Impact of human metapneumovirus and human cytomegalovirus versus other respiratory viruses on the lower respiratory tract infections of lung transplant recipients

Gerna, Giuseppe; Vitulo, Patrizio; Rovida, Francesca; Lilleri, Daniele; Pellegrini, Carlo; Oggionni, Tiberio; Campanini, Giulia; Baldanti, Fausto; Revello, Maria Grazia

doi:10.1002/jmv.20555

Cited by 99 publications

(95 citation statements)

References 36 publications

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“…14 DNAemia was quantified by real-time PCR according to a procedure previously reported. 15 HCMV DNA copy number was determined from DNA aliquots extracted from 10 ml whole blood (NuclisensEasy MAG extractor, BioMe´rieux, Durham, NC, USA) according to Boom et al 16 Results were multiplied by 100 to achieve copy number per ml. The detection limit of the assay is 1000 DNA copies per ml blood.…”

Section: Virological Follow-upmentioning

confidence: 99%

Validation of a DNAemia cutoff for preemptive therapy of cytomegalovirus infection in adult hematopoietic stem cell transplant recipients

Gerna

Lilleri

Caldera

et al. 2008

Bone Marrow Transplant

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A randomized trial comparing a DNAemia cutoff of 10 000 copies per ml whole blood and first pp65 antigenemia positivity for initiation of preemptive therapy of human cytomegalovirus (HCMV) infection in adult hematopoietic stem cell transplant recipients was completed. DNAemia was chosen for cutoff definition since it is more automatable and standardizable than antigenemia, and more closely reflects the actual viral replication. The primary end point of the study was to compare the number of patients treated in the two arms. A total of 83 patients (42 in the DNAemia, and 41 in the antigenemia arm) were enrolled in the study. The incidence of HCMV infection, as detected by the relevant randomization assay (76% in the DNAemia versus 85% in the antigenemia arm), was comparable in the two arms, whereas the number of patients treated was significantly lower in the DNAemia arm (63 versus 80%, P ¼ 0.02). A single patient in the DNAemia arm suffered from biopsy-proven HCMV gastric disease diagnosed in the absence of detectable virus in blood. The incidence of graft-versus-host disease, and transplantation-related mortality did not differ between the two arms. In conclusion, our study shows that the use of a cutoff significantly reduces the number of patients requiring antiviral treatment, thus sparing unnecessary drug administration.

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Section: Virological Follow-upmentioning

confidence: 99%

Validation of a DNAemia cutoff for preemptive therapy of cytomegalovirus infection in adult hematopoietic stem cell transplant recipients

Gerna

Lilleri

Caldera

et al. 2008

Bone Marrow Transplant

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“…9,10 In the southern hemisphere, hMPV infection has been reported in healthy children, [11][12][13] but no data are available in HSCT recipients. Sa˜o Paulo is a city with a subtropical climate in the southeast region of Brazil.…”

Section: Introductionmentioning

confidence: 99%

Frequency of human metapneumovirus infection in hematopoietic SCT recipients during 3 consecutive years

Oliveira

Machado

Tateno

et al. 2008

Bone Marrow Transplant

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“…Quantitative DNAemia results were expressed as HCMV DNA copies (ml blood) 21 (Gerna et al, 2006). When requested, results were also translated into IU ml 21 with reference to the WHO International HCMV DNA Standard (Furione et al, 2012).…”

Section: Methodsmentioning

confidence: 99%

Differential kinetics of human cytomegalovirus load and antibody responses in primary infection of the immunocompetent and immunocompromised host

Gerna

Lilleri²,

Fornara

et al. 2015

Journal of General Virology

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The comparative long-term kinetics of human cytomegalovirus (HCMV) load and HCMV-specific antibody responses in the immunocompetent and immunocompromised solid-organ transplanted host during primary HCMV infection was investigated. In total, 40 immunocompetent subjects and 17 transplanted patients were examined for viral load as well as for IgG antibody responses to HCMV glycoproteins gH/gL/pUL128L, gH/gL and gB, and neutralizing antibodies in ARPE-19 epithelial cells and human fibroblasts. In parallel, the CD4 + and CD8 + HCMV-specific T-cell responses were determined by cytokine flow cytometry. Transplanted patients reached significantly higher viral DNA peaks, which persisted longer than in immunocompetent subjects. The ELISA-IgG responses to the pentamer, gH/gL and gB were significantly higher in primary infections of the immunocompetent until six months after onset, with the two antibody levels then overlapping from six to 12 months. Antibody levels neutralizing infection of epithelial cells were significantly higher in transplanted patients after six months, persisting for up to a year after transplantation. This trend was not observed for antibodies neutralizing infection of human fibroblasts, which showed higher titres in the immunocompetent over the entire one-year followup. In conclusion, in immunocompromised patients the viral load peak was much higher, while the neutralizing antibody response exceeded that detected in the immunocompetent host starting six months after onset of follow-up, often concomitantly with a lack of specific CD4 + T cells. In this setting, the elevated antibody response occurred in the presence of differentiated follicular helper T cells in the blood, which decreased in number as did antibody titres upon reappearance of HCMV-specific CD4 + T cells.

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Impact of human metapneumovirus and human cytomegalovirus versus other respiratory viruses on the lower respiratory tract infections of lung transplant recipients

Cited by 99 publications

References 36 publications

Validation of a DNAemia cutoff for preemptive therapy of cytomegalovirus infection in adult hematopoietic stem cell transplant recipients

Validation of a DNAemia cutoff for preemptive therapy of cytomegalovirus infection in adult hematopoietic stem cell transplant recipients

Frequency of human metapneumovirus infection in hematopoietic SCT recipients during 3 consecutive years

Differential kinetics of human cytomegalovirus load and antibody responses in primary infection of the immunocompetent and immunocompromised host

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