Presentation, Diagnosis, and Management of Enterovirus Infections in Neonates

Abstract

The nonpoliovirus enteroviruses commonly infect newborns, with consequences ranging from asymptomatic infection and benign illness, to severe, life-threatening disease. Frequently occurring symptoms include fever, irritability, lethargy, anorexia, and rash. Although most illnesses are mild, severe disease develops in a subset of newborns infected in the first 2 weeks of life. Severe disease may consist of sepsis, meningoencephalitis, myocarditis, pneumonia, hepatitis, and/or coagulopathy. Substantial mortality rates have been reported, and long-term sequelae may occur among survivors. Risk factors and clinical features associated with severe disease include absence of neutralizing antibody to the infecting serotype, maternal illness prior to or at delivery, prematurity, illness onset within the first few days of life, multiorgan disease, severe hepatitis, positive serum viral culture, and specific infecting serotype (e.g. group B coxsackieviruses and echovirus 11). Whereas the mainstay of diagnosis has traditionally been viral isolation in tissue culture, the polymerase chain reaction has been demonstrated to be more sensitive than culture, highly specific, and rapid. Immunoglobulin has been used as a therapeutic agent for neonates with enterovirus disease; however, clinical efficacy has not been proven. Specific antiviral therapy for enteroviruses is in development. Pleconaril is an investigational agent that inhibits viral attachment to host cell receptors and uncoating of viral nucleic acid. It has broad and potent anti-enterovirus activity, excellent oral bioavailability, and is well tolerated. Some clinical trials have demonstrated benefit in children and adults with enterovirus meningitis, and in adults with upper respiratory tract infections caused by picornaviruses (rhinoviruses or enteroviruses). Data summarizing compassionate use for severe enterovirus diseases (including neonatal sepsis) also suggest possible benefit. Limited pharmacokinetic data are available in infants and neonates. A multicenter, placebo-controlled, randomized trial of pleconaril in neonates with severe hepatitis, coagulopathy, and/or myocarditis is currently being conducted.

Characteristics of Young Infants in Whom Human Parechovirus, Enterovirus or Neither Were Detected in Cerebrospinal Fluid During Sepsis Evaluations

“…3 Less common but more severe presentations include frank encephalitis, hepatitis, sepsis syndrome and/or myocarditis. 4 Clinical presentations of HPeV mostly appear similar to EV. HPeV1 has been the most commonly reported type.…”

GeneXpert Enterovirus Assay: One-Year Experience in a Routine Laboratory Setting and Evaluation on Three Proficiency Panels

“…Infection with enteroviruses is associated with protean clinical manifestations, ranging from asymptomatic or mild febrile illness to severe and potentially fatal syndromes, including paralysis, aseptic meningitis, encephalitis, myocarditis, and neonatal systemic infection (1). Enteroviruses are the most common cause of aseptic meningitis in both children and adults and may cause up to 90% of cases of aseptic meningitis for which an etiology is identified (1,14,18,19). The rapid detection and the rapid characterization of enteroviral meningitis are essential for making decisions for patient management and treatment (5,15,17,20).…”

Severe Hepatitis Associated with an Echovirus 18 Infection in an Immune-Compromised Adult

“…Indeed, the majority of severe echovirus 18 cases in the literature report central nervous system (CNS) disease, although sepsis has also been described in neonates (7,8). Hepatitis caused by other enterovirus serotypes has been reported in neonates and is frequently associated with thrombocytopenia and coagulopathy, which were also present in our patient (5,9,10).…”

“…Enterovirus infections typically peak in the summer and fall, consistent with the timing of disease in this case. Enteroviruses can cause a wide range of clinical syndromes, from a mild, nonspecific illness to severe disseminated disease (5). Nonpoliovirus enteroviruses have a known tropism for the central nervous system, which explains their propensity to cause meningitis and encephalitis (6).…”