ESPID Reports and Reviews
Clinical Significance of Multiple Respiratory Virus Detection Cristiana M. Nascimento-Carvalho, MD, PhD* and Olli Ruuskanen, MD, PhD† Key Words: respiratory infection, respiratory virus, respiratory virus coinfection, viral infection
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espiratory viruses can be detected in >90% of children with lower respiratory tract infections, such as bronchiolitis, due to the use of sensitive nucleic acid amplification tests (NAATs) for virus detection.1 NAATs also detect common respiratory viral coinfections, defined as the detection of >1 viral pathogen in the same sample. Even 4–5 different respiratory viruses have been detected in children with acute respiratory infection (ARI).2 In this review, we will discuss the clinical significance of multiple respiratory virus detection (MRVD) that should be the preferred term for this phenomenon3 because it has not been shown that all viruses detected are causing infection. It is possible that some of them are just innocent bystanders inducing no inflammatory response. A large number of studies have shown that MRVD occurs in 20%–40% of children with lower respiratory tract infections, but this finding is less common in adults.2–5 The occurrence of different respiratory viruses in MRVD varies widely in different studies. In a recent study on community-acquired pneumonia among 2222 US children, 38%, 34% and 35%, respectively, of respiratory syncytial virus (RSV), human rhinovirus and human metapneumovirus detections were associated with other viruses compared with 72% of adenovirus and 76% of coronavirus detections.6 In that study, human bocavirus was not tested for. Human bocavirus occurs most commonly associated with other viruses, which has raised the question of From the *Department of Pediatrics, Federal University of Bahia School of Medicine, Salvador, Brazil; and †Department of Pediatrics, Turku University Hospital, Turku, Finland. C.M.N.-C. is a senior investigator at the Brazilian Council for Scientific and Technological Development (CNPq). The authors have no other conflicts of interest to disclose. Address for correspondence: Cristiana M. NascimentoCarvalho, MD, PhD, Department of Pediatrics, Federal University of Bahia School of Medicine, Rua Prof. Aristides Novis, 105/1201B, Salvador, Bahia, CEP 40210-630, Brazil. E-mail: [email protected]. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved. ISSN: 0891-3668/16/3503-0338 DOI: 10.1097/INF.0000000000001032
its potential pathogenicity and significance.7 However, enteroviruses are seldom associated with other viruses. In many studies, human bocavirus plus human rhinovirus is the most common MRVD. Prolonged asymptomatic excretion of a virus detectable by NAATs plus a new infection with a second positive NAATs result might imply MRVD at the molecular level without being a dual clinical infection. With the use of virus culture or virus antigen detection, dual respiratory virus infections have seldomly been detected. In 1997, Drews et al8 reviewed 8 studies with a total of 1341 cases of respiratory viral infection detected by virus culture, serologic tests or polymerase chain reaction (PCR). Dual viral infection was noted in 67 (5%) cases. By considering the results of cell culture alone, 1200 infections were analyzed and 2.3% of them were MRVD. The age range was broad in patients either with MRVD (
Clinical Significance of Multiple Respiratory Virus Detection Cristiana M. Nascimento-Carvalho, MD, PhD* and Olli Ruuskanen, MD, PhD† Key Words: respiratory infection, respiratory virus, respiratory virus coinfection, viral infection
R
espiratory viruses can be detected in >90% of children with lower respiratory tract infections, such as bronchiolitis, due to the use of sensitive nucleic acid amplification tests (NAATs) for virus detection.1 NAATs also detect common respiratory viral coinfections, defined as the detection of >1 viral pathogen in the same sample. Even 4–5 different respiratory viruses have been detected in children with acute respiratory infection (ARI).2 In this review, we will discuss the clinical significance of multiple respiratory virus detection (MRVD) that should be the preferred term for this phenomenon3 because it has not been shown that all viruses detected are causing infection. It is possible that some of them are just innocent bystanders inducing no inflammatory response. A large number of studies have shown that MRVD occurs in 20%–40% of children with lower respiratory tract infections, but this finding is less common in adults.2–5 The occurrence of different respiratory viruses in MRVD varies widely in different studies. In a recent study on community-acquired pneumonia among 2222 US children, 38%, 34% and 35%, respectively, of respiratory syncytial virus (RSV), human rhinovirus and human metapneumovirus detections were associated with other viruses compared with 72% of adenovirus and 76% of coronavirus detections.6 In that study, human bocavirus was not tested for. Human bocavirus occurs most commonly associated with other viruses, which has raised the question of From the *Department of Pediatrics, Federal University of Bahia School of Medicine, Salvador, Brazil; and †Department of Pediatrics, Turku University Hospital, Turku, Finland. C.M.N.-C. is a senior investigator at the Brazilian Council for Scientific and Technological Development (CNPq). The authors have no other conflicts of interest to disclose. Address for correspondence: Cristiana M. NascimentoCarvalho, MD, PhD, Department of Pediatrics, Federal University of Bahia School of Medicine, Rua Prof. Aristides Novis, 105/1201B, Salvador, Bahia, CEP 40210-630, Brazil. E-mail: [email protected]. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved. ISSN: 0891-3668/16/3503-0338 DOI: 10.1097/INF.0000000000001032
its potential pathogenicity and significance.7 However, enteroviruses are seldom associated with other viruses. In many studies, human bocavirus plus human rhinovirus is the most common MRVD. Prolonged asymptomatic excretion of a virus detectable by NAATs plus a new infection with a second positive NAATs result might imply MRVD at the molecular level without being a dual clinical infection. With the use of virus culture or virus antigen detection, dual respiratory virus infections have seldomly been detected. In 1997, Drews et al8 reviewed 8 studies with a total of 1341 cases of respiratory viral infection detected by virus culture, serologic tests or polymerase chain reaction (PCR). Dual viral infection was noted in 67 (5%) cases. By considering the results of cell culture alone, 1200 infections were analyzed and 2.3% of them were MRVD. The age range was broad in patients either with MRVD (
