The burden of bacterial antimicrobial resistance in the WHO European region in 2019: a cross-country systematic analysis

Background Antimicrobial resistance (AMR) represents one of the most crucial threats to public health and modern health care. Previous studies have identified challenges with estimating the magnitude of the problem and its downstream effect on human health and mortality. To our knowledge, this study presents the most comprehensive set of regional and country-level estimates of AMR burden in the WHO European region to date. Methods We estimated deaths and disability-adjusted life-years attributable to and associated with AMR for 23 bacterial pathogens and 88 pathogen–drug combinations for the WHO European region and its countries in 2019. Our methodological approach consisted of five broad components: the number of deaths in which infection had a role, 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 antimicrobial drug of interest, and the excess risk of mortality (or duration of an infection) associated with this resistance. These components were then used to estimate the disease burden by using two counterfactual scenarios: deaths attributable to AMR (considering an alternative scenario where infections with resistant pathogens are replaced with susceptible ones) and deaths associated with AMR (considering an alternative scenario where drug-resistant infections would not occur at all). Data were solicited from a wide array of international stakeholders; these included research hospitals, surveillance networks, and infection databases maintained by private laboratories and medical technology companies. We generated 95% uncertainty intervals (UIs) for final estimates as the 25th and 975th ordered values across 1000 posterior draws, and models were cross-validated for out-of-sample predictive validity. Findings We estimated 541 000 deaths (95% UI 370 000–763 000) associated with bacterial AMR and 133 000 deaths (90 100–188 000) attributable to bacterial AMR in the whole WHO European region in 2019. The largest fatal burden of AMR in the region came from bloodstream infections, with 195 000 deaths (104 000–333 000) associated with resistance, followed by intra-abdominal infections (127 000 deaths [81 900–185 000]) and respiratory infections (120 000 deaths [94 500–154 000]). Seven leading pathogens were responsible for about 457 000 deaths associated with resistance in 53 countries of this region; these pathogens were, in descending order of mortality, Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, Pseudomonas aeruginosa, Enterococcus faecium, Streptococcus pneumoniae, and Acinetobacter baumannii. Methicillin-resistant S aureus was shown to be the leading pathogen–drug combination in 27 countries for deaths attributable to AMR, while aminopenicillin-resistant E coli predominated in 47 countries for deaths associated with AMR. Interpretation The high levels of resistance for several important bacterial pathogens and pathogen–drug combinations, together with the high mortality rates associated with these pathogens, show that AMR is a serious threat to public health in the WHO European region. Our regional and cross-country analyses open the door for strategies that can be tailored to leading pathogen–drug combinations and the available resources in a specific location. These results underscore that the most effective way to tackle AMR in this region will require targeted efforts and investments in conjunction with continuous outcome-based research endeavours. Funding Bill & Melinda Gates Foundation, Wellcome Trust, and Department of Health and Social Care using UK aid funding managed by the Fleming Fund.Coauthors affiliated with this organisation provided feedback on the initial maps and drafts of this manuscript. MA acknowledges partial support by the Romanian National Authority for Scientific Research and Innovation, under the UEFISCDI PN-III-P4-ID-PCCF-2016-0084 research grant. VBG and VKG acknowledge funding support from the National Health and Medical Research Council Australia. CH is partially supported by a grant from the Romanian National Authority for Scientific Research and Innovation, CNDS-UEFISCDI, project number PN-III-P4-ID-PCCF-2016-0084, and by a grant from the Romanian Ministry of Research Innovation and Digitalization, MCID, project number ID-585-CTR-42-PFE-2021. SH was supported by the operational programme Research, Development and Education, Postdoc2MUNI (CZ.02.2.69/0.0/0.0/18_053/0016952). GL was supported by national funds through the Fundação para a Ciência e Tecnologia (FCT) under the Scientific Employment Stimulus–Individual Call (CEECIND/01768/2021). AGM was supported by the National Institute for Health and Care Research (NIHR) Manchester Biomedical Research Centre and by an NIHR Clinical Lectureship in Respiratory Medicine. AP is partially supported by a grant of the Romanian National Authority for Scientific Research and Innovation, CNDS-UEFISCDI, project number PN-III-P4-ID-PCCF-2016-0084. JP was supported by FCT through the Scientific Employment Stimulus–Individual Call (CEECIND/00394/2017 and UID/DTP/04138/2019). AS acknowledges support from Health Data Research UK. LRS was supported by project CENTRO-04-3559-FSE-000162, Fundo Social Europeu. SBZ acknowledges receiving a scholarship from the Australian Government Research Training Program in support of his academic career.publishedVersio

Global mortality associated with 33 bacterial pathogens in 2019: a systematic analysis for the Global Burden of Disease Study 2019

Background: Reducing the burden of death due to infection is an urgent global public health priority. Previous studies have estimated the number of deaths associated with drug-resistant infections and sepsis and found that infections remain a leading cause of death globally. Understanding the global burden of common bacterial pathogens (both susceptible and resistant to antimicrobials) is essential to identify the greatest threats to public health. To our knowledge, this is the first study to present global comprehensive estimates of deaths associated with 33 bacterial pathogens across 11 major infectious syndromes. Methods: We estimated deaths associated with 33 bacterial genera or species across 11 infectious syndromes in 2019 using methods from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, in addition to a subset of the input data described in the Global Burden of Antimicrobial Resistance 2019 study. This study included 343 million individual records or isolates covering 11 361 study-location-years. We used three modelling steps to estimate the number of deaths associated with each pathogen: deaths in which infection had a role, the fraction of deaths due to infection that are attributable to a given infectious syndrome, and the fraction of deaths due to an infectious syndrome that are attributable to a given pathogen. Estimates were produced for all ages and for males and females across 204 countries and territories in 2019. 95% uncertainty intervals (UIs) were calculated for final estimates of deaths and infections associated with the 33 bacterial pathogens following standard GBD methods by taking the 2·5th and 97·5th percentiles across 1000 posterior draws for each quantity of interest. Findings: From an estimated 13·7 million (95% UI 10·9–17·1) infection-related deaths in 2019, there were 7·7 million deaths (5·7–10·2) associated with the 33 bacterial pathogens (both resistant and susceptible to antimicrobials) across the 11 infectious syndromes estimated in this study. We estimated deaths associated with the 33 bacterial pathogens to comprise 13·6% (10·2–18·1) of all global deaths and 56·2% (52·1–60·1) of all sepsis-related deaths in 2019. Five leading pathogens—Staphylococcus aureus, Escherichia coli, Streptococcus pneumoniae, Klebsiella pneumoniae, and Pseudomonas aeruginosa—were responsible for 54·9% (52·9–56·9) of deaths among the investigated bacteria. The deadliest infectious syndromes and pathogens varied by location and age. The age-standardised mortality rate associated with these bacterial pathogens was highest in the sub-Saharan Africa super-region, with 230 deaths (185–285) per 100 000 population, and lowest in the high-income super-region, with 52·2 deaths (37·4–71·5) per 100 000 population. S aureus was the leading bacterial cause of death in 135 countries and was also associated with the most deaths in individuals older than 15 years, globally. Among children younger than 5 years, S pneumoniae was the pathogen associated with the most deaths. In 2019, more than 6 million deaths occurred as a result of three bacterial infectious syndromes, with lower respiratory infections and bloodstream infections each causing more than 2 million deaths and peritoneal and intra-abdominal infections causing more than 1 million deaths. Interpretation: The 33 bacterial pathogens that we investigated in this study are a substantial source of health loss globally, with considerable variation in their distribution across infectious syndromes and locations. Compared with GBD Level 3 underlying causes of death, deaths associated with these bacteria would rank as the second leading cause of death globally in 2019; hence, they should be considered an urgent priority for intervention within the global health community. Strategies to address the burden of bacterial infections include infection prevention, optimised use of antibiotics, improved capacity for microbiological analysis, vaccine development, and improved and more pervasive use of available vac ines. These estimates can be used to help set priorities for vaccine need, demand, and development. Funding: Bill & Melinda Gates Foundation, Wellcome Trust, and Department of Health and Social Care, using UK aid funding managed by the Fleming Fund. © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license **Please note that there are multiple authors for this article therefore only the name of the first 30 including Federation University Australia affiliate “Muhammad Aziz Rahman” is provided in this record*

The burden of antimicrobial resistance in the Americas in 2019: a cross-country systematic analysis

Background Antimicrobial resistance (AMR) is an urgent global health challenge and a critical threat to modern health care. Quantifying its burden in the WHO Region of the Americas has been elusive—despite the region’s long history of resistance surveillance. This study provides comprehensive estimates of AMR burden in the Americas to assess this growing health threat. Methods We estimated deaths and disability-adjusted life-years (DALYs) attributable to and associated with AMR for 23 bacterial pathogens and 88 pathogen–drug combinations for countries in the WHO Region of the Americas in 2019. We obtained data from mortality registries, surveillance systems, hospital systems, systematic literature reviews, and other sources, and applied predictive statistical modelling to produce estimates of AMR burden for all countries in the Americas. Five broad components were the backbone of our approach: the number of deaths where infection had a role, 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 pathogens resistant to an antibiotic class, and the excess risk of mortality (or duration of an infection) associated with this resistance. We then used these components to estimate the disease burden by applying two counterfactual scenarios: deaths attributable to AMR (compared to an alternative scenario where resistant infections are replaced with susceptible ones), and deaths associated with AMR (compared to an alternative scenario where resistant infections would not occur at all). We generated 95% uncertainty intervals (UIs) for final estimates as the 25th and 975th ordered values across 1000 posterior draws, and models were cross-validated for out-of-sample predictive validity. Findings We estimated 569,000 deaths (95% UI 406,000–771,000) associated with bacterial AMR and 141,000 deaths (99,900–196,000) attributable to bacterial AMR among the 35 countries in the WHO Region of the Americas in 2019. Lower respiratory and thorax infections, as a syndrome, were responsible for the largest fatal burden of AMR in the region, with 189,000 deaths (149,000–241,000) associated with resistance, followed by bloodstream infections (169,000 deaths [94,200–278,000]) and peritoneal/intra-abdominal infections (118,000 deaths [78,600–168,000]). The six leading pathogens (by order of number of deaths associated with resistance) were Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, Streptococcus pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii. Together, these pathogens were responsible for 452,000 deaths (326,000–608,000) associated with AMR. Methicillin-resistant S. aureus predominated as the leading pathogen–drug combination in 34 countries for deaths attributable to AMR, while aminopenicillin-resistant E. coli was the leading pathogen–drug combination in 15 countries for deaths associated with AMR. Interpretation Given the burden across different countries, infectious syndromes, and pathogen–drug combinations, AMR represents a substantial health threat in the Americas. Countries with low access to antibiotics and basic health-care services often face the largest age-standardised mortality rates associated with and attributable to AMR in the region, implicating specific policy interventions. Evidence from this study can guide mitigation efforts that are tailored to the needs of each country in the region while informing decisions regarding funding and resource allocation. Multisectoral and joint cooperative efforts among countries will be a key to success in tackling AMR in the Americas.publishedVersio

Targeting efficiency and take-up of Oportunidades, a conditional cash transfer, in urban Mexico in 2008

Oportunidades is a Conditional Cash Transfer (CCT) that uses a proxy means-test targeting model to select eligible households for the programme. According to the Income and Expenditure Household Survey of 2008, approximately two in every three eligible rural households participate in Oportunidades, whereas only one in every three eligible urban households receives the Oportunidades cash transfer. This research explores the factors behind this lack of take-up, the costs of participation and the implications of targeting inefficiency on the programme’s impact on income poverty. It argues that a sample selection model is a pertinent tool of analysis as it informs on the distribution of cash transfers conditional on household eligibility. This conditional distribution is also used to understand the costs of participation as a latent variable. Eligible households are less likely to invest in human capital and neither the cash transfer nor the income forgone by children and teenagers are sufficient to overcome these costs of participation. By identifying a method to quantify behavioural change of households, I associate the costs of participation to the difficulties of inducing health-related behavioural change among recipients and eligible non-recipients. At an aggregate state level, targeting inefficiency is not fully explained by only looking at the budget constraints of the programme. In fact, targeting efficiency is positively associated to aggregate behavioural change and negatively associated to aggregate costs for participation at state level. Yet, targeting efficiency does not guarantee impact on income poverty and Oportunidades’ highest impact on income poverty also associated with the inclusion of non-eligible households in the programme. This research reconsiders the importance of the context in which CCTs are implemented and informs on the conflicting aims of CCTs: providing income poverty relief via cash transfers and incentivizing behavioural change by conditioning the cash transfer in health and education investment. </p

Least developed countries and the Multidimensional Poverty Index (MPI): OPHI research briefing 10

In 2011, the Multidimensional Poverty Index (MPI) was released for 109 countries. Of these, 39 countries are identified as ‘least developed countries’ (LDCs). This note provides briefing facts regarding MPI in these countries.Copyright © Oxford Poverty & Human Development Initiative 2012

Burden of disease among the world\u27s poorest billion people: An expert-informed secondary analysis of Global Burden of Disease estimates.

BACKGROUND: The health of populations living in extreme poverty has been a long-standing focus of global development efforts, and continues to be a priority during the Sustainable Development Goal era. However, there has not been a systematic attempt to quantify the magnitude and causes of the burden in this specific population for almost two decades. We estimated disease rates by cause for the world’s poorest billion and compared these rates to those in high-income populations. METHODS: We defined the population in extreme poverty using a multidimensional poverty index. We used national-level disease burden estimates from the 2017 Global Burden of Disease Study and adjusted these to account for within-country variation in rates. To adjust for within-country variation, we looked to the relationship between rates of extreme poverty and disease rates across countries. In our main modeling approach, we used these relationships when there was consistency with expert opinion from a survey we conducted of disease experts regarding the associations between household poverty and the incidence and fatality of conditions. Otherwise, no within-country variation was assumed. We compared results across multiple approaches for estimating the burden in the poorest billion, including aggregating national-level burden from the countries with the highest poverty rates. We examined the composition of the estimated disease burden among the poorest billion and made comparisons with estimates for high-income countries. RESULTS: The composition of disease burden among the poorest billion, as measured by disability-adjusted life years (DALYs), was 65% communicable, maternal, neonatal, and nutritional (CMNN) diseases, 29% non-communicable diseases (NCDs), and 6% injuries. Age-standardized DALY rates from NCDs were 44% higher in the poorest billion (23,583 DALYs per 100,000) compared to high-income regions (16,344 DALYs per 100,000). Age-standardized DALY rates were 2,147% higher for CMNN conditions (32,334 DALYs per 100,000) and 86% higher for injuries (4,182 DALYs per 100,000) in the poorest billion, compared to high-income regions. CONCLUSION: The disease burden among the poorest people globally compared to that in high income countries is highly influenced by demographics as well as large disparities in burden from many conditions. The comparisons show that the largest disparities remain in communicable, maternal, neonatal, and nutritional diseases, though NCDs and injuries are an important part of the “unfinished agenda” of poor health among those living in extreme poverty

The burden of bacterial antimicrobial resistance in the WHO European region in 2019: a cross-country systematic analysis

Background Antimicrobial resistance (AMR) represents one of the most crucial threats to public health and modern health care. Previous studies have identified challenges with estimating the magnitude of the problem and its downstream effect on human health and mortality. To our knowledge, this study presents the most comprehensive set of regional and country-level estimates of AMR burden in the WHO European region to date. Methods We estimated deaths and disability-adjusted life-years attributable to and associated with AMR for 23 bacterial pathogens and 88 pathogen–drug combinations for the WHO European region and its countries in 2019. Our methodological approach consisted of five broad components: the number of deaths in which infection had a role, 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 antimicrobial drug of interest, and the excess risk of mortality (or duration of an infection) associated with this resistance. These components were then used to estimate the disease burden by using two counterfactual scenarios: deaths attributable to AMR (considering an alternative scenario where infections with resistant pathogens are replaced with susceptible ones) and deaths associated with AMR (considering an alternative scenario where drug-resistant infections would not occur at all). Data were solicited from a wide array of international stakeholders; these included research hospitals, surveillance networks, and infection databases maintained by private laboratories and medical technology companies. We generated 95% uncertainty intervals (UIs) for final estimates as the 25th and 975th ordered values across 1000 posterior draws, and models were cross-validated for out-of-sample predictive validity. Findings We estimated 541 000 deaths (95% UI 370 000–763 000) associated with bacterial AMR and 133 000 deaths (90 100–188 000) attributable to bacterial AMR in the whole WHO European region in 2019. The largest fatal burden of AMR in the region came from bloodstream infections, with 195 000 deaths (104 000–333 000) associated with resistance, followed by intra-abdominal infections (127 000 deaths [81 900–185 000]) and respiratory infections (120 000 deaths [94 500–154 000]). Seven leading pathogens were responsible for about 457 000 deaths associated with resistance in 53 countries of this region; these pathogens were, in descending order of mortality, Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, Pseudomonas aeruginosa, Enterococcus faecium, Streptococcus pneumoniae, and Acinetobacter baumannii. Methicillin-resistant S aureus was shown to be the leading pathogen–drug combination in 27 countries for deaths attributable to AMR, while aminopenicillin-resistant E coli predominated in 47 countries for deaths associated with AMR. Interpretation The high levels of resistance for several important bacterial pathogens and pathogen–drug combinations, together with the high mortality rates associated with these pathogens, show that AMR is a serious threat to public health in the WHO European region. Our regional and cross-country analyses open the door for strategies that can be tailored to leading pathogen–drug combinations and the available resources in a specific location. These results underscore that the most effective way to tackle AMR in this region will require targeted efforts and investments in conjunction with continuous outcome-based research endeavours. Funding Bill & Melinda Gates Foundation, Wellcome Trust, and Department of Health and Social Care using UK aid funding managed by the Fleming Fund