Aspergillus fumigatus-a systematic review to inform the World Health Organization priority list of fungal pathogens.

Recognizing the growing global burden of fungal infections, the World Health Organization established a process to develop a priority list of fungal pathogens (FPPL). In this systematic review, we aimed to evaluate the epidemiology and impact of invasive infections caused by Aspergillus fumigatus to inform the first FPPL. The pre-specified criteria of mortality, inpatient care, complications and sequelae, antifungal susceptibility, risk factors, preventability, annual incidence, global distribution, and emergence were used to search for relevant articles between 1 January 2016 and 10 June 2021. Overall, 49 studies were eligible for inclusion. Azole antifungal susceptibility varied according to geographical regions. Voriconazole susceptibility rates of 22.2% were reported from the Netherlands, whereas in Brazil, Korea, India, China, and the UK, voriconazole susceptibility rates were 76%, 94.7%, 96.9%, 98.6%, and 99.7%, respectively. Cross-resistance was common with 85%, 92.8%, and 100% of voriconazole-resistant A. fumigatus isolates also resistant to itraconazole, posaconazole, and isavuconazole, respectively. The incidence of invasive aspergillosis (IA) in patients with acute leukemia was estimated at 5.84/100 patients. Six-week mortality rates in IA cases ranged from 31% to 36%. Azole resistance and hematological malignancy were poor prognostic factors. Twelve-week mortality rates were significantly higher in voriconazole-resistant than in voriconazole-susceptible IA cases (12/22 [54.5%] vs. 27/88 [30.7%]; P = .035), and hematology patients with IA had significantly higher mortality rates compared with solid-malignancy cases who had IA (65/217 [30%] vs. 14/78 [18%]; P = .04). Carefully designed surveillance studies linking laboratory and clinical data are required to better inform future FPPL.

Pichia kudriavzevii (Candida krusei): A systematic review to inform the World Health Organisation priority list of fungal pathogens.

In response to the growing global threat of fungal infections, in 2020 the World Health Organisation (WHO) established an Expert Group to identify priority fungi and develop the first WHO fungal priority pathogen list (FPPL). The aim of this systematic review was to evaluate the features and global impact of invasive infections caused by Pichia kudriavzevii (formerly known as Candida krusei). PubMed and Web of Science were used to identify studies published between 1 January 2011 and 18 February 2021 reporting on the criteria of mortality, morbidity (defined as hospitalisation and length of stay), drug resistance, preventability, yearly incidence, and distribution/emergence. Overall, 33 studies were evaluated. Mortality rates of up to 67% in adults were reported. Despite the intrinsic resistance of P. kudriavzevii to fluconazole with decreased susceptibility to amphotericin B, resistance (or non-wild-type rate) to other azoles and echinocandins was low, ranging between 0 and 5%. Risk factors for developing P. kudriavzevii infections included low birth weight, prior use of antibiotics/antifungals, and an underlying diagnosis of gastrointestinal disease or cancer. The incidence of infections caused by P. kudriavzevii is generally low (∼5% of all Candida-like blood isolates) and stable over the 10-year timeframe, although additional surveillance data are needed. Strategies targeting the identified risk factors for developing P. kudriavzevii infections should be developed and tested for effectiveness and feasibility of implementation. Studies presenting data on epidemiology and susceptibility of P. kudriavzevii were scarce, especially in low- and middle-income countries (LMICs). Thus, global surveillance systems are required to monitor the incidence, susceptibility, and morbidity of P. kudriavzevii invasive infections to inform diagnosis and treatment. Timely species-level identification and susceptibility testing should be conducted to reduce the high mortality and limit the spread of P. kudriavzevii in healthcare facilities.

Fusarium species,Scedosporium species, and Lomentospora prolificans: A systematic review to inform the World Health Organization priority list of fungal pathogens.

Recognizing the growing global burden of fungal infections, the World Health Organization established a process to develop a priority list of fungal pathogens (FPPL). In this systematic review, we aimed to evaluate the epidemiology and impact of infections caused by Fusarium spp., Scedosporium spp., and Lomentospora prolificans to inform the first FPPL. PubMed and Web of Sciences databases were searched to identify studies published between January 1, 2011 and February 23, 2021, reporting on mortality, complications and sequelae, antifungal susceptibility, preventability, annual incidence, and trends. Overall, 20, 11, and 9 articles were included for Fusarium spp., Scedosporium spp., and L. prolificans, respectively. Mortality rates were high in those with invasive fusariosis, scedosporiosis, and lomentosporiosis (42.9%-66.7%, 42.4%-46.9%, and 50.0%-71.4%, respectively). Antifungal susceptibility data, based on small isolate numbers, showed high minimum inhibitory concentrations (MIC)/minimum effective concentrations for most currently available antifungal agents. The median/mode MIC for itraconazole and isavuconazole were ≥16 mg/l for all three pathogens. Based on limited data, these fungi are emerging. Invasive fusariosis increased from 0.08 cases/100 000 admissions to 0.22 cases/100 000 admissions over the time periods of 2000-2009 and 2010-2015, respectively, and in lung transplant recipients, Scedosporium spp. and L. prolificans were only detected from 2014 onwards. Global surveillance to better delineate antifungal susceptibility, risk factors, sequelae, and outcomes is required.

Adapting response to a measles outbreak in a context of high vaccination and breakthrough cases: an example from Vaud, Switzerland, January to March 2024.

A measles outbreak with 51 cases occurred in the canton of Vaud, Switzerland, between January and March 2024. The outbreak was triggered by an imported case, and 37 (72.5%) subsequent cases were previously vaccinated individuals. Epidemiological investigations showed that vaccinated measles cases were symptomatic and infectious. In a highly vaccinated population, it is important to raise awareness among healthcare professionals to suspect and test for measles virus when an outbreak is declared, irrespective of the vaccination status of the patients.

Estimating the return on investment of selected infection prevention and control interventions in healthcare settings for preparing against novel respiratory viruses: modelling the experience from SARS-CoV-2 among health workers.

Background: Insufficient infection prevention and control (IPC) practices in healthcare settings increase the SARS-CoV-2 infection risk among health workers. This study aimed to examine the level of preparedness for future outbreaks. Methods: We modelled the experience from the COVID-19 pandemic and assessed the return on investment on a global scale of three IPC interventions to prevent SARS-CoV-2 infections among health workers: enhancing hand hygiene; increasing access to personal protective equipment (PPE); and combining PPE, with a scale-up of IPC training and education (PPE+). Our analysis covered seven geographic regions, representing a combination of World Health Organization (WHO) regions and the Organisation for Economic Co-operation and Development (OECD) countries. Across all regions, we focused on the first 180 days of the pandemic in 2020 between January 1st and June 30th. We used an extended version of a susceptible-infectious-recovered compartmental model to measure the level of IPC preparedness. Data were sourced from the WHO COVID-19 Detailed Surveillance Database. Findings: In all regions, the PPE + intervention would have averted the highest number of new SARS-CoV-2 infections compared to the other two interventions, ranging from 6562 (95% CI 4873-8779) to 38,170 (95% CI 33,853-41,901) new infections per 100,000 health workers in OECD countries and in the South-East Asia region, respectively. Countries in the South-East Asia region and non-OECD countries in the Western Pacific region were poised to achieve the highest level of savings by scaling up the PPE + intervention. Interpretation: Our results not only support efforts to make an economic case for continuing investments in IPC interventions to halt the COVID-19 pandemic and protect health workers, but could also contribute to efforts to improve preparedness for future outbreaks. Funding: This work was funded by WHO, with support by the German Federal Ministry of Health for the WHOResearch and Development Blueprint for COVID-19.

Risk factors for SARS-CoV-2 infection among health workers in India: a case control study.

Background: COVID-19 was declared as a Public Health Emergency of International Concern on 30th January 2020. Compared to the general population, healthcare workers and their families have been identified to be at a higher risk of getting infected with COVID-19. Therefore, it is crucial to understand the risk factors responsible for the transmission of SARS-CoV-2 infection among health workers in different hospital settings and to describe the range of clinical presentations of SARS-CoV-2 infection among them. Methodology: A nested case-control study was conducted among healthcare workers who were involved in the care of COVID-19 cases for assessing the risk factors associated with it. To get a holistic perspective, the study was conducted in 19 different hospitals from across 7 states (Kerala, Tamil Nadu, Andhra Pradesh, Karnataka, Maharashtra, Gujarat, and Rajasthan) of India covering the major government and private hospitals that were actively involved in COVID-19 patient care. The study participants who were not vaccinated were enrolled using the incidence density sampling technique from December 2020 to December 2021. Results: A total of 973 health workers consisting of 345 cases and 628 controls were recruited for the study. The mean age of the participants was observed to be 31.17 ± 8.5 years, with 56.3% of them being females. On multivariate analysis, the factors that were found to be significantly associated with SARS-CoV-2 were age of more than 31 years (adjusted odds ratio [aOR] 1.407 [95% CI 1.53-1.880]; p = 0.021), male gender (aOR 1.342 [95% CI 1.019-1.768]; p = 0.036), practical mode of IPC training on personal protective equipment (aOR 1. 1.935 [95% CI 1.148-3.260]; p = 0.013), direct exposure to COVID-19 patient (aOR 1.413 [95% CI 1.006-1.985]; p = 0.046), presence of diabetes mellitus (aOR 2.895 [95% CI 1.079-7.770]; p = 0.035) and those received prophylactic treatment for COVID-19 in the last 14 days (aOR 1.866 [95% CI 0.201-2.901]; p = 0.006). Conclusion: The study was able to highlight the need for having a separate hospital infection control department that implements IPC programs regularly. The study also emphasizes the need for developing policies that address the occupational hazards faced by health workers.

Global knowledge gaps on antimicrobial resistance in the human health sector: A scoping review.

OBJECTIVES: To identify and summarize existing global knowledge gaps on antimicrobial resistance (AMR) in human health, focusing on the World Health Organization (WHO) bacterial priority pathogens, Mycobacterium tuberculosis, and selected fungi. METHODS: We conducted a scoping review of gray and peer-reviewed literature, published in English from January 2012 through December 2021, that reported on the prevention, diagnosis, treatment, and care of drug-resistant infections. We extracted relevant knowledge gaps and, through an iterative process, consolidated those into thematic research questions. RESULTS: Of 8409 publications screened, 1156 were included, including 225 (19.5%) from low- and middle-income countries. A total of 2340 knowledge gaps were extracted, in the following areas: antimicrobial research and development, AMR burden and drivers, resistant tuberculosis, antimicrobial stewardship, diagnostics, infection prevention and control, antimicrobial consumption and use data, immunization, sexually transmitted infections, AMR awareness and education, policies and regulations, fungi, water sanitation and hygiene, and foodborne diseases. The knowledge gaps were consolidated into 177 research questions, including 78 (44.1%) specifically relevant to low- and middle-income countries and 65 (36.7%) targeting vulnerable populations. CONCLUSION: This scoping review presents the most comprehensive compilation of AMR-related knowledge gaps to date, informing a priority-setting exercise to develop the WHO Global AMR Research Agenda for the human health sector.

Associated deaths and disability-adjusted life-years caused by infections with antibiotic-resistant bacteria in Switzerland, 2010 to 2019.

BackgroundCassini et al. (2019) estimated that, in 2015, infections with 16 different antibiotic-resistant bacteria resulted in ca 170 disability-adjusted life-years (DALYs) per 100,000 population in the European Union and European Economic area (EU/EEA). The corresponding estimate for Switzerland was about half of this (87.8 DALYs per 100,000 population) but still higher than that of several EU/EEA countries (e.g. neighbouring Austria (77.2)).AimIn this study, the burden caused by the same infections due to antibiotic-resistant bacteria ('AMR burden') in Switzerland from 2010 to 2019 was estimated and the effect of the factors 'linguistic region' and 'hospital type' on this estimate was examined.MethodsNumber of infections, DALYs and deaths were estimated according to Cassini et al. (2019) whereas separate models were built for each linguistic region/hospital type combination.ResultsDALYs increased significantly from 3,995 (95% uncertainty interval (UI): 3;327-4,805) in 2010 to 6,805 (95% UI: 5,820-7,949) in 2019. Linguistic region and hospital type stratifications significantly affected the absolute values and the slope of the total AMR burden estimates. DALYs per population were higher in the Latin part of Switzerland (98 DALYs per 100,000 population; 95% UI: 83-115) compared with the German part (57 DALYs per 100,000 population; 95% UI: 49-66) and in university hospitals (165 DALYs per 100,000 hospitalisation days; 95% UI: 140-194) compared with non-university hospitals (62 DALYs per 100,000 hospitalisation days; 95% UI: 53-72).ConclusionsThe AMR burden estimate in Switzerland has increased significantly between 2010 and 2019. Considerable differences depending on the linguistic region and the hospital type were identified - a finding which affects the nationwide burden estimation.

Economic evaluations of interventions to prevent and control health-care-associated infections: a systematic review.

Almost 9 million health-care-associated infections have been estimated to occur each year in European hospitals and long-term care facilities, and these lead to an increase in morbidity, mortality, bed occupancy, and duration of hospital stay. The aim of this systematic review was to review the cost-effectiveness of interventions to limit the spread of health-care-associated infections), framed by WHO infection prevention and control core components. The Embase, National Health Service Economic Evaluation Database, Database of Abstracts of Reviews of Effects, Health Technology Assessment, Cinahl, Scopus, Pediatric Economic Database Evaluation, and Global Index Medicus databases, plus grey literature were searched for studies between Jan 1, 2009, and Aug 10, 2022. Studies were included if they reported interventions including hand hygiene, personal protective equipment, national-level or facility-level infection prevention and control programmes, education and training programmes, environmental cleaning, and surveillance. The British Medical Journal checklist was used to assess the quality of economic evaluations. 67 studies were included in the review. 25 studies evaluated methicillin-resistant Staphylococcus aureus outcomes. 31 studies evaluated screening strategies. The assessed studies that met the minimum quality criteria consisted of economic models. There was some evidence that hand hygiene, environmental cleaning, surveillance, and multimodal interventions were cost-effective. There were few or no studies investigating education and training, personal protective equipment or monitoring, and evaluation of interventions. This Review provides a map of cost-effectiveness data, so that policy makers and researchers can identify the relevant data and then assess the quality and generalisability for their setting.

Antimicrobial resistance in patients with COVID-19: a systematic review and meta-analysis.

BACKGROUND: Frequent use of antibiotics in patients with COVID-19 threatens to exacerbate antimicrobial resistance. We aimed to establish the prevalence and predictors of bacterial infections and antimicrobial resistance in patients with COVID-19. METHODS: We did a systematic review and meta-analysis of studies of bacterial co-infections (identified within ≤48 h of presentation) and secondary infections (>48 h after presentation) in outpatients or hospitalised patients with COVID-19. We searched the WHO COVID-19 Research Database to identify cohort studies, case series, case-control trials, and randomised controlled trials with populations of at least 50 patients published in any language between Jan 1, 2019, and Dec 1, 2021. Reviews, editorials, letters, pre-prints, and conference proceedings were excluded, as were studies in which bacterial infection was not microbiologically confirmed (or confirmed via nasopharyngeal swab only). We screened titles and abstracts of papers identified by our search, and then assessed the full text of potentially relevant articles. We reported the pooled prevalence of bacterial infections and antimicrobial resistance by doing a random-effects meta-analysis and meta-regression. Our primary outcomes were the prevalence of bacterial co-infection and secondary infection, and the prevalence of antibiotic-resistant pathogens among patients with laboratory-confirmed COVID-19 and bacterial infections. The study protocol was registered with PROSPERO (CRD42021297344). FINDINGS: We included 148 studies of 362 976 patients, which were done between December, 2019, and May, 2021. The prevalence of bacterial co-infection was 5·3% (95% CI 3·8-7·4), whereas the prevalence of secondary bacterial infection was 18·4% (14·0-23·7). 42 (28%) studies included comprehensive data for the prevalence of antimicrobial resistance among bacterial infections. Among people with bacterial infections, the proportion of infections that were resistant to antimicrobials was 60·8% (95% CI 38·6-79·3), and the proportion of isolates that were resistant was 37·5% (26·9-49·5). Heterogeneity in the reported prevalence of antimicrobial resistance in organisms was substantial (I2=95%). INTERPRETATION: Although infrequently assessed, antimicrobial resistance is highly prevalent in patients with COVID-19 and bacterial infections. Future research and surveillance assessing the effect of COVID-19 on antimicrobial resistance at the patient and population level are urgently needed. FUNDING: WHO.

Infection prevention and control risk factors in health workers infected with SARS-CoV-2 in Jordan: A case control study.

BACKGROUND: Despite under-reporting, health workers (HWs) accounted for 2 to 30% of the reported COVID-19 cases worldwide. In line with data from other countries, Jordan recorded multiple case surges among HWs. METHODS: Based on the standardized WHO UNITY case-control study protocol on assessing risk factors for SARS-CoV-2 infection in HWs, HWs with confirmed COVID-19 were recruited as cases from eight hospitals in Jordan. HWs exposed to COVID-19 patients in the same setting but without infection were recruited as controls. The study lasted approximately two months (from early January to early March 2021). Regression models were used to analyse exposure risk factors for SARS-CoV-2 infection in HWs; conditional logistic regressions were utilized to estimate odds ratios (ORs) adjusted for the confounding variables. RESULTS: A total of 358 (102 cases and 256 controls) participants were included in the analysis. The multivariate analysis showed that being exposed to COVID-19 patients within 1 metre for more than 15 minutes increased three-fold the odds of infection (OR 2.92, 95% CI 1.25-6.86). Following IPC standard precautions when in contact with patients was a significant protective factor. The multivariate analysis showed that suboptimal adherence to hand hygiene increased the odds of infection by three times (OR 3.18; 95% CI 1.25-8.08). CONCLUSION: Study findings confirmed the role of hand hygiene as one of the most cost-effective measures to combat the spreading of viral infections. Future studies based on the same protocol will enable additional interpretations and confirmation of the Jordan experience.

Developing a priority global research agenda for antimicrobial resistance in the human health sector: protocol for a scoping review.

INTRODUCTION: To accelerate the response to the public health threat by antimicrobial resistance (AMR), the WHO is developing a Global Research Agenda for AMR in the human health sector that aims to provide a global and transparent assessment of priority knowledge gaps related to critical bacteria-including Mycobacterium tuberculosis-and fungi that inform control and response strategies to tackle AMR by 2030. A literature scoping review represents the first phase in a stepwise process, and we hereby outline the protocol to review current knowledge gaps and research questions on AMR in the human health sector. METHODS AND ANALYSIS: This literature scoping review will follow the Arksey and O'Malley (2005) methodology and will include: (1) a hand search to identify relevant WHO guidelines and documents suggested by the WHO Steering Group for the AMR Global Research Agenda; (2) a grey literature search through a stakeholder mapping process and google searches of organisational websites; (3) a systematic search of relevant systematic reviews through bibliographic databases (PubMed, Embase and Web of Science); (4) screening of the reference lists of included studies. We will include relevant publications from the last 10 years (January 2012 to December 2021). Two researchers separately will review the yielded citations to determine eligibility based on predefined criteria. Relevant research questions with attributes will be extracted using a tool developed through an iterative process by the research team. Each identified research question will be classified and aggregated according to a conceptual framework (ie, 'knowledge matrix'), composed of three themes (ie, Prevention, Diagnosis and Care & Treatment) and four cross-cutting domains (ie, Descriptive, Discovery, Development, Delivery). We will present numerical and thematic summaries of the knowledge matrix. A qualitative content analysis is out of the scope of this protocol. ETHICS AND DISSEMINATION: The scoping review process will only involve identification, selection and analysis of documents available for use in the public domain, and will not include any personal information on individuals, therefore ethical approval is not required. The findings will be disseminated through a peer-reviewed publication and stakeholder meetings.

The first WHO global survey on infection prevention and control in health-care facilities.

BACKGROUND: WHO core components for infection prevention and control (IPC) are important building blocks for effective IPC programmes. To our knowledge, we did the first WHO global survey to assess implementation of these programmes in health-care facilities. METHODS: In this cross-sectional survey, IPC professionals were invited through global outreach and national coordinated efforts to complete the online WHO IPC assessment framework (IPCAF). The survey was created in English and was then translated into ten languages: Arabic, Chinese, English, French, German, Italian, Japanese, Russian, Spanish, and Thai. Post-stratification weighting was applied and countries with low response rates were excluded to improve representativeness. Weighted median scores and IQRs as well as weighted proportions (Nw) meeting defined IPCAF minimum requirements were reported. Indicators associated with the IPCAF score were assessed using a generalised estimating equation. FINDINGS: From Jan 16 to Dec 31, 2019, 4440 responses were received from 81 countries. The overall weighted IPCAF median score indicated an advanced level of implementation (605, IQR 450·4-705·0), but significantly lower scores were found in low-income (385, 279·7-442·9) and lower-middle-income countries (500·4, 345·0-657·5), and public facilities (515, 385-637·8). Core component 8 (built environment; 90·0, IQR 75·0-100·0) and core component 2 (guidelines; 87·5, 70·0-97·5) scored the highest, and core component 7 (workload, staffing, and bed occupancy; 70·0, 50-90) and core component 3 (education and training; 70 ·0, 50·0-85·0) scored the lowest. Overall, only 15·2% (Nw: 588 of 3873) of facilities met all IPCAF minimum requirements, ranging from 0% (0 of 417) in low-income countries to 25·6% (278 of 1087) in primary facilities, 9% (24 of 268) in secondary facilities, and 19% (18 of 95) in tertiary facilities in high-income countries. INTERPRETATION: Despite an overall high IPCAF score globally, important gaps in IPC facility implementation and core components across income levels hinder IPC progress. Increased support for more effective and sustainable IPC programmes is crucial to reduce risks posed by outbreaks to global health security and to ensure patient and health worker safety. FUNDING: WHO and the Infection Control Programme, University of Geneva Hospitals and Faculty of Medicine. TRANSLATIONS: For the French and Spanish translations of the abstract see Supplementary Materials section.

Implementation of hand hygiene in health-care facilities: results from the WHO Hand Hygiene Self-Assessment Framework global survey 2019.

BACKGROUND: Hand hygiene is at the core of effective infection prevention and control (IPC) programmes. 10 years after the development of the WHO Multimodal Hand Hygiene Improvement Strategy, we aimed to ascertain the level of hand hygiene implementation and its drivers in health-care facilities through a global WHO survey. METHODS: From Jan 16 to Dec 31, 2019, IPC professionals were invited through email and campaigns to complete the online Hand Hygiene Self-Assessment Framework (HHSAF). A geospatial clustering algorithm selected unique health-care facilities responses and post-stratification weighting was applied to improve representativeness. Weighted median HHSAF scores and IQR were reported. Drivers of the HHSAF score were determined through a generalised estimation equation. FINDINGS: 3206 unique responses from 90 countries (46% WHO Member States) were included. The HHSAF score indicated an intermediate hand hygiene implementation level (350 points, IQR 248-430), which was positively associated with country income level and health-care facility funding structure. System Change had the highest score (85 points, IQR 55-100), whereby alcohol-based hand rub at the point of care has become standard practice in many health-care facilities, especially in high-income countries. Institutional Safety Climate had the lowest score (55 points, IQR 35-75). From 2015 to 2019, the median HHSAF score in health-care facilities participating in both HHSAF surveys (n=190) stagnated. INTERPRETATION: Most health-care facilities had an intermediate level of hand hygiene implementation or higher, for which health-care facility funding and country income level were important drivers. Availability of resources, leadership, and organisational support are key elements to further improve quality of care and provide access to safe care for all. FUNDING: WHO, Geneva University Hospitals and Faculty of Medicine, and WHO Collaborating Center on Patient Safety, Geneva, Switzerland.

Early epidemiological investigations: World Health Organization UNITY protocols provide a standardized and timely international investigation framework during the COVID-19 pandemic.

BACKGROUND: The declaration of Coronavirus disease 2019 (COVID-19) as a Public Health Emergency of International Concern (PHEIC) on 30 January 2020 required rapid implementation of early investigations to inform appropriate national and global public health actions. METHODS: The suite of existing pandemic preparedness generic epidemiological early investigation protocols was rapidly adapted for COVID-19, branded the 'UNITY studies' and promoted globally for the implementation of standardized and quality studies. Ten protocols were developed investigating household (HH) transmission, the first few cases (FFX), population seroprevalence (SEROPREV), health facilities transmission (n = 2), vaccine effectiveness (n = 2), pregnancy outcomes and transmission, school transmission, and surface contamination. Implementation was supported by WHO and its partners globally, with emphasis to support building surveillance and research capacities in low- and middle-income countries (LMIC). RESULTS: WHO generic protocols were rapidly developed and published on the WHO website, 5/10 protocols within the first 3 months of the response. As of 30 June 2021, 172 investigations were implemented by 97 countries, of which 62 (64%) were LMIC. The majority of countries implemented population seroprevalence (71 countries) and first few cases/household transmission (37 countries) studies. CONCLUSION: The widespread adoption of UNITY protocols across all WHO regions indicates that they addressed subnational and national needs to support local public health decision-making to prevent and control the pandemic.

Global incidence and mortality of neonatal sepsis: a systematic review and meta-analysis.

BACKGROUND: Neonates are at major risk of sepsis, but data on neonatal sepsis incidence are scarce. We aimed to assess the incidence and mortality of neonatal sepsis worldwide. METHODS: We performed a systematic review and meta-analysis. 13 databases were searched for the period January 1979-May 2019, updating the search of a previous systematic review and extending it in order to increase data inputs from low-income and middle-income countries (LMICs). We included studies on the population-level neonatal sepsis incidence that used a clinical sepsis definition, such as the 2005 consensus definition, or relevant ICD codes. We performed a random-effects meta-analysis on neonatal sepsis incidence and mortality, stratified according to sepsis onset, birth weight, prematurity, study setting, WHO region and World Bank income level. RESULTS: The search yielded 4737 publications, of which 26 were included. They accounted for 2 797 879 live births and 29 608 sepsis cases in 14 countries, most of which were middle-income countries. Random-effects estimator for neonatal sepsis incidence in the overall time frame was 2824 (95% CI 1892 to 4194) cases per 100 000 live births, of which an estimated 17.6% 9 (95% CI 10.3% to 28.6%) died. In the last decade (2009-2018), the incidence was 3930 (95% CI 1937 to 7812) per 100 000 live births based on four studies from LMICs. In the overall time frame, estimated incidence and mortality was higher in early-onset than late-onset neonatal sepsis cases. There was substantial between-study heterogeneity in all analyses. Studies were at moderate to high risk of bias. CONCLUSION: Neonatal sepsis is common and often fatal. Its incidence remains unknown in most countries and existing studies show marked heterogeneity, indicating the need to increase the number of epidemiological studies, harmonise neonatal sepsis definitions and improve the quality of research in this field. This can help to design and implement targeted interventions, which are urgently needed to reduce the high incidence of neonatal sepsis worldwide.

Epidemiology and burden of sepsis acquired in hospitals and intensive care units: a systematic review and meta-analysis.

PURPOSE: Sepsis is recognized as a global public health problem, but the proportion due to hospital-acquired infections remains unclear. We aimed to summarize the epidemiological evidence related to the burden of hospital-acquired (HA) and ICU-acquired (ICU-A) sepsis. METHODS: We searched MEDLINE, Embase and the Global Index Medicus from 01/2000 to 03/2018. We included studies conducted hospital-wide or in intensive care units (ICUs), including neonatal units (NICUs), with data on the incidence/prevalence of HA and ICU-A sepsis and the proportion of community and hospital/ICU origin. We did random-effects meta-analyses to obtain pooled estimates; inter-study heterogeneity and risk of bias were assessed. RESULTS: Of the 13,239 studies identified, 51 met the inclusion criteria; 22 were from low- and middle-income countries. Twenty-eight studies were conducted in ICUs, 13 in NICUs, and ten hospital-wide. The proportion of HA sepsis among all hospital-treated sepsis cases was 23.6% (95% CI 17-31.8%, range 16-36.4%). In the ICU, 24.4% (95% CI 16.7-34.2%, range 10.3-42.5%) of cases of sepsis with organ dysfunction were acquired during ICU stay and 48.7% (95% CI 38.3-59.3%, range 18.7-69.4%) had a hospital origin. The pooled hospital incidence of HA sepsis with organ dysfunction per 1000 patients was 9.3 (95% CI 7.3-11.9, range 2-20.6)). In the ICU, the pooled incidence of HA sepsis with organ dysfunction per 1000 patients was 56.5 (95% CI 35-90.2, range 9.2-254.4) and it was particularly high in NICUs. Mortality of ICU patients with HA sepsis with organ dysfunction was 52.3% (95% CI 43.4-61.1%, range 30.1-64.6%). There was a significant inter-study heterogeneity. Risk of bias was low to moderate in ICU-based studies and moderate to high in hospital-wide and NICU studies. CONCLUSION: HA sepsis is of major public health importance, and the burden is particularly high in ICUs. There is an urgent need to improve the implementation of global and local infection prevention and management strategies to reduce its high burden among hospitalized patients.