Frequent Respiratory Viral Infections in Children with Febrile Neutropenia - A Prospective Follow-Up Study.
OBJECTIVE
Febrile neutropenia is common in children undergoing chemotherapy for the treatment of malignancies. In the majority of cases, the cause of the fever is unknown. Although respiratory viruses are commonly associated with this condition, the etiologic significance of this finding remains unclear and is therefore the subject of this study.


METHODS
Nasopharyngeal aspirates were collected during 87 episodes of febrile neutropenia in children age 0-18 years, being treated at a children's oncology unit between January 2013 and June 2014. Real-time polymerase chain reaction was used to determine the presence of 16 respiratory viruses. Follow-up samples were collected from children who tested positive for one or more respiratory viruses. Rhinoviruses were genotyped by VP4/VP2 sequencing. Fisher's exact test and Mann-Whitney U test were used for group comparisons.


RESULTS
At least one respiratory virus was detected in samples from 39 of 87 episodes of febrile neutropenia (45%), with rhinoviruses the most frequently detected. Follow-up samples were collected after a median of 28 days (range, 9-74 days) in 32 of the 39 virus-positive episodes. The respiratory viral infection had resolved in 25 episodes (78%). The same virus was detected at follow-up in one coronavirus and six rhinovirus episodes. Genotyping revealed a different rhinovirus species in two of the six rhinovirus infections.


CONCLUSIONS
The frequency of respiratory viral infections in this group of patients suggests an etiologic role in febrile neutropenia. However, these findings must be confirmed in larger patient cohorts.
Department of Medicine Solna, Infectious Diseases Unit, Center for Molecular Medicine, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden.
Martina
M
Söderman
Department of Medicine Solna, Infectious Diseases Unit, Center for Molecular Medicine, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden.
Samuel
S
Rhedin
Department of Medicine Solna, Infectious Diseases Unit, Center for Molecular Medicine, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden.|Unit for Highly Pathogenic Viruses, Public Health Agency of Sweden; Stockholm, Sweden.
Thomas
T
Tolfvenstam
Department of Clinical Microbiology, Karolinska University Hospital, Stockholm, Sweden.|Department of Microbiology Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
Maria
M
Rotzén-Östlund
Department of Clinical Microbiology, Karolinska University Hospital, Stockholm, Sweden.|Department of Microbiology Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
Jan
J
Albert
Department of Medicine Solna, Infectious Diseases Unit, Center for Molecular Medicine, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden.
Kristina
K
Broliden
Department of Medicine Solna, Infectious Diseases Unit, Center for Molecular Medicine, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden.|Astrid Lindgrens Children's Hospital, Karolinska University Hospital, Stockholm, Sweden.
Anna
A
Lindblom
D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D017934:Coronavirus / Q000145:classification / Q000235:genetics / Q000302:isolation & purification; D018352:Coronavirus Infections / Q000150:complications / Q000175:diagnosis* / Q000473:pathology / Q000821:virology; D064147:Febrile Neutropenia / Q000150:complications / Q000175:diagnosis* / Q000473:pathology / Q000821:virology; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009305:Nasopharynx / Q000821:virology; D009369:Neoplasms / Q000150:complications / Q000473:pathology / Q000821:virology; D009894:Opportunistic Infections / Q000150:complications / Q000175:diagnosis* / Q000473:pathology / Q000821:virology; D010850:Picornaviridae Infections / Q000150:complications / Q000175:diagnosis* / Q000473:pathology / Q000821:virology; D011446:Prospective Studies; D018357:Respiratory Syncytial Virus Infections / Q000150:complications / Q000175:diagnosis* / Q000473:pathology / Q000821:virology; D012136:Respiratory Syncytial Viruses / Q000145:classification / Q000235:genetics / Q000302:isolation & purification; D012141:Respiratory Tract Infections / Q000150:complications / Q000175:diagnosis* / Q000473:pathology / Q000821:virology; D012229:Rhinovirus / Q000145:classification / Q000235:genetics / Q000302:isolation & purification