Clinical Utility of Cytomegalovirus Viral Load in Bronchoalveolar Lavage in Lung Transplant Recipients

Chemaly, Roy F.; Yen‐Lieberman, Belinda; Chapman, Jeffrey T.; Reilly, Amy; Bekele, B. Nebiyou; Gordon, Steven M.; Procop, Gary W.; Shrestha, Nabin K.; Isada, Carlos M.; DeCamp, Malcolm M.; Avery, Robin K.

doi:10.1111/j.1600-6143.2005.00747.x

Cited by 74 publications

(77 citation statements)

References 20 publications

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“…The amount of light emitted is quantified and is proportional to the amount of DNA in the clinical sample. The clinical application of HCA has been demonstrated in several studies conducted on SOT recipients (141,(167)(168)(169), and these studies suggested the correlation between high viral load and the risk of CMV disease. Few studies have reported lower sensitivities than those of antigenemia and PCR-based assays (165,170).…”

Section: Nat In Sot Recipientsmentioning

confidence: 99%

“…There have also been investigations to determine whether the degree of viral load is correlated with respiratory disease (141,146). In a study of 27 lung transplant recipients, CMV loads of Ͼ500,000 copies/ml of BAL fluid were highly correlated with biopsy-proven CMV pneumonitis (141).…”

Section: Nucleic Acid-based Methodsmentioning

confidence: 99%

“…The detection of CMV in BAL fluid may or may not be indicative of CMV pneumonia (68,73,(141)(142)(143)(144)(145). Shedding of CMV in saliva and respiratory secretions is not uncommon, and the demonstration of CMV DNA in these respiratory samples in the absence of compatible clinical signs and symptoms (or in the absence of biopsy confirmation) is of unclear significance and does not necessarily indicate CMV pneumonia (141). In the presence of compatible clinical symptoms, however, the demonstration of CMV DNA may be helpful and may obviate risky lung biopsy in certain situations.…”

Section: Nucleic Acid-based Methodsmentioning

confidence: 99%

“…Ideally, CMV should be demonstrated at the site of tissue invasion, such as BAL fluid for CMV pneumonia, CSF for CMV encephalitis and meningitis, and vitreous humor for CMV retinitis, among others (3,138). The degree of viral load in these clinical specimens, including BAL fluid and CSF, has been associated directly with the severity of infection (73,138,141). However, clinicians are hesitant to perform such invasive biopsy procedures on immunocompromised and often critically ill patients.…”

Section: Rapid Diagnosismentioning

confidence: 99%

“…The HCA is a solution hybridization antibody capture assay that uses a cRNA probe to hybridize with the CMV DNA target (reported to be 17% of the CMV genome) (141,(164)(165)(166). The target-probe complex (termed a DNA-RNA hybrid) is captured by antibodies specific to the hybrid, and the resulting signal (chemiluminescence) is then measured by a luminometer.…”

Section: Nat In Sot Recipientsmentioning

confidence: 99%

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Clinical Utility of Viral Load in Management of Cytomegalovirus Infection after Solid Organ Transplantation

2013

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SUMMARY The negative impact of cytomegalovirus (CMV) infection on transplant outcomes warrants efforts toward improving its prevention, diagnosis, and treatment. During the last 2 decades, significant breakthroughs in diagnostic virology have facilitated remarkable improvements in CMV disease management. During this period, CMV nucleic acid amplification testing (NAT) evolved to become one of the most commonly performed tests in clinical virology laboratories. NAT provides a means for rapid and sensitive diagnosis of CMV infection in transplant recipients. Viral quantification also introduced several principles of CMV disease management. Specifically, viral load has been utilized (i) for prognostication of CMV disease, (ii) to guide preemptive therapy, (iii) to assess the efficacy of antiviral treatment, (iv) to guide the duration of treatment, and (v) to indicate the risk of clinical relapse or antiviral drug resistance. However, there remain important limitations that require further optimization, including the interassay variability in viral load reporting, which has limited the generation of standardized viral load thresholds for various clinical indications. The recent introduction of an international reference standard should advance the major goal of uniform viral load reporting and interpretation. However, it has also become apparent that other aspects of NAT should be standardized, including sample selection, nucleic acid extraction, amplification, detection, and calibration, among others. This review article synthesizes the vast amount of information on CMV NAT and provides a timely review of the clinical utility of viral load testing in the management of CMV in solid organ transplant recipients. Current limitations are highlighted, and avenues for further research are suggested to optimize the clinical application of NAT in the management of CMV after transplantation.

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Section: Nat In Sot Recipientsmentioning

confidence: 99%

Section: Nucleic Acid-based Methodsmentioning

confidence: 99%

Section: Nucleic Acid-based Methodsmentioning

confidence: 99%

Section: Rapid Diagnosismentioning

confidence: 99%

Section: Nat In Sot Recipientsmentioning

confidence: 99%

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Clinical Utility of Viral Load in Management of Cytomegalovirus Infection after Solid Organ Transplantation

2013

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Cytomegalovirus infection in hematologic malignancy settings other than the allogeneic transplant

Marchesi¹,

Pimpinelli

Ensoli

et al. 2017

Hematological Oncology

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Cytomegalovirus (CMV) infection in clinical settings other than the allogeneic transplant represents a poorly explored issue. Thus, we performed a comprehensive review of the medical literature about CMV infection in patients undergoing autologous hematopoietic stem cell transplant and in other nontransplant-related hematologic patients. In autologous hematopoietic stem cell transplant, a CMV reactivation is reported to occur in up to 41% of CMV seropositive patients, when a prospective monitoring of antigenemia and/or viremia by polymerase chain reaction was adopted. However, more contained frequencies, up to 12%, have been reported when the monitoring criteria were based on a clinically driven diagnostic strategy. The most relevant risk factors appear to be CD34 + selected autografts, total body irradiation, and prior treatment with Alemtuzumab, Fludarabine, or Bortezomib, respectively. Other possible risk factors (ie, prior treatment with Rituximab, T-cell lymphomas, and pretransplant HBcIgG seropositivity) are still debated. In nontransplant settings, the data are very heterogeneous; thus, CMV infection incidence and risk factors are more difficult to establish. Overall, the rate of CMV infection/reactivation ranges between 2 and 67%. High-dose steroids, advanced disease, poor performance status, and treatment with Alemtuzumab, Fludarabine, Bortezomib, and Rituximab appear as the most relevant, though putative, risk factors. Intravenous Ganciclovir represents the gold standard for first-line treatment of CMV infection in these patients. Oral Valganciclovir and Foscarnet are other possible options. Extensive prophylaxis and preemptive therapy are not generally recommended, with the exception of high-risk patients.

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Comparing cytomegalovirus diagnostics by cell culture and quantitative nucleic acid testing in broncho‐alveolar lavage fluids

Leuzinger

Stolz

Gosert

et al. 2020

Journal of Medical Virology

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Many clinical laboratories have replaced virus isolation in cell‐culture (VIC) for cytomegalovirus (CMV) by quantitative‐nucleic‐acid testing (QNAT), rendering clinically relevant CMV‐replication difficult to distinguish from CMV‐shedding or latent infection. We compared direct VIC in 1109 consecutive bronchoalveolar lavage fluids (BALFs) and a well‐validated CMV‐QNAT (Basel‐CMV‐UL111a‐77bp). In the retrospective Group 1 (N = 694) and Group 2 (N = 303), CMV‐QNAT was performed within 48 h from 2‐fold and 10‐fold concentrated total nucleic acid (TNA) eluates, respectively. In Group 3 (N = 112), 2‐fold and 10‐fold concentrated TNA eluates were prospectively analyzed in parallel to VIC. CMV was detected by VIC in 79 of 694 (11%) and 26 of 303 (9%) of Groups 1 and 2, but in 114 of 694 (16%) and 57 of 303 (17%) by CMV‐QNAT, respectively. Median CMV loads were significantly higher in VIC‐positive than in VIC‐negative BALF. The likelihood for CMV detection by VIC was 85% for BALF CMV‐ loads >4 log10 copies/ml. In the prospective Group 3, CMV was detected by VIC in 10 of 112 (9%), and in 14 of 112 (13%) and 20 of 112 (18%) by CMV‐QNAT, when using 2‐fold and 10‐fold concentrated TNA eluates, respectively. Notably, CMV was undetectable by CMV‐QNAT in 10 VIC‐positive cases of Groups 1 and 2, but in none of Group 3. We conclude that CMV‐QNAT can be adopted to BALF diagnostics but requires several careful steps in validation. CMV‐QNAT loads >10 000 copies/ml in BALF may indicate significant CMV replication as defined by VIC, if short shipment and processing procedures can be guaranteed. Discordance of detecting CMV in time‐matched plasma samples emphasises the role of local pulmonary CMV replication, for which histopathology remains the gold standard of proven CMV pneumonia.

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Clinical Utility of Cytomegalovirus Viral Load in Bronchoalveolar Lavage in Lung Transplant Recipients

Cited by 74 publications

References 20 publications

Clinical Utility of Viral Load in Management of Cytomegalovirus Infection after Solid Organ Transplantation

Clinical Utility of Viral Load in Management of Cytomegalovirus Infection after Solid Organ Transplantation

Cytomegalovirus infection in hematologic malignancy settings other than the allogeneic transplant

Comparing cytomegalovirus diagnostics by cell culture and quantitative nucleic acid testing in broncho‐alveolar lavage fluids

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