scholarly journals Evolution and emergence of multidrug-resistant Mycobacterium tuberculosis in Chisinau, Moldova

2021 ◽  
Author(s):  
Tyler S. Brown ◽  
Vegard Eldholm ◽  
Ola Brynildsrud ◽  
Magnus Osnes ◽  
Natalie Stennis ◽  
...  
Keyword(s):  
Public Health ◽  
Population Size ◽  
Sequence Data ◽  
Multidrug Resistant ◽  
Capital City ◽  
Whole Genome Sequence ◽  
Hospital Treatment ◽  
Drug Resistant ◽  
National Guidelines ◽  
Tb Control

1.ABSTRACTBackgroundDrug-resistant tuberculosis is a high priority threat to global public health. There are still critical gaps in understanding how novel drug-resistant M. tuberculosis strains emerge and, once emergent, what drives the differential propagation of certain epidemiologically-successful strains over others. This study sought to describe the joint evolutionary and epidemiological histories of a novel multidrug-resistant M. tuberculosis strain recently identified in the capital city of the Republic of Moldova (MDR Ural/4.2).MethodsUsing whole genome sequence data and Bayesian phylogenomic methods, we reconstruct the stepwise acquisition of drug-resistance mutations in the MDR Ural/4.2 strain, estimate its historical bacterial population size over time, and infer the migration history of this strain between Eastern European countries.ResultsWe infer that MDR Ural/4.2 likely evolved (via acquisition of rpoB S450L, which confers resistance to rifampin) in the early 1990s, during a period of social turmoil following Moldovan independence from the Soviet Union. This strain subsequently underwent substantial population size expansion in the early 2000s, at a time when national guidelines encouraged in hospital treatment of TB patients. We infer exportation of this strain and its INH-resistant ancestral precursor from Moldova to neighboring countries starting as early as 1985.ConclusionsOur findings underscore how public health practice and social determinants of health shape the conditions under which M. tuberculosis evolves, and demonstrates how historical changes in these conditions shape present-day challenges in TB control. These findings underscore the need for regional coordination in TB control across Eastern Europe.

scholarly journals Evolution and emergence of multidrug-resistant Mycobacterium tuberculosis in Chisinau, Moldova

2021 ◽  
Vol 7 (8) ◽  
Author(s):  
Tyler S. Brown ◽  
Vegard Eldholm ◽  
Ola Brynildsrud ◽  
Magnus Osnes ◽  
Natalie Levy ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Population Size ◽  
Type Species ◽  
Sequence Data ◽  
Multidrug Resistant ◽  
Capital City ◽  
Whole Genome Sequence ◽  
Drug Resistant ◽  
Content Type ◽  
Link Type

The evolution and emergence of drug-resistant tuberculosis (TB) has been studied extensively in some contexts, but the ecological drivers of these two processes remain poorly understood. This study sought to describe the joint evolutionary and epidemiological histories of a novel multidrug-resistant Mycobacterium tuberculosis strain recently identified in the capital city of the Republic of Moldova (MDR Ural/4.2), where genomic surveillance of drug-resistant M. tuberculosis has been limited thus far. Using whole genome sequence data and Bayesian phylogenomic methods, we reconstruct the stepwise acquisition of drug resistance mutations in the MDR Ural/4.2 strain, estimate its historical bacterial population size over time, and infer the migration history of this strain between Eastern European countries. We infer that MDR Ural/4.2 likely evolved (via acquisition of rpoB S450L, which confers resistance to rifampin) in the early 1990s, during a period of social turmoil following Moldovan independence from the Soviet Union. This strain subsequently underwent substantial population size expansion in the early 2000s, at a time when national guidelines encouraged inpatient treatment of TB patients. We infer exportation of this strain and its isoniazid-resistant ancestral precursor from Moldova to neighbouring countries starting as early as 1985. Our findings suggest temporal and ecological associations between specific public health practices, including inpatient hospitalization of drug-resistant TB cases from the early 2000s until 2013, and the evolution of drug-resistant M. tuberculosis in Moldova. These findings underscore the need for regional coordination in TB control and expanded genomic surveillance efforts across Eastern Europe.

scholarly journals Mycobacterium tuberculosis whole genome sequence data support repurposing antileprosy antibiotic as antituberculosis

2020 ◽  
Author(s):  
Jamal SAAD ◽  
Jenny GALLOU ◽  
Nathalie BERIRU ◽  
Michel DRANCOURT ◽  
Sophie BARON
Keyword(s):  
Pulmonary Tuberculosis ◽  
In Silico ◽  
Antibiotic Susceptibility ◽  
Sequence Data ◽  
Multidrug Resistant ◽  
Whole Genome Sequence ◽  
Drug Resistant ◽  
Routine Method ◽  
Extensively Drug Resistant ◽  
Sequence Variations

Background We implanted WGS as the routine method to profile the antibiotic susceptibility of M. tuberculosis isolates focusing on in silico resistance to antileprosy drugs that we recently proposed to reposition for the treatment of pulmonary tuberculosis. Methods We prospectively performed WGS of 112 M. tuberculosis isolates recovered from respiratory tract samples of 106 patients diagnosed with pulmonary tuberculosis between 2017 and 2019 and defined their antibiotic susceptibility profile to 17 antibiotics including antileprotics drugs. Results We incidentally observed 08 sequence variations in 07 genes, specific to seven sublineages. Altogether, we observed 09 (8%) rifampicin-resistant, 05 (4.4%) multidrug-resistant and 02 (1.7%) extensively-drug resistant isolates; whereas only one isolate exhibited in silico resistance to clofazimine. Conclusion These results support repurposing of antileprosis antibiotics as antituberculosis; and offer new targets for genotyping M. tuberculosis.

scholarly journals Bridging the TB data gap: in silico extraction of rifampicin-resistant tuberculosis diagnostic test results from whole genome sequence data

2019 ◽  
Author(s):  
Kamela Charmaine S. Ng ◽  
Jean Claude S. Ngabonziza ◽  
Pauline Lempens ◽  
Bouke Catherine de Jong ◽  
Frank van Leth ◽  
...  
Keyword(s):  
Sequence Data ◽  
Whole Genome Sequence ◽  
Whole Genome ◽  
Data Generation ◽  
Continuous Analysis ◽  
Middle Income ◽  
Tb Control ◽  
Sequencing Technologies ◽  
Surveillance Programs ◽  
Low And Middle Income

AbstractBackgroundMycobacterium tuberculosis rapid diagnostic tests (RDTs) are widely employed in routine laboratories and national surveys for detection of rifampicin-resistant (RR)-TB. However, as next generation sequencing technologies have become more commonplace in research and surveillance programs, RDTs are being increasingly complemented by whole genome sequencing (WGS). While comparison between RDTs is difficult, all RDT results can be derived from WGS data. This can facilitate continuous analysis of RR-TB burden regardless of the data generation technology employed. By converting WGS to RDT results, we enable comparison of data with different formats and sources particularly for low and middle income high TB burden countries that employ different diagnostic algorithms for drug resistance surveys. This allows national TB control programs (NTPs) and epidemiologists to utilize all available data in the setting for improved RR-TB surveillance.MethodsWe developed the Python-based MTB Genome to Test (MTBGT) tool that transforms WGS-derived data into laboratory-validated results of the primary RDTs – Xpert MTB/RIF, XpertMTB/RIF Ultra, GenoType MDRTBplus v2.0, and GenoscholarNTM+MDRTB II. The tool was validated through RDT results of RR-TB strains with diverse resistance patterns and geographic origins and applied on routine-derived WGS data.ResultsThe MTBGT tool correctly transformed the SNP data into the RDT results and generated tabulated frequencies of the RDT probes as well as rifampicin susceptible cases. The tool supplemented the RDT probe reactions output with the RR-conferring mutation based on identified SNPs. The MTBGT tool facilitated continuous analysis of RR-TB and Xpert probe reactions from different platforms and collection periods in Rwanda.ConclusionOverall, the MTBGT tool allows low and middle income countries to make sense of the increasingly generated WGS in light of the readily available RDT results, and assess whether currently implemented RDTs adequately detect RR-TB in their setting. With its feature to transform WGS to RDT results and facilitate continuous RR-TB data analysis, the MTBGT tool may bridge the gap between and among data from periodic surveys, continuous surveillance, research, and routine tests, and may be integrated within the existing national connectivity platform for use by the NTP and epidemiologists to improve setting-specific RR-TB control. The MTBGT source code and accompanying documentation is available at https://github.com/KamelaNg/MTBGT.

scholarly journals Molecular epidemiology of Candida auris in Qatar using whole genome sequence data

2021 ◽  
Vol 3 (12) ◽  
Author(s):  
Husam Salah ◽  
Sathyavathi Sundararaju ◽  
Lamya Dalil ◽  
Patrick Tang ◽  
Walid Al-Wali ◽  
...  
Keyword(s):  
Sequence Data ◽  
Multidrug Resistant ◽  
Hospital Environment ◽  
Whole Genome Sequence ◽  
Whole Genome ◽  
Resistance Mutations ◽  
Candida Auris ◽  
East Region ◽  
Echinocandin Resistance ◽  
Middle East Region

Candida auris is an emerging, multidrug resistant fungal pathogen that has become a public health threat worldwide. Candida auris spreads easily among patients within and between hospitals, and the incidence of infections has increased substantially in the last decade. Multiple C. auris outbreaks have been reported worldwide including India, USA and United Kingdom. Infections and outbreaks caused by C. auris have also been reported in the Middle East region including Kuwait, Oman, Saudi Arabia, and Qatar; however, the origin of these isolates is largely unknown. This study uses whole genome sequencing (WGS) data to determine the epidemiology and the drug resistance mutations from C. auris in Qatar. Forty samples isolated from the patients and the hospital environment were sequenced by Illumina Nextseq. Core genome SNPs revealed that all isolates belonged to the Indian lineage, which could be originated from the expatriate labour from South Asia. The genetic variability among the isolates was low but comprised of more than one genetic cluster. The environmental isolates were identical to the clinical isolates, and the isolates from patients of different hospitals/outbreaks clustered together, suggesting the transmission of C. auris could be linked to infected/colonized patients and the hospital environment. Mutations associated with azole and echinocandin resistance were discussed.

scholarly journals Phenotypic characterization of carbapenem non-susceptible gram-negative bacilli isolated from clinical specimens

PLoS ONE ◽  
2021 ◽  
Vol 16 (12) ◽  
pp. e0256556
Author(s):  
Abera Abdeta ◽  
Adane Bitew ◽  
Surafel Fentaw ◽  
Estifanos Tsige ◽  
Dawit Assefa ◽  
...  
Keyword(s):  
Public Health ◽  
Prevention And Control ◽  
Multidrug Resistant ◽  
Gram Negative Bacteria ◽  
Drug Resistant ◽  
Gram Negative ◽  
Extensively Drug Resistant ◽  
Gram Negative Organisms ◽  
And Control ◽  
Public Health Institute

Background Multidrug resistant, extremely drug-resistant, pan-drug resistant, carbapenem-resistant, and carbapenemase-producing gram-negative bacteria are becoming more common in health care settings and are posing a growing threat to public health. Objective The study was aimed to detect and phenotypically characterize carbapenem no- susceptible gram-negative bacilli at the Ethiopian Public Health Institute. Materials and methods A prospective cross-sectional study was conducted from June 30, 2019, to May 30, 2020, at the national reference laboratory of the Ethiopian Public Health Institute. Clinical samples were collected, inoculated, and incubated for each sample in accordance with standard protocol. Antimicrobial susceptibility testing was conducted using Kirby-Bauer disk diffusion method. Identification was done using the traditional biochemical method. Multidrug-resistant and extensively drug-resistant isolates were classified using a standardized definition established by the European Centre for Disease Prevention and Control and the United States Centers for Disease Prevention and Control. Gram-negative organisms with reduced susceptibility to carbapenem antibiotics were considered candidate carbapenemase producers and subjected to modified carbapenem inactivation and simplified carbapenem inactivation methods. Meropenem with EDTA was used to differentiate metallo-β-lactamase (MBL) from serine carbapenemase. Meropenem (MRP)/meropenem + phenylboronic acid (MBO) were used to differentiate Klebsiella pneumoniae carbapenemase (KPC) from other serine carbapenemase producing gram-negative organisms. Results A total of 1,337 clinical specimens were analyzed, of which 429 gram-negative bacterial isolates were recovered. Out of 429 isolates, 319, 74, and 36 were Enterobacterales, Acinetobacter species, and Pseudomonas aeruginosa respectively. In our study, the prevalence of multidrug-resistant, extensively drug-resistant, carbapenemase-producing, and carbapenem nonsusceptible gram-negative bacilli were 45.2%, 7.7%, 5.4%, and 15.4% respectively. Out of 429 isolates, 66 demonstrated reduced susceptibility to the antibiotics meropenem and imipenem. These isolates were tested for carbapenemase production of which 34.8% (23/66) were carbapenemase producers. Out of 23 carbapenemase positive gram-negative bacteria, ten (10) and thirteen (13) were metallo-beta-lactamase and serine carbapenemase respectively. Three of 13 serine carbapenemase positive organisms were Klebsiella pneumoniae carbapenemase. Conclusion This study revealed an alarming level of antimicrobial resistance (AMR), with a high prevalence of multidrug-resistant (MDR) and extremely drug-resistant, carbapenemase-producing gram-negative bacteria, particularly among intensive care unit patients at the health facility level. These findings point to a scenario in which clinical management of infected patients becomes increasingly difficult and necessitates the use of “last-resort” antimicrobials likely exacerbating the magnitude of the global AMR crisis. This mandates robust AMR monitoring and an infection prevention and control program.

scholarly journals Meningococcal Deduced Vaccine Antigen Reactivity (MenDeVAR) Index: a Rapid and Accessible Tool that Exploits Genomic Data in Public Health and Clinical Microbiology Applications

2020 ◽  
Author(s):  
Charlene M.C. Rodrigues ◽  
Keith A. Jolley ◽  
Andrew Smith ◽  
J. Claire Cameron ◽  
Ian M. Feavers ◽  
...  
Keyword(s):  
Public Health ◽  
Sequence Data ◽  
Cross Reactivity ◽  
Vaccine Antigen ◽  
Whole Genome Sequence ◽  
Clinical Settings ◽  
Whole Genome ◽  
Outbreak Management ◽  
Individual Gene ◽  
Antigen Reactivity

AbstractAs microbial genomics makes increasingly important contributions to clinical and public health microbiology, the interpretation of whole genome sequence data by non-specialists becomes essential. In the absence of capsule-based vaccines, two protein-based vaccines have been used for the prevention of invasive serogroup B meningococcal disease (IMD), since their licensure in 2013/14. These vaccines have different components and different coverage of meningococcal variants. Hence, decisions regarding which vaccine to use in managing serogroup B IMD outbreaks require information about the index case isolate including: (i) the presence of particular vaccine antigen variants; (ii) the expression of vaccine antigens; and (iii) the likely susceptibility of its antigen variants to antibody-dependent bactericidal killing. To obtain this information requires a multitude of laboratory assays, impractical in real-time clinical settings, where the information is most urgently needed. To facilitate assessment for public health and clinical purposes, we synthesised genomic and experimental data from published sources to develop and implement the ‘Meningococcal Deduced Vaccine Antigen Reactivity’ (MenDeVAR) Index, which is publicly-available on PubMLST (https://pubmlst.org). Using whole genome sequences or individual gene sequences obtained from IMD isolates or clinical specimens, MenDeVAR provides rapid evidence-based information on the presence and possible immunological cross-reactivity of different meningococcal vaccine antigen variants. The MenDeVAR Index enables practitioners who are not genomics specialists to assess the likely reactivity of vaccines for individual cases, outbreak management, or the assessment of public health vaccine programmes. MenDeVAR has been developed in consultation with, but independently of, both vaccine manufacturers.

scholarly journals Epidemiological Profile and Antimicrobial Resistance Pattern of Enteric Fever in a Tertiary Care Hospital of North India – a Seven Year Ambispective Study

2018 ◽  
Vol 61 (4) ◽  
pp. 125-130 ◽  
Author(s):  
Anuradha Makkar ◽  
Shilpi Gupta ◽  
Inam Danish Khan ◽  
Rajiv Mohan Gupta ◽  
KS Rajmohan ◽  
...  
Keyword(s):  
Public Health ◽  
Enteric Fever ◽  
Tertiary Care Hospital ◽  
Tertiary Care ◽  
Public Health Problem ◽  
Multidrug Resistant ◽  
North India ◽  
Major Public Health Problem ◽  
Care Hospital ◽  
Drug Resistant

Introduction: Enteric-fever is a major public-health problem in developing countries emerging as multidrug-resistant, Nalidixic-acid resistant and extremely drug-resistant Salmonella (Pakistan, 2016), has intensified the use of WHO watch/reserve group antimicrobials such as azithromycin and meropenem. Methods: This ambispective-study was conducted on 782 non-repeat blood-culture isolates of S. Typhi, S. Paratyphi A and S. Paratyphi B obtained from 29,184 blood cultures received at a 1000-bedded tertiary-care hospital of North-India from 2011–2017. Identification and antibiograms were obtained by Vitek-2 compact and Kirby-Bauer’s disc diffusion with resistance to ampicillin, chloramphenicol and cotrimoxazole being labeled as multidrug-resistant. Decreased ciprofloxacin-susceptibility and ciprofloxacin-resistance were defined as MIC 0.125–0.5 and >1 μg/ml. Results: S. Typhi and S. Paratyphi A in a ratio of 3.9:1 were seen between July–September predominantly distributed between 6–45 year age group. Resistance to co-trimoxazole, chloramphenicol, ceftriaxone and azithromycin was 6.1%, 13.8%, 16.1 and 5.78% respectively. Multidrug-resistant S. typhi and S. paratyphi A were 2.73% and 1.91% respectively. Conclusion: Enteric-fever is a major public-health problem in India. Emergence of multidrug-resistant, Nalidixic-acid resistant and extremely-drug resistant Salmonella mandates ongoing surveillance for targeted empirical therapy and containment of spread. Repeated epidemics call for water, sanitation, hygiene and vaccination strategies to sustain herd-immunity.

scholarly journals Emergence of a Multidrug-Resistant Hypervirulent Klebsiella pneumoniae Sequence Type 23 Strain with a Rare blaCTX-M-24-Harboring Virulence Plasmid

2019 ◽  
Vol 63 (3) ◽  
Author(s):  
Dingxia Shen ◽  
Guannan Ma ◽  
Cuidan Li ◽  
Xinmiao Jia ◽  
Chuan Qin ◽  
...  
Keyword(s):  
Public Health ◽  
Klebsiella Pneumoniae ◽  
Genetic Basis ◽  
Virulence Genes ◽  
Multidrug Resistant ◽  
Sequence Type ◽  
Hybrid Plasmid ◽  
Virulence Plasmid ◽  
Drug Resistant ◽  
Content Type

ABSTRACT Here, we report a multidrug-resistant hypervirulent Klebsiella pneumoniae (MDR-HvKP) strain of sequence type 23 (ST23) with a rare hybrid plasmid harboring virulence genes and blaCTX-M-24, and we analyze the genetic basis for relationship between genotypes and MDR-hypervirulence phenotypes. Further analysis indicates that the hybrid plasmid is formed by IS903D-mediated intermolecular transposition of the blaCTX-M-24 gene into the virulence plasmid. The emergence of MDR-HvKP strains, especially those carrying drug-resistant virulent plasmids, poses unprecedented threats/challenges to public health. This is a dangerous trend and should be closely monitored.

scholarly journals Current strategies to treat tuberculosis

F1000Research ◽  
2016 ◽  
Vol 5 ◽  
pp. 2579 ◽  
Author(s):  
Anthony T. Podany ◽  
Susan Swindells
Keyword(s):  
Public Health ◽  
Clinical Development ◽  
Drug Resistant ◽  
Significant Progress ◽  
Tb Control ◽  
Treatment Regimens ◽  
Long Period ◽  
Novel Treatment ◽  
Immunodeficiency Virus ◽  
Active Disease

Tuberculosis (TB) has been a leading cause of death for more than a century. While effective therapies exist, treatment is long and cumbersome. TB control is complicated by the overlapping problems created by global inadequacy of public health infrastructures, the interaction of the TB and human immunodeficiency virus (HIV) epidemics, and the emergence of drug-resistant TB. After a long period of neglect, there is now significant progress in the development of novel treatment regimens for TB. Focusing on treatment for active disease, we review pathways to TB regimen development and the new and repurposed anti-TB agents in clinical development.

scholarly journals Genome-based transmission modeling separates imported tuberculosis from recent transmission within an immigrant population

2017 ◽  
Author(s):  
Diepreye Ayabina ◽  
Janne O Rønning ◽  
Kristian Alfsnes ◽  
Nadia Debech ◽  
Ola B Brynildsrud ◽  
...  
Keyword(s):  
Sequence Data ◽  
Whole Genome Sequence ◽  
Time Of Arrival ◽  
Immigrant Community ◽  
Tb Control ◽  
Control Programs ◽  
Rates Of Evolution ◽  
Recent Transmission ◽  
Genotype Cluster ◽  
Low Incidence

AbstractBackgroundIn many countries tuberculosis incidence is low and largely shaped by immigrant populations from high-burden countries. This is the case in Norway, where more than 80 per cent of TB cases are found among immigrants from high-incidence countries. A variable latent period, low rates of evolution and structured social networks make separating import from within-border transmission a major conundrum to TB-control efforts in many low-incidence countries.MethodsClinical Mycobacterium tuberculosis isolates belonging to an unusually large genotype cluster associated with people born in the Horn of Africa, have been identified in Norway over the last two decades. We applied modeled transmission based on whole-genome sequence data to estimate infection times for individual patients. By contrasting these estimates with time of arrival in Norway, we estimate on a case-by-case basis whether patients were likely to have been infected before or after arrival.ResultsIndependent import was responsible for the majority of cases, but we estimate that about a quarter of the patients had contracted TB in Norway.ConclusionsThis study illuminates the transmission dynamics within an immigrant community. Our approach is broadly applicable to many settings where TB control programs can benefit from understanding when and where patients acquired tuberculosis.

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