Journal of Postgraduate Medicine, Education and Research

Register      Login

VOLUME 56 , ISSUE 4 ( October-December, 2022 ) > List of Articles


One-third of Children with Febrile Neutropenia and Upper Respiratory Tract Infection Have an Identifiable Viral Isolate in Nasopharyngeal Aspirate: A Prospective Observational Study

Ananta Rao Kancharapu, Pritam Singha Roy, Radha Kanta Ratho, Subhabrata Sarkar, Amita Trehan, Deepak Bansal

Keywords : Acute lymphoblastic leukemia, Immunocompromised, Leukemia, Polymerase chain reaction, Treatment, Virus

Citation Information : Kancharapu AR, Roy PS, Ratho RK, Sarkar S, Trehan A, Bansal D. One-third of Children with Febrile Neutropenia and Upper Respiratory Tract Infection Have an Identifiable Viral Isolate in Nasopharyngeal Aspirate: A Prospective Observational Study. J Postgrad Med Edu Res 2022; 56 (4):174-178.

DOI: 10.5005/jp-journals-10028-1599

License: CC BY-NC 4.0

Published Online: 31-12-2022

Copyright Statement:  Copyright © 2022; The Author(s).


Background: Upper respiratory tract infections (URTI) are common during episodes of febrile neutropenia (FN) in children receiving chemotherapy. Identification of viral organisms in children with FN and URTI may aid in reducing the duration of antibiotics. Materials and methods: The prospective study was conducted over 1½ years (July 2012–December 2013). Nasopharyngeal aspirates (NPA) of children (age ≤14 years) with acute leukemia or non-Hodgkin lymphoma with FN and symptoms of URTI (rhinorrhea with/without cough) were obtained. Reverse transcription polymerase chain reaction (RT-PCR) was utilized to identify respiratory syncytial virus (RSV), human parainfluenza virus 3 (HPIV-3), and human metapneumovirus (HMPV). Real-time PCR was performed for the detection of influenza A and B. Results: A total of 57 patients with a mean age of 6 years (range: 0.5–14) were included. The majority (89.5%) had acute lymphoblastic leukemia (ALL). About 21 viral isolates were identified in 19 (33%) patients. Influenza A and B (62%) topped the list, followed by RSV and HPIV-3 (14% each) and HMPV (10%). Blood cultures returned sterile from all. All patients recovered uneventfully from the episode of FN. Age (p = 0.35), absolute neutrophil count (ANC) (p = 0.68), or phase of chemotherapy (p = 0.36) were not identified as risk factors for the identification of the viral etiology. A higher proportion of samples collected during winter/spring were PCR-positive as compared to summer/autumn (56.7% vs 14.8%; p = 0.036). Conclusion: One-third of children with FN and URTI had an identifiable viral etiology. Future trials may be conducted to explore if antibiotics can be stopped early in patients with low-risk FN and URTI with an identifiable viral etiology. Clinical significance: The study contributes to data for antibiotic stewardship for managing children with low-risk FN and URTI.

PDF Share
  1. Meena JP, Brijwal M, Seth R, et al. Prevalence and clinical outcome of respiratory viral infections among children with cancer and febrile neutropenia. Pediatr Hematol Oncol 2019;36(6):330–343. DOI: 10.1080/08880018.2019.1631920
  2. Cerdeira Barreiro N, Santiago-García B, Casas I, et al. Detection of respiratory viruses in the clinical outcome of children with fever and neutropenia. Pediatr Infect Dis J 2020;39(6):533–538. DOI: 10.1097/INF.0000000000002611
  3. Hijano DR, Maron G, Hayden RT. Respiratory viral infections in patients with cancer or undergoing hematopoietic cell transplant. Front Microbiol 2018;9:3097. DOI: 10.3389/fmicb.2018.03097
  4. Zimmer AJ, Freifeld AG. Optimal management of neutropenic fever in patients with cancer. J Oncol Pract 2019;15(1):19–24. DOI: 10.1200/JOP.18.00269
  5. Mahony JB. Detection of respiratory viruses by molecular methods. Clin Microbiol Rev 2008;21(4):716–747. DOI: 10.1128/CMR.00037-07
  6. Bharaj P, Sullender WM, Kabra SK, et al. Respiratory viral infections detected by multiplex PCR among pediatric patients with lower respiratory tract infections seen at an urban hospital in Delhi from 2005 to 2007. Virol J 2009;6(1):89. DOI: 10.1186/1743-422X-6-89
  7. Bouscambert-Duchamp M, Lina B, Trompette A, et al. Detection of human metapneumovirus RNA sequences in nasopharyngeal aspirates of young French children with acute bronchiolitis by real-time reverse transcriptase PCR and phylogenetic analysis. J Clin Microbiol 2005;43(3):1411–1414. DOI: 10.1128/JCM.43.3.1411-1414.2005
  8. Soudani N, Caniza MA, Assaf-Casals A, et al. Prevalence and characteristics of acute respiratory virus infections in pediatric cancer patients. J Med Virol 2019;91(7):1191–1201. DOI: 10.1002/jmv.25432
  9. Shinn K, Wetzel M, DeGroote NP, et al. Impact of respiratory viral panel testing on length of stay in pediatric cancer patients admitted with fever and neutropenia. Pediatr Blood Cancer 2020;67(11):e28570. DOI: 10.1002/pbc.28570
  10. Büyükkapu-Bay S, Kebudi R, Görgün Ö, et al. Respiratory viral infection`s frequency and clinical outcome in symptomatic children with cancer: a single center experience from a middle-income country. Turk J Pediatr 2018;60(6):653–659. DOI: 10.24953/turkjped.2018.06.005
  11. Aydin Köker S, Demirağ B, Tahta N, et al. A 3-year retrospective study of the epidemiology of acute respiratory viral infections in pediatric patients with cancer undergoing chemotherapy. J Pediatr Hematol Oncol 2019;41(4):e242–e246. DOI: 10.1097/MPH.0000000000001418
  12. Hakim H, Dallas R, Zhou Y, et al. Acute respiratory infections in children and adolescents with acute lymphoblastic leukemia. Cancer 2016;122(5):798–805. DOI: 10.1002/cncr.29833
  13. Söderman M, Rhedin S, Tolfvenstam T, et al. Frequent respiratory viral infections in children with febrile neutropenia - a prospective follow-up study. PloS One 2016;11(6):e0157398. DOI: 10.1371/journal.pone.0157398
  14. Torres JP, Labraña Y, Ibañez C, et al. Frequency and clinical outcome of respiratory viral infections and mixed viral-bacterial infections in children with cancer, fever and neutropenia. Pediatr Infect Dis J 2012;31(9):889–893. DOI: 10.1097/INF.0b013e31825c4b7e
  15. Hou N, Wang K, Zhang H, et al. Comparison of detection rate of 16 sampling methods for respiratory viruses: a Bayesian network meta-analysis of clinical data and systematic review. BMJ Glob Health 2020;5(11):e003053. DOI: 10.1136/bmjgh-2020-003053
  16. Lambert SB, Whiley DM, O’Neill NT, et al. Comparing nose-throat swabs and nasopharyngeal aspirates collected from children with symptoms for respiratory virus identification using real-time polymerase chain reaction. Pediatrics 2008;122(3):e615–e620. DOI: 10.1542/peds.2008-0691
  17. Heikkinen T, Marttila J, Salmi AA, et al. Nasal swab versus nasopharyngeal aspirate for isolation of respiratory viruses. J Clin Microbiol 2002;40(11):4337–4339. DOI: 10.1128/JCM.40.11.4337-4339.2002
  18. Wai AK, Kwok WO, Chan MS, et al. Patients’ perceptions of nasopharyngeal aspiration in the emergency department of a teaching hospital in Hong Kong. Emerg Med J 2007;24(1):35–36. DOI: 10.1136/emj.2006.039701
  19. van Elden LJ, van Kraaij MG, Nijhuis M, et al. Polymerase chain reaction is more sensitive than viral culture and antigen testing for the detection of respiratory viruses in adults with hematological cancer and pneumonia. Clin Infect Dis 2002;34(2):177–183. DOI: 10.1086/338238
  20. Jansen RR, Biemond BJ, Schinkel J, et al. Febrile neutropenia: significance of elaborated screening for respiratory viruses, and the comparison of different sampling methods, in neutropenic patients with hematological malignancies. Virol J 2013;10(1):212. DOI: 10.1186/1743-422X-10-212
  21. Freifeld AG, Bow EJ, Sepkowitz KA, et al. Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 update by the infectious diseases society of America. Clin Infect Dis 2011;52(4):e56–e93. DOI: 10.1093/cid/cir073
  22. Freymuth F, Vabret A, Cuvillon-Nimal D, et al. Comparison of multiplex PCR assays and conventional techniques for the diagnostic of respiratory virus infections in children admitted to hospital with an acute respiratory illness. J Med Virol 2006;78(11):1498–1504. DOI: 10.1002/jmv.20725
  23. Kuypers J, Campbell AP, Cent A, et al. Comparison of conventional and molecular detection of respiratory viruses in hematopoietic cell transplant recipients. Transpl Infect Dis 2009;11(4):298–303. DOI: 10.1111/j.1399-3062.2009.00400.x
  24. Memoli MJ, Athota R, Reed S, et al. The natural history of influenza infection in the severely immunocompromised vs nonimmunocompromised hosts. Clin Infect Dis 2014;58(2):214–224. DOI: 10.1093/cid/cit725
  25. Cheng FW, Lee V, Shing MM, et al. Prolonged shedding of respiratory syncytial virus in immunocompromised children: implication for hospital infection control. J Hosp Infect 2008;70(4):383–385. DOI: 10.1016/j.jhin.2008.08.014
  26. Peltola V, Waris M, Kainulainen L, et al. Virus shedding after human rhinovirus infection in children, adults and patients with hypogammaglobulinaemia. Clin Microbiol Infect 2013;19(7):E322–E327. DOI: 10.1111/1469-0691.12193
  27. Das S, Dunbar S, Tang YW. Laboratory diagnosis of respiratory tract infections in children - the state of the art. Front Microbiol 2018;9:2478. DOI: 10.3389/fmicb.2018.02478
  28. Koskenvuo M, Möttönen M, Rahiala J, et al. Mixed bacterial-viral infections in septic children with leukemia. Pediatr Infect Dis J 2007;26(12):1133–1136. DOI: 10.1097/INF.0b013e318146207c
  29. Rondinelli PI, Ribeiro Kde C, de Camargo B. A proposed score for predicting severe infection complications in children with chemotherapy-induced febrile neutropenia. J Pediatr Hematol Oncol 2006;28(10):665–670. DOI: 10.1097/01.mph.0000212996.94929.0b
  30. Das A, Trehan A, Oberoi S, Bansal D. Validation of risk stratification for children with febrile neutropenia in a pediatric oncology unit in India. Pediatr Blood Cancer 2017;64(6):e26333. DOI: 10.1002/pbc.26333
  31. Santolaya ME, Alvarez AM, Acuña M, et al. Efficacy and safety of withholding antimicrobial treatment in children with cancer, fever and neutropenia, with a demonstrated viral respiratory infection: a randomized clinical trial. Clin Microbiol Infect 2017;23(3):173–178. DOI: 10.1016/j.cmi.2016.11.001
PDF Share
PDF Share

© Jaypee Brothers Medical Publishers (P) LTD.