Video:Human cytomegalovirus infection

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Description

Human cytomegalovirus infection is typically unnoticed in healthy people, but can be life-threatening for the immunocompromised, such as HIV-infected persons, organ transplant recipients, or newborn infants.[1]Valganciclovir is an antiviral drug that is effective and is given orally for this infection.[2]

Presentation

Human betaherpesvirus 5 infection classically results in three symptoms: fever, peaking in the late afternoon or early evening; throat inflammation, usually exudative; and symmetrical large lymph nodes.[3]

Complications

Though infrequent, complications are the following in the affected individual:pneumonia, hemolytic anemia, hepatitis, and retinitis.[3]

Risk factor 1

CMV infection or reactivation in people whose immune systems are compromised causes illness and increases the risk of death.[4][5]Specific disease entities recognized in those people are: CMV hepatitis, which may cause fulminant liver failure.[6], Cytomegalovirus retinitis which is inflammation of the retina,[7] and Cytomegalovirus colitis which is inflammation of the large bowel.[8]

Risk factor 2

HCMV is one of the vertically transmitted infections that lead to congenital abnormalities. Congenital HCMV infection occurs when the mother develops an infection during pregnancy. A small percent develop multiple handicaps, and develop cytomegalic inclusion disease with nonspecific signs that resemble rubella; others later develop cerebral calcification .[9][10][11]

Transmission

The mode of HCMV transmission from person to person is unknown, but is presumed to occur through bodily fluids, including saliva, urine, blood, and tears.[12] Cytomegalovirus is most commonly transmitted through kissing and sexual intercourse. It can also be transferred from an infected mother to her unborn child.[13]

Mechanism

Once infection has occurred, the virus remains latent in lymphocytes in the body for the rest of the person's life. Overt disease rarely occurs unless immunity is suppressed either by drugs, infection or old age. Initial HCMV infection, which often is asymptomatic, is followed by a prolonged, inapparent infection during which the virus resides in mononuclear cells without causing detectable damage or clinical illness.[14][15][16]

Diagnosis

The virus can be cultured from specimens obtained from urine, throat swabs, bronchial lavages and tissue samples to detect active infection. Both qualitative and quantitative polymerase chain reaction testing for CMV are available as well, allowing physicians to monitor the viral load of people infected with CMV.[14][3][17]

Differential diagnosis

The differential diagnosis of Human cytomegalovirus infection is based on the following:HIV, viral hepatitis, Epstein Barr virus and Infectious mononucleosis.[15]

Treatment

Ganciclovir treatment is used for people with depressed immunity who have life-threatening illnesses. Valganciclovir is an antiviral drug that is also effective and is given orally: it is a pro-drug that gets converted into ganciclovir in the body, but is much better absorbed orally than the latter. The therapeutic effectiveness is frequently compromised by the emergence of drug-resistant virus isolates. [18][19][20]

Antiviral resistance

Two HCMV proteins are implicated in antiviral resistance against therapeutic drugs: pUL97 and pUL54. Specific mutations in pUL97 can cause reduced phosphorylation activity of this viral protein kinase. Thus, fewer monophosphorylated – and thus active – GCV can be synthesized,[21] leading to antiviral resistance against GCV. About 90 percent of all GCV resistances are caused by such mutations in UL97.[22]

History

Cytomegalovirus was first observed by German pathologist Hugo Ribbert in 1881. He noticed enlarged cells with enlarged nuclei in an infants cells.[23]

Research

In terms of research cytomegalovirus vaccines candidates are the CMV-MVA Triplex vaccine and the CMVpp65-A0201 peptide vaccine. Both vaccine candidates are sponsored by the City of Hope National Medical Center. As of 2016, the development is in clinical phase 2 trial stage.[24][25]As of 2021 research is ongoing with no current vaccine available, though there are several candidates[26]

References

  1. ↑ Ryan KJ, Ray CG, eds. (2004). Sherris Medical Microbiology (4th ed.). McGraw Hill. pp. 556, 566–9. ISBN 978-0-8385-8529-0.
  2. ↑ Cvetković, Risto S.; Wellington, Keri (2005). "Valganciclovir: a review of its use in the management of CMV infection and disease in immunocompromised patients". Drugs. 65 (6): 859–878. doi:10.2165/00003495-200565060-00012. ISSN 0012-6667.
  3. ↑ 3.0 3.1 3.2 Landolfo, Santo; Gariglio, Marisa; Gribaudo, Giorgio; Lembo, David (June 2003). "The human cytomegalovirus". Pharmacology & Therapeutics. 98 (3): 269–297. doi:10.1016/S0163-7258(03)00034-2. Archived from the original on 5 February 2023. Retrieved 5 February 2023.
  4. ↑ Navarro, David (July 2016). "Expanding role of cytomegalovirus as a human pathogen". Journal of Medical Virology. 88 (7): 1103–1112. doi:10.1002/jmv.24450. ISSN 0146-6615.
  5. ↑ Cook CH (2007). "Cytomegalovirus reactivation in "immunocompetent" patients: a call for scientific prophylaxis". The Journal of Infectious Diseases. 196 (9): 1273–1275. doi:10.1086/522433. PMID 17922387.
  6. ↑ Da Cunha, Teresa; Wu, George Y. (28 February 2021). "Cytomegalovirus Hepatitis in Immunocompetent and Immunocompromised Hosts". Journal of Clinical and Translational Hepatology. 9 (1): 106–115. doi:10.14218/JCTH.2020.00088. ISSN 2225-0719. Archived from the original on 13 November 2022. Retrieved 1 February 2023.
  7. ↑ "CMV retinitis: MedlinePlus Medical Encyclopedia". medlineplus.gov. Archived from the original on 30 December 2022. Retrieved 1 February 2023.
  8. ↑ Azer, Samy A.; Limaiem, Faten (2022). "Cytomegalovirus Colitis". StatPearls. StatPearls Publishing. Archived from the original on 17 March 2022. Retrieved 1 February 2023.
  9. ↑ Lim, Yinru; Lyall, Hermione (1 June 2017). "Congenital cytomegalovirus – who, when, what-with and why to treat?". Journal of Infection. 74: S89–S94. doi:10.1016/S0163-4453(17)30197-4. ISSN 0163-4453. Archived from the original on 2 February 2023. Retrieved 1 February 2023.
  10. ↑ Weisblum, Yiska; Panet, Amos; Haimov-Kochman, Ronit; Wolf, Dana G. (November 2014). "Models of vertical cytomegalovirus (CMV) transmission and pathogenesis". Seminars in Immunopathology. 36 (6): 615–625. doi:10.1007/s00281-014-0449-1. ISSN 1863-2300. Archived from the original on 31 October 2022. Retrieved 2 February 2023.
  11. ↑ "Cytomegalic inclusion disease - About the Disease - Genetic and Rare Diseases Information Center". rarediseases.info.nih.gov. Archived from the original on 27 January 2023. Retrieved 7 February 2023.
  12. ↑ Larsen, Laura. Sexually Transmitted Diseases Sourcebook. Health Reference Series Detroit: Omnigraphics, Inc., 2009. Online.
  13. ↑ Human Herpesviruses: Biology, Therapy, and Immunoprophylaxis. Cambridge University Press. 2007. ISBN 978-0-521-82714-0. Retrieved 14 August 2024.
  14. ↑ 14.0 14.1 "Human Cytomegalovirus (HCMV) – Revised". Transfusion Medicine and Hemotherapy. 37 (6): 365–375. 2010. doi:10.1159/000322141. Archived from the original on 7 December 2022. Retrieved 29 January 2023.
  15. ↑ 15.0 15.1 Gupta, Mohit; Shorman, Mahmoud (2022). "Cytomegalovirus". StatPearls. StatPearls Publishing. Archived from the original on 12 November 2022. Retrieved 12 February 2023.
  16. ↑ "About Cytomegalovirus and Congenital CMV Infection | CDC". www.cdc.gov. 8 June 2022. Archived from the original on 16 October 2017. Retrieved 12 February 2023.
  17. ↑ Razonable, Raymund R; Inoue, Naoki; Pinninti, Swetha G; Boppana, Suresh B; Lazzarotto, Tiziana; Gabrielli, Liliana; Simonazzi, Giuliana; Pellett, Philip E; Schmid, D Scott (5 March 2020). "Clinical Diagnostic Testing for Human Cytomegalovirus Infections". The Journal of Infectious Diseases. 221 (Supplement_1): S74–S85. doi:10.1093/infdis/jiz601.
  18. ↑ Nevins, T. E.; Dunn, D. L. (June 1992). "Use of ganciclovir for cytomegalovirus infection". Journal of the American Society of Nephrology: JASN. 2 (12 Suppl): S270–273. doi:10.1681/ASN.V212s270. ISSN 1046-6673. Archived from the original on 17 June 2022. Retrieved 4 February 2023.
  19. ↑ Hakki, Morgan (1 April 2020). "Moving Past Ganciclovir and Foscarnet: Advances in CMV Therapy". Current Hematologic Malignancy Reports. 15 (2): 90–102. doi:10.1007/s11899-020-00557-6. ISSN 1558-822X. Archived from the original on 7 February 2023. Retrieved 8 February 2023.
  20. ↑ Cvetković, Risto S.; Wellington, Keri (2005). "Valganciclovir: a review of its use in the management of CMV infection and disease in immunocompromised patients". Drugs. 65 (6): 859–878. doi:10.2165/00003495-200565060-00012. ISSN 0012-6667.
  21. ↑ Biron KK, Fyfe JA, Stanat SC, Leslie LK, Sorrell JB, Lambe CU, Coen DM (1986). "A human cytomegalovirus mutant resistant to the nucleoside analog 9-([2-hydroxy-1-(hydroxymethyl)ethoxy]methyl)guanine (BW B759U) induces reduced levels of BW B759U triphosphate". Proc. Natl. Acad. Sci. U.S.A. 83 (22): 8769–8773. Bibcode:1986PNAS...83.8769B. doi:10.1073/pnas.83.22.8769. PMC 387013. PMID 3022304.
  22. ↑ Chou S (1999). "Antiviral drug resistance in human cytomegalovirus". Transpl. Infect. Dis. 1 (2): 105–114. doi:10.1034/j.1399-3062.1999.010204.x. PMID 11428978. S2CID 23668301.
  23. ↑ Ho, Monto (1 June 2008). "The history of cytomegalovirus and its diseases". Medical Microbiology and Immunology. 197 (2): 65–73. doi:10.1007/s00430-007-0066-x. ISSN 1432-1831.
  24. ↑ "Multi-antigen CMV-MVA Triplex Vaccine in Reducing CMV Complications in Patients Previously Infected With CMV and Undergoing Donor Hematopoietic Cell Transplant". ClinicalTrials.gov. 21 July 2015. Archived from the original on 29 January 2016. Retrieved 23 January 2016.
  25. ↑ "Vaccine Therapy in Reducing the Frequency of Cytomegalovirus Events in Patients With Hematologic Malignancies Undergoing Donor Stem Cell Transplant". ClinicalTrials.gov. 12 March 2015. Archived from the original on 29 January 2016. Retrieved 23 January 2016.
  26. ↑ Scarpini, Sara; Morigi, Francesca; Betti, Ludovica; Dondi, Arianna; Biagi, Carlotta; Lanari, Marcello (25 May 2021). "Development of a Vaccine against Human Cytomegalovirus: Advances, Barriers, and Implications for the Clinical Practice". Vaccines. 9 (6): 551. doi:10.3390/vaccines9060551. PMC 8225126. PMID 34070277.
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