Clinical utility of bronchoalveolar lavage cytomegalovirus viral loads in the diagnosis of cytomegalovirus pneumonitis in infants

Abstract

Cytomegalovirus (CMV) pneumonitis is a significant cause of morbidity and mortality of children in Africa. The current practice for diagnosing CMV pneumonitis in this setting is based on interpretation of clinical, laboratory, and radiological findings. There is a need for a sensitive and specific laboratory test to objectively distinguish between patients with CMV pneumonitis and those with CMV infection, and non‐CMV pneumonia. In this study, we compared plasma and non‐bronchoscopic bronchoalveolar lavage (NBBAL) CMV viral loads in patients with CMV pneumonitis and those with CMV infection and non‐CMV pneumonia. Receiver operator characteristic curve analysis was used to establish a threshold and assess utility of viral loads in the diagnosis of CMV pneumonitis. We assessed the urea dilution method, and expression of viral loads relative to the total amount of extracted nucleic acids in correcting for NBBAL dilution. CMV quantification in NBBAL specimens was more predictive of CMV pneumonitis than blood CMV quantification. The threshold of 4.03 log IU/ml in NBBAL specimens has good predictive value and can be used to guide management of infants with suspected CMV pneumonitis. Adjusting for dilution of NBBAL specimens by using the urea dilution method or by expressing the viral load relative to the total nucleic acids extracted did not provide additional analytical benefits. J. Med. Virol. 89:1080–1087, 2017. © 2016 Wiley Periodicals, Inc.

Challenges and Clinical Implications of the Diagnosis of Cytomegalovirus Lung Infection in Children

“…As previously described by us and others [28,73,74], the most consistent findings in up to 80% of patients are the development of ground glass and airspace opacities (Fig. 1), indicating various degrees of lung parenchymal (alveolar) involvement [69,73]. Additional findings include volume loss [75], the presence of pulmonary nodules in almost one third of patients, and interstitial infiltrates in about half of affected children [69,76,77].…”

“…Human CMV is a ubiquitous pathogen highly prevalent in children, estimated to affect more than one third of school age children and adolescents in the USA [66,67] with higher rates in certain areas worldwide and among certain populations [3,27,67,68]. CMV lung infections can be diagnosed by detecting the presence of virus in serum and/or respiratory samples, obtained by bronchoscopy or tracheal aspiration, being the virus detection directly in the respiratory tract more predictive of CMV pneumonitis [69]. In regard to viral detection in the circulation, among the techniques available, PCR detection has been proven more sensitive for the detection of CMV and preferred over others such as the measurement of the viral phosphoprotein 65 (pp65), a marker of active viral replication, in blood and CMV blood cultures [70].…”

“…1), indicating various degrees of lung parenchymal (alveolar) involvement [69,73]. Additional findings include volume loss [75], the presence of pulmonary nodules in almost one third of patients, and interstitial infiltrates in about half of affected children [69,76,77]. The above changes are often seen in chest radiographs; however, they may be subtle or may not be visualized, requiring confirmation by chest computed tomography, often performed to assist further diagnostic and therapeutic decisions.…”

The Potential Harm of Cytomegalovirus Infection in Immunocompetent Critically Ill Children

“…Thus, even in the setting of moderate illness, systemic CMV replication is common in African children. In a prospective study that included 53 HIV-uninfected South African children ≤2 years old admitted to ICU with severe pneumonia, 12 (23%) were defined as having CMV pneumonitis based on DNA detection in BAL fluid and other clinical characteristics ( 80 ). Many of these children were treated with ganciclovir, but the published data are insufficient to determine whether disseminated CMV or antiviral treatment in HIV-uninfected children were associated with clinical outcomes ( 80 ).…”

“…As in adult studies, CMV replication in blood is likely to be the best measure of uncontrolled systemic viral infection in critically ill children. Although CMV in BAL fluid may simply represent shedding, high viral loads are predictive of CMV pneumonitis in transplant recipients and, perhaps, in critically ill children ( 80 , 84 , 85 ). Thus, pediatric ICU studies should incorporate CMV testing of BAL fluid, should it be collected for clinical purposes.…”