scholarly journals Genomic analysis of Klebsiella pneumoniae isolates from Malawi reveals acquisition of multiple ESBL determinants across diverse lineages

2019 ◽  
Vol 74 (5) ◽  
pp. 1223-1232 ◽  
Author(s):  
Patrick Musicha ◽  
Chisomo L Msefula ◽  
Alison E Mather ◽  
Chrispin Chaguza ◽  
Amy K Cain ◽  
...  
Keyword(s):  
Population Structure ◽  
Klebsiella Pneumoniae ◽  
Genomic Sequence ◽  
Genomic Analysis ◽  
Carbapenem Resistance ◽  
Sub Saharan Africa ◽  
Genetic Determinants ◽  
Association Analyses ◽  
Sub Saharan ◽  
Global Population

Abstract Objectives ESBL-producing Klebsiella pneumoniae (KPN) pose a major threat to human health globally. We carried out a WGS study to understand the genetic background of ESBL-producing KPN in Malawi and place them in the context of other global isolates. Methods We sequenced genomes of 72 invasive and carriage KPN isolates collected from patients admitted to Queen Elizabeth Central Hospital, Blantyre, Malawi. We performed phylogenetic and population structure analyses on these and previously published genomes from Kenya (n = 66) and from outside sub-Saharan Africa (n = 67). We screened for presence of antimicrobial resistance (AMR) genetic determinants and carried out association analyses by genomic sequence cluster, AMR phenotype and time. Results Malawian isolates fit within the global population structure of KPN, clustering into the major lineages of KpI, KpII and KpIII. KpI isolates from Malawi were more related to those from Kenya, with both collections exhibiting more clonality than isolates from the rest of the world. We identified multiple ESBL genes, including blaCTX-M-15, several blaSHV, blaTEM-63 and blaOXA-10, and other AMR genes, across diverse lineages of the KPN isolates from Malawi. No carbapenem resistance genes were detected; however, we detected IncFII and IncFIB plasmids that were similar to the carbapenem resistance-associated plasmid pNDM-mar. Conclusions There are multiple ESBL genes across diverse KPN lineages in Malawi and plasmids in circulation that are capable of carrying carbapenem resistance. Unless appropriate interventions are rapidly put in place, these may lead to a high burden of locally untreatable infection in vulnerable populations.

scholarly journals Genomic and antigenic diversity of carried Klebsiella pneumoniae isolates mirrors that of invasive isolates in Blantyre, Malawi

2021 ◽  
Author(s):  
Joseph M Lewis ◽  
Madalitso Mphasa ◽  
Rachel Banda ◽  
Mathew A Beale ◽  
Jane Mallewa ◽  
...  
Keyword(s):  
Population Structure ◽  
Klebsiella Pneumoniae ◽  
Vaccine Development ◽  
Genomic Analysis ◽  
Cost Effective ◽  
Invasive Disease ◽  
Sub Saharan Africa ◽  
Genomic Context ◽  
Extended Spectrum Beta Lactamase ◽  
O Antigen

Klebsiella pneumoniae is an antimicrobial resistance (AMR) associated pathogen of global importance, and polyvalent vaccines targeting K. pneumoniae O-antigens are in development. Genomes from sub-Saharan Africa (sSA) are underrepresented in global sequencing efforts. We therefore carried out a genomic analysis of extended-spectrum beta-lactamase (ESBL)-producing K. pneumoniae complex isolates colonising adults in Blantyre, Malawi, placed these isolates in a global genomic context, and compared colonising to invasive isolates from the main public hospital in Blantyre. 203 isolates from stool and rectal swabs from adults were whole-genome sequenced and compared to a publicly available multicountry collection of 484 K. pneumoniae genomes sampled to cover maximum diversity of the species, 150 previously sequenced Malawian and 66 Kenyan isolates from blood or sterile sites. We inferred phylogenetic relationships and analysed the diversity of genetic loci linked to AMR, virulence, capsule (K-) and LPS O-antigen (O-types). We find that the diversity of Malawian Klebsiella isolates is representative of the species population structure, but with local success and expansion of sequence types (STs) ST14, ST15, ST340 and ST307. Siderophore and hypermucoidy genes were more frequent in invasive versus carriage isolates (present in 13% vs 1%, p < 0.001) but still generally lacking in most invasive isolates. The population structure and distribution of O-antigen types was similar in Malawian invasive and carriage isolates, with O4 being more common in Malawian isolates (14%) than in previously published studies (2-5%). We conclude that host factors, pathogen opportunity or alternate virulence loci not linked to invasive disease elsewhere are likely to be the major determinants of invasive disease in Malawi. Distinct ST and O-type distributions in Malawi highlights the need for geographically aware sampling to robustly define secular trends in Klebsiella diversity. Colonising and invasive isolates in Blantyre are similar and hence O-typing of colonising Klebsiella isolates may be a rapid and cost-effective approach to describe global diversity and guide vaccine development.

Emerging carbapenem resistance in ESKAPE organisms in sub-Saharan Africa and the way forward

2021 ◽  
Vol 1 (1) ◽  
pp. 3-6
Author(s):  
John Njeru
Keyword(s):  
Public Health ◽  
Carbapenem Resistance ◽  
Developed Countries ◽  
Sub Saharan Africa ◽  
Resistant Bacteria ◽  
Carbapenem Resistant ◽  
Public Health Threat ◽  
Enterobacter Species ◽  
Significant Public Health ◽  
Sub Saharan

The epidemiology of Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species (ESKAPE) and their role in the development and spread of multidrug resistance (MDR) is not well characterized in sub-Saharan Africa (SSA). Carbapenems possess a broad spectrum of activity and are often reserved for the treatment of MDR infections in developed countries. However, the emergence of carbapenem resistance is increasingly being reported and therefore presents a significant public health threat. Although carbapenems are generally unavailable in African hospitals due to high cost, a small number of studies have reported the occurrence of carbapenem-resistant bacteria (CRB) in SSA. This, therefore, shows that carbapenem resistance (CR) is emerging in Africa. Thus, there is a critical need for deploying robust national and regional multidisciplinary, collaborative, and regulatory approaches aiming at elucidating the epidemiology of CR, its burden on the health care system, and strategies for compacting the development and spread of CR. This report hopes to highlight the epidemiology of carbapenem resistance and the main drivers of antibiotic resistance in SSA and proposes future strategies that can be used to combat the emergence of carbapenem resistance in the region

scholarly journals Genomic investigation of a suspected Klebsiella pneumoniae outbreak in a neonatal care unit in sub-Saharan Africa

2021 ◽  
Vol 7 (11) ◽  
Author(s):  
Jennifer Cornick ◽  
Patrick Musicha ◽  
Chikondi Peno ◽  
Ezgi Seager ◽  
Pui-Ying Iroh Tam ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Resistance Genes ◽  
Type Species ◽  
Bloodstream Infections ◽  
Sub Saharan Africa ◽  
Content Type ◽  
Link Type ◽  
Sub Saharan ◽  
Neonatal Care Unit ◽  
Suspected Outbreak

A special-care neonatal unit from a large public hospital in Malawi was noted as having more frequent, difficult-to-treat infections, and a suspected outbreak of multi-drug-resistant Klebsiella pneumoniae was investigated using genomic characterisation. All K. pneumoniae bloodstream infections (BSIs) from patients in the neonatal ward (n=62), and a subset of K. pneumoniae BSI isolates (n=38) from other paediatric wards in the hospital, collected over a 4 year period were studied. After whole genome sequencing, the strain sequence types (STs), plasmid types, virulence and resistance genes were identified. One ST340 clone, part of clonal complex 258 (CC258) and an ST that drives hospital outbreaks worldwide, harbouring numerous resistance genes and plasmids, was implicated as the likely cause of the outbreak. This study contributes molecular information necessary for tracking and characterizing this important hospital pathogen in sub-Saharan Africa.

scholarly journals Genomic investigation of a suspected multi-drug resistant Klebsiella pneumoniae outbreak in a neonatal care unit in sub-Saharan Africa

2020 ◽  
Author(s):  
Jennifer Cornick ◽  
Patrick Musicha ◽  
Chikondi Peno ◽  
Ezgi Saeger ◽  
Pui-ying Iroh Toh ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Resistance Genes ◽  
Sub Saharan Africa ◽  
Whole Genome ◽  
Drug Resistant ◽  
Sub Saharan ◽  
Neonatal Care Unit ◽  
Suspected Outbreak

ABSTRACTA suspected outbreak of multi-drug resistant (MDR) Klebsiella pneumoniae in a Malawian neonatal unit was investigated using whole-genome sequencing. Strain-types, virulence and resistance genes of K. pneumoniae isolated from patients from the hospital over a four-year period were identified. A MDR ST340 clone was implicated as the likely outbreak cause.

scholarly journals Evolution of Carbapenem-Resistant Serotype K1 Hypervirulent Klebsiella pneumoniae by Acquisition of blaVIM-1-Bearing Plasmid

2019 ◽  
Vol 63 (9) ◽  
Author(s):  
Ning Dong ◽  
Qiaoling Sun ◽  
Yonglu Huang ◽  
Lingbin Shu ◽  
Lianwei Ye ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Genomic Analysis ◽  
Carbapenem Resistance ◽  
Sequence Type ◽  
Mosaic Structure ◽  
Multiple Gene ◽  
Content Type ◽  
Carbapenem Resistant ◽  
Simultaneous Expression

ABSTRACT We report the identification of a carbapenem-resistant, hypervirulent Klebsiella pneumoniae (hvKp) strain which produced the carbapenemase VIM-1. Genomic analysis showed that the strain belonged to sequence type ST23 and serotype K1, a major hvKp clone, and harbored three resistance-encoding plasmids. Among them, a blaVIM-1-bearing plasmid was found to possess a mosaic structure presumably generated by multiple gene mobilization events. This finding indicates that hvKp actively acquires mobile resistance-encoding elements, facilitating simultaneous expression of hypervirulence and carbapenem-resistance.

scholarly journals Antimalarial peroxides

2009 ◽  
Vol 74 (11) ◽  
pp. 1155-1193 ◽  
Author(s):  
Dejan Opsenica ◽  
Bogdan Solaja
Keyword(s):  
Artemisia Annua ◽  
Antimalarial Activity ◽  
Sub Saharan Africa ◽  
World Health ◽  
Active Principle ◽  
Therapeutic Practice ◽  
Endemic Malaria ◽  
Sub Saharan ◽  
Health Organization ◽  
Global Population

The problem of endemic malaria continues unabated globally. Malaria affects 40 % of the global population, causing an estimated annual mortality of 1.5-2.7 million people. The World Health Organization (WHO) estimates that 90 % of these deaths occur in sub-Saharan Africa among infants under the age of five. While a vaccine against malaria continues to be elusive, chemotherapy remains the most viable alternative towards treatment of the disease. During last years, the situation has become urgent in many ways, but mainly because of the development of chloroquine-resistant (CQR) strains of Plasmodium falciparum (Pf). The discovery that artemisinin (ART, 1), an active principle of Artemisia annua L., expresses a significant antimalarial activity, especially against CQR strains, opened new approaches for combating malaria. Since the early 1980s, hundreds of semi-synthetic and synthetic peroxides have been developed and tested for their antimalarial activity, the results of which were extensively reviewed. In addition, in therapeutic practice, there is no reported case of drug resistance to these antimalarial peroxides. This review summarizes recent achievements in the area of peroxide drug development for malaria chemotherapy.

scholarly journals Population genomic analysis of Cryptococcus Brazilian isolates reveals an African type subclade distribution

2021 ◽  
Author(s):  
Corinne Maufrais ◽  
Luciana de Oliveira ◽  
Rafael W Bastos ◽  
Frédérique Moyrand ◽  
Flavia C G Reis ◽  
...  
Keyword(s):  
Population Structure ◽  
South America ◽  
Genomic Analysis ◽  
Opportunistic Pathogen ◽  
South American ◽  
Brazilian Isolate ◽  
Population Genomic ◽  
The World ◽  
Lineage Specificity ◽  
Global Population

Abstract The genomes of a large number of Cryptococcus neoformans isolates have been sequenced and analyzed in recent years. These genomes have been used to understand the global population structure of this opportunistic pathogen. However, only a small number of South American isolates have been considered in these studies, and the population structure of C. neoformans in this part of the world remains elusive. Here, we analyzed the genomic sequences of 53 Brazilian Cryptococcus isolates and deciphered the C. neoformans population structure in this country. Our data reveal an African-like structure that suggested repeated intercontinental transports from Africa to South America. We also identified a mutator phenotype in one VNBII Brazilian isolate, exemplifying how fast-evolving isolates can shape the Cryptococcus population structure. Finally, phenotypic analyses revealed wide diversity but not lineage specificity in the expression of classical virulence traits within the set of isolates.

scholarly journals Restoring degraded soil through climate smart agriculture

2020 ◽  
pp. 119-124
Author(s):  
Iyere-Usiahon P.N.O ◽  
Ndor E ◽  
Jayeoba O. J ◽  
Kuje J
Keyword(s):  
Soil Degradation ◽  
Agricultural Development ◽  
Sub Saharan Africa ◽  
Soil Pressure ◽  
Degraded Soil ◽  
Increase In Productivity ◽  
Sub Saharan ◽  
Development Approach ◽  
Smart Agriculture ◽  
Global Population

Research has shown that the global population is increasing geometrically, and the soil pressure is increasing, leading to soil degradation. In Sub-Saharan Africa (SSA), soil degradation has led to the loss of about 615 million hectares while in Nigeria the effect is enormous, considering that Nigeria is the most populous nation in Africa and highly dependent on agriculture. To manage the soil better, there is a need for an approach that is sustainable, resilient, and can reduce Green House Gases. Such an approach is found in Climate-Smart Agriculture (CSA) which is one agricultural development approach aimed at a sustainable increase in productivity and resilience, while also reducing/removing emissions of greenhouse gases. The CSA practices are based on soil conservation that is suitable for a particular locality.

scholarly journals The effect of recombination on the evolution of a population of Neisseria meningitidis

2020 ◽  
Author(s):  
Neil MacAlasdair ◽  
Maiju Pesonen ◽  
Ola Brynildsrud ◽  
Vegard Eldholm ◽  
Paul A. Kristiansen ◽  
...  
Keyword(s):  
Population Structure ◽  
Burkina Faso ◽  
Neisseria Meningitidis ◽  
Large Scale ◽  
Invasive Disease ◽  
Pathogen Transmission ◽  
Sub Saharan Africa ◽  
Health Concern ◽  
Recombination Hotspots ◽  
Sub Saharan

Neisseria meningitidis (the meningococcus) is a major human pathogen with a history of high invasive disease burden, particularly in sub-Saharan Africa. Our current understanding of the evolution of meningococcal genomes is limited by the rarity of large-scale genomic population studies and lack of in-depth investigation of the genomic events associated with routine pathogen transmission. Here we fill this knowledge gap by a detailed analysis of 2,839 meningococcal genomes obtained through a carriage study of over 50,000 samples collected systematically in Burkina Faso, West Africa, before, during, and after the serogroup A vaccine rollout, 2009-2012. Our findings indicate that the meningococcal genome is highly dynamic, with recombination hotspots and frequent gene sharing across deeply separated lineages in a structured population. Furthermore, our findings illustrate the profound effect of population structure on genome flexibility, with some lineages in Burkina Faso being orders of magnitude more recombinant than others. We also examine the effect of selection on the population, in particular how it is correlated with recombination. We find that recombination principally acts to prevent the accumulation of deleterious mutations, although we do also find an example of recombination acting to speed the adaptation of a gene. In general, we show the importance of recombination in the evolution of a geographically expansive population with deep population structure in a short timescale. This has important consequences for our ability to both foresee the outcomes of vaccination programmes and, using surveillance data, predict when lineages of the meningococcus are likely to become a public health concern.

scholarly journals Ultra-rapid metagenotyping of the human gut microbiome

2020 ◽  
Author(s):  
Zhou Jason Shi ◽  
Boris Dimitrov ◽  
Chunyu Zhao ◽  
Stephen Nayfach ◽  
Katherine S. Pollard
Keyword(s):  
Population Structure ◽  
High Performance ◽  
Human Microbiome ◽  
Metagenomic Sequencing ◽  
Nucleotide Polymorphisms ◽  
Genetic Determinants ◽  
Human Gut ◽  
Single Nucleotide ◽  
Sequencing Errors ◽  
Global Population

AbstractSequence variation is used to quantify population structure and identify genetic determinants of phenotypes that vary within species. In the human microbiome and other environments, single nucleotide polymorphisms (SNPs) are frequently detected by aligning metagenomic sequencing reads to catalogs of genes or genomes. But this requires high-performance computing and enough read coverage to distinguish SNPs from sequencing errors. We solved these problems by developing the GenoTyper for Prokaytotes (GT-Pro), a suite of novel methods to catalog SNPs from genomes and use exact k-mer matches to perform ultra-fast reference-based SNP calling from metagenomes. Compared to read alignment, GT-Pro is more accurate and two orders of magnitude faster. We discovered 104 million SNPs in 909 human gut species, characterized their global population structure, and tracked pathogenic strains. GT-Pro democratizes strain-level microbiome analysis by making it possible to genotype hundreds of metagenomes on a personal computer.Software availabilityGT-Pro is available at https://github.com/zjshi/gt-pro.

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