A pilot study on the role of cytomegalovirus & human herpesvirus-6 infections in Indian bone marrow transplant recipients

Abstract

Background & objectives: Studies from Western transplant centers have shown the importance of cytomegalovirus (CMV) in infections among immunosuppressed post-transplant patients (both solid and bone marrow transplant recipients). Human herpesvirus-6 (HHV-6) infection is also important. Since such data are lacking from India, we carried out a pilot study to investigate the role of these two viruses in infections among Indian allogeneic bone marrow transplant (BMT) recipients. Methods: A total of 21 BMT patients who developed acute graft versus host disease (GVHD), two patients who developed chronic GVHD, and eight recipients who did not develop GVHD but had skin rash/elevated liver enzymes, persistent cytopaenia or interstitial pneumonitis with a high clinical suspicion of possible CMV association were studied for markers of CMV and HHV-6 infections. Results: CMV DNAemia was documented in 9 (42.8%) and CMV IgM in 4(19%) of the 21 patients with acute GVHD. HHV-6 DNAemia was not seen in any patient with acute GVHD but 2 (9.5%) had HHV-6 IgM. Of the 2 patients with chronic GVHD, 1 was positive for CMV DNA and IgM, and both were negative for HHV-6 markers. The lower incidence of CMV DNAemia in our recipients may be attributable to the presence of neutralizing antibody (anti gB/AD-1) among the 17 CMV and HHV-6 DNAemia negative recipients, 4(23.5%) had neutralizing antibodies (S/N ratio >5). Of the 13 CMV DNAemia positive recipients, only one (7.7%) was positive for neutralizing antibodies. Among the 5 neutralizing antibody (S/N ratio =5) positive recipients, 4 (80%) were negative for CMV DNAemia. The one nPCR positive was revealed only at high DNA (>0.1μg) input indicating low CMV signal strength. Interpretation & conclusion: The present study shows the use of DNAemia ill detecting CMV infections among BMT recipients. All recipients bad high avidity CMV IgG (Al > 50%) confirming CMV reactivation or reinfection in these patients. There was evidence from this study suggesting that neutralizing antibodies may play a role in controlling CMV reactivation: We found no significant HHV-6 association with GVHD in Indian allogeneic BMT recipients.