Molecular Epidemiology Of Tuberculosis Research Articles

Bibliometric analysis of tuberculosis molecular epidemiology based on CiteSpace.

Tuberculosis is a communicable disease that is a major cause of ill health. Bibliometrics is an important statistical methodology used to analyze articles and other publications in the literature study. In this study, publications on molecular epidemiology were analyzed using bibliometric analysis. The statistical analysis of influential publications, journals, countries and authors was first conducted. The Web of Science database was searched for publications on the molecular epidemiology of tuberculosis with the keywords "tuberculosis" and "molecular epidemiology" in the title. The number of publications, citation analysis, co-authorship of the author, institution and country, keyword co-occurrence, and reference co-citations were analyzed. A total of 225 journal articles were retrieved. The mean citation was 37.72 per article and 292.69 per year. The annual publications on molecular epidemiology fluctuated within a certain range in the past. Journal of Clinical Microbiology is the most published journal with 33 articles. RASTOGI N is the most prolific author with 11 articles. The top 1 research institution is Inst Pasteur Guadeloupe. Stratified by the number of publications, the USA was the most prolific country. It also cooperates closely with other countries. Burstness analysis of references and keywords showed that the developing research trends in this field mainly focused on "genetic diversity" and "lineage" during the past decade. The annual publications on tuberculosis molecular epidemiology fluctuated within a specific range in the past decade. The USA continues to dominate research output and funding. The exchange of expertise, ideas, and technology is of paramount importance in this field. More frequent and deeper cooperation among countries or institutions will be essential in the future.

Molecular epidemiology of tuberculosis in the Somali region, eastern Ethiopia.

BackgroundTuberculosis (TB) is one of the leading causes of morbidity and mortality in low-income countries like Ethiopia. However, because of the limited laboratory infrastructure there is a shortage of comprehensive data on the genotypes of clinical isolates of Mycobacterium tuberculosis (M. tuberculosis) complex (MTBC) in peripheral regions of Ethiopia. The objective of this study was to characterize MTBC isolates in the Somali region of eastern Ethiopia.MethodsA cross-sectional study was conducted in three health institutions between October 2018 and December 2019 in the capital of Somali region. A total of 323 MTBC isolates (249 from pulmonary TB and 74 from extrapulmonary TB) were analyzed using regions of difference 9 (RD 9)-based polymerase chain reaction (PCR) and spoligotyping.ResultsOf the 323 MTBC isolates, 99.7% (95% CI: 99.1–100%) were M. tuberculosis while the remaining one isolate was M. bovis based on RD 9-based PCR. Spoligotyping identified 71 spoligotype patterns; 61 shared types and 10 orphans. A majority of the isolates were grouped in shared types while the remaining grouped in orphans. The M. tuberculosis lineages identified in this study were lineage 1, 2, 3, 4, and 7 with the percentages of 7.4, 2.2, 28.2, 60.4, and 0.6%, respectively. Most (87.9%) of the isolates were classified in clustered spoligotypes while the remaining 12.1% isolates were singletons. The predominant clustered spoligotypes identified were SIT 149, SIT 21, SIT 26, SIT 53, and SIT 52, each consisting of 17.6, 13.3, 8.4, 7.4, and 5%, respectively. Lineage 3 and lineage 4, as well as the age group (15–24), were associated significantly with clustering.ConclusionThe MTBC isolated from TB patients in Somali region were highly diverse, with considerable spoligotype clustering which suggests active TB transmission. In addition, the Beijing spoligotype was isolated in relatively higher frequency than the frequencies of its isolation from the other regions of Ethiopia warranting the attention of the TB Control Program of the Somali region.

Molecular epidemiology of tuberculosis in northern Australia

Australia has one of the lowest rates of tuberculosis (TB) globally; however, the rates of TB in the Northern Territory (NT) Top End and in Far North Queensland are consistently higher than the national average. Genomic sequencing of Mycobacterium tuberculosis (MTB) is increasingly being implemented for transmission surveillance and antimicrobial resistance prediction. Genomic epidemiological studies in northern Australia have demonstrated the utility of sequencing for tracking TB transmission. In the NT Top End, this has demonstrated that most TB transmission is occurring in remote regions, with recent transmission and reactivation from latency contributing to incident TB. In Far North Queensland, genomics has been used to track transmission of a multidrug-resistant MTB clone across the Torres Strait. The next steps include implementation of MTB genomic sequencing in jurisdictional laboratories with real-time cross-jurisdictional analysis to inform public health management of TB.

Molecular Epidemiology of Tuberculosis in Cattle and Human Patients in ‎Bauchi and Gombe States, Northeastern Nigeria

Tuberculosis (TB) is recognized as the most important threat to human and animal health causing morbidity, mortality, and economic losses. A study was conducted to assess the epidemiology and zoonotic implications of TB in two states of northeastern Nigeria, using abattoir surveillance, culture, and molecular typing methods. The human sputum of in-patients from selected hospitals within the study areas was also collected, cultured, and subjected to molecular typing. Out of the 250 human sputa collected, 74 (29.6%) were positive for culture and 40(16%) were positive on Bioline® analysis. Also, of the 200 tissues collected, 62(32.5%) were AFB positive and 25(12.5%) were positive on culture and 18(9.0%) were positive on Bioline® analysis. All positive isolates on Bioline® analyses were further subjected to Genotype® MBTC analysis. A total of (n = 58) isolates; sputum (n=40) and tissue (n=18), identified as MBTC were further subjected to Genotype MBTC® Hain assay PCR analysis. in order to differentiate them into their various species. Of the MBTC isolates from the tissues, 8(4.0%) were found to be Mycobacterium bovis, 5(2.5%) were Mycobacterium tuberculosis and the remaining 5(2.5%) were unidentified using the standard banding patterns. The 40 MBTC from sputum showed 30 (75%) as Mycobacterium tuberculosis 6(15%) were Mycobacterium bovis, 3(7.5%) were Mycobacterium africanum and 1(0.4%) was unidentified using the standard banding patterns. In conclusion, the study revealed the public health importance of bTB in the study area. There is also the need for public health awareness programs on the zoonotic nature of bTB among the abattoir workers and the herdsmen.

Molecular epidemiology of tuberculosis in Tasmania and genomic characterisation of its first known multi-drug resistant case.

BackgroundThe origin and spread of tuberculosis (TB) in Tasmania and the types of strains of Mycobacterium tuberculosis complex (MTBC) present in the population are largely unknown.ObjectiveThe aim of this study was to perform the first genomic analysis of MTBC isolates from Tasmania to better understand the epidemiology of TB in the state.MethodsWhole-genome sequencing was performed on cultured isolates of MTBC collected from 2014–2016. Single-locus variant analysis was applied to determine the phylogeny of the isolates and the presence of drug-resistance mutations. The genomic data were then cross-referenced against public health surveillance records on each of the cases.ResultsWe determined that 83.3% of TB cases in Tasmania from 2014–2016 occurred in non-Australian born individuals. Two possible TB clusters were identified based on single locus variant analysis, one from November-December 2014 (n = 2), with the second from May-August 2015 (n = 4). We report here the first known isolate of multi-drug resistant (MDR) M. tuberculosis in Tasmania from 2016 for which we established its drug resistance mutations and potential overseas origin. In addition, we characterised a case of M. bovis TB in a Tasmanian-born person who presented in 2014, approximately 40 years after the last confirmed case in the state’s bovids.ConclusionsTB in Tasmania is predominantly of overseas origin with genotypically-unique drug-susceptible isolates of M. tuberculosis. However, the state also exhibits features of TB that are observed in other jurisdictions, namely, the clustering of cases, and drug resistance. Early detection of TB and contact tracing, particularly of overseas-born cases, coordinated with rapid laboratory drug-susceptibility testing and molecular typing, will be essential for Tasmania to reach the World Health Organisation’s TB eradication goals for low-incidence settings.

Molecular Epidemiology of Tuberculosis and Transmission Dynamics of Mycobacterium tuberculosis Complex in Morocco

Molecular Epidemiology of Tuberculosis and Transmission Dynamics of Mycobacterium tuberculosis Complex in Morocco

Molecular Epidemiology of Tuberculosis: A Review of Tools and Applications

Molecular Epidemiology of Tuberculosis: A Review of Tools and Applications

Molecular epidemiology of tuberculosis in Brazil: a translational research perspective*

Molecular epidemiology of tuberculosis in Brazil: a translational research perspective*

Genomic Epidemiology of Tuberculosis.

The application of next generation sequencing technologies has opened the door to a new molecular epidemiology of tuberculosis, in which we can now look at transmission at a resolution not possible before. At the same time, new technical and analytical challenges have appeared, and we are still exploring the wider potential of this new technology. Whole genome sequencing in tuberculosis still requires bacterial cultures. Thus, although whole genome sequencing has revolutionized the interpretation of transmission patterns, it is not yet ready to be applied at the point-of-care. In this chapter, I will review the promises and challenges of genomic epidemiology, as well as some of the new questions that have arisen from the use of this new technology. In addition, I will examine the role of molecular epidemiology within the general frame of global tuberculosis control and how genomic epidemiology can contribute towards the elimination of the disease.

Molecular epidemiology of tuberculosis: Opportunities & challenges in disease control.

Molecular epidemiology of tuberculosis: Opportunities & challenges in disease control.

Molecular epidemiology of tuberculosis in Victoria, Australia, reveals low level of transmission.

Victoria, Australia. To measure the level of Mycobacterium tuberculosis transmission in Victoria. Retrospective analysis of mycobacterial interspersed repetitive unit-variable number of tandem repeats (MIRU-VNTR) typing profiles from all first M. tuberculosis complex (MTC) isolates obtained from patients residing in Victoria from 2003 to 2010 was performed. State TB reference laboratory records were matched with Department of Health notification records to obtain further laboratory, demographic, contact investigation, clinical and treatment data. These data were used to assign patients to one of four categories: 1) no epidemiological link, 2) possible link, 3) likely transmission event and 4) laboratory contamination. A total of 2377 MTC isolates were genotyped using 15-locus MIRU-VNTR. Of the 2298 M. tuberculosis isolates, 1029 (44.8%) had unique genotypic profiles and were considered epidemiologically unrelated, while 1269 (55.2%) isolates shared a profile with one or more other strains, defined as a genotypic cluster. Systematic investigation of all 268 genotypic clusters, including 24-locus MIRU-VNTR on selected isolates, led to a further 862 patients being classified as unrelated, bringing the total number of patients with no epidemiological links to 1891 (82.3%). Of the remaining patients, 294 (12.8%) were classified as having possible epidemiological links, 96 (4.2%) were classified as having known epidemiological links representing likely transmission events and 17 (0.7%) as the result of laboratory cross-contamination. There is considerable genotypic diversity among Victorian MTC isolates, and the level of transmission is low.

Molecular epidemiology of tuberculosis in Kaohsiung City located at southern Taiwan, 2000-2008.

BackgroundWe present the first comprehensive analysis of Mycobacterium tuberculosis (MTB) isolates circulating in southern Taiwan. In this 9-year population-based study, the TB situation in the Kaohsiung region was characterized by genotypic analysis of 421 MTB isolates.MethodsAll 421 isolates of MTB were analyzed by spoligotyping and MIRU-VNTR typing. Drug-resistance patterns were also analyzed.ResultsThe percentage of EAI (East African-Indian) strains increased across sampling years (2000–2008) in southern Taiwan, whereas the proportion of Beijing lineages remained unchanged. Clustering was more frequent with EAI genotype infections (odds ratio = 3.6, p<0.0001) when compared to Beijing genotypes. Notably, MTB resistance to streptomycin (STR) had significantly increased over time, but resistance to other antibiotics, including multidrug resistance, had not. Three major genes (gidB, rpsL and rrs) implicated in STR resistance were sequenced and specific mutations identified.ConclusionsThis study revealed that EAI strains were highly transmissible and that STR resistance has increased between 2000 and 2008 in Kaohsiung, Taiwan.

Molecular epidemiology of tuberculosis in Sicily, Italy: what has changed after a decade?

BackgroundWe aimed to investigate the molecular epidemiology of Mycobacterium tuberculosis complex (MTBC) isolates in the province of Palermo, Sicily, Italy, by characterizing 183 isolates identified in the years 2004-2012. A comparison with 104 MTBC strains identified in the same geographic area in the years 1994-2000 was also carried out.MethodsOne hundred eighty-three MTBC isolates identified in Palermo, Italy, in the years 2004-2012 were analyzed by spoligotyping and the 24 mycobacterial interspersed repetitive unit (MIRU)-variable-number tandem-repeat (VNTR) method typing. Susceptibility testing to streptomycin, isoniazid, rifampin and ethambutol was also performed. Furthermore, the spoligotyping dataset obtained from 104 MTBC isolates identified from 1994 to 2000 was reanalyzed. Distribution into lineages and clustering of isolates in the two periods was compared.ResultsOne hundred seventy-seven out of the 183 isolates of MTBC submitted to molecular typing were fully characterized. Of these, 108 were from Italian-born and 69 from foreign-born individuals. Eleven different lineages and 35 families-subfamilies were identified with the most represented lineages being Haarlem (26.5%), T (19.2%), LAM (13.6%) and S (8.5%). Except for the Haarlem lineage, where isolates from foreign-born patients were overrepresented, the distribution of isolates in the families belonging to the Euro-American clone reflected the proportions of the two subpopulations. A total of 27 (15.2%) strains were clustered and three clusters were mixed. Approximately 25% of the 183 MTBC isolates under study proved to be resistant to at least one antiTB drug, with only three isolates categorized as multidrug resistant (MDR). When MTBC isolates identified in the years 1994-2000 were reanalyzed, lineages T (30.8%), LAM (29.8%), Haarlem (16.3%) and S (13.5%) proved to be predominant. No MTBC isolates belonging to CAM, U, CAS, Turkish and Ural lineages were identified.ConclusionsA wide heterogeneity was detected among the MTBC strains isolated in the years 2004-2012. Six lineages were not present among the isolates of the period 1994-2000. Comparison between distribution of lineages in the two consecutive periods depicts rapid and deep changes in the TB epidemiology in Palermo, Italy. An universal and continued laboratory-based surveillance of TB in Sicily is required.Electronic supplementary materialThe online version of this article (doi:10.1186/s12879-014-0602-4) contains supplementary material, which is available to authorized users.

Update on the epidemiology, diagnosis and therapy of tuberculosis in HIV-infected patients

Globally, the diagnosis and treatment of tuberculosis (TB) in HIV-co-infection has improved dramatically over the last 10 years. Nonetheless, the mortality of co-infected patients remains elevated. In European countries, the proportion of HIV-infected patients amongst all TB cases varies greatly; in Germany it is about 4 - 5%. HIV-infection changes the molecular epidemiology of TB and the drug resistance situation. In endemic areas, HIV-infected patients are often re-infected after completion of treatment for active TB. HIV has a profound influence on the anti-TB-immune response and antiretroviral therapy (ART) cannot completely restore normal immune function. The clinical presentation in advanced HIV-infection is atypical and disseminated disease is common. New "Point-of-Care" test methods are poised to improve the diagnoses of TB in HIV-infection; however, further research is required. The treatment of co-infection is complicated by drug interactions and the immune reconstitution syndrome (IRIS). New concepts and treatment regimens for chemoprevention of TB are necessary, especially for HIV-infected persons.

Molecular epidemiology of tuberculosis in Cambodian children.

SUMMARY We analysed Mycobacterium tuberculosis strains from children, hospitalized from January 2004 to July 2008 in the largest paediatric hospital complex in Cambodia. Specimens were tested for drug susceptibility and genotypes. From the 260 children, 161 strains were available. The East African-Indian genotype family was the most common (59.0%), increasing in frequency with distance from the Phnom Penh area, while the frequency of the Beijing genotype family strains decreased. The drug resistance pattern showed a similar geographical gradient: lowest in the northwest (4.6%), intermediate in the central (17.1%), and highest in the southeastern (30.8%) parts of the country. Three children (1.9%) had multidrug-resistant tuberculosis. The Beijing genotype and streptomycin resistance were significantly associated (P < 0.001). As tuberculosis in children reflects recent transmission patterns in the community, multidrug resistance levels inform about the current quality of the tuberculosis programme.

Extensive Genetic Diversity among Clinical Isolates of Mycobacterium tuberculosis in Central Province of Iran.

Human tuberculosis caused by Mycobacterium tuberculosis (Mtb) remains a significant disease in many countries. According to Iran's borders with Afghanistan and Pakistan, which are among the 22 high burden countries around the world, this study was conducted to analyze the current molecular epidemiology of tuberculosis and survey genetic diversity of Mtb strains in Markazi Province in center of Iran. In this experimental study, 75 sputum specimens and one gastric lavage from all smear-positive TB patients admitted to the public hospitals across the Markazi Province were cultured on specific mycobacterial culture media. Genomic DNA was digested by PvuII and transferred to positively charged nylon membrane by southern blotting method and hybridization by PGRS and DR probes. Genotyping of the isolates by PGRS-RFLP and DR-RFLP displayed a wide range of genetic diversity as 25 and 26 genotypes were identified, respectively. Generally speaking, despite the relatively limited number of isolates in the study, high age of patients and also large heterogeneity found in the setting are both in opposition to active circulation of Mtb strains between patients under study either Iranian or Afghan nationals. Thus, it seems that reactivation of latent infection has had the main role in the spread of tuberculosis.

Differential findings regarding molecular epidemiology of tuberculosis between two consecutive periods in the context of steady increase of immigration

The demographic characteristics of the population of Madrid, with a steady increase in immigrants, from 4.7% in 1998 to 17.4% in 2007, provide an opportunity to study in depth the transmission of TB. Our aim was to compare two 3-year longitudinal molecular studies of TB to define transmission patterns and predictors of clustering. Two prospective population-based molecular and epidemiological studies (2002–2004 and 2005–2007) of TB patients were conducted in nine urban districts in Madrid using the same methodology. During the period 2002–2007, 2248 cases of TB were reported, and the incidence decreased from 23.5 per 100 000 in 2002 to 20.8 in 2007 (p <0.001). A total of 1269 isolates were molecularly characterized and included in the study. The comparison between the two periods showed that the percentage of foreign-born patients among TB cases increased from 36.2% to 45.7% (p <0.001). Furthermore, the percentage of clustered cases decreased (36.6% vs. 30.6%; p 0.028), and this decline was associated with a decrease of clustered cases among men and people under 35 years. We also observed a decrease in cases belonging to clusters containing >6 people (14.2% vs. 8.2%; p <0.001), and in cases belonging to mixed clusters containing Spanish-born and foreign-born patients (18.5% vs. 11.1%, p <0.001). Our molecular epidemiology study provides clues to interpret the decrease in the incidence of TB in a context of steady increase of immigration. In our region, the decrease in the incidence of TB can be explained predominantly as a result of a decline in recent transmission.

English

There is scarcity of data on molecular epidemiology of tuberculosis (TB) in many of the high burden countries of sub-Saharan Africa including Nigeria. This may be due to inadequate diagnostic and research capacities. There is a need to build capacity on molecular epidemiologic techniques in order to enhance TB diagnosis, treatment and prevention strategies. Some of the more popular molecular typing methods being used globally include IS6110-based restriction fragment length polymorphism (RFLP),polymerase chain reaction (PCR) -based methods such as spacer oligonucleotide typing or spoligotyping, mycobacterial interspersed repetitive units-multilocus variable number tandem repeats (MIRU-VNTR), single –nucleotide polymorphisms and large –sequence polymorphism analysis. Among other things, molecular technique(s) to be adopted for use in a particular setting depend on the state of the infrastructure including laboratory facilities, presence of skilled personnel and cost. In Nigeria however, availability of PCR-based diagnostic assay –MTBDR plus assay (HAIN- Lifesciences, Germany) in some TB reference laboratories may serve as a springboard for introduction of advanced TB molecular epidemiologic tools in the country. Key words: Molecular epidemiologic tools, tuberculosis, Nigeria.

A snapshot on the molecular epidemiology of tuberculosis in western Sicily

(MTB) strains isolated in 1994-1998 in Palermo, Italy, showed that 87.4% of the patients were likely to be infected by unrelated isolates, reactivation largely exceeding recent infection. In the last 10 years striking demographic and sociological changes have occurred, such as an increasing immigration and the growing elderly population. Sicily, in particular, has been recently affected by large waves of immigration from Africa and immigration from eastern European countries is also increasing. A follow-up study on the molecular epidemiology of TB 10 years later was performed.

A Model-Based Bayesian Estimation of the Rate of Evolution of VNTR Loci in Mycobacterium tuberculosis

Variable numbers of tandem repeats (VNTR) typing is widely used for studying the bacterial cause of tuberculosis. Knowledge of the rate of mutation of VNTR loci facilitates the study of the evolution and epidemiology of Mycobacterium tuberculosis. Previous studies have applied population genetic models to estimate the mutation rate, leading to estimates varying widely from around to per locus per year. Resolving this issue using more detailed models and statistical methods would lead to improved inference in the molecular epidemiology of tuberculosis. Here, we use a model-based approach that incorporates two alternative forms of a stepwise mutation process for VNTR evolution within an epidemiological model of disease transmission. Using this model in a Bayesian framework we estimate the mutation rate of VNTR in M. tuberculosis from four published data sets of VNTR profiles from Albania, Iran, Morocco and Venezuela. In the first variant, the mutation rate increases linearly with respect to repeat numbers (linear model); in the second, the mutation rate is constant across repeat numbers (constant model). We find that under the constant model, the mean mutation rate per locus is (95% CI: ,)and under the linear model, the mean mutation rate per locus per repeat unit is (95% CI: ,). These new estimates represent a high rate of mutation at VNTR loci compared to previous estimates. To compare the two models we use posterior predictive checks to ascertain which of the two models is better able to reproduce the observed data. From this procedure we find that the linear model performs better than the constant model. The general framework we use allows the possibility of extending the analysis to more complex models in the future.