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      Severe cytomegalovirus infection in apparently immunocompetent patients: a systematic review

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          Abstract

          Background

          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.

          Methods

          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.

          Results

          We retrieved 89 articles reporting on severe CMV infection in 290 immunocompetent adults. Among these reports, the gastrointestinal tract (colitis) and the central nervous system (meningitis, encephalitis, transverse myelitis) were the most frequent sites of severe CMV infection. Manifestations from other organ-systems included haematological disorders (haemolytic anaemia, thrombocytopenia), thrombosis of the venous or arterial vascular system, ocular involvement (uveitis), and lung disease (pneumonitis). The clinical practice reported in the literature has been to prescribe antiviral treatment for the most severe manifestations of monophasic meningoencephalitis (seizures and coma), ocular involvement, and lung involvement due to CMV.

          Conclusion

          Severe life-threatening complications of CMV infection in immunocompetent patients may not be as rare as previously thought.

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          Most cited references19

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          Seroprevalence of cytomegalovirus infection in the United States, 1988-1994.

          Cytomegalovirus (CMV) is a leading cause of congenital illness and disability, including hearing loss and mental retardation. However, there are no nationwide estimates of CMV seroprevalence among pregnant women or the overall population of the United States. To determine CMV prevalence in a representative sample of the US population, we tested serum samples for CMV-specific immunoglobulin G from participants aged > or =6 years (n=21,639) in the third National Health and Nutrition Examination Survey (1988-1994). The prevalence of CMV infection was 58.9% in individuals > or =6 years old. CMV seroprevalence increased gradually with age, from 36.3% in 6-11-year-olds to 90.8% in those aged > or =80 years. CMV seroprevalence differed by race and/or ethnicity as follows: 51.2% in non-Hispanic white persons, 75.8% in non-Hispanic black persons, and 81.7% in Mexican Americans. Racial and/or ethnic differences in CMV seroprevalence persisted when controlling for household income level, education, marital status, area of residence, census region, family size, country of birth, and type of medical insurance. Among women, racial and/or ethnic differences were especially significant; between ages 10-14 years and 20-24 years, seroprevalence increased 38% for non-Hispanic black persons, 7% for non-Hispanic white persons, and <1% for Mexican Americans. On the basis of these results, we estimate that each year in the United States approximately 340,000 non-Hispanic white persons, 130,000 non-Hispanic black persons, and 50,000 Mexican American women of childbearing age experience a primary CMV infection. Given the number of women at risk and the significance of congenital disease, development of programs for the prevention of CMV infection, such as vaccination or education, is of considerable public health importance.
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            Meta-analysis of outcome of cytomegalovirus colitis in immunocompetent hosts.

            There are only a few anecdotal reports of cytomegalovirus (CMV) colitis in immunocompetent hosts. The impact of the disease in this patient population remains poorly understood. The aim of this study was to perform a meta-analysis using individual patient data to determine outcomes of CMV colitis in immunocompetent patients and identify risk factors that might influence prognosis. A literature search was performed from 1980 to 2003 looking for immunocompetent patients with CMV colitis. Immunocompetence was defined as absence of congenital or acquired immune deficiency, transplant, or immunosuppressive medication. Patients were divided by age ( or =55) and grouped according to coexisting illnesses. Kaplan-Meier curves were plotted to assess survival. Variables included age, sex, site of acquisition of infection, extent of disease, coexisting illnesses, and treatment modality. A total of 44 patients were identified, with an average age of 61.1. Only 10 were free of any comorbidity. The mean follow-up was 13.4 months. Spontaneous remission occurred in 31.8%, mostly individuals 55. There was a higher mortality rate among male patients > or =55 (56.9%; P = 0.08), patients with immune-modulating diseases (75.2%; P = 0.10), and those having a colectomy (68.9%; P = 0.09). This analysis underlines the rarity of CMV colitis in patients with an intact immune system. Advanced age, male gender, presence of immune-modulating comorbidities, and need for surgical intervention are factors negatively influencing survival. Conversely, young healthy patients have a good prognosis with no intervention.
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              Severe cytomegalovirus infection in immunocompetent patients.

              Severe cytomegalovirus (CMV) infection is rare in previously healthy immunocompetent individuals; to our knowledge, only thirty-four such cases have been reported in the worldwide literature. Multiorgan involvement was associated with a high mortality rate among these patients. Disease that clinically involves only the liver or lungs could be fatal; in contrast, none of the patients with isolated central nervous system infection died. Although few patients were treated with specific antiviral therapy, five of six patients with severe infection recovered after receiving therapy with ganciclovir or foscarnet. The rarity of severe CMV disease in immunocompetent patients probably precludes the performance of a clinical trial to evaluate the efficacy of specific antiviral therapy. However, the historically poor prognosis in the absence of such therapy suggests that rapid diagnosis of CMV disease and early instigation of specific treatment may be important.
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                Author and article information

                Journal
                Virol J
                Virology Journal
                BioMed Central
                1743-422X
                2008
                27 March 2008
                : 5
                : 47
                Affiliations
                [1 ]Alfa Institute of Biomedical Sciences (AIBS), Athens, Greece
                [2 ]Department of Medicine, Henry Dunant Hospital, Athens, Greece
                [3 ]Department of Medicine, Tufts University School of Medicine, Boston, Massachusetts, USA
                Article
                1743-422X-5-47
                10.1186/1743-422X-5-47
                2289809
                18371229
                05f258b5-6150-4d7c-afe1-7404a15b047a
                Copyright © 2008 Rafailidis et al; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                Categories
                Review

                Microbiology & Virology
                Microbiology & Virology

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