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 Table of Contents  
CASE REPORT
Year : 2014  |  Volume : 3  |  Issue : 4  |  Page : 211-213

Disseminated neonatal herpes simplex virus infection presenting with pneumonia and progressive respiratory failure


Department of Pediatrics, Wake Forest School of Medicine, Winston Salem, North Carolina, USA

Date of Web Publication14-Nov-2014

Correspondence Address:
Avinash K Shetty
Department of Pediatrics, Wake Forest School of Medicine, Medical Center Blvd, Meads Hall, 3rd Floor, Winston Salem, North Carolina 27157
USA
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/2249-4847.144752

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  Abstract 

Disseminated neonatal herpes simplex virus (HSV) infection represents the most severe form of neonatal herpes, and is associated with high morbidity and mortality. Early recognition of disseminated HSV disease in the neonate can be difficult, since the clinical presentation often mimics bacterial sepsis with absence of cutaneous vesicles. We describe a 5-day-old male infant with disseminated HSV-2 disease, who initially presented with pneumonia and progressive respiratory failure requiring extracorporeal membrane oxygenation. Laboratory data were significant for leukopenia, thrombocytopenia and disseminated intravascular coagulation. Chest radiograph showed diffuse pulmonary infiltrates. Tracheal aspirate cultures grew HSV-2. The patient was treated with a 3 weeks course of intravenous acyclovir. The key feature in this case is to recognize that HSV can present in neonates with rapidly progressive pneumonitis and sepsis syndrome.

Keywords: Disseminated disease, neonatal herpes, pneumonia


How to cite this article:
Shetty AK, Givner LB. Disseminated neonatal herpes simplex virus infection presenting with pneumonia and progressive respiratory failure. J Clin Neonatol 2014;3:211-3

How to cite this URL:
Shetty AK, Givner LB. Disseminated neonatal herpes simplex virus infection presenting with pneumonia and progressive respiratory failure. J Clin Neonatol [serial online] 2014 [cited 2021 Feb 27];3:211-3. Available from: https://www.jcnonweb.com/text.asp?2014/3/4/211/144752


  Introduction Top


Disseminated neonatal herpes simplex virus (HSV) infection represents the most severe form of neonatal herpes, and is associated with high morbidity and mortality. [1] Early recognition of disseminated HSV disease in the neonate can be challenging, since the clinical presentation often is confused with bacterial sepsis. We describe a 5-day-old infant with disseminated HSV-2 disease, who initially presented with pneumonia and progressive respiratory failure.


  Case report Top


A 5-day-old male was admitted to our neonatal intensive care unit (NICU) because of respiratory failure. The baby was born at 39 weeks gestation by vaginal delivery and weighed 3645 g. Apgar scores were 7 and 8 at 1 min and 5 min, respectively. Mother had artificial rupture of membranes 10 h prior to delivery. There was no maternal history or clinical findings suggestive of genital HSV infection prior to or during pregnancy. In addition, the maternal HSV serologic status was unknown. He developed respiratory distress soon after birth and required oxygen supplementation for 6 h. After obtaining a blood culture, ampicillin, and gentamicin were administered. The infant improved clinically and was discharged on day 2 of life when blood cultures were negative for bacteria. On day 5 of life, he developed respiratory distress resulting in referral to our NICU.

Physical examination revealed a critically ill infant with a temperature of 101΀F, heart rate of 160 beats/min, respiratory rate of 70 breaths/min, blood pressure of 55/37 mm Hg, and an oxygen saturation of 79% on room air. Examination was notable for nasal flaring, severe subcostal and intercostal retractions, and bilateral coarse breath sounds. There was no rash, adenopathy or hepatosplenomegaly. An arterial blood gas revealed a pH of 7.33, a partial pressure of oxygen of 45 mm Hg, and a partial pressure of carbon dioxide of 52 mm Hg. The patient was promptly intubated and intravenous (IV) ampicillin and cefotaxime were begun.

Laboratory data was significant for leukopenia (white blood cell count, 4100 cells/mm 3 ), thrombocytopenia (platelet count, 23,000/mm 3 ) and disseminated intravascular coagulation (DIC) (Prothrombin time, 20 s [normal = 11-15 s], partial thromoboplastin time 34 s [normal < 31 s] and fibrinogen level, 78 mg/dl [normal = 180-363 mg/dl]). Liver enzymes were normal. Tracheal aspirate Gram stain revealed rare white blood cells and 2+ yeast. Chest radiograph showed diffuse pulmonary infiltrates [Figure 1]. A lumbar puncture (LP) was not performed due to severe thrombocytopenia and coagulopathy.
Figure 1: Chest radiograph showing bilateral opacification due to diffuse pulmonary infiltrates

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Our patient was begun on empiric IV acyclovir and HSV-2 infection was subsequently confirmed by cell culture of the tracheal aspirate. His clinical course was complicated by progressive respiratory failure requiring extracorporeal membrane oxygenation (ECMO) on hospital day 2. Thereafter, his clinical status improved gradually. He was on ECMO for 9 days and the ventilator for 17 days. Following a 3 weeks course of IV acyclovir for disseminated HSV type 2 disease with pneumonitis, he was discharged home after 32 days of hospitalization.


  Discussion Top


The key feature in this case is to recognize that HSV can present in neonates with rapidly progressive pneumonitis and sepsis syndrome. Other viruses such as enterovirus and adenovirus also can present with a clinical picture mimicking bacterial sepsis. Although in a term infant in the 1 st week of life, the differential diagnosis surely includes bacterial sepsis (Group B Streptococcus, Escherichia coli, or Listeria monocytogenes), invasive fungal disease would be very unusual. Noninfectious etiologies include cardiac disease and inborn errors of metabolism.

Candidiasis is a major cause of morbidity and mortality among low birth weight infants in the NICU but fungal infection would be very unusual in an otherwise healthy term infant during the 1 st week of life. Risk factors for invasive candida infections in premature infants include exposure to broad-spectrum antibiotics (e.g. third-generation cephalosporins or carbapenems) and presence of indwelling central venous catheters. In the present case, the presence of yeast on the tracheal aspirate likely indicates colonization and not infection. Thus, we started acyclovir therapy after obtaining tracheal aspirate for viral culture given the clinical suspicion of HSV sepsis.

Genital herpes is a sexually transmitted infection caused by HSV-2 or HSV-1. [1] The overall incidence of neonatal HSV infection in the U.S. is 9.6/100,000 live births. [2] HSV-2 accounts for 75% of neonatal herpes cases. [3] Most neonates who acquire HSV infection do so at the time of delivery (~85%) following fetal exposure to infected maternal genital secretions, although transmission can also occur through an ascending viral infection with membrane rupture or with apparently intact membranes. [3] HSV transmission also can occur earlier in utero (5%), or postnatally (10%) from a parent or other caregiver, often from nongenital infection. [4] Women with primary genital HSV infection are at the highest risk (25-60%) of transmitting the virus to the newborn baby, compared to women with recurrent genital HSV infection (<2%). [3] Clinical distinction between primary and recurrent genital HSV infection is difficult.

Neonatal HSV disease may present as: (1) Skin, eye and/or mouth (SEM) disease (45% of cases); (2) central nervous system (CNS) disease (30%); and (3) disseminated disease, involving multiple visceral organs (lung, liver, adrenal glands, or brain) (25%). [3],[4] Disseminated disease is the most severe form of neonatal HSV infection. [4],[5] Infants with disseminated disease usually present between 10 and 12 days of life. [5] The clinical presentation is often characterized by sepsis syndrome, with pneumonitis (37-41%), hepatitis, and severe coagulopathy. [4],[5] Other manifestations of disseminated disease include skin lesions (80%) and encephalitis (60-75%). [5]

Viral sepsis, especially due to HSV should be in the differential of any critically ill infant presenting acutely with sepsis syndrome, pneumonitis, and DIC. Early clinical diagnosis of disseminated neonatal HSV infection is difficult, since the clinical presentation often mimics bacterial sepsis and skin vesicles may be absent, as in this case. [4],[5],[6] Further, more than three-quarters of neonates who acquire HSV are born to mothers with no history or clinical findings suggestive of genital HSV infection prior to or during pregnancy, as in this case. [3]

The diagnosis of neonatal HSV disease may be made by isolation of virus from skin lesions (if present) or surface cultures (conjunctivae, mouth, nasopharynx, and anus) or other appropriate sites (e.g. tracheal aspirate, as in this case). [3],[4] Direct fluorescent antibody and enzyme immunoassay can be used but false-negative results can occur. [3] An LP should be performed in all cases of possible neonatal herpes to evaluate for CNS involvement. [3] Polymerase chain reaction (PCR) of cerebrospinal fluid and whole blood and other sites as appropriate (e.g. tracheal aspirate) should be obtained as part of the diagnostic evaluation of neonatal herpes. [3],[4],[7] Advances in real-time PCR-based methods hold promise for rapid detection of viruses in critically ill infants with pneumonia. [8]

Intravenous acyclovir (60 mg/kg/day in 3 divided doses) is the treatment of choice for neonatal HSV disease. [3],[6] Duration of therapy is 21 days for CNS or disseminated disease (with or without pneumonitis), and 14 days for SEM disease. [3] Disseminated neonatal HSV disease with pneumonitis and respiratory failure may require aggressive critical care support including ECMO. [9]

Without antiviral therapy, the risk of mortality is ~85% in disseminated neonatal HSV infection. [4] Even with receipt of high-dose acyclovir therapy, the 12-month mortality is ~ 30% for disseminated disease, often due to respiratory failure, hepatitis, and DIC. [5],[6] In a recent study, the risk of death from disseminated HSV infection was 75%, even with ECMO support. [9] Thus, it is important to promptly begin acyclovir therapy, while further diagnostic evaluation is undertaken, as in the present case.

In pregnant women with genital HSV infection, antiviral prophylaxis, starting at 36 weeks of gestation can suppress recurrences of genital lesions, reduce viral shedding at delivery and the need for cesarean section. [10] The American College of Obstetrics and Gynecology recommends antiviral suppressive therapy in pregnant women with recently acquired genital herpes. [10] Experts recommend a 7-10 day course of oral acyclovir (400 mg 3 times/day) or valacyclovir (500 mg twice daily) in pregnant women with a first-episode of genital HSV infection. [1] However, the role of maternal antiviral suppressive therapy in prevention of neonatal HSV infection is unclear and warrants further studies. [1],[4]


  Conclusion Top


Disseminated HSV infection must be considered in any infant younger than 4 weeks of age presenting with rapidly progressive pneumonitis and sepsis.

 
  References Top

1.Corey L, Wald A. Maternal and neonatal herpes simplex virus infections. N Engl J Med 2009;361:1376-85.  Back to cited text no. 1
    
2.Flagg EW, Weinstock H. Incidence of neonatal herpes simplex virus infections in the United States, 2006. Pediatrics 2011;127:e1-8.  Back to cited text no. 2
    
3.American Academy of Pediatrics. Herpes simplex. In: Pickering LK, Baker CJ, Kimberlin DW, Long SS, editors. 2012 Red Book: Report of the Committee on Infectious Diseases. 29 th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2012. p. 398-408.  Back to cited text no. 3
    
4.Pinninti SG, Kimberlin DW. Maternal and neonatal herpes simplex virus infections. Am J Perinatol 2013;30:113-9.  Back to cited text no. 4
    
5.Kimberlin DW, Lin CY, Jacobs RF, Powell DA, Frenkel LM, Gruber WC, et al. Natural history of neonatal herpes simplex virus infections in the acyclovir era. Pediatrics 2001;108:223-9.  Back to cited text no. 5
    
6.Kimberlin DW, Lin CY, Jacobs RF, Powell DA, Corey L, Gruber WC, et al. Safety and efficacy of high-dose intravenous acyclovir in the management of neonatal herpes simplex virus infections. Pediatrics 2001;108:230-8.  Back to cited text no. 6
    
7.Akhtar N, Ni J, Stromberg D, Rosenthal GL, Bowles NE, Towbin JA. Tracheal aspirate as a substrate for polymerase chain reaction detection of viral genome in childhood pneumonia and myocarditis. Circulation 1999;99:2011-8.  Back to cited text no. 7
    
8.Aramburo A, van Schaik S, Louie J, Boston E, Messenger S, Wright C, et al. Role of real-time reverse transcription polymerase chain reaction for detection of respiratory viruses in critically ill children with respiratory disease: Is it time for a change in algorithm? Pediatr Crit Care Med 2011;12:e160-5.  Back to cited text no. 8
    
9.Prodhan P, Wilkes R, Ross A, Garcia X, Bhutta AT, Rycus P, et al. Neonatal herpes virus infection and extracorporeal life support. Pediatr Crit Care Med 2010;11:599-602.  Back to cited text no. 9
    
10.ACOG Committee on Practice Bulletins. ACOG Practice Bulletin. Clinical management guidelines for obstetrician-gynecologists. No. 82 June 2007. Management of herpes in pregnancy. Obstet Gynecol 2007;109:1489-98.  Back to cited text no. 10
    


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