Phylodynamic Methods Research Articles

Cocirculation of Two Transmission Lineages of Echovirus 6 in Jinan, China, as Revealed by Environmental Surveillance and Sequence Analysis

Enterovirus environmental surveillance on sewage from the city of Jinan, Shandong Province, China, was initiated in 2008. Thirty echovirus 6 (E6) strains-1 in 2008 and 29 in 2010-were isolated and identified. Most E6 isolates (n = 21) came from the sewage collected on August 2010, revealing high local E6 activity at that time. Interestingly, the VP1 sequences of most isolates, even from the same sewage, were not identical. Phylogenetic analysis of VP1 sequences revealed two lineages for these isolates, with 78.0 to 80.0% nucleotide identities with one another, 94.8 to 100.0% identity within the major lineage, and 92.7 to 98.5% identity within the minor one. The VP1 sequences of environmental isolates, clinical isolates from 1998 to 2010, and global E6 were subjected to evolutionary analysis using Bayesian phylodynamic methods. The inferred E6 VP1 ancestral sequence dated back to 1901 (range, 1873 to 1928) and evolved with 7.047 × 10(-3) substitutions per site per year. Shandong E6 segregated into three clusters, and the two environmental lineages belonged to clusters A and C, which originated in 2003 and 1992, respectively. The antigenicity analysis via neutralization assay confirmed great antigenic differences between Shandong isolates and a prototype strain. These findings underscore the value of continuous environmental surveillance and genetic analysis to monitor circulating enteroviruses in the population and give further insight into E6 evolution.

The Global Spread of Hepatitis C Virus 1a and 1b: A Phylodynamic and Phylogeographic Analysis

Hepatitis C virus (HCV) is estimated to affect 130-180 million people worldwide. Although its origin is unknown, patterns of viral diversity suggest that HCV genotype 1 probably originated from West Africa. Previous attempts to estimate the spatiotemporal parameters of the virus, both globally and regionally, have suggested that epidemic HCV transmission began in 1900 and grew steadily until the late 1980s. However, epidemiological data suggest that the expansion of HCV may have occurred after the Second World War. The aim of our study was to elucidate the timescale and route of the global spread of HCV. We show that the rarely sequenced HCV region (E2P7NS2) is more informative for molecular epidemiology studies than the more commonly used NS5B region. We applied phylodynamic methods to a substantial set of new E2P7NS2 and NS5B sequences, together with all available global HCV sequences with information in both of these genomic regions, in order to estimate the timescale and nature of the global expansion of the most prevalent HCV subtypes, 1a and 1b. We showed that transmission of subtypes 1a and 1b "exploded" between 1940 and 1980, with the spread of 1b preceding that of 1a by at least 16 y (95% confidence interval 15-17). Phylogeographic analysis of all available NS5B sequences suggests that HCV subtypes 1a and 1b disseminated from the developed world to the developing countries. The evolutionary rate of HCV appears faster than previously suggested. The global spread of HCV coincided with the widespread use of transfused blood and blood products and with the expansion of intravenous drug use but slowed prior to the wide implementation of anti-HCV screening. Differences in the transmission routes associated with subtypes 1a and 1b provide an explanation of the relatively earlier expansion of 1b. Our data show that the most plausible route of the HCV dispersal was from developed countries to the developing world. Please see later in the article for the Editors' Summary.

Post-bulbar and coexisting ulceration: unique features of peptic ulcer in Hyderabad.

Post-bulbar ulceration is uncommon, but a pilot study in Hyderabad showed a high incidence. We therefore carried out a prospective endoscopic study of the distribution of peptic ulceration and its relation to symptoms and demography. Of the 360 consecutive patients referred for endoscopy, 113 (92 men, 21 women) had peptic ulceration. Median age 35 years, median duration one year. Five patients (4%) had gastric ulcer, 77 (68%) had duodenal ulcer, and 31 (28%) had coexisting gastric and duodenal ulcer. The duodenal ulcer was found in the pyloric canal in 14% of patients, in the bulb in 80%, and the post-bulbar region in 56% of patients. Sixty seven per cent of duodenal ulcers were located at more than one site. The incidence of post-bulbar v bulbar ulcer was 1:1.5. Deformed bulb was seen in 50% of duodenal ulcer patients, but haemorrhage and stenosis were uncommon. Except for nocturnal pain, there were no differences in symptoms between the groups. Forty two per cent of patients smoked, 15% chewed tobacco, and 18% drank alcohol; almost all were men. Sixty four per cent drank tea. The staple diet (85%) was rice, and 70% used tamarind and spices daily. Duodenal ulcer was three times more common than gastric ulcer with a high incidence of post-bulbar and coexisting ulcer. It affected a younger and predominantly male population, and was not associated with a higher rate of complication.