To the Editors:
Enterovirus can cause a wide spectrum of diseases in childhood, from asymptomatic infection to fatal encephalitis and myocarditis. Severe enterovirus infection in neonates is often characterized by a sepsis-like illness with high morbidity and mortality and it is not easily distinguished from a serious bacterial infection. We detected twin neonates who developed echovirus 30 infection, complicated by sepsis and hepatic failure with favorable outcome.
The patients were twin infants born in July, at 35 weeks of gestation, to a 31-year-old healthy mother by cesarean section because of transverse presentation. Apgar scores were 9/10 in both infants. Twin A developed neonatal distress at 30 minutes of life and needed nCPAP. Twenty-four hours later, the patient became lethargic, with septic appearance and a body temperature of 38°C. Laboratory investigation for presumed infection was performed and antibiotic therapy was empirically initiated. Laboratory results obtained showed a white blood cell count of 18.500/μL (31% segmented neutrophils, 20% band forms, 12% metamyelocytes), C-reactive protein (CPR) <5 mg/L, platelet count of 36.000/μL, reduced prothrombin activity (16%), and elevated liver function tests (aspartate (AST) and alanine (ALT) aminotransferase levels at 454 and 23 UI/L, respectively). Twin B remained afebrile and had a healthy appearance. Laboratory investigation was performed given the clinical context, and results were similar to the other twin. Thrombocytopenia and coagulopathy progressed despite frequent platelet and fresh frozen plasma transfusions. Liver enzyme levels were elevated on day of life 7 (AST: 3.234 UI/L; ALT: 755 UI/L). Ventricular contractility by cardiac ultrasound was normal. Spinal tap was not performed because of coagulopathy, but both cranial ultrasound and electroencephalogram were normal. Enterovirus RNA was detected by Real-time PCR (Nuclisens EasyQ Enterovirus) from nasopharynx, rectum, and plasma in both twins on day of life 5. Finally, RNA extract was submitted to the Enterovirus National Reference center of Majadahonda Madrid for genotyping with positive detection of Echovius-30. On reinterviewing the mother, a history of maternal flu-like syndrome 1 week before delivery was elicited. The result of a viral study in the mother was negative. Both infants had normal development and normal liver function at 1 year follow-up.
Potential indicators of an enteroviral etiology1 include presentation during summer and autumn, lack of risk factors for bacterial sepsis, history of maternal illness in the 2 weeks before delivery, and low CPR values. Severe infection in neonates presenting as hepatic failure is rare. To our knowledge, there is only 1 similar case in the literature related to echovirus-30.2 The association between raised liver enzymes and coagulopathy with mortality in echovirus infection has been recognized.3
Pleconaril, a potent viral replication inhibitor, is currently being tested for neonatal enteroviral infection in a randomized double-blinded placebo-controlled multicenter study.4 It was originally designed against rhinovirus infection but failed to get approval by the FDA because of CYP3A induction and potential drug interaction.5
Rosa Maria Pino-Ramírez, MD
África Pertierra-Cortada, MD
Martín Iriondo-Sanz, MD, PhD
Xavier Krauel-Vidal, MD, PhD
Department of Neonatology
Carmen Muñoz-Almagro, MD, PhD
Department of Microbiology
Agrupació Sanitària Sant Joan de
Déu-Clínic, P.° Sant Joan de Déu
1. Abzug MJ. Prognosis for neonates with enterovirus hepatitis and coagulopathy. Pediatr Infec Dis J
2. Chen CA, Tsao PN, Chou HC, Hsieh WS, Huang LM. Severe echovirus 30 infection in twin neonates. J Formos Med Assoc
3. Bryant PA, Tingay D, Curtis N, et al. Neonatal coxsackie B virus infection-a tratable disease? Eur J Pediatr
identifier NCT00031512 [ClinicalTrials.gov web site]. Available at: http://clinicaltrials.gov/ct/gui/show/NCT00031512?order=1
. Accessed July 30, 2007.
5. Desmond RA, Accortt NA, Talley L, Villano SA, Soong SJ, Whitley RJ. Enteroviral meningitis: natural history and outcome of pleconaril therapy. Antimicrob Agents Chemother