Severe enterovirus disease in febrile neonates

Abstract

Introduction

Fever in newborn infants may be due to an invasive infection with potential morbidity and mortality. Our aim was to describe the characteristics and outcome of group of febrile neonates with severe enterovirus infection compared to a group of neonates with severe bacterial infection.

Patients and methods

Prospective study including all neonates (<29 days old) admitted to a teaching hospital for fever (>38 °C), with positive bacterial cultures or enterovirus detection in sterile samples, from September 2003 to December 2004. Clinical information, analytical data at admission (complete leukocyte count and C-reactive protein concentrations), blood, urine, and cerebrospinal fluid culture results, molecular detection of enterovirus by polymerase chain reaction (PCR), and outcome were recorded.

Results

Invasive bacterial infections were observed in 62 patients: urinary tract infection (n=57, including 8 cases of bacteremia), sepsis (n=3), and meningitis (n=2). Molecular tests for enterovirus were positive in 10 patients. C-reactive protein values were significantly higher in neonates with bacterial infection than in those with enterovirus infection (62,3 versus 9 mg/L, P=0,008). Two patients with Streptococcus agalactiae meningitis, 1 with Staphylococcus aureus sepsis and 3 with enterovirus infection (manifested as myocarditis, hepatitis, and meningoencephalitis) required admission to the pediatric intensive care unit. Among these, 1 newborn with S. agalactiae and 2 of the 3 with enterovirus infection died.

Conclusions

In our series, enterovirus infection was an important cause of severe invasive disease. Specific viral diagnosis can contribute to the management of febrile neonates.

Resumen

Introducción

En el recién nacido, el síndrome febril puede obedecer a una infección invasiva, que puede conllevar una elevada morbi-mortalidad. Nuestro objetivo fue describir las características y evolución clínica de un grupo de neonatos con fiebre sin foco debida a infección grave por enterovirus, en comparación con otro grupo de neonatos con infección bacteriana grave.

Pacientes y métodos

Estudio prospectivo de todos los recién nacidos (edad<de 29 días de vida) admitidos en un Hospital universitario por fiebre (>38 °C) y cultivo bacteriano positivo o detección de enterovirus en muestras estériles, desde septiembre de 2003 a diciembre 2004. Se recogieron datos clínicos y analíticos (recuento leucocitario y proteína C reactiva) en el momento del ingreso, hemocultivo, urinocultivo y cultivo de líquido cefalorraquídeo, detección molecular de enterovirus mediante reacción en cadena de la polimerasa (PCR) y evolución final.

Resultados

Se recogieron 62 pacientes con infección bacteriana grave: infección del tracto urinario (n=57, incluyendo 8 casos con bacteriemia), sepsis (n=3), meningitis (n=2). La PCR para enterovirus fue positiva en 10 pacientes. La proteína C reactiva fue significativamente más elevada en los niños con infección bacteriana que en los casos de infección por enterovirus (62,3 versus 9 mg/L, p=0,008). Dos pacientes, uno con meningitis por Streptococcus agalactiae y otro con sepsis por S aureus, y tres pacientes con infección por enterovirus (manifestadas como miocarditis, hepatitis y meningoencefalitis) requirieron ingreso en la unidad de cuidados intensivos pediátrica. De estos, el recién nacido con infección por S agalactiae y dos de los 3 pacientes con infección por enterovirus fueron exitus.

Conclusiones

En nuestra serie, la infección por enterovirus fue una causa importante de enfermedad grave. El diagnóstico viral específico podría contribuir al manejo del neonato febril.

Introduction

Fever is the main symptom of infection and sometimes the only clinical manifestation of a serious infectious disease, particularly in newborns. Approximately 10% of fevers in children under the age of 90 days are due to potentially harmful bacterial infections.¹ Differentiating patients with serious febrile illnesses from those who suffer more benign infectious processes has always been a challenge for pediatricians, and has resulted in aggressive approaches to fever management at these early ages. The usual diagnostic and therapeutic approach to a neonate with fever includes hospitalization, collection of blood urine, and cerebrospinal fluid (CSF) for bacterial culture, and empirical parenteral antibiotic treatment.² Additional microbiological analyses are performed depending on the clinical suspicion at admission and later evolution. The combination of anamnestic data, clinical examination, and laboratory findings can sometimes help to identify infants at a high risk for a life-threatening bacterial infection. Medical advances in the prevention and control of neonatal bacterial infections have been extensively reported, whereas less is known about the medical management of viral infections.³

Enterovirus infection is a significant cause of fever in young infants4, 5, 6, 7 and shows a mild and self–limited clinical course in most cases. Nonetheless, serious enterovirus infections leading to hepatitis, myocarditis or septicemia have been reported.8, 9, 10 Molecular detection of enterovirus by polymerase chain reaction (PCR) techniques may provide an early etiologic diagnosis in febrile infants and facilitate the initial management of these patients.

In this study, we describe the characteristics and outcome of enterovirus infections and compare them to those of classical bacterial infections in a series of febrile neonates attended at a pediatric emergency department.