Early predictors of neurodevelopmental outcome in symptomatic congenital cytomegalovirus infection

Noyola, Daniel E.; Demmler, Gail J.; Nelson, Christopher T.; Griesser, C.; Williamson, W. D.; Atkins, Jane T.; Rozelle, Judith C; Turcich, Marie; Llorente, Antolin M.; Sellers-Vinson, Sherry; Reynolds, Ann; Bale, James F.; Gerson, Paul; Yow, Martha D.

doi:10.1067/mpd.2001.112061

Cited by 274 publications

(170 citation statements)

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“…10,[13][14][15][16] Prognostic indicators for the larger group of asymptomatic CMV-infected children are lacking, so there are few objective elements to support neonatal counseling, with a high risk for poor family compliance at follow-up. Our study investigated the diagnostic and prognostic significance of neonatal virological tests (pp65 antigenemia and DNAemia) in relation to psychomotor sequelae and hearing loss in symptomatic and asymptomatic congenitally CMV-infected newborns.…”

Section: Figurementioning

confidence: 99%

“…Studies that have been performed to define the prognostic value of clinical, laboratory, and instrumental findings in symptomatic infected newborns have reported contradictory findings. 10,[13][14][15][16] Moreover, insufficient data are available on the possibility of an early definition of outcome in the larger group of asymptomatic newborns. The identification of Ն1 prognostic markers in newborns who have congenital CMV infection and are at increased risk for sequelae could allow careful monitoring to institute prompt rehabilitative and therapeutic strategies to curb subsequent damage.…”

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confidence: 99%

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Neonatal Cytomegalovirus Blood Load and Risk of Sequelae in Symptomatic and Asymptomatic Congenitally Infected Newborns

Lanari¹,

Lazzarotto

Venturi³

et al. 2006

Pediatrics

242

163

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OBJECTIVE. Human cytomegalovirus (CMV) is a ubiquitous human-specific DNA virus and is the main cause of congenital virus infection in developed countries leading to psychomotor impairment and deafness. Diagnostic techniques for CMV detection have greatly improved during recent years with the advent of sophisticated serological and virological methods. The aim of the present study was to assess the diagnostic and prognostic value of detection and quantification of virus in neonatal blood samples of symptomatic and asymptomatic newborns with CMV congenital infection.METHODS. Between January 1997 and December 2003, we studied 99 newborns who were born to women with primary, recurrent, and undefined CMV infection during pregnancy. CMV congenital infection was identified by isolation of the virus in urine within the second week of life. Fifty-eight of 99 infants were infected and were assessed clinically for disease in the newborn period and classified as having symptomatic or asymptomatic infection on the basis of physical, instrumental, and laboratory findings. The infants were followed up from birth according to a protocol of the tertiary NICU at the University of Bologna in a prospective study of long-term sequelae of congenital infection. Forty-seven blood samples were obtained from 47 infants in the neonatal period: 34 were examined for pp65 antigenemia test and 44 for qualitative and quantitative polymerase chain reaction (PCR and qPCR). Sequelae at 12 months were evaluated in a group of 50 infants.RESULTS. Antigenemia was positive in only 10 of 34 samples of infected newborns (29.4% sensitivity). PCR was performed in 44 samples of infected newborns and was positive in all (100% sensitivity). qPCR showed a finding of Ն100 copies per 10 5 of polymorphonuclear leukocytes (PMNLs) in 39 of 44 samples; in the other 5 cases, the number of copies per 10 5 PMNLs was Ͻ100. Between symptomatic and asymptomatic newborns, the mean values of viral blood load determined by qPCR turned out to be significantly higher in symptomatic newborns. Mean values of neonatal blood viral load were statistically higher in newborns who developed sequelae than in those who did not. Of 20 children with a neonatal viral blood load of Ͻ1000 copies per 10 5 PMNLs, 19 did not develop sequelae (negative predictive value: 95%), whereas 2 of 3 with a viral blood load of Ͼ10 000 copies did develop sequelae.CONCLUSIONS. Different viremia value ranges are correlated to a different risk of sequelae: ϳ70% sequelae were found in newborns with a qPCR higher than 10 000 copies per 10 5 PMNLs. Low neonatal viral blood load detected by pp65 antigenemia test and qPCR was highly predictive of absence of sequelae: DNAemia Ͻ1000 copies per 10 5 PMNLs has a negative predictive value of 95%. As an independent predictive factor of outcome, neonatal viremia is another useful element for neonatal counseling and therapeutic choices in symptomatic and asymptomatic newborns.H UMAN CYTOMEGALOVIRUS (CMV) is a ubiquitous human-specific DNA virus that belongs to t...

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Section: Figurementioning

confidence: 99%

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confidence: 99%

Neonatal Cytomegalovirus Blood Load and Risk of Sequelae in Symptomatic and Asymptomatic Congenitally Infected Newborns

Lanari¹,

Lazzarotto

Venturi³

et al. 2006

Pediatrics

242

163

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“…HCMV infection causes clinical disease in 75% of patients in the first year after transplantation (58), while primary maternal infection is a major cause of congenital birth defects including hearing loss and mental retardation (5,33,45). Because of the danger posed by this virus, development of an effective vaccine is considered of highest priority (51).…”

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confidence: 99%

Isolation of Human Monoclonal Antibodies That Potently Neutralize Human Cytomegalovirus Infection by Targeting Different Epitopes on the gH/gL/UL128-131A Complex

Macagno¹,

Bernasconi²,

Vanzetta³

et al. 2010

J Virol

300

366

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Human cytomegalovirus (HCMV) is a widely circulating pathogen that causes severe disease in immunocompromised patients and infected fetuses. By immortalizing memory B cells from HCMV-immune donors, we isolated a panel of human monoclonal antibodies that neutralized at extremely low concentrations (90% inhibitory concentration [IC 90 ] values ranging from 5 to 200 pM) HCMV infection of endothelial, epithelial, and myeloid cells. With the single exception of an antibody that bound to a conserved epitope in the UL128 gene product, all other antibodies bound to conformational epitopes that required expression of two or more proteins of the gH/gL/UL128-131A complex. Antibodies against gB, gH, or gM/gN were also isolated and, albeit less potent, were able to neutralize infection of both endothelial-epithelial cells and fibroblasts. This study describes unusually potent neutralizing antibodies against HCMV that might be used for passive immunotherapy and identifies, through the use of such antibodies, novel antigenic targets in HCMV for the design of immunogens capable of eliciting previously unknown neutralizing antibody responses.Human cytomegalovirus (HCMV) is a member of the herpesvirus family which is widely distributed in the human population and can cause severe disease in immunocompromised patients and upon infection of the fetus. HCMV infection causes clinical disease in 75% of patients in the first year after transplantation (58), while primary maternal infection is a major cause of congenital birth defects including hearing loss and mental retardation (5,33,45). Because of the danger posed by this virus, development of an effective vaccine is considered of highest priority (51).HCMV infection requires initial interaction with the cell surface through binding to heparan sulfate proteoglycans (8) and possibly other surface receptors (12,23,64,65). The virus displays a broad host cell range (24, 53), being able to infect several cell types such as endothelial cells, epithelial cells (including retinal cells), smooth muscle cells, fibroblasts, leukocytes, and dendritic cells (21,37,44,54). Endothelial cell tropism has been regarded as a potential virulence factor that might influence the clinical course of infection (16, 55), whereas infection of leukocytes has been considered a mechanism of viral spread (17,43,44). Extensive propagation of HCMV laboratory strains in fibroblasts results in deletions or mutations of genes in the UL131A-128 locus (1,18,21,36,62,63), which are associated with the loss of the ability to infect endothelial cells, epithelial cells, and leukocytes (15,43,55,61). Consistent with this notion, mouse monoclonal antibodies (MAbs) to UL128 or UL130 block infection of epithelial and endothelial cells but not of fibroblasts (63). Recently, it has been shown that UL128, UL130, and UL131A assemble with gH and gL to form a five-protein complex (thereafter designated gH/gL/UL128-131A) that is an alternative to the previously described gCIII complex made of gH, gL, and gO (22,28,48,63).In immunoco...

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“…2 Of infected infants who are symptomatic at birth, the majority develop neurologic sequelae, including progressive sensorineural hearing loss (SNHL) and poor neurodevelopmental outcomes. [4][5][6][7] SNHL, sometimes delayed, can also occur in 10% to 15% of congenitally infected infants who are asymptomatic at birth. 8,9 In contrast, postnatal infection in term infants rarely has significant clinical consequences.…”

Section: Discussionmentioning

confidence: 99%

Incidence and Impact of CMV Infection in Very Low Birth Weight Infants

2014

PEDIATRICS

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Early predictors of neurodevelopmental outcome in symptomatic congenital cytomegalovirus infection

Cited by 274 publications

References 21 publications

Neonatal Cytomegalovirus Blood Load and Risk of Sequelae in Symptomatic and Asymptomatic Congenitally Infected Newborns

Neonatal Cytomegalovirus Blood Load and Risk of Sequelae in Symptomatic and Asymptomatic Congenitally Infected Newborns

Isolation of Human Monoclonal Antibodies That Potently Neutralize Human Cytomegalovirus Infection by Targeting Different Epitopes on the gH/gL/UL128-131A Complex

Incidence and Impact of CMV Infection in Very Low Birth Weight Infants

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