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The American Journal of Tropical... Oct 2019National border areas are special places for the spread of (MTB). These regions concentrate vulnerable populations and constant population movements. Understanding the...
National border areas are special places for the spread of (MTB). These regions concentrate vulnerable populations and constant population movements. Understanding the dynamics of the transmission of MTB is fundamental to propose control measures and to monitor drug resistance. We conducted a population-based prospective study of tuberculosis (TB) to evaluate molecular characteristics of MTB isolates circulating in Roraima, a state on the border of Venezuela and Guyana. Eighty isolates were genotyped by IS-RFLP (restriction fragment length polymorphism), spoligotyping, and 24-locus mycobacterial interspersed repetitive unit-variable number of repeats tandem (MIRU-VNTR). Drug susceptibility tests were performed by using the proportion method and GeneXpert MTB/RIF (Cepheid, Sunnyvale, CA). Isolates showing a phenotypic resistance profile were submitted to polymerase chain reaction (PCR) and sequencing. Spoligotyping showed 40 distinct patterns with a high prevalence of Latin-American and Mediterranean (LAM), Haarlem (H), and the "ill-defined" T clades. Mycobacterial interspersed repetitive unit -VNTR and IS-RFLP showed clustering rates of 21.3% and 30%, respectively. Drug resistance was detected in 11 (15.1%) isolates, and all were found to have primary resistance; among these, six (8.2%) isolates were streptomycin mono-resistant, four (5.4%) isoniazid mono-resistant, and one (1.3%) multidrug resistant. This is the first study on the molecular epidemiology and drug resistance profile of MTB from Roraima. Herein, we describe high diversity of genetic profiles circulating in this region that may be driven by the introduction of new strain types because of large population flow in this region. In summary, our results showed that analyses of these circulating strains can contribute to a better understanding of TB epidemiology in the northern Brazilian border and be useful to establish public health policies on TB prevention.
Topics: Adolescent; Adult; Brazil; Cluster Analysis; Drug Resistance, Bacterial; Female; Genetic Variation; Genotype; Humans; Male; Middle Aged; Minisatellite Repeats; Molecular Epidemiology; Mycobacterium tuberculosis; Polymorphism, Restriction Fragment Length; Prospective Studies; Tuberculosis; Young Adult
PubMed: 31392954
DOI: 10.4269/ajtmh.19-0324 -
Journal of Medical Virology Nov 2019Chikungunya, caused by the chikungunya virus (CHIKV) mostly presents as acute and chronic articular inflammatory manifestations. Interleukin 1 receptor antagonist...
Chikungunya, caused by the chikungunya virus (CHIKV) mostly presents as acute and chronic articular inflammatory manifestations. Interleukin 1 receptor antagonist (IL-1RN) is a potent endogenous competitive inhibitor of IL-1α and 1β and has an anti-inflammatory role. The present study evaluated the possible association of IL1RN variable number tandem-repeat (VNTR) alleles and genotypes, and CHIKV stimulated IL-1RN cytokine production with resistance and/or susceptibility to chikungunya infection and disease state in 224 patients with chikungunya (61 patients with acute chikungunya and 163 patients with chronic chikungunya) and 355 healthy controls. Polymerase chain reaction, CHIKV stimulated cytokine assay and luminex platform were used for assessing polymorphism and protein levels respectively. The study revealed a significant association of IL1RN*1/*1 genotype under recessive genetic model with the risk of developing chikungunya infection. Our findings also indicated that IL1RN *2 allele under dominant mode was associated with protection to chronic chikungunya. The results also revealed a higher production of IL-1 RN protein in patients with chronic chikungunya. To conclude, the results suggest the association of ILRN VNTR polymorphism and IL-RN protein levels with chronic chikungunya.
Topics: Adolescent; Adult; Aged; Alleles; Chikungunya Fever; Child; Child, Preschool; Chronic Disease; Cytokines; Female; Genetic Association Studies; Genetic Predisposition to Disease; Genotype; Humans; India; Interleukin 1 Receptor Antagonist Protein; Male; Middle Aged; Minisatellite Repeats; Polymorphism, Genetic; Young Adult
PubMed: 31294845
DOI: 10.1002/jmv.25546 -
Clinical Laboratory Oct 2020Brucellosis is considered a main health concern in humans and animals. Neither familiar molecular methods nor the classical biotyping techniques are acceptable for...
BACKGROUND
Brucellosis is considered a main health concern in humans and animals. Neither familiar molecular methods nor the classical biotyping techniques are acceptable for subtyping Brucella spp. Loci containing variable number tandem repeats (VNTRs) have recently demonstrated their practicality in typing isolates from human and animal origin despite the excessive genetic homogeneity in the genus Brucella.
METHODS
The genotypic characteristics of sixty-six Brucella melitensis and thirty-four Brucella abortus isolates from veterinary samples and human brucellosis cases in Iran during 2014 - 2018. They were analyzed using multiple-locus variable-number tandem-repeat analysis (MLVA) which consisted of sixteen primer pairs and designed and classified as belonging to one of the three panels: panel 1 (MLVA-8: eight loci including Bruce06, Bruce08, Bruce11, Bruce12, Bruce42, Bruce43, Bruce45, and Bruce55), panel 2A (three loci including Bruce18, Bruce19, and Bruce21), and panel 2B (five loci including Bruce04, Bruce07, Bruce09, Bruce16, and Bruce30); MLVA-11 (panels 1 and 2A), and MLVA-16 (panels 1, 2A, and 2B) using BioNumerics software (Version 7.6).
RESULTS
Using panel 1, 2A, and 2B (MLVA-16), 59 genotypes with a genetic similarity coefficient ranging from 91 to 100% were obtained from the 100 Brucella spp. isolates. For all isolates, only genotype 36 and genotype 26 were obtained using panels 1 and 2A, respectively. The B. abortus isolates showed variations at 9 different genotypes, while B. melitensis isolates have been dispersed in 50 different genotypes. Bruce16 and Bruce4 showed the highest discriminatory power.
CONCLUSIONS
The MLVA-16 assay appeared to be a useful and important molecular genotyping tool that is capable of proving epidemiological linkages in outbreak and trace-back investigations and is helpful in improving the effectiveness of brucellosis control programs.
Topics: Animals; Brucella melitensis; Brucellosis; DNA, Bacterial; Genotype; Humans; Iran; Minisatellite Repeats
PubMed: 33073952
DOI: 10.7754/Clin.Lab.2020.200119 -
Scientific Reports Apr 2020Tuberculosis (TB) is a significant public health problem in Ecuador with an incidence of 43 per 100,000 inhabitants and an estimated multidrug-resistant-TB prevalence in...
Tuberculosis (TB) is a significant public health problem in Ecuador with an incidence of 43 per 100,000 inhabitants and an estimated multidrug-resistant-TB prevalence in all TB cases of 9%. Genotyping of Mycobacterium tuberculosis (MTBC) is important to understand regional transmission dynamics. This study aims to describe the main MTBC lineages and sublineages circulating in the country. A representative sample of 373 MTBC strains from 22 provinces of Ecuador, with data comprising geographic origin and drug susceptibility, were genotyped using 24 loci-MIRU-VNTR. For strains with an ambiguous sublineage designation, the lineage was confirmed by Regions of Difference analysis or by Whole Genome Sequencing. We show that lineage 4 is predominant in Ecuador (98.3% of the strains). Only 4 strains belong to lineages 2-sublineage Beijing and two strains to lineage 3-sublineage Delhi. Lineage 4 strains included sublineages LAM (45.7%), Haarlem (31.8%), S (13.1%), X (4.6%), Ghana (0.6%) and NEW (0.3%). The LAM sublineage showed the strongest association with antibiotic resistance. The X and S sublineages were found predominantly in the Coastal and the Andean regions respectively and the reason for the high prevalence of these strains in Ecuador should be addressed in future studies. Our database constitutes a tool for MIRU-VNTR pattern comparison of M. tuberculosis isolates for national and international epidemiologic studies and phylogenetic purposes.
Topics: Antitubercular Agents; DNA, Bacterial; Drug Resistance, Microbial; Ecuador; Genetic Variation; Humans; Minisatellite Repeats; Molecular Epidemiology; Multilocus Sequence Typing; Mycobacterium tuberculosis; Phylogeny; Tuberculosis; Whole Genome Sequencing
PubMed: 32277077
DOI: 10.1038/s41598-020-62824-z -
Microbial Drug Resistance (Larchmont,... Jan 2022To determine the molecular strain typing and drug resistance pattern of serovar Typhi prevalent in Northwest Pakistan. A total of 2,138 blood samples of suspected...
To determine the molecular strain typing and drug resistance pattern of serovar Typhi prevalent in Northwest Pakistan. A total of 2,138 blood samples of suspected typhoid patients from Northwest Pakistan were collected followed by identification of Typhi through biochemical, serological, and species-specific gene amplification. These isolates were typed by variable-number tandem repeat (VNTR) profiling and investigated for drug resistance. The overall prevalence of Typhi was found to be 8.8% ( = 189). Thirty different VNTR strain types of Typhi were detected and the most prevalent strain types were T1 and T4, whereas T27 was less prevalent strain. Among the 189 isolates 175 (92.5%) isolates were multidrug resistant, whereas 12 (5.8%) isolates were extensively drug resistant. Resistance to imipenem in Typhi was not observed. Most of the isolates have genes encoding for resistance to fluoroquinolones, including ( = 164), ( = 160), ( = 164), ( = 160), (6')-- ( = 163), ( = 15), and ( = 3). Similarly, chloramphinicol ( = 147), azithromycin ( = 3), and co-trimoxazole ( = 145 resistance genes were detected among Typhi isolates. In this study, T1 and T4 type Typhi strains were predominantly prevalent in Northwest Pakistan. Antibiotic resistance among Typhi isolates were observed. Findings of the study would be helpful to devise an appropriate antibiotic policy to control the emergence of drug-resistant Typhi in Pakistan.
Topics: Anti-Bacterial Agents; Cross Infection; Drug Resistance, Multiple, Bacterial; Genes, Bacterial; Humans; Microbial Sensitivity Tests; Minisatellite Repeats; Molecular Typing; Pakistan; Salmonella typhi; Tertiary Care Centers
PubMed: 34357814
DOI: 10.1089/mdr.2020.0304 -
Tuberculosis (Edinburgh, Scotland) Sep 2019The molecular epidemiology of Mycobacterium tuberculosis (M. tuberculosis, Mtb) is poorly documented in Ethiopia. The data that exists has not yet been collected in an... (Meta-Analysis)
Meta-Analysis
The molecular epidemiology of Mycobacterium tuberculosis (M. tuberculosis, Mtb) is poorly documented in Ethiopia. The data that exists has not yet been collected in an overview metadata form. Thus, this review summarizes available literature on the genomic diversity, geospatial distribution and transmission patterns of Mtb lineages (L) and sublineages in Ethiopia. Spoligotyping and Mycobacterial Interspersed Repetitive Units-Variable Number Tandem Repeats (MIRU-VNTR) based articles were identified from MEDLINE via PubMed and Scopus. The last date of article search was done on 12th February 2019. Articles were selected following the PRISMA flow diagram. The proportion of (sub)lineages was summarized at national level and further disaggregated by region. Clustering and recent transmission index (RTI) were determined using metan command and random effect meta-analysis model. The meta-analysis was computed using Stata 14 (Stata Corp. College Station, TX, USA). Among 4371 clinical isolates, 99.5% were Mtb and 0.5% were M. bovis. Proportionally, L4, L3, L1 and L7 made up 62.3%, 21.7%, 7.9% and 3.4% of the total isolates, respectively. Among sublineages, L4.2. ETH/SIT149, L4.10/SIT53, L3. ETH1/SIT25 and L4.6/SIT37 were the leading clustered isolates accounting for 14.4%, 9.7%, 7.2% and 5.5%, respectively. Based on MIRU-VNTR, the rate of clustering was 41% and the secondary case rate from a single source case was estimated at 29%. Clustering and recent transmission index was higher in eastern and southwestern Ethiopia compared with the northwestern part of the country. High level of genetic diversity with a high rate of clustering was noted which collectively mirrored the phenomena of micro-epidemics and super-spreading. The largest set of clustered strains deserves special attention and further characterization using whole genome sequencing (WGS) to better understand the evolution, genomic diversity and transmission dynamics of Mtb.
Topics: Bacterial Typing Techniques; Bias; Cluster Analysis; Ethiopia; Genetic Variation; Humans; Minisatellite Repeats; Mycobacterium tuberculosis; Phylogeny; Tuberculosis
PubMed: 31430694
DOI: 10.1016/j.tube.2019.101858 -
European Journal of Human Genetics :... Feb 2023Despite substantial efforts in identifying both rare and common variants affecting disease risk, in the majority of diseases, a large proportion of unexplained genetic...
Despite substantial efforts in identifying both rare and common variants affecting disease risk, in the majority of diseases, a large proportion of unexplained genetic risk remains. We propose that variable number tandem repeats (VNTRs) may explain a proportion of the missing genetic risk. Herein, in a pilot study with a retrospective cohort design, we tested whether VNTRs are causal modifiers of breast cancer risk in 347 female carriers of the BRCA1 185delAG pathogenic variant, an important group given their high risk of developing breast cancer. We performed targeted-capture to sequence VNTRs, called genotypes with adVNTR, tested the association of VNTRs and breast cancer risk using Cox regression models, and estimated the effect size using a retrospective likelihood approach. Of 303 VNTRs that passed quality control checks, 4 VNTRs were significantly associated with risk to develop breast cancer at false discovery rate [FDR] < 0.05 and an additional 4 VNTRs had FDR < 0.25. After determining the specific risk alleles, there was a significantly earlier age at diagnosis of breast cancer in carriers of the risk alleles compared to those without the risk alleles for seven of eight VNTRs. One example is a VNTR in exon 2 of LINC01973 with a per-allele hazard ratio of 1.58 (1.07-2.33) and 5.28 (2.79-9.99) for the homozygous risk-allele genotype. Results from this first systematic study of VNTRs demonstrate that VNTRs may explain a proportion of the unexplained genetic risk for breast cancer.
Topics: Female; Humans; Minisatellite Repeats; Breast Neoplasms; Retrospective Studies; Likelihood Functions; Pilot Projects; Risk Factors; Alleles; BRCA1 Protein
PubMed: 36434258
DOI: 10.1038/s41431-022-01238-z -
BMC Infectious Diseases Mar 2023Mycobacterium tuberculosis genotyping has been crucial to determining the distribution and impact of different families on disease clinical presentation. The aim of the...
BACKGROUND
Mycobacterium tuberculosis genotyping has been crucial to determining the distribution and impact of different families on disease clinical presentation. The aim of the study was to evaluate the associations among sociodemographic and clinical characteristics and M. tuberculosis lineages from patients with pulmonary tuberculosis in Orizaba, Veracruz, Mexico.
METHODS
We analyzed data from 755 patients whose isolates were typified by 24-loci mycobacterial interspersed repetitive unit-variable number of tandem repeats (MIRU-VNTR). The associations among patient characteristics and sublineages found were evaluated using logistic regression analysis.
RESULTS
Among M. tuberculosis isolates, 730/755 (96.6%) were assigned to eight sublineages of lineage 4 (Euro-American). Alcohol consumption (adjusted odds ratio [aOR] 1.528, 95% confidence interval (CI) 1.041-2.243; p = 0.030), diabetes mellitus type 2 (aOR 1.625, 95% CI 1.130-2.337; p = 0.009), sputum smear positivity grade (3+) (aOR 2.198, 95% CI 1.524-3.168; p < 0.001) and LAM sublineage isolates (aOR 1.023, 95% CI 1.023-2.333; p = 0.039) were associated with the presence of cavitations. Resistance to at least one drug (aOR 25.763, 95% CI 7.096-93.543; p < 0.001) and having isolates other than Haarlem and LAM sublineages (aOR 6.740, 95% CI 1.704-26.661; p = 0.007) were associated with treatment failure. In a second model, multidrug resistance was associated with treatment failure (aOR 31.497, 95% CI 5.119-193.815; p < 0.001). Having more than 6 years of formal education was not associated with treatment failure.
CONCLUSIONS
Knowing M. tuberculosis genetic diversity plays an essential role in disease development and outcomes, and could have important implications for guiding treatment and improving tuberculosis control.
Topics: Humans; Mycobacterium tuberculosis; Tuberculosis, Pulmonary; Tuberculosis; Minisatellite Repeats; Phylogeny; Genotype
PubMed: 36918814
DOI: 10.1186/s12879-023-08055-9 -
British Journal of Biomedical Science 2022The MIR137 gene acts as a tumor-suppressor gene in colon and gastric cancers. The aim of this study was to investigate the association of functional variable number...
The MIR137 gene acts as a tumor-suppressor gene in colon and gastric cancers. The aim of this study was to investigate the association of functional variable number tandem repeat (VNTR) polymorphism rs58335419 locating in the upstream of the MIR137 gene with the risk of colon and gastric cancers. Totally, 429 individuals were contributed in the study, including 154 colon and 120 gastric cancer patients and 155 healthy controls. The target VNTR was genotyped using PCR and electrophoresis for all samples. Statistical analysis was performed using SPSS 21.0 software and by T, χ2 and logistic regression tests. Excluding the rare genotypes, our results showed that genotype 3/5 (95% CI = 1.08-3.73, OR = 2.01, = 0.026) significantly increased the risk of colon cancer but not gastric cancer (95% CI = 0.88-3.30, OR = 1.70, = 0.114). Also, in the stratification analysis for VNTRs and sex, genotypes 3/4 (95% CI = 1.00-6.07, OR = 2.46, = 0.049) and 3/5 (95% CI = 1.25-7.18, OR = 2.99, = 0.014) significantly increased the risk of colon cancer in men but not in women. In addition, all genotypes including the rare genotypes as a group, significantly increase the risk of gastric (95% CI = 1.14-3.00, OR = 1.85, = 0.012) and colon (95% CI = 1.38-3.43, OR = 2.17, = 0.001) cancers compared to the genotype 3/3 as a reference. The results show that increasing the copy of VNTR in the MIR137 gene, increases the risk of colon and gastric cancers and can serve as a marker for susceptibility to colon and gastric cancers.
Topics: Case-Control Studies; Colonic Neoplasms; Female; Gene Frequency; Genetic Predisposition to Disease; Genotype; Humans; Male; MicroRNAs; Minisatellite Repeats; Polymorphism, Genetic; Stomach Neoplasms
PubMed: 35996520
DOI: 10.3389/bjbs.2021.10095 -
Journal of Medical Microbiology Nov 2021The Philippines, comprising three island groups, namely, Luzon, Visayas and Mindanao, experienced an increase in cholera outbreaks in 2016. Previous studies have shown...
The Philippines, comprising three island groups, namely, Luzon, Visayas and Mindanao, experienced an increase in cholera outbreaks in 2016. Previous studies have shown that isolates obtained from the Philippines are novel hybrid El Tor strains that have evolved in the country and are clearly distinct from those found in Mozambique and Cameroon. The characterization of the strains isolated from outbreaks has been limited to phenotypic characteristics, such as biochemical and serological characteristics, in most previous studies. We performed multilocus variable-number tandem repeat (VNTR) analysis (MLVA) for isolates obtained from 2015 to 2016 to further characterize and understand the emergence and dissemination of the strains in the Philippines. A total of 139 . O1 Ogawa biotype El Tor isolates were obtained from the Philippines during diarrhoeal outbreaks in 18 provinces between 2015 and 2016. VNTR data were analysed to classify the MLVA profiles where the large-chromosome types (LCTs) were applied for grouping. We identified 50 MLVA types among 139 isolates originating from 18 provinces, and 14 LCTs. The distribution of the LCTs was variable, and a few were located in specific areas or even in specific provinces. Based on eBURST analysis, 99 isolates with 7 LCTs and 32 MLVA types belonged to 1 group, suggesting that they were related to each other. LCT A was predominant (=67) and was isolated from Luzon and Visayas. LCT A had 14 MLVA types; however, it mostly emerged during a single quarter of a year. Eight clusters were identified, each of which involved specific MLVA type(s). The largest cluster involved 23 isolates showing 3 MLVA types, 21 of which were MLVA type A-14 isolated from Negros Occidental during quarter 4 of 2016. Comparative analysis showed that almost all isolates from the Philippines were distinct from those in other countries. The genotypic relationship of the isolates obtained during outbreaks in the Philippines was studied, and their emergence and dissemination were elucidated. MLVA revealed the short-term dynamics of genotypes in the Philippines.
Topics: Cholera; Disease Outbreaks; Humans; Minisatellite Repeats; Philippines; Vibrio cholerae O1
PubMed: 34817317
DOI: 10.1099/jmm.0.001443