Outline the clinical features, diagnostic tests and initial drug treatment of cytomegalovirus (CMV) infection in an immunosuppressed patient.
Clinical features (4 marks)
CMV infection can range from asymptomatic viraemia to CMV syndrome and tissue invasive disease.
CMV syndrome is defined as the presence of detectable viral replication in blood accompanied by attributable symptoms and signs: fever, malaise, arthralgia, leukopenia, thrombocytopenia.
Tissue-invasive CMV disease has clinical symptoms and signs of end-organ disease:
GI – diarrhoea, fever, abdominal pain, bloody stool
Hepatic – LFT abnormalities Neurological – Encephalitis, GBS Pneumonitis
Can reactivate in critical illness.
Diagnosis (4 marks)
Serology IgM and IgG – can indicate past infection
PCR CMV DNA – blood / CSF/BAL – copies per ml / standard units / ml
Biopsy if tissue invasive disease with typical histology cellular and nuclear enlargement, inclusion bodies
Viral cultures in past – slow, high cost, long turnaround
Treatment (2 marks)
Stop/reduce immunosuppressive drugs if possible Ganciclovir
Foscarnet (IV), Cidofovir (IV) Consider IVIG or CMV IG
Overall poor knowledge of this topic. Many candidates gave a list of clinical syndromes associated with CMV without detail of the clinical features as required by the stem. Many of the diagnostic tests discussed were generic tests of potentially affected end organ function, rather than tests that would secure the specific diagnosis. The stem asked specifically for drug treatment. Some candidates gave details of supportive therapy and resuscitation that were not necessary.
Clinical manifestations of CMV:
CMV syndrome is defined as viraemia plus any two of the following:
This definition is based on Ljungman et al (2016).
Diagnosis of CMV
Gandhi, Maher K., and Rajiv Khanna. "Human cytomegalovirus: clinical aspects, immune regulation, and emerging treatments." The Lancet infectious diseases 4.12 (2004): 725-738.
Tejedor Cerdena, María Auxiliadora, et al. "Cytomegalovirus ileitis in an immunocompetent patient." Rev Esp Enferm Dig 103 (2011): 154-6.
Grilli, Elisabetta, et al. "Cytomegalovirus pneumonia in immunocompetent host: case report and literature review." Journal of Clinical Virology 55.4 (2012): 356-359.
Limaye, Ajit P., et al. "Cytomegalovirus reactivation in critically ill immunocompetent patients." Jama 300.4 (2008): 413-422.
Osawa, Ryosuke, and Nina Singh. "Cytomegalovirus infection in critically ill patients: a systematic review." Critical care 13.3 (2009): R68.
Jain, Manisha, Shalini Duggal, and Tulsi Das Chugh. "Cytomegalovirus infection in non-immunosuppressed critically ill patients." The Journal of Infection in Developing Countries 5.08 (2011): 571-579.
Chou, Suowen. "Newer methods for diagnosis of cytomegalovirus infection." Review of Infectious Diseases 12.Supplement 7 (1990): S727-S736.
Razonable, Raymund R., and Randall T. Hayden. "Clinical utility of viral load in management of cytomegalovirus infection after solid organ transplantation."Clinical microbiology reviews 26.4 (2013): 703-727.
Vancikova, Z., and P. Dvorak. "Cytomegalovirus infection in immunocompetent and immunocompromised individuals--a review." Current drug targets. Immune, endocrine and metabolic disorders 1.2 (2001): 179-187.
Eddleston, M., et al. "Severe cytomegalovirus infection in immunocompetent patients." Clinical infectious diseases 24.1 (1997): 52-56.
Andrews, Peter A., Vincent C. Emery, and Chas Newstead. "Summary of the British Transplantation Society guidelines for the prevention and management of CMV disease after solid organ transplantation." Transplantation 92.11 (2011): 1181-1187.
Kotton, Camille N., et al. "Updated international consensus guidelines on the management of cytomegalovirus in solid-organ transplantation." Transplantation96.4 (2013): 333-360.
Jacobson, Mark A. "Review of the toxicities of foscarnet." JAIDS Journal of Acquired Immune Deficiency Syndromes 5 (1992): S11-17.
Lalezari, Jacob P., et al. "Randomized, controlled study of the safety and efficacy of intravenous cidofovir for the treatment of relapsing cytomegalovirus retinitis in patients with AIDS." JAIDS Journal of Acquired Immune Deficiency Syndromes 17.4 (1998): 339-344.
Boeckh, Michael. "Complications, diagnosis, management, and prevention of CMV infections: current and future." ASH Education Program Book 2011.1 (2011): 305-309.
Kotton, C. N. "CMV: prevention, diagnosis and therapy." American Journal of Transplantation 13.s3 (2013): 24-40.
Fryer, J. F., et al. "Collaborative study to evaluate the proposed 1st WHO international standard for human cytomegalovirus (HCMV) for nucleic acid amplification (NAT)-based assays WHO/BS/10.2138." World Health Organiztion, Geneva, Switzerland (2010).
Ljungman, P., et al. "Use of intravenous immune globulin in addition to antiviral therapy in the treatment of CMV gastrointestinal disease in allogeneic bone marrow transplant patients: a report from the European Group for Blood and Marrow Transplantation (EBMT). Infectious Diseases Working Party of the EBMT." Bone marrow transplantation 21.5 (1998): 473-476.
Erard, V., et al. "Cytomegalovirus pneumonia after hematopoietic cell transplantation: outcomes and factors associated with mortality." Interscience Conference on Antimicrobial Agents and Chemotherapy. Chicago, IL. 2007. - this is not even available as an abstract, but is widely cited; a reference to it an be found in the following article:
Travi, Giovanna, and Steven A. Pergam. "Cytomegalovirus pneumonia in hematopoietic stem cell recipients." Journal of intensive care medicine 29.4 (2014): 200-212.
Ljungman, Per, et al. "Definitions of cytomegalovirus infection and disease in transplant patients for use in clinical trials." Clinical Infectious Diseases (2016): ciw668.