The morbidity and mortality associated with cytomegalovirus cmv infection in immunocompromised patients especially in hiv infected patients and transplant recipients , as well as with congenital cmv infection are well known. In contrast, relatively little attention has been paid to the morbidity and mortality that cmv infection may cause in immunocompetent patients. We reviewed the evidence associated with severe manifestations of cmv infection in apparently immunocompetent patients and the potential role of antiviral treatment for these infections. We searched in pubmed, scopus, and the cochrane library for the period of 1950–2007 to identify relevant articles. Severe life threatening complications of cmv infection in immunocompetent patients may not be as rare as previously thought. The online version of this article doi: 10.1186/1743 422x 5 47 contains supplementary material, which is available to authorized users. Cytomegalovirus cmv can cause severe disease in immunocompromised patients, either via reactivation of latent cmv infection or via acquisition of primary cmv infection.

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Clinical syndromes that may be observed in this setting include encephalitis, pneumonitis, hepatitis, uveitis, retinitis, colitis, and graft rejection. Furthermore, cmv infection affecting the human embryo, a host with immature immunologic responses, is often associated with serious complications, such as microcephaly, mental retardation, spastic paralysis, hepatosplenomegaly, anaemia, thrombocytopenia, deafness, and optic nerve atrophy leading to blindness. To the contrary, in immunocompetent patients, primary cmv infection typically runs an undifferentiated viral syndrome, or is manifested by a mononucleosis like syndrome.

Infections in the immunocompetent and immunosupressed are not rare seroprevalence for cmv worldwide ranges from 60%–100% 1 . Symptomatic cmv infection in non immunocompromised hosts has traditionally been considered to have a benign, self limited course. However, in the medical literature there are a considerable number of reports of severe clinical manifestations of cmv infection in immunocompetent patients. An issue that has not been comprehensively resolved is the potential role of specific antiviral treatment for immunocompetent patients with pronounced clinical manifestations related to cmv infection.

Although current opinion is that cmv infection in immunocompetent patients does not require treatment, the risks and benefits of specific antiviral treatment for severely ill patients are not adequately addressed. In this context, we sought to review the biomedical literature for reports regarding severe cmv infections in immunocompetent patients, and to evaluate, on the basis of existing evidence, the role of antiviral treatment, if any, for these patients. We performed a systematic review of the literature regarding serious manifestations of cmv infection in apparently immunocompetent individuals. Two reviewers pir and egm independently searched pubmed, scopus, and the cochrane library for relevant articles published between 1950 and 2007. Search terms applied were cmv , cytomegalovirus , severe , immunocompetent , fulminant , and fatal , in various combinations. The reference lists of relevant articles retrieved by the searches were also reviewed.

Reports included in our review were limited to those written in english, german, or french. We included any study that reported severe cmv infection in immunocompetent patients. We defined as severe any cmv infection for which the patient was hospitalized and/or the infection was deemed to be of a life threatening degree.

The various types of cmv infections were grouped with regard to the afflicted body system or site, as defined by the authors of the original reports, into infections of: the gastrointestinal tract the central nervous system lungs eyes or skin. Immunological competence was defined by the absence of: a congenital or acquired immunodeficiency syndrome a history of allogeneic transplantation except for corneal transplantation or immunosuppressive treatment including antineoplastic chemotherapy, and long term glucocorticosteroid therapy. We excluded cases of congenital cmv infection, patients with inflammatory bowel disease that had received systemic or topical steroids in the month preceding the cmv infection, and, patients with clinical syndromes that are attributed to aberrant immunological responses triggered by the presence of cmv, rather than to tissue damage related to active replication of the virus such as the guillain barré syndrome. Serological studies indicating an acute cmv infection included the presence of positive igm anti cmv antibodies, or of a significant increase in the titre of igg anti cmv antibodies in paired samples obtained during the infection. Three reviewers pir, egm, icv independently assessed all retrieved articles, on the basis of title and abstract, for the purpose of determining eligibility for inclusion in the systematic review. Any differences in the extracted data between the three reviewers were resolved in meetings of all authors. Cure was defined as the complete resolution of symptoms and signs attributed to the cmv infection, in conjunction with normalization of any related laboratory abnormalities.

Improvement was defined as partial resolution of symptoms and signs attributed to the cmv infection, with clinical stability of any associated residual organ dysfunction. Failure was defined as lack of improvement, or deterioration, or death attributed to the cmv infection. Death due to other concomitant illness was not taken into account in determining infection outcome. Cytomegalovirus cmv continues to have a tremendous impact in solid organ transplantation despite remarkable advances in its diagnosis, prevention and treatment. It can affect allograft function and increase patient morbidity and mortality through a number of direct and indirect effects.