Frequent detection of cytomegalovirus (CMV) DNA in the lower respiratory tract in CMV‐seropositive pediatric patients with underlying chronic bronchopulmonary diseases lacking canonical immunosuppression

Escribano, Amparo; Chilet, Marifina; Clari, María Ángeles; Lucas, Raquel; Costa, Elisa; Bravo, Dayana; Muñoz-Cobo, Beatriz; Borrás, Rafael; Navarro, David

doi:10.1002/jmv.23499

Cited by 5 publications

(7 citation statements)

References 18 publications

(25 reference statements)

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“…As previously mentioned, a number of recent studies in immune competent hosts have assumed that detectable CMV‐DNA in BAL or tracheal aspirates is evidence of CMV replication/reactivation [Heininger et al, ; Chilet et al, ; Smith et al, ; Heininger et al, ; Coisel et al, ; Doan et al, ; Escribano et al, ; Friedrichs et al, ; Cinel et al, ]. Unfortunately, there are few data evaluating healthy immune competent seropositive hosts, and none during the era of quantitative PCR.…”

Section: Discussionmentioning

confidence: 99%

“…These studies also vary by population tested (i.e., burn, trauma, medical, and surgical patients). Lungs are widely considered to be an important site of CMV latency, and many investigators have evaluated tracheal aspirates and bronchoalveolar lavage (BAL) for reactivation [Heininger et al, , ; Chilet et al, ; Smith et al, ; Blanquer et al, ; Coisel et al, ; Doan et al, ; Escribano et al, ; Friedrichs et al, ; Cinel et al, ]. To date, it has been assumed that detection of CMV DNA in the BAL of non‐immune suppressed patients is consistent with CMV reactivation.…”

Section: Introductionmentioning

confidence: 99%

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Broncholaveolar lavage to detect cytomegalovirus infection, latency, and reactivation in immune competent hosts

et al. 2016

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Roughly 1/3rd of immune competent patients will reactivate latent cytomegalovirus (CMV) during critical illness. There are no standard methods to detect reactivation, and some investigators have postulated that presence of DNA in BAL fluid is indicative of viral replication. To test this hypothesis, we used a murine model that allows inclusion of matched healthy controls which is not possible in human studies. BALB/c mice infected with Smith-murine CMV or PBS (mock) had BAL evaluated 7, 14, or 21 days after acute infections, during latency, or during bacterial sepsis. Plaque assay, PCR, and rtPCR were performed on BALs and concomitantly obtained lung tissue. BAL cellular compositions, including tetramer evaluation of CMV-specific T cells were evaluated by flow cytometry. CMV DNA were detected in BAL at all time-points during acute infection, becoming undetectable in all mice during latency, then were detected again during bacterial sepsis, peaking 3 weeks after onset. mCMV specific T-cells were most numerous in BAL after acute viral infections, decreasing to low levels during latency, then fluctuating during bacterial sepsis. Specifically, mCMV-specific T-cells contracted at sepsis onset, expanding 2–4 weeks post-sepsis, presumably in response to increased viral loads at that time point. Altogether, our results support the use of BAL PCR for the diagnosis of CMV replication in immune competent hosts. Additionally, we demonstrate dynamic changes in CMV-specific T cells that occur in BAL during CMV infection and during sepsis induced viral reactivation.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Broncholaveolar lavage to detect cytomegalovirus infection, latency, and reactivation in immune competent hosts

et al. 2016

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“…The presence of CMV DNA in plasma is considered a good marker of virus replication, whereas the sole presence of CMV DNA in tracheal aspirates may either reflect local virus replication or merely the presence of myeloid cells harboring the virus in a latent state [Escribano et al, ]. Thus, an episode of active CMV infection was defined by the presence of CMV DNA in plasma and tracheal aspirates, plasma alone, or by the detection of increasing CMV DNA loads in tracheal aspirates with undetectable levels in plasma.…”

Section: Methodsmentioning

confidence: 99%

Evaluation of cytomegalovirus (CMV)-specific t-cell immunity for the assessment of the risk of active CMV infection in non-immunosuppressed surgical and trauma intensive care unit patients

et al. 2013

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The current study was designed to assess the predictive value of the evaluation of cytomegalovirus (CMV)-specific T-cell immunity early following admission to the intensive care unit for inferring the risk of active CMV infection in non-immunosuppressed surgical and trauma patients. A total of 31 CMV-seropositive patients were included. Patients were screened for the presence of CMV DNA in plasma and in tracheal aspirates by real-time PCR. Enumeration of CMV pp65 and IE-1-specific IFN-γ CD8(+) and CD4(+) T cells was performed by flow cytometry for intracellular cytokine staining. Virological and immunological monitoring was conducted once or twice a week. Active CMV infection occurred in 17 out of 31 patients. Undetectable levels of pp65 and IE-1-specific IFN-γ CD8(+) and CD4(+) T-cell subsets cells were observed in 10 patients who developed active CMV infection and in one who did not (at a median of 2 days following ICU admission). Peak CMV DNA loads in both tracheal aspirates and plasma were substantially higher (P = 0.018 and P = 0.091, respectively) in patients with undetectable IFN-γ T-cell responses than in patients with detectable responses. The expansion of both CMV-specific T-cell subsets following detection of active CMV infection was demonstrated in 9 out of 14 patients with active CMV infection. In conclusion, the evaluation of CMV pp65 and IE-1-specific IFN-γ-producing CD8(+) and CD4(+) T cells early following ICU admission may allow the identification of patients most at risk of either having or developing an episode of active CMV infection, particularly those associated with high-level virus replication.

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“…An episode of active CMV infection was defined by the presence of CMV DNA in plasma and tracheal aspirates, plasma alone, or by the detection of increasing CMV DNA loads in tracheal aspirates with undetectable levels in plasma [Escribano et al, ]. Sole detection of CMV DNA in saliva was not considered a marker of active CMV infection.…”

Section: Methodsmentioning

confidence: 99%

“…It is unlikely that further studies aimed at evaluating clinical factors as risk markers for the occurrence of active CMV infection will help to narrow the subset of patients at highest risk for CMV reactivation [Kalil and Florescu, 2009]. In this context, data published recently suggest that enumeration of functional NK cells and CMV-specific interferon-g-producing T cells may help predict the imminent occurrence of active CMV infection [Chiche et al, 2012;Clari et al, 2013]. The current study was undertaken to evaluate the value of several biological factors for predicting the development of active CMV infection in a cohort of critically ill patients.…”

Section: Introductionmentioning

confidence: 99%

Looking for biological factors to predict the risk of active cytomegalovirus infection in non‐immunosuppressed critically ill patients

Bravo

Clari

Aguilar

et al. 2013

Journal of Medical Virology

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The identification of non-immunosuppressed critically ill patients most at risk for developing cytomegalovirus (CMV) reactivation is potentially of great clinical relevance. The current study was aimed at determining (i) whether single nucleotide polymorphisms in the genes coding for chemokine receptor 5 (CCR5), interleukin-10 IL-10), and monocyte chemoattractant protein-1 (MCP-1) have an impact on the incidence rate of active CMV infection, (ii) whether serum levels of CMV-specific IgGs are associated with the risk of CMV reactivation, and (iii) whether detection of CMV DNA in saliva precedes that in the lower respiratory tract or the blood compartment. A total of 36 out of 78 patients (46%) developed an episode of active CMV infection. The incidence rate of active CMV infection was not significantly associated with any single nucleotide polymorphisms. A trend towards a lower incidence of active CMV infection (P = 0.06) was noted in patients harboring the IL10 C/C genotype. Patients carrying the CCR5 A/A genotype had high CMV DNA loads in tracheal aspirates. The serum levels of CMV IgGs did not differ significantly between patients with a subsequent episode of active CMV infection (median, 217 IU/mL) or without one (median, 494 IU/mL). Detection of CMV DNA in saliva did not usually precede that in plasma and/or tracheal aspirates. In summary, the analysis of single nucleotide polymorphisms in the IL10 and CCR5 genes might help to determine the risk of active CMV infection or the level of CMV replication within episodes, respectively, in non-immunosuppressed critically ill patients.

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Frequent detection of cytomegalovirus (CMV) DNA in the lower respiratory tract in CMV‐seropositive pediatric patients with underlying chronic bronchopulmonary diseases lacking canonical immunosuppression

Cited by 5 publications

References 18 publications

Broncholaveolar lavage to detect cytomegalovirus infection, latency, and reactivation in immune competent hosts

Broncholaveolar lavage to detect cytomegalovirus infection, latency, and reactivation in immune competent hosts

Evaluation of cytomegalovirus (CMV)-specific t-cell immunity for the assessment of the risk of active CMV infection in non-immunosuppressed surgical and trauma intensive care unit patients

Looking for biological factors to predict the risk of active cytomegalovirus infection in non‐immunosuppressed critically ill patients

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