tokyo - - M marinum + +
M oenavense - -
danish - -
M scrofulaceum - -
glaxo - - M smegmatis - -
montreal - - M szulgai + +
pasteur - - M terrae - -
M vaccae - -
M xenopi - -
30. EFFETTO DELLA VICINANZA
Effetto della vicinanza
30
25
20
15
OR
10
5
0
4 3 2 1 4 3 2 1
ESAT6 PPD
-5
Test/Distanza
Ewer K, et al. . Lancet 2003; 361: 1168-73
31. VALORE PREDITTIVO VERSO
SVILUPPO DI TBA
• Doherty et al (JCM 2002)
• 2-year follow up of 24 household contacts in Ethiopia
RR TBA with 95% CI vs Test +
6
5
4
3
2
1
0
ESAT6 PPD
32. Mantoux vs test IFN-γ
Clinical Organismo T-cell Mantoux IFN- γ
presente
TB guarita No M Pos Neg ?
TB attiva Si E Pos Pos
LTBI Si E Pos Pos
BCG Vac No M Pos/Neg Neg
Esposizione a ? NTM M +/ -E Pos (?) Neg
NTM
33. VANTAGGI OPERATIVI DI TEST IFΓ
Specificità è Riduce Da studiare l’impatto
trattamenti inutili
Non necessita di una visita Resta la necessità di
di ritorno per la lettura del comunicare i risultati
test
Personale ? (counceling)
Minore variabilità Da studiare
nell’esecuzione e nella
lettura dei risultati
Standardizzazione per In sviluppo
quanto riguarda i reagenti
Nessun rischio di possibili Vero
effetti collaterali sistemici
Non è affetto da effetti di Vero
potenziamento (booster).
34. SVANTAGGI OPERATIVI IGRA
Il campione di sangue deve essere processato in
temi rapidi
Costi elevati
• QF tube 30 € per test
Elevata massa critica di test per una ragionevole
economia di scala, con possibile ritardo nell’esame
e nei provvedimenti conseguenti
Necessita di un laboratorio con attrezzatura
minima
Rischio per prelievi ematici in popolazioni con
elevato rischio di infezione HIV e da HBsB e C
• Rifiuto del prelievo da parte di gruppi di soggetti a rischio
36. TEST SERIALI
UNA VOLTA POSITIVO
SEMPRE POSITIVO ?
NON E’ UTILE RIPETERE
37. KEY QUESTIONS
What are appropriate cut-off points for different
groups?
What is the normal variation in T-cell responses?
What is the risk of active disease in those with
positive and negative IGRA results? How does this
relate to risk associated with positive TST?
Is there a cut-off point that will predict incipient
active TB?
How should conversions and reversions be defined
(incrementally), and how often do they occur?
Pai, M et al, Lancet Infect Dis 2007; 7: 428-38
CDC 2010
38. PROBLEMI APERTI
Infezione TB o TB latente
• persistenza di micobatteri della tubercolosi nell’organismo
in assenza di evidenza clinica, batteriologica e radiologica di
malattia tubercolare
L’assenza di GOLD standard non permette di valutare sensibilità
e specificità verso la
VERA CONDIZIONE DA CERCARE E TRATTARE
Specificità e VP+ dei test verosimilmente molto più bassa di
quanto stimato
IL TEST TUBERCOLINICO (E GLI IGRA) E’ UN TEST
NON UNA CONDIZIONE
39. PROBLEMI APERTI
Che cosa cerchiamo ?
Infezione TB o TB latente
• persistenza di micobatteri della tubercolosi nell’organismo in
assenza di evidenza clinica, batteriologica e radiologica di
malattia tubercolare
Che cosa misuriamo ?
• persistente risposta delle cellule T specifiche per i micobatteri
in assenza di evidenza clinica di malattia tubercolare
40. All Theories of
memory cell
development would
suggest that memory
T cell formation is a
function of
withdrawal of antigen
(Kaech et al 2002)
?????????????
41. CAMBIAMENTI CON IL
TRATTAMENTO
Ø Modello 1:
• Il trattamento eradica l’antigene
è Riduzione IFγ
Ø Modello 2
§ Il trattamento stimola l’immunità
è Aumento IFγ
Ø Modello 3: Nessun effetto
• LA RISPOSTA AI TEST DOPO L’ERADICAZIONE
DELL’ANTIGENE SCOMPARE
• IN TEMPI NON NOTI (anni)
• IN UNA PROPORZIONE NON DETERMINATA DI SOGGETTI
42. LATENT TUBERCULOSIS INFECTION
OR LASTING IMMUNE RESPONSES
TO M. TUBERCULOSIS?
• Latency, as assayed by TST and IGRA, is a:
• state of persistent mycobacteria-specific T-cell
responses in the absence of clinical evidence for
tuberculosis disease (A).
• Whether latent tuberculosis infection depends on the
presence of living mycobacteria is presently unclear
( A).
• The tuberculin skin test and IGRAs measures:
• “lasting tuberculosis immune responses”
• not “latent tuberculosis infection” (A).
• can not discriminate active from latent infection (A).
Mack, U., et al. (2009). TBNET consensus statement." Eur Respir J 33(5): 956-973
43. NUOVI TEST
DIRETTI
Identificazione dei micobatteri quiescenti
(GOLD STANDARD)
INDIRETTI
Isolamento di AG (o relazioni tra risposte ai
diversi AG) specifici per la latenza