A genome epidemiological study of mycobacterium tuberculosis in subpopulations with high and low incidence rate in Guangxi, South China.
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ABSTRACT: Background
Tuberculosis (TB) is caused by a bacterium called Mycobacterium tuberculosis (Mtb). China is the third in top 8 high TB burden countries and Guangxi is one of the high incidence areas in South China. Determine bacterial factors that affected TB incidence rate is a step toward Ending the TB epidemic.Results
Genomes of M. tuberculosis cultures from a relatively high and low incidence region in Guangxi have been sequenced. 347 of 358(96.9%) were identified as M. tuberculosis. All the strains belong to Lineage 2 and Lineage 4, except for one in Lineage 1. We found that the genetic structure of the M. tuberculosis population in each county varies enormously. Low incidence rate regions have a lower prevalence of Beijing genotypes than other regions. Four isolates which harbored mutT4-48 also had mutT2-58 mutations. It is suggested that strains from the ancestors of modern Beijing lineage is circulating in Guangxi. Strains of modern Beijing lineage (OR=2.04) were more likely to acquire drug resistances than Lineage 4. Most of the lineage differentiation SNPs are related to cell wall biosynthetic pathways.Conclusions
These results provided a higher resolution to better understand the history of transmission of M. tuberculosis from/to South China. And the incidence rate of tuberculosis might be affected by bacterial population structure shaped by demographic history. Our findings also support the hypothesis that Modern Beijing lineage originated in South China.
SUBMITTER: Lin D
PROVIDER: S-EPMC8377953 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundTuberculosis (TB) remains a serious public health problem with substantial financial burden in China. The incidence of TB in Guangxi province is much higher than that in the national level, however, there is no predictive study of TB in recent years in Guangxi, therefore, it is urgent to construct a model to predict the incidence of TB, which could provide help for the prevention and control of TB.MethodsBox-Jenkins model methods have been successfully applied to predict the incidence of infectious disease. In this study, based on the analysis of TB incidence in Guangxi from January 2012 to June 2019, we constructed TB prediction model by Box-Jenkins methods, and used root mean square error (RMSE), mean absolute error (MAE) and mean absolute percentage error (MAPE) to test the performance and prediction accuracy of model.ResultsFrom January 2012 to June 2019, a total of 587,344 cases of TB were reported and 879 cases died in Guangxi. Based on TB incidence from January 2012 to December 2018, the SARIMA((2),0,(2))(0,1,0)12 model was established, the AIC and SC of this model were 2.87 and 2.98, the fitting accuracy indexes, such as RMSE, MAE and MAPE were 0.98, 0.77 and 5.8 respectively; the prediction accuracy indexes, such as RMSE, MAE and MAPE were 0.62, 0.45 and 3.77, respectively. Based on the SARIMA((2),0,(2))(0,1,0)12 model, we predicted the TB incidence in Guangxi from July 2019 to December 2020.ConclusionsThis study filled the gap in the prediction of TB incidence in Guangxi in recent years. The established SARIMA((2),0,(2))(0,1,0)12 model has high prediction accuracy and good prediction performance. The results suggested the change trend of TB incidence predicted by SARIMA((2),0,(2))(0,1,0)12 model from July 2019 to December 2020 was similar to that in the previous two years, and TB incidence will experience slight decrease, the predicted results can provide scientific reference for the prevention and control of TB in Guangxi, China.
| S-EPMC7178605 | biostudies-literature
Project description:Low pathogenic avian influenza virus (LPAIV) usually causes mild disease or asymptomatic infection in poultry. However, some LPAIV strains can be transmitted to humans and cause severe infection. Genetic rearrangement and recombination of even low pathogenic influenza may generate a novel virus with increased virulence, posing a substantial risk to public health. Southern China is regarded as the world "influenza epicenter", due to a rash of outbreaks of influenza in recent years. In this study, we conducted an epidemiological survey of LPAIV at different live bird markets (LBMs) in Guangxi province, Southern China. From January 2009 to December 2011, we collected 3,121 cotton swab samples of larynx, trachea and cloaca from the poultry at LBMs in Guangxi. Virus isolation, hemagglutination inhibition (HI) assay, and RT-PCR were used to detect and subtype LPAIV in the collected samples. Of the 3,121 samples, 336 samples (10.8%) were LPAIV positive, including 54 (1.7%) in chicken and 282 (9.1%) in duck. The identified LPAIV were H3N1, H3N2, H6N1, H6N2, H6N5, H6N6, H6N8, and H9N2, which are combinations of seven HA subtypes (H1, H3, H4, H6, H9, H10 and H11) and five NA subtypes (N1, N2, N5, N6 and N8). The H3 and H9 subtypes are predominant in the identified LPAIVs. Among the 336 cases, 29 types of mixed infection of different HA subtypes were identified in 87 of the cases (25.9%). The mixed infections may provide opportunities for genetic recombination. Our results suggest that the LPAIV epidemiology in poultry in the Guangxi province in southern China is complicated and highlights the need for further epidemiological and genetic studies of LPAIV in this area.
| S-EPMC3813733 | biostudies-literature
Project description:BACKGROUND:At present, there are few studies on polymorphism of Mycobacterium tuberculosis (Mtb) gene and how it affects the TB epidemic. This study aimed to document the differences of polymorphisms between tuberculosis hot and cold spot areas of Guangxi Zhuang Autonomous Region, China. METHODS:The cold and hot spot areas, each with 3 counties, had been pre-identified by TB incidence for 5?years from the surveillance database. Whole genome sequencing analysis was performed on all sputum Mtb isolates from the detected cases during January and June 2018. Single nucleotide polymorphism (SNP) of each isolate compared to the H37Rv strain were called and used for lineage and sub-lineage identification. Pairwise SNP differences between every pair of isolates were computed. Analyses of Molecular Variance (AMOVA) across counties of the same hot or cold spot area and between the two areas were performed. RESULTS:As a whole, 59.8% (57.7% sub-lineage 2.2 and 2.1% sub-lineage 2.1) and 39.8% (17.8% sub-lineage 4.4, 6.5% sub-lineage 4.2 and 15.5% sub-lineage 4.5) of the Mtb strains were Lineage 2 and Lineage 4 respectively. The percentages of sub-lineage 2.2 (Beijing family strains) are significantly higher in hot spots. Through the MDS dimension reduction, the genomic population structure in the three hot spot counties is significantly different from those three cold spot counties (T-test p?=?0.05). The median of SNPs distances among Mtb isolates in cold spots was greater than that in hot spots (897 vs 746, Rank-sum test p?<?0.001). Three genomic clusters, each with genomic distance ?12 SNPs, were identified with 2, 3 and 4 consanguineous strains. Two clusters were from hot spots and one was from cold spots. CONCLUSION:Narrower genotype diversity in the hot area may indicate higher transmissibility of the Mtb strains in the area compared to those in the cold spot area.
| S-EPMC7329418 | biostudies-literature
Project description:ObjectiveTo evaluate the infectivity of Mycobacterium tuberculosis (M.tb) genotypes of index cases in the classroom of adolescent schools in Guangxi, China.MethodsAdolescent school tuberculosis (TB) contact investigations were conducted for all reported index TB cases from November 2016 to December 2017 in Guangxi, China. Genotypes of index cases and contact cases were identified by 15-loci mycobacterial interspersed repetitive units-variable number tandem repeat and spoligotyping. Outcome variable was 5 levels' order of tuberculin skin test (TST) results to new active TB [0-5 mm, 6-9 mm, 10-14 mm, ≥ 15 mm (without TB), and ≥15 mm (with TB)]. Multivariate ordered logistic regression analysis was performed to evaluate the independent effect of genotypes of index case on contact screening outcome.ResultsBeijing genotype occurred more commonly in female index patients. One genotypic cluster of two index cases and one cluster of two contact cases were detected. The association between infectivity of Beijing genotype of index cases and outcome of contact investigation was statistically significant in univariate analysis but no so after adjustment for characteristics of contacts and sex of index cases (P value=0.057). Female index cases increased the chance for TB infection/being active TB among contacts (ordinal odds ratio = 1.39, 95% confidence interval: 1.21, 1.60). Contacts who studied in the middle school, who with non-Han ethnicity and who without BCG scar had increased risk for TB infection/being active TB.ConclusionThere was not enough evidence from our data to support that Beijing strains were more infective than non-Beijing strains in TB transmission in school setting.
| S-EPMC6487147 | biostudies-literature
Project description:ImportanceThe World Health Organization End TB (Tuberculosis) Strategy aims to decrease the global incidence and mortality of TB by 90% and 95%, respectively, as of 2035.ObjectiveTo characterize the recent epidemiological trend of pulmonary TB (PTB) in mainland China based on the national surveillance data.Design, setting, and participantsThis cross-sectional study collected demographic and clinical data of all patients reported in the national Tuberculosis Information Management System of China from January 1, 2005, to November 21, 2016. Data were analyzed from December 1, 2019, to July 31, 2020.ExposuresPulmonary TB was defined as bacteriologically confirmed or clinically diagnosed TB in the lung parenchyma or the tracheobronchial tree.Main outcomes and measuresTemporal and spatial variation of annual incidence and demographic features of PTB in mainland China.ResultsIn total, 10 582 903 patients with PTB were reported in mainland China from 2005 to 2016. The median age of patients with PTB was 46 (interquartile range [IQR], 30-61) years, and 28.53% were 60 years or older. Most patients with PTB were male (69.8%) and farmers or herders (70.0%). The mean (SD) incidence of PTB was 66.61 (8.09) per 100 000 population. The annual incidence decreased from 72.95 per 100 000 population in 2005 to 52.18 per 100 000 population in 2016, and the reduction was greater in the eastern and central regions (31.6%; from 69.43 to 47.48 per 100 000 population) than in the western region (21.0%; from 82.06 to 64.82 per 100 000 population). Xinjiang Uygur Autonomous Region (135.03 per 100 000 population), Guizhou Province (115.98 per 100 000 population), and the Tibet Autonomous Region (101.98 per 100 000 population) had the highest mean annual incidences. The median time from onset of illness to diagnosis decreased from 36 (IQR, 16-92) days from 2005 to 2007 to 31 (IQR, 15-63) days in 2008 and later (P < .001) and was longer in the western region than in the eastern and central regions (41 [IQR, 20-91] vs 30 [IQR, 13-61] days; P < .001).Conclusions and relevanceAlthough this study found that the incidence of PTB in mainland China showed a downward trend from 2005 to 2016, to achieve the World Health Organization 2035 goal, innovative and more efficient prevention and control strategies are needed, particularly among the most susceptible population, that is, farmers and herders in western China.
| S-EPMC8035653 | biostudies-literature
Project description:BackgroundTuberculosis (TB) remains one of the top ten causes of death each year globally. While the risk of migrant TB is linked to the TB incidence in their country of origin, the migration process can increase the TB risk.ObjectiveWe aimed to synthesis the evidence on key differences in the epidemiological profile of TB between migrants from high TB incidence birth countries and non-migrants resident in low to medium incidence TB countries.MethodsWe conducted a systematic review where the population was all active TB cases in countries with low to medium TB incidence (<40/100,000 population), the exposure was migration to a low or medium TB incidence country and the comparator was non-migrant TB cases in low or medium incidence countries. Overall proportions were compared between migrants and non-migrants, using Fisher's exact test. Meta-analysis of proportions was carried out for the primary outcome (active TB) while meta-analyses of odds ratios (ORs) were performed using a random effects model for secondary outcomes; sputum-smear positivity, any first line drug resistance, multi-drug resistance (MDR), clustered cases, HIV coinfections and successful treatment. Heterogeneity was evaluated and sources were investigated using subgroup and sensitivity analysis.ResultsSignificant differences were found in the overall proportions of high TB incidence migrants and non-migrants for MDR cases, clustered cases, HIV coinfections and successful treatment, as well as a significant difference in the OR among MDR cases (3.91).ConclusionThis review has demonstrated significant differences in key epidemiological indicators between high TB incidence migrants and non-migrants, indicating policy implications.
| S-EPMC7930366 | biostudies-literature
Project description:BackgroundThe increase in multidrug-resistant tuberculosis (MDR-TB) severely hampers tuberculosis prevention and control in China, a country with the second highest MDR-TB burden globally. The first nationwide drug-resistant tuberculosis surveillance program provides an opportunity to comprehensively investigate the epidemiological/drug-resistance characteristics, potential drug-resistance mutations, and effective population changes of Chinese MDR-TB.MethodsWe sequenced 357 MDR strains from 4600 representative tuberculosis-positive sputum samples collected during the survey (70 counties in 31 provinces). Drug-susceptibility testing was performed using 18 anti-tuberculosis drugs, representing the most comprehensive drug-resistance profile to date. We used 3 statistical and 1 machine-learning methods to identify drug-resistance genes/single-nucleotide polymorphisms (SNPs). We used Bayesian skyline analysis to investigate changes in effective population size.ResultsEpidemiological/drug-resistance characteristics showed different MDR profiles, co-resistance patterns, preferred drug combination/use, and recommended regimens among 7 Chinese administrative regions. These factors not only reflected the serious multidrug co-resistance and drug misuse but they were also potentially significant in facilitating the development of appropriate regimens for MDR-TB treatment in China. Further investigation identified 86 drug-resistance genes/intergenic regions/SNPs (58 new), providing potential targets for MDR-TB diagnosis and treatment. In addition, the effective population of Chinese MDR-TB displayed a strong expansion during 1993-2000, reflecting socioeconomic transition within the country. The phenomenon of expansion was restrained after 2000, likely attributable to the advances in diagnosis/treatment technologies and government support.ConclusionsOur findings provide an important reference and improved understanding of MDR-TB in China, which are potentially significant in achieving the goal of precision medicine with respect to MDR-TB prevention and treatment.
| S-EPMC6637280 | biostudies-literature
Project description:Immigrants from regions with a high incidence of tuberculosis (TB) are a risk group for TB in low-incidence countries such as Switzerland. In a previous analysis of a nationwide collection of 520 Mycobacterium tuberculosis isolates from 2000 to 2008, we identified 35 clusters comprising 90 patients based on standard genotyping (24-locus mycobacterial interspersed repetitive-unit-variable-number tandem-repeat [MIRU-VNTR] typing and spoligotyping). Here, we used whole-genome sequencing (WGS) to revisit these transmission clusters. Genome-based transmission clusters were defined as isolate pairs separated by ≤12 single nucleotide polymorphisms (SNPs). WGS confirmed 17/35 (49%) MIRU-VNTR typing clusters; the other 18 clusters contained pairs separated by >12 SNPs. Most transmission clusters (3/4) of Swiss-born patients were confirmed by WGS, as opposed to 25% (4/16) of the clusters involving only foreign-born patients. The overall clustering proportion was 17% (90 patients; 95% confidence interval [CI], 14 to 21%) by standard genotyping but only 8% (43 patients; 95% CI, 6 to 11%) by WGS. The clustering proportion was 17% (67/401; 95% CI, 13 to 21%) by standard genotyping and 7% (26/401; 95% CI, 4 to 9%) by WGS among foreign-born patients and 19% (23/119; 95% CI, 13 to 28%) and 14% (17/119; 95% CI, 9 to 22%), respectively, among Swiss-born patients. Using weighted logistic regression, we found weak evidence of an association between birth origin and transmission (adjusted odds ratio of 2.2 and 95% CI of 0.9 to 5.5 comparing Swiss-born patients to others). In conclusion, standard genotyping overestimated recent TB transmission in Switzerland compared to WGS, particularly among immigrants from regions with a high TB incidence, where genetically closely related strains often predominate. We recommend the use of WGS to identify transmission clusters in settings with a low incidence of TB.
| S-EPMC4922098 | biostudies-literature
Project description:Transcriptional profiling of mycobacterium tuberculosis clinical isolates in China comparing extensively drug-resistant tuberculosis with drug sensitive one.
2009-04-04 | GSE15540 | GEO
Project description:BackgroundDiagnosis of Mycobacterium tuberculosis (MTB) infection can be confirmed by Xpert assays within hours. However, when sample size does not allow performing both culture and Xpert, or if Xpert is negative, then formal diagnosis of MTB relies on culture and time to detection of growth (TDG) becomes critical for clinical management.ObjectivesTo determine TDG in Xpert negative samples, or in samples in which Xpert could not be performed, in a low-incidence area for MTB.MethodsRetrospective analysis (2015-2020) of a database including all cultures for mycobacteria in a University Hospital covering approximately 500'000 inhabitants. Analysis was restricted to culture positive (C+) samples for MTB for which 1/Xpert was negative or could not be performed because of limited sample volume, and 2/collected from subjects treated less than 24 hours. TDG was analyzed according to microscopy, origin of sample (pulmonary or not) and presence of cavitation.ResultsAmong 837 C+ samples for MTB, 236 samples (80% of respiratory origin) from 147 patients fulfilled study criteria; 78 samples (49 patients, 33%) were acid-fast bacilli (AFB) positive. Median (IQR) TDG was 25 (17; 40) days for all samples. TDG exceeded 28 days in 43% of samples and was significantly shorter in AFB+ vs AFB- samples, and samples from cavitary vs non cavitary or extra-thoracic disease.ConclusionsIn Xpert negative samples, or samples for which Xpert could not be performed, TDG exceeded 4 weeks in 43% of samples. AFB+ and samples from cavitary lung disease had a significantly shorter TDG.
| S-EPMC8418320 | biostudies-literature