SALT LAKE CITY, Utah - According to a recent study, nonpolio enteroviral infections commonly cause fever in infants 90 days of age or younger. Additionally, the use of polymerase chain reaction (PCR) to identify febrile infants with nonpolio enteroviral infections may decrease length of hospital stay, unnecessary antibiotic administration and hospital charges.
Infants who were enterovirus-positive were significantly less likely to have severe bacterial infection than infants who were enterovirus-negative. However, all enterovirus-infected infants were hospitalized and received broad-spectrum intravenous antibiotics, said Carrie L. Byington, MD, lead author of the study.
"The use of enterovirus PCR is not meant to replace the current evaluation for sepsis, but to act as a diagnostic adjunct in determining which infants are at lowest risk for serious bacterial infection. Five of the six infants with concomitant serious bacterial infection were recognized at the time of presentation, either by clinical or laboratory findings," she said.
Patients who were enterovirus-positive with cerebrospinal pleocytosis had the longest hospital stays and highest charges of any infants admitted for suspected sepsis. These infants would potentially benefit the most from rapid diagnosis.
"Rapid viral testing in algorithms for the evaluation of febrile infants for suspected sepsis should be considered. Eliminating infants with confirmed viral infections from the pool of all febrile infants, as shown in this study, increases significantly the probability of identifying a bacterial infection in the remaining infants," she explained.
Included in the study were all unimmunized, febrile infants 90 days of age or younger admitted to Primary Children's Medical Center here for sepsis evaluation from December 1996 to December 1997.
In the study were 345 febrile infants and 86 afebrile, control infants. All febrile infants had at least one specimen for PCR analysis. Most, 323 patients, had two or more specimens for analysis, and 238 had three or more. Eighty-nine febrile infants were diagnosed with enteroviral infections; 88 of them had a positive enterovirus PCR assay from one or more specimens.
"Blood, urine, cerebrospinal fluid (CSF) and throat swabs were tested for enteroviruses using a PCR assay. Alternate PCR assays separated polio and nonpolio enteroviruses. Results of bacterial cultures, outcomes and hospital charges were obtained. Blood from afebrile, control infants 90 days of age or younger was also tested for enteroviruses," said Byington, departments of pediatrics and pediatric infectious diseases at the University of Utah, Salt Lake City.
The incidence of enteroviral infection varied depending on the time of the year: 3.2% in January to 50% in August and October. Five enterovirus-positive, febrile patients had concomitant urinary tract infections, and one had concomitant bacteremia. Infants with confirmed enteroviral infection were significantly less likely to have bacterial infection than those who did not have an enterovirus infection.
"Infants who had enterovirus averaged 30 days of age. Most likely, they had primary enterovirus infection, which resulted in fever. Enteroviral infections were detected in fewer than 5% of afebrile, unimmunized control infants. No asymptomatic enteroviral infections were detected in afebrile neonates. No infections with polioviruses were detected in either off-season study patients or control infants. Concerns regarding asymptomatic viremia secondary to oral polio vaccine administration is likely to become less important in the future, because most American pediatricians have adopted a sequential schedule for polio immunization with inactivated polio vaccine given during early infancy," she explained.
The study found that enterovirus PCR improves diagnostic capability significantly. "Although enterovirus culture is readily available in our institution, it was ordered for only 3.7% of the febrile infants enrolled in this study, which reflects clinicians' perception of the utility of viral culture," Byington added.
The enterovirus PCR assay had excellent sensitivity and specificity. In febrile patients who had both types of testing, PCR was twice as sensitive as enterovirus culture.
"We are confident that PCR is a reliable and sensitive method of enterovirus detection," Byington said.
Most sensitive for the diagnosis of enteroviral infection was the PCR of both blood and CSF. Whole blood was useful in diagnosing enteroviral infection in infants both with and without meningitis. Almost 70% of infants who were positive for enterovirus had a positive PCR from blood.
"Enterovirus PCR of blood, in combination with CSF enterovirus PCR, is important in establishing the diagnosis of enteroviral infection. In this study, the cerebrospinal fluid PCR assay did not identify four cases of presumed enteroviral meningitis. All four infants had CSF pleocytosis; three had a positive blood PCR; and one had a positive throat PCR. The addition of the urine and throat swab PCR did not improve our ability to diagnose enteroviral infection significantly," she explained.
Interestingly, enteroviral infections were not only detected in the summer and fall as expected. In fact, they were detected throughout the year. While previous studies have found a male predominance, this study did not find any gender differences in the incidence of enteroviral infection.
"Although nonspecific febrile illnesses are widely assumed to be the most common presentation of enteroviral infection, they make up only 9% of reported cases of enteroviral infection in infants. This study confirms that nonspecific febrile illnesses are common but underdiagnosed. Without the use of PCR, more than 95% of the enteroviral infections identified in this study would have remained undiagnosed," she said.
Central nervous system involvement was present in 75% of enterovirus-positive infants. Almost 90% with a positive blood PCR had either a positive CSF PCR or CSF pleocytosis.
"The finding that the vast majority of infants had evidence of central nervous system infection may be explained by the enterovirus serotypes that predominated in our community in 1997, primarily echoviruses 6 and 30. Alternatively, it may reflect the actual incidence of central nervous system invasion in young infants by all enterovirus serotypes that, before the availability of PCR, was unrecognized because of the lack of cerebrospinal fluid pleocytosis and the lack of sensitivity of viral culture," she added.
For more information:
- Byington CL, Taggart EW, Carroll KC, et al. A polymerase chain reaction-based epidemiologic investigation of the incidence of nonpolio enteroviral infections in febrile and afebrile infants 90 days and younger. Pediatrics. 999;103:e27.
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