Molecular Epidemiology of Enteroviruses Associated with Hand, Foot, and Mouth Disease in the Mainland of China

Hand, foot, and mouth disease （HFMD） is a common contagious illness which occurs worldwide both sporadically and in epidemics. The disease mainly affects, children and the typical symptoms, which may resolve spontaneously, include mucocutaneous papulovesicular lesions on the hands, feet, mouth, and buttocks. In rare cases, however, the patients may also develop neurological complications such as neurogenic pulmonary edema,

HIV/AIDS in Asia:The Shape of Epidemics and Their Molecular Epidemiology

The Asia-Pacific region is a home to 60% of the population in the world and to approximately one quarter of people with HIV/AIDS. Close to a million of people has been infected and a half million people died of AIDS annually in Asia,becoming the second largest epicenter of global AIDS epidemic. Molecular epidemiology has been useful tool to track a course of HIV spread. In-depth knowledge from the studies on molecular epidemiology elucidates the dynamics of HIV spread and the interrelationship of epidemics in the different regions in Asia.

Characterization of Avian Influenza A(H7N9) Virus Prevalence in Humans and Poultry in Huai′an,China：Molecular Epidemiology,Phylogenetic,and Dynamics Analyses

Objective To trace the source of human H7N9 cases in Huai＇an and elucidate the genetic characterization of Huai＇an strains associated with both humans and birds in live poultry market.Methods An enhanced surveillance was implemented when the first human H7N9 case was confirmed in Huai＇an.Clinical specimens,cloacal swabs,and fecal samples were collected and screened by real-time reverse transcription-polymerase chain reaction（RT-PCR） for H7N9 virus.The positive samples were subjected to further RT-PCR and genome sequencing.The phylodynamic patterns of H7N9 virus within and separated from Huai＇an and evolutionary dynamics of the virus were analyzed.Results Six patients with H7N9 infection were previously exposed to live poultry market and presented symptoms such as fever（〉38.0 °C） and headaches.Results of this study support the hypothesis that live poultry markets were the source of human H7N9 exposure.Phylogenetic analysis revealed that all novel H7N9 viruses,including Huai＇an strains,could be classified into two distinct clades,A and B.Additionally,the diversified H7N9 virus circulated in live poultry markets in Huai＇an.Interestingly,the common ancestors of the Huai＇an H7N9 virus existed in January 2012.The mean nucleotide substitution rates for each gene segment of the H7N9 virus were（3.09-7.26）×10-3 substitutions/site per year（95% HPD：1.72×10-3 to 1.16×10-2）.Conclusion Overall,the source of exposure of human H7N9 cases in Huai＇an was live poultry market,and our study highlights the presence of divergent genetic lineage of H7N9 virus in both humans and poultry specimens in Huai＇an.

Molecular Epidemiology and Sequencing of the G-L Intergenic Region of Rabies Viruses Isolated in China

一组 25 个狂犬病病毒(RABV ) ，从 24 条狗和一个人的盒子恢复了，在在 2004 和 2006 之间的中国从各种各样的区域被收集。G-L intergenic 区域的基因、种系发生的分析在 25 街 RABV 被执行孤立， CTN 疫苗 7 拉紧代。学习基于 519 bp 核苷酸顺序的比较，包含 G-L intergenic 区域。中国街紧张的核苷酸顺序相同从 95.5% ～ 100% 。种系发生的分析证明中国的所有孤立清楚地在 Lyssavirus 遗传型 1 支持了所有中国病毒的放置，他们根据他们的地理起源是分布式的。所有仔细中国紧张被联系，但是他们能仍然被划分成二个组：一些街紧张和一些 CTN 紧张。这研究基于 G-L Intergenic 区域的序列关于狂犬病病毒的分子的传染病学介绍细节。关键词狂犬病病毒 - 分子的传染病学 - G-L intergenic 区域 - 中国 CLC 数字 R373.33 基础条款：第 10 国家 five-year-plan (2004BA718 b03 ) 的关键技术 R&D

Neosporosis: An Overview of Its Molecular Epidemiology and Pathogenesis

Neospora caninum (N. caninum), a cyst-forming protozoan parasite, is a major cause of bovine abortions and neonatal mortality worldwide. N. caninum has a broad intermediate host range, and its sexual cycle occurs exclusively in canids. Another species of Neospora, Neospora hughesi (N. hughesi), has been identified and causes myeloencephalitis in horses. Although molecular epidemiology studies are in their infancy, the 18S ribosomal RNA (rRNA) and ITS1 regions within the small subunit ribosomal RNA (ssuRNA) and an N. caninum species-specific DNA probe (pNc5) have been used extensively to differentiate Neospora from other closely related apicomplexan parasites. While these repetitive regions have higher sensitivity and specificity than housekeeping or antigen genes, they suffer from low discriminatory power and fail to capture intra-species diversity. Similarly, although multiple minisatellite or microsatellite marker studies have shown clear geographic substructures within Neospora, strains are often misclassified due to a convergence in the size of different alleles at microsatellite loci, known as homoplasy. Only one strain, N. caninum Liverpool (Nc-Liv), has been genome sequenced and compared with its closest relative, Toxoplasma gondii (T. gondii). Hence, detailed population genomics studies based on whole-genome sequences from multiple strains worldwide are needed in order to better understand the current population genetic structure of Neospora, and ultimately to determine more effective vaccine candidates against bovine neosporosis. The aim of this review is to outline our current understanding of the molecular epidemiology and genomics of Neospora in juxtaposition with the closely related apicomplexan parasites Hammondia hammondi and T. gondii.

Biochemical and Molecular Epidemiology of Cancer

Examples of practical approaches to molecular epidemiology of human cancer are described. Biomarkers of carcinogen exposure or inherited host factors for cancer susceptibility are discussed. Major advances have been made in the detection of carcinogen-macromolecular adducts through the use of high performance liquid chromatography, immunoaffinity chromatography, the 32P-postlabeling assay, enzyme immunoassays, gas chromatography/mass spectroscopy and synchronous spectrophotofluorimetry. The polycyclic aromatic hydrocarbon- DNA adducts are the most extensively studied in this field and together with antibodies to these adducts found in human serum, they have become useful indicators of exposure to carcinogens. Assays for various kinds of alky 1-DNA adducts have also been developed and the presence of these adducts have been documented in human tissues. Carcinogen-protein adducts have proven to be useful molecular dosimeters of carcinogen exposure. For example, 4-aminobiphenyl hemoglobin adducts are highly correlated with exposure to tobacco smoke. The study of the molecular aspects of interindividual differences in the metabolism and activation of xenobiotics and other genetic markers [DNA-restriction fragment length polymorphisms (RFLPs), mutations, and functional loss of specific genes in carcinogenesis] is an emerging new field that is discussed in the context of genetic susceptibility to cancer. The cytochrome P450 phenotypes and acetylation phenotype are examples of genetic markers that indicate an individual's potential for metabolism of exogenous substances. Further, inherited genetic polymorphic markers, e.g., DNA-RFLPs at protooncogene loci (HRAS-1 and L-myc) have been examined in a case-control study of lung cancer. Data concerning mutations of protooncogenes (H-, K-, and N-RAS) and tumor suppressor genes (retinoblastoma and p53 genes) in various common cancers are providing evidence of multiple genetic lesions that occur during the multistage process of carcinogenesis.

Molecular epidemiology of hepatitis B virus in Asia

Although safe and effective vaccines against hepatitis B virus(HBV) have been available for three decades, HBV infection remains the leading cause of chronic hepatitis, cirrhosis and hepatocellular carcinoma(HCC) worldwide, especially in Asian countries. HBV has been classified into at least 9 genotypes according to the molecular evolutionary analysis of the genomic DNA sequence and shown to have a distinct geographical distribution. Novel HBV genotypes/subgenotypes have been reported, especially from Southeast Asian countries. The clinical characteristics and therapeutic effectiveness of interferon(IFN) and nucleos(t)ide analogues vary among different HBV genotypes. Mutations at T1653 C in subgenotype C2 from Japan and South Korea, C/A1753 T and C1858 T in subgenotype C1 from Vietnam, and C1638 T and T1753 V in subgenotype B3 from Indonesia were reported to be associated with advanced liver diseases including HCC. Genotype distribution in Japan has been changed by an increasing ratio of subgenotype A2 in chronic hepatitis B. While a large number of epidemiological and clinical studies have been reported from Asian countries, most of the studies were conducted in developed countries such as Taiwan, China, South Korea and Japan. In this review, the most recent publications on the geographical distribution of genetic variants of HBV and related issues such as disease progression and therapy in Asia are updated and summarized.

Molecular epidemiology of HIV-1 strains in the south-east and east of Turkey

Objective:To detect the subtype characterization and drug-resistant mutations in HIV-1 strains after the refugee movement from Syria to Turkey between 2011 and 2014 in south east border lines. Methods: A total of 65 patients were included in this study, of which 57(88%) patients were antiretroviral therapy-naive patients. HIV-1 RNA was detected and quantii ed by realtime PCR assay. HIV-1 subtypes and circulating recombinant forms(CRFs) were identii ed by phylogenetic analysis(neighbor-joining method), and drug-resistant mutations were analyzed.Results: Three major HIV groups were indicated. Two of these groups were located in subtype B. The other group showed heterogeneity. Subtype B(48/65, 73.8%), followed by CRFs(12/65, 18.5%) was the most common strain. Subtype of CRFs consisted of CRF01_AE(9/65, 13.8%) and CRF02_AG(3/65, 4.6%). Subtype C(1/65, 1.5%), sub-subtypes A1(2/65, 3.1%) and F1(2/65, 3.1%) were also detected with low prevalence. The rate of overall primary antiretroviral resistance was 4.9%(3/61). Drug-resistant rate for non-nucleoside reverse transcriptase inhibitors was 4.9%. The thymidine analogue mutation rate was 13.1%(8/61).Conclusions: HIV molecular epidemiology studies are necessary to determine transmission patterns and spread. Subtype B and CRF01_AE, CRF02_AG are the most prevalent strains in the south-east of Turkey. However, subtype C, sub-subtypes A1 and F1 are of low prevalence but persist in the south-east of Turkey. In the near future, changing of HIV epidemiology will be possible in Turkey due to migration movement in border lines and resistance testing will play an important role in HIV management.

Analysis on drug-resistance and molecular epidemiology of Acinetobacter baumannii isolated from the clinical samples in two Chinese hospitals

In the present study, the drug-resistance genes encoding β-lactamases, aminoglycoside modifying enzymes, DNA topoisomerases and integron as well as their molecular epidemiology were investigated by means of analyzing the drug-resistance and molecular epidemiology of Acinebacter baumannii isolated from the clinical samples in two hospitals in Changzhou and Huzhou city of Jiangsu and Zhejiang province from July 2000 to March 2005. The minimal inhibitory concentrations （MICs） of these 307 isolates were detected by automatic microbiological system, and 35 strains against 5-fluoroquinolones were performed by agar dilution assay. Meanwhile, the resistant genes in 80 isolates were amplified by PCR with identification by DNA sequencer. It was found that most of the 307 isolates of A. baumannii were resistant to multiple antibiotics tested, in which the resistance rates of the isolates against piperacillin, piperacillin/tazobactam, amoxacillin/clavulanic acid, cefotaxime, ceftazidime, cefepime, gentamicin, amikacin, ciprofloxacin, chloramphenicol and sulfamethoxazole/trimethoprim were all above 35%, but those of imipenem and meropenem were quite low, ranged only 2.6% and 3.3 %. In addition, it was also demonstrated that the positive rates of TEM and SHV β-lactamase genes accounted for 93.8% and 22.5% respectively, and those of the aminoglycoside-modifying enzyme genes including aacC1, aacC2, aacC3, aacC4, aacC4A, aphA6, ant（2″）-Ⅰ and ant（3″）- Ⅰ were 58.8%, 8.8%, 7.5%, 28.8%, 45.0%, 2.5%, 28.8% and 65.0% respectively. The mutations in the quinolone-resistant determining region （QRDR） of gyrA and parC genes indicated that substitution in Ser-83 residue of GyrA protein was most frequently occurred among strains with MIC for ciprofloxacin of more than 4 μg/ml, whereas a double mutation at Ser-83 residue of gyrA and Ser-80 of parC was found in strains with MIC of ciprofloxacin of more than 8 μg/ml. As to the positive rates of class 1 integron （Int Ⅰ -1） and qacE△1-sul-1, it was found to be 60.0% and 77.5% respectively, and the rates of resistant genes of strains isolated in these two hospitals varied considerably. The results obtained in the present study indicate the presence of the multiple resistant genes in strains of A. baumannii, and great measures should be taken to control the spread of the resistant strains carrying the resistant genes.

Epidemic and Maintenance of Rabies in Chinese Ferret Badgers (Melogale moschata) indicated by Epidemiology and the Molecular Signatures of Rabies Viruses

An epidemic of Chinese ferret badger-associated human rabies was investigated in Wuyuan county, Jiangxi province and rabies viruses isolates from ferret badgers in different districts in Jiangxi and Zhejiang provinces were sequenced with their nucleotides and amino acids and aligned for epidemiological analysis. The results showed that the human rabies in Wuyuan are only associated with ferret badger bites; the rabies virus can be isolated in a high percentage of ferret badgers in the epidemic areas in Jiangxi and Zhejiang provinces; the isolates share the same molecular features in nucleotides and have characteristic amino acid signatures, i.e., 2 sites in the nucleoprotein and 3 sites in the glycoprotein, that are distinct from virus isolates from dogs in the same region. We conclude that rabies in Chinese ferret badgers has formed an independent transmission cycle and ferret badgers may serve as another important rabies reservoir independent of dog rabies in China.

Molecular epidemiology of DNA repair gene polymorphisms and head and neck cancer

Although tobacco and alcohol consumption are two common risk factors of head and neck cancer （HNC）, other specific etiologic causes, such as viral infection and genetic susceptibility factors, remain to be understood. Hu- man DNA is often damaged by numerous endogenous and exogenous mutagens or carcinogens, and genetic vari- ants in interaction with environmental exposure to these agents may explain interindividual differences in HNC risk. Single nucleotide polymorphisms （SNPs） in genes involved in the DNA damage-repair response are reported to be risk factors for various cancer types, including HNC. Here, we reviewed epidemiological studies that have assessed the associations between HNC risk and SNPs in DNA repair genes involved in base-excision repair, nucleotide-excision repair, mismatch repair, double-strand break repair and direct reversion repair pathways. We found, however, that only a few SNPs in DNA repair genes were found to be associated with significantly in- creased or decreased risk of HNC, and, in most cases, the effects were moderate, depending upon locus-locus in- teractions among the risk SNPs in the pathways. We believe that, in the presence of exposure, additional pathway- based analyses of DNA repair genes derived from genome-wide association studies （GWASs） in HNC are needed.

Molecular Epidemiology and Risk Factors of Herpes Simplex Virus Type 2 in Pregnant Women

Background:Herpes simplex virus type 2(HSV-2)infection is the main cause of genital and neonatal herpes infections.It has considerable public health importance among women as the virus may lead to adverse outcomes in pregnancy and neonatal infection.This study determines the molecular epidemiology and risk factors ofHSV-2 infection among pregnant women.Methods:In this cross-sectional study,all pregnant women admitted to three university hospitals for natural birth and Caesarean sections were enrolled.HSV detection and typing were carried out based on PCR and reverse dot blotting method,respectively.ANOVA and bivariate correlations were used to analyze the data.Results:In this study,the prevalence of genital herpes infection was 5.7%.A significant positive correlation was found between age group<25 years and HSV-2 shedding(P=0.026).Twelve participants(60%)with HSV-2 shedding were younger than 25.A significant correlation was found between the presence of genital lesion and HSV-2(P=0.02).Among participants with HSV-2 infection,the use of condom was low.Neonatal complications were not seen in newborns from mothers with HSV-2 shedding.Conclusion:PCR assay may help in promoting early diagnosis and more effective treatment for patients.Also,it shortens hospital stay and enhances patients?condition.HSV-2 transmission is rapid following the onset of sexual activity and likely to result in the significant prevalence of genital disease.

Molecular Epidemiology of Nontuberculous Mycobacteria in a German CF Center and Clinical Course of NTM Positive Patients

Goal of this study was to analyse the clinical course of cystic fibrosis (CF) patients with nontuberculous mycobacteria (NTM) in their respiratory secretions and to investigate the molecular epidemiology of the most prevalent NTM species by multilocus sequence analysis (MLSA). The respiratory specimen and the clinical parameters forced expiratory volume in one second (FEV1), body-mass-index (BMI), erythrocyte sedimentation rate (ESR) 1 h and immunoglobulin G (IgG) of 357 CF patients, 0 - 52.4 years, mean FEV1 2009 81.5% pred were analysed between 1998 and 2010. In 13 patients NTM were detected. 12 of 13 patients carried M. abscessus, for one patient the NTM species was not characterized. 4 patients carried a second NTM species (M. avium, M. chelonae (2x), M. intracellulare). 6 patients exhibited a significant decline in FEV1, however changes in BMI, IgG and ESR were discordant. Molecular genotyping of M. abscessus isolates revealed a unique MLSA pattern in 6 patients. 2 patients harboured identical strains, and one patient a closely related strain. Whether the presence of identical strains is attributed to the acquisition of NTM clones from common environmental sources or to patient-to-patient transmission cannot be definitely clarified. Although cross-in- fection of the three patients with identical/closely related strains in the present cohort is highly unlikely, we recommend strict hygiene measures for all CF patients harbouring NTM.

Molecular Epidemiological Characteristics of Streptococcus pyogenes Strains Involved in an Outbreak of Scarlet Fever in China,2011

Objective To investigate molecular characterization of streptococcus pyogenes isolates involved in an outbreak of scarlet fever in China in 2011. Methods Seventy-four 5treptococcol pyogenes involved in an outbreak of scarlet fever were isolated from pediatric patients in the areas with high incidence in China from May to August of 2011. Emm genotyping, pulsed-field gel electrophoresis （PFGE）, superantigen （SAg） genes and antimicrobial susceptibility profiling were analyzed for these isolates. Results A total of 4 different emm types were identified. Emm12 was the most prevalent type which contained four predominating PFGE patterns corresponding to four different virulence and superantigen profiles. Emm12（79.7%） and emml （14.9%） accounted for approximately 94% of all the isolates. The speA gene was all negative in emm12 isolates and positive in emml isolates. All strains were resistant to erythromycin, and 89.4% of them were resistant to erythromycin, tracycline, and clindamycin simultaneously. Conclusion Several highly diversified clones with a high macrolide resistance rate comprise a predominant proportion of circulating strains, though no new emm type was found in this outbreak. The data provide a baseline for further surveillance of scarlet fever, which may contribute to the explanation of the outbreak and development of a GAS vaccine in China.

Molecular analysis of hepatitis B virus isolates in Mexico:Predominant circulation of hepatitis B virus genotype H

AIM: To determine the genotypes in Mexican hepatitis Bvirus (HBV) isolates and characterize their precore andcore promoter mutations.METHODS: Forty-nine HBV isolates of Mexico obtainedfrom sera of 15 hepatitis patients, 6 hemodialysis pa-tients, 20 men seeking HIV testing, and 8 AIDS patientswere analyzed. HBV isolates were amplified by PCR,and genotyped by line probe assay (INNO-LiPA HBVGenotyping; INNOGENETICS N V, Ghent, Belgium).HBV genotype confirmation was performed by DNAsequencing part of the sAg region. Precore and core pro-moter mutation characterization was performed by lineprobe assay (INNO-LiPA HBV PreCore; INNOGENETICS NV, Ghent, Belgium).RESULTS: Overall, HBV genotype H was found in 37(75.5%) out of the 49 isolates studied. HBV genotypesG, A, and D were found in 5 (10.2%), 4 (8.2%), and 3(6.1%) isolates, respectively. HBV genotype H was pre-dominant in isolates from hemodialysis patients (100%),hepatitis patients (80%), and men seeking HIV test-ing (75%), and accounted for half of infections in AIDSpatients (50%). Six (12.2%) out of the 49 HBV isolatesshowed both wild type and mutant populations at pre-core codon 28. These mixed wild type and precore mu-tant populations were observed in one HBV genotype Aisolate and in all HBV genotype G isolates. A dual variantcore promoter mutation was observed in 1 (2%) of theisolates, which was genotype H.CONCLUSION: HBV genotype H is highly predominantin HBV isolates of Mexico followed by genotypes G, Aand D. A low frequency of precore and core promotermutations is observed in HBV Mexican isolates.

Molecular Epidemiological Analysis of Echovirus 19 Isolated From an Outbreak Associated With Hand, Foot, and Mouth Disease (HFMD) in Shandong Province of China

To elucidate the genetic characterization and molecular epidemiological features of Echovirus 19 （El9） isolates collected from an outbreak associated with hand, foot and mouth disease （HFMD） in Tai＇an city of Shandong Province of China from July to September, 2003. Methods Thirty seven Echovirus 19 isolates were isolated from stool specimens and throat swabs collected during the outbreak, then major capsid （VP1） genomic sequence was determined, and phylogenetic tree was done based on the VP1 sequences among these 37 and other El9 viruses deposited in the Genbank. Also a representative strain named CHN-SD03-TN12 was selected for sequencing of 5′-untranslated regions （5′-UTR）. Results The identity rate was about 98.9%-100% among all these 37 El9 viruses. The genetic relationships between these 37 El9 isolates and other strains reported were also depicted. The identity rate was about 78.4%-78.9% compared with El9 reference strain Burke. The substitutions in the sequence of 5′-UTR resulted in changes in the conjectural properties of 5′-UTR of El9 viruses. Condusion The genetic features of El9 viruses isolated during the outbreak in Shandong Province in 2003 may be associated with a genetic and antigenic drift that changes the virulence of the Shandong isolates, but the molecular changes in Shandong El9 viruses contributing to their phenotype remain to be further illuminated. However, the sequences described in this paper substantiate the changes taken place in capsid VPI and 5′UTR regions. These substitutions may contribute to their tropism and virulence, and play a significant role in pathogenesis and clinical manifestations of the disease.

Molecular epidemiological study on pre-X region of hepatitis B virus and identification of hepatocyte proteins interacting with whole-X protein by yeast two-hybrid

AIM: To identify the pre-X region in hepatitis B virus (HBV)genome and to study the relationship between the genotype and the pre-X region. To investigate the biological function of whole-X (pre-X plus X) protein, we performed yeast two-hybrid to screen proteins in liver interacting with whole-X protein.METHODS: The pre-X region of HBV was amplified by polymerase chain reaction (PCR) method, and was cloned to pGEM Teasy vector. After the target region was sequenced, Vector 8.0 software was used to analyze the sequences. The whole-X bait plasmid was constructed by using yeast two-hybrid system 3. Yeast strain AH109 was transformed. After expression of the whole-X protein in AH109 yeast strains was proved, yeast two-hybrid screening was performed by mating AH109 with Y187 containing liver cDNA library plasmid. The mated yeast was plated on quadruple dropout medium and assayed for α-gal activity. The interaction between whole-X protein and the protein obtained from positive colonies was further confirmed by repeating yeast two-hybrid. After extracting and sequencing of plasmid from blue colonies, we carried out analysis by bioinformatics. RESULTS: After sequencing, 27 of 45 clones (60%) were found encoding the pre-X peptide. Eighteen of twenty-seven clones (66.7%) of pre-X coding sequences were found from genotype C. Five positive colonies that interacted with whole-X protein were obtained and sequenced; namely, fetuin B, UDP glycosyltransferase 1 family-polypeptide A9, mannose-P-dolichol utilization defect 1, fibrinogen-B beta polypeptide, transmembrane 4 superfamily member 4CD81 (TM4SF4).CONCLUSION: The pre-X gene exists in HBV genome.Genes of proteins interacting with whole-X protein in hepatocytes were successfully cloned. These results brought some new clues for studying the biological functions of whole-X protein.

Bladder cancer epidemiology and genetic susceptibility

Bladder cancer is the most common malignancy of the urinary system. The incidence of bladder cancer of men is higher than that of women （approximately 4：1）. Here, we summarize the bladder cancer-related risk factors, in- cluding environmental and genetic factors. In recent years, although the mortality rate induced by bladder cancer has been stable or decreased gradually, the public health effect may be pronounced. The well-established risk fac- tors for bladder cancer are cigarette smoking and occupational exposure. Genetic factors also play important roles in the susceptibility to bladder cancer. A recent study demonstrated that hereditary non-polyposis colorectal cancer is associated with increased risk of bladder cancer. Since 2008, genome-wide association study （GWAS） has been used to identify the susceptibility loci for bladder cancer. Further gene-gene or gene-environment interaction stud- ies need to be conducted to provide more information for the etiology of bladder cancer.

Molecular Epidemiological Analysis of Group A Streptococci Isolated from Children in Chaoyang District of Beijing, 2011:emm Types, Virulence Factor Genes and Erythromycin Resistant Genes

Group A streptococcus （GAS） causes a wide range of diseases in the human population. GAS diseases are more common in children than in adults, with clinical manifestations ranging from pharyngitis and impetigo to invasive infections and post streptococcal sequelae, such as acute rheumatic fever and acute post-streptococcal glomerulonephritis[1]. GAS harbors a host of virulence factors that contribute to its complex pathogenicity and differences in the disease severity and frequency. M protein, one of the major virulence factors, is encoded by the emm gene induces a type of specific host immune response and confers antiphagocytic properties.

A MOLECULAR EPIDEMIOLOGIC MARKER OF HEPATOCELLULAR CARCINOMA FROM AFLATOXIN B1 CONTAMINATED AREA IN THE SOUTHWEST OF GUANGXI

HCC specimens from high and low AFB1 risk areas in Guangxi showed different frequency of p53 mutational hot spot, which were 20/35 (57%) and 1/10 by DNA sequencing and 36/52 (69%) and 2/10 by RFLP analysis respectively. Their differences were significant (P<0.01). Mutational points of p53 gene induced by AFB1 mutagen almost exclusively clustered at codon 249 third nucleotide and by the form of G to T transversion only. We call it 'AFB1 mutational hot spot'. It turns out to be a significant marker for molecular epidemio logic survey to decide how many HCC and which individuals are induced by AFB1 mutagen, and if emergence of this marker in HCC is frequent in certain region it indicated that there is heavy contamination by AFB1.