Advertisement

Prolonged shedding of type 55 human adenovirus in immunocompetent adults with adenoviral respiratory infections

  • Kyungmin Huh
  • Inseon Kim
  • Jaehun Jung
  • Ji Eun Lee
  • Byung Woo Jhun
  • Se Hun Gu
  • Dong Hyun Song
  • Eun Young Lee
  • Ho Jung Jeong
  • Hongseok YooEmail author
Original Article
  • 31 Downloads

Abstract

Human adenovirus (HAdV) is a common pathogen causing respiratory infections with outbreaks reported in the military and community. However, little information is available on the shedding kinetics. We performed a prospective study of immunocompetent adults confirmed with HAdV respiratory infection by multiplex real-time PCR during an outbreak of HAdV-55. Consecutive respiratory specimens of sputum or nasopharyngeal swab were collected from each patient every 2 days. Viral load was measured by real-time quantitative PCR. Of 32 enrolled patients, 27 (84.4%) had pneumonia. Five patients (15.6%) received cidofovir. Viral load was highest in the earliest samples at 8.69 log10 copies/mL. In a linear regression model, viral load declined consistently in a log-linear fashion at the rate of − 0.15 log10 copies/mL per day (95% confidence interval (CI): − 0.18, − 0.12; R2 = 0.32). However, the regression model estimated the viral shedding duration to be 55 days. The rate of decline in viral load did not differ between patients who received cidofovir and who did not. Patients with prominent respiratory symptoms or extensive involvement on chest radiograph had higher volume of viral excretion. Prolonged viral shedding was observed in otherwise healthy adults with HAdV-55 respiratory infection. This finding should be considered in the establishment of infection control and prevention strategies.

Keywords

Adenovirus Pneumonia Respiratory infections Virus shedding 

Abbreviations

CI

Confidence interval

CVL

Cumulative viral load

GMVL

Geometric mean viral load

HAdV

Human adenovirus

Notes

Acknowledgments

Authors wish to express our sincere gratitude to the nurses who contributed to the collection of respiratory specimens, and to the patients who chose to participate in our study. Also, we thank Professor Yae-Jean Kim for the critical reading of our manuscript.

Funding

This work was supported by a grant from the Armed Forces Medical Command of the Republic of Korea [2016-KMMRP-012].

Compliance with ethical standards

Conflict of interest

I.K is an employee for Biosewoom, Inc., which is a manufacturer and distributor of a commercial diagnostic kit using multiplex PCR for respiratory virus used in this study. All other authors have nothing to declare.

Ethical approval

This study was approved by the Institutional Review Board of the Armed Forces Medical Command (AFMC-16011-IRB-16-008).

Informed consent

Written informed consents were obtained from all participating patients.

References

  1. 1.
    Lynch JP 3rd, Kajon AE (2016) Adenovirus: epidemiology, global spread of novel serotypes, and advances in treatment and prevention. Semin Respir Crit Care Med 37:586–602.  https://doi.org/10.1055/s-0036-1584923 CrossRefGoogle Scholar
  2. 2.
    Jennings LC, Anderson TP, Beynon KA, Chua A, Laing RT, Werno AM, Young SA, Chambers ST, Murdoch DR (2008) Incidence and characteristics of viral community-acquired pneumonia in adults. Thorax 63:42–48.  https://doi.org/10.1136/thx.2006.075077 CrossRefGoogle Scholar
  3. 3.
    Jain S, Self WH, Wunderink RG, Fakhran S, Balk R, Bramley AM, Reed C, Grijalva CG, Anderson EJ, Courtney DM, Chappell JD, Qi C, Hart EM, Carroll F, Trabue C, Donnelly HK, Williams DJ, Zhu Y, Arnold SR, Ampofo K, Waterer GW, Levine M, Lindstrom S, Winchell JM, Katz JM, Erdman D, Schneider E, Hicks LA, McCullers JA, Pavia AT, Edwards KM, Finelli L (2015) Community-acquired pneumonia requiring hospitalization among U.S. adults. N Engl J Med 373:415–427.  https://doi.org/10.1056/NEJMoa1500245 CrossRefGoogle Scholar
  4. 4.
    Ryan MA, Gray GC, Smith B, McKeehan JA, Hawksworth AW, Malasig MD (2002) Large epidemic of respiratory illness due to adenovirus types 7 and 3 in healthy young adults. Clin Infect Dis 34:577–582.  https://doi.org/10.1086/338471 CrossRefGoogle Scholar
  5. 5.
    Gu L, Qu J, Sun B, Yu X, Li H, Cao B (2016) Sustained viremia and high viral load in respiratory tract secretions are predictors for death in immunocompetent adults with adenovirus pneumonia. PLoS One 11:e0160777.  https://doi.org/10.1371/journal.pone.0160777 CrossRefGoogle Scholar
  6. 6.
    Heo JY, Lee JE, Kim HK, Choe KW (2014) Acute lower respiratory tract infections in soldiers, South Korea, April 2011-March 2012. Emerg Infect Dis 20:875–877.  https://doi.org/10.3201/eid2005.131692 CrossRefGoogle Scholar
  7. 7.
    Kajon AE, Dickson LM, Metzgar D, Houng HS, Lee V, Tan BH (2010) Outbreak of febrile respiratory illness associated with adenovirus 11a infection in a Singapore military training cAMP. J Clin Microbiol 48:1438–1441.  https://doi.org/10.1128/jcm.01928-09 CrossRefGoogle Scholar
  8. 8.
    Yoo H, Gu SH, Jung J, Song DH, Yoon C, Hong DJ, Lee EY, Seog W, Hwang IU, Lee D, Jeong ST, Huh K (2017) Febrile respiratory illness associated with human adenovirus type 55 in South Korea military, 2014-20161. Emerg Infect Dis 23:1016–1020.  https://doi.org/10.3201/eid2306.161848 CrossRefGoogle Scholar
  9. 9.
    Jeon K, Kang CI, Yoon CH, Lee DJ, Kim CH, Chung YS, Kang C, Choi CM (2007) High isolation rate of adenovirus serotype 7 from South Korean military recruits with mild acute respiratory disease. Eur J Clin Microbiol Infect Dis 26:481–483.  https://doi.org/10.1007/s10096-007-0312-6 CrossRefGoogle Scholar
  10. 10.
    Fox JP, Brandt CD, Wassermann FE, Hall CE, Spigland I, Kogon A, Elveback LR (1969) The virus watch program: a continuing surveillance of viral infections in metropolitan New York families. VI. Observations of adenovirus infections: virus excretion patterns, antibody response, efficiency of surveillance, patterns of infections, and relation to illness. Am J Epidemiol 89:25–50CrossRefGoogle Scholar
  11. 11.
    Naghipour M, Hart CA, Dove W, Leatherbarrow AJ, Cuevas LE (2009) Adenovirus infections within a family cohort in Iran. Pediatr Pulmonol 44:749–753.  https://doi.org/10.1002/ppul.20785 CrossRefGoogle Scholar
  12. 12.
    Siegel JD, Rhinehart E, Jackson M, Chiarello L (2007) 2007 guideline for isolation precautions: preventing transmission of infectious agents in health care settings. Am J Infect Control 35:S65–S164.  https://doi.org/10.1016/j.ajic.2007.10.007 CrossRefGoogle Scholar
  13. 13.
    Kajon AE, Lu X, Erdman DD, Louie J, Schnurr D, George KS, Koopmans MP, Allibhai T, Metzgar D (2010) Molecular epidemiology and brief history of emerging adenovirus 14-associated respiratory disease in the United States. J Infect Dis 202:93–103.  https://doi.org/10.1086/653083 CrossRefGoogle Scholar
  14. 14.
    Scott MK, Chommanard C, Lu X, Appelgate D, Grenz L, Schneider E, Gerber SI, Erdman DD, Thomas A (2016) Human adenovirus associated with severe respiratory infection, Oregon, USA, 2013-2014. Emerg Infect Dis 22:1044–1051.  https://doi.org/10.3201/eid2206.151898 CrossRefGoogle Scholar
  15. 15.
    Zhao S, Wan C, Ke C, Seto J, Dehghan S, Zou L, Zhou J, Cheng Z, Jing S, Zeng Z, Zhang J, Wan X, Wu X, Zhao W, Zhu L, Seto D, Zhang Q (2014) Re-emergent human adenovirus genome type 7d caused an acute respiratory disease outbreak in Southern China after a twenty-one year absence. Sci Rep 4:7365.  https://doi.org/10.1038/srep07365 CrossRefGoogle Scholar
  16. 16.
    Zhu Z, Zhang Y, Xu S, Yu P, Tian X, Wang L, Liu Z, Tang L, Mao N, Ji Y, Li C, Yang Z, Wang S, Wang J, Li D, Xu W (2009) Outbreak of acute respiratory disease in China caused by B2 species of adenovirus type 11. J Clin Microbiol 47:697–703.  https://doi.org/10.1128/JCM.01769-08 CrossRefGoogle Scholar
  17. 17.
    Hierholzer JC, Pumarola A (1976) Antigenic characterization of intermediate adenovirus 14-11 strains associated with upper respiratory illness in a military camp. Infect Immun 13:354–359Google Scholar
  18. 18.
    Salama M, Amitai Z, Amir N, Gottesman-Yekutieli T, Sherbany H, Drori Y, Mendelson E, Carmeli Y, Mandelboim M (2016) Outbreak of adenovirus type 55 infection in Israel. J Clin Virol 78:31–35.  https://doi.org/10.1016/j.jcv.2016.03.002 CrossRefGoogle Scholar
  19. 19.
    Chmielewicz B, Benzler J, Pauli G, Krause G, Bergmann F, Schweiger B (2005) Respiratory disease caused by a species B2 adenovirus in a military camp in Turkey. J Med Virol 77:232–237.  https://doi.org/10.1002/jmv.20441 CrossRefGoogle Scholar
  20. 20.
    Sarantis H, Johnson G, Brown M, Petric M, Tellier R (2004) Comprehensive detection and serotyping of human adenoviruses by PCR and sequencing. J Clin Microbiol 42:3963–3969.  https://doi.org/10.1128/jcm.42.9.3963-3969.2004 CrossRefGoogle Scholar
  21. 21.
    Ip DK, Lau LL, Chan KH, Fang VJ, Leung GM, Peiris MJ, Cowling BJ (2016) The dynamic relationship between clinical symptomatology and viral shedding in naturally acquired seasonal and pandemic influenza virus infections. Clin Infect Dis 62:431–437.  https://doi.org/10.1093/cid/civ909 Google Scholar
  22. 22.
    Fielding JE, Kelly HA, Mercer GN, Glass K (2014) Systematic review of influenza A(H1N1)pdm09 virus shedding: duration is affected by severity, but not age. Influenza Other Respir Viruses 8:142–150.  https://doi.org/10.1111/irv.12216 CrossRefGoogle Scholar
  23. 23.
    Okiro EA, White LJ, Ngama M, Cane PA, Medley GF, Nokes DJ (2010) Duration of shedding of respiratory syncytial virus in a community study of Kenyan children. BMC Infect Dis 10:15.  https://doi.org/10.1186/1471-2334-10-15 CrossRefGoogle Scholar
  24. 24.
    Peltola V, Waris M, Kainulainen L, Kero J, Ruuskanen O (2013) Virus shedding after human rhinovirus infection in children, adults and patients with hypogammaglobulinaemia. Clin Microbiol Infect 19:E322–E327.  https://doi.org/10.1111/1469-0691.12193 CrossRefGoogle Scholar
  25. 25.
    Sun B, He H, Wang Z, Qu J, Li X, Ban C, Wan J, Cao B, Tong Z, Wang C (2014) Emergent severe acute respiratory distress syndrome caused by adenovirus type 55 in immunocompetent adults in 2013: a prospective observational study. Crit Care 18:456.  https://doi.org/10.1186/s13054-014-0456-6 CrossRefGoogle Scholar
  26. 26.
    Tan D, Zhu H, Fu Y, Tong F, Yao D, Walline J, Xu J, Yu X (2016) Severe community-acquired pneumonia caused by human adenovirus in immunocompetent adults: a multicenter case series. PLoS One 11:e0151199.  https://doi.org/10.1371/journal.pone.0151199 CrossRefGoogle Scholar
  27. 27.
    Gray GC, Chorazy ML (2009) Human adenovirus 14a: a new epidemic threat. J Infect Dis 199:1413–1415.  https://doi.org/10.1086/598522 CrossRefGoogle Scholar
  28. 28.
    Kwong JC (2016) Editorial commentary: symptoms and viral shedding in naturally acquired influenza infections. Clin Infect Dis 62:438–439.  https://doi.org/10.1093/cid/civ914 Google Scholar
  29. 29.
    Giannella M, Alonso M, Garcia de Viedma D, Lopez Roa P, Catalan P, Padilla B, Munoz P, Bouza E (2011) Prolonged viral shedding in pandemic influenza A(H1N1): clinical significance and viral load analysis in hospitalized patients. Clin Microbiol Infect 17:1160–1165.  https://doi.org/10.1111/j.1469-0691.2010.03399.x CrossRefGoogle Scholar
  30. 30.
    Ison MG, Hayden RT (2016) Adenovirus. Microbiol Spectr 4.  https://doi.org/10.1128/microbiolspec.DMIH2-0020-2015
  31. 31.
    Naesens L, Lenaerts L, Andrei G, Snoeck R, Van Beers D, Holy A, Balzarini J, De Clercq E (2005) Antiadenovirus activities of several classes of nucleoside and nucleotide analogues. Antimicrob Agents Chemother 49:1010–1016.  https://doi.org/10.1128/AAC.49.3.1010-1016.2005 CrossRefGoogle Scholar
  32. 32.
    Hoffman JA, Shah AJ, Ross LA, Kapoor N (2001) Adenoviral infections and a prospective trial of cidofovir in pediatric hematopoietic stem cell transplantation. Biol Blood Marrow Transplant 7:388–394CrossRefGoogle Scholar
  33. 33.
    Ganapathi L, Arnold A, Jones S, Patterson A, Graham D, Harper M, Levy O (2016) Use of cidofovir in pediatric patients with adenovirus infection. F1000Res 5:758.  https://doi.org/10.12688/f1000research.8374.1 CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Division of Infectious Diseases, Department of Medicine, Samsung Medical CenterSungkyunkwan University School of MedicineSeoulRepublic of Korea
  2. 2.Biosewoom, Inc.SeoulRepublic of Korea
  3. 3.Armed Forces Medical CommandSeongnamRepublic of Korea
  4. 4.Division of Pulmonary and Critical Care Medicine, Department of MedicineArmed Forces Capital HospitalSeongnamRepublic of Korea
  5. 5.Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical CenterSungkyunkwan University School of MedicineSeoulRepublic of Korea
  6. 6.Agency for Defense DevelopmentDaejeonRepublic of Korea
  7. 7.Department of Laboratory and Diagnostic MedicineArmed Forces Capital HospitalSeongnamRepublic of Korea

Personalised recommendations