Contributors: Ward, Zachary, Yeh, Jennifer, Bhakta, Nickhill, Frazier, A Lindsay, Girardi, Fabio, Atun, Rifat
... Simulation results (means and 95% uncertainty intervals) for: Ward ZJ, Yeh JM, Bhakta N, Frazier AL, Girardi F, Atun R. Global childhood cancer survival estimates and priority-setting: a simulation-based analysis. Lancet Oncol 2019; 20(7): 972-983.
Contributors: Webb, Emily, Mpairwe, Harriet
... Dataset produced as part of a study to investigate asthma control and management among schoolchildren in urban Uganda. Each row represents one child with asthma. Variables include data on asthma symptoms and management approaches.
Contributors: Knight, Gwen, Leclerc, Quentin J., Naylor, Nichola R., Aiken, Alexander M., Coll, Francesc, Knight, Gwenan M
... R code for a Shiny app that generates Empiric Prescribing recommendations. The app won the Wellcome Trust Data Re-Use AMR prize 2019. The tool uses open-access antimicrobial resistance (AMR) surveillance datasets, including the newly available ATLAS dataset from Pfizer, to derive a composite index of antibiotic resistance for common infection syndromes.
Cost-effectiveness of reflex laboratory-based cryptococcal antigen screening for the prevention and treatment of cryptococcal meningitis in Botswana
Contributors: Tenforde, Mark W., Muthoga, Charles, Callaghan, Andrew, Ponetshego, Ponego, Ngidi, Julia, Mine, Madisa, Jordan, Alexander, Chiller, Tom, Larson, Bruce A., Jarvis, Joseph N.
... This project contains the underlying data used for this modeling study, including a description of all estimates and their sources under tab “Screening Parameter Estimates”. Data are available under the terms of the Creative Commons Zero "No rights reserved" data waiver (CC0 1.0 Public domain dedication).
Comparative fitness analysis of D-cycloserine resistant mutants reveals both fitness-neutral and high-fitness cost genotypes
Contributors: Evangelopoulos, Dimitrios, Prosser, Gareth A., Rodgers, Angela, Dagg, Belinda M., Khatri, Bhagwati, Ho, Mei Mei, Gutierrez, Maximiliano G., Cortes, Teresa
... Drug resistant infections represent one of the most challenging medical problems of our time. D-cycloserine is an antibiotic used for six decades without significant appearance and dissemination of antibiotic resistant strains, making it an ideal model compound to understand what drives resistance evasion. We therefore investigated why Mycobacterium tuberculosis fails to become resistant to D-cycloserine. To address this question, we employed a combination of bacterial genetics, genomics, biochemistry and fitness analysis in vitro, in macrophages and in mice. Altogether, our results suggest that the ultra-low rate of emergence of D-cycloserine resistance mutations is the dominant biological factor delaying the appearance of clinical resistance to this antibiotic. Furthermore, we also identified potential compensatory mechanisms able to minimize the severe fitness costs of primary D-cycloserine resistance conferring mutations.
“The recent emergence of a highly related virulent Clostridium difficile clade with unique characteristics”
Contributors: Shaw, Helen Alexandra, Preston, Mark D., Vendrik, Karuna E.W., Cairns, Michelle D, Browne, Hilary P., Stabler, Richard, Crobach, Monique J.T., Corver, Jeroen, Pituch, Hanna, Ingebretsen, Andre
... Clostridium difficile is a major global human pathogen divided into five clades, of which clade 3 is the least characterised and consists predominantly of PCR ribotype (RT) 023 strains. Our aim was to analyse and characterise this clade.
Table 1 - Fueling Open Innovation for Malaria Transmission-Blocking Drugs: Hundreds of Molecules Targeting Early Parasite Mosquito Stages
Contributors: Delves, Michael, Lafuente-Monasterio, M. Jose, Upton, Leanna, Ruecker, Andrea, Leroy, Didier, Gamo, Francisco-Javier, Sinden, Robert
... Despite recent successes at controlling malaria, progress has stalled with an estimated 219 million cases and 435,000 deaths in 2017 alone. Combined with emerging resistance to front line antimalarial therapies in Southeast Asia, there is an urgent need for new treatment options and novel approaches to halt the spread of malaria. Plasmodium, the parasite responsible for malaria propagates through mosquito transmission. This imposes an acute bottleneck on the parasite population and transmission-blocking interventions exploiting this vulnerability are recognized as vital for malaria elimination.
Informal genomic surveillance of regional distribution of Salmonella Typhi genotypes and antimicrobial resistance via returning travellers
Contributors: Ingle, Danielle J., Nair, Satheesh, Hartman, Hassan, Ashton, Philip M., Dyson, Zoe A., Day, Martin, Freedman, Joanne, Chattaway, Marie A., Holt, Kathryn E., Dallman, Timothy J.
... Salmonella enterica serovar Typhi (S. Typhi) is the causative agent of typhoid fever, a systemic human infection with a burden exceeding 20 million cases each year that occurs disproportionately among children in low and middle income countries. Antimicrobial therapy is the mainstay for treatment, but resistance to multiple agents is common. Here we report genotypes and antimicrobial resistance (AMR) determinants detected from routine whole-genome sequencing (WGS) of 533 S. Typhi isolates referred to Public Health England between April 2014 and March 2017, 488 (92%) of which had accompanying patient travel information obtained via an enhanced surveillance questionnaire. The majority of cases involved S. Typhi 4.3.1 (H58) linked with travel to South Asia (59%). Travel to East and West Africa were associated with genotypes 4.3.1 and 3.3.1, respectively. Point mutations in the quinolone resistance determining region (QRDR), associated with reduced susceptibility to fluoroquinolones, were very common (85% of all cases) but the frequency varied significantly by region of travel: 95% in South Asia, 43% in East Africa, 27% in West Africa. QRDR triple mutants, resistant to ciprofloxacin, were restricted to 4.3.1 lineage II and associated with travel to India, accounting for 23% of cases reporting travel to the country. Overall 24% of isolates were MDR, however the frequency varied significantly by region and country of travel: 27% in West Africa, 52% in East Africa, 55% in Pakistan, 24% in Bangladesh, 3% in India. MDR determinants were plasmid-borne (IncHI1 PST2 plasmids) in S. Typhi 3.1.1 linked to West Africa, but in all other regions MDR was chromosomally integrated in 4.3.1 lineage I. We propose that routine WGS data from travel-associated cases in industrialised countries could serve as informal sentinel AMR genomic surveillance data for countries where WGS is not available or routinely performed.
Vitamin D status and risk of incident tuberculosis disease: A nested case-control study, systematic review, and individual-participant data meta-analysis
Contributors: Aibana, Omowunmi, Huang, Chuan-Chin, Aboud, Said, Arnedo-Pena, Alberto, Becerra, Mercedes C, Bellido-Blasco, Juan Bautista, Bhosale, Ramesh, Calderon, Roger, Chiang, Silvia, Contreras, Carmen
... Few studies have evaluated the association between preexisting vitamin D deficiency and incident tuberculosis (TB). We assessed the impact of baseline vitamins D levels on TB disease risk.
Data and code from: Estimating the burden of dengue and the impact of release of wMel Wolbachia infected mosquitoes in Indonesia: a modelling study
Contributors: O'reilly, Kathleen, Hendrickx, Emilie, Kharisma, Dinar D., Wilastonegoro, Nandyan N., Carrington, Lauren B., Elyazar, Iqbal R. F., Kucharsk, Adam J., Lowe, Rachel, Flasche, Stefan, Pigott, David M.
... Wolbachia-infected mosquitoes reduce dengue virus transmission, and city-wide releases in Yogyakarta city, Indonesia, are showing promising entomological results. Accurate estimates of the burden of dengue, its spatial distribution and the potential impact of Wolbachia are critical in guiding funder and government decisions on its future wider use.