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1.
Experimental Infection of Rabbits with Rabbit and Genotypes 1 and 4 Hepatitis E Viruses 总被引:1,自引:0,他引:1
Hongxia Ma Lin Zheng Yunbo Liu Chenyan Zhao Tim J. Harrison Yuyuan Ma Shuhua Sun Jingang Zhang Youchun Wang 《PloS one》2010,5(2)
Background
A recent study provided evidence that farmed rabbits in China harbor a novel hepatitis E virus (HEV) genotype. Although the rabbit HEV isolate had 77–79% nucleotide identity to the mammalian HEV genotypes 1 to 4, their genomic organization is very similar. Since rabbits are used widely experimentally, including as models of infection, we investigated whether they constitute an appropriate animal model for human HEV infection.Methods
Forty-two SPF rabbits were divided randomly into eleven groups and inoculated with six different isolates of rabbit HEV, two different doses of a second-passage rabbit HEV, and with genotype 1 and 4 HEV. Sera and feces were collected weekly after inoculation. HEV antigen, RNA, antibody and alanine aminotransferase in sera and HEV RNA in feces were detected. The liver samples were collected during necropsy subject to histopathological examination.Findings
Rabbits inoculated with rabbit HEV became infected with HEV, with viremia, fecal virus shedding and high serum levels of viral antigens, and developed hepatitis, with elevation of the liver enzyme, ALT. The severity of disease corresponded to the infectious dose (genome equivalents), with the most severe hepatic disease caused by strain GDC54-18. However, only two of nine rabbits infected with HEV genotype 4, and none infected with genotype 1, developed hepatitis although six of nine rabbits inoculated with the genotype 1 HEV and in all rabbits inoculated with the genotype 4 HEV seroconverted to be positive for anti-HEV IgG antibody by 14 weeks post-inoculation.Conclusions
These data indicate that rabbits are an appropriate model for rabbit HEV infection but are not likely to be useful for the study of human HEV. The rabbit HEV infection of rabbits may provide an appropriate parallel animal model to study HEV pathogenesis. 相似文献2.
Xianfeng Cheng Song Wang Xing Dai Chengbo Shi Yufeng Wen Ming Zhu Shenwei Zhan Jihong Meng 《PloS one》2012,7(12)
Background
The identification of hepatitis E virus (HEV) from rabbits motivated us to assess the possibility of using rabbits as a non-human primate animal model for HEV infection and vaccine evaluation.Methodology/Principal Findings
First, 75 rabbits were inoculated with seven strains of genotypes 1, 3, 4, and rabbit HEV, to determine the appropriate strain, administrative route and viral dosage. Second, 15 rabbits were randomly divided into three groups and vaccinated with 0 µg (placebo), 10 µg and 20 µg of HEV candidate vaccine, HEV p179, respectively. After three doses of the vaccination, the rabbits were challenged with 3.3×105 genome equivalents of genotype 4 HEV strain H4-NJ703. The strain of genotype 1 HEV was not found to be infectious for rabbits. However, approximately 80% of the animals were infected by two rabbit HEV strains. All rabbits inoculated with a genotype 3 strain were seroconverted but did not show viremia or fecal viral shedding. Although two genotype 4 strains, H4-NJ153 and H4-NJ112, only resulted in part of rabbits infected, another strain of genotype 4, H4-NJ703, had an infection rate of 100% (five out of five) when administrated intravenously. However, only two out of fifteen rabbits showed virus excretion and seroconversion when inoculated orally with H4-NJ703 of three different dosages. In the vaccine evaluation study, rabbits vaccinated with 20 µg of the HEV p179 produced anti-HEV with titers of 1∶104–1∶105 and were completely protected from infection. Rabbits vaccinated with 10 µg produced anti-HEV with titers of 1∶103–1∶104 and were protected from hepatitis, but two out of the five rabbits showed virus shedding.Conclusions/Significance
Rabbits may be served as an alternative to the non-human primate models for HEV infection and vaccine evaluation when certain virus strains, appropriate viral dosages, and the intravenous route of inoculation are selected. 相似文献3.
Zhang Y Wang J Guo W Wang H Zhu S Wang D Bai R Li X Yan D Wang H Zhang Y Zhu Z Tan X An H Xu A Xu W 《PloS one》2011,6(11):e27895
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. 相似文献4.
Background and Aims
Genotype by environment (G × E) interactions are important for the long-term persistence of plant species in heterogeneous environments. It has often been suggested that disease is a key factor for the maintenance of genotypic diversity in plant populations. However, empirical evidence for this contention is scarce. Here virus infection is proposed as a possible candidate for maintaining genotypic diversity in their host plants.Methods
The effects of White clover mosaic virus (WClMV) on the performance and development of different Trifolium repens genotypes were analysed and the G × E interactions were examined with respect to genotype-specific plant responses to WClMV infection. Thus, the environment is defined as the presence or absence of the virus.Key Results
WClMV had a negative effect on plant performance as shown by a decrease in biomass and number of ramets. These effects of virus infection differ greatly among host genotypes, representing a strong G × E interaction. Moreover, the relative fitness and associated ranking of genotypes changed significantly between control and virus treatments. This shift in relative fitness among genotypes suggests the potential for WClMV to provoke differential selection on T. repens genotypes, which may lead to negative frequency-dependent selection in host populations.Conclusions
The apparent G × E interaction and evident repercussions for relative fitness reported in this study stress the importance of viruses for ecological and evolutionary processes and suggest an important role for viruses in shaping population dynamics and micro-evolutionary processes. 相似文献5.
Alka Malhotra Sayuko Kobes Clifton Bogardus William C. Knowler Leslie J. Baier Robert L. Hanson 《PloS one》2014,9(7)
Background
Genotype imputation is commonly used in genetic association studies to test untyped variants using information on linkage disequilibrium (LD) with typed markers. Imputing genotypes requires a suitable reference population in which the LD pattern is known, most often one selected from HapMap. However, some populations, such as American Indians, are not represented in HapMap. In the present study, we assessed accuracy of imputation using HapMap reference populations in a genome-wide association study in Pima Indians.Results
Data from six randomly selected chromosomes were used. Genotypes in the study population were masked (either 1% or 20% of SNPs available for a given chromosome). The masked genotypes were then imputed using the software Markov Chain Haplotyping Algorithm. Using four HapMap reference populations, average genotype error rates ranged from 7.86% for Mexican Americans to 22.30% for Yoruba. In contrast, use of the original Pima Indian data as a reference resulted in an average error rate of 1.73%.Conclusions
Our results suggest that the use of HapMap reference populations results in substantial inaccuracy in the imputation of genotypes in American Indians. A possible solution would be to densely genotype or sequence a reference American Indian population. 相似文献6.
Background
The new field of paleomicrobiology allows past outbreaks to be identified by testing dental pulp of human remains with PCR.Methods
We identified a mass grave in Douai, France dating from the early XVIIIth century. This city was besieged during the European war of Spanish succession. We tested dental pulp from 1192 teeth (including 40 from Douai) by quantitative PCR (qPCR) for R. prowazekii and B. quintana. We also used ultra-sensitive suicide PCR to detect R. prowazekii and genotyped positive samples.Results and Discussion
In the Douai remains, we identified one case of B. quintana infection (by qPCR) and R. prowazekii (by suicide PCR) in 6/21 individuals (29%). The R. prowazekii was genotype B, a genotype previously found in a Spanish isolate obtained in the first part of the XXth century.Conclusion
Louse-borne outbreaks were raging during the XVIIIth century; our results support the hypothesis that typhus was imported into Europe by Spanish soldiers from America. 相似文献7.
Yiyi Zhang Wendy S. Post Alan Cheng Elena Blasco-Colmenares Gordon F. Tomaselli Eliseo Guallar 《PloS one》2013,8(4)
Introduction
Altered thyroid status exerts a major effect on the heart. Individuals with hypo- or hyperthyroidism showed various changes in electrocardiograms. However, little is known about how variations in thyroid hormone levels within the normal range affect electrical activities of the heart in the general population.Methods and Results
We conducted a cross-sectional analysis of 5,990 men and women from the Third National Health and Nutrition Examination Survey. Serum total T4 was measured by immunoassay and TSH was measured by chemiluminescent assay. We categorized T4 and TSH into 7 groups with cut-offs at the 5th, 20th, 40th, 60th, 80th, and 95th percentiles of the weighted population distribution. Electrocardiographic parameters were measured from the standard 12-lead electrocardiogram. We found a positive linear association between serum total T4 level and heart rate in men, and a U-shape association between T4 and PR interval in men and women. TSH level was positively associated with QRS interval in men, while a U-shape association between TSH and QRS was observed in women. No clear graded association between thyroid hormones and corrected QT or JT was found, except that men in the highest category of T4 levels appeared to have longer corrected QT and JT, and men in the lowest category of T4 appeared to have shorter corrected QT and JT.Conclusions
Variation in thyroid hormone levels in the general population, even within the normal range, was associated with various ECG changes. 相似文献8.
Masahide Usami Yoshitaka Iwadare Masaki Kodaira Kyota Watanabe Momoko Aoki Chiaki Katsumi Kumi Matsuda Kazunori Makino Sonoko Iijima Maiko Harada Hiromi Tanaka Yoshinori Sasaki Tetsuya Tanaka Hirokage Ushijima Kazuhiko Saito 《PloS one》2012,7(11)
Background
To evaluate relationships between traumatic symptoms and environmental damage conditions among children who survived the 2011 Great East Japan Earthquake and Tsunami.Methods
The subjects were 12,524 children in kindergartens, elementary schools, and junior high schools in Ishinomaki City, Miyagi Prefecture, Japan. The Post Traumatic Stress Symptoms for Children 15 items (PTSSC-15), a self-completion questionnaire on traumatic symptoms, was distributed to the children and a questionnaire regarding environmental damage conditions affecting the children was distributed to their teachers. Of 12,524 questionnaires distributed, an effective response was obtained from 11,692 (93.3%).Results
The PTSSC-15 score was significantly higher in females than in males among 4th to 6th grade students in elementary schools and among junior high school students. In terms of traumatic symptoms and environmental damage conditions, with the exception of kindergartners, children who had their houses damaged or experienced separation from family members had a significantly higher PTSSC-15 score than children who did not experience environmental damage. Except for kindergartners and 4th- to 6th-grade elementary school students, children who experienced evacuation had a significantly higher PTSSC-15 score.Conclusions
This study demonstrated relationships between traumatic symptoms and environmental damage conditions in children who had suffered from the disaster. Factors examined in studying the relationship between environmental damage conditions and traumatic symptoms were gender, age, house damage, evacuation experience, and bereavement experience. It was critical not only to examine the traumatic symptoms of the children but also to collect accurate information about environmental damage conditions. 相似文献9.
Hui Liu Jia Lin Xing Chun Zhu Yuan Hao Li Mei Fan Rong Rong Zhang Ding Zhi Fang 《Biological research》2014,47(1)
Background
Diets are the important players in regulating plasma lipid profiles. And the R219K polymorphism at the gene of ATP-binding cassette transporter 1(ABCA1) was reported to be associated with the profiles. However, no efforts have been made to investigate the changes of lipid profiles after a high-carbohydrate and low-fat diet in different subjects with different genotypes of this polymorphism. This study was to evaluate the effects of ABCA1 R219K polymorphism on serum lipid and apolipoprotein (apo) ratios induced by a high-carbohydrate/low-fat (high-CHO) diet. After a washout diet of 54.1% carbohydrate for 7 days, 56 healthy young subjects (22.89 ± 1.80 years old) were given a high-CHO diet of 70.1% carbohydrate for 6 days. Height, weight, waist circumference, hip circumference, glucose (Glu), triglyceride (TG), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), apoA-1 and apoB-100 were measured on the 1st, 8th and 14th days of this study. Body mass index (BMI), waist-to-hip ratios (WHR), log(TG/HDL-C), TC/HDL-C, LDL-C/HDL-C and apoA-1/apoB-100 were calculated. ABCA1 R219K was analyzed by a PCR-RFLP method.Results
The results indicate that the male subjects of all the genotypes had higher WHR than their female counterparts on the 1st, 8th and 14th days of this study. The male K carriers had higher log(TG/HDL-C) and TC/HDL-C than the female carriers on the 1st and 14th days, and higher LDL-C/HDL-C on the 14th day. When compared with that on the 8th day, TC/HDL-C was decreased regardless of the genotypes and genders on the 14th day. Log(TG/HDL-C) was increased in the males with the RR genotype and the female K carriers. Lowered BMI, Glu and LDL-C/HDL-C were found in the male K carriers, but only lowered BMI in the female K carriers and only lowered LDL-C/HDL-C in the females with the RR genotype.Conclusions
These results suggest that ABCA1 R219K polymorphism is associated differently in males and females with elevated log(TG/HDL-C) and decreased LDL-C/HDL-C induced by the high-CHO diet. 相似文献10.
Background
Genotype imputation is commonly used as an initial step in genomic selection since the accuracy of genomic selection does not decline if accurately imputed genotypes are used instead of actual genotypes but for a lower cost. Performance of imputation has rarely been investigated in crossbred animals and, in particular, in pigs. The extent and pattern of linkage disequilibrium differ in crossbred versus purebred animals, which may impact the performance of imputation. In this study, first we compared different scenarios of imputation from 5 K to 8 K single nucleotide polymorphisms (SNPs) in genotyped Danish Landrace and Yorkshire and crossbred Landrace-Yorkshire datasets and, second, we compared imputation from 8 K to 60 K SNPs in genotyped purebred and simulated crossbred datasets. All imputations were done using software Beagle version 3.3.2. Then, we investigated the reasons that could explain the differences observed.Results
Genotype imputation performs as well in crossbred animals as in purebred animals when both parental breeds are included in the reference population. When the size of the reference population is very large, it is not necessary to use a reference population that combines the two breeds to impute the genotypes of purebred animals because a within-breed reference population can provide a very high level of imputation accuracy (correct rate ≥ 0.99, correlation ≥ 0.95). However, to ensure that similar imputation accuracies are obtained for crossbred animals, a reference population that combines both parental purebred animals is required. Imputation accuracies are higher when a larger proportion of haplotypes are shared between the reference population and the validation (imputed) populations.Conclusions
The results from both real data and pedigree-based simulated data demonstrate that genotype imputation from low-density panels to medium-density panels is highly accurate in both purebred and crossbred pigs. In crossbred pigs, combining the parental purebred animals in the reference population is necessary to obtain high imputation accuracy.Electronic supplementary material
The online version of this article (doi:10.1186/s12711-015-0134-4) contains supplementary material, which is available to authorized users. 相似文献11.
Background
Commercial breeding programs seek to maximise the rate of genetic gain while minimizing the costs of attaining that gain. Genomic information offers great potential to increase rates of genetic gain but it is expensive to generate. Low-cost genotyping strategies combined with genotype imputation offer dramatically reduced costs. However, both the costs and accuracy of imputation of these strategies are highly sensitive to several factors. The objective of this paper was to explore the cost and imputation accuracy of several alternative genotyping strategies in pedigreed populations.Methods
Pedigree and genotype data from a commercial pig population were used. Several alternative genotyping strategies were explored. The strategies differed in the density of genotypes used for the ancestors and the individuals to be imputed. Parents, grandparents, and other relatives that were not descendants, were genotyped at high-density, low-density, or extremely low-density, and associated costs and imputation accuracies were evaluated.Results
Imputation accuracy and cost were influenced by the alternative genotyping strategies. Given the mating ratios and the numbers of offspring produced by males and females, an optimized low-cost genotyping strategy for a commercial pig population could involve genotyping male parents at high-density, female parents at low-density (e.g. 3000 SNP), and selection candidates at very low-density (384 SNP).Conclusions
Among the selection candidates, 95.5 % and 93.5 % of the genotype variation contained in the high-density SNP panels were recovered using a genotyping strategy that costs respectively, $24.74 and $20.58 per candidate. 相似文献12.
Sheng-Wen Huang Hui-Li Cheng Hsin-Yi Hsieh Chia-Lun Chang Huey-Pin Tsai Pin-Hwa Kuo Shih-Min Wang Ching-Chuan Liu Ih-Jen Su Jen-Ren Wang 《Journal of biomedical science》2014,21(1):33
Background
Clinical manifestations of enterovirus 71 (EV71) range from herpangina, hand-foot-and-mouth disease (HFMD), to severe neurological complications. Unlike the situation of switching genotypes seen in EV71 outbreaks during 1998–2008 in Taiwan, genotype B5 was responsible for two large outbreaks in 2008 and 2012, respectively. In China, by contrast, EV71 often persists as a single genotype in the population and causes frequent outbreaks. To investigate genetic changes in viral evolution, complete EV71 genome sequences were used to analyze the intra-genotypic evolution pattern in Taiwan, China, and the Netherlands.Results
Genotype B5 was predominant in Taiwan’s 2008 outbreak and was re-emergent in 2012. EV71 strains from both outbreaks were phylogenetically segregated into two lineages containing fourteen non-synonymous substitutions predominantly in the non-structural protein coding region. In China, genotype C4 was first seen in 1998 and caused the latest large outbreak in 2008. Unlike shifting genotypes in Taiwan, genotype C4 persisted with progressive drift through time. A majority of non-synonymous mutations occurred in residues located in the non-structural coding region, showing annual increases. Interestingly, genotype B1/B2 in the Netherlands showed another stepwise evolution with dramatic EV71 activity increase in 1986. Phylogeny of the VP1 coding region in 1971–1986 exhibited similar lineage turnover with genotype C4 in China; however, phylogeny of the 3D-encoding region indicated separate lineage appearing after 1983, suggesting that the 3D-encoding region of genotype B2 was derived from an unidentified ancestor that contributed to intra-genotypic evolution in the Netherlands.Conclusions
Unlike VP1 coding sequences long used for phylogenetic study of enteroviruses due to expected host immune escape, our study emphasizes a dominant role of non-synonymous mutations in non-structural protein regions that contribute to (re-)emergent genotypes in continuous stepwise evolution. Dozens of amino acid substitutions, especially in non-structural proteins, were identified via genetic changes driven through intra-genotypic evolution worldwide. These identified substitutions appeared to increase viral fitness in the population, affording valuable insights not only for viral evolution but also for prevention, control, and vaccine against EV71 infection. 相似文献13.
Priyanka Banerjee Rajiv Kumar Mondal Madhuparna Nandi Sumantra Ghosh Mousumi Khatun Nabendu Chakraborty Swatilekha Bhattacharya Arindam RoyChoudhury Soma Banerjee Amal Santra Samir Sil Abhijit Chowdhury Pradip Bhaumik Simanti Datta 《PloS one》2014,9(10)
Background/Aims
HBV has been classified into ten genotypes (A–J) and multiple subgenotypes, some of which strongly influence disease outcome and their distribution also correlate with human migration. HBV infection is highly prevalent in India and its diverse population provides an excellent opportunity to study the distinctiveness of HBV, its evolution and disease biology in variegated ethnic groups. The North-East India, having international frontiers on three sides, is one of the most ethnically and linguistically diverse region of the country. Given the paucity of information on molecular epidemiology of HBV in this region, the study aimed to carry out an in-depth genetic characterization of HBV prevailing in North-East state of Tripura.Methods
From sera of chronically HBV infected patients biochemical/serological tests, HBV DNA quantification, PCR-amplification, sequencing of PreS/S or full-length HBV genomes were done. HBV genotype/subgenotype determination and sequence variability were assessed by MEGA5-software. The evolutionary divergence times of different HBV subgenotypes were estimated by DNAMLK/PHYLIP program while jpHMM method was used to detect any recombination event in HBV genomes.Results
HBV genotypes D (89.5%), C (6.6%) and A (3.9%) were detected among chronic carriers. While all HBV/A and HBV/C isolates belonged to subgenotype-A1 and C1 respectively, five subgenotypes of HBV/D (D1–D5) were identified including the first detection of rare D4. These non-recombinant Indian D4 (IndD4) formed a distinct phylogenetic clade, had 2.7% nucleotide divergence and recent evolutionary radiation than other global D4. Ten unique amino acids and 9 novel nucleotide substitutions were identified as IndD4 signatures. All IndD4 carried T120 and R129 in ORF-S that may cause immune/vaccine/diagnostic escape and N128 in ORF-P, implicated as compensatory Lamivudine resistance mutation.Conclusions
IndD4 has potential to undermine vaccination programs or anti-viral therapy and its introduction to North-East India is believed to be linked with the settlement of ancient Tibeto-Burman migrants from East-Asia. 相似文献14.
Maureen J. Donlin Nathan A. Cannon Rajeev Aurora Jia Li Abdus S. Wahed Adrian M. Di Bisceglie John E. Tavis for the Virahep-C Study Group 《PloS one》2010,5(2)
Background
Hepatitis C virus (HCV) has six major genotypes, and patients infected with genotype 1 respond less well to interferon-based therapy than other genotypes. African American patients respond to interferon α-based therapy at about half the rate of Caucasian Americans. The effect of HCV''s genetic variation on treatment outcome in both racial groups is poorly understood.Methodology
We determined the near full-length pre-therapy consensus sequences from 94 patients infected with HCV genotype 1a or 1b undergoing treatment with peginterferon α-2a and ribavirin through the Virahep-C study. The sequences were stratified by genotype, race and treatment outcome to identify HCV genetic differences associated with treatment efficacy.Principal Findings
HCV sequences from patients who achieved sustained viral response were more diverse than sequences from non-responders. These inter-patient diversity differences were found primarily in the NS5A gene in genotype 1a and in core and NS2 in genotype 1b. These differences could not be explained by host selection pressures. Genotype 1b but not 1a African American patients had viral genetic differences that correlated with treatment outcome.Conclusions & Significance
Higher inter-patient viral genetic diversity correlated with successful treatment, implying that there are HCV genotype 1 strains with intrinsic differences in sensitivity to therapy. Core, NS3 and NS5A have interferon-suppressive activities detectable through in vitro assays, and hence these activities also appear to function in human patients. Both preferential infection with relatively resistant HCV variants and host-specific factors appear to contribute to the unusually poor response to therapy in African American patients. 相似文献15.
16.
Cíntia Bittar Ana Carolina Gomes Jardim Lilian Hiromi Tomonari Yamasaki Claudia Márcia Aparecida Carareto Jo?o Renato Rebello Pinho Philippe Lemey Isabel Maria Vicente Guedes de Carvalho-Mello Paula Rahal 《PloS one》2013,8(4)
Background
Hepatitis C is a disease spread throughout the world. Hepatitis C virus (HCV), the etiological agent of this disease, is a single-stranded positive RNA virus. Its genome encodes a single precursor protein that yields ten proteins after processing. NS5A, one of the non-structural viral proteins, is most associated with interferon-based therapy response, the approved treatment for hepatitis C in Brazil. HCV has a high mutation rate and therefore high variability, which may be important for evading the immune system and response to therapy. The aim of this study was to analyze the evolution of NS5A quasispecies before, during, and after treatment in patients infected with HCV genotype 3a who presented different therapy responses.Methods
Viral RNA was extracted, cDNA was synthesized, the NS5A region was amplified and cloned, and 15 clones from each time-point were sequenced. The sequences were analyzed for evolutionary history, genetic diversity and selection.Results
This analysis shows that the viral population that persists after treatment for most non-responder patients is present in before-treatment samples, suggesting it is adapted to evade treatment. In contrast, the population found in before treatment samples from most end-of-treatment responder patients either are selected out or appears in low frequency after relapse, therefore changing the population structure. The exceptions illustrate the uniqueness of the evolutionary process, and therefore the treatment resistance process, in each patient.Conclusion
Although evolutionary behavior throughout treatment showed that each patient presented different population dynamics unrelated to therapy outcome, it seems that the viral population from non-responders that resists the treatment already had strains that could evade therapy before it started. 相似文献17.
TN Buu D van Soolingen MN Huyen NT Lan HT Quy EW Tiemersma K Kremer MW Borgdorff FG Cobelens 《PloS one》2012,7(8):e42323
Background
Studies have shown that the Mycobacterium tuberculosis Beijing genotype is an emerging pathogen that is frequently associated with drug resistance. This suggests that drug resistant Beijing strains have a relatively high transmission fitness compared to other drug-resistant strains.Methods and Findings
We studied the relative transmission fitness of the Beijing genotype in relation to anti-tuberculosis drug resistance in a population-based study of smear-positive tuberculosis patients prospectively recruited and studied over a 4-year period in rural Vietnam. Transmission fitness was analyzed by clustering of cases on basis of three DNA typing methods. Of 2531 included patients, 2207 (87%) were eligible for analysis of whom 936 (42%) were in a DNA fingerprint cluster. The clustering rate varied by genotype with 292/786 (37%) for the Beijing genotype, 527/802 (67%) for the East-African Indian (EAI) genotype, and 117/619 (19%) for other genotypes. Clustering was associated with the EAI compared to the Beijing genotype (adjusted odds ratio (ORadj) 3.4: 95% CI 2.8–4.4). Patients infected with streptomycin-resistant strains were less frequently clustered than patients infected with streptomycin-susceptible strains when these were of the EAI genotype (ORadj 0.6, 95% CI 0.4–0.9), while this pattern was reversed for strains of the Beijing genotype (ORadj 1.3, 95% CI 1.0–1.8, p for difference 0.002). The strong association between Beijing and MDR-TB (ORadj 7.2; 95% CI 4.2–12.3) existed only if streptomycin resistance was present.Conclusions
Beijing genotype strains showed less overall transmissibility than EAI strains, but when comparisons were made within genotypes, Beijing strains showed increased transmission fitness when streptomycin-resistant, while the reverse was observed for EAI strains. The association between MDR-TB and Beijing genotype in this population was strongly dependent on resistance to streptomycin. Streptomycin resistance may provide Beijing strains with a fitness advantage over other genotypes and predispose to multidrug resistance in patients infected with Beijing strains. 相似文献18.
Jian-Te Lee Pei-Lan Shao Luan-Yin Chang Ning-Shao Xia Pei-Jer Chen Chun-Yi Lu Li-Min Huang 《PloS one》2013,8(6)
Objectives
Hepatitis E virus (HEV) is an emerging pathogen. We evaluated the seroprevalence of HEV infection among swine farmers and the general population in Taiwan, a nonendemic country.Methods
We conducted a cross-sectional seroepidemiologic study in rural Taiwan in 2012 and 2013. The study included swine farmers, health examination attendees, pregnant women, and students. A commercial enzyme-linked immunosorbent assay was used to detect immunoglobulin G (IgG) and IgM against HEV. Pertinent information was collected using a questionnaire.Results
In total, 660 participants were enrolled in the study, including 156 swine farmers, 314 health examination attendees, 100 pregnant women, and 90 students. IgG anti-HEV was detected in 29.5% of swine farmers, 11.5% of health examination attendees, 2% of pregnant women, and 1.1% of students. Two subjects were positive for IgM anti-HEV. Logistic regression analysis revealed that swine farmers had an approximately 3.5-fold increased risk (odds ratio [OR], 3.46; 95% confidence interval [CI], 1.91–6.27; p<0.0001) for being seropositive for IgG anti-HEV as compared to the general population. Age was positively associated with seropositive rate (OR, 1.07 per year; 95% CI, 1.05–1.09; p<0.0001).Conclusion
HEV infection is prevalent in Taiwan. The seroprevalence of HEV infection is high in swine farmers and in the elderly population. 相似文献19.
Background
The rubella vaccine was introduced into the immunization program in 1995 in the Shandong province, China. A series of different rubella vaccination strategies were implemented at different stages of measles control in Shandong province.Methodology/Principal Findings
The average reported incidence rate of rubella cases remained at a low level in Shandong province after 1999. However, rubella epidemics occurred repeatedly in 2001/2002, 2006, and 2008/2009. The age of the onset of rubella cases gradually increased during 1999–2010, which showed that most cases were found among the 10 years old in 1999 and among the 17 years old in 2010. Phylogenetic analysis was performed and a phylogenetic tree was constructed based on the World Health Organization standard sequence window for rubella virus isolates. All rubella viruses isolated in Shandong province were divided into 4 genotypes: 1E, 1F, 2A, and 2B. Genotype 1E viruses accounted for the majority (79%) of all these viruses. The similarity of nucleotide and amino acid sequences among genotype 1E viruses was 98.2–100% and 99.1–100%, respectively. All Shandong genotype 1E strains, differed from international genotype 1E strains, belonged to cluster 1 and interdigitated with the viruses from other provinces in mainland China. The effective number of infections indicated by a Bayesian skyline plot remained constant from 2001 to 2009.Conclusions/Significance
The gradual shift of disease burden to an older age group occurred after a rubella-containing vaccine was introduced into the childhood immunization schedule in 1995 in Shandong province. Four genotypes, including 1E, 1F, 2A, and 2B, were found in Shandong province during 2000–2009. Genotype 1E, rather than genotype 1F, became the predominant genotype circulating in Shandong province from 2001. All Shandong genotype 1E viruses belong to the genotype 1E/cluster 1; they have constantly circulated, and co-evolved and co-circulated, with those from other provinces. 相似文献20.