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Journal of Hazardous Materials Mar 2022Antibiotic resistance is considered one of the biggest threats to public health and has become a major concern for governments and international organizations. Combating...
Antibiotic resistance is considered one of the biggest threats to public health and has become a major concern for governments and international organizations. Combating this problem starts with improving global surveillance of antibiotic resistance genes (ARGs) and applying standardized protocols, both in a clinical and environmental context, in agreement with the One Health approach. Exceptional efforts should be directed to controlling ARGs conferring resistance to Critically Important Antimicrobials (CIA). In this study, a systematic literature review to synthesize data on the identification of mcr genes using a PCR technique was performed. Additionally, a novel set of PCR primers for mcr-1 - mcr-9 genes detection was proposed. The developed primers were in silico and experimentally validated by comparison with mcr-specific PCR primers reported in the literature. This validation, besides being a proof-of-concept for primers' usefulness, provided insight into the distribution of mcr genes in municipal wastewater, clay and river sediments, glacier moraine, manure, seagulls and auks feces and daphnids from four countries. This analysis proved that commonly used primers may deliver false results, and some mcr genes may be overlooked in tested samples. Newly-developed PCR primers turned out to be relevant for the screening of mcr genes in various environments.
Topics: Anti-Bacterial Agents; Colistin; Drug Resistance, Bacterial; Plasmids; Polymerase Chain Reaction
PubMed: 34883371
DOI: 10.1016/j.jhazmat.2021.127936 -
Annals of the New York Academy of... Mar 2022Antimicrobial resistance (AMR) is a public health threat globally. Carbapenems are β-lactam antibiotics used as last-resort agents for treating antibiotic-resistant... (Meta-Analysis)
Meta-Analysis
Antimicrobial resistance (AMR) is a public health threat globally. Carbapenems are β-lactam antibiotics used as last-resort agents for treating antibiotic-resistant infections. Mobile genetic elements (MGEs) play an important role in the dissemination and expression of antimicrobial resistance genes (ARGs), including the mobilization of ARGs within and between species. The presence of MGEs around carbapenem-hydrolyzing enzymes, called carbapenemases, in bacterial isolates in Africa is concerning. The association between MGEs and carbapenemases is described herein. Specific plasmid replicons, integrons, transposons, and insertion sequences were found flanking specific and different carbapenemases across the same and different clones and species isolated from humans, animals, and the environment. Notably, similar genetic contexts have been reported in non-African countries, supporting the importance of MGEs in driving the intra- and interclonal and species transmission of carbapenemases in Africa and globally. Technical and budgetary limitations remain challenges for epidemiological analysis of carbapenemases in Africa, as studies undertaken with whole-genome sequencing remained relatively few. Characterization of MGEs in antibiotic-resistant infections can deepen our understanding of carbapenemase epidemiology and facilitate the control of AMR in Africa. Investment in genomic epidemiology will facilitate faster clinical interventions and containment of outbreaks.
Topics: Animals; Anti-Bacterial Agents; Bacterial Proteins; Carbapenems; Humans; One Health; Plasmids; beta-Lactamases
PubMed: 34753206
DOI: 10.1111/nyas.14703 -
Journal of Applied Microbiology Feb 2022This systematic review focuses on obtaining the most relevant information from multiple studies that detected a mobilized colistin resistance mcr gene in Salmonella for... (Review)
Review
This systematic review focuses on obtaining the most relevant information from multiple studies that detected a mobilized colistin resistance mcr gene in Salmonella for a better comprehension of its global distribution. A group of strategic and systematic keywords were combined to retrieve research data on the detection frequency of the mcr gene globally from four database platforms (Google Scholar, Science Direct, PubMed and Scielo). Forty-eight studies attended all the eligibility criteria and were selected. China was the country with the highest frequency of Salmonella strains with the mcr gene, and Europe exhibited a wide diversity of countries with positive mcr strains. In addition, animals and humans carried the highest frequency of positive strains for the mcr gene. Salmonella Typhimurium was the most frequent serovar carrying the mcr gene. Apparently, colistin overuse in animal husbandry has increased the selective pressure of antimicrobial resistance, resulting in the emergence of a plasmid-mediated colistin resistance mcr gene in China. The mcr-positive Salmonella strains are recently predominant worldwide, which is probably due to the capacity of this gene to be swiftly horizontally transmissible. The transmission ability of mcr-positive Salmonella strains to humans through the consumption of contaminated animal-based food is a public health concern.
Topics: Animals; Anti-Bacterial Agents; Colistin; Drug Resistance, Bacterial; Humans; Microbial Sensitivity Tests; Plasmids; Salmonella typhimurium
PubMed: 34480840
DOI: 10.1111/jam.15282 -
Annals of the New York Academy of... Oct 2021In the following systematic review and meta-analyses, we report several conclusions about resistance to carbapenem and polymyxin last-resort antibiotics for treating... (Meta-Analysis)
Meta-Analysis
Risk factors for, and molecular epidemiology and clinical outcomes of, carbapenem- and polymyxin-resistant Gram-negative bacterial infections in pregnant women, infants, and toddlers: a systematic review and meta-analyses.
In the following systematic review and meta-analyses, we report several conclusions about resistance to carbapenem and polymyxin last-resort antibiotics for treating multidrug-resistant bacterial infections among pregnant women and infants. Resistance to carbapenems and polymyxins is increasing, even in otherwise vulnerable groups such as pregnant women, toddlers, and infants, for whom therapeutic options are limited. In almost all countries, carbapenem-/polymyxin-resistant Klebsiella pneumoniae, Escherichia coli, and Acinetobacter baumannii infect and/or colonize neonates and pregnant women, causing periodic outbreaks with very high infant mortalities. Downregulation of plasmid-borne bla , bla , bla , bla bla , bla , and ompK35/36 in clonal strains accelerates the horizontal and vertical transmissions of carbapenem resistance among these pathogens. New Delhi metallo-β-lactamase (NDM)-positive isolates in infants/neonates have been mainly detected in China and India, while OXA-48-positive isolates in infants/neonates have been mainly detected in Africa. NDM-positive isolates in pregnant women have been found only in Madagascar. Antibiotic therapy, prolonged hospitalization, invasive procedures, mechanical ventilation, low birth weight, and preterm delivery have been common risk factors associated with carbapenem/polymyxin resistance. The use of polymyxins to treat carbapenem-resistant infections may be selecting for resistance to both agents, restricting therapeutic options for infected infants and pregnant women. Currently, low- and middle-income countries have the highest burden of these pathogens. Antibiotic stewardship, periodic rectal and vaginal screening, and strict infection control practices in neonatal ICUs are necessary to forestall future outbreaks and deaths.
Topics: Adolescent; Adult; Anti-Bacterial Agents; Carbapenems; Child, Preschool; Drug Resistance, Multiple, Bacterial; Female; Gram-Negative Bacterial Infections; Humans; Infant; Infant, Newborn; Middle Aged; Molecular Epidemiology; Mortality; Polymyxins; Pregnancy; Pregnancy Complications, Infectious; Risk Assessment; Risk Factors; Young Adult
PubMed: 34212401
DOI: 10.1111/nyas.14650 -
Germs Dec 2020Updated and comprehensive data on the mechanism underlying colistin resistance is lacking in Africa. (Review)
Review
INTRODUCTION
Updated and comprehensive data on the mechanism underlying colistin resistance is lacking in Africa.
LITERATURE SEARCH
Herein, we aimed to review available literature on the molecular mechanisms of colistin resistance in Africa. PubMed, Google Scholar, and African Journal online databases were searched on the 15th of January 2020 for original research articles that reported mechanisms of colistin resistance in any of the 54 African countries.
REVIEW
Of the 1473 studies identified through initial database search, 36 met the inclusion criteria. Colistin resistance was mostly observed in isolated from human clinical samples. Plasmid-mediated colistin resistance mechanism (26; 72.2%) was the most frequently reported resistance mechanism. About three-quarters (27; 75.0%) of the 36 studies were done in North Africa. In this zone, the mobilized colistin resistance () genes were mostly detected in harboring three plasmid types, , , and , from animal samples (n=9; 42.8%). Of the six studies performed in Southern Africa, four reported mostly detected from human samples (n=2; 50.0%) in isolates carrying , , and with diverse range of STs. One hitherto unknown mutation, the mutation in the gene was detected in colistin resistant isolates in this region, which was absent in colistin susceptible isolates. In West and Central Africa, two and one studies, respectively, reported gene exclusively in isolates.
CONCLUSIONS
Transferable plasmid mediated colistin resistance is rapidly emerging in Africa with as the predominant genetic variant in human, animals, and environmental samples.
PubMed: 33489952
DOI: 10.18683/germs.2020.1229 -
Vaccine Jan 2021Recent deadly outbreaks of Marburg virus underscore the need for an effective vaccine. A summary of the latest research is needed for this WHO priority pathogen. This... (Review)
Review
BACKGROUND
Recent deadly outbreaks of Marburg virus underscore the need for an effective vaccine. A summary of the latest research is needed for this WHO priority pathogen. This systematic review aimed to determine progress towards a vaccine for Marburg virus.
METHODS
Article search criteria were developed to query PubMed for peer-reviewed articles from 1990 through 2019 on Marburg virus vaccine clinical trials in humans and pre-clinical studies in non-human primates (NHP). Abstracts were reviewed by two authors. Relevant articles were reviewed in full. Discrepancies were resolved by a third author. Data abstracted included year, author, title, vaccine construct, number of subjects, efficacy, and demographics. Assessment for risk of bias was performed using the Syrcle tool for animal studies, and the Cochrane Collaboration risk of bias tool for human studies.
RESULTS
101 articles were identified; 27 were related to Marburg vaccines. After full text review, 21 articles were selected. 215 human subjects were in three phase 1 clinical trials, and 203 NHP in 18 studies. Vaccine constructs were DNA plasmids, recombinant vesicular stomatitis virus (VSV) vectors, adenovirus vectors, virus-like particles (VLP), among others. Two human phase 1 studies of DNA vaccines had 4 adverse effects requiring vaccine discontinuation among 128 participants and 31-80% immunogenicity. In NHP challenge studies, 100% survival was seen in 6 VSV vectored vaccines, 2 DNA vaccines, 2 VLP vaccines, and in 1 adenoviral vectored vaccine.
CONCLUSION
In human trials, two Marburg DNA vaccines provided either low immunogenicity or a failure to elicit durable immunity. A variety of NHP candidate Marburg vaccines demonstrated favorable survival and immunogenicity parameters, to include VSV, VLP, and adenoviral vectored vaccines. Elevated binding antibodies appeared to be consistently associated with protection across the NHP challenge studies. Further human trials are needed to advance vaccines to limit the spread of this highly lethal virus.
Topics: Animals; Ebolavirus; Hemorrhagic Fever, Ebola; Humans; Marburgvirus; Primates; Viral Vaccines
PubMed: 33309082
DOI: 10.1016/j.vaccine.2020.11.042 -
MSystems Nov 2020Antibiotic resistance (AR) remains a major threat to public and animal health globally. However, AR ramifications in developing countries are worsened by limited...
Antibiotic resistance (AR) remains a major threat to public and animal health globally. However, AR ramifications in developing countries are worsened by limited molecular diagnostics, expensive therapeutics, inadequate numbers of skilled clinicians and scientists, and unsanitary environments. The epidemiology of Gram-negative bacteria, their AR genes, and geographical distribution in Africa are described here. Data were extracted and analyzed from English-language articles published between 2015 and December 2019. The genomes and AR genes of the various species, obtained from the Pathosystems Resource Integration Center (PATRIC) and NCBI were analyzed phylogenetically using Randomized Axelerated Maximum Likelihood (RAxML) and annotated with Figtree. The geographic location of resistant clones/clades was mapped manually. Thirty species from 31 countries and 24 genera from 41 countries were analyzed from 146 articles and 3,028 genomes, respectively. Genes mediating resistance to β-lactams (including , , , , , and ), fluoroquinolones (, , , and mutations, etc.), aminoglycosides (including and ), sulfonamides (), trimethoprim (), tetracycline [(A/B/C/D/G/O/M/39)], colistin (), phenicols (, ), and fosfomycin () were mostly found in spp. and , and also in , , , , , etc., on mostly IncF-type, IncX, ColRNAI, and IncR plasmids, within 1 gene cassettes, insertion sequences, and transposons. Clonal and multiclonal outbreaks and dissemination of resistance genes across species and countries and between humans, animals, plants, and the environment were observed; ST103, ST101, ST1/2, and ST69/515 were common strains. Most pathogens were of human origin, and zoonotic transmissions were relatively limited. Antibiotic resistance (AR) is one of the major public health threats and challenges to effective containment and treatment of infectious bacterial diseases worldwide. Here, we used different methods to map out the geographical hot spots, sources, and evolutionary epidemiology of AR. , , , , , spp., , , , etc., were common pathogens shuttling AR genes in Africa. Transmission of the same clones/strains across countries and between animals, humans, plants, and the environment was observed. We recommend spp. or as better sentinel species for AR surveillance.
PubMed: 33234606
DOI: 10.1128/mSystems.00897-20 -
International Journal of Antimicrobial... Jan 2021Extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-E) and carbapenemase-producing Enterobacteriaceae (CPE) are widespread. Here we used the 'One Health'...
Epidemiology and prevalence of extended-spectrum β-lactamase- and carbapenemase-producing Enterobacteriaceae in humans, animals and the environment in West and Central Africa.
Extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-E) and carbapenemase-producing Enterobacteriaceae (CPE) are widespread. Here we used the 'One Health' approach to determine knowledge gaps on ESBL-E and CPE in West and Central Africa. We searched all articles on ESBL-E and CPE in these African regions published in PubMed, African Journals Online and Google Scholar from 2000 onwards. Among the 1201 articles retrieved, we selected 165 studies (West Africa, 118; Central Africa, 47) with data from 22 of the 26 West and Central Africa countries. Regarding the settings, 136 articles focused only on humans (carriage and/or infection), 6 articles on humans and animals, 13 on animals, 1 on humans and the environment, 8 on the environment and 1 on humans, animals and environments. ESBL-E prevalence ranged from 11-72% in humans and 7-79% in aquatic environments (wastewater). In animals, ESBL-E prevalence hugely varied: 0% in cattle, 11-36% in chickens, 20% in rats, 21-71% in pigs and 32-75% in dogs. The bla gene was the predominant ESBL-encoding gene and was associated with plasmids of incompatibility groups F, H, K, Y, N, I1 and R. CPE were studied only in humans. Class B metallo-β-lactamases (NDM) and class D oxacillinases (OXA-48 and OXA-181) were the most common carbapenemases. Our results show major knowledge gaps, particularly on ESBL and CPE in animals and the environment, that might limit antimicrobial resistance management in these regions. The results also emphasise the urgent need to improve active surveillance programmes in each country and to support antimicrobial stewardship.
Topics: Africa, Central; Africa, Western; Animals; Anti-Bacterial Agents; Bacterial Proteins; Cattle; Chickens; Dogs; Drug Resistance, Bacterial; Enterobacteriaceae; Enterobacteriaceae Infections; Environmental Microbiology; Humans; Plasmids; Prevalence; Rats; Swine; beta-Lactamases
PubMed: 33075511
DOI: 10.1016/j.ijantimicag.2020.106203 -
Advanced Drug Delivery Reviews 2020Vaccines are one of the most powerful technologies supporting public health. The adaptive immune response induced by immunization arises following appropriate activation...
Vaccines are one of the most powerful technologies supporting public health. The adaptive immune response induced by immunization arises following appropriate activation and differentiation of T and B cells in lymph nodes. Among many parameters impacting the resulting immune response, the presence of antigen and inflammatory cues for an appropriate temporal duration within the lymph nodes, and further within appropriate subcompartments of the lymph nodes- the right timing and location- play a critical role in shaping cellular and humoral immunity. Here we review recent advances in our understanding of how vaccine kinetics and biodistribution impact adaptive immunity, and the underlying immunological mechanisms that govern these responses. We discuss emerging approaches to engineer these properties for future vaccines, with a focus on subunit vaccines.
Topics: Adjuvants, Immunologic; B-Lymphocytes; Drug Carriers; Humans; Immunity, Humoral; Inflammation Mediators; Liposomes; Lymph Nodes; Nanoparticles; Plasmids; RNA, Messenger; T-Lymphocytes; Tissue Distribution; Vaccines
PubMed: 32598970
DOI: 10.1016/j.addr.2020.06.019 -
Microbial Drug Resistance (Larchmont,... Jan 2021We have conducted a systematic review to update available information on plasmid-mediated colistin resistance (mobilized colistin resistance []) genes in North African...
We have conducted a systematic review to update available information on plasmid-mediated colistin resistance (mobilized colistin resistance []) genes in North African countries. We have searched the articles of PubMed, Scopus, and Web of Science databases reporting plasmid-mediated colistin resistance bacteria isolated in North African countries. After searching and selection, 30 studies that included 208 positive isolates were included. Different positive strains frequencies were recorded and ranged from 2% in clinical isolates to 12.3% in environmental samples. was the predominant species recorded and these microorganisms showed high resistance to ciprofloxacin and cotrimoxazole. IncHI2 plasmids are probably the key vectors responsible for the dissemination of genes in these countries. This review highlighted that the -positive isolates are circulating in different ecological niches with different frequencies. Therefore, actions should be implemented to prevent the dissemination of the genes within and outside of these countries, such as microbiological and molecular surveillance programs and restriction use of colistin in farming.
Topics: Anti-Bacterial Agents; Colistin; Drug Resistance, Bacterial; Drug Resistance, Multiple, Bacterial; Humans; Plasmids
PubMed: 32522081
DOI: 10.1089/mdr.2019.0471