eMedicine Specialties > Infectious Diseases > Viral Infections

Adenoviruses: Differential Diagnoses & Workup

Author: Sandra G Gompf, MD, FACP, FIDSA, Section Chief, Associate Professor of Infectious Diseases and International Medicine, Infectious Diseases, James A Haley Veterans Hospital
Coauthor(s): Richard L Oehler, MD, FACP, Assistant Professor, Department of Internal Medicine, Division of Infectious Diseases and Tropical Medicine, Univ of South Florida College of Medicine; Assistant Epidemiologist, Division of Infectious Diseases, Tampa VA Medical Center
Contributor Information and Disclosures

Updated: Dec 3, 2007

Differential Diagnoses

Bronchitis
Pneumonia, Bacterial
Influenza
Pneumonia, Community-Acquired
Pharyngitis, Bacterial
Pneumonia, Viral
Pharyngitis, Viral
Upper Respiratory Infection

Other Problems to Be Considered

Allergic conjunctivitis
Bronchiolitis
Glaucoma
Measles
Respiratory Syncytial Virus Infection
Scleritis
Tracheobronchitis
Uveitis
Whooping cough

Workup

Laboratory Studies

  • Adenovirus is stable in routine viral transport medium, including specimens of nasopharyngeal, rectal, and corneal secretions; urine; and unfixed biopsy tissue. Detection is enhanced if specimens are taken as early in the clinical course as possible and promptly shipped cold or frozen to the appropriate laboratory.
  • Many adenovirus serotypes can be isolated in cell culture lines commonly used in diagnostic virology laboratories; however, others fail to grow. Primary human embryonic kidney cells support growth of many fastidious adenovirus serotypes, but their additional cost may be prohibitive in some settings. Adeno-associated virus has also been known to contaminate this cell line. Other cell lines may not support the growth of ocular strains well, may be less sensitive, or may not be maintainable to support slower-growing strains.
  • Seroreactivity to adenovirus is common. By age 4 years, approximately half of all children have positive adenovirus titers. As a result, serology is less useful in the acute clinical setting. If a serologic diagnosis is pursued, serum should be obtained as early as possible in the clinical course, followed by a second titer 2-4 weeks later. A 4-fold rise in acute titers to convalescent titers is diagnostic.
  • Indirect immunofluorescence assays may be used for direct examination of tissue specimens.
  • Polymerase chain reaction and other rapid molecular diagnostic assays in the management of infection in immunosuppressed persons are in the process of investigation,15,16 and a standard approach has not yet been validated. Serial quantitative polymerase chain reaction seems promising, particularly in pediatric transplantation patients, in whom a rise in viremia has been documented in cases of fatal adenoviral sepsis.17
  • Serotyping is generally in the domain of epidemiology and research and is not typically used in clinical practice. However, as specific syndromes are associated with specific serotypes and as molecular methods advance to allow rapid detection and typing, these assays may become clinically useful.
  • Certain serotypes of enteric adenovirus have been seen in stool specimens using electron microscopy, but they have been difficult to isolate in routine tissue culture. These types have been referred to as noncultivatable enteric adenoviruses. Adenovirus has been identified using electron microscopy and immunohistochemistry techniques. The isolation of enteric adenovirus infection in recipients of small bowel transplants in whom allograft damage is a risk may warrant stool cultures or biopsy.
  • The following laboratory studies are suggested in the given syndromes, both to diagnose adenoviral infections and to evaluate for other diagnoses in the differential of each syndrome.
    • Acute respiratory disease
      • Nasopharyngeal swab for culture of respiratory viruses (eg, influenza virus, adenovirus) is suggested.
      • Consider Monospot assay or respiratory syncytial virus culture for Epstein-Barr virus and respiratory syncytial virus.
      • Consider rapid group A Streptococcus throat swab and culture.
    • Pharyngoconjunctival fever
      • Nasopharyngeal swab for culture of respiratory viruses (eg, influenza virus, adenovirus) is suggested.
      • Consider Monospot assay or respiratory syncytial virus culture for Epstein-Barr virus and respiratory syncytial virus.
      • Consider rapid group A Streptococcus throat swab and culture.
    • Epidemic keratoconjunctivitis: Viral and bacterial swab cultures of conjunctival secretions and scrapings are suggested.
    • Acute hemorrhagic cystitis or nephritis: Urinalysis and cultures for bacterial and viral pathogens are suggested.
    • Gastroenteritis: Consider stool Wright stain, ova and parasites examination, culture for bacterial enteric pathogens, rotavirus assay, and Clostridium difficile toxin assay.

Imaging Studies

  • Pneumonia: Plain radiography or CT scanning demonstrates typically diffuse and reticulonodular infiltrates; however, findings may be lobar.
  • Hepatitis: Liver ultrasonography may be helpful to exclude obstructive causes of transaminitis or hyperbilirubinemia.
  • Nephritis: Renal ultrasonography is helpful to exclude obstructive causes of renal insufficiency or renal swelling that may indicate infection.

Other Tests

  • Urine cytology should be considered to exclude other causes hemorrhagic cystitis does not resolve within 5 days.

Procedures

  • Biopsy may be considered in the setting of pneumonia, hepatitis, nephritis, enteritis, or other suspected end-organ involvement in immunocompromised patients, particularly in transplant recipients. Histology, molecular detection, and immunohistochemical staining may be the only means of definitive diagnosis.

Histologic Findings

  • Pneumonia: Obliterative bronchiolitis is seen; viral intranuclear and intracytoplasmic inclusions with positive immunohistochemical staining specific for adenovirus are noted.
  • Enteritis: Denudation of the gastrointestinal mucosa with edema may be seen. Also, acute and chronic inflammatory infiltrate involving the full thickness of the bowel wall may be noted. Viral intranuclear and intracytoplasmic inclusions with positive immunohistochemical staining specific for adenovirus are noted within infected cells.
  • Hepatitis: Viral intranuclear and intracytoplasmic inclusions with positive immunohistochemical staining specific for adenovirus are noted within infected cells.
  • Nephritis: Viral intranuclear and intracytoplasmic inclusions with positive immunohistochemical staining specific for adenovirus are noted within infected cells. Tubular epithelium is typically involved until late; extension may occur thereafter to the Bowman capsule and the glomerulus.

More on Adenoviruses

Overview: Adenoviruses
Differential Diagnoses & Workup: Adenoviruses
Treatment & Medication: Adenoviruses
Follow-up: Adenoviruses
Multimedia: Adenoviruses
References
[ CLOSE WINDOW ]

References

  1. Havenga MJ, Lemckert AA, Ophorst OJ, et al. Exploiting the natural diversity in adenovirus tropism for therapy and prevention of disease. J Virol. May 2002;76(9):4612-20. [Medline].

  2. Ritter T, Lehmann M, Volk H. Improvements in gene therapy: averting the immune response to adenoviral vectors. BioDrugs. 2002;16(1):3-10. [Medline].

  3. Vora GJ, Lin B, Gratwick K et al. Co-infections of adenovirus species in previously vaccinated patients. Emerg Infect Dis. June 2006;12:921-30. [Medline].

  4. Shah KV. SV40 and human cancer: a review of recent data. Int J Cancer. Jan 15 2007;120(2):215-23. [Medline].

  5. Martini F, Corallini A, Balatti V, Sabbioni S, Pancaldi C, Tognon M. Simian virus 40 in humans. Infect Agent Cancer. 2007;2:13. [Medline].

  6. Kajon AE, Moseley JM, Metzgar D, Huong HS, Wadleigh A, Ryan MA. Molecular epidemiology of adenovirus type 4 infections in US military recruits in the postvaccination era (1997-2003). J Infect Dis. Jul 1 2007;196(1):67-75. [Medline].

  7. Russell KL, Hawksworth AW, Ryan MA et al. Vaccine-preventable adenoviral respiratory illness in US military recruits,1999-2004. Vaccine. April 2006;15:2835-42. [Medline].

  8. CDC. Acute Respiratory Disease Associated with Adenovirus Serotype 14 --- Four States, 2006--2007. MMWR Weekly [serial online]. November 16, 2007;56:Available from: CDC. Accessed November 27, 2007. Available at http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5645a1.htm.

  9. Wirsing von König CH, Rott H, Bogaerts H, Schmitt HJ. A serologic study of organisms possibly associated with pertussis-like coughing. Pediatr Infect Dis J. Jul 1998;17(7):645-9. [Medline].

  10. Versteegh FG, Mooi-Kokenberg EA, Schellekens JF, Roord JJ. Bordetella pertussis and mixed infections. Minerva Pediatr. Apr 2006;58(2):131-7. [Medline].

  11. Bruno B, Zager RA, Boeckh MJ, et al. Adenovirus nephritis in hematopoietic stem-cell transplantation. Transplantation. Apr 15 2004;77(7):1049-57. [Medline].

  12. Jalal H, Bibby DF, Tang JW, Bennett J, Kyriakou C, Peggs K. First reported outbreak of diarrhea due to adenovirus infection in a hematology unit for adults. J Clin Microbiol. Jun 2005;43(6):2575-80. [Medline].

  13. Hedderwick SA, Greenson JK, McGaughy VR, Clark NM. Adenovirus cholecystitis in a patient with AIDS. Clin Infect Dis. Apr 1998;26(4):997-9. [Medline].

  14. Ison MG. Adenovirus infections in transplant recipients. Clin Infect Dis. Aug 1 2006;43(3):331-9. [Medline].

  15. Pehler-Harrington K, Khanna M, Waters CR, Henrickson KJ. Rapid detection and identification of human adenovirus species by adenoplex, a multiplex PCR-enzyme hybridization assay. J Clin Microbiol. Sep 2004;42(9):4072-6. [Medline].

  16. Walls T, Hawrami K, Shingadia D, et al. Polymerase chain reaction in the management of disseminated adenovirus infection after stem cell transplantation. Pediatr Infect Dis J. Dec 2004;23(12):1167-9. [Medline].

  17. Seidemann K, Heim A, Pfister ED, et al. Monitoring of adenovirus infection in pediatric transplant recipients by quantitative PCR: report of six cases and review of the literature. Am J Transplant. Dec 2004;4(12):2102-8. [Medline].

  18. Watkins SJ, Mesyanzhinov VV, Kurochkina LP, Hawkins RE. The 'adenobody' approach to viral targeting: specific and enhanced adenoviral gene delivery. Gene Ther. Oct 1997;4(10):1004-12. [Medline].

  19. Carter BA, Karpen SJ, Quiros-Tejeira RE, et al. Intravenous Cidofovir therapy for disseminated adenovirus in a pediatric liver transplant recipient. Transplantation. Oct 15 2002;74(7):1050-2. [Medline].

  20. Hayashi M, Lee C, de Magalhaes-Silverman M. Adenovirus infections in BMT patients successfully treated with cidofovir. Blood. 2000;96 (suppl 1):189a.

  21. Muller WJ, Levin MJ, Shin YK, Robinson C, Quinones R, Malcolm J. Clinical and in vitro evaluation of cidofovir for treatment of adenovirus infection in pediatric hematopoietic stem cell transplant recipients. Clin Infect Dis. Dec 15 2005;41(12):1812-6. [Medline].

  22. Yusuf U, Hale GA, Carr J, Gu Z, Benaim E, Woodard P. Cidofovir for the treatment of adenoviral infection in pediatric hematopoietic stem cell transplant patients. Transplantation. May 27 2006;81(10):1398-404. [Medline].

  23. Feuchtinger T, Lücke J, Hamprecht K, Richard C, Handgretinger R, Schumm M. Detection of adenovirus-specific T cells in children with adenovirus infection after allogeneic stem cell transplantation. Br J Haematol. Feb 2005;128(4):503-9. [Medline].

  24. Fanourgiakis P, Georgala A, Vekemans M, Triffet A, De Bruyn JM, Duchateau V. Intravesical instillation of cidofovir in the treatment of hemorrhagic cystitis caused by adenovirus type 11 in a bone marrow transplant recipient. Clin Infect Dis. Jan 1 2005;40(1):199-201. [Medline].

  25. Ryan MA, Gray GC, Smith B, et al. Large epidemic of respiratory illness due to adenovirus types 7 and 3 in healthy young adults. Clin Infect Dis. Mar 1 2002;34(5):577-82. [Medline].

  26. Vora GJ, Lin B, Gratwick K et al. o-infections of adenovirus species in previously vaccinated patients. Emerg Infect Dis. June 2006;12:921-30. [Medline].

  27. Barraza EM, Ludwig SL, Gaydos JC et al. Reemergence of adenovirus type 4 acute respiratory disease in military trainees:report of an outbreak during a lapse in vaccination. J Infect Dis. June 1999;179:1531-3. [Medline].

  28. Baltzer AW, Whalen JD, Wooley P, et al. Gene therapy for osteoporosis: evaluation in a murine ovariectomy model. Gene Ther. Dec 2001;8(23):1770-6. [Medline].

  29. Blasiole DA, Metzgar D, Daum LT, et al. Molecular analysis of adenovirus isolates from vaccinated and unvaccinated young adults. J Clin Microbiol. Apr 2004;42(4):1686-93. [Medline].

  30. Boeckh M, Nichols WG. 42nd Annual Meeting of the American Society of Hematology: Nonherpesvirus Infections in Transplant Recipients. Medscape-Hematology-Oncology Conference Summaries. 2000;Available at: http://www.medscape.com/px/urlinfo.

  31. Chakrabarti S, Collingham KE, Pillay D. Adenovirus infections in haematopoietic stem cell transplant recipients: is there a role for immunotherapy?. Blood. 2000;96 (suppl 1):191a.

  32. Elnifro EM, Cooper RJ, Dady I, Hany S, Mughal ZM, Klapper PE. Three nonfatal cases of neonatal adenovirus infection. J Clin Microbiol. Nov 2005;43(11):5814-5. [Medline].

  33. Emovon OE, Chavin J, Rogers K, Self S. Adenovirus in kidney transplantation: an emerging pathogen?. Transplantation. May 15 2004;77(9):1474-5. [Medline].

  34. Erdman D. EIN epi: Life-threatening adenovirus pneumonia. Emerging Infections Network (EIN) listserv. Available at http://127.0.0.1:4664/cache?event_id=15089&schema_id=1&q=adenovirus&s=VG3cyBjbnInL9-lHEXtU0ht5098. Accessed April 26, 2007.

  35. Gray GC, Callahan JD, Hawksworth AW, et al. Respiratory diseases among U.S. military personnel: countering emerging threats. Emerg Infect Dis. May-Jun 1999;5(3):379-85. [Medline].

  36. Gray GC, Goswami PR, Malasig MD, et al. Adult adenovirus infections: loss of orphaned vaccines precipitates military respiratory disease epidemics. Clinical Infectious Diseases. 2000;31:663-70. [Medline].

  37. Gris O, Güell JL, Wolley-Dod C, Adan A. Diffuse lamellar keratitis and corneal edema associated with viral keratoconjunctivitis 2 years after laser in situ keratomileusis. J Cataract Refract Surg. Jun 2004;30(6):1366-70. [Medline].

  38. Hendrix RM, Lindner JL, Benton FR, et al. Large, persistent epidemic of adenovirus type 4-associated acute respiratory disease in U.S. army trainees. Emerg Infect Dis. Nov-Dec 1999;5(6):798-801. [Medline].

  39. Hierholzer JC. Adenoviruses. In: Murray PR, Baron EJ, Pfaller MA, Tenover FC, Yolken RH, eds. Manual of Clinical Microbiology. 6th ed. Washington, DC: ASM Press; 1995:947-55.

  40. Horwitz MS. Adenoviruses. In: Gorbach SL, Bartlett JG, Blacklow NR, eds. Infectious Diseases. 2nd ed. Philadelphia, Pa: WB Saunders; 1998:. 2012-21.

  41. Horwitz MS. Adenoviruses. In: Fields BN, Knipe DM, Howley PM, Chanock RM, eds. Fields Virology. 3rd ed. Philadelphia, Pa: Lippincott-Raven; 1996:2149-71.

  42. Howard DS, Phillips II GL, Reece DE, et al. Adenovirus infections in hematopoietic stem cell transplant recipients. Clin Infect Dis. Dec 1999;29(6):1494-501. [Medline].

  43. Jeon K, Kang CI, Yoon CH, Lee DJ, Kim CH, Chung YS. High isolation rate of adenovirus serotype 7 from South Korean military recruits with mild acute respiratory disease. Eur J Clin Microbiol Infect Dis. Jun 1 2007;[Medline].

  44. Kapoor N, Shah AJ, Hoffman J. Cidofovir for the treatment of adenoviral infections in pediatric hematopoietic stem cell transplant. Blood. 2000;96 (suppl 1):189a.

  45. Koneman EW, Allen SD, Janda WM, Schreckenberger PC. Adenoviruses. In: Color Atlas of Diagnostic Microbiology. 5th ed. Philadelphia, Pa: Lippincott-Raven; 1997:1203, 1216-17, 1260.

  46. Lankester AC, Heemskerk B, Claas EC, Schilham MW, Beersma MF, Bredius RG. Effect of ribavirin on the plasma viral DNA load in patients with disseminating adenovirus infection. Clin Infect Dis. Jun 1 2004;38(11):1521-5. [Medline].

  47. Ljungman P. Treatment of adenovirus infections in the immunocompromised host. Eur J Clin Microbiol Infect Dis. Aug 2004;23(8):583-8. [Medline].

  48. McNeill KM, Ridgely Benton F, Monteith SC, et al. Epidemic spread of adenovirus type 4-associated acute respiratory disease between U.S. Army installations. Emerg Infect Dis. Jul-Aug 2000;6(4):415-9. [Medline].

  49. Mosby. Ribavirin. In: Mosby's Drug Consult. 15th ed. St. Louis, Mo: Mosby; 2005.

  50. Musher DM. How contagious are common respiratory tract infections?. N Engl J Med. Mar 27 2003;348(13):1256-66. [Medline].

  51. Nagafuji K, Aoki K, Henzan H, et al. Cidofovir for treating adenoviral hemorrhagic cystitis in hematopoietic stem cell transplant recipients. Bone Marrow Transplant. Nov 2004;34(10):909-14. [Medline].

  52. Parizhskaya M, Walpusk J, Mazariegos G, Jaffe R. Enteric adenovirus infection in pediatric small bowel transplant recipients. Pediatr Dev Pathol. Mar-Apr 2001;4(2):122-8. [Medline].

  53. Ribaud P, Scieux C, Freymuth F, et al. Successful treatment of adenovirus disease with intravenous cidofovir in an unrelated stem-cell transplant recipient. Clin Infect Dis. Mar 1999;28(3):690-1. [Medline].

  54. Russell KL, Broderick MP, Franklin SE et al. Transmission dynamics and prospective environmental sampling of adenovirus in amilitary recruit setting. J Infect Dis. October 2006;194:877-85. [Medline].

  55. Sander DM. The Big Picture Book of Viruses: Adenoviridae. 1995;Available at: http://www.tulane.edu/~dmsander/Big_Virology/BVDNAadeno.html. [Full Text].

  56. Strair RK, Sheay W, Goodell L, et al. Adenovirus infection of primary malignant lymphoid cells. Leuk Lymphoma. Jan 2002;43(1):37-49. [Medline].

  57. Suparno C, Milligan DW, Moss PA, Mautner V. Adenovirus infections in stem cell transplant recipients: recent developments in understanding of pathogenesis, diagnosis and management. Leuk Lymphoma. May 2004;45(5):873-85. [Medline].

  58. Venard V, Carret A, Corsaro D, et al. Genotyping of adenoviruses isolated in an outbreak in a bone marrow transplant unit shows that diverse strains are involved. J Hosp Infect. Jan 2000;44(1):71-4. [Medline].

  59. Yazawa K, Fisher WE, Brunicardi FC. Current Progress in Suicide Gene Therapy for Cancer. World J Surg. Apr 15 2002;26(7):[Medline].

[ CLOSE WINDOW ]

Further Reading

[ CLOSE WINDOW ]

Keywords

adenoviruses, acute respiratory disease, ARD, pharyngoconjunctival fever, epidemic keratoconjunctivitis, acute hemorrhagic cystitis, nephritis, gastroenteritis, adenoviral infection, immunocompromise, immunosuppression, transplantation, transplants, transplantation complications, transplant complication, gene therapy, adenovirus, Mastadenovirus, viral gene therapy, cystic fibrosis, osteoporosis, lytic infection

[ CLOSE WINDOW ]

Contributor Information and Disclosures

Author

Sandra G Gompf, MD, FACP, FIDSA, Section Chief, Associate Professor of Infectious Diseases and International Medicine, Infectious Diseases, James A Haley Veterans Hospital
Sandra G Gompf, MD, FACP, FIDSA is a member of the following medical societies: American College of Physicians and Infectious Diseases Society of America
Disclosure: Nothing to disclose.

Coauthor(s)

Richard L Oehler, MD, FACP, Assistant Professor, Department of Internal Medicine, Division of Infectious Diseases and Tropical Medicine, Univ of South Florida College of Medicine; Assistant Epidemiologist, Division of Infectious Diseases, Tampa VA Medical Center
Richard L Oehler, MD, FACP is a member of the following medical societies: American College of Physicians, American Medical Association, Infectious Diseases Society of America, and Society for Healthcare Epidemiology of America
Disclosure: Nothing to disclose.

Medical Editor

David Hall Shepp, MD, Program Director, Fellowship in Infectious Diseases, Department of Medicine, North Shore University Hospital; Associate Professor, New York University School of Medicine
David Hall Shepp, MD is a member of the following medical societies: Infectious Diseases Society of America
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

Richard B Brown, MD, FACP, Chief, Division of Infectious Diseases, Baystate Medical Center; Professor, Department of Internal Medicine, Tufts University School of Medicine
Richard B Brown, MD, FACP is a member of the following medical societies: Alpha Omega Alpha, American College of Chest Physicians, American College of Physicians, American Medical Association, American Society for Microbiology, Infectious Diseases Society of America, and Massachusetts Medical Society
Disclosure: Nothing to disclose.

CME Editor

Eleftherios Mylonakis, MD, Clinical and Research Fellow, Department of Internal Medicine, Division of Infectious Diseases, Massachusetts General Hospital
Eleftherios Mylonakis, MD is a member of the following medical societies: American Association for the Advancement of Science, American College of Physicians, American Society for Microbiology, and Infectious Diseases Society of America
Disclosure: Nothing to disclose.

Chief Editor

Burke A Cunha, MD, Professor of Medicine, State University of New York School of Medicine at Stony Brook; Chief, Infectious Disease Division, Winthrop-University Hospital
Burke A Cunha, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, and Infectious Diseases Society of America
Disclosure: Nothing to disclose.

 
 
HONcode

We subscribe to the
HONcode principles of the
Health On the Net Foundation

All material on this website is protected by copyright, Copyright© 1994- by Medscape.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.