Global, regional, and national age-specific progress towards the 2020 milestones of the WHO End TB Strategy: a systematic analysis for the Global Burden of Disease Study 2021

PurposePneumonia remains a significant global health concern, particularly among those requiring admission to the intensive care unit (ICU). Despite the availability of international guidelines there remains heterogeneity in clinical management. The D-PRISM study aimed to develop a global overview of how pneumonias (ie, community-acquired (CAP), hospital-acquired (HAP), and Ventilator-associated pneumonia (VAP)) are diagnosed and treated in the ICU and compare differences in clinical practice worldwide.MethodsThe D-PRISM study was a multinational, survey-based investigation to assess the diagnosis and treatment of pneumonia in the ICU. A self-administered online questionnaire was distributed to intensive care clinicians from 72 countries between September to November 2022. The questionnaire included sections on professional profiles, current clinical practice in diagnosing and managing CAP, HAP, and VAP, and the availability of microbiology diagnostic tests.ResultsA total of 1296 valid responses were collected from ICU clinicians, spread between low-and-middle income (LMIC) and high-income countries (HIC), with LMIC respondents comprising 51% of respondents. There is heterogeneity across the processes of diagnosis, including in clinical assessment where 30%(389) did not require radiological evidence to diagnose pneumonia, variable collection of microbiological samples and use and practice in bronchoscopy. Modal antibiotic treatment duration was 5–7 days for all types of pneumonia.ConclusionsThis study highlighted variations in clinical practice and diagnostic capabilities for pneumonia, particularly issues …

The Lancet

BackgroundEstimates of demographic metrics are crucial to assess levels and trends of population health outcomes. The profound impact of the COVID-19 pandemic on populations worldwide has underscored the need for timely estimates to understand this unprecedented event within the context of long-term population health trends. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 provides new demographic estimates for 204 countries and territories and 811 additional subnational locations from 1950 to 2021, with a particular emphasis on changes in mortality and life expectancy that occurred during the 2020–21 COVID-19 pandemic period.Methods22 223 data sources from vital registration, sample registration, surveys, censuses, and other sources were used to estimate mortality, with a subset of these sources used exclusively to estimate excess mortality due to the COVID-19 …

Heliyon

Role of clustered regularly interspaced short palindromic repeats (CRISPR)-like sequences in antibiotic resistance and biofilm formation isn't clear. This study investigated association of CRISPR-like sequences with antibiotic resistance and biofilm formation in H. pylori isolates. Thirty-six of H. pylori isolates were studied for existence of CRISPR-like sequences using PCR method and their correlation with biofilm formation and antibiotic resistance. Microtiter-plate technique was utilized for investigating antibiotic resistance profile of isolates against amoxicillin, tetracycline, metronidazole and clarithromycin. Biofilm formation of isolates was analyzed by microtiter-plate-based-method. Out of 23 CRISPR-like positive isolates, 19 had ability of biofilm formation and 7 of 13 CRISPR-like negative isolates were able to form biofilm (Pvalue = 0.445). In CRISPR-like positive isolates, 11 (48%), 18 (78%), 18 (78%) and 23 …

Nature Communications

Chewing tobacco use poses serious health risks; yet it has not received as much attention as other tobacco-related products. This study synthesizes existing evidence regarding the health impacts of chewing tobacco while accounting for various sources of uncertainty. We conducted a systematic review and meta-analysis of chewing tobacco and seven health outcomes, drawing on 103 studies published from 1970 to 2023. We use a Burden of Proof meta-analysis to generate conservative risk estimates and find weak-to-moderate evidence that tobacco chewers have an increased risk of stroke, lip and oral cavity cancer, esophageal cancer, nasopharynx cancer, other pharynx cancer, and laryngeal cancer. We additionally find insufficient evidence of an association between chewing tobacco and ischemic heart disease. Our findings highlight a need for policy makers, researchers, and communities at risk to devote …

Informatics in Medicine Unlocked

Helicobacter pylori (H. pylori) is mainly considered for causing chronic gastritis, which can lead to several secondary complications like peptic ulcer and pre-malignant lesions for example atrophic gastritis, intestinal dysplasia and metaplasia, with the etiological factor of developing gastric cancer. Recent research demonstrates that H.pylori colonizes the stomach mucosa of more than fifty populations around the globe. This research focuses on unveiling hub genes, and diagnostic and drug targets against said organism by utilizing various types of networking biology and biophysical approaches. In data retrieval, the GSE19826 dataset was obtained from the gene expression omnibus database and microarray data set from array express. Geo2r analysis predicted a total number of 7 DEGs and 10 hub genes, next functional protein association network analysis (STRING) unveiled that among 10 Hub genes only 3 …

The Lancet

BackgroundEstimates of demographic metrics are crucial to assess levels and trends of population health outcomes. The profound impact of the COVID-19 pandemic on populations worldwide has underscored the need for timely estimates to understand this unprecedented event within the context of long-term population health trends. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 provides new demographic estimates for 204 countries and territories and 811 additional subnational locations from 1950 to 2021, with a particular emphasis on changes in mortality and life expectancy that occurred during the 2020–21 COVID-19 pandemic period.Methods22 223 data sources from vital registration, sample registration, surveys, censuses, and other sources were used to estimate mortality, with a subset of these sources used exclusively to estimate excess mortality due to the COVID-19 …

Proceedings of the National Academy of Sciences

Schistosomiasis is a neglected tropical disease affecting over 150 million people. Hotspots of Schistosoma transmission—communities where infection prevalence does not decline adequately with mass drug administration—present a key challenge in eliminating schistosomiasis. Current approaches to identify hotspots require evaluation 2–5 y after a baseline survey and subsequent mass drug administration. Here, we develop statistical models to predict hotspots at baseline prior to treatment comparing three common hotspot definitions, using epidemiologic, survey-based, and remote sensing data. In a reanalysis of randomized trials in 589 communities in five endemic countries, a regression model predicts whether Schistosoma mansoni infection prevalence will exceed the WHO threshold of 10% in year 5 (“prevalence hotspot”) with 86% sensitivity, 74% specificity, and 93% negative predictive value (NPV …

The Lancet

BackgroundRegular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations.MethodsThe Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational …

The Lancet

BackgroundEstimates of demographic metrics are crucial to assess levels and trends of population health outcomes. The profound impact of the COVID-19 pandemic on populations worldwide has underscored the need for timely estimates to understand this unprecedented event within the context of long-term population health trends. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 provides new demographic estimates for 204 countries and territories and 811 additional subnational locations from 1950 to 2021, with a particular emphasis on changes in mortality and life expectancy that occurred during the 2020–21 COVID-19 pandemic period.Methods22 223 data sources from vital registration, sample registration, surveys, censuses, and other sources were used to estimate mortality, with a subset of these sources used exclusively to estimate excess mortality due to the COVID-19 …

The Lancet Neurology

BackgroundDisorders affecting the nervous system are diverse and include neurodevelopmental disorders, late-life neurodegeneration, and newly emergent conditions, such as cognitive impairment following COVID-19. Previous publications from the Global Burden of Disease, Injuries, and Risk Factor Study estimated the burden of 15 neurological conditions in 2015 and 2016, but these analyses did not include neurodevelopmental disorders, as defined by the International Classification of Diseases (ICD)-11, or a subset of cases of congenital, neonatal, and infectious conditions that cause neurological damage. Here, we estimate nervous system health loss caused by 37 unique conditions and their associated risk factors globally, regionally, and nationally from 1990 to 2021.MethodsWe estimated mortality, prevalence, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years …

Current estimates of fungal disease incidence and mortality are imprecise. Population at risk denominators were used to estimate annual incidence for 2019–21. Extensive literature searches from 2010 to 2023 were combined with over 85 papers on individual country and global disease burden. Crude and attributable mortality were estimated using a combination of untreated mortality, the proportion of patients who are treated, and percentage survival in treated patients. Awareness, guidelines, and accessibility of diagnostics and therapies informed the ratio of treated to untreated cases. Estimates do not include influenza or COVID-19 outbreaks. Data from more than 120 countries were included. Annually, over 2 113 000 people develop invasive aspergillosis in the context of chronic obstructive pulmonary disease, intensive care, lung cancer, or haematological malignancy, with a crude annual mortality of 1 801 …

The Lancet

BackgroundRegular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations.MethodsThe Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational …

Reviews on Recent Clinical Trials

BackgroundMitochondrial dysfunction and impaired mitophagy are integral to myocyte loss and the progression of heart failure. Urolithin A (UA), a microbiota-produced metabolite of ellagitannins and ellagic acid, is a known stimulator of mitophagy and mitochondrial biogenesis that has shown cardioprotective effects in experimental models.MethodsA randomized, double-blind, placebo-controlled 2× 2 crossover trial was conducted on 10 patients with HF with reduced ejection fraction (HFrEF). The trial design involved two 4-week intervention periods of UA (500 mg BID) and placebo, separated by a 2-week washout phase. The patients underwent two-dimensional echocardiogram examination as well as blood sampling at the beginning and end of each period.ResultsAll patients completed the study. The results failed to reveal any significant effect of UA supplementation on echocardiographic measures (LVEF, LVEDD, LVESV, and TAPSE). Plasma concentrations of pro-BNP, glucose, and CRP (p> 0.05) were also not altered. Serum HDL-C levels were increased with UA compared with placebo (+ 6.46±2.33 mg/dL, p= 0.026), whereas other lipid indices (LDL-C, triglycerides, total cholesterol, and VLDL-C) remained unchanged (p> 0.05).ConclusionThe results of the present study do not support any positive effect of UA supplementation in improving echocardiographic and biochemical indices of HFrEF. Further studies with higher doses of UA and longer supplementation duration are encouraged to be conducted.

The Lancet

BackgroundRegular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations.MethodsThe Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational …

The Lancet

BackgroundEstimates of demographic metrics are crucial to assess levels and trends of population health outcomes. The profound impact of the COVID-19 pandemic on populations worldwide has underscored the need for timely estimates to understand this unprecedented event within the context of long-term population health trends. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 provides new demographic estimates for 204 countries and territories and 811 additional subnational locations from 1950 to 2021, with a particular emphasis on changes in mortality and life expectancy that occurred during the 2020–21 COVID-19 pandemic period.Methods22 223 data sources from vital registration, sample registration, surveys, censuses, and other sources were used to estimate mortality, with a subset of these sources used exclusively to estimate excess mortality due to the COVID-19 …

Iranian Journal of Allergy, Asthma and Immunology

Patients with inborn errors of immunity (IEI) are among the high-risk groups regarding COVID-19. Receiving booster doses (third and fourth) in addition to the standard doses is recommended in these patients. This study investigated the antibody response before and after a booster dose of Sinopharm vaccine in IEI patients. Thirty patients (> 12 years) with antibody deficiencies, referred to Imam Khomeini Hospital and Children's Medical Center in Tehran, were enrolled in this prospective cross-sectional study. All patients were fully vaccinated with the BBIBP-CorV vaccine (2 doses of Sinopharm). Initial measurements of anti-receptor-binding domain (anti-RBD) and anti-nucleocapsid (anti-N) IgG antibody responses were conducted by enzyme-linked immunosorbent assay (ELISA). Subsequently, all patients received a booster dose of the vaccine. Four to six weeks after booster injection, the levels of antibodies were re-evaluated. Twenty patients with common variable immunodeficiency (CVID), 7 cases with agammaglobulinemia and 3 patients with hyper IgM syndrome were studied. Anti-RBD IgG and anti-N IgG antibodies increased in all patients after the booster. Our results indicated the need of receiveing booster doses of the COVID-19 vaccine in patients with antibody deficiencies, even for enhancing humoral immune response specially in patients with CVID.

Background There is currently very little research evidence on the benefits and safety of liraglutide in the management of weight regain or inadequate weight loss following metabolic and bariatric surgery. This study aimed to determine the clinical effectiveness and tolerability of liraglutide as an adjunct therapy for managing weight regain and inadequate weight loss following sleeve gastrectomy (SG).Methods This was a retrospective analysis of medical records conducted at a private clinic in Kuwait.ResultsData of 57 post-SG patients were included in the analysis. The mean (±SD) pre-treatment weight was 96.12 (29.26) kg. Following a median liraglutide treatment duration of approximately 3 months, the mean post-treatment weight was 90.19 (26.82) kg. This represents a statistically significant mean weight loss of 5.94 (6.31) kg (p < 0.001), corresponding to a loss of 6.20% of pre-treatment weight. Patients aged 31-40 years achieved a greater post-treatment weight loss of 7.63 (7.41) kg, a loss of 7.80%, relative to age groups after treatment (p = 0.047). Patients who tolerated ≥2.4 mg of liraglutide recorded a higher mean weight loss of 8.42 (7.63) kg, a loss of 8.10% (p = 0.010).Conclusion The use of liraglutide may be an effective adjunct treatment for weight optimization following SG. Maximizing the tolerable dose may yield greater weight reduction.

Clinical Kidney Journal

Background The study aimed to estimate the attributable burden to kidney dysfunction as a metabolic risk factor in the North Africa and Middle East (NAME) region and its 21 countries in 1990–2019. Methods The data used in this study were obtained from the Global Burden of Diseases (GBD) 2019 study, which provided estimated measures of deaths, disability-adjusted life years (DALYs), and other epidemiological indicators of burden. To provide a better insight into the differences in the level of social, cultural, and economic factors, the Socio-Demographic Index (SDI) was used. Results In the NAME region in 2019, the number of deaths attributed to kidney dysfunction was 296 632 (95% uncertainty interval: 249 965–343 962), which was about 2.5 times higher than in the year 1990. Afghanistan, Egypt, and Saudi Arabia had the highest, and Kuwait …

The Lancet

BackgroundRegular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations.MethodsThe Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational …

The Lancet Infectious Diseases

Mucosal vaccines that prevent SARS-CoV-2 infection might provide benefits beyond existing intramuscularly administered vaccines: through enhanced individual-level protection against disease, and population-level reduction of viral carriage and transmission. Secreted neutralising antibodies are most likely to be the crucial effectors for such vaccines generating a mucosal response. 1 However, it is unclear to what extent intramuscular administration of SARS-CoV-2 vaccines enhances neutralising antibody titres in the mucosal compartment, nor the breadth of variants that are neutralised. In response, we describe an adapted version of our high-throughput live virus microneutralisation assay for mucosal samples to establish the effect of fourth dose intramuscular mRNA vaccination on neutralising antibodies against six SARS-CoV-2 variants (Omicron BA. 1, BA. 2, BA. 5, BQ. 1.1, XBB. 1.5, and XBB. 1.16) in paired …

The Lancet Infectious Diseases

BackgroundGlobal evaluations of the progress towards the WHO End TB Strategy 2020 interim milestones on mortality (35% reduction) and incidence (20% reduction) have not been age specific. We aimed to assess global, regional, and national-level burdens of and trends in tuberculosis and its risk factors across five separate age groups, from 1990 to 2021, and to report on age-specific progress between 2015 and 2020.MethodsWe used the Global Burden of Diseases, Injuries, and Risk Factors Study 2021 (GBD 2021) analytical framework to compute age-specific tuberculosis mortality and incidence estimates for 204 countries and territories (1990–2021 inclusive). We quantified tuberculosis mortality among individuals without HIV co-infection using 22 603 site-years of vital registration data, 1718 site-years of verbal autopsy data, 825 site-years of sample-based vital registration data, 680 site-years of mortality …

The Lancet Infectious Diseases

BackgroundA three-dose dengue vaccine (CYD-TDV) was licensed for use in children aged 9 years and older starting in 2015 in several dengue-endemic countries. In 2016, the Philippine Department of Health implemented a dengue vaccination programme, which was discontinued because of safety concerns. We assessed the relative risk of developing virologically confirmed dengue among children who did or did not receive a single dose of CYD-TDV by previous dengue virus (DENV) infections at baseline classified as none, one, and two or more infections.MethodsIn this longitudinal, prospective, population-based cohort study, we enrolled healthy children (aged 9–14 years) residing in Bogo or Balamban, Cebu, Philippines, between May 2, and June 2, 2017, before a mass dengue vaccination campaign, via the Rural Health Unit in Bogo and three Rural Health Units in Balamban. We collected demographic …

The Lancet Infectious Diseases

BackgroundA human hookworm vaccine is being developed to protect children against iron deficiency and anaemia associated with chronic infection with hookworms. Necator americanus aspartic protease-1 (Na-APR-1) and N americanus glutathione S-transferase-1 (Na-GST-1) are components of the blood digestion pathway critical to hookworm survival in the host. Recombinant Na-GST-1 and catalytically inactive Na-APR-1 (Na-APR-1[M74]) adsorbed to Alhydrogel were safe and immunogenic when delivered separately or co-administered to adults in phase 1 trials in non-endemic and endemic areas. We aimed to investigate the safety and immunogenicity of these antigens in healthy children in a hookworm-endemic area.MethodsThis was a randomised, controlled, observer-blind, phase 1, dose-escalation trial, conducted in a clinical research centre, in 60 children aged six to ten years in Lambaréné, a …

The Lancet Infectious Diseases

BackgroundGlobal evaluations of the progress towards the WHO End TB Strategy 2020 interim milestones on mortality (35% reduction) and incidence (20% reduction) have not been age specific. We aimed to assess global, regional, and national-level burdens of and trends in tuberculosis and its risk factors across five separate age groups, from 1990 to 2021, and to report on age-specific progress between 2015 and 2020.MethodsWe used the Global Burden of Diseases, Injuries, and Risk Factors Study 2021 (GBD 2021) analytical framework to compute age-specific tuberculosis mortality and incidence estimates for 204 countries and territories (1990–2021 inclusive). We quantified tuberculosis mortality among individuals without HIV co-infection using 22 603 site-years of vital registration data, 1718 site-years of verbal autopsy data, 825 site-years of sample-based vital registration data, 680 site-years of mortality …

The Lancet Infectious Diseases

BackgroundGlobal evaluations of the progress towards the WHO End TB Strategy 2020 interim milestones on mortality (35% reduction) and incidence (20% reduction) have not been age specific. We aimed to assess global, regional, and national-level burdens of and trends in tuberculosis and its risk factors across five separate age groups, from 1990 to 2021, and to report on age-specific progress between 2015 and 2020.MethodsWe used the Global Burden of Diseases, Injuries, and Risk Factors Study 2021 (GBD 2021) analytical framework to compute age-specific tuberculosis mortality and incidence estimates for 204 countries and territories (1990–2021 inclusive). We quantified tuberculosis mortality among individuals without HIV co-infection using 22 603 site-years of vital registration data, 1718 site-years of verbal autopsy data, 825 site-years of sample-based vital registration data, 680 site-years of mortality …

The Lancet Infectious Diseases

BackgroundThe COVID-19 pandemic is reported to have affected the epidemiology of respiratory syncytial virus (RSV), which could have important implications for RSV prevention and control strategies. We aimed to assess the hospitalisation burden of RSV-associated acute lower respiratory infection (ALRI) in children younger than 5 years during the pandemic period and the possible changes in RSV epidemiology from a global perspective.MethodsWe conducted a systematic literature search for studies published between Jan 1, 2020, and June 30, 2022, in MEDLINE, Embase, Global Health, Web of Science, the WHO COVID-19 Research Database, CINAHL, LILACS, OpenGrey, CNKI, WanFang, and CqVip. We included unpublished data on RSV epidemiology shared by international collaborators. Eligible studies reported data on at least one of the following measures for children (aged <5 years) hospitalised …

The Lancet Infectious Diseases

BackgroundDespite a global epidemiological transition towards increased burden of non-communicable diseases, communicable diseases continue to cause substantial morbidity and mortality worldwide. Understanding the burden of a wide range of infectious diseases, and its variation by geography and age, is pivotal to research priority setting and resource mobilisation globally.MethodsWe estimated disability-adjusted life-years (DALYs) associated with 85 pathogens in 2019, globally, regionally, and for 204 countries and territories. The term pathogen included causative agents, pathogen groups, infectious conditions, and aggregate categories. We applied a novel methodological approach to account for underlying, immediate, and intermediate causes of death, which counted every death for which a pathogen had a role in the pathway to death. We refer to this measure as the burden associated with infection …

The Lancet Infectious Diseases

BackgroundStaphylococcus aureus bloodstream infection is treated with at least 14 days of intravenous antimicrobials. We assessed the efficacy and safety of an early switch to oral therapy in patients at low risk for complications related to S aureus bloodstream infection.MethodsIn this international, open-label, randomised, controlled, non-inferiority trial done in 31 tertiary care hospitals in Germany, France, the Netherlands, and Spain, adult patients with low-risk S aureus bloodstream infection were randomly assigned after 5–7 days of intravenous antimicrobial therapy to oral antimicrobial therapy or to continue intravenous standard therapy. Randomisation was done via a central web-based system, using permuted blocks of varying length, and stratified by study centre. The main exclusion criteria were signs and symptoms of complicated S aureus bloodstream infection, non-removable foreign devices, and severe …

The Lancet Infectious Diseases

Mucosal vaccines that prevent SARS-CoV-2 infection might provide benefits beyond existing intramuscularly administered vaccines: through enhanced individual-level protection against disease, and population-level reduction of viral carriage and transmission. Secreted neutralising antibodies are most likely to be the crucial effectors for such vaccines generating a mucosal response. 1 However, it is unclear to what extent intramuscular administration of SARS-CoV-2 vaccines enhances neutralising antibody titres in the mucosal compartment, nor the breadth of variants that are neutralised. In response, we describe an adapted version of our high-throughput live virus microneutralisation assay for mucosal samples to establish the effect of fourth dose intramuscular mRNA vaccination on neutralising antibodies against six SARS-CoV-2 variants (Omicron BA. 1, BA. 2, BA. 5, BQ. 1.1, XBB. 1.5, and XBB. 1.16) in paired …

The Lancet Infectious Diseases

The SARS-CoV-2 variant JN. 1 swiftly became the global dominant strain1, 2 due to a spike protein Leu455Ser substitution, boosting transmissibility and immune-escape capabilities, surpassing its predecessor BA. 2.86 and other variants. 1, 3, 4 These alterations have resulted in a surge of COVID-19 cases, reflected in wastewatersurveillance data surpassing rates, observed during the initial omicron wave. However, concerns persist that JN. 1 might have an increased capacity to replicate in the gut, potentially leading to infected individuals shedding a higher number of viral copies than previously seen. As there is currently a lack of available data for fecal viral shedding, we are presenting the initial longitudinal and quantitative faecal shedding data for SARS-CoV-2 RNA in individuals infected with XBB. 1.5, EG. 5.1, HV. 1, JD. 1.1, BA. 2.86, and JN. 1. 856 faecal samples were obtained from 113 non-hospitalised …

The Lancet Infectious Diseases

BackgroundStaphylococcus aureus bloodstream infection is treated with at least 14 days of intravenous antimicrobials. We assessed the efficacy and safety of an early switch to oral therapy in patients at low risk for complications related to S aureus bloodstream infection.MethodsIn this international, open-label, randomised, controlled, non-inferiority trial done in 31 tertiary care hospitals in Germany, France, the Netherlands, and Spain, adult patients with low-risk S aureus bloodstream infection were randomly assigned after 5–7 days of intravenous antimicrobial therapy to oral antimicrobial therapy or to continue intravenous standard therapy. Randomisation was done via a central web-based system, using permuted blocks of varying length, and stratified by study centre. The main exclusion criteria were signs and symptoms of complicated S aureus bloodstream infection, non-removable foreign devices, and severe …

The Lancet Infectious Diseases

BackgroundDespite a global epidemiological transition towards increased burden of non-communicable diseases, communicable diseases continue to cause substantial morbidity and mortality worldwide. Understanding the burden of a wide range of infectious diseases, and its variation by geography and age, is pivotal to research priority setting and resource mobilisation globally.MethodsWe estimated disability-adjusted life-years (DALYs) associated with 85 pathogens in 2019, globally, regionally, and for 204 countries and territories. The term pathogen included causative agents, pathogen groups, infectious conditions, and aggregate categories. We applied a novel methodological approach to account for underlying, immediate, and intermediate causes of death, which counted every death for which a pathogen had a role in the pathway to death. We refer to this measure as the burden associated with infection …

The Lancet Infectious Diseases

Chronic Chagas disease is caused by the protozoan Trypanosoma cruzi and affects around 6 million people in Latin America. Additionally, migration is favouring the spread of T cruzi infection throughout the world. 1 After initial infection, about 60% of T cruzi-infected people enter the indeterminate stage of chronic Chagas disease, characterised by persistent positive blood serology with normal 12-lead ECG, normal chest x-ray, and normal digestive tract imaging. About 20% of infected patients will go on to develop chronic Chagas disease cardiomyopathy up to 20 years after initial infection. 1 Benznidazole monotherapy is associated to high negative T cruzi real-time PCR conversion rates sustained at 6 months or 1 year following treatment in the indeterminate stage of chronic Chagas disease, but side-effects lead to therapy discontinuation or interruption in 32–37% of patients. 2, 3 However, real-time PCR …

The Lancet Infectious Diseases

BackgroundGlobal evaluations of the progress towards the WHO End TB Strategy 2020 interim milestones on mortality (35% reduction) and incidence (20% reduction) have not been age specific. We aimed to assess global, regional, and national-level burdens of and trends in tuberculosis and its risk factors across five separate age groups, from 1990 to 2021, and to report on age-specific progress between 2015 and 2020.MethodsWe used the Global Burden of Diseases, Injuries, and Risk Factors Study 2021 (GBD 2021) analytical framework to compute age-specific tuberculosis mortality and incidence estimates for 204 countries and territories (1990–2021 inclusive). We quantified tuberculosis mortality among individuals without HIV co-infection using 22 603 site-years of vital registration data, 1718 site-years of verbal autopsy data, 825 site-years of sample-based vital registration data, 680 site-years of mortality …

The Lancet Infectious Diseases

BackgroundThe effectiveness of BCG vaccine for adult pulmonary tuberculosis remains uncertain. In this study, we aimed to evaluate the effect of vaccination with BCG-Denmark to prevent initial and sustained interferon-γ release assay conversion in Brazilian health-care workers.MethodsThis substudy is a nested randomised controlled trial embedded within the BRACE trial (NCT04327206). Specifically, this substudy enrolled Brazilian health-care workers (aged ≥18 years) from three sites in Brazil (Manaus, Campo Grande, and Rio de Janeiro) irrespective of previously receiving BCG vaccination. Participants were excluded if they had contraindications to BCG vaccination, more than 1 month of treatment with specific tuberculosis treatment drugs, previous adverse reactions to BCG, recent BCG vaccination, or non-compliance with assigned interventions. Those eligible were randomly assigned (1:1) to either the …

The Lancet Infectious Diseases

BackgroundAndes virus (ANDV) is a zoonotic Orthohantavirus leading to hantavirus cardiopulmonary syndrome. Although most transmissions occur through environmental exposure to rodent faeces and urine, rare person-to-person transmission has been documented, mainly for close contacts. This study investigates the presence and infectivity of ANDV in body fluids from confirmed cases and the duration of viraemia.MethodsIn this prospective study, 131 participants with confirmed ANDV infection were enrolled in Chile in a prospective study between 2008 and 2022. Clinical samples (buffy coat, plasma, gingival crevicular fluid [GCF], saliva, nasopharyngeal swabs [NPS], and urine) were collected weekly for 3 weeks together with clinical and epidemiological data. Samples were categorised as acute or convalescent (up to and after 16 days following onset of symptoms). Infectivity of positive fluids was assessed …

The Lancet Infectious Diseases

In The Lancet Infectious Diseases, Luis Eduardo Lopéz Cortés and colleagues reported the results of the SIMPLIFY study, a multicentre, non-inferiority, open-label, randomised controlled trial investigating de-escalation of antipseudomonal β-lactams in patients with bloodstream infections caused by Enterobacterales. 1 De-escalation is an antimicrobial stewardship strategy aimed at reducing the emergence of multidrug-resistant bacteria, collateral damage from the empirical use of broad-spectrum antibiotics. It consists of stopping drugs given as part of combination therapy or replacing broad-spectrum antibiotics with narrower-spectrum antibiotics. 2 Lopéz Cortés and colleagues randomly assigned patients to either continue empirical anti-pseudomonal β-lactams or to de-escalate according to a preestablished list of antibiotics without anti-pseudomonal activity. This list included ciprofloxacin, and its use was …

The Lancet Infectious Diseases

BackgroundRezafungin, a new US Food and Drug Administration-approved, long-acting echinocandin to treat candidaemia and invasive candidiasis, was efficacious with a similar safety profile to caspofungin in clinical trials. We conducted pooled analyses of the phase 2 STRIVE and phase 3 ReSTORE rezafungin trials.MethodsReSTORE was a multicentre, double-blind, double-dummy, randomised phase 3 trial conducted at 66 tertiary care centres in 15 countries. STRIVE was a multicentre, double-blind, double-dummy, randomised phase 2 trial conducted at 44 centres in 10 countries. Adults (≥18 years) with candidaemia or invasive candidiasis were treated with once-a-week intravenous rezafungin (400 mg and 200 mg) or once-a-day intravenous caspofungin (70 mg and 50 mg). Efficacy was evaluated in a pooled modified intent-to-treat (mITT) population. Primary efficacy endpoint was day 30 all-cause …

The Lancet Infectious Diseases

Of the many effective vaccines developed to combat the COVID-19 pandemic, the most notable were novel mRNA vaccines. Despite their high efficacy against the original Wuhan-Hu-1 strain and early SARS-CoV-2 variants, mRNA vaccines elicit a relatively short duration of immunity, exacerbated by immune evasion by variants leading to lower efficacy; 1 for example, mRNA vaccine effectiveness against omicron declined to below 20% within 6 months of vaccination. 2 Additionally, new variants are continuing to emerge, 3 so the ongoing risk of COVID-19 outbreaks due to persistent viral circulation necessitates ongoing development of new vaccines to prolong vaccine-induced immunity, ideally for at least 1 year to meet new annual immunisation recommendations. 3 We recently reported that a booster dose of the novel mRNA vaccine, ARCT-154 (Arcturus Therapeutics Holdings, San Diego, CA, USA), a self …