Abstract
Background
Fever without source (FWS) is defined as a fever in which an extensive history and clinical examination fail to identify a cause. Although the vast majority of children with FWS have a self-limited viral infection, up to 10–25% have a serious bacterial infection (SBI). Therefore, many children require invasive diagnostic tests, hospital admission, and empirical administration of broad-spectrum antibiotics. The aim of this study was to assess the respective role of Human enterovirus (HEV), human parechovirus (HPeV), adenovirus (ADV) and herpesvirus type 6 (HHV6) viremia in children <3 years old presenting with FWS.
Methods
Prospective monocentric diagnostic study. Between November 2015 to December 2017, children <3 year olds with FWS had, in addition to the standardized institutional work-up for FWS, plasma tested by real-time (reverse-transcription) polymerase chain reaction (PCR) for ADV, HHV6, HEV, and HPeV. Specimens with cycle threshold values <40 were considered positive. Quantification was performed on positive specimens for HEV, ADV, and HHV6 specimens when volume permitted.
Results
One hundred thirty-five patients had plasma PCR for ADV, HHV6, HEV, and HPeV. Male:female ratio was 1.45:1 and median age was 2.4 months (interquartile range 1.3–9.7). Among those, 47/135 (34.8%) had at least 1 virus detected in the plasma. More specifically, HEV was detected in 19 patients (14.1%), HHV6 in 15 (11.1%), HPeV in 8 (5.9%), and ADV in 7 (5.2%). Co-infection with 2 viruses was detected in 2 patients (ADV/HEV and ADV/HPeV). No patient with positive plasma PCR had a positive blood or CSF culture. Two patients with positive plasma PCR fulfilled American Academy of Pediatrics criteria for urinary tract infection. The first was HEV+ in plasma and CSF, midstream urine was positive for leukocytes and grew E. coli 106 CFU/mL, whereas the second was HHV6+ in plasma and catheter urine was positive leukocytes/nitrites and grew P. mirabilis 105 CFU/mL.
Conclusion
This epidemiological study highlights the frequent detection of active enteroviral, adenoviral, and HHV6 infections in plasma of children with FWS. Virus–virus and virus–bacteria co-infections are rare. Further studies are needed to establish causality between FWS and viremia.
Disclosures
A. G. L’Huillier, Gertrude Von Meissner foundation: Investigator, Research grant. Ernst and Lucie Schmidheiny foundation: Investigator, Research grant. Research and Development Grant, Geneva University Hospitals: Investigator, Research grant. L. Kaiser, Swiss National Funds: Investigator, Research grant. A. Galetto-Lacour, Gertrude Von Meissner foundation: Investigator, Research grant. Ernst and Lucie Schmidheiny foundation: Investigator, Research grant. Research and Development Grant, Geneva University Hospitals: Investigator, Research grant.
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