PPT Gori "Immunologia TB/HIV"

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PPT Gori "Immunologia TB/HIV"

  1. 1. Immunologia  TB/HIV   Andrea  Gori   UO  Mala/e  Infe23ve   AO  San  Gerardo,  Monza     Università  Milano-­‐Bicocca   andrea.gori@unimib.it     Milano,  21-­‐22  Marzo  2014     !
  2. 2. Interferon  Gamma  Release  Assay  (IGRA)  tes;ng  
  3. 3. Clinical  u;lity  of  interferon  gamma  release   assays  (IGRAs)  
  4. 4. Biological  phenomena  of  mother-­‐newborn  immune   interac;on  which  can  theore;cally  affect  newborn   immune  responses  to  microbial  an;gens    
  5. 5. Sensi;vity  of  IGRAs  in  HIV-­‐infected  individuals   with  confirmed  ac;ve  tuberculosis  
  6. 6. Propor;on  of  indeterminate  IGRA  results  in   HIV-­‐infected  persons  screened  for  LTBI  
  7. 7. Impact  of  CD4+  cell  count  on  the  propor;on  of   posi;ve  IGRA  results  
  8. 8. Impact  of  CD4+  cell  count  on  the  propor;on  of   indeterminate  IGRA  results  
  9. 9. IGRA  test  for  the  Diagnosis  of  LTBI  in  HIV-­‐ Infected  Individuals   -  Current  evidence  suggests  that  IGRA  perform  similarly  to  the  TST   at  iden3fying  HIV+  individuals  who  could  benefit  from  LTBI   treatment     -  Important  ques3ons  remain  unanswered  despite  the  substan3al   body  of  literature  on  IGRAs:   -  HIV+  individuals  with  a  nega3ve  IGRA  result  may  have  a  low  risk  of   progression  to  ac3ve  TB   -  IGRAs  (par3cularly  TSPOT)  may  be  more  sensi3ve  than  TST  in  HIV-­‐ infected  individuals  and  less  affected  by  advanced  immunosuppression     -  Clinical  Trials  are  needed  to  more  defini3vely  determine  whether  IGRAs   could  improve  the  iden3fica3on  of  people  living  with  HIV   -  Un3l  such  data  are  available,  the  decision  to  use  IGRA  or  TST  (or  both)   will  depend  on  na3onal  guidelines  as  well  as  resource  and  ogis3c   considera3ons.  
  10. 10. -  The  diagnos3c  value  of  interferon-­‐γ  release  assays  (IGRAs)  for   ac3ve  tuberculosis  in  low-­‐  and  middle-­‐income  countries  is   unclear   -  There  was  no  consistent  evidence  that  either  IGRA  was  more   sensi3ve  than  the  tuberculin  skin  test  for  ac3ve  tuberculosis   diagnosis   -  Conclusions:  neither  the  tuberculin  skin  test  nor  IGRAs  have   value  for  ac3ve  tuberculosis  diagnosis,  especially  in  the   context  of  HIV  coinfec3on   Interferon-­‐γ  Release  Assays  for  Ac;ve  Pulmonary   Tuberculosis  Diagnosis  
  11. 11. Comparison  of  sensi;vity  of  T-­‐SPOT  VS  QFT-­‐GIT   among  persons  with  suspected  ac;ve  tuberculosis  
  12. 12. Sensi;vity  of  QFT-­‐GIT  and  T-­‐SPOT  in  HIV-­‐  and  HIV +  persons  with  confirmed  ac;ve  tuberculosis  
  13. 13. Sensi;vity  difference  between  IGRA  and  TST Plots  display  %  differences  (IGRA  sensi3vity–TST  sensi3vity)  for  confirmed  ac3ve   pulmonary  tuberculosis  
  14. 14. Interferon-­‐γ  Release  Assays  for  Ac;ve   Pulmonary  Tuberculosis  Diagnosis     -  As  in  the  case  of  the  TST,  the  data  suggest  no  role  for  using   IGRAs  for  ac3ve  tuberculosis  diagnosis  for  adults  living  in  low-­‐   and  middle-­‐income  countries   -  These  data  should  not  help  inform  evidence-­‐based  policies  on   the  role  of  IGRAs  in  ac3ve  tuberculosis  diagnosis     -  Indeed,  a  WHO  Expert  Group  considering  this  evidence  recently   recommended  that  IGRAs  should  not  be  used  as  a  replacement   for  conven3onal  microbiological  diagnosis  of  pulmonary  and   extrapulmonary  
  15. 15. -  Tuberculosis  is  unique  among  the  major  infec3ous  diseases  in   that  it  lacks  accurate  rapid  point-­‐of-­‐care  diagnos3c  tests   -  Failure  to  control  the  spread  of  tuberculosis  is  largely  due  to  our   inability  to  detect  and  treat  all  infec3ous  cases  of  pulmonary   tuberculosis  in  a  3mely  fashion,  allowing  con3nued   Mycobacterium  tuberculosis  transmission  within  communi3es  
  16. 16. Analysis  of  Mtb-­‐specific  T  cell  responses  in  the   valida;on  cohort    
  17. 17. Quan;ta;ve  and  qualita;ve  analysis  of  Mtb-­‐ specific  T  cell  responses   Latent  infec3on   Ac3ve  disease  
  18. 18. Func;onal  profile  of  Mtb-­‐specific  CD4+  T  cells   on  the  basis  of  IFN-­‐γ,  IL-­‐2  or  TNF-­‐α  produc;on    
  19. 19. Percentages  of  CFP-­‐10–  or  ESAT-­‐6–specific   single-­‐posi;ve  TNF-­‐α–producing  CD4+  T  cells    
  20. 20. Profile  of  Mtb-­‐specific  CD4+  T  cells  during   untreated  TB  disease  and  then  aZer  TB  treatment  
  21. 21.   M.  tuberculosis–specific  CD4+  T  cell  responses   and  latent  infec;on  or  ac;ve  disease   -  Rapid  diagnosis  of  ac3ve  Mycobacterium  tuberculosis  (Mtb)   infec3on  remains  a  clinical  and  laboratory  challenge     -  We  have  analyzed  the  cytokine  profile  IFN-­‐γ,  TNF-­‐α  and  IL-­‐2   of  Mtb-­‐specific  T  cells  by  polychroma3c  flow  cytometry   -  Substan3al  increase  in  the  propor3on  of  single-­‐posi3ve  TNF-­‐ α  Mtb-­‐specific  CD4+  T  cells  in  subjects  with  ac3ve  disease,   and  this  parameter  was  the  strongest  predictor  of  diagnosis   of  ac3ve  disease  versus  latent  infec3on   -  Therefore,  the  propor3on  of  single-­‐posi3ve  TNF-­‐α  Mtb-­‐ specific  CD4+  T  cells  is  a  new  tool  for  the  rapid  diagnosis  of   ac3ve  tuberculosis  disease  
  22. 22. Division  of  Onco-­‐Haemathology,  “San  Gerardo”   Hospital,  University  Milano-­‐Bicocca   Monza,  Italy   Luisa  Verga   Fausto  Rossini   Pietro  Pioltelli   Enrico  Pogliani       Division  of  Division  of  Pathology,  “San  Gerardo”   Hospital,     University  Milan-­‐Bicocca   Monza,  Italy   Ambrogio  Brenna   Serena  Cu`n   Giorgio  Catore`       Division  of  Microbiology  and  Virology  Laboratories,   “San  Gerardo”  Hospital,  Monza,  Italy   Sergio  Malandrin   Annalisa  Cavallero       Haemathology  and  Transfusion  Center,  “San   Gerardo”  Hospital,  Monza,  Italy   Paolo  Perseghin   Arianna  Incontri     Chair  of  Immunology,   University  of  Milan,  Milan,  Italy   Daria  Trabaaoni   Marina  Saresella   Mara  Biasin   Mario  (Mago)  Clerici   Department  of  Infec;ous  Diseases,     “L.  Sacco”  Hospital,  University  of  Milan   Milan,  Italy,     Fabio  Franze`   Fabio  Zanini   Stefano  Rusconi   Stefania  Piconi   Giuliano  Rizzardini       Clinic  of  Infec;ous  Diseases,  “San  Paolo”  Hospital,   University  of  Milan   Milan,  Italy   Giulia  Marche`     Camilla  Tinca;   Antonella  d’Arminio  Monforte     Divisione  di  Mala`e  Infe`ve   A.O.  “San  Gerardo”   Monza   Giuseppe  Lapadula   Silvia  Costarelli   Alessandra  Bandera   Marianna  Rossi   Nicola  Squillace   Alessandro  Soria   Antonio  Muscatello   Sebas;ano  Leone   Guglielmo  Migliorino  
  23. 23. BACK  UP  SLIDES  
  24. 24. Interferon  Gamma  Release  Assay  (IGRA)  tes;ng  
  25. 25. summary curves from the HSROC model contain a summary operating point (red square) representing summarized sensitivity and specificity point estimates for individual study estimates (open circles). The 95% confidence region is delineated by the area in the orange dashed line.  

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