Taane Clark

Projects 47

• CompMutTB View project →
• Genomic-surveillance of-Anopheles-mosquitoes-on-the-Bijagós-Archipelago View project →
• Global Drug resistance study View project →
• Kampala Study Read summary →

  Kampala Study

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  In collaboration with the Wellcome Trust Sanger Institute, Makerere University Medical School and the TB lab at the Joint Clinical Research Centre, Uganda we have analysed the genome of 51 clinical isolates of M. tuberculosis. The sample includes drug resistant strains and longitudinal samples from individual patients. They were collected during a project Strategies for the management of multi-drug resistant tuberculosis in Kampala, Uganda funded by the Wellcome Trust. It was a four year project and was a collaboration of scientists from Uganda, UK and USA.

• Karonga Diversity Study Read summary →

  Karonga Diversity Study

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  There are few population-based studies in a high prevalence area that can apply long-term large-scale whole genome sequencing. It is more challenging to interpret transmission networks when there are many possible sources of infection. Understanding transmission in these high prevalence areas would have the greatest public health benefit. The Karonga Prevention Study (KPS) in northern Malawi has been conducting research on mycobacterial infections in the region since the 1980s, with incidence of new smear positive TB around 100/100,000 and HIV prevalence is 10%. Currently, we have over 2,000 Mycobacterium tuberculosis whole genome sequences and substantial meta data available, including HIV, household membership, contact histories and GPS data, which can be used to model explicitly important questions associated with transmission, including the role of HIV and of M. tuberculosis (sub)lineage on transmissibility. We have published initial analyses from this area (Guerra-Assuncão, et al. 2015) showing decreasing transmission over time and variation between M. tuberculosis lineages 1–4, which are not confounded by host differences. By applying more advanced computational techniques to time-labelled phylogeny and transmission chain construction it will be possible to gain greater insights into molecular evolution and multiple outbreaks, including the estimation of between-patient mutation rate and ages of mutations, as well as identifying potential significant variants associated with transmission.

• New reference genomes for Plasmodium ovale spp will assist large-scale genomic studies of these neglected malaria parasites. View project →
• Next generation targeted amplicon sequencing for insecticide resistance mutations in Aedes aegypti View project →
• Sero-epidemiological study of arbovirus infection in Cabo Verde View project →
• Barcoding method for the genetic surveillance of insecticide resistance and species identification in Anopheles gambiae View project →
• A molecular barcode to inform the geographical origin and transmission dynamics of Plasmodium vivax View project →
• COVID-profiler View project →
• COVID-19 serological and vaccine targets View project →
• Using deep learning to identify recent positive selection in malaria parasite sequence data View project →
• Environmental detection, quantification, and molecular characterization of Anopheles stephensi and Aedes aegypti View project →
• Mass drug administration with dihydroartemisinin-piperaquine impact on drug resistance View project →
• Distinctive genetic structure and selection patterns in Plasmodium vivax from South Asia and East Africa View project →
• Population dynamics and drug resistance mutations in Guinea-Bissau View project →
• Drug resistance profile and clonality of Plasmodium falciparum parasites in Cape Verde View project →
• Drug resistance surveillance of Plasmodium falciparum in Ouélessébougou, Mali View project →
• Flavivirus integrations in Aedes aegypti View project →
• Geographical classification of malaria parasites through applying machine learning View project →
• Characterizing the Impact of Primer-Template Mismatches on Recombinase Polymerase Amplification View project →
• Identification of two insecticide resistance markers in Ethiopian Anopheles stephensi mosquitoes View project →
• New insights into sulfadoxine-pyrimethamine antimalarial drug resistance View project →
• Analysis of Klebsiella pneumoniae from Portuguese hospitals reveals insights into circulating amr View project →
• Genomic analysis of hypervirulent Klebsiella pneumoniae reveals potential genetic markers View project →
• Genomic analysis of global Klebsiella pneumoniae plasmids View project →
• Methylation analysis of Klebsiella pneumoniae from Portuguese hospitals View project →
• A phylogenomic approach for the analysis of colistin resistance-associated genes in Klebsiella pneumoniae View project →
• Extended-spectrum beta-lactam and carbapenem-resistant Klebsiella pneumoniae polyclonal outbreak View project →
• Genomic Epidemiology of Carbapenemase Producing Klebsiella pneumoniae Strains Enables the Detection of a Misidentified Klebsiella variicola KPC-3 View project →
• Mixed infections in genotypic drug-resistant Mycobacterium tuberculosis (GMM4TB) View project →
• Malaria-MOI, A flexible and scalable tool for predicting multiplicity of infection in malaria parasites. View project →
• Tracing MRSA Transmission Read summary →

  Tracing MRSA Transmission

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  Recent evidence suggests hospital transmission of methicillin-resistant Staphylococcus aureus (MRSA) is uncommon in UK centres that have implemented sustained infection control programmes. We investigated whether a healthcare-network analysis could shed light on transmission paths currently sustaining MRSA levels in UK hospitals. A cross-sectional observational study was performed in two NHS hospital groups and a general district hospital in South-East London. All MRSA patients identified at inpatient, outpatient and community settings between 1st November 2011 and 29th February 2012 were included. We identified genetically-defined MRSA transmission clusters in individual hospitals and across the healthcare-network, and examined genetic differentiation of ST22 MRSA isolates within and between hospitals and inpatient or outpatient and community settings, as informed by average and median pairwise single nucleotide polymorphisms (SNPs) and SNP-based proportions of nearly identical isolates. 248/610 (40.7%) MRSA patients were linked in 90 transmission-clusters, of which 27 spanned multiple hospitals. Analysis of a large 32 patient ST22-MRSA cluster showed that 26/32 patients (81·3%) had multiple contacts with one another during ward stays at any hospital. No residential, outpatient or significant community healthcare contacts were identified. Genetic differentiation between ST22 MRSA inpatient isolates from different hospitals was less than between inpatient isolates from the same hospitals (p ≤ 0.01). Overall, there is evidence of frequent ward-based transmission of MRSA brought about by frequent patient admissions to multiple hospitals. Limiting in-ward transmission requires sharing of MRSA-status data between hospitals. This work was in partnership with Jonathan Edgeworth (KCL), and is now published

• Population genetic analysis of Plasmodium vivax View project →
• Population dynamics around Lake Victoria, Kenya View project →
• Population genetic analysis of Plasmodium knowlesi View project →
• Predicting the most likely evolutionary trajectories in the step-wise accumulation of resistance mutations View project →
• primedRPA, primer design for recombinase polymerase amplification assays View project →
• Tracing Salmonella transmission in The Philippines Read summary →

  Tracing Salmonella transmission in The Philippines

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  Salmonellosis, caused by Salmonella, is among the most frequently reported foodborne diseases worldwide, including in the Philippines. While numerous potential means of transmission exist, commercial chicken and pig meat has been identified as one of the most important food vehicles for these organisms. Treatment options for salmonellosis are decreasing as the underlying bacteria continue to show resistance to antimicrobial drugs. Multi-drug resistant isolates of Salmonella are present in the Philippines. To fully understand transmission dynamics and virulence across the food chains requires the genomic characterisation of isolates. Whole-genome sequencing (WGS) technology has become a fast and affordable tool that is revolutionizing the fields of genetics, microbiology, and ecology, as well as public health surveillance and response. WGS analysis can potentially be a rapid and cost-effective approach to define resistance genotypes, predict resistance phenotypes and identify identical isolate genomes that are part of a transmission chains. Across domains in the food chain in Manilla and Pampanga, including markets and retailers, we propose to test poultry and swine meat for Salmonella, and sequence the pathogens. We will build phylogenies and compare inferred phenotypes to laboratory determined virulence and drug resistance outcomes.

• Selective whole genome amplification of Plasmodium malariae reveals insights into pop structure View project →
• Philippines TB Drug Resistance Study Read summary →

  Philippines TB Drug Resistance Study

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  The Philippines is a high burden country for both TB and multi-drug resistant-TB (MDR-TB) (WHO, 2015). Whole genome sequencing of M. tuberculosis can be used to characterise strain-types linked to virulence, identify drug resistance mutations, assist clinical treatment decision-making, as well as establish who may have transmitted to whom and thus allow targeted resources to hotspot areas to reduce transmission. The UK-Philippine collaboration proposes to characterise M. tuberculosis samples from subjects from the recently completed Philippine-wide 2nd DR Survey (n>1,000). M. tuberculosis strains at the Research Institute for Tropical Medicine’s National Tuberculosis Reference Laboratory (RITM-NTRL, Philippines) will be sequenced with the assistance of the Philippines Genome Centre (PGC) using cutting-edge whole genome sequencing technology. This project aims to determine the genomic diversity of M. tuberculosis in the Philippines.

• V-Campaign Read summary →

  V-Campaign

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  We have established a network (V-CAMPAIGN) to introduce genomic technologies that will allow the developing an understanding of how mosquito control initiatives and patient therapies affect genetic diversity in both the vectors and pathogens; and their consequent impact. This goal will be achieved by integrating sequencing and genotyping of mosquito samples (including their pathogens) from Asia (Malaysia and Philippines), Africa (Kenya, Malawi and Cabo Verde) and South America (Brazil), and analyzing the resulting genetic data with epidemiological meta data (e.g. vector control measures, geographical location, species, mosquito abundance, insecticide use) together.

• Global genetic diversity of var2csa in Plasmodium falciparum, pregnancy & vaccine development View project →
• Genetic diversity of Plasmodium vivax isolates from pregnant women View project →
• Using an ecological study approach to investigate potential co-acting risk factors for an unusual pattern of microcephaly in Brazil View project →
• Surveillance of Aedes aegypti populations, Zika virus infection, insecticide resistance and genetic diversity View project →