Sub point title This is the example for point placement. This is the example for point placement. This is the example for point placement. CMV THE Cytomegalovirus
OUTLINE RISK FACTORS CMV DISEASE DIAGNOSIS APPROACHES DEFINITION STRUCTURE: ENVELOPED DOUBLE-STRANDED DNA HERPESVIRIDAE FAMILY 3 WAYS OF INFECTION: ENDOGENOUS REACTIVATION OF CMV IN RECIPIENTS DONOR-DERIRED INFECTION TRANSMITTED VIA THE GRAFT ACCQUIRED FROM GENERAL POPULATION PATHOLOGY: THE MOST IMPORTANT VIRAL PATHOGEN THE MOST PREVALENT OPPORTUNITIC A MAJOR CAUSE OF MORBIDITY IN SOT A PREVANTABLE CAUSE OF MORTALITY IN SOT DEFINITION 1
PATHOLOGY: THE MOST IMPORTANT VIRAL PATHOGEN THE MOST PREVALENT OPPORTUNITIC INFECTION A MAJOR CAUSE OF MORBIDITY IN SOT A PREVANTABLE CAUSE OF MORTALITY IN SOT ABOUT CMV? RISK FACTORS CMV DISEASE DIAGNOSIS APPROACHES DEFINITION STRUCTURE: ENVELOPED DOUBLE-STRANDED DNA HERPESVIRIDAE FAMILY 3 WAYS OF INFECTION: ENDOGENOUS REACTIVATION OF CMV IN RECIPIENTS DONOR-DERIVED INFECTION TRANSMITTED VIA THE GRAFT ACCQUIRED FROM GENERAL POPULATION DEFINITION TRANSMISION 1
ABOUT CMV? RISK FACTORS CMV DISEASE DIAGNOSIS APPROACHES DEFINITION URINE ALLOGRAPT GENERAL SECRETION BLOOD SAVILA TRANSMISION CMV DISEASE ASYMPTOMATIC CMV INFECTION DIRECT CONSEQUENCES INDIRECT CONSEQUENCES PATHOLOGY: THE MOST IMPORTANT VIRAL PATHOGEN THE MOST PREVALENT OPPORTUNITIC A MAJOR CAUSE OF MORBIDITY IN SOT A PREVANTABLE CAUSE OF MORTALITY IN SOT STRUCTURE: ENVELOPED DOUBLE-STRANDED DNA HERPESVIRIDAE FAMILY 3 WAYS OF INFECTION: ENDOGENOUS REACTIVATION OF CMV IN RECIPIENTS DONOR-DERIRED INFECTION TRANSMITTED VIA THE GRAFT ACCQUIRED FROM GENERAL POPULATION 2 2.1 2.2 2.3
CMV DISEASE This is the example for point placement. Main point 1 ASYMPTOMATIC CMV INFECTION DIRECT CONSEQUENCES TRANSMISION CMV syndrome Thrombo cytopenia Malaise Fever Leukopenia
CMV DISEASE DIRECT CONSEQUENCES INDIRECT CONSEQUENCES TRANSMISION Tissue – invasive CMV disease: CMV GI Disease Pneumonia Encephalitis R etinitis CMV syndrome INDIRECT CONSEQUENCES Acute and chronic allograft section Bacterial and fungal opportunistic infection CMV syndrome Thrombo cytopenia Malaise Fever Leukopenia
Malaise DIRECT CONSEQUENCES CMV GI Pneumonia INDIRECT CONSEQUENCES Bacterial and fungal opportunistic infection Acute and chronic allograft rejection INDIRECT CONSEQUENCES DIAGNOSIS Tissue – invasive CMV disease: CMV GI Pneumonia Encephalitis R etinitis 3
Acute and chronic allograft section Bacterial and fungal opportunistic infection Malaise DIRECT CONSEQUENCES INDIRECT CONSEQUENCES DIAGNOSIS HISTOPATHOLOGY CMV SEROLOGY MOLECULAR TESTS VIRAL CULTURE ANTIGENEMIA ASSAYS DIAGNOSIS Bacterial and fungal opportunistic infection Acute and chronic allograft section 3
Malaise DIAGNOSIS HISTOPATHOLOGY CMV SEROLOGY VIRAL CULTURE MOLECULAR TESTS ANTIGENEMIA ASSAYS Presence the tissue - invasive CMV disease Disadvantage: an invasive procedure to obtain However, Histopathology is recommended in cases 3
Malaise DIAGNOSIS HISTOPATHOLOGY CMV SEROLOGY VIRAL CULTURE MOLECULAR TESTS ANTIGENEMIA ASSAYS Disadvantage: an invasive procedure to obtain the expected tissue However, Histopathology is recommended in cases Presence the tissue - invasive CMV disease 3
Malaise DIAGNOSIS HISTOPATHOLOGY CMV SEROLOGY VIRAL CULTURE MOLECULAR TESTS ANTIGENEMIA ASSAYS However, Histopathology is recommended in some cases Disadvantage: an invasive procedure to obtain Presence the tissue - invasive CMV disease concomitant pathology Suspected patients All negative test results 3
Malaise DIAGNOSIS CMV SEROLOGY VIRAL CULTURE MOLECULAR TESTS ANTIGENEMIA ASSAYS However, Histopathology is recommended in cases Disadvantage: an invasive procedure to obtain Presence the tissue - invasive CMV disease HISTOPATHOLOGY another concomitant pathology Copathogen is Suspected All other test results are negative Detecting CMV IgM – IgG A limited utility Delayed immunosuppression KTR 3
Malaise DIAGNOSIS CMV SEROLOGY VIRAL CULTURE MOLECULAR TESTS ANTIGENEMIA ASSAYS HISTOPATHOLOGY concomitant pathology Suspected patients All negative test results Detecting CMV IgM – IgG A limited utility Impaired immune systems in KTR VIRAL CULTURE 3
Malaise DIAGNOSIS CMV SEROLOGY VIRAL CULTURE MOLECULAR TESTS ANTIGENEMIA ASSAYS HISTOPATHOLOGY Detecting CMV IgM – IgG A limited utility Delayed immunosuppression KTR Highly specific Modestly sensitive Slow turn-around time 3
Malaise DIAGNOSIS CMV SEROLOGY VIRAL CULTURE MOLECULAR TESTS ANTIGENEMIA ASSAYS HISTOPATHOLOGY Delayed immunosuppression KTR Highly specific Modestly sensitive Slow turn-around time Isolate CMV in non-blood clinical specimens More popular in children than adults 3
Malaise DIAGNOSIS CMV SEROLOGY VIRAL CULTURE MOLECULAR TESTS ANTIGENEMIA ASSAYS HISTOPATHOLOGY Delayed immunosuppression KTR Highly specific Modestly sensitive Slow turn-around time Isolate CMV in non-blood clinical specimens More popular in children than adults 3
Malaise DIAGNOSIS CMV SEROLOGY VIRAL CULTURE MOLECULAR TESTS ANTIGENEMIA ASSAYS HISTOPATHOLOGY Delayed immunosuppression KTR Highly specific Modestly sensitive Slow turn-around time Isolate CMV in non-blood clinical specimens More popular in children than adults A semi quantiative assay, detecting PP65 antigen in peripheral blood leukocytes 3
Malaise VIRAL CULTURE ANTIGENEMIA ASSAYS HISTOPATHOLOGY A semi quantiative assay, detecting PP65 antigen in peripheral blood leukocytes DIAGNOSIS SENSITIVITY: >> Viral culture ~ NAT by PCR USEFUL FOR : Pre-emptive Therapy (PET) - Rapid - Sensitive diagnosis DISADVANTAGE: Time consuming in processing clinical diagnosis - Useless on leukopenic patients MOLECULAR TESTS RNA reflects active CMV replication The most common method to diagnosis after SOT DNA reflects latent viral DNA complification 3
Malaise ANTIGENEMIA ASSAYS A semi quantiative assay, detecting PP65 antigen in peripheral blood leukocytes DIAGNOSIS SENSITIVITY: >> Viral culture ~ NAT by PCR USEFUL FOR : Pre-emptive Therapy (PET) - Rapid - Sensitive diagnosis DISADVANTAGE: Time consuming in processing clinical diagnosis - Useless on leukopenic patients MOLECULAR TESTS RNA reflects active CMV replication The most common method to diagnosis after SOT DNA reflects latent viral DNA amplification RISK FACTORS 3 4
Malaise ANTIGENEMIA ASSAYS A semi quantiative assay, detecting PP65 antigen in peripheral blood leukocytes DIAGNOSIS SENSITIVITY: >> Viral culture ~ NAT by PCR USEFUL FOR : Pre-emptive Therapy (PET) - Rapid - Sensitive diagnosis DISADVANTAGE: Time consuming in processing clinical diagnosis - Useless on leukopenic patients MOLECULAR TESTS RNA reflects active CMV replication The most common method to diagnosis after SOT DNA reflects latent viral DNA complification RISK FACTORS 3 4
Malaise DIAGNOSIS MOLECULAR TESTS RNA reflects active CMV replication The most common method to diagnosis after SOT DNA reflects latent viral DNA complification RISK FACTORS The incidence of CMV infection is highly dependent on the serostatus HIGHEST RISK D(+)/R(-) INTERMEDIATE RISK D(+)/R(+) or D(-)/R(+) LOWEST RISK D(-)/R(-) Classification guide to different approaching strategies 3 4
Malaise RISK FACTORS The incidence of CMV infection is highly dependent on the serostatus Classification guide to different approaching strategies PROPHYLAXIS PRE-EMTIVE THERAPY HYBRID STRATEGY 5 PRE-EMTIVE THERAPY 5.2 HYBRID STRATEGY 5.3 PROPHYLAXIS 5.1 4
Malaise RISK FACTORS Classification guide to different approaching strategies APPROACHES 5 The administration of Antiviral drugs to patients for a certain period after transplantation 4 PRE-EMTIVE THERAPY 5.2 HYBRID STRATEGY 5.3 PROPHYLAXIS 5.1
Malaise RISK FACTORS Classification guide to different approaching strategies APPROACHES 5 PRE-EMTIVE THERAPY 5.2 HYBRID STRATEGY 5.3 PROPHYLAXIS 5.1 The administration of Antiviral drugs to patients for a certain period after transplantation 4
Malaise APPROACHES 5 PROPHYLAXIS 5.1 HYBRID STRATEGY 5.3 PRE-EMTIVE THERAPY 5.2 The administration of Antiviral drugs to patients for a certain period after transplantation
Malaise APPROACHES 5 PROPHYLAXIS 5.1 HYBRID STRATEGY 5.3 PRE-EMTIVE THERAPY 5.2 The administration of Antiviral drugs to patients for a certain period after transplantation AP should be started ASAP.
Malaise APPROACHES 5 HYBRID STRATEGY 5.3 PRE-EMTIVE THERAPY 5.2 AP should be started ASAP. PROPHYLAXIS 5.1 The duration depend on the D/R serostatus No recommend D(-)/R(-) as long as they receive CMV(-) blood or Leuko-depleted blood products. 10 days Monitoring at regular internals (usually once/a week) for evidence of early CMV replication
Malaise APPROACHES 5 HYBRID STRATEGY 5.3 PRE-EMTIVE THERAPY 5.2 AP should be started ASAP. PROPHYLAXIS 5.1 The duration depend on the D/R serostatus No recommend D(-)/R(-) result until CMV(-) in blood test or Leuko-depleted blood product. 10 days Monitoring at regular intervals (usually once/a week) for evidence of early CMV replication
Malaise APPROACHES 5 HYBRID STRATEGY 5.3 PRE-EMTIVE THERAPY 5.2 AP should be started ASAP. PROPHYLAXIS 5.1 The duration depend on the D/R serostatus No recommend D(-)/R(-) result until CMV(-) in blood test or Leuko-depleted blood product. Resume weekly monitoring until week 12 Treat until “negative” threshold achieved Start valganciclovir or IV ganciclovir at treatment dose Assay positive at threshold No positive assay or threshold not reached. Stop testing at week 12 Test patients weekly at weeks 1-12 post-transplant Select appropriate population to employ preemptive therapy Validate appropriate threshold for site-specific assay (NAT or Ag) The viral load threshold for initation of PET isn’t confirmed among different laboratory centers
Malaise APPROACHES 5 HYBRID STRATEGY 5.3 PRE-EMTIVE THERAPY 5.2 PROPHYLAXIS 5.1 The viral load threshold for initation of PET isn’t confirmed among different laboratory centers Resume weekly monitoring until week 12 Treat until “negative” threshold achieved Start valganciclovir or IV ganciclovir at treatment dose Assay positive at threshold No positive assay or threshold not reached. Stop testing at week 12 Test patients weekly at weeks 1-12 post-transplant Select appropriate population to employ preemptive therapy Validate appropriate threshold for site-specific assay (NAT or Ag)
Malaise APPROACHES 5 PRE-EMTIVE THERAPY 5.2 HYBRID STRATEGY 5.3 PROPHYLAXIS 5.1 The viral load threshold for initation of PET isn’t confirmed among different laboratory centers Oral VALGANCICLOVIR IV GANCICLOVIR 900mg twice a day 5mg/kg every 12h
Malaise APPROACHES 5 PRE-EMTIVE THERAPY 5.2 HYBRID STRATEGY 5.3 VALGANCICLOVIR IV GANCICLOVIR 900mg twice a day 5mg/kg every 12h
Malaise APPROACHES 5 PRE-EMTIVE THERAPY 5.2 HYBRID STRATEGY 5.3 Short-term AP allowed by PET during the period of CMV disease
Malaise APPROACHES 5 PRE-EMTIVE THERAPY 5.2 HYBRID STRATEGY 5.3 Short-term AP allowed by PET during the period of CMV disease
APPROACHES 5 PRE-EMTIVE THERAPY 5.2 HYBRID STRATEGY 5.3 Short-term AP allowed by PET during the period of CMV disease D-R- D-R+ D+R+ D+R- Risk of CMV disease No intervention Pre-emptive Therapy Prophylaxis
APPROACHES 5 PRE-EMTIVE THERAPY 5.2 HYBRID STRATEGY 5.3 Short-term AP allowed by PET during the period of CMV disease D-R- D-R+ D+R+ D+R- Risk of CMV disease No intervention Pre-emptive Therapy Prophylaxis