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Licensed Unlicensed Requires Authentication Published by De Gruyter May 16, 2018

Detection of cytomegalovirus in saliva from infants undergoing sepsis evaluation in the neonatal intensive care unit: the VIRIoN-C study

Andrea Ronchi, Christopher P. Ouellette, Asuncion Mejías, Douglas Salamon, Amy Leber, Lorenza Pugni, Fabio Mosca and Pablo J. Sánchez

Abstract

Objective

To determine the frequency of detection of cytomegalovirus (CMV) among infants evaluated for late-onset sepsis in the neonatal intensive care unit (NICU).

Methods

This study was a prospective cohort study.

Results

During the 13-month study, 84 infants underwent 116 sepsis evaluations, and CMV DNA was detected in saliva in three (4%) infants (median: gestational age 28 weeks, birth weight 950 g), representing 5% (n=6) of all sepsis evaluations. One infant had CMV DNA detected in saliva in all four sepsis evaluations. Two infants had acquired CMV infection, while the timing of CMV acquisition could not be determined in one infant. Two of the three infants had concomitant Gram-negative bacteremia and urinary tract infections (UTIs), two developed severe bronchopulmonary dysplasia (BPD) and none died.

Conclusion

Detection of CMV DNA in saliva occurred in 4% of infants and 5% of sepsis evaluations. Persistence of CMV DNA shedding in saliva made attribution of clinical illness difficult to ascertain.


Corresponding author: Pablo J. Sánchez, MD, Department of Pediatrics, Divisions of Neonatal-Perinatal Medicine and Pediatric Infectious Diseases, University of Texas Southwestern Medical Center, Dallas, TX, USA; Department of Pediatrics, Divisions of Neonatology and Pediatric Infectious Diseases, Nationwide Children’s Hospital – The Ohio State University College of Medicine, Columbus, OH, USA; Center for Perinatal Research, The Research Institute at Nationwide Children’s Hospital, Columbus, OH, USA; and Nationwide Children’s Hospital – The Ohio State University, 700 Children’s Drive, RB3, WB5245, Columbus, OH 43205-2664, USA, Tel.: +614-355-6638
aAndrea Ronchi and Christopher P. Ouellette: These authors contributed equally to this work.

Acknowledgments

The authors thank the following employees of Parkland Memorial Hospital: John Gard, Pharm. D., Melody Bush, RPh, Sara Mureeba, Pharm. D., and Sheeba Tharayil, Pharm. D. of the NICU pharmacy for assistance with identification of study patients, Lea Maria Pereira Mendes of Language Services for support in patient recruitment and consenting and the NICU nurses for assistance with sample collection.

  1. Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

  2. Research funding: None declared.

  3. Employment or leadership: None declared.

  4. Honorarium: None declared.

  5. Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

References

1. Kelly MS, Benjamin DK, Puopolo KM, Laughon MM, Clark RH, Mukhopadhyay S, et al. Postnatal cytomegalovirus infection and the risk for bronchopulmonary dysplasia. JAMA Pediatr 2015;169:e153785.10.1001/jamapediatrics.2015.3785Search in Google Scholar PubMed PubMed Central

2. Kimberlin DW. Sequelae following postnatally acquired cytomegalovirus infection in very low-birth-weight neonates: back to the future. JAMA Pediatr 2015;169:e153841.10.1001/jamapediatrics.2015.3841Search in Google Scholar PubMed

3. Goelz R, Hamprecht K, Klingel K, Poets CF. Intestinal manifestations of postnatal and congenital cytomegalovirus infection in term and preterm infants. J Clin Virol 2016;83:29–36.10.1016/j.jcv.2016.08.289Search in Google Scholar PubMed

4. Tran L, Ferris M, Norori J, Stark M, Craver R, Dowd S, et al. Necrotizing enterocolitis and cytomegalovirus infection in a premature infant. Pediatrics 2013;131:e318–22.10.1542/peds.2011-1971Search in Google Scholar PubMed

5. Turner KM, Lee HC, Boppana SB, Carlo WA, Randolph DA. Incidence and impact of CMV infection in very low birth weight infants. Pediatrics 2014;133:e609–15.10.1542/peds.2013-2217Search in Google Scholar PubMed PubMed Central

6. Takahashi R, Tagawa M, Sanjo M, Chiba H, Ito T, Yamada M, et al. Severe postnatal cytomegalovirus infection in a very premature infant. Neonatology 2007;92:236–9.10.1159/000103982Search in Google Scholar PubMed

7. Josephson CD, Caliendo AM, Easley KA, Knezevic A, Shenvi N, Hinkes MT, et al. Blood transfusion and breast milk transmission of cytomegalovirus in very low-birth-weight infants: a prospective cohort study. JAMA Pediatr 2014;168:1054–62.10.1001/jamapediatrics.2014.1360Search in Google Scholar PubMed PubMed Central

8. Ronchi A, Michelow IC, Chapin KC, Bliss JM, Pugni L, Mosca F, et al. Viral respiratory tract infections in the neonatal intensive care unit: the VIRIoN-I study. J Pediatr 2014;165:690–6.10.1016/j.jpeds.2014.05.054Search in Google Scholar PubMed PubMed Central

9. Delaney M, Mayock D, Knezevic A, Norby-Slycord C, Kleine E, Patel R, et al. Postnatal cytomegalovirus infection: a pilot comparative effectiveness study of transfusion safety using leukoreduced-only transfusion strategy. Transfusion 2016;56:1945–50.10.1111/trf.13605Search in Google Scholar PubMed PubMed Central

10. Lunze K, Bloom DE, Jamison DT, Hamer DH. The global burden of neonatal hypothermia: systematic review of a major challenge for newborn survival. BMC Med 2013;11:24.10.1186/1741-7015-11-24Search in Google Scholar PubMed PubMed Central

11. Baraff LJ. Management of infants and young children with fever without source. Pediatr Ann 2008;37:673–9.Search in Google Scholar

12. Sola-Visner M, Saxonhouse MA, Brown RE. Neonatal thrombocytopenia: what we do and don’t know. Early Hum Dev 2008;84:499–506.10.1016/j.earlhumdev.2008.06.004Search in Google Scholar PubMed

13. Jobe AH, Bancalari E. Bronchopulmonary dysplasia. Am J Respir Crit Care Med 2001;163:1723–9.10.1164/ajrccm.163.7.2011060Search in Google Scholar PubMed

14. Sanchez JL, Storch GA. Multiplex, quantitative, real-time PCR assay for cytomegalovirus and human DNA. J Clin Microbiol 2002;40:2381–6.10.1128/JCM.40.7.2381-2386.2002Search in Google Scholar PubMed PubMed Central

15. Rosenthal LS, Fowler KB, Boppana SB, Britt WJ, Pass RF, Schmid SD, et al. Cytomegalovirus shedding and delayed sensorineural hearing loss: results from longitudinal follow-up of children with congenital infection. Pediatr Infect Dis J 2009;28:515–20.10.1097/INF.0b013e318198c724Search in Google Scholar PubMed PubMed Central

16. Sissons JG, Bain M, Wills MR. Latency and reactivation of human cytomegalovirus. J Infect 2002;44:73–7.10.1053/jinf.2001.0948Search in Google Scholar PubMed

17. Pinninti SG, Ross SA, Shimamura M, Novak Z, Palmer AL, Ahmed A, et al. Comparison of saliva PCR assay versus rapid culture for detection of congenital cytomegalovirus infection. Pediatr Infect Dis J 2015;34:536–7.10.1097/INF.0000000000000609Search in Google Scholar PubMed PubMed Central

18. Ross SA, Ahmed A, Palmer AL, Michaels MG, Sanchez PJ, Bernstein DI, et al. Detection of congenital cytomegalovirus infection by real-time polymerase chain reaction analysis of saliva or urine specimens. J Infect Dis 2014;210:1415–8.10.1093/infdis/jiu263Search in Google Scholar PubMed PubMed Central

19. Mukhopadhyay S, Meyer SA, Permar SR, Puopolo KM. Symptomatic postnatal cytomegalovirus testing among very low-birth-weight infants: indications and outcomes. Am J Perinatol 2016;33:894–902.10.1055/s-0036-1581080Search in Google Scholar PubMed PubMed Central

20. Lanzieri TM, Dollard SC, Josephson CD, Schmid DS, Bialek SR. Breast milk-acquired cytomegalovirus infection and disease in VLBW and premature infants. Pediatrics 2013;131:e1937–45.10.1542/peds.2013-0076Search in Google Scholar PubMed PubMed Central

21. Lombardi G, Garofoli F, Manzoni P, Stronati M. Breast milk-acquired cytomegalovirus infection in very low birth weight infants. J Matern Neonatal Med 2012;25(Suppl. 3):57–62.10.3109/14767058.2012.712345Search in Google Scholar PubMed

22. Okulu E, Akin IM, Atasay B, Ciftci E, Arsan S, Turmen T. Severe postnatal cytomegalovirus infection with multisystem involvement in an extremely low birth weight infant. J Perinatol 2012;32:72–4.10.1038/jp.2011.58Search in Google Scholar PubMed

23. Fischer C, Meylan P, Bickle Graz M, Gudinchet F, Vaudaux B, Berger C, et al. Severe postnatally acquired cytomegalovirus infection presenting with colitis, pneumonitis and sepsis-like syndrome in an extremely low birthweight infant. Neonatology 2010;97:339–45.10.1159/000260137Search in Google Scholar PubMed

24. Hamprecht K, Maschmann J, Jahn G, Poets CF, Goelz R. Cytomegalovirus transmission to preterm infants during lactation. J Clin Virol 2008;41:198–205.10.1016/j.jcv.2007.12.005Search in Google Scholar PubMed

25. Neuberger P, Hamprecht K, Vochem M, Maschmann J, Speer CP, Jahn G, et al. Case-control study of symptoms and neonatal outcome of human milk-transmitted cytomegalovirus infection in premature infants. J Pediatr 2006;148:326–31.10.1016/j.jpeds.2005.09.030Search in Google Scholar PubMed

26. Vochem M, Hamprecht K, Jahn G, Speer CP. Transmission of cytomegalovirus to preterm infants through breast milk. Pediatr Infect Dis J 1998;17:53–8.10.1097/00006454-199801000-00012Search in Google Scholar PubMed

27. Maschmann J, Hamprecht K, Dietz K, Jahn G, Speer CP. Cytomegalovirus infection of extremely low-birth weight infants via breast milk. Clin Infect Dis 2001;33:1998–2003.10.1086/324345Search in Google Scholar PubMed

28. Yasuda A, Kimura H, Hayakawa M, Ohshiro M, Kato Y, Matsuura O, et al. Evaluation of cytomegalovirus infections transmitted via breast milk in preterm infants with a real-time polymerase chain reaction assay. Pediatrics 2003;111(6 Pt 1):1333–6.10.1542/peds.111.6.1333Search in Google Scholar PubMed

29. Heinonen S, Jartti T, Garcia C, Oliva S, Smitherman C, Anguiano E, et al. Rhinovirus detection in symptomatic and asymptomatic children: value of host transcriptome analysis. Am J Respir Crit Care Med 2016;193:772–82.10.1164/rccm.201504-0749OCSearch in Google Scholar PubMed PubMed Central


Article note

The study was presented in part at the Pediatric Academic Societies’ Annual Meeting, Baltimore, MD, April 30–May 3, 2016.


Received: 2018-01-14
Accepted: 2018-04-11
Published Online: 2018-05-16
Published in Print: 2018-12-19

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