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Global burden of bacterial antimicrobial resistance 1990-2021: a systematic analysis with forecasts to 2050.
Get PDFBACKGROUND: Antimicrobial resistance (AMR) poses an important global health challenge in the 21st century. A previous study has quantified the global and regional burden of AMR for 2019, followed with additional publications that provided more detailed estimates for several WHO regions by country. To date, there have been no studies that produce comprehensive estimates of AMR burden across locations that encompass historical trends and future forecasts.
METHODS: We estimated all-age and age-specific deaths and disability-adjusted life-years (DALYs) attributable to and associated with bacterial AMR for 22 pathogens, 84 pathogen-drug combinations, and 11 infectious syndromes in 204 countries and territories from 1990 to 2021. We collected and used multiple cause of death data, hospital discharge data, microbiology data, literature studies, single drug resistance profiles, pharmaceutical sales, antibiotic use surveys, mortality surveillance, linkage data, outpatient and inpatient insurance claims data, and previously published data, covering 520 million individual records or isolates and 19 513 study-location-years. We used statistical modelling to produce estimates of AMR burden for all locations, including those with no data. Our approach leverages the estimation of five broad component quantities: the number of deaths involving sepsis; the proportion of infectious deaths attributable to a given infectious syndrome; the proportion of infectious syndrome deaths attributable to a given pathogen; the percentage of a given pathogen resistant to an antibiotic of interest; and the excess risk of death or duration of an infection associated with this resistance. Using these components, we estimated disease burden attributable to and associated with AMR, which we define based on two counterfactuals; respectively, an alternative scenario in which all drug-resistant infections are replaced by drug-susceptible infections, and an alternative scenario in which all drug-resistant infections were replaced by no infection. Additionally, we produced global and regional forecasts of AMR burden until 2050 for three scenarios: a reference scenario that is a probabilistic forecast of the most likely future; a Gram-negative drug scenario that assumes future drug development that targets Gram-negative pathogens; and a better care scenario that assumes future improvements in health-care quality and access to appropriate antimicrobials. We present final estimates aggregated to the global, super-regional, and regional level.
FINDINGS: In 2021, we estimated 4·71 million (95% UI 4·23-5·19) deaths were associated with bacterial AMR, including 1·14 million (1·00-1·28) deaths attributable to bacterial AMR. Trends in AMR mortality over the past 31 years varied substantially by age and location. From 1990 to 2021, deaths from AMR decreased by more than 50% among children younger than 5 years yet increased by over 80% for adults 70 years and older. AMR mortality decreased for children younger than 5 years in all super-regions, whereas AMR mortality in people 5 years and older increased in all super-regions. For both deaths associated with and deaths attributable to AMR, meticillin-resistant Staphylococcus aureus increased the most globally (from 261 000 associated deaths [95% UI 150 000-372 000] and 57 200 attributable deaths [34 100-80 300] in 1990, to 550 000 associated deaths [500 000-600 000] and 130 000 attributable deaths [113 000-146 000] in 2021). Among Gram-negative bacteria, resistance to carbapenems increased more than any other antibiotic class, rising from 619 000 associated deaths (405 000-834 000) in 1990, to 1·03 million associated deaths (909 000-1·16 million) in 2021, and from 127 000 attributable deaths (82 100-171 000) in 1990, to 216 000 (168 000-264 000) attributable deaths in 2021. There was a notable decrease in non-COVID-related infectious disease in 2020 and 2021. Our forecasts show that an estimated 1·91 million (1·56-2·26) deaths attributable to AMR and 8·22 million (6·85-9·65) deaths associated with AMR could occur globally in 2050. Super-regions with the highest all-age AMR mortality rate in 2050 are forecasted to be south Asia and Latin America and the Caribbean. Increases in deaths attributable to AMR will be largest among those 70 years and older (65·9% [61·2-69·8] of all-age deaths attributable to AMR in 2050). In stark contrast to the strong increase in number of deaths due to AMR of 69·6% (51·5-89·2) from 2022 to 2050, the number of DALYs showed a much smaller increase of 9·4% (-6·9 to 29·0) to 46·5 million (37·7 to 57·3) in 2050. Under the better care scenario, across all age groups, 92·0 million deaths (82·8-102·0) could be cumulatively averted between 2025 and 2050, through better care of severe infections and improved access to antibiotics, and under the Gram-negative drug scenario, 11·1 million AMR deaths (9·08-13·2) could be averted through the development of a Gram-negative drug pipeline to prevent AMR deaths.
INTERPRETATION: This study presents the first comprehensive assessment of the global burden of AMR from 1990 to 2021, with results forecasted until 2050. Evaluating changing trends in AMR mortality across time and location is necessary to understand how this important global health threat is developing and prepares us to make informed decisions regarding interventions. Our findings show the importance of infection prevention, as shown by the reduction of AMR deaths in those younger than 5 years. Simultaneously, our results underscore the concerning trend of AMR burden among those older than 70 years, alongside a rapidly ageing global community. The opposing trends in the burden of AMR deaths between younger and older individuals explains the moderate future increase in global number of DALYs versus number of deaths. Given the high variability of AMR burden by location and age, it is important that interventions combine infection prevention, vaccination, minimisation of inappropriate antibiotic use in farming and humans, and research into new antibiotics to mitigate the number of AMR deaths that are forecasted for 2050.
FUNDING: UK Department of Health and Social Care's Fleming Fund using UK aid, and the Wellcome Trust
Electronic monitoring device informed interventions for treatment adherence and clinical outcomes in children and adolescents: A systematic review.
Get PDFOBJECTIVE: To systematically review literature from randomised controlled trials (RCTs) investigating the effectiveness of electronic monitoring device informed interventions on adherence and clinical outcomes in children and adolescents with chronic conditions.
STUDY DESIGN: A systematic review was conducted. An electronic literature search covering studies, with no pre-specified starting date up to June 2024, was performed in Medline, EMBASE, Web of Science, Cochrane and Trials databases was conducted.
PARTICIPANTS: RCTs of electronic monitoring device informed interventions in individuals aged 0 to 18 years with chronic conditions, were identified, with no restriction on geography or publication date.
METHODS: Extracted data was synthesised. As a result of differences in definitions and analysis of adherence and clinical outcomes across the studies a pooled meta-analysis was not possible therefore, a descriptive analysis was conducted. Risk of bias across all studies was assessed using the Cochrane Collaboration risk of bias tool.
RESULTS: 11 RCTs, with 1485 children and adolescents were included. Studies were all from high- and middle-income countries, conducted among children and adolescents with asthma, and one each among children and adolescents with kidney transplant, multiple sclerosis, and epilepsy. Eight of the 11 studies reported a positive effect on adherence. Only four studies reported a positive effect on clinical outcomes and seven studies found no effect on clinical outcomes.
CONCLUSIONS: Electronic monitoring device interventions show promise in improving adherence in children and adolescents with chronic conditions, in a limited number of chronic conditions, mostly asthma. Evidence for the efficacy of electronic monitoring device informed interventions on clinical outcomes and from low-income settings is lacking.
SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42022312057, registered in March 2022.
TWEETABLE ABSTRACT: Electronic monitoring device informed interventions may improve treatment adherence in children and adolescents with chronic conditions but evidence from low-income settings is lacking @nyasha_dzavakwa @KatharinaKranz4 @dopapus @hilda_mujuru @rashida_abbferr @vickysimms_epi
Estimating the impact of vaccination: lessons learned in the first phase of the Vaccine Impact Modelling Consortium [version 1; peer review: 2 approved, 1 approved with reservations] .
Get PDFEstimates of the global health impact of immunisation are important for quantifying historical benefits as well as planning future investments and strategy. The Vaccine Impact Modelling Consortium (VIMC) was established in 2016 to provide reliable estimates of the health impact of immunisation. In this article we examine the consortium in its first five-year phase. We detail how vaccine impact was defined and the methods used to estimate it as well as the technical infrastructure required to underpin robust reproducibility of the outputs. We highlight some of the applications of estimates to date, how these were communicated and what their effect were. Finally, we explore some of the lessons learnt and remaining challenges for estimating the impact of vaccines and forming effective modelling consortia then discuss how this may be addressed in the second phase of VIMC. Modelled estimates are not a replacement for surveillance; however, they can examine theoretical counterfactuals and highlight data gaps to complement other activities. VIMC has implemented strategies to produce robust, standardised estimates of immunisation impact. But through the first phase of the consortium, critical lessons have been learnt both on the technical infrastructure and the effective engagement with modellers and stakeholders. To be successful, a productive dialogue with estimate consumers, producers and stakeholders needs to be underpinned by a rigorous and transparent analytical framework as well as an approach for building expertise in the short and long term
Comparisons of genome assembly tools for characterization of Mycobacterium tuberculosis genomes using hybrid sequencing technologies.
Get PDFBACKGROUND: Next-generation sequencing of Mycobacterium tuberculosis, the infectious agent causing tuberculosis, is improving the understanding of genomic diversity of circulating lineages and strain-types, and informing knowledge of drug resistance mutations. An increasingly popular approach to characterizing M. tuberculosis genomes (size: 4.4 Mbp) and variants (e.g., single nucleotide polymorphisms (SNPs)) involves the de novo assembly of sequence data.
METHODS: We compared the performance of genome assembly tools (Unicycler, RagOut, and RagTag) on sequence data from nine drug resistant M. tuberculosis isolates (multi-drug (MDR) n = 1; pre-extensively-drug (pre-XDR) n = 8) generated using Illumina HiSeq, Oxford Nanopore Technology (ONT) PromethION, and PacBio platforms.
RESULTS: Our investigation found that Unicycler-based assemblies had significantly higher genome completeness (~98.7%; p values = 0.01) compared to other assembler tools (RagOut = 98.6%, and RagTag = 98.6%). The genome assembly sizes (bp) across isolates and sequencers based on RagOut was significantly longer (p values < 0.001) (4,418,574 ± 8,824 bp) than Unicycler and RagTag assemblies (Unicycler = 4,377,642 ± 55,257 bp, and RagTag = 4,380,711 ± 51,164 bp). RagOut-based assemblies had the fewest contigs (~32) and the longest genome size (4,418,574 bp; vs. H37Rv reference size 4,411,532 bp) and therefore were chosen for downstream analysis. Pan-genome analysis of Illumina and PacBio hybrid assemblies revealed the greatest number of detected genes (4,639 genes; H37Rv reference contains 3,976 genes), while Illumina and ONT hybrid assemblies produced the highest number of SNPs. The number of genes from hybrid assemblies with ONT and PacBio long-reads (mean: 4,620 genes) was greater than short-read assembly alone (4,478 genes). All nine RagOut hybrid genome assemblies detected known mutations in genes associated with MDR-TB and pre-XDR-TB.
CONCLUSIONS: Unicycler software performed the best in terms of achieving contiguous genomes, whereas RagOut improved the quality of Unicycler's genome assemblies by providing a longer genome size. Overall, our approach has demonstrated that short-read and long-read hybrid assembly can provide a more complete genome assembly than short-read assembly alone by detecting pan-genomes and more genes, including IS6110, and SNPs
COVID-19 vaccines are effective at preventing symptomatic and severe infection among healthcare workers: A clinical review.
Get PDFINTRODUCTION: Health care workers (HCWs) have been at increased risk of infection during the SARS-CoV-2 pandemic and as essential workers have been prioritised for vaccination. Due to increased exposure HCW are considered a predictor of what might happen in the general population, particularly working age adults. This study aims to summarise effect of vaccination in this 'at risk' cohort.
METHODS: Ovid MEDLINE and Embase were searched, and 358 individual articles were identified. Of these 49 met the inclusion criteria for review and 14 were included in a meta-analysis.
RESULTS: Participants included were predominantly female and working age. Median time to infection was 51 days. Reported vaccine effectiveness against infection, symptomatic infection, and infection requiring hospitalisation were between 5 and 100 %, 34 and 100 %, and 65 and 100 % (respectively). No vaccinated HCW deaths were recorded in any study. Pooled estimates of protection against infection, symptomatic infection, and hospitalisation were, respectively, 84.7 % (95 % CI 72.6-91.5 %, p < 0.0001), 86.0 % (95 % CI 67.2 %-94.0 %; p < 0.0001), and 96.1 % (95 % CI 90.4 %-98.4 %). Waning protection against infection was reported by four studies, although protection against hospitalisation for severe infection persists for at least 6 months post vaccination.
CONCLUSIONS: Vaccination against SARS-CoV2 in HCWs is protective against infection, symptomatic infection, and hospitalisation. Waning protection is reported but this awaits more mature studies to understand durability more clearly. This study is limited by varying non-pharmacological responses to COVID-19 between included studies, a predominantly female and working age population, and limited information on asymptomatic transmission or long COVID protection
Intravenous ferric carboxymaltose versus oral ferrous sulphate for the treatment of moderate to severe postpartum anaemia in Nigerian women (IVON-PP): protocol for an open-label randomised controlled type 1 hybrid effectiveness-implementation trial.
Get PDFINTRODUCTION: Postpartum anaemia is often caused by iron deficiency with onset during the antepartum period and can be exacerbated by excessive blood loss at birth. Its prevalence is estimated as 50-80% in low-income and middle-income countries. It poses adverse consequences on the mother and negatively impacts her ability to care for her newborn. Prompt treatment of postpartum anaemia is thus important. Adherence to oral iron is reportedly low in Nigeria due to its side effects and forgetfulness by the mothers. Intravenous iron such as ferric carboxymaltose, given as a single dose, might help overcome adherence issues, but investigation in a high-quality randomised control trial in Nigeria is first required while evaluation of challenges around its implementation is also warranted.
OBJECTIVE: To determine the clinical effectiveness, tolerability and safety, of using intravenous ferric carboxymaltose (intervention) vs oral ferrous sulphate (control) for treating moderate to severe iron deficiency anaemia in postpartum women and to evaluate implementation of ferric carboxymaltose in treating postpartum anaemia in Nigeria.
METHODS AND ANALYSIS: This study is an open-label randomised controlled trial with a concurrent implementation study. It is a hybrid type 1 effectiveness-implementation design conducted in four states across Northern and Southern Nigeria. A total of 1400 eligible and consenting women with postpartum moderate to severe anaemia (haemoglobin concentration <100 g/L) will be randomised to intravenous ferric carboxymaltose; a single dose at 20 mg/kg to a maximum of 1000 mg infusion administered at enrolment (intervention) or oral ferrous sulphate; 200 mg (65 mg elemental iron) two times per day from enrolment until 6 weeks postpartum (control). The primary outcome, proportion of participants who are anaemic (Hb <110 g/L) at 6 weeks postpartum will be analysed by intention-to-treat. Haemoglobin concentration, full blood count, serum iron, serum ferritin, transferrin saturation and total iron binding capacity will be measured at specific intervals. Implementation outcomes such as acceptability and feasibility of using ferric carboxymaltose for postpartum anaemia treatment in Nigeria will be assessed.
ETHICS AND DISSEMINATION: This study is approved by the ethics committee of the teaching hospitals, Ministry of Health of the four states as required, National Health Research Ethics Committee and the drug regulatory agency, National Agency for Food and Drug Administration and Control (NAFDAC). Findings of this research will be presented at conferences and will be published in international peer-reviewed journals and shared with stakeholders within and outside Nigeria. TRIAL
REGISTRATION NUMBER: International standard randomised controlled trial number: ISRCTN51426226
Global, regional, and national burden of HIV/AIDS, 1990-2021, and forecasts to 2050, for 204 countries and territories: the Global Burden of Disease Study 2021.
Get PDFBACKGROUND: As set out in Sustainable Development Goal 3.3, the target date for ending the HIV epidemic as a public health threat is 2030. Therefore, there is a crucial need to evaluate current epidemiological trends and monitor global progress towards HIV incidence and mortality reduction goals. In this analysis, we assess the current burden of HIV in 204 countries and territories and forecast HIV incidence, prevalence, and mortality up to 2050 to allow countries to plan for a sustained response with an increasing number of people living with HIV globally. METHODS: We used the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 analytical framework to compute age-sex-specific HIV mortality, incidence, and prevalence estimates for 204 countries and territories (1990-2021). We aimed to analyse all available data sources, including data on the provision of HIV programmes reported to UNAIDS, published literature on mortality among people on antiretroviral therapy (ART) identified by a systematic review, household surveys, sentinel surveillance antenatal care clinic data, vital registration data, and country-level case report data. We calibrated a mechanistic simulation of HIV infection and natural history to available data to estimate HIV burden from 1990 to 2021 and generated forecasts to 2050 through projection of all simulation inputs into the future. Historical outcomes (1990-2021) were simulated at the 1000-draw level to support propagation of uncertainty and reporting of uncertainty intervals (UIs). Our approach to forecasting utilised the transmission rate as the basis for projection, along with new rate-of-change projections of ART coverage. Additionally, we introduced two new metrics to our reporting: prevalence of unsuppressed viraemia (PUV), which represents the proportion of the population without a suppressed level of HIV (viral load <1000 copies per mL), and period lifetime probability of HIV acquisition, which quantifies the hypothetical probability of acquiring HIV for a synthetic cohort, a simulated population that is aged from birth to death through the set of age-specific incidence rates of a given time period. FINDINGS: Global new HIV infections decreased by 21·9% (95% UI 13·1-28·8) between 2010 and 2021, from 2·11 million (2·02-2·25) in 2010 to 1·65 million (1·48-1·82) in 2021. HIV-related deaths decreased by 39·7% (33·7-44·5), from 1·19 million (1·07-1·37) in 2010 to 718 000 (669 000-785 000) in 2021. The largest declines in both HIV incidence and mortality were in sub-Saharan Africa and south Asia. However, super-regions including central Europe, eastern Europe, and central Asia, and north Africa and the Middle East experienced increasing HIV incidence and mortality rates. The number of people living with HIV reached 40·0 million (38·0-42·4) in 2021, an increase from 29·5 million (28·1-31·0) in 2010. The lifetime probability of HIV acquisition remains highest in the sub-Saharan Africa super-region, where it declined from its 1995 peak of 21·8% (20·1-24·2) to 8·7% (7·5-10·7) in 2021. Four of the seven GBD super-regions had a lifetime probability of less than 1% in 2021. In 2021, sub-Saharan Africa had the highest PUV of 999·9 (857·4-1154·2) per 100 000 population, but this was a 64·5% (58·8-69·4) reduction in PUV from 2003 to 2021. In the same period, PUV increased in central Europe, eastern Europe, and central Asia by 116·1% (8·0-218·2). Our forecasts predict a continued global decline in HIV incidence and mortality, with the number of people living with HIV peaking at 44·4 million (40·7-49·8) by 2039, followed by a gradual decrease. In 2025, we projected 1·43 million (1·29-1·59) new HIV infections and 615 000 (567 000-680 000) HIV-related deaths, suggesting that the interim 2025 targets for reducing these figures are unlikely to be achieved. Furthermore, our forecasted results indicate that few countries will meet the 2030 target for reducing HIV incidence and HIV-related deaths by 90% from 2010 levels. INTERPRETATION: Our forecasts indicate that continuation of current levels of HIV control are not likely to attain ambitious incidence and mortality reduction targets by 2030, and more than 40 million people globally will continue to require lifelong ART for decades into the future. The global community will need to show sustained and substantive efforts to make the progress needed to reach and sustain the end of AIDS as a public threat. FUNDING: The Bill & Melinda Gates Foundation and the National Institute of Allergy and Infectious Diseases
Prevalence of vision impairment, diabetic retinopathy and disability in adults 50+ in the occupied Palestinian territories.
Get PDFThe Rapid Assessment of Avoidable Blindness methodology is a population-based survey of vision impairment among the population 50 and above, with optional modules on diabetes, diabetic retinopathy and disability. The first Rapid Assessment of Avoidable Blindness study in the occupied Palestinian territories (oPt) was conducted in 2008. Prevalence of blindness (50+) was 3.4%. 80% of blindness was avoidable. Between July 2018 and April 2019, we completed a nationally-representative follow up survey in oPt using the Rapid Assessment of Avoidable Blindness methodology including the optional modules. We tested distance visual acuity (presenting and pinhole) using a bespoke mobile data collection application. 4223 Palestinians aged 50 years and above were enumerated, of whom 3847 participated (response rate 91.1%). Prevalence of any vision impairment (presenting vision impairment <6/12 in the better seeing eye), blindness (<3/60), severe vision impairment (<6/60 but ≥3/60), moderate vision impairment (<6/18 but ≥6/60) and mild vision impairment (<6/12 but ≥6/18) were 25.8% (95% confidence interval [CI] 23.8-27.8%), 2.6% (1.9-3.2%), 1.4% (1.0-1.8%), 10.2% (9.1-11.2%) and 11.6% (10.3-12.8%), respectively. Avoidable causes of poor vision accounted for 82.4% of blindness, 83.3% of severe vision impairment, 82.0% of moderate vision impairment and 90.2% of mild vision impairment. Diabetes prevalence (reported or suspected based on random blood glucose ≥200 milligrams/decilitre) was 33.8% (32.1-35.5). Half of diabetes participants had diabetic retinopathy and/or maculopathy. Prevalence of disability (reported functional limitations) was 23.8% (21.0-26.5), and higher in women than men. The prevalence of vision impairment and blindness in oPt compared with 2008 was similar. Prevalence of diabetes, diabetic retinopathy and disability were all high, highlighting key areas for public health prioritization among older adults in oPt
Cross-sectional analysis of soft drinks consumption patterns post-taxation in Saudi Arabia.
Get PDFBACKGROUND: Sweetened soft drinks consumption contributes to the increasing prevalence of obesity in Saudi Arabia. In 2017, Saudi Arabia began imposing tax on sugar-sweetened drinks to combat obesity.
AIM: To investigate the determinants of soft drinks consumption patterns among adults in Saudi Arabia 5 years after consumer tax implementation.
METHODS: This cross-sectional study was conducted among 1935 adults in Saudi Arabia, aged 20-60 years, predominantly female (80.4%). Data were collected using an online questionnaire that focused on the sociodemographic and anthropometric characteristics and consumption patterns of participants, as well as their attitudes towards soft drink consumption. Spearman's correlation and principal component analysis were used to evaluate the factors influencing soft drink consumption. Statistical significance was set at P < 0.05.
RESULTS: A significant majority of the participants (82.9%, n = 1605) reported consuming sweetened soft drinks 1-3 times per month. Habitual consumption was the most cited reason (27.1%), followed by consumption at social gatherings (12.9%) and while eating at restaurants (12.4%). Advertising was the least (7.1%) consumption influencing factor. Correlation analysis revealed that availability (0.358, P < 0.05), social gatherings (0.357, P < 0.05) and affordability (0.336, P < 0.05) were significantly associated with consumption frequency.
CONCLUSION: Despite increased taxes on soft drinks in Saudi Arabia, consumption remains largely habitual among adults. The minimal impact of advertising and normalized price perceptions suggest that alternative strategies are required to effectively reduce soft drink consumption among this population
TB prevention activities in the WHO European Region.
Get PDFBACKGROUND: TB preventive treatment (TPT) is the primary available healthcare intervention to reduce the risk of progression from TB infection to TB disease. The WHO Regional Office for Europe established the European Prevention and Systematic Screening Initiative to End TB (PASS) to scale up activities related to the programmatic management of TPT. In the absence of a system to measure and monitor preventive activities, a baseline assessment survey was carried out to provide a reference to monitor the scale-up of the intervention.
METHODS: This was a semi-structured survey including 52 questions that was developed, implemented in the WHO-hosted LimeSurvey data form and sent to focal points in the 55 countries and territories in the European Region between September and October 2023. The questions covered TPT, systematic screening and infection prevention and control.
RESULTS: A total of 28 questionnaires were returned, corresponding to an overall 51% response rate. Most national policies for TPT and TB screening are in line with the latest WHO guidelines. However, implementation of TB screening, prevention, and infection control activities is lagging. Results are presented separately for high-priority and low-priority countries.
CONCLUSION: The survey identified several important areas that the PASS initiative will focus on to accelerate efforts towards reaching the targets set at the 2027 UN High-Level Meeting on TB for preventive therapy in the European Region. This will require a massive scale-up of efforts and larger investments, as well as coordinated approaches and interventions across the ‘cascade’ of prevention, from the identification of target populations to the completion of treatment