Aiqiang Xu

Molecular Evidence of Persistent Epidemic and Evolution of Subgenotype B1 Coxsackievirus A16-Associated Hand, Foot, and Mouth Disease in China

ABSTRACT The molecular epidemiology of CVA16 in China between 1999 and 2008 reflects a pattern of endemic cocirculation of clusters B1a and B1b within subgenotype B1 viruses. The annual evolution rate of CVA16 was estimated as approximately 0.91 × 10−2 substitutions per synonymous nucleotide/year and is slightly lower than that of HEV71.

Emergence and Transmission Pathways of Rapidly Evolving Evolutionary Branch C4a Strains of Human Enterovirus 71 in the Central Plain of China

Background Large-scale outbreaks of hand, foot, and mouth disease (HFMD) occurred repeatedly in the Central Plain of China (Shandong, Anhui, and Henan provinces) from 2007 until now. These epidemics have increased in size and severity each year and are a major public health concern in mainland China. Principal Findings Phylogenetic analysis was performed and a Bayesian Markov chain Monte Carlo tree was constructed based on the complete VP1 sequences of HEV71 isolates. These analyses showed that the HFMD epidemic in the Central Plain of China was caused by at least 5 chains of HEV71 transmission and that the virus continued to circulate and evolve over the winter seasons between outbreaks. Between 1998 and 2010, there were 2 stages of HEV71 circulation in mainland China, with a shift from evolutionary branch C4b to C4a in 2003–2004. The evolution rate of C4a HEV71 was 4.99×10-3 substitutions per site per year, faster than the mean of all HEV71 genotypes. The most recent common ancestor estimates for the Chinese clusters dated to October 1994 and November 1993 for the C4a and C4b evolutionary branches, respectively. Compared with all C4a HEV71 strains, a nucleotide substitution in all C4b HEV71 genome (A to C reversion at nt2503 in the VP1 coding region, which caused amino acid substitution of VP1–10: Gln to His) had reverted. Conclusions The data suggest that C4a HEV71 strains introduced into the Central Plain of China are responsible for the recent outbreaks. The relationships among HEV71 isolates determined from the combined sequence and epidemiological data reveal the underlying seasonal dynamics of HEV71 circulation. At least 5 HEV71 lineages circulated in the Central Plain of China from 2007 to 2009, and the Shandong and Anhui lineages were found to have passed through a genetic bottleneck during the low-transmission winter season.

Identification and Control of a Poliomyelitis Outbreak in Xinjiang, China

BACKGROUND The last case of infection with wild-type poliovirus indigenous to China was reported in 1994, and China was certified as a poliomyelitis-free region in 2000. In 2011, an outbreak of infection with imported wild-type poliovirus occurred in the province of Xinjiang. METHODS We conducted an investigation to guide the response to the outbreak, performed sequence analysis of the poliovirus type 1 capsid protein VP1 to determine the source, and carried out serologic and coverage surveys to assess the risk of viral propagation. Surveillance for acute flaccid paralysis was intensified to enhance case ascertainment. RESULTS Between July 3 and October 9, 2011, investigators identified 21 cases of infection with wild-type poliovirus and 23 clinically compatible cases in southern Xinjiang. Wild-type poliovirus type 1 was isolated from 14 of 673 contacts of patients with acute flaccid paralysis (2.1%) and from 13 of 491 healthy persons who were not in contact with affected persons (2.6%). Sequence analysis implicated an imported wild-type poliovirus that originated in Pakistan as the cause of the outbreak. A public health emergency was declared in Xinjiang after the outbreak was confirmed. Surveillance for acute flaccid paralysis was enhanced, with daily reporting from all public and private hospitals. Five rounds of vaccination with live, attenuated oral poliovirus vaccine (OPV) were conducted among children and adults, and 43 million doses of OPV were administered. Trivalent OPV was used in three rounds, and monovalent OPV type 1 was used in two rounds. The outbreak was stopped 1.5 months after laboratory confirmation of the index case. CONCLUSIONS The 2011 outbreak in China showed that poliomyelitis-free countries remain at risk for outbreaks while the poliovirus circulates anywhere in the world. Global eradication of poliomyelitis will benefit all countries, even those that are currently free of poliomyelitis.

A genome-wide association study identifies polymorphisms in the HLA-DR region associated with non-response to hepatitis B vaccination in Chinese Han populations

Vaccination against hepatitis B virus is an effective and routine practice that can prevent infection. However, 5-10% of healthy adults fail to produce protective levels of antibody against the hepatitis B vaccination. It has been reported that host genetic variants might affect the immune response to hepatitis B vaccination. Here, we reported a genome-wide association study in a Chinese Han population consisting of 108 primary high-responders and 77 booster non-responders to hepatitis B vaccination using the Illumina HumanOmniExpress Beadchip. We identified 21 SNPs at 6p21.32 were significantly associated with non-response to booster hepatitis B vaccination (P-value <1 × 10(-6)). The most significant SNP in the region was rs477515, located ∼12 kb upstream of the HLA-DRB1 gene. Its P-value (4.81 × 10(-8)) exceeded the Bonferroni-corrected genome-wide significance threshold. Four tagging SNPs (rs477515, rs28366298, rs3763316 and rs13204672) that capture genetic information of these 21 SNPs were validated in three additional Chinese Han populations, consisting of 1336 primary high-responders and 420 primary non-responders. The four SNPs continued to show significant associations with non-response to hepatitis B vaccination (P-combined = 3.98 × 10(-13)- 1.42 × 10(-8)). Further analysis showed that the rs477515 was independently associated with non-response to hepatitis B vaccination with correction for other three SNPs in our GWAS and the known hepatitis B vaccine immunity associated SNP in previous GWAS. Our findings suggest that the rs477515 was an independent marker associated with non-response to hepatitis B vaccination and HLA-DR region might be a critical susceptibility locus of hepatitis B vaccine-induced immunity.

Hypertension Prevalence, Awareness, Treatment, and Control and Sodium Intake in Shandong Province, China: Baseline Results From Shandong–Ministry of Health Action on Salt Reduction and Hypertension (SMASH), 2011

Introduction In China, population-based blood pressure levels and prevalence of hypertension are increasing. Meanwhile, sodium intake, a major risk factor for hypertension, is high. In 2011, to develop intervention priorities for a salt reduction and hypertension control project in Shandong Province (population 96 million), a cross-sectional survey was conducted to collect information on sodium intake and hypertension prevalence, awareness, treatment, and control. Methods Complex, multistage sampling methods were used to select a provincial-representative adult sample. Blood pressure was measured and a survey conducted among all participants; condiments were weighed in the household, a 24-hour dietary recall was conducted, and urine was collected. Hypertension was determined by blood pressure measured on a single occasion and self-reported use of antihypertension medications. Results Overall, 23.4% (95% confidence interval [CI], 20.9%–26.0%) of adults in Shandong were estimated to have hypertension. Among those classified as having hypertension, approximately one-third (34.5%) reported having hypertension, approximately one-fourth (27.5%) reported taking medications, and one-seventh (14.9%) had their blood pressure controlled (<140/<90 mm Hg). Estimated total average daily dietary sodium intake was 5,745 mg (95% CI, 5,428 mg–6,063 mg). Most dietary sodium (80.8%) came from salt and high-salt condiments added during cooking: a sodium intake of 4,640 mg (95% CI, 4,360 mg–4,920 mg). The average daily urinary sodium excretion was 5,398 mg (95% CI, 5,112 mg–5,683 mg). Conclusion Hypertension and excessive sodium intake in adults are major public health problems in Shandong Province, China.

Dietary Sodium Intake: Knowledge, Attitudes and Practices in Shandong Province, China, 2011

Objective To investigate the knowledge, attitudes and practices (KAP) for dietary sodium intake among adult residents of Shandong Province, China Methods In 2011, we conducted a cross sectional survey among a representative sample of 15,350 adults aged 18 to 69 years using a standardized questionnaire to assess their KAP for sodium. Variation in the KAPs by gender, and residence location were compared using the Chi-square tests. Predictors for the ‘intention to’ and ‘currently taking action to’ reduce sodium intake were determined by multivariate logistic regression with adjustment for confounding factors. Results KAPs for dietary sodium intake among urban residents was generally more favorable than among rural residents. Women were likely to have more favorable KAPs than men. About four fifth of subjects reported that they favored a low sodium diets. However, 31% reported that consumption of less sodium results in less physical strength. Overall, 70% indicated their intention to reduce sodium intake, although only 39 % reported that they had taken action to reduce sodium. Multiple logistic regression analyses indicated that favorable actions to dietary sodium reduction were more likely to occur among those who were aware of the link between sodium and hypertension, and less likely among those who had unfavorable attitudes towards dietary sodium reduction. Conclusion Increasing knowledge levels about the benefits of sodium reduction will be a key success factor for effective sodium reduction initiatives and is linked to favorable behavioral change. Emphasis should be placed on the rural area.

Molecular epidemiology of human enterovirus associated with aseptic meningitis in Shandong Province, China, 2006-2012.

Background Human enteroviruses (HEVs) are common causes of acute meningitis. However, there is limited information about HEV associated with aseptic meningitis in mainland China because it has not been classified as a notifiable disease. Objectives To characterize the HEVs associated with sporadic aseptic meningitis in China and to analyze their genetic features. Study Design Cerebrospinal fluid, throat swab and feces specimens were collected from patients with aseptic meningitis in 5 sentinel hospitals in Shandong Province, China between 2006 and 2012. Virological investigation (viral isolation and molecular identification) and phylogenetic analysis were performed. Results A total of 437 hospitalized patients were reported, and enteroviruses were detected in the specimens from 84 patients (19.2%) and were identified into 17 serotypes. The nine main serotypes were echovirus (E) 30 (27.4%), EV71 (13.1%), coxsackievirus (CV) B1 (9.5%), CVB3 (7.1%), CVB5 (7.1%), E6 (7.1%), E9 (7.1%), CVA9 (6.0%), and CVA10 (3.6%). Monthly distribution of isolated enteroviruses revealed a major peak in summer-fall season and a small second peak in winter constituted totally by EV71. Sequence analysis on VP1 coding region suggested Shandong strains had great genetic divergence with isolates from other countries. Conclusions Multiple serotypes were responsible for enterovirus meningitis in mainland China. Aseptic meningitis caused by EV71 and coxsackie A viruses–the predominant pathogens for the hand, foot, and mouth disease–is currently an important concern in mainland China.

Suicide rates in Shandong, China, 1991-2010: Rapid decrease in rural rates and steady increase in male-female ratio

BACKGROUND China has one of the highest suicide rates in the world; however, the recent trends in suicide have not been adequately studied. This study aimed to examine the potential changes in the rates and characteristics in a Chinese population. METHODS Data on suicide deaths in 1991-2010 were extracted from the Shandong Disease Surveillance Point (DSP) mortality dataset based on ICD-10 codes. The temporal trend in age-adjusted suicide rates for each subpopulation was tested using log-linear Poisson regression analysis. RESULTS From 1991 to 2010, there was a marked decrease in the overall suicide rate in Shandong, with an average reduction of 8% per year. The decrease trend was stronger in rural than in urban areas and more evident in females than in males. Similar decreases were observed for all age groups. Pesticide ingestion and hanging remained the top two methods for suicide. LIMITATIONS There are likely quality concerns in the morality data, such as underreporting and misclassification, as well as low accuracy in determining the underlying causes of deaths. The representativeness of the DSP system may also be problematic due to the rapid changes in economy and demography. CONCLUSIONS Completed suicides in Shandong have sharply declined over the past 20 years. Higher rates in females versus males and in rural versus urban areas, which were previously considered to be distinguishing features of suicide in China, are becoming less pronounced.

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

ABSTRACT 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.

Epidemiological analysis of injury in Shandong Province, China.

BackgroundInjury is an emerging public health problem with social development and modernization in developing countries. To describe the prevalence and burden of injury and provide elaborate information for policy development, we conducted a community-based household survey in the Shandong Province of China.MethodsThe survey was conducted in 2004. Participants were selected by a multi-stage random sampling method. Information on injuries occurring in 2003 was collected in four cities and six rural counties in Shandong Province, China.ResultsThe estimated incidence rate of injury in Shandong Province was 67.7 per 1,000. Injury incidence was higher in rural areas (84.3 per 1,000) than in urban areas (42.9 per 1,000), and was higher among males (81.1 per 1,000) than females (54.1 per 1,000).The average years of potential life lost is 37.7 years for each fatal injury. All injuries together caused 6,080,407 RMB yuan of direct and indirect economic loss, with traffic injuries accounting for 44.8% of the total economic loss.ConclusionInjury incidence was higher among males than females, and in rural areas than in urban areas. Youngsters suffered the highest incidence of injury. Injury also caused large losses in terms of both economics and life, with traffic injuries contributing the most to this loss. Strategies for prevention of injury should be developed.