ORCID Profile
0000-0002-3637-7155
Current Organisations
National Institute for Communicable Diseases
,
University of the Witwatersrand
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Publisher: Research Square Platform LLC
Date: 26-05-2023
DOI: 10.21203/RS.3.RS-2923767/V1
Abstract: Shigellosis, a leading cause of diarrhoeal mortality and morbidity globally, predominantly affects children under five years of age living in low- and middle-income countries. While whole genome sequence analysis (WGSA) has been effectively used to further our understanding of shigellosis epidemiology, antimicrobial resistance, and transmission, it has been under-utilised in sub-Saharan Africa. In this study, we applied WGSA to large sub-s le of surveillance isolates from South Africa, collected from 2011 to 2015, focussing on Shigella flexneri 2a and Shigella sonnei. We found each serotype was epidemiologically distinct. The four identified S. flexneri 2a clusters having distinct geographical distributions, and antimicrobial resistance (AMR) and virulence profiles, while the four sub-Clades of S. sonnei varied in virulence plasmid retention. Our results support serotype specific ecology as a driver for epidemiological differences, show AMR is not required for epidemiological success in S. flexneri, and that the HIV epidemic may have promoted Shigella population expansion.
Publisher: Microbiology Society
Date: 11-2019
Publisher: Oxford University Press (OUP)
Date: 05-2023
DOI: 10.1093/OFID/OFAD044
Abstract: The global response to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic demonstrated the value of timely and open sharing of genomic data with standardized metadata to facilitate monitoring of the emergence and spread of new variants. Here, we make the case for the value of Salmonella Typhi (S. Typhi) genomic data and demonstrate the utility of freely available platforms and services that support the generation, analysis, and visualization of S. Typhi genomic data on the African continent and more broadly by introducing the Africa Centres for Disease Control and Prevention's Pathogen Genomics Initiative, SEQAFRICA, Typhi Pathogenwatch, TyphiNET, and the Global Typhoid Genomics Consortium.
Publisher: Cold Spring Harbor Laboratory
Date: 12-07-2023
DOI: 10.1101/2023.07.10.23292487
Abstract: Carbapenem-resistant Acinetobacter baumannii (CRAb) has emerged as a major and often fatal cause of bloodstream infections among hospitalized patients in low- and middle-income countries (LMICs). CRAb outbreaks are hypothesized to arise from reservoirs in the hospital environment, but outbreak investigations in LMICs are seldom able to incorporate whole genome sequencing (WGS) due to resource limitations. We performed WGS at the National Institute for Communicable Diseases (Johannesburg, South Africa) on stored A. baumannii isolates (n=43) collected during 2021–2022 from a 530-bed referral hospital in Gaborone, Botswana where CRAb infection incidence was noted to be rising. This included blood culture isolates from patients (aged 2 days – 69 years), and environmental isolates collected at the hospital’s 33-bed neonatal unit. Multilocus sequence typing (MLST), antimicrobial/biocide resistance gene identification, and phylogenetic analyses were performed using publicly accessible analysis pipelines. Single nucleotide polymorphism (SNP) matrices were used to assess clonal lineage. MLST revealed 79% of isolates were sequence type 1 (ST1), including all 19 healthcare-associated blood isolates and three out of five environmental isolates. Genes encoding for carbapenemases ( bla NDM-1 , bla OXA-23 ) and biocide resistance ( qacE ) were present in all 22 ST1 isolates. Phylogenetic analysis of the ST1 clade demonstrated spatial clustering by hospital unit. Nearly identical isolates spanned wide ranges in time ( year), suggesting ongoing transmission from environmental sources. One highly similar clade (average difference of 2.3 SNPs) contained all eight neonatal blood isolates and three environmental isolates from the neonatal unit. These results were critical in identifying environmental reservoirs (e.g. sinks) and developing remediation strategies. Using a phylogenetically informed approach, we also identified diagnostic genes useful for future tracking of outbreak clones without the need for WGS. This work highlights the power of South-South and South-North partnerships in building public health laboratory capacity in LMICs to detect and contain the spread of antimicrobial resistance.
Publisher: Cold Spring Harbor Laboratory
Date: 30-12-2022
DOI: 10.1101/2022.12.28.22283969
Abstract: The Global Typhoid Genomics Consortium was established to bring together the typhoid research community to aggregate and analyse Salmonella enterica serovar Typhi (Typhi) genomic data to inform public health action. This analysis, which marks twenty-one years since the publication of the first Typhi genome, represents the largest Typhi genome sequence collection to date (n=13,000), and provides a detailed overview of global genotype and antimicrobial resistance (AMR) distribution and temporal trends, generated using open analysis platforms (GenoTyphi and Pathogenwatch). Compared with previous global snapshots, the data highlight that genotype 4.3.1 (H58) has not spread beyond Asia and Eastern/Southern Africa in other regions, distinct genotypes dominate and have independently evolved AMR. Data gaps remain in many parts of the world, and we show potential of travel-associated data to provide informal “sentinel” surveillance for such locations. The data indicate ciprofloxacin non-susceptibility ( resistance determinant) is widespread across geographies and genotypes, with high-level resistance (≥3 determinants) reaching 20% prevalence in South Asia. Extensively drug-resistant (XDR) typhoid has become dominant in Pakistan (70% in 2020), but has not yet become established elsewhere. Ceftriaxone resistance has emerged in eight non-XDR genotypes, including a ciprofloxacin-resistant lineage (4.3.1.2.1) in India. Azithromycin resistance mutations were detected at low prevalence in South Asia, including in two common ciprofloxacin-resistant genotypes. The Consortium’s aim is to encourage continued data sharing and collaboration to monitor the emergence and global spread of AMR Typhi, and to inform decision-making around the introduction of typhoid conjugate vaccines (TCVs) and other prevention and control strategies.
No related grants have been discovered for Anthony Smith.