Neutralizing antibody rather than cellular immune response is maintained for nearly 20 years among Japanese encephalitis SA14-14-2 vaccinees in an endemic setting.

Japanese encephalitis (JE), caused by infection with Japanese encephalitis virus (JEV), is the most important viral encephalitis in Asia. JE incidence has significantly decreased by immunization with live-attenuated vaccine SA14-14-2. However, the duration of immune response overtime after vaccination is inconclusive and may be associated with the risk of JE occurrence in adults. A cross-sectional study was conducted in 961 JE-vaccinated local residents aged 19-20 years in Beijing, China. 620 (65%) and 513 (53%) individuals were anti-JEV IgG antibody and neutralizing antibody (nAb) positive, respectively. The geometric mean titer (GMT) of nAb was 1:11, suggesting a seroprotection among the study population. As for IFN-γ production, peripheral blood mononuclear cell (PBMC) samples isolated from 60 subjects showed negative response following the stimulation with concentrated JEV particles. Overall, longer persistence of nAb response among vaccinees is observed than that of cellular immune response after 17-18 years of vaccination. Taken together, our results not only provide the data for evaluating herd immunity against JEV among vaccinated adults in Beijing but also offer useful information for JE prevention and control in endemic areas.

Exploring the Prevalence of Clozapine Phenotypic Poor Metabolizers in 4 Asian Samples: They Ranged Between 2% and 13.

PURPOSE/BACKGROUND: Clozapine clearance is influenced by sex, smoking status, ethnicity, coprescription of inducers or inhibitors, obesity, and inflammation. In 126 Beijing inpatients, we measured repeated trough steady-state serum concentrations and identified 4% (5/126) who were phenotypical poor metabolizers (PMs); none were ultrarapid metabolizers (UMs). They were defined as being 2 SDs beyond the means of total clozapine concentration/dose ratios stratified by sex and smoking. Using this definition, this study explores the prevalence of PMs and UMs using data from 4 already published Asian samples. Three samples were East Asian (Beijing 2, Taipei, and Seoul); one was from South India (Vellore). FINDINGS/RESULTS: The prevalence of phenotypical PMs ranged from 2% to 13%, but inflammation was not excluded. The prevalence was 7% (14/191) for Beijing 2, 11% (8/70) for Taipei, 13% (9/67) for Seoul, and 2% (2/101) for the Vellore sample. Five phenotypic PMs appeared to be associated with extreme obesity. Phenotypic UM prevalence ranged from 0% to 1.6% but may be partly explained by lack of adherence. A Vellore phenotypic UM appeared to be associated with induction through high coffee intake. IMPLICATIONS/CONCLUSIONS: Approximately 10% of Asians may be clozapine PMs and may need only 50 to 150 mg/d to get therapeutic concentrations. Future studies combining gene sequencing for new alleles with repeated concentrations and careful control of confounders including inhibitors, inflammation, and obesity should provide better estimations of the prevalence of phenotypic clozapine PMs across races. Clozapine UM studies require excluding potent inducers, careful supervision of compliance in inpatient settings, and multiple serum concentrations.

Genomic sequencing is required for identification of tuberculosis transmission in Hawaii.

BACKGROUND: Tuberculosis (TB) caused an estimated 1.4 million deaths and 10.4 million new cases globally in 2015. TB rates in the United States continue to steadily decline, yet rates in the State of Hawaii are perennially among the highest in the nation due to a continuous influx of immigrants from the Western Pacific and Asia. TB in Hawaii is composed of a unique distribution of genetic lineages, with the Beijing and Manila families of Mycobacterium tuberculosis (Mtb) comprising over two-thirds of TB cases. Standard fingerprinting methods (spoligotyping plus 24-loci Mycobacterial Interspersed Repetitive Units-Variable Number Tandem Repeats [MIRU-VNTR] fingerprinting) perform poorly when used to identify actual transmission clusters composed of isolates from these two families. Those typing methods typically group isolates from these families into large clusters of non-linked isolates with identical fingerprints. Next-generation whole-genome sequencing (WGS) provides a new tool for molecular epidemiology that can resolve clusters of isolates with identical spoligotyping and MIRU-VNTR fingerprints. METHODS: We performed WGS and SNP analysis and evaluated epidemiological data to investigate 19 apparent TB transmission clusters in Hawaii from 2003 to 2017 in order to assess WGS' ability to resolve putative Mtb clusters from the Beijing and Manila families. This project additionally investigated MIRU-VNTR allele prevalence to determine why standard Mtb fingerprinting fails to usefully distinguish actual transmission clusters from these two Mtb families. RESULTS: WGS excluded transmission events in seven of these putative clusters, confirmed transmission in eight, and identified both transmission-linked and non-linked isolates in four. For epidemiologically identified clusters, while the sensitivity of MIRU-VNTR fingerprinting for identifying actual transmission clusters was found to be 100%, its specificity was only 28.6% relative to WGS. We identified that the Beijing and Manila families' significantly lower Shannon evenness of MIRU-VNTR allele distributions than lineage 4 was the cause of standard fingerprinting's poor performance when identifying transmission in Beijing and Manila family clusters. CONCLUSIONS: This study demonstrated that WGS is necessary for epidemiological investigation of TB in Hawaii and the Pacific.

Non-medical use of prescription drugs and cultural orientation among college students in China.

BACKGROUND: Due to a dramatic increase in the past 20 years, the non-medical use of prescription drugs (NMUPD) has become a global public health issue. College students have high prevalence of NMUPD in the United States. However, limited studies have been conducted among Chinese students. The purposes of this study were to examine the prevalence of NMUPD among college students in two urban centers (Beijing and Macau) in China and assess its relationships with cultural orientation (collectivism - primary focus on the group and individualism - primary focus on the individual). METHODS: In January-April 2017, 849 undergraduates (72.2% female) from Beijing and Macau, with an average age of 20 completed online surveys about their demographics, NMUPD, and cultural orientation. RESULTS: Overall, 62.9% (lifetime) and 33.4% (past three-months) of students in Beijing reported NMUPD, while 35.9% (lifetime) and 21.8% (past three-months) of students in Macau reported NMUPD. The most commonly non-medically used class of medicine (lifetime) was analgesics (62.9% Beijing; 35.5% Macau), followed by sedatives (4.0% Beijing; 0.9% Macau), anxiolytics (2.7% Beijing; 0.6% Macau), and stimulants (1.0% Beijing; 0.2% Macau). Multivariate analyses suggested a positive association of individualism with lifetime NMUPD (OR = 1.78, 95% CI = 1.15, 2.75, p < .01 in Beijing; OR = 1.53, 95% CI = 1.16, 2.02, p < .01 in Macau). CONCLUSION: NMUPD in Chinese college students appears to be common. More discussion is needed in China about regulation of prescription drugs. Future culturally-tailored NMUPD-risk reduction intervention programs may be beneficial to Chinese college students.

Comparison of Echocardiographic Parameters Between Healthy Highlanders in Tibet and Lowlanders in Beijing.

Yang, Ying, Duo-Ji Zha-Xi, Wei Mao, Guang Zhi, Bin Feng, and Yun-Dai Chen. Comparison of echocardiographic parameters between healthy highlanders in Tibet and lowlanders in Beijing. High Alt Med Biol. 19:259-264, 2018.-The hearts of highlanders exhibit distinct features compared with the hearts of lowlanders. However, previous findings have not been verified in a large-scale Tibetan population study. The aim of this study was to present differences in echocardiography results among healthy native Tibetans, acclimatized Han highlanders, and Han lowlanders at sea level. A total of 1820 healthy Tibetans and 224 healthy Han highlanders were drawn from a representative sample of residents in Tibet. Echocardiography was performed on each participant at the sampled local medical centers. Echocardiographic data from 2332 healthy Han lowlanders were obtained from a database of a medical examination center in Beijing. Using propensity score matching to balance differences in demographic features, we evaluated the effects of altitude and ethnicity in three paired comparisons. The results revealed that the great arteries were larger in the Han population than in the Tibetan population regardless of altitude (all p < 0.05). No differences were found in the right atrium between different altitudes and ethnicities. The diameters and thicknesses of the right ventricle (RV) were larger in the Tibetans than in the Han lowlanders (i.e., 30.0 mm (26.0, 34.0) versus 28.6 mm (25.5, 31.8) for the basal right ventricular linear dimension). The left heart in diastole was largest in the Han lowlanders (i.e., 46.3 ± 3.9 mm versus 43.0 mm [40.0, 44.0] in Han highlanders and 45.8 mm [43.0, 48.8] versus 42.0 mm [39.0, 45.0] in Tibetans for the diameter of the left ventricle [LV] at end-diastole). Moreover, the interventricular septum was thicker in the high-altitude population than in the low-altitude population (all p < 0.05). Compared with the Tibetans, the Han highlanders exhibited enhanced ventricular functions (65.0% [60.0, 69.0] versus 68.0% [63.0, 69.0] for LV ejection fraction and 22.0 mm [20.0, 26.0] versus 24.0 mm [21.0, 27.0] for tricuspid annular plane systolic excursion, both p < 0.05). In conclusion, a small left heart and a large RV may be consequences of hypoxic exposure at high altitudes irrespective of ethnic origin.

Genetic polymorphisms study of pharmacogenomic VIP variants in Han ethnic of China's Shaanxi province.

BACKGROUND: Multiple factors include genetic and non-genetic interactions induce to different drug response among different individuals. Lots of researches proved that different frequencies of genetic variants exists different ethnic groups. The aim of this study was to screen Han volunteers in Shaanxi for VIP gene polymorphisms. MATERIALS AND METHODS: We genotyped 80 Very Important Pharmacogenes (VIP) (selected from the PharmGKB database) in 192 unrelated, healthy Han ethnic adults from Shaanxi, the northwest of China, and then analyzed genotyping data wtih Structure and F-statistics (Fst) analysis. RESULTS: We compared our data with 15 other populations (Deng, Kyrgyz, Tajik, Uygur and 11 HapMap populations), and found the frequency distribution of Han population in Shaanxi is most similar with CHB. Also, Structure and Fst showed that Shaanxi Han has a closest genetic background with CHB. CONCLUSIONS: Our study have supplemented the Han Chinese data related to pharmacogenomics and illustrated differences in genotypic frequencies of selected VIP variants' among the Han population and 15 other populations.

Mycobacterium tuberculosis phylogeography in the context of human migration and pathogen's pathobiology: Insights from Beijing and Ural families.

Here, I review the population structure and phylogeography of the two contrasting families of Mycobacterium tuberculosis, Beijing and Ural, in the context of strain pathobiology and human history and migration. Proprietary database (12-loci MIRU-VNTR profiles of 3067 Beijing genotype isolates) was subjected to phylogenetic and statistical analysis. The highest rate (90%) and diversity (HGI 0.80-0.95) of the Beijing genotype in North China suggest it to be its area of origin. Under VNTR-based MDS analysis the interpopulation genetic distances correlated with geography over uninterrupted landmasses. In contrast, large water distances together with long time generated remarkable outliers. Weak and less expected affinities of the distant M. tuberculosis populations may reflect hidden epidemiological links due to unknown migration. Association with drug-resistance or increased virulence/transmissibility along with particular human migration flows shape global dissemination of some Beijing clones. The paucity of data on the Ural genotype prevents from high-resolution analysis that was mainly based on the available spoligotyping data. The North/East Pontic area marked with the highest prevalence of the Ural family may have been the area of its origin and primary dispersal in Eurasia. Ural strains are not marked by increased pathogenic capacities, increased transmissibility and association with drug resistance (but most recent reports describe an alarming increase of MDR Ural strains in some parts of eastern Europe and northwestern Russia). Large-scale SNP or WGS population-based studies targeting strains from indigenous populations and, eventually, analysis of ancient DNA will better test these hypotheses. Host genetics factors likely play the most prominent role in differential dissemination of particular M. tuberculosis genotypes.