Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Diagnosis, gB genotype distribution and viral load of symptomatic congenitally infected CMV patients in Cuba

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

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3

Similar content being viewed by others

References

  1. 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.

    Google Scholar 

  2. 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.

    Article  Google Scholar 

  3. 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.

    Article  CAS  Google Scholar 

  4. 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.

    Article  CAS  Google Scholar 

  5. 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.

    Article  CAS  Google Scholar 

  6. 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.

    Article  Google Scholar 

  7. 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.

    Article  Google Scholar 

  8. 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.

    Article  Google Scholar 

  9. 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.

    Article  Google Scholar 

  10. 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.

    Article  CAS  Google Scholar 

  11. 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.

    Article  CAS  Google Scholar 

  12. 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.

    Article  CAS  Google Scholar 

  13. 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.

    Article  Google Scholar 

  14. 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.

    Article  CAS  Google Scholar 

  15. 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.

  16. Kenneson A, Cannon MJ . Review and meta-analysis of the epidemiology of congenital cytomegalovirus (CMV) infection. Rev Med Virol 2007; 17: 253–276.

    Article  Google Scholar 

  17. 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.

    Article  Google Scholar 

  18. 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.

    Article  CAS  Google Scholar 

  19. Neu N, Duchon J, Zachariah P . TORCH infections. Clin Perinatol 2015; 42: 77–103 viii.

    Article  Google Scholar 

  20. Kliegman RM, Stanton B, Geme JS, Schor NF . Nelson Textbook of Pediatrics. Elsevier - Health Sciences Division: Philadelphia, 2011.

    Google Scholar 

  21. 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.

    Article  CAS  Google Scholar 

  22. 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.

    Article  CAS  Google Scholar 

  23. 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.

    Article  CAS  Google Scholar 

  24. 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.

    Article  CAS  Google Scholar 

  25. 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.

    Article  CAS  Google Scholar 

  26. 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.

    Article  CAS  Google Scholar 

  27. 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.

    Article  CAS  Google Scholar 

  28. 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.

    Article  Google Scholar 

  29. 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.

    Article  CAS  Google Scholar 

  30. 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.

    Article  Google Scholar 

  31. 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.

    Article  Google Scholar 

  32. 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.

    Article  CAS  Google Scholar 

  33. 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.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to C Correa.

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

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

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

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/jp.2016.95

This article is cited by

Search

Quick links