Cytomegalovirus (CMV) DNA quantification in bronchoalveolar lavage fluid of immunocompromised patients with CMV pneumonia

Abstract

Cytomegalovirus (CMV) pneumonia causes major morbidity and mortality. Its diagnosis requires demonstration of viral cytopathic changes in tissue, entailing risks of lung biopsy. This study aimed to determine CMV viral load (VL) thresholds in bronchoalveolar lavage fluid (BALF) for diagnosis of CMV pneumonia in immunocompromised patients. CMV VL in BALF was studied in 17 patients (83% transplant recipients) and 21 control subjects with and without CMV pneumonia, respectively, using an FDA- 09/162). Receiver operating characteristic curve analysis produced a BALF CMV VL threshold of 34 800, IU/mL with 91.7% sensitivity and 100.0% specificity for diagnosis of possible, probable, and proven CMV pneumonia in transplant patients, while a threshold of 656 000 IU/mL yielded 100% sensitivity and specificity among biopsyproven cases. For all immunocompromised patients, a VL threshold of 274 IU/mL was selected. VL thresholds also were normalized to BALF cell count yielding a threshold of 0.32 IU/10 6 cells with 91.7% sensitivity and 90.5% specificity for possible, probable, and proven CMV pneumonia in transplant recipients. Monitoring CMV VL in BALF may be a less invasive method for diagnosing CMV pneumonia in immunocompromised patients. K E Y W O R D Sbronchoalveolar lavage, cytomegalovirus, nucleic acid test, viral load

Cytomegalovirus infection in malignant pleural mesothelioma

“…However, we did not observe evidence that this HCMV viremia was driven by infection at the tumor site. Our data suggest that active HCMV infection may be an unrecognized complication in MPM patients, putting them at risk for HCMV pneumonia as is observed in bone marrow and solid organ transplant recipients [ 14 , 30 – 33 ].…”

“…In healthy persons, HCMV infection is often asymptomatic. However, HCMV reactivation is of high concern in immune suppressed populations where it can progress to end-organ disease [ 20 , 35 ], often presenting as a pulmonary HCMV infection (pneumonia) [ 19 , 33 ], an observation confirmed in a MCMV mouse model [ 11 ]. Immune compromised populations, such as those with HIV, are also at risk for HCMV disease [ 18 , 31 , 36 ].…”

Progress and Challenges in the Prevention, Diagnosis, and Management of Cytomegalovirus Infection in Transplantation

“…Recent studies (Tables 4 and 5) indicate the diagnostic potential of qPCR for CMV DNA in BAL fluid but also highlight the challenges in establishing a precise diagnostic viral load threshold. Tables 4 and 5 include studies reported since 2010 that assessed the utility of BAL CMV qPCR for the diagnosis of CMV pneumonia in recipients of a lung transplant or HCT (62)(63)(64)(65)(66)(67)(68)(69). In these studies, transplant recipients with CMV pneumonia had higher median CMV BAL fluid viral loads than did non-CMV pneumonia cases, although there was an overlap between cases and controls.…”

Cytomegalovirus in Lung Transplant

“…While low levels of CMV DNA in BAL fluid may represent asymptomatic viral replication, higher levels may indicate active disease. Various levels with varying sensitivity and specificity have been reported [32][33][34][35][36][37], and though there is no specific threshold, it is generally accepted that viral copies > 500,000/mL are more likely associated with CMV pneumonitis [38]. Concurrent histopathology increases sensitivity and specificity of detection of CMV pneumonitis [34].…”

“…Intravenous ganciclovir and the oral prodrug valganciclovir have been studied for universal prophylaxis and are the most commonly used agents today [12]. Universal prophylaxis effectively prevents disease, is relatively easy to implement, may prevent other opportunistic infections, and may improve survival by preventing rejection secondary to infection [32]. Universal prophylaxis has been shown to prevent CMV disease in 58-80% of patients [16,66].…”