Subject(s)
Adult , Case-Control Studies , Cytomegalovirus Infections/congenital , DNA, Viral/analysis , Enzyme-Linked Immunosorbent Assay , Female , Hospitals, Urban , Humans , Incidence , India/epidemiology , Infant, Newborn , Male , Pilot Projects , Polymerase Chain Reaction , Pregnancy , Reference Values , Risk FactorsABSTRACT
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 > or = 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 > or = 5) positive recipients, 4 (80%) were negative for CMV DNAemia. The one nPCR positive was revealed only at high DNA (> 0.1 microgram) input indicating low CMV signal strength. INTERPRETATION & CONCLUSION: The present study shows the use of DNAemia in detecting CMV infections among BMT recipients. All recipients had high avidity CMV IgG (AI > 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.
Subject(s)
Adolescent , Adult , Bone Marrow Transplantation/adverse effects , Child , Child, Preschool , Cytomegalovirus Infections/etiology , Herpesvirus 6, Human , Humans , Infant , Pilot Projects , Roseolovirus Infections/etiologyABSTRACT
BACKGROUND & OBJECTIVES: Cytomegalovirus (CMV) disease in seroendemic transplant populations is due to reactivation of the virus, or reinfection. In this context, the antibody response is likely to influence presentation, clinical severity and outcome of the disease, and may provide a diagnostic and prognostic marker. This study was carried out in Indian renal transplant patients and healthy adults to characterize the antibody response to cytomegalovirus. METHODS: Thirty three transplant recipients with CMV illness (symptomatology with IgM and/or nPCR positive status), 20 recipients who were asymptomatic in the 6 months of follow up after transplantation and 62 healthy controls were investigated for markers of CMV infection. These individuals were tested for IgG avidity and neutralizing antibody by ELISA techniques. RESULTS: All 53 transplant recipients were found to have an IgG avidity index of > 50 per cent. Antibody to a CMV envelope glycoprotein gB/AD-1 (putative neutralizing antibody) was expressed as S/N ratio and was > or = 5 in asymptomatic (65%) and symptomatic (27%) immunosuppressed renal transplant recipients. However, none of the 53 CMV IgG positive healthy controls were positive for neutralizing antibodies S/N ratio > or = 5 (S/N ratio = sample mean OD/mean OD of 3 negative controls in each run). We observed the simultaneous presence of CMV PCR signal in leukocytes and neutralizing antibody (S/N ratio > or = 5) in the plasma in 22 (41.5%) of the 53 renal transplant recipients. INTERPRETATION & CONCLUSIONS: In this study among the immunosuppressed transplant patients we observed an association between symptomatic disease and the relative absence of neutralizing antibodies. The neutralizing antibodies are less frequently demonstrable among controls; while appearance in a higher proportion of asymptomatic recipients especially in association with high IgG avidity (> 90%) is suggestive of its role in control of CMV disease despite reactivation as evidenced by DNAemia while on immunosuppressive therapy.