Late-onset cytomegalovirus (CMV) in lung transplant recipients: can CMV serostatus guide the duration of prophylaxis?

Evidence supports the use of 12 months of cytomegalovirus prophylaxis in all at-risk lung transplants; whether cytomegalovirus serostatus can be used to further optimize this duration remains to be determined. The purpose of this retrospective study was to determine if cytomegalovirus serostatus of both donor and recipient were associated with late-onset cytomegalovirus. The primary outcome was the proportion of lung transplants that developed cytomegalovirus infection or disease during the 180-day period following 6 months of prophylaxis in each at-risk serotype. Two hundred forty-four consecutive lung transplants were evaluated, 131 were included. The proportion of recipients with cytomegalovirus differed significantly between serotypes (20 of 41 [48.8%] D+/R- vs. 19 of 56 [33.9%] D+/R+ vs. 2 of 34 [5.9%] D-/R+; p < 0.001). In a multivariate model, older age (odds ratio [OR], 1.05, 95% confidence interval [CI] 1.004-1.099; p = 0.03) and D+/R- serostatus (OR, 3.83; 95% CI 1.674-8.770; p = 0.002) were associated with cytomegalovirus. Among R+ lung transplants, D- serostatus was associated with the absence of cytomegalovirus (OR, 0.12; 95% CI 0.0263-0.563; p = 0.007). These findings suggest that in the valganciclovir era, cytomegalovirus serostatus of both donor and recipient may identify lung transplants at heightened risk for late-onset cytomegalovirus.

Incidence and morbidity of human metapneumovirus and other community-acquired respiratory viruses in lung transplant recipients.

To determine the role of human metapneumovirus (HMPV) in respiratory tract infections (RTIs) of lung transplant recipients, 60 patients were prospectively enrolled in this study spanning from September 2005 to November 2007. Community-acquired respiratory viruses (CARVs) were identified by polymerase chain reaction and tissue culture in respiratory secretions. Of 112 RTIs, 51 were associated with > or =1 CARV, including 7 HMPV, 13 respiratory syncytial virus (RSV), 19 parainfluenza virus 1, 2, or 3 (PIV), 16 influenza A or B (FLU), and 3 human rhinoviruses (HRV). Sixteen CARV-RTIs had multiple pathogens. While the standard protocol was to admit all paramyxoviral RTIs for inhaled ribavirin, 16% CARV-RTIs required hospitalization because of the severity of their respiratory compromise, including 25% of HPMV-single-agent RTI, 38% of RSV single-agent RTI, 10% of PIV-single-agent RTI, and 19% of multiple-agent RTIs. None of those with non-CARV RTIs required hospitalization. The incidence of clinically diagnosed acute graft rejection in the first 2 months after an RTI varied from 0 for single-agent HRV to 88% for single-agent RSV (25% for single-agent HMPV). A new diagnosis of chronic graft rejection in the first year after an RTI was made in approximately 25% of the RTIs and did not significantly vary with the etiologic agent. No deaths occurred during this study. In conclusion, HMPV was associated with 6% of the RTIs in lung transplant recipients and its morbidity was similar to the average moribidity of CARVs.

Immunogenicity of a fusion protein linking the beta subunit carboxyl terminal peptide (CTP) of human chorionic gonadotropin to the B subunit of Escherichia coli heat-labile enterotoxin (LTB).

Human chorionic gonadotropin (hCG) is currently under investigation as an antigenic target in both anti-cancer and anti-fertility vaccines. Formulations studied to date show promise in clinical trials for both applications yet are expensive to produce and require frequented administration in order to maintain an effective antibody titer. We have engineered a fusion protein consisting of Escherichia coli heat-labile enterotoxin subunit B (LTB) genetically linked at its C terminus via a nine amino acid linker to the 37 amino acid carboxyl terminal peptide (CTP) of the hCG beta chain. This LTB-CTP fusion protein is stably expressed in bacteria and forms pentamers of full-length protein subunits. Purified LTB-CTP protein hCG-specific antibodies in mice without additional adjuvants.