PPT Bocchino "Diagnosi dell'infezione tubercolare"

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PPT Bocchino "Diagnosi dell'infezione tubercolare"

  1. 1. Diagnosi  dell’infezione  tubercolare   Dott.ssa Marialuisa Bocchino   Dipar4mento  di  Medicina  Clinica  e  Chirurgia   Università  degli  Studi  di  Napoli  “Federico  II”  
  2. 2. PL  Lin,  J  Immunol  2010  
  3. 3. PJ  Cardona,  Arch  Immunol  Ther  Exp  2010  
  4. 4. Mod.E6  
  5. 5. Mycobacterium, spp   ESAT-6 CFP-10 M. tuberculosis M. bovis M. africanum M. kansasii M. marinum M. szulgai M. flavescens + + + + + + + + + + + + + + RD-­‐1  related  an-gens  
  6. 6. QFT-­‐IT  procedure  
  7. 7. TS-­‐TB  procedure  
  8. 8. •   Epidemiological  seQng   •   Test  characteris4cs   •   Technical  laboratory  exper4se     •   Clinical  seQng   •   Targeted  popula4on                                    
  9. 9.   Low  prevalence  se6ngs:   BeSer  sensi4vity  and  specificity  than  TST   BeSer  correla4on  with  TB  exposure   Variable  concordance  with  TST  in  close  TB  contacts   Unknown  predic4ve  value     High  prevalence  se6ngs:   Reduced  sensi4vity  and  specificity   Reduced  correla4on  with  TB  exposure   Good  concordance  with  TST  in  TB  close  contacts   Unknown  predic4ve  value     Repeated  infec-ons,  exposure  to  NTM,  effector  T  cells  turnover,  T  reg  cells  turnover,  host  response,   mycobacterial  strains,  technical  exper-se,  vaccine  adop-on     Latent  tuberculosis  infec-on:  IGRA  performance   Menzies  et  al.,  Ann  Intern  Med  2008  
  10. 10. hSp://www.bcgatlas.org   World  Atlas  of  BCG  Policies  and  Prac-ces  
  11. 11. TST  sensi4vity   R  Diel,  Chest  2010  
  12. 12. QFT-­‐IT  sensi4vity   R  Diel,  Chest  2010  
  13. 13. TS-­‐TB  sensi4vity   R  Diel,  Chest  2010  
  14. 14. R  Diel,  Chest  2010   IGRA  specificity   QFT-­‐IT   TS-­‐TB  
  15. 15. The  pooled  rate  of  indeterminate  results  was  low,  2.1%   (95%  CI,  0.02-­‐0.023)  for  the  QFT-­‐IT  and  3.8%  (95%  CI,     0.035-­‐0.042)  for  the  TS-­‐TB,  increasing  to  4.4%     (95%  CI,  0.039-­‐0.05)  and  6.1%  (95%  CI,  0.052-­‐0.071)     respec4vely,  among  immunocompromised  hosts.   R  Diel,  Chest  2010  
  16. 16. M  Bocchino,  Expert  Rev  Mol  Diagn  2009  
  17. 17. RN  van  zyl  Smit,  PLoS  ONE  2009   Boos-ng   ü Only  one  study  was  performed  in  a  high  burden  seQng   ü Five  studies  used  TS-­‐TB,  and  6  the  QFT-­‐IT   ü Five  studies  concluded  that  boos4ng  did  not  occur   ü The  effect  appears  to  be  more  prevalent  in  individuals  already  IGRA-­‐posi4ve   ü The  effect  seems  apparent  ager  the  first  3  days  and  wanes  ager  3  months   ü Only  a  small  percentage  (2-­‐12%)  of  IGRA-­‐nega4ve  individuals  boost  ager  a  TST   ü IGRA  tes4ng  beSer  to  be  performed  before  or  within  72  hours  of  the  TST        
  18. 18. ü General  recommenda4ons  for  use  of  IGRAs   ü Test  selec4on   ü Situa4ons  in  which  IGRA  is  preferred  but  a  TST  is  acceptable   (homeless  persons,  drug-­‐users,  BCG  vaccinated  persons)   ü Situa4ons  in  which  a  TST  is  preferred  but  an  IGRA  is  acceptable   (children  aged  <5  years)   ü Situa4ons  in  which  either  a  TST  or  an  IGRA  may  be  used  without  preference   (close  TB  contacts,  occupa4onal  exposure)   ü Situa4ons  in  which  tes4ng  with  both  an  IGRA  and  a  TST  may  be  considered   (high  suspicion  of  false-­‐nega4ve  or  false-­‐posi4ve  results,  indeterminate,  borderline  or  invalid  results)   ü Medical  management  ager  tes4ng     Updated  Guidelines  for  Using  Interferon  Gamma  Release  Assays  to  Detect  Mycobacterium   tuberculosis  Infec3on  -­‐-­‐-­‐  United  States,  2010   Recommenda4ons  and  Reports   June  25,  2010  /  59(RR05);1-­‐25  
  19. 19. Algorithm  of  all  possible  outcomes  resul-ng  from  parallel     IGRA  and  TST  tes-ng   Lalvani  A  et  al.     BMB  2009                                    
  20. 20. Areas  for  Addi-onal  Research   Are  IGRAs  beSer  at  predic4ng  subsequent  ac4ve  tuberculosis  than  TST?   Are  persons  with  discordant  TST  and  IGRA  results  at  increased  risk  for  ac4ve  tuberculosis  compared  with  persons  with     concordant  nega4ve  results?Are  higher  IFN-­‐γ  responses  associated  with  a  greater  risk  for  developing  ac4ve  tuberculosis?   Do  IGRAs  perform  differently  in  children  than  in  adults,  in  those  with  extrapulmonary  versus  pulmonary  tuberculosis,  in  those     with  HIV  infec4on  versus  those  without  HIV  infec4on,  in  those  recently  infected  as  compared  with  those  infected  years  earlier,     and  in  those  with  latent  infec4on  as  compared  with  those  with  ac4ve  tuberculosis?   Why  do  simultaneously  performed  TST,  QFT-­‐GIT,  QFT-­‐G,  and  T-­‐Spot  results  differ?   Can  sensi4vity  and  specificity  of  IGRAs  be  improved  by  modifica4on  in  tes4ng  methods,  applica4on  of  different  interpreta4on   criteria,  or  inclusion  of  addi4onal  an4gens?   What  is  the  best  approach  for  determining  cut  points  for  IGRA  interpreta4on,  including  situa4ons  where  Nil  values  are  high  or     Mitogen  values  are  low?   To  what  extent  does  inclusion  of  a  "borderline"  interpreta4on  improve  IGRA  accuracy?  What  causes  varia4on  in  IGRA  results     and  to  what  extent?   What  magnitude  of  change  in  IFN-­‐γ  response  indicates  new  infec4on?   Ager  exposure,  how  long  does  it  take  for  an  IGRA  to  become  posi4ve?   What  is  the  clinical  significance  of  IGRA  reversion?   What  methods  should  be  used  to  monitor  IGRA  quality?   Is  there  an  associa4on  between  lymphocyte  count  and  IFN-­‐γ  response  (with  or  without  HIV  infec4on)?   What  effect  does  treatment  of  M.  tuberculosis  infec4on  have  on  IGRA  results?   How  do  host  and  bacterial  gene4c  factors  affect  IGRA  results?  

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