ORCID Profile
0000-0003-2309-1171
Current Organisation
University of Oxford
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Publisher: eLife Sciences Publications, Ltd
Date: 10-08-2021
DOI: 10.7554/ELIFE.62997
Abstract: National Malaria Control Programmes (NMCPs) currently make limited use of parasite genetic data. We have developed GenRe-Mekong, a platform for genetic surveillance of malaria in the Greater Mekong Subregion (GMS) that enables NMCPs to implement large-scale surveillance projects by integrating simple s le collection procedures in routine public health procedures. S les from symptomatic patients are processed by SpotMalaria, a high-throughput system that produces a comprehensive set of genotypes comprising several drug resistance markers, species markers and a genomic barcode. GenRe-Mekong delivers Genetic Report Cards, a compendium of genotypes and phenotype predictions used to map prevalence of resistance to multiple drugs. GenRe-Mekong has worked with NMCPs and research projects in eight countries, processing 9623 s les from clinical cases. Monitoring resistance markers has been valuable for tracking the rapid spread of parasites resistant to the dihydroartemisinin-piperaquine combination therapy. In Vietnam and Laos, GenRe-Mekong data have provided novel knowledge about the spread of these resistant strains into previously unaffected provinces, informing decision-making by NMCPs. GenRe-Mekong provides detailed knowledge about drug resistance at a local level, and facilitates data sharing at a regional level, enabling cross-border resistance monitoring and providing the public health community with valuable insights. The project provides a rich open data resource to benefit the entire malaria community. The GenRe-Mekong project is funded by the Bill and Melinda Gates Foundation (OPP11188166, OPP1204268). Genotyping and sequencing were funded by the Wellcome Trust (098051, 206194, 203141, 090770, 204911, 106698/B/14/Z) and Medical Research Council (G0600718). A proportion of s les were collected with the support of the UK Department for International Development (201900, M006212), and Intramural Research Program of the National Institute of Allergy and Infectious Diseases.
Publisher: F1000 Research Ltd
Date: 12-06-2018
DOI: 10.12688/WELLCOMEOPENRES.13751.1
Abstract: Background: Village Malaria Workers (VMWs) are lay people trained to provide a valuable role in frontline testing and treatment of malaria in rural villages in Cambodia. Emergence of artemisinin-resistant malaria highlights the essential role of such VMWs in surveillance and early treatment of malaria. Smartphone technology offers huge potential to support VMWs in isolated and resource-poor settings. Methods: We investigated the feasibility of issuing established VMWs with a smartphone, bespoke Android application and solar charger to support their role. 27 VMWs in K ong Cham and Kratie provinces participated. Results: 26/27 of the smartphones deployed were working well at study completion twelve months later. Interviews with VMWs using quantitative and qualitative methods revealed pride, ease of use and reports of faster communication with the smartphone. VMWs also expressed a strong wish to help people presenting with non-malarial fever, for which further potential supportive smartphone applications are increasingly available. Conclusions: As a result of this pilot study, two smartphone based reporting systems for malaria have been developed at the Cambodian National Malaria Center, and the programme is now being extended nationwide. The full code for the smartphone application is made available to other researchers and healthcare providers with this article. Smartphones represent a feasible platform for developing the VMW role to include other health conditions, thus maintaining the relevance of these important community health workers.
Publisher: eLife Sciences Publications, Ltd
Date: 16-11-2022
Publisher: Public Library of Science (PLoS)
Date: 14-10-2021
DOI: 10.1371/JOURNAL.PNTD.0009858
Abstract: Scrub typhus is an acute febrile illness caused by intracellular bacteria from the genus Orientia . It is estimated that one billion people are at risk, with one million cases annually mainly affecting rural areas in Asia-Oceania. Relative to its burden, scrub typhus is understudied, and treatment recommendations vary with poor evidence base. These knowledge gaps could be addressed by establishing an in idual participant-level data (IPD) platform, which would enable pooled, more detailed and statistically powered analyses to be conducted. This study aims to assess the characteristics of scrub typhus treatment studies and explore the feasibility and potential value of developing a scrub typhus IPD platform to address unanswered research questions. We conducted a systematic literature review looking for prospective scrub typhus clinical treatment studies published from 1998 to 2020. Six electronic databases (Ovid Embase, Ovid Medline, Ovid Global Health, Cochrane Library, Scopus, Global Index Medicus), ClinicalTrials.gov, and WHO ICTRP were searched. We extracted data on study design, treatment tested, patient characteristics, diagnostic methods, geographical location, outcome measures, and statistical methodology. Among 3,100 articles screened, 127 were included in the analysis. 12,079 participants from 12 countries were enrolled in the identified studies. ELISA, PCR, and eschar presence were the most commonly used diagnostic methods. Doxycycline, azithromycin, and chlor henicol were the most commonly administered antibiotics. Mortality, complications, adverse events, and clinical response were assessed in most studies. There was substantial heterogeneity in the diagnostic methods used, treatment administered (including dosing and duration), and outcome assessed across studies. There were few interventional studies and limited data collected on specific groups such as children and pregnant women. There were a limited number of interventional trials, highlighting that scrub typhus remains a neglected disease. The heterogeneous nature of the available data reflects the absence of consensus in treatment and research methodologies and poses a significant barrier to aggregating information across available published data without access to the underlying IPD. There is likely to be a substantial amount of data available to address knowledge gaps. Therefore, there is value for an IPD platform that will facilitate pooling and harmonisation of currently scattered data and enable in-depth investigation of priority research questions that can, ultimately, inform clinical practice and improve health outcomes for scrub typhus patients.
Publisher: Wiley
Date: 02-09-2022
DOI: 10.1111/GCB.16395
Abstract: Scrub typhus is a climate‐sensitive and life‐threatening vector‐borne disease that poses a growing public health threat. Although the climate‐epidemic associations of many vector‐borne diseases have been studied for decades, the impacts of climate on scrub typhus remain poorly understood, especially in the context of global warming. Here we incorporate Chinese national surveillance data on scrub typhus from 2010 to 2019 into a climate‐driven generalized additive mixed model to explain the spatiotemporal dynamics of this disease and predict how it may be affected by climate change under various representative concentration pathways (RCPs) for three future time periods (the 2030s, 2050s, and 2080s). Our results demonstrate that temperature, precipitation, and relative humidity play key roles in driving the seasonal epidemic of scrub typhus in mainland China with a 2‐month lag. Our findings show that the change of projected spatiotemporal dynamics of scrub typhus will be heterogeneous and will depend on specific combinations of regional climate conditions in future climate scenarios. Our results contribute to a better understanding of spatiotemporal dynamics of scrub typhus, which can help public health authorities refine their prevention and control measures to reduce the risks resulting from climate change.
Publisher: JMIR Publications Inc.
Date: 02-10-2020
DOI: 10.2196/19762
Abstract: Reporting cumulative antimicrobial susceptibility testing data on a regular basis is crucial to inform antimicrobial resistance (AMR) action plans at local, national, and global levels. However, analyzing data and generating a report are time consuming and often require trained personnel. This study aimed to develop and test an application that can support a local hospital to analyze routinely collected electronic data independently and generate AMR surveillance reports rapidly. An offline application to generate standardized AMR surveillance reports from routinely available microbiology and hospital data files was written in the R programming language (R Project for Statistical Computing). The application can be run by double clicking on the application file without any further user input. The data analysis procedure and report content were developed based on the recommendations of the World Health Organization Global Antimicrobial Resistance Surveillance System (WHO GLASS). The application was tested on Microsoft Windows 10 and 7 using open access ex le data sets. We then independently tested the application in seven hospitals in Cambodia, Lao People’s Democratic Republic, Myanmar, Nepal, Thailand, the United Kingdom, and Vietnam. We developed the AutoMated tool for Antimicrobial resistance Surveillance System (AMASS), which can support clinical microbiology laboratories to analyze their microbiology and hospital data files (in CSV or Excel format) onsite and promptly generate AMR surveillance reports (in PDF and CSV formats). The data files could be those exported from WHONET or other laboratory information systems. The automatically generated reports contain only summary data without patient identifiers. The AMASS application is downloadable from www.amass.website/. The participating hospitals tested the application and deposited their AMR surveillance reports in an open access data repository. The AMASS is a useful tool to support the generation and sharing of AMR surveillance reports.
Publisher: eLife Sciences Publications, Ltd
Date: 23-06-2021
Publisher: Public Library of Science (PLoS)
Date: 07-12-2020
DOI: 10.1371/JOURNAL.PNTD.0008858
Abstract: Scrub typhus is a major cause of morbidity and mortality in Southeast Asia. Diagnosis of scrub typhus is difficult due to a lack of accessible validated diagnostic tools. Despite its objectivity, the diagnostic accuracy of ELISA tests is influenced by methodological and patient factors. This study aims to evaluate the performance of a novel in-house ELISA developed in the Mahidol Oxford Tropical Medicine Research Unit (MORU) for anti-scrub typhus group IgM and IgG compared to the “gold standard” reference IFA and PCR, and to determine whether the in-house ELISA can be used as a seroepidemiological screening tool and/or stand-alone test for scrub typhus. A total of 1,976 admission and 1,438 participant follow-up sera collected in the Lao PDR (Laos) were tested with ELISA for IgM and IgG. S les with an ELISA OD≥0.50 were tested with IFA for IgM and/or IgG. A strong positive relationship was present between ELISA ODs and IFA titers for admission IgM ( r 2 : 0.70, p .005) and IgG ( r 2 : 0.76, p .005), and for follow-up IgM and IgG (both r 2 : 0.76, p .005) s les. The best compromise between sensitivity and specificity for the ELISA OD cut-off is likely to be between 0.8–1.0 for IgM antibodies and 1.2–1.8 for IgG antibodies. These results demonstrate that the diagnostic accuracy of the MORU in-house scrub typhus group ELISA is comparable to that of IFA, with similar results as reported for the commonly used InBios Scrub Typhus Detect ELISA, validating the use of the in-house ELISA. The optimal ELISA cut-off would depend on the use of the test, and the desired sensitivity and specificity. Further studies are required to authenticate the use of these cut-offs in other endemic regions. This in-house ELISA has the potential to replace the imperfect IFA, which could ultimately reduce the burden of scrub typhus by improving the rate of scrub typhus diagnoses in endemic low-resource areas.
Publisher: Public Library of Science (PLoS)
Date: 05-03-2020
Publisher: JMIR Publications Inc.
Date: 03-05-2020
Abstract: eporting cumulative antimicrobial susceptibility testing data on a regular basis is crucial to inform antimicrobial resistance (AMR) action plans at local, national, and global levels. However, analyzing data and generating a report are time consuming and often require trained personnel. his study aimed to develop and test an application that can support a local hospital to analyze routinely collected electronic data independently and generate AMR surveillance reports rapidly. n offline application to generate standardized AMR surveillance reports from routinely available microbiology and hospital data files was written in the R programming language (R Project for Statistical Computing). The application can be run by double clicking on the application file without any further user input. The data analysis procedure and report content were developed based on the recommendations of the World Health Organization Global Antimicrobial Resistance Surveillance System (WHO GLASS). The application was tested on Microsoft Windows 10 and 7 using open access ex le data sets. We then independently tested the application in seven hospitals in Cambodia, Lao People’s Democratic Republic, Myanmar, Nepal, Thailand, the United Kingdom, and Vietnam. e developed the AutoMated tool for Antimicrobial resistance Surveillance System (AMASS), which can support clinical microbiology laboratories to analyze their microbiology and hospital data files (in CSV or Excel format) onsite and promptly generate AMR surveillance reports (in PDF and CSV formats). The data files could be those exported from WHONET or other laboratory information systems. The automatically generated reports contain only summary data without patient identifiers. The AMASS application is downloadable from www.amass.website/. The participating hospitals tested the application and deposited their AMR surveillance reports in an open access data repository. he AMASS is a useful tool to support the generation and sharing of AMR surveillance reports.
Publisher: F1000 Research Ltd
Date: 24-11-2022
DOI: 10.12688/WELLCOMEOPENRES.18533.1
Abstract: Background: Scrub typhus is a neglected life-threatening vector-borne disease mainly caused by the bacterium Orientia tsutsugamushi , which is occasionally transmitted to humans during feeding of larval mites. It has been estimated that more than 1 billion persons potentially threatened and 1 million clinical cases occur annually across the world however, it is unclear how this estimate was computed (and what the original source was) and much remains unknown regarding its global burden and risk factors. This systematic review aims to provide a comprehensive overview of the spatial-temporal distribution of scrub typhus, associated burden and risk factors at global, national and subnational resolutions, and to review the burden estimation models used at those different scales. Methods: A systematic search for literature on scrub typhus occurrence, risk factors and modelling methods will be conducted. PubMed and five other databases will be searched for published literature, and Google Scholar and nine other databases will be used to search for grey literatures. All titles/abstracts of the searched records will be separately assessed by two reviewers, who will then screen the full-text of potential records to decide eligibility. Two reviewers will independently perform corresponding data extraction and finally cross-check using designed standardized forms. Data will be tabulated, synthesized descriptively, and summarized narratively for each review question. Where appropriate, meta-analyses will be conducted. The risk of bias will be assessed, and potential publication bias will be detected. Discussion: This review will provide a comprehensive understanding of the current occurrence, spatial-temporal distribution, and burden of scrub typhus, identify associated risk factors from global to subnational resolutions, consolidate the best practice modeling framework(s) to estimate the burden of scrub typhus at various geographic/temporal resolutions, and decompose the relative contributions of various risk factors at scale. PROSPERO Registration: CRD42022315209
Publisher: eLife Sciences Publications, Ltd
Date: 06-12-2022
DOI: 10.7554/ELIFE.83433
Abstract: Tafenoquine is a newly licensed antimalarial drug for the radical cure of Plasmodium vivax malaria. The mechanism of action and optimal dosing are uncertain. We pooled in idual data from 1102 patients and 72 healthy volunteers studied in the pre-registration trials. We show that tafenoquine dose is the primary determinant of efficacy. Under an Emax model, we estimate the currently recommended 300 mg dose in a 60 kg adult (5 mg/kg) results in 70% of the maximal obtainable hypnozoiticidal effect. Increasing the dose to 7.5 mg/kg (i.e. 450 mg) would result in 90% reduction in the risk of P. vivax recurrence. After adjustment for dose, the tafenoquine terminal elimination half-life, and day 7 methaemoglobin concentration, but not the parent compound exposure, were also associated with recurrence. These results suggest that the production of oxidative metabolites is central to tafenoquine’s hypnozoiticidal efficacy. Clinical trials of higher tafenoquine doses are needed to characterise their efficacy, safety and tolerability.
Publisher: F1000 Research Ltd
Date: 24-02-2021
DOI: 10.12688/WELLCOMEOPENRES.16168.1
Abstract: MalariaGEN is a data-sharing network that enables groups around the world to work together on the genomic epidemiology of malaria. Here we describe a new release of curated genome variation data on 7,000 Plasmodium falciparum s les from MalariaGEN partner studies in 28 malaria-endemic countries. High-quality genotype calls on 3 million single nucleotide polymorphisms (SNPs) and short indels were produced using a standardised analysis pipeline. Copy number variants associated with drug resistance and structural variants that cause failure of rapid diagnostic tests were also analysed. Almost all s les showed genetic evidence of resistance to at least one antimalarial drug, and some s les from Southeast Asia carried markers of resistance to six commonly-used drugs. Genes expressed during the mosquito stage of the parasite life-cycle are prominent among loci that show strong geographic differentiation. By continuing to enlarge this open data resource we aim to facilitate research into the evolutionary processes affecting malaria control and to accelerate development of the surveillance toolkit required for malaria elimination.
Publisher: F1000 Research Ltd
Date: 13-07-2021
DOI: 10.12688/WELLCOMEOPENRES.16168.2
Abstract: MalariaGEN is a data-sharing network that enables groups around the world to work together on the genomic epidemiology of malaria. Here we describe a new release of curated genome variation data on 7,000 Plasmodium falciparum s les from MalariaGEN partner studies in 28 malaria-endemic countries. High-quality genotype calls on 3 million single nucleotide polymorphisms (SNPs) and short indels were produced using a standardised analysis pipeline. Copy number variants associated with drug resistance and structural variants that cause failure of rapid diagnostic tests were also analysed. Almost all s les showed genetic evidence of resistance to at least one antimalarial drug, and some s les from Southeast Asia carried markers of resistance to six commonly-used drugs. Genes expressed during the mosquito stage of the parasite life-cycle are prominent among loci that show strong geographic differentiation. By continuing to enlarge this open data resource we aim to facilitate research into the evolutionary processes affecting malaria control and to accelerate development of the surveillance toolkit required for malaria elimination.
Publisher: F1000 Research Ltd
Date: 10-03-2022
DOI: 10.12688/WELLCOMEOPENRES.16393.2
Abstract: In rural areas of South and Southeast Asia malaria is declining but febrile illnesses still account for substantial morbidity and mortality. Village health workers (VHWs) are often the first point of contact with the formal health system, and for patients with febrile illnesses they can provide early diagnosis and treatment of malaria. However, for the majority of febrile patients, VHWs lack the training, support and resources to provide further care. Consequently, treatable bacterial illnesses are missed, antibiotics are overused and poorly targeted, and patient attendance wanes along with declining malaria. This Open Letter announces the start of a new initiative, the Rural Febrile Illness (RFI) project, the first in a series of projects to be implemented as part of the South and Southeast Asian Community-based Trials Network (SEACTN) research programme. This multi-country, multi-site project will run in Bangladesh, Cambodia, Lao PDR, Thailand, and Myanmar. It will define the epidemiological baseline of febrile illness in nine remote and underserved areas of Asia where malaria endemicity is declining and access to health services is limited. The RFI project aims to determine the incidence, causes and outcomes of febrile illness understand the opportunities, barriers and appetite for adjustment of the role of VHWs to include management of non-malarial febrile illnesses and establish a network of community healthcare providers and facilities capable of implementing interventions designed to triage, diagnose and treat patients presenting with febrile illnesses within these communities in the future.
Publisher: F1000 Research Ltd
Date: 26-03-2021
DOI: 10.12688/WELLCOMEOPENRES.16393.1
Abstract: In rural areas of South and Southeast Asia malaria is declining but febrile illnesses still account for substantial morbidity and mortality. Village health workers (VHWs) are often the first point of contact with the formal health system, and for patients with febrile illnesses they can provide early diagnosis and treatment of malaria. However, for the majority of febrile patients, VHWs lack the training, support and resources to provide further care. Consequently, treatable bacterial illnesses are missed, antibiotics are overused and poorly targeted, and patient attendance wanes along with declining malaria. This Open Letter announces the start of a new initiative, the Rural Febrile Illness (RFI) project, the first in a series of projects to be implemented as part of the South and Southeast Asian Community-based Trials Network (SEACTN) research programme. This multi-country, multi-site project will begin in Bangladesh, Cambodia, Lao PDR, and Myanmar and will define the epidemiological baseline of febrile illness in five remote and underserved areas of Asia where malaria endemicity is declining and access to health services is limited. The RFI project aims to determine the incidence, causes and outcomes of febrile illness understand the opportunities, barriers and appetite for adjustment of the role of VHWs to include management of non-malarial febrile illnesses and establish a network of community healthcare providers and facilities capable of implementing interventions designed to triage, diagnose and treat patients presenting with febrile illnesses within these communities in the future.
Publisher: F1000 Research Ltd
Date: 20-10-2023
Publisher: Public Library of Science (PLoS)
Date: 15-02-2019
Publisher: F1000 Research Ltd
Date: 16-01-2023
DOI: 10.12688/WELLCOMEOPENRES.18681.1
Abstract: We describe the MalariaGEN Pf7 data resource, the seventh release of Plasmodium falciparum genome variation data from the MalariaGEN network. It comprises over 20,000 s les from 82 partner studies in 33 countries, including several malaria endemic regions that were previously underrepresented. For the first time we include dried blood spot s les that were sequenced after selective whole genome lification, necessitating new methods to genotype copy number variations. We identify a large number of newly emerging crt mutations in parts of Southeast Asia, and show ex les of heterogeneities in patterns of drug resistance within Africa and within the Indian subcontinent. We describe the profile of variations in the C-terminal of the csp gene and relate this to the sequence used in the RTS,S and R21 malaria vaccines. Pf7 provides high-quality data on genotype calls for 6 million SNPs and short indels, analysis of large deletions that cause failure of rapid diagnostic tests, and systematic characterisation of six major drug resistance loci, all of which can be freely downloaded from the MalariaGEN website.
Publisher: Public Library of Science (PLoS)
Date: 23-08-2019
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Nicholas Day.