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 Table of Contents  
Year : 2021  |  Volume : 8  |  Issue : 1  |  Page : 33-35

Contemplate enteroviral etiology: Not all neonatal sepsis syndromes are bacterial

Department of Neonatology, Kerala Institute of Medical Sciences, Thiruvananthapuram, Kerala, India

Date of Submission19-Jun-2020
Date of Decision27-Nov-2020
Date of Acceptance27-Feb-2021
Date of Web Publication30-Jun-2021

Correspondence Address:
Femitha Pournami
Department of Neonatology, Kerala Institute of Medical Sciences, Thiruvananthapuram - 695 029, Kerala
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/IJAMR.IJAMR_143_20

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Sepsis is one of the most common clinical diagnosis made in neonatal intensive care units. However, there are not so uncommon situations when the laboratory results do not support bacterial infections. Viral infections are under-recognized and often missed in sick neonates. We describe a case series of neonatal nonpolio enteroviral sepsis confirmed by the polymerase chain reaction. Although the first patient expired, early recognition of etiology in the index case helped control an outbreak.

Keywords: Enterovirus, neonatal, outbreak, viral polymerase chain reaction

How to cite this article:
Pournami F, Kumar MK, Nandakumar A, Prabhakar J, Jain N. Contemplate enteroviral etiology: Not all neonatal sepsis syndromes are bacterial. Int J Adv Med Health Res 2021;8:33-5

How to cite this URL:
Pournami F, Kumar MK, Nandakumar A, Prabhakar J, Jain N. Contemplate enteroviral etiology: Not all neonatal sepsis syndromes are bacterial. Int J Adv Med Health Res [serial online] 2021 [cited 2023 Mar 25];8:33-5. Available from: https://www.ijamhrjournal.org/text.asp?2021/8/1/33/319773

  Background and Introduction Top

The clinical syndrome of sepsis is a common challenge to the neonatal physician. Its, symptoms are nonspecific and multiorgan involvement is usual.[1] Literature reveals that in spite of negative blood cultures, a large proportion of neonates continue to receive broad-spectrum antibiotics for “suspect sepsis.”[2] Considering alternate diagnoses may change the line of management, help anticipate complications, and contribute to infection control. We describe three “septic” neonates referred from the same unit who were confirmed to have enteroviral infection.

  Case Studies Top

Our unit received a late preterm neonate on day 6 of life with a history of fever, poor feeding, and lethargy noted from the 3rd day. The baby was born at 35 weeks to a mother with a history of mild dysuria around 3 weeks before delivery, but no fever, rash, or gastrointestinal symptoms. Her urine culture was reported sterile. Antenatal scans were normal. The baby cried at birth and was roomed in with mother after initial stabilization. Fever and lethargy first noted at 60 hours of life were treated at the referring hospital with intravenous antibiotics for early-onset sepsis. He was referred to our hospital for dropping platelet counts and unremitting fever. We received the baby to our “Isolation unit” with features of early shock as evidenced by cold peripheries and tachycardia. He required fluid resuscitation, broad-spectrum antibiotics and acyclovir. Over the next few hours, baby developed worsening sensorium, gallop rhythm, and increasing oxygen requirements. Baby was ventilated, and inotropic supports were initiated. Platelet transfusions were given. Differential diagnoses considered were sepsis, viral illnesses, hemophagocytosis, hemochromatosis, and inborn errors of metabolism (IEM). Investigations revealed neutrophilic leukocytosis, normal hemoglobin, and severe thrombocytopenia. CRP was negative (<10 mg/L); liver enzymes were elevated; triglycerides were normal; and ferritin was elevated (10400 ng/ml). Investigations to rule out IEM were negative. Echocardiogram indicated features of myocardial dysfunction. Magnetic resonance imaging showed evidence of encephalitis [Figure 1]. A plummeting platelet count did not allow a lumbar puncture. Blood culture reported no bacterial or fungal growth at 24 h of incubation. Intravenous immunoglobulin (IVIg) at 1 g/kg was administered for a clinical diagnosis of myocarditis, hepatitis, and encephalitis. The baby succumbed 36 hours after admission. The blood polymerase chain reaction (PCR) (microbiological labs, Coimbatore) reported a high load of nonpolio enterovirus (EV). The same hospital referred a baby the very next day with a similar clinical picture, except that he was stable in room air and required only intravenous fluids and low dose inotropes. This baby improved with supportive care and IVIg. Suspicion of viral sepsis was confirmed by a positive blood PCR report of moderate load EV. A third baby who was being treated for transient tachypnea in the same neonatal intensive care unit, had improved and had been roomed in with mother. She developed low-grade fever and poor suck. This baby was promptly referred to us. She fortunately improved rapidly with minimal supports and monitoring. Blood PCR was reported positive for low load of EV. Lumbar puncture was conducted on the second infant-biochemistry; cell counts and culture were negative for meningitis. PCR was not done on the cerebrospinal fluid (CSF) as it entailed additional costs to the family. The clinical summary of the three infants is presented in [Table 1].
Table 1: Clinical features and laboratory evidence of the three infants

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Figure 1: Magnetic resonance imaging of the first patient. (a) Diffusion-weighted image showing cortical hyperintensity in bilateral parietal occipital regions; (b) Corresponding hypointense areas on apparent diffusion coefficient; suggestive of encephalitis

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As there were three cases referred in succession from the same unit and the pattern suggested initial perinatal transmission followed by possible horizontal spread, the referring unit was informed about the need for the institution of appropriate infection control measures.

  Discussion Top

Epidemiological studies suggest a discrepancy between the reported low incidence of enteroviral illnesses in neonates and higher detection when suspected and rigorously pursued.[3] Bacterial cultures are obtained very often for nonspecific symptoms and signs of neonatal sepsis. However, gaps in the awareness about viral etiology, low availability of viral cultures, and PCR techniques often lead to missed diagnoses.[4] Identifying neonatal EV infection can have implications in various areas: complications such as myocarditis can be anticipated, supportive therapy optimized, inappropriate antibiotics eluded, and most essentially, infection control practices instituted in a suitable manner.[5]

The above case series pattern follows a typical EV outbreak. Neonatal EV infections may be acquired from an infected mother, another contact, or as a nosocomial infection through feco-oral or respiratory routes.[6] Viral shedding can continue for several weeks after the onset of infection and can occur without the signs of clinical illness. EV may survive on environmental surfaces for periods long enough to allow the transmission from fomites.[7] The spectrum in neonates widely varies, ranging from asymptomatic, mild febrile illness to severe, sometimes fatal, acute sepsis-like syndrome, meningoencephalitis, and hepatitis. A high viral load and early onset of disease is suggestive of perinatal transmission. These babies show rapid deterioration also due to the lack of protective antibodies from a nonimmune mother.[8] We may contemplate that the first baby who presented early in postnatal life was potentially infected transplacentally or through delivery during contact with maternal secretions. Subsequent cases may have been horizontal acquisition as the other two babies who were being cared for in the unit for unrelated problems, had later onset of disease, progressively milder severity, and lower loads of virus in PCR. Manifestations of neonatal EV infections may range from asymptomatic, nonspecific febrile illness to severe fatal multi-system disease referred to as neonatal EV sepsis. Up to 40% can present as aseptic meningitis, and 30% as hepatic necrosis. History suggestive of nonspecific febrile illnesses may be elicited in the mothers' clinical course. Severe disease can present in the early neonatal period as temperature instability, rash, respiratory illness, myocardial involvement, and shock. Neonatal myocarditis is most often caused by Coxsackie B and Echovirus. Mortality as high as 30% has been reported. Meningoencephalitis may not always be associated with CSF pleocytosis. Extensive white matter injury is known and can result in devastating long-term consequences. Severe hepatic disease could result in fulminant and fatal liver failure.[9]

A rapid PCR test in blood/CSF samples makes for the timely identification of EV infections. The test has a sensitivity of 95%, specificity of 100%, positive predictive value of 100%, and negative predictive value of 98%.[10] Although evidence for use is not robust, IVIg is often administered to infected neonates. Early use (within 3 days of illness) has been reported to improve survival in sick neonates who present with myocarditis and hepatitis. Pleconaril is a capsid-binding antiviral drug that has shown in vitro activity and efficacy against serious EV infections. Pocapavir is being used in trials.[9]

Although the literature is rife with reviews about neonatal viral infections including enteroviral, parechoviral, and rotaviral, we suppose that reminding physicians who care for neonates about this etiology is imperative.

  Conclusion Top

When an exhaustive workup for bacterial sepsis draws a blank, one must consider viral illnesses. Judicious use of PCR for confirmation may assist in timely control of an impending outbreak.

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Conflicts of interest

There are no conflicts of interest.

  References Top

Camacho-Gonzalez A, Spearman PW, Stoll BJ. Neonatal infectious diseases: Evaluation of neonatal sepsis. Pediatr Clin North Am 2013;60:367-89.  Back to cited text no. 1
Hornik CP, Fort P, Clark RH, Watt K, Benjamin DK Jr., Smith PB, et al. Early and late onset sepsis in very-low-birth-weight infants from a large group of neonatal intensive care units. Early Hum Dev 2012;88 Suppl 2:S69-74.  Back to cited text no. 2
Hawkes MT, Vaudry W. Nonpolio enterovirus infection in the neonate and young infant. Paediatr Child Health 2005;10:383-8.  Back to cited text no. 3
Sawyer MH. Enterovirus infections: Diagnosis and treatment. Pediatr Infect Dis J 1999;18:1033-9.  Back to cited text no. 4
Morriss FH Jr., Lindower JB, Bartlett HL, Atkins DL, Kim JO, Klein JM, et al. Neonatal enterovirus infection: Case series of clinical sepsis and positive cerebrospinal fluid polymerase chain reaction test with myocarditis and cerebral white matter injury complications. AJP Rep 2016;6:e344-51.  Back to cited text no. 5
Lin TY, Kao HT, Hsieh SH, Huang YC, Chiu CH, Chou YH, et al. Neonatal enterovirus infections: Emphasis on risk factors of severe and fatal infections. Pediatr Infect Dis J 2003;22:889-94.  Back to cited text no. 6
Zaoutis T, Klein JD. Enterovirus infections. Pediatr Rev 1998;19:183-91.  Back to cited text no. 7
Modlin JF. Perinatal echovirus infection: Insights from a literature review of 61 cases of serious infection and 16 outbreaks in nurseries. Rev Infect Dis 1986;8:918-26.  Back to cited text no. 8
Chuang YY, Huang YC. Enteroviral infection in neonates. J Microbiol Immunol Infect 2019;52:851-7.  Back to cited text no. 9
Kost CB, Rogers B, Oberste MS, Robinson C, Eaves BL, Leos K, et al. Multicenter beta trial of the GeneXpert enterovirus assay. J Clin Microbiol 2007;45:1081-6.  Back to cited text no. 10


  [Figure 1]

  [Table 1]


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