Multiplex MassTag-PCR for Respiratory Pathogens in Pediatric Nasopharyngeal Washes Negative by Conventional Diagnostic Testing Shows a High Prevalence of Viruses Belonging to a Newly Recognized Rhinovirus Clade

Overview

Journal J Clin Virol

Specialty Microbiology

Date 2008 Aug 5

PMID 18674964

Citations 48

Authors

Samuel R Dominguez

Thomas Briese

Gustavo Palacios

Jeffrey Hui

Joseph Villari

Vishal Kapoor

Rafal Tokarz

Mary P Glode

Marsha S Anderson

Christine C Robinson

Kathryn V Holmes

W Ian Lipkin

Affiliations

Soon will be listed here.

Abstract

Background: Respiratory infections are the most common infectious diseases in humans worldwide and are a leading cause of death in children less than 5 years of age.

Objectives: Identify candidate pathogens in pediatric patients with unexplained respiratory disease.

Study Design: Forty-four nasopharyngeal washes collected during the 2004-2005 winter season from pediatric patients with respiratory illnesses that tested negative for 7 common respiratory pathogens by culture and direct immunofluorescence assays were analyzed by MassTag-PCR. To distinguish human enteroviruses (HEV) and rhinoviruses (HRV), samples positive for picornaviruses were further characterized by sequence analysis.

Results: Candidate pathogens were detected by MassTag PCR in 27 of the 44 (61%) specimens that previously were rated negative. Sixteen of these 27 specimens (59%) contained picornaviruses; of these 9 (57%) contained RNA of a recently discovered clade of rhinoviruses. Bocaviruses were detected in three patients by RT-PCR.

Conclusions: Our study confirms that multiplex MassTag-PCR enhances the detection of pathogens in clinical specimens, and shows that previously unrecognized rhinoviruses, that potentially form a species HRV-C, may cause a significant amount of pediatric respiratory disease.

Citing Articles

Designing a multi-epitope vaccine candidate against human rhinovirus C utilizing immunoinformatics approach.

Mamun T, Ali M, Hosen M, Rahman J, Islam M, Akib M Front Immunol. 2025; 15():1364129.

PMID: 39840071 PMC: 11747413. DOI: 10.3389/fimmu.2024.1364129.

Human respiratory organoids sustained reproducible propagation of human rhinovirus C and elucidation of virus-host interaction.

Li C, Yu Y, Wan Z, Chiu M, Huang J, Zhang S Nat Commun. 2024; 15(1):10772.

PMID: 39738014 PMC: 11686133. DOI: 10.1038/s41467-024-55076-2.

Deficient inflammasome activation permits an exaggerated asthma phenotype in rhinovirus C-infected immature mice.

Han M, Ishikawa T, Stroupe C, Breckenridge H, Bentley J, Hershenson M Mucosal Immunol. 2021; 14(6):1369-1380.

PMID: 34354243 PMC: 8542611. DOI: 10.1038/s41385-021-00436-0.

RV-C infections result in greater clinical symptoms and epithelial responses compared to RV-A infections in patients with CRS.

Willis A, Calton J, Calton J, Kim A, Lee R, Torabzadeh E Allergy. 2020; 75(12):3264-3267.

PMID: 32510622 PMC: 9171905. DOI: 10.1111/all.14435.

CDHR3 extracellular domains EC1-3 mediate rhinovirus C interaction with cells and as recombinant derivatives, are inhibitory to virus infection.

Watters K, Palmenberg A PLoS Pathog. 2018; 14(12):e1007477.

PMID: 30532249 PMC: 6301718. DOI: 10.1371/journal.ppat.1007477.

References

Renwick N, Schweiger B, Kapoor V, Liu Z, Villari J, Bullmann R . A recently identified rhinovirus genotype is associated with severe respiratory-tract infection in children in Germany. J Infect Dis. 2008; 196(12):1754-60. PMC: 7109967. DOI: 10.1086/524312. View

Kistler A, Avila P, Rouskin S, Wang D, Ward T, Yagi S . Pan-viral screening of respiratory tract infections in adults with and without asthma reveals unexpected human coronavirus and human rhinovirus diversity. J Infect Dis. 2007; 196(6):817-25. PMC: 7109683. DOI: 10.1086/520816. View

Arruda E, Pitkaranta A, Witek Jr T, Doyle C, Hayden F . Frequency and natural history of rhinovirus infections in adults during autumn. J Clin Microbiol. 1997; 35(11):2864-8. PMC: 230076. DOI: 10.1128/jcm.35.11.2864-2868.1997. View

Atmar R, Glezen W, Greenberg S . Spectrum of clinical illness in hospitalized patients with "common cold" virus infections. Clin Infect Dis. 2000; 31(1):96-100. PMC: 7109925. DOI: 10.1086/313937. View

Coiras M, Aguilar J, Garcia M, Casas I, Perez-Brena P . Simultaneous detection of fourteen respiratory viruses in clinical specimens by two multiplex reverse transcription nested-PCR assays. J Med Virol. 2004; 72(3):484-95. PMC: 7166637. DOI: 10.1002/jmv.20008. View

Miller E, Lu X, Erdman D, Poehling K, Zhu Y, Griffin M . Rhinovirus-associated hospitalizations in young children. J Infect Dis. 2007; 195(6):773-81. PMC: 7109786. DOI: 10.1086/511821. View

Briese T, Palacios G, Kokoris M, Jabado O, Liu Z, Renwick N . Diagnostic system for rapid and sensitive differential detection of pathogens. Emerg Infect Dis. 2005; 11(2):310-3. PMC: 3320438. DOI: 10.3201/eid1102.040492. View

Fendrick A, Monto A, Nightengale B, Sarnes M . The economic burden of non-influenza-related viral respiratory tract infection in the United States. Arch Intern Med. 2003; 163(4):487-94. DOI: 10.1001/archinte.163.4.487. View

Griffin M, Walker F, Iwane M, Weinberg G, Staat M, Erdman D . Epidemiology of respiratory infections in young children: insights from the new vaccine surveillance network. Pediatr Infect Dis J. 2004; 23(11 Suppl):S188-92. DOI: 10.1097/01.inf.0000144660.53024.64. View

10.

Klig J . Current challenges in lower respiratory infections in children. Curr Opin Pediatr. 2004; 16(1):107-12. DOI: 10.1097/00008480-200402000-00019. View

11.

Lu X, Chittaganpitch M, Olsen S, Mackay I, Sloots T, Fry A . Real-time PCR assays for detection of bocavirus in human specimens. J Clin Microbiol. 2006; 44(9):3231-5. PMC: 1594719. DOI: 10.1128/JCM.00889-06. View

12.

Dominguez S, Anderson M, Glode M, Robinson C, Holmes K . Blinded case-control study of the relationship between human coronavirus NL63 and Kawasaki syndrome. J Infect Dis. 2006; 194(12):1697-701. PMC: 7199878. DOI: 10.1086/509509. View

13.

Makela M, Puhakka T, Ruuskanen O, Leinonen M, Saikku P, Kimpimaki M . Viruses and bacteria in the etiology of the common cold. J Clin Microbiol. 1998; 36(2):539-42. PMC: 104573. DOI: 10.1128/JCM.36.2.539-542.1998. View

14.

Manoha C, Espinosa S, Aho S, Huet F, Pothier P . Epidemiological and clinical features of hMPV, RSV and RVs infections in young children. J Clin Virol. 2007; 38(3):221-6. DOI: 10.1016/j.jcv.2006.12.005. View

15.

McErlean P, Shackelton L, Lambert S, Nissen M, Sloots T, Mackay I . Characterisation of a newly identified human rhinovirus, HRV-QPM, discovered in infants with bronchiolitis. J Clin Virol. 2007; 39(2):67-75. PMC: 7172271. DOI: 10.1016/j.jcv.2007.03.012. View

16.

Klig J, Shah N . Office pediatrics: current issues in lower respiratory infections in children. Curr Opin Pediatr. 2005; 17(1):111-8. DOI: 10.1097/01.mop.0000150599.31091.f0. View

17.

Rakes G, Arruda E, Ingram J, Hoover G, ZAMBRANO J, Hayden F . Rhinovirus and respiratory syncytial virus in wheezing children requiring emergency care. IgE and eosinophil analyses. Am J Respir Crit Care Med. 1999; 159(3):785-90. DOI: 10.1164/ajrccm.159.3.9801052. View

18.

Kusel M, de Klerk N, Holt P, Kebadze T, Johnston S, Sly P . Role of respiratory viruses in acute upper and lower respiratory tract illness in the first year of life: a birth cohort study. Pediatr Infect Dis J. 2006; 25(8):680-6. DOI: 10.1097/01.inf.0000226912.88900.a3. View

19.

Palacios G, Briese T, Kapoor V, Jabado O, Liu Z, Venter M . MassTag polymerase chain reaction for differential diagnosis of viral hemorrhagic fever. Emerg Infect Dis. 2006; 12(4):692-5. PMC: 3294712. DOI: 10.3201/eid1204.051515. View

20.

Lau S, Yip C, Tsoi H, Lee R, So L, Lau Y . Clinical features and complete genome characterization of a distinct human rhinovirus (HRV) genetic cluster, probably representing a previously undetected HRV species, HRV-C, associated with acute respiratory illness in children. J Clin Microbiol. 2007; 45(11):3655-64. PMC: 2168475. DOI: 10.1128/JCM.01254-07. View