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Detection of a historic reservoir of bedaquiline/clofazimine resistance-associated variants in Mycobacterium tuberculosis
No full textDrug resistance in tuberculosis (TB) poses a major ongoing challenge to public health. The recent inclusion of bedaquiline into TB drug regimens has improved treatment outcomes, but this advance is threatened by the emergence of strains of Mycobacterium tuberculosis (Mtb) resistant to bedaquiline. Clinical bedaquiline resistance is most frequently conferred by off-target resistance-associated variants (RAVs) in the mmpR5 gene (Rv0678), the regulator of an efflux pump, which can also confer cross-resistance to clofazimine, another TB drug. Methods We compiled a dataset of 3682 Mtb genomes, including 180 carrying variants in mmpR5, and its immediate background (i.e. mmpR5 promoter and adjacent mmpL5 gene), that have been associated to borderline (henceforth intermediate) or confirmed resistance to bedaquiline. We characterised the occurrence of all nonsynonymous mutations in mmpR5 in this dataset and estimated, using time-resolved phylogenetic methods, the age of their emergence. Results We identified eight cases where RAVs were present in the genomes of strains collected prior to the use of bedaquiline in TB treatment regimes. Phylogenetic reconstruction points to multiple emergence events and circulation of RAVs in mmpR5, some estimated to predate the introduction of bedaquiline. However, epistatic interactions can complicate bedaquiline drug-susceptibility prediction from genetic sequence data. Indeed, in one clade, Ile67fs (a RAV when considered in isolation) was estimated to have emerged prior to the antibiotic era, together with a resistance reverting mmpL5 mutation. Conclusions The presence of a pre-existing reservoir of Mtb strains carrying bedaquiline RAVs prior to its clinical use augments the need for rapid drug susceptibility testing and individualised regimen selection to safeguard the use of bedaquiline in TB care and control
theosanderson/hospitalmedicines
No full textSimple app to explore NHS medicines usage data for hospitals
Projection of temperature-related mortality in 854 European cities under climate change and adaptation scenarios
No full textThis repository contains the data and results from the paper by Masselot et al. published in Nature Medicine. It provides projections of excess death rates and burden for the period 2015-2099 for five age groups in 854 cities across 30 countries, under three Shared Socioeconomic Pathway (SSP) scenarios, and four adaptation scenarios. The results include point estimates for five-year periods and four global warming levels, along with 95% empirical confidence intervals. The fully reproducible analysis code using the data and producing the results included in this repository is provided in GitHub. The results can further be visualised and explored in a dedicated shiny ap
Rapid Assessment of Avoidable Blindness Report: China, Jiangxi, Wanzai (2007)
No full textA report including output of standardised analysis of vision and eye health survey data including tables of vision impairment prevalence and service coverage estimate
Rapid Assessment of Avoidable Blindness Report: Hungary (2015)
No full textA report including output of standardised analysis of vision and eye health survey data including tables of vision impairment prevalence and service coverage estimate
Rapid Assessment of Avoidable Blindness Report: Vietnam, Phu Tho (2015)
No full textA report including output of standardised analysis of vision and eye health survey data including tables of vision impairment prevalence and service coverage estimate
Rapid Assessment of Avoidable Blindness Report: Papua New Guinea, Highlands (2017)
No full textA report including output of standardised analysis of vision and eye health survey data including tables of vision impairment prevalence and service coverage estimate
Additional file 1 of Mixed-method evaluation study of a targeted mass drug administration of long-acting anti-malarials among children aged 3 months to 15 years in the Bossangoa sub-prefecture, Ouham, Central African Republic, during the COVID-19 pandemic
No full textStructured interviews for the head of household or a designate in: "Mixed-method evaluation study of a targeted mass drug administration of long-acting anti-malarials among children aged 3 months to 15 years in the Bossangoa sub-prefecture, Ouham, Central African Republic, during the COVID-19 pandemic"
Rapid Assessment of Avoidable Blindness Report: Kenya, Eastern, Embu (2007)
No full textA report including output of standardised analysis of vision and eye health survey data including tables of vision impairment prevalence and service coverage estimate
Rapid Assessment of Avoidable Blindness Report: Kenya, Rift Valley, Kericho (2007)
No full textA report including output of standardised analysis of vision and eye health survey data including tables of vision impairment prevalence and service coverage estimate