Background & Aims-Although randomized trials of adults infected with hepatitis C virus (HCV) have shown that ribavirin increases efficacy of pegylated interferon (PEG), such trials have not been performed in children. We conducted a randomized, controlled trial of PEG and ribavirin, compared with PEG and placebo, in children 5-17 years old with chronic hepatitis C.

Background Antiviral-resistant or refractory CMV infection is challenging, and salvage therapies, foscarnet and cidofovir, have significant toxicities. Several investigational anti-CMV agents are under development, but more information is needed on outcomes of current treatments, to facilitate clinical trial design for new drugs. Methods Records of solid organ (SOT) and hematopoietic cell transplant (HCT) recipients at a single center over a 10-year period were reviewed retrospectively to characterize those who had received foscarnet treatment for ganciclovir-resistant or refractory CMV infection. Data were collected on virologic responses, mortality, and nephrotoxicity. Results Of 39 patients (22 SOT, 17 HCT), 15 had documented ganciclovir resistance mutations and 11/39 (28%) had tissue-invasive CMV. Median duration of foscarnet was 32 days. Virologic failure occurred in 13/39 (33%) and relapses of viremia occurred in 31%. Mortality was 12/39 (31%) and was higher in HCT than SOT (p=0.001), although ganciclovir resistance was more common in SOT (p = 0.003). Doses of ganciclovir or valganciclovir were low in 10/39 (26%) at some time prior to switching to foscarnet. Renal dysfunction occurred in 20/39 (51%) by end of treatment and in 7/25 (28%) after 6 months. Conclusions Outcomes of existing treatment for ganciclovir-resistant or refractory CMV are suboptimal, in terms of virologic clearance, renal dysfunction, and mortality. These data should provide background information for future clinical trials of newer antiviral agents.

• Cell-free (plasma) EBV DNA performs better than cellular EBV DNA as a marker of a broad range of EBV 1 diseases.• Within a largely immunocompromised and hospitalized cohort, detection of EBV DNA in plasma is uncommon in the absence of EBV 1 disease.

The human complement regulatory protein membrane cofactor protein (CD46) is the cellular receptor for measles virus (MV), whereas decay accelerating factor (DAF; CD55), a structurally similar complement regulatory protein, does not bind MV. To characterize the interaction between MV and CD46, mutants of the CD46 protein and hybrid molecules between CD46 and DAF were tested for their ability to act as MV receptors. The transmembrane domain and cytoplasmic tail of CD46 were not required for receptor function as cells expressing the CD46 extracellular domain linked to the glycosyl-phosphatidylinositol tail of DAF were rendered susceptible to MV infection. Chimeric proteins exchanging the four extracellular short consensus repeat (SCR) domains between CD46 and DAF indicated that only molecules with both SCR1 and SCR2 from CD46 allowed a productive MV infection. Further, monoclonal antibodies (mAbs) against SCR1 or SCR2 of CD46 blocked MV infection, whereas a mAb against SCR3 and SCR4 did not. The latter mAb blocks C3b/C4b binding (which maps to SCR3 and SCR4) whereas the former mAbs do not. Thus, our data indicate that both SCRI and SCR2 make up the MV receptor determinant in CD46. These results also suggest avenues for development of therapeutic agents to inhibit MV binding and thus infection and disease.Measles virus (MV) is among the most contagious infections of humans. Although an effective MV vaccine has been in use since the 1960s, >40 million infections and -2 million deaths occur yearly from measles (1). Vaccine failure is primarily due to interference by maternal antibodies that prevents vaccination in young children up to 15 months of age (2). High-dose vaccination in children of this age has not been effective and in fact has increased morbidity and mortality after MV infection (3, 4). Thus, a window of time exists when susceptibility to MV in young children is high and vaccination is not effective. Anti-MV therapeutics that could inhibit the spread or severity of MV infection may be useful during this period.Understanding the interaction between the virus and host cell opens avenues for the design of effective antiviral agents. We (5) and others (6, 7) have identified the MV receptor as CD46 (membrane cofactor protein). CD46 is a member of the regulators of complement activation (RCA) family located on human chromosome 1 (8, 9). Proteins in this family protect the host from attack by its own complement system by regulating the activation state and deposition on host cells of complement proteins. CD46 binds complement components C3b and C4b and acts as a cofactor for their cleavage by serine protease factor I (8). The structural hallmark of proteins in the RCA family is the short consensus repeat (SCR) domain, an "60-amino acid domain with four conserved cysteines forming two disulfide bonds (10, 11). Members of the RCA family vary widely in the numbers of SCRs they possess, from 4 [CD46 and decay accelerating factor (DAF/CD55) to as many as 30 (CR1/CD35) (8). CD46 and DAF are unique in that they...

ABSTRACT

Laboratory strains of measles viruses (MV), such as Edmonston and

SUMMARY Hepatitis B virus (HBV) is an enveloped virus with a small (3.2-kb) partially double-stranded DNA genome that causes acute and chronic infections. The impact of these infections on public health worldwide is enormous, with an estimated prevalence of 2 billion acute infections and 360 million chronic infections globally. This review focuses on chronic hepatitis B and the molecular assays used in its diagnosis and management. Background information, including that about features of the hepatitis B virion, viral replication, and epidemiology of infection, that is important for understanding chronic hepatitis B and molecular diagnostic tests for HBV is provided. To facilitate an understanding of the utility of molecular testing for chronic hepatitis B, the four stages of chronic hepatitis B infection that are currently recognized, as well as an additional entity, occult hepatitis B, that can be diagnosed only by sensitive nucleic acid amplification methods, are reviewed in detail, including available therapeutic agents. The molecular diagnostic content focuses on tests for HBV DNA quantification, genotyping, and mutation detection (including precore/core promoter and antiviral resistance mutations). The discussion of these tests encompasses their current utility and performance characteristics, drawing from current clinical guidelines and other studies from the literature. In recognition of the continual evolution of this field, the final section describes emerging molecular markers with future diagnostic potential.

Quantification of Epstein-Barr virus (EBV) in peripheral blood is important for the diagnosis and management of serious EBV diseases, including posttransplant lymphoproliferative disorder. A variety of PCRbased methods are currently in use; however, there is little information on their comparability. This study assessed the relative performance of different quantitative assays. A multicenter comparative study was performed at eight sites using three panels consisting of serial dilutions of quantified EBV DNA and extracts from a total of 19 whole-blood specimens. Samples were distributed and tested blindly. Instrumentation, probe chemistries, amplification targets, and other test-related aspects varied considerably between laboratories. Each laboratory's calibration curve indicated strong evidence of a consistent log-linear relationship between viral load and cycle threshold, suggesting that intralaboratory tracking of a given patient would yield similar relative quantitative trends among the participating test sites. There was strong concordance among laboratories with respect to qualitative test results; however, marked quantitative discordance was seen. For most samples, the across-laboratory interquartile range of the reported viral load (in copies/l) was roughly 0.6 log-units, and for one sample the overall range was approximately 4.2 log-units. While intralaboratory tracking of patients may yield similar results, these data indicate a need for caution when attempting to compare clinical results obtained at different institutions and suggest the potential value to be gained by more standardized testing methodology.