Predictors for Early Identification of Hepatitis C Virus Infection.

Hepatitis C virus (HCV) infection can cause permanent liver damage and hepatocellular carcinoma, and deaths related to HCV deaths have recently increased. Chronic HCV infection is often undiagnosed such that the virus remains infective and transmissible. Identifying HCV infection early is essential for limiting its spread, but distinguishing individuals who require further HCV tests is very challenging. Besides identifying high-risk populations, an optimal subset of indices for routine examination is needed to identify HCV screening candidates. Therefore, this study analyzed data from 312 randomly chosen blood donors, including 144 anti-HCV-positive donors and 168 anti-HCV-negative donors. The HCV viral load in each sample was measured by real-time polymerase chain reaction method. Receiver operating characteristic curves were used to find the optimal cell blood counts and thrombopoietin measurements for screening purposes. Correlations with values for key indices and viral load were also determined. Strong predictors of HCV infection were found by using receiver operating characteristics curves to analyze the optimal subsets among red blood cells, monocytes, platelet counts, platelet large cell ratios, and mean corpuscular hemoglobin concentrations. Sensitivity, specificity, and area under the receiver operator characteristic curve (P < 0.0001) were 75.6%, 78.5%, and 0.859, respectively.

Phylodynamic reconstruction of the spatiotemporal transmission and demographic history of coxsackievirus B2.

BACKGROUND: Studies regarding coxsackievirus (CV) tend to focus on epidemic outbreaks, an imbalanced topology is considered to be an indication of acute infection with partial cross-immunity. In enteroviruses, a clear understanding of the characteristics of tree topology, transmission, and its demographic dynamics in viral succession and circulation are essential for identifying prevalence trends in endemic pathogens such as coxsackievirus B2 (CV-B2). This study applied a novel Bayesian evolutionary approach to elucidate the phylodynamic characteristics of CV-B2. A dataset containing 51 VP1 sequences and a dataset containing 34 partial 3D(pol) sequencing were analyzed, where each dataset included Taiwan sequences isolated during 1988-2013. RESULTS: Four and five genotypes were determined based on the 846-nucleotide VP1 and 441-nucleotide 3D(pol) (6641-7087) regions, respectively, with spatiotemporally structured topologies in both trees. Some strains with tree discordance indicated the occurrence of recombination in the region between the VP1 and 3D(pol) genes. The similarities of VP1 and 3D(pol) gene were 80.0%-96.8% and 74.7%-91.9%, respectively. Analyses of population dynamics using VP1 dataset indicated that the endemic CV-B2 has a small effective population size. The balance indices, high similarity, and low evolutionary rate in the VP1 region indicated mild herd immunity selection in the major capsid region. CONCLUSIONS: Phylodynamic analysis can reveal demographic trends and herd immunity in endemic pathogens.

Phylodynamic analysis of the canine distemper virus hemagglutinin gene.

BACKGROUND: Canine distemper (CD) is one of the most contagious and lethal viral diseases in dogs. Despite the widespread use of vaccines, the prevalence of the CD virus (CDV) has increased at an alarming rate in recent years. In this phylodynamic study, we investigated the spatiotemporal modes of dispersal, viral demographic trends, and effectiveness of vaccines for CDV. A total of 188 full-length CDV hemagglutinin (H) gene sequences dataset were subjected to recombination analysis, including seven from modified live vaccine (MLV) strains and 12 from Taiwan specimens. After excluding the MLV strains and potential recombinant strains, alignments of 176 of 188 previous CDV strains were further used to analyze phylodynamic characteristics, and evidence of selection, and co-evolution. RESULTS: The CDV genotype consisted of MLV-associated genotypes such as America-1 and Rockborn-like strains, which were characterized by long terminal branches and no distinct geographical patterns among lineages. In contrast, wild-type isolates clustered into lineages with a spatiotemporal structure and short terminal branches. Co-circulation and extensive diversification were simultaneously observed. The sequence variation signature was shaped by both geographic diversity and host tropism. Codon 506 was identified as a multi-epistatic interacting in the H protein. CONCLUSIONS: The topological signature revealed in this study suggests different epidemic scenarios. For example, a ladder-like backbone is a hallmark of directional selection, and cladogenesis at long terminal branches indicates the emergence of a surviving lineage. The stable effective viral population of CDV indicate the effectiveness of vaccines currently used to control the virus.

Transmission and Demographic Dynamics of Coxsackievirus B1.

The infectious activity of coxsackievirus B1 (CV-B1) in Taiwan was high from 2008 to 2010, following an alarming increase in severe neonate disease in the United States (US). To examine the relationship between CV-B1 strains isolated in Taiwan and those from other parts of the world, we performed a phylodynamic study using VP1 and partial 3Dpol (414 nt) sequences from 22 strains of CV-B1 isolated in Taiwan (1989-2010) and compared them to sequences from strains isolated worldwide. Phylogenetic trees were constructed by neighbor-joining, maximum likelihood, and Bayesian Monte Carlo Markov Chain methods. Four genotypes (GI-IV) in the VP1 region of CV-B1 and three genotypes (GA-C) in the 3Dpol region of enterovirus B were identified and had high support values. The phylogenetic analysis indicates that the GI and GIII strains in VP1 were geographically distributed in Taiwan (1993-1994) and in India (2007-2009). On the other hand, the GII and GIV strains appear to have a wider spatiotemporal distribution and ladder-like topology A stair-like phylogeny was observed in the VP1 region indicating that the phylogeny of the virus may be affected by different selection pressures in the specified regions. Further, most of the GI and GII strains in the VP1 tree were clustered together in GA in the 3D tree, while the GIV strains diverged into GB and GC. Taken together, these data provide important insights into the population dynamics of CV-B1 and indicate that incongruencies in specific gene regions may contribute to spatiotemporal patterns of epidemicity for this virus.