Human herpesviruses can cause significant morbidity and mortality in pediatric solid

Human herpesviruses can cause significant morbidity and mortality in pediatric solid organ transplant recipients. the only patient presenting with an EBV syndrome. However, two other patients without evidence of EBV disease had single samples with high EBV burden. Rapid reduction in both EBV and CMV burden occurred with antiviral treatment. These data suggest that viral burden analysis using internal calibration standard-polymerase chain reaction for CMV, and possibly other herpesviruses, is an effective method for monitoring pediatric transplant patients for significant herpesvirus infection and response to therapy. Transplantation is being used as an effective treatment strategy for the correction of organ defects due to congenital malformation or the cytotoxic effects of chemicals and infectious agents. This therapeutic approach relies on the ability to shape the recipients immune system to accept the foreign organ. This has been greatly facilitated by the use of a variety of immunosuppressive drugs, including cyclosporin, FK506, prednisone, and mycophenolate, which suppress the cellular arm of the immune system. However, this approach to immunosuppression is associated with a serious side effect: an increased incidence of life-threatening diseases caused by infectious agents that are normally controlled by the immune systems of immunocompetent individuals. Among the agents that seriously affect immunocompromised individuals are the herpesviruses. The eight human herpesviruses identified to dateherpes simplex viruses 1 and 2 (HSV1 and HSV2), varicella-zoster virus (VZV), Epstein-Barr virus (EBV), cytomegalovirus (CMV), human herpesvirus types 6 and 7 (HHV6 and HHV7), and Kaposis sarcoma-associated herpesvirus (KSHV or HHV8)have been associated with significant morbidity and mortality in a variety of immunosuppressed patient populations. 1, 2, 3, 4, 5, 6, 7 For solid organ transplant recipients, localized infection can lead to inflammatory responses and tissue destruction in many different target organs, especially lung, liver, and gastrointestinal tract. For example, 13 to 30% of liver transplant recipients will develop pneumonia associated with CMV infection. 8 In many cases, herpesvirus infection targets the transplanted organ and contributes to organ rejection. 9, 10, 11, 12 For example, 17% of liver allograft recipients have been found to develop CMV-mediated hepatitis; in the high-risk subgroup (seronegative recipients with seropositive donors), the incidence of CMV disease approaches 50%. 9, 10, 11 In this case, initial evidence of infection often comes from the detection of elevated levels of liver enzymes in the circulation. Because elevated liver enzymes are also associated with immune-mediated organ rejection, histological evaluation of organ biopsy is often necessary to distinguish between these etiologies. 13 Finally, EBV appears to be unique among the herpesviruses in that it MYO10 can also stimulate the proliferation of infected lymphocytes, in some cases leading to post-transplant lymphoproliferative disorder (PTLD), with many characteristics similar to malignant non-Hodgkins lymphoma. 5, 14, 15, 16, 17 Fortunately, a variety of virus-specific antiviral drugs and treatment approaches has been developed for patients with significant herpesvirus infection. Herpes simplex esophagitis is effectively treated MBX-2982 IC50 with acyclovir. 18 Ganciclovir in combination with hyperimmune globulin is an effective therapeutic approach for CMV-mediated disease. 8, 19, 20 EBV-associated PTLD appears to be most effectively treated by tapering of the doses of the immunosuppressive drugs used to prevent transplant organ rejection. 17, 21 Because different viruses can give rise to similar organ pathologies, 22, 23, 24, 25, MBX-2982 IC50 26, 27, 28, 29 selection of the appropriate therapeutic approach involves accurate diagnosis of disease etiology. Monitoring transplant recipients for significant herpesvirus infections has proved to be a diagnostic challenge for two reasons. First, the results of serology tests commonly used to diagnose viral infection can MBX-2982 IC50 be dramatically influenced by the immunosuppressed state of the patient in ways that are not easily predicted. Second, there is a high prevalence of past infection by some of these viruses, which enter a latent state after primary infection, such that most humans are asymptomatic but continue to harbor latent MBX-2982 IC50 virus. This is especially true for four of these viruses that cause significant problems for the transplant population: EBV, CMV, HHV6, and HHV7. Thus, sensitive techniques like polymerase chain reaction (PCR) to identify MBX-2982 IC50 viral nucleic acids can often detect viral genomes in plasma and circulating lymphocytes of asymptomatic individuals. For these reasons, serology and standard PCR approaches have been problematic for the diagnosis of.