Abstract
Objective:
Cytomegalovirus (CMV) is the leading cause of viral congenital infection. Some viral factors have been proposed to be CMV pathogenicity markers. The objective of this study was to investigate the frequency of congenital CMV infection in symptomatic patients and the possible association with the CMV glycoprotein B (gB) genotype and viral load.
Study Design:
A total of 361 newborns (NB) and 158 pregnant women (PW) with clinically suspected CMV infection were enrolled. Studied samples included urine, saliva, serum, vaginal swabs and amniotic fluid. CMV infection was diagnosed by multiplex nested PCR. CMV gB genotyping was performed on infected samples, followed by viral load determination.
Results:
Overall, 18.7% of the tested patients were positive for CMV infection, 19.7% of NB were congenitally infected and 16.5% of PW showed active CMV infection. gB-2 was the most prevalent genotype detected (39/97 patients). gB CMV mixed infections were detected in 12 patients. gB-2 was associated with mono-infections (P<0.01). Mixed infections showed higher levels of viral load compared with gB mono-infection (P=0.03). Hepatomegaly, splenomegaly, jaundice, sepsis-like syndrome and malformations were the most prevalent clinical findings. gB-4 was more frequently associated with sepsis-like syndrome than other gB genotypes (P=0.04, odds ratio=4.3, confidence interval: 0.9 to 21.6). The difference in medians of CMV load was statistically significant among patients presenting different clinical signs (P=0.04).
Conclusions:
This study showed that CMV is a frequent cause of congenital infection in symptomatic Cuban patients. Despite gB2 being the most frequently detected, gB-4 was the only genotype associated with clinical features (sepsis-like syndrome in NB). No other associations among specific genotypes and clinical characteristics were found. Further studies are needed to clarify the role that viral load and genotype play in the outcome of congenital infection.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Mocarski ES, Shenk T, Pass RF . Cytomegaloviruses. In: Knipe DM, Howley PM (eds). Fields Virology vol. II. Lippincott Williams & Wilkins: Philadelphia, 2007, pp 2703–2772.
de Vries JJ, van Zwet EW, Dekker FW, Kroes AC, Verkerk PH, Vossen AC . The apparent paradox of maternal seropositivity as a risk factor for congenital cytomegalovirus infection: a population-based prediction model. Rev Med Virol 2013; 23: 241–249.
Freed DC, Tang Q, Tang A, Li F, He X, Huang Z et al. Pentameric complex of viral glycoprotein H is the primary target for potent neutralization by a human cytomegalovirus vaccine. Proc Natl Acad Sci USA 2013; 110: E4997–E5005.
Pignatelli S, Dal Monte P, Rossini G, Landini MP . Genetic polymorphisms among human cytomegalovirus (HCMV) wild-type strains. Rev Med Virol 2004; 14: 383–410.
Fries BC, Chou S, Boeckh M, Torok-Storb B . Frequency distribution of cytomegalovirus envelope glycoprotein genotypes in bone marrow transplant recipients. J Infect Dis 1994; 169: 769–774.
Yu ZS, Zou CC, Zheng JY, Zhao ZY . Cytomegalovirus gB genotype and clinical features in Chinese infants with congenital infections. Intervirology 2006; 49: 281–285.
Arellano-Galindo J, Villanueva-Garcia D, Cruz-Ramirez JL, Yalaupari-Mejia JP, Uribe-Gutierrez G, Velazquez-Guadarrama N et al. Detection and gB genotyping of CMV in Mexican preterm infants in the context of maternal seropositivity. J Infect Dev Ctries 2014; 8: 758–767.
Pati SK, Pinninti S, Novak Z, Chowdhury N, Patro RK, Fowler K et al. Genotypic diversity and mixed infection in newborn disease and hearing loss in congenital cytomegalovirus infection. Pediatr Infect Dis J 2013; 32: 1050–1054.
Kouri V, Correa CB, Verdasquera D, Martinez PA, Alvarez A, Aleman Y et al. Diagnosis and screening for cytomegalovirus infection in pregnant women in Cuba as prognostic markers of congenital infection in newborns: 2007-2008. Pediatr Infect Dis J 2010; 29: 1105–1110.
Tenorio A, Echevarria JE, Casas I, Echevarria JM, Tabarés E . Detection and typing of human herpesviruses by multiplex polymerase chain reaction. J Virol Methods 1993; 44: 261–269.
Tarrago D, Quereda C, Tenorio A . Different cytomegalovirus glycoprotein B genotype distribution in serum and cerebrospinal fluid specimens determined by a novel multiplex nested PCR. J Clin Microbiol 2003; 41: 2872–2877.
Lazzarotto T, Guerra B, Lanari M, Gabrielli L, Landini MP . New advances in the diagnosis of congenital cytomegalovirus infection. J Clin Virol 2008; 41: 192–197.
Revello MG, Gerna G . Diagnosis and management of human cytomegalovirus infection in the mother, fetus and newborn infant. Clin Microbiol Rev 2002; 15: 680–715.
Greiner M, Pfeiffer D, Smith RD . Principles and practical application of the receiver-operating characteristic analysis for diagnostic tests. Prev Vet Med 2000; 45: 23–41.
Baquero-Artigao F, Grupo de estudio de la infección congénita por citomegalovirus de la Sociedad Española de Infectología Pediátrica. Consensus document from the Spanish Society of Paediatric Infectious Diseases (SEIP) on the diagnosis and treatment of congenital cytomegalovirus infection. An Pediatr (Barc) 2009; 71: 535–547.
Kenneson A, Cannon MJ . Review and meta-analysis of the epidemiology of congenital cytomegalovirus (CMV) infection. Rev Med Virol 2007; 17: 253–276.
Gandhoke I, Aggarwal R, Lal S, Khare S . Congenital CMV infection in symptomatic infants in Delhi and surrounding areas. Indian J Pediatr 2006; 73: 1095–1097.
Gandhoke I, Aggarwal R, Hussain SA, Pasha ST, Sethi P, Thakur S et al. Congenital CMV infection; diagnosis in symptomatic infants. Indian J Med Microbiol 2009; 27: 222–225.
Neu N, Duchon J, Zachariah P . TORCH infections. Clin Perinatol 2015; 42: 77–103 viii.
Kliegman RM, Stanton B, Geme JS, Schor NF . Nelson Textbook of Pediatrics. Elsevier - Health Sciences Division: Philadelphia, 2011.
Paradowska E, Studzin'ska M, Nowakowska D, Wilczyn'ski J, Rycel M . Distribution of UL144, US28 and UL55 genotypes in Polish newborns with congenital cytomegalovirus infections. Eur J Clin Microbiol Infect Dis 2012; 31: 1335–1345.
Kouri V, Gonzalez EE, Martinez PA, Capo V, Gonzalez R, Perez L et al. Distinct genotypic distribution of cytomegalovirus (CMV) envelope glycoprotein B (gB) in a Cuban cohort of patients with different CMV diseases. Scand J Infect Dis 2007; 39: 1038–1044.
Rycel M, Wujcicka W, Zawilińska B, Paradowska E, Suski P, Gaj Z et al. Mixed infections with distinct cytomegalovirus glycoprotein B genotypes in Polish pregnant women, fetuses, and newborns. Eur J Clin Microbiol Infect Dis 2015; 34: 585–591.
Barbi M, Binda S, Caroppo S, Primache V, Dido P, Guidotti P et al. CMV gB genotypes and outcome of vertical transmission: study on dried blood spots of congenitally infected babies. J Clin Virol 2001; 21: 75–79.
Picone O, Costa JM, Leruez-Ville M, Ernault P, Olivi M, Ville Y . Cytomegalovirus (CMV) glycoprotein B genotype and CMV DNA load in the amniotic fluid of infected fetuses. Prenat Diagn 2004; 24: 1001–1006.
Zhang X, Huang YP, Gao HN, Yang MF, Zhao H, Hu JH et al. Quantification of cytomegalovirus glycoprotein Bn DNA in hematopoietic stem cell transplant recipients by real-time PCR. PLoS One 2012; 7: e51224.
de Vries JJ, Wessels E, Korver AM, van der Eijk AA, Rusman LG, Kroes AC et al. Rapid genotyping of cytomegalovirus in dried blood spots by multiplex real-time PCR assays targeting the envelope glycoprotein gB and gH genes. J Clin Microbiol 2012; 50: 232–237.
Ross SA, Novak Z, Pati S, Patro RK, Blumenthal J, Danthuluri VR et al. Mixed infection and strain diversity in congenital cytomegalovirus infection. J Infect Dis 2011; 204: 1003–1007.
Boppana SB, Rivera LB, Fowler KB, Mach M, Britt WJ . Intrauterine transmission of cytomegalovirus to infants of women with preconceptional immunity. N Engl J Med 2001; 344: 1366–1371.
Lanari M, Lazzarotto T, Venturi V, Papa I, Gabrielli L, Guerra B et al. Neonatal cytomegalovirus blood load and risk of sequelae in symptomatic and asymptomatic congenitally infected newborns. Pediatrics 2006; 117: e76–e83.
Boppana SB, Fowler KB, Pass RF, Rivera LB, Bradford RD . Congenital cytomegalovirus infection: association between virus burden in infancy and hearing loss. J Pediatr 2005; 146: 817–823.
Guerra B, Lazzarotto T, Quarta S, Lanari M, Bovicelli L, Nicolosi A . Prenatal diagnosis of symptomatic congenital cytomegalovirus infection. Am J Obstet Gynecol 2000; 183: 476–482.
Ross SA, Novak Z, Fowler KB, Arora N, Britt WJ, Boppana SB . Cytomegalovirus blood viral load and hearing loss in young children with congenital infection. Pediatr Infect Dis J 2009; 28: 588–592.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Competing interests
The authors declare no conflict of interest.
Additional information
Supplementary Information accompanies the paper on the Journal of Perinatology website
Supplementary information
Rights and permissions
About this article
Cite this article
Correa, C., Kourí, V., Pérez, L. et al. Diagnosis, gB genotype distribution and viral load of symptomatic congenitally infected CMV patients in Cuba. J Perinatol 36, 837–842 (2016). https://doi.org/10.1038/jp.2016.95
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/jp.2016.95