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• Re: Herpes virus must be considered as one of the causes for late onset sepsis
  Christian P. Speer
  Published on: 22 October 2015
• Herpes virus must be considered as one of the causes for late onset sepsis
  Dushyant Batra
  Published on: 20 July 2015

• Published on: 22 October 2015

  Re: Herpes virus must be considered as one of the causes for late onset sepsis

  • Christian P. Speer
  • Other Contributors:
    • Ying Dong

  A culture-negative neonatal sepsis is more than herpes virus infection

  Ying Dong a, Christian P. Speer b

  a Department of Paediatrics, Children's Hospital of Fudan University, Shanghai, China

  b University Children's Hospital, University of Wurzburg, Wurzburg, Germany

  We highly appreciate the authors' contribution to the full picture of pathogens causing systemic late-onset neonatal inf...

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  A culture-negative neonatal sepsis is more than herpes virus infection

  Ying Dong a, Christian P. Speer b

  a Department of Paediatrics, Children's Hospital of Fudan University, Shanghai, China

  b University Children's Hospital, University of Wurzburg, Wurzburg, Germany

  We highly appreciate the authors' contribution to the full picture of pathogens causing systemic late-onset neonatal infection. The letter by Dr. Batra and Dr. Smith highlights the morbidity and mortality of neonatal herpes infection, and in a broader sense, calls to our attention the differential diagnosis and treatment of culture-negative neonatal sepsis. It should be noted, however, that bacteria still remain to be the primary causative agents of neonatal sepsis, and negative culture results do not necessarily rule out the possibility of bacterial infections given the inherent limitation of culture technology and nonculturability of many potential pathogenic bacteria.1 With rapid development in molecular- based methods such as polymerase chain reaction (PCR) and denaturing gradient gel electrophoresis, previous culture-negative cases deemed to have other pathogenic origins may actually turn out to be bacterial infections. Should the possibility of bacterial and fungal sepsis be reliably excluded, a viral etiology has to be considered. Apart from herpes virus, enteroviruses as well as parechoviruses are also demonstrated to be frequent viral causes of neonatal infections, with herpes virus identified in 17.5 per 100,000 live births and the latter two affecting up to 12% of neonates followed until one month of life. 2, 3, 4 The prevalence and the spectrum of viruses as well as the predominant virus in late-onset neonatal infections have yet to be revealed due to a lack of population- based epidemiological data. Virus infections have a spectrum of clinical manifestations ranging from nonspecific mild symptoms to sepsis-like illness which can result in rapid deterioration. 2, 3, 4 Enteroviruses, parechoviruses as well as herpes viruses were shown to be able to cause devastating infections among neonates, with risk factors and mortality rate yet to be adequately elucidated. Current data show that the mortality rate could be as high as 42% for enterovirus and 47% for herpes virus. 2, 4 Concerns about the adverse outcomes of severe viral infections prompt some clinicians to consider incorporating an antiviral agent into the empirical treatment of neonatal sepsis. However, this process may be confounded by the harm of using antiviral agents against sepsis proven otherwise and the difficulty in applying specified molecular techniques to confirm viral infections especially in resource-limited regions.

  We agree with Dr. Batra and Dr. Smith that the differentiation of systemic viral infections from bacterial late onset sepsis at presentation seem to be extremely difficult. Neonatologists and pediatricians should be highly vigilant and include viral infections in the differential diagnosis of late onset sepsis. No doubt, whenever herpes infection is suspected, a prompt treatment with acyclovir has to be initiated. However, we are hesitant to recommend intravenous acyclovir directed against herpes viruses as a routine strategy to be included in protocols on late onset sepsis. Besides the above mentioned open questions, future research should focus on rapid and reliable diagnostic procedures and markers of early diagnosis of neonatal infections which will allow a differentiation between bacterial, fungal and viral organisms. The authors have no potential conflict of interests.

  References

  1. Kellenberger E. Exploring the unknown. The silent revolution of microbiology. EMBO Rep 2001; 2:5-7.

  2. Tebruegge M, Curtis N. Enterovirus infections in neonates. Semin Fetal Neonatal Med 2009;14:222-7.

  3. Cilla A, Megias G, Suarez J, et al. Human parechovius and enterovirus in neonates: Distinct infections with overlapping features. Early Hum Dev 2015;91:475-8.

  4. Batra D, Davies P, Manktelow BN, Smith C. The incidence and presentation of neonatal herpes in a single UK tertiary centre, 2006-2013. Arch Dis Child 2014; 99:916-21.

  Conflict of Interest:

  None declared

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  Conflict of Interest:
  None declared.

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• Published on: 20 July 2015

  Herpes virus must be considered as one of the causes for late onset sepsis

  • Dushyant Batra, Consultant Neonatology
  • Other Contributors:
    • Patrick Davies, Craig Smith

  Dear Editor, Archives of Disease of childhood: Foetal and Neonatal edition

  We read the review article by Dong et al(1) with interest. We wanted to congratulate the authors on a very balanced and clinically relevant review; highlighting the epidemiological, therapeutic and preventative aspects of late onset sepsis caused by bacteria and fungi. We believe that the review would have been even more clinically releva...

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  Dear Editor, Archives of Disease of childhood: Foetal and Neonatal edition

  We read the review article by Dong et al(1) with interest. We wanted to congratulate the authors on a very balanced and clinically relevant review; highlighting the epidemiological, therapeutic and preventative aspects of late onset sepsis caused by bacteria and fungi. We believe that the review would have been even more clinically relevant, if it had included viral sepsis e.g. herpes simplex virus (HSV) infection. In a recent UK based study(2) we demonstrated a high neonatal herpes sepsis incidence (17.5 per 100,000 live births) highlighting the non- specific clinical presentation and high mortality of this disease. The majority of cases in our study presented between days 3 and 14 of life; with non-specific symptoms, with or without a herpetic rash. The differentiation from bacterial late onset sepsis at presentation is extremely difficult. Extrapolation of our data implies UK mortality due to herpes of over 1.5 times that of group B streptococcal sepsis(3).

  Unless attending clinicians are vigilant and expand the differential diagnoses of suspected late onset sepsis, there will be increased morbidity and mortality from neonatal herpes infections. Raised Alanine transaminase (ALT) can be an early marker for HSV infection and should be part of the bloods for evaluation of sepsis. Intravenous acyclovir should routinely be included in the protocols of late onset sepsis.

  Dushyant Batra Patrick Davies Craig Smith Nottingham University Hospitals NHS Trust, Nottingham UK

  References: 1. Dong Y, Speer CP. Late onset sepsis: recent developments. Arch Dis Child Fetal Neonatal Ed 2015;100:F257-F263 doi;10.1136/archdischild-2014- 306213 2. Batra D, Davies P, Manktelow BN, Smith C. The incidence and presentation of neonatal herpes in a single UK tertiary centre, 2006-2013. Arch Dis Child 2014;99:916-921. 3. Edmond KM, Kortsalioudaki C, Scott S, et al. Group B streptococcal disease in infants aged younger than 3 months: systematic review and meta- analysis. Lancet 2012;379:547-556.

  Conflict of Interest:

  None declared

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  Conflict of Interest:
  None declared.

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