Update and review: state-of-the-art management of cytomegalovirus infection and disease following thoracic organ transplantation.

Purpose: Cytomegalovirus (CMV) is among the most important viral pathogens affecting solid organ recipients. The direct effects of CMV (eg, infection and its sequela; tissue invasive disease) are responsible for significant morbidity and mortality. In addition, CMV is associated with numerous indirect effects, including immunomodulatory effects, acute and chronic rejection, and opportunistic infections. Due to the potentially devastating effects of CMV, transplant surgeons and physicians have been challenged to fully understand this infectious complication and find the best ways to prevent and treat it to ensure optimal patient outcomes. Summary: Lung, heart, and heart-lung recipients are at considerably high risk of CMV infection. Both direct and indirect effects of CMV in these populations have potentially lethal consequences. The use of available treatment options depend on the level of risk of each patient population for CMV infection and disease. Those at the highest risk are CMV negative recipients of CMV positive organs (D+/R-), followed by D+/R+, and D-/R+. More than 1 guideline exists delineating prevention and treatment options for CMV, and new guidelines are being developed. It is hoped that new treatment algorithms will provide further guidance to the transplantation community. The first part describes the overall effects of CMV, both direct and indirect; risk factors for CMV infection and disease; methods of diagnosis; and currently available therapies for prevention and treatment. Part 2 similarly addresses antiviral-resistant CMV, summarizing incidence, risk factors, methods of diagnosis, and treatment options. Parts 3 and 4 present cases to illustrate issues surrounding CMV in heart and lung transplantation, respectively. Part 3 discusses the possible mechanisms by which CMV can cause damage to the coronary allograft and potential techniques of avoiding such damage, with emphasis on fostering strong CMV-specific immunity. Part 4 highlights the increased incidence of CMV infection and disease among lung transplant recipients and its detrimental effect on survival. The possible benefits of extended-duration anti-CMV prophylaxis are explored, as are those of combination prophylaxis with valganciclovir and CMVIG. Conclusion: Through improved utilization of information regarding optimized antiviral therapy for heart and lung transplant recipients to prevent and treat CMV infection and disease and through increased understanding of clinical strategies to assess, treat, and monitor patients at high risk for CMV recurrence and resistance, the health care team will be able to provide the coordinated effort needed to improve patient outcome

Management of cytomegalovirus antibody negative patients undergoing heart transplantation.

In a series of 61 consecutive patients undergoing heart, heart and lung, and lung transplantation, 24 patients were known to be cytomegalovirus (CMV) antibody negative on the day of transplantation. Enzyme linked immunosorbent assays (ELISA) for CMV IgG were performed on donor samples on the day of operation. In 16 of the 24 susceptible patients the test was negative and the only preventive measure taken was the use of blood and blood products from CMV-antibody negative blood donors. None of these patients acquired primary infection with CMV. In another six patients the donor serum was found to contain CMV specific IgG, and in these patients, including one heart and lung transplant recipient, prophylaxis with CMV specific hyperimmune globulin was given. All six patients developed CMV IgM antibodies and in five there was an associated but clinically mild illness. None of these patients required treatment. In the remaining two patients ELISA tests on the donor sera gave equivocal results and hyperimmune globulin was withheld. Both patients developed primary CMV infection of greater severity than those given hyperimmune globulin and one required treatment. Reference tests confirmed that the donor sera contained CMV antibodies. Primary CMV infection in susceptible patients after heart transplantation can be avoided by the use of screened blood and blood products where the organ donor is seronegative to CMV and it can be improved by the use of prophylactic hyperimmune globulin where the donor is CMV antibody positive