Follow-up SARS-CoV-2 serological study of a health care worker cohort following COVID-19 booster vaccination.

BACKGROUND: Studies have shown that Omicron breakthrough infections can occur at higher SARS-CoV-2 antibody levels compared to previous variants. Estimating the magnitude of immunological protection induced from COVID-19 vaccination and previous infection remains important due to varying local pandemic dynamics and types of vaccination programmes, particularly among at-risk populations such as health care workers (HCWs). We analysed a follow-up SARS-CoV-2 serological survey of HCWs at a tertiary COVID-19 referral hospital in Germany following the onset of the Omicron variant. METHODS: The serological survey was conducted in January 2022, one year after previous surveys in 2020 and the availability of COVID-19 boosters including BNT162b2, ChAdOx1-S, and mRNA-1273. HCWs voluntarily provided blood for serology and completed a comprehensive questionnaire. SARS-CoV-2 serological analyses were performed using an Immunoglobulin G (IgG) enzyme-linked immunosorbent assay (ELISA). Antibody levels were reported according to HCW demographic and occupational characteristics, COVID-19 vaccination and SARS-CoV-2 infection history, and multivariate linear regression was used to evaluate these associations. RESULTS: In January 2022 (following the fourth COVID-19 wave in Germany including the onset of the Omicron variant), 1482/1517 (97.7%) HCWs tested SARS-CoV-2 seropositive, compared to 4.6% in December 2020 (second COVID-19 wave). Approximately 80% had received three COVID-19 vaccine doses and 15% reported a previous laboratory-confirmed SARS-CoV-2 infection. SARS-CoV-2 IgG geometric mean titres ranged from 335 (95% Confidence Intervals [CI]: 258-434) among those vaccinated twice and without previous infection to 2204 (95% CI: 1919-2531) among those vaccinated three times and with previous infection. Heterologous COVID-19 vaccination combinations including a mRNA-1273 booster were significantly associated with the highest IgG antibody levels compared to other schemes. There was an 8-to 10-fold increase in IgG antibody levels among 31 HCWs who reported a SARS-CoV-2 infection in May 2020 to January 2022 after COVID-19 booster vaccination. CONCLUSIONS: Our findings demonstrate the importance of ongoing COVID-19 booster vaccination strategies in the context of variants such as Omicron and despite hybrid immunity from previous SARS-CoV-2 infections, particularly for at-risk populations such as HCWs. Where feasible, effective types of booster vaccination, such as mRNA vaccines, and the appropriate timing of administration should be carefully considered.

Reported antibiotic use among patients in the multicenter ANDEMIA infectious diseases surveillance study in sub-saharan Africa.

BACKGROUND: Exposure to antibiotics has been shown to be one of the drivers of antimicrobial resistance (AMR) and is critical to address when planning and implementing strategies for combatting AMR. However, data on antibiotic use in sub-Saharan Africa are still limited. Using hospital-based surveillance data from the African Network for Improved Diagnostics, Epidemiology and Management of Common Infectious Agents (ANDEMIA), we assessed self-reported antibiotic use in multiple sub-Saharan African countries. METHODS: ANDEMIA included 12 urban and rural health facilities in Côte d'Ivoire, Burkina Faso, Democratic Republic of the Congo, and Republic of South Africa. Patients with acute respiratory infection (RTI), acute gastrointestinal infection (GI) and acute febrile disease of unknown cause (AFDUC) were routinely enrolled, and clinical, demographic, socio-economic and behavioral data were collected using standardized questionnaires. An analysis of ANDEMIA data from February 2018 to May 2022 was conducted. Reported antibiotic use in the ten days prior to study enrolment were described by substance and by the WHO AWaRe classification ("Access", "Watch", "Reserve", and "Not recommended" antibiotics). Frequency of antibiotic use was stratified by location, disease syndrome and individual patient factors. RESULTS: Among 19,700 ANDEMIA patients, 7,258 (36.8%) reported antibiotic use. A total of 9,695 antibiotics were reported, including 54.7% (n = 5,299) from the WHO Access antibiotic group and 44.7% (n = 4,330) from the WHO Watch antibiotic group. The Watch antibiotic ceftriaxone was the most commonly reported antibiotic (n = 3,071, 31.7%). Watch antibiotic use ranged from 17.4% (56/322) among RTI patients in Côte d'Ivoire urban facilities to 73.7% (630/855) among AFDUC patients in Burkina Faso urban facilities. Reported antibiotic use included WHO Not recommended antibiotics but no Reserve antibiotics. CONCLUSIONS: Reported antibiotic use data from this multicenter study in sub-Saharan Africa revealed a high proportion of WHO Watch antibiotics. Differences in Watch antibiotic use were found by disease syndrome, country and health facility location, which calls for a more differentiated approach to antibiotic use interventions including further evaluation of accessibility and affordability of patient treatment.

Seroprevalence of anti-SARS-CoV-2 antibodies and risk of viral exposure among healthcare workers in the South Kivu province, eastern Democratic Republic of the Congo: a cross-sectional study.

OBJECTIVES: Healthcare workers (HCWs) are on the frontline of combating COVID-19, hence are at elevated risk of contracting an infection with SARS-CoV-2. The present study aims to measure the impact of SARS-CoV-2 on HCWs in central sub-Saharan Africa. SETTING: A cross-sectional serological study was conducted at six urban and five rural hospitals during the first pandemic wave in the South Kivu province, Democratic Republic of the Congo (DRC). PARTICIPANTS: Serum specimens from 1029 HCWs employed during the first pandemic wave were collected between August and October 2020, and data on demographics and work-related factors were recorded during structured interviews. PRIMARY AND SECONDARY OUTCOME MEASURES: The presence of IgG antibodies against SARS-CoV-2 was examined by ELISA. Positive specimens were further tested using a micro-neutralisation assay. Factors driving SARS-CoV-2 seropositivity were assessed by multivariable analysis. RESULTS: Overall SARS-CoV-2 seroprevalence was high among HCWs (33.1%), and significantly higher in urban (41.5%) compared with rural (19.8%) hospitals. Having had presented with COVID-19-like symptoms before was a strong predictor of seropositivity (31.5%). Personal protective equipment (PPE, 88.1% and 11.9%) and alcohol-based hand sanitizer (71.1% and 28.9%) were more often available, and hand hygiene was more often reported after patient contact (63.0% and 37.0%) in urban compared with rural hospitals, respectively. This may suggest that higher exposure during non-work times in high incidence urban areas counteracts higher work protection levels of HCWs. CONCLUSIONS: High SARS-CoV-2 seropositivity indicates widespread transmission of the virus in this region of DRC. Given the absence of publicly reported cases during the same time period at the rural sites, serological studies are very relevant in revealing infection dynamics especially in regions with low diagnostic capacities. This, and discrepancies in the application of PPE between urban and rural sites, should be considered in future pandemic response programmes.

Antimicrobial resistance in Germany and Europe - A systematic review on the increasing threat accelerated by climate change.

Background: Antimicrobial Resistance (AMR) is one of the top ten global public health threats facing humanity, alongside climate change. Here, we aim to summarise the effects of climate change (i.e. raise of temperature, change in humidity or precipitation) on spread of antibiotic resistance and on infections with antibiotic-resistant bacteria in Germany. Methods: We conducted a literature search with articles published between January 2012 and July 2022. Two authors screened titles, abstracts and full texts and extracted the data systematically. Results: From originally 2,389 titles, we identified six studies, which met our inclusion criteria. These studies show that an increase in temperature may lead to higher antibiotic resistance rates and an increased risk of colonisation as well as spread of pathogens. Furthermore, the number of healthcare-associated infections increases with increased temperature. Data indicate that higher antibiotic use is present in areas with warmer mean temperature. Conclusions: European data are scarce, but all studies identified point towards an increasing AMR burden due to climate change. However, further studies are needed to draw attention to the links between climatic factors and AMR and develop targeted preventive measures.

Multicountry study of SARS-CoV-2 and associated risk factors among healthcare workers in Côte d'Ivoire, Burkina Faso and South Africa.

BACKGROUND: Reports on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spread across Africa have varied, including among healthcare workers (HCWs). This study assessed the comparative SARS-CoV-2 burden and associated risk factors among HCWs in three African countries. METHODS: A multicentre study was conducted at regional healthcare facilities in Côte d'Ivoire (CIV), Burkina Faso (BF) and South Africa (SA) from February to May 2021. HCWs provided blood samples for SARS-CoV-2 serology and nasopharyngeal/oropharyngeal swabs for testing of acute infection by polymerase chain reaction and completed a questionnaire. Factors associated with seropositivity were assessed with logistic regression. RESULTS: Among 719 HCWs, SARS-CoV-2 seroprevalence was 34.6% (95% confidence interval 31.2 to 38.2), ranging from 19.2% in CIV to 45.7% in BF. A total of 20 of 523 (3.8%) were positive for acute SARS-CoV-2 infection. Female HCWs had higher odds of SARS-CoV-2 seropositivity compared with males, and nursing staff, allied health professionals, non-caregiver personnel and administration had higher odds compared with physicians. HCWs also reported infection prevention and control (IPC) gaps, including 38.7% and 29% having access to respirators and IPC training, respectively, in the last year. CONCLUSIONS: This study was a unique comparative HCW SARS-CoV-2 investigation in Africa. Seroprevalence estimates varied, highlighting distinctive population/facility-level factors affecting COVID-19 burden and the importance of established IPC programmes to protect HCWs and patients.

Baseline study for improving diagnostic stewardship at secondary health care facilities in Nigeria.

BACKGROUND: Blood culture diagnostics are critical tools for sepsis management and antimicrobial resistance (AMR) surveillance. A baseline study was conducted to assess reported sepsis case finding, blood culture diagnostics, antimicrobial susceptibility testing (AST) and antimicrobial use at secondary health care facilities to inform the development of diagnostic stewardship improvement strategies in Nigeria. METHODS: A cross-sectional online survey was conducted among 25 public secondary health care facilities in Abuja, Federal Capital Territory (FCT) and Lagos State in Nigeria to evaluate the capacity for pathogen identification and AST. Data were then prospectively extracted on all patients with reported suspected sepsis from electronic medical records from selected departments at two facilities in the Federal Capital Territory from October 2020 to May 2021 to further assess practices concerning sepsis case-finding, clinical examination findings, samples requested, and laboratory test results. Data were descriptively analysed, and a multivariate logistic regression analysis was conducted to determine factors associated with blood culture requests. RESULTS: In the online survey, 32% (8/25) of facilities reported performing blood cultures. Only one had access to a clinical microbiologist, and 28% (7/25) and 4% (1/25) used standard bacterial organisms for quality control of media and quality control strains for AST, respectively. At the two facilities where data abstraction was performed, the incidence of suspected sepsis cases reported was 7.1% (2924/41066). A majority of these patients came from the paediatrics department and were outpatients, and the median age was two years. Most did not have vital signs and major foci of infection documented. Blood cultures were only requested for 2.7% (80/2924) of patients, of which twelve were positive for bacteria, mainly Staphylococcus aureus. No clinical breakpoints were used for AST. Inpatients (adjusted odds ratio [aOR]: 7.5, 95% CI: 4.6-12.3) and patients from the urban health care facility (aOR:16.9, 95% CI: 8.1-41.4) were significantly more likely to have a blood culture requested. CONCLUSION: Low blood culture utilisation remains a key challenge in Nigeria. This has implications for patient care, AMR surveillance and antibiotic use. Diagnostic stewardship strategies should focus on improving access to clinical microbiology expertise, practical guidance on sepsis case finding and improving blood culture utilisation and diagnostics.

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.

Longitudinal SARS-CoV-2 seroepidemiological investigation among healthcare workers at a tertiary care hospital in Germany.

BACKGROUND: SARS-CoV-2 cases in Germany increased in early March 2020. By April 2020, cases among health care workers (HCW) were detected across departments at a tertiary care hospital in Berlin, prompting a longitudinal investigation to assess HCW SARS-CoV-2 serostatus with an improved testing strategy and associated risk factors. METHODS: In May/June and December 2020, HCWs voluntarily provided blood for serology and nasopharyngeal/oropharyngeal (NP/OP) samples for real-time polymerase chain reaction (PCR) and completed a questionnaire. A four-tiered SARS-CoV-2 serological testing strategy including two different enzyme-linked immunosorbent assays (ELISA) and biological neutralization test (NT) was used. ELISA-NT correlation was assessed using Pearson's correlation coefficient. Sociodemographic and occupational factors associated with seropositivity were assessed with multivariate logistic regression. RESULTS: In May/June, 18/1477 (1.2%) HCWs were SARS-CoV-2 seropositive, followed by 56/1223 (4.6%) in December. Among those tested in both, all seropositive in May/June remained seropositive by ELISA and positive by NT after 6 months. ELISA ratios correlated well with NT titres in May/June (R = 0.79) but less so in December (R = 0.41). Those seropositive reporting a past SARS-CoV-2 positive PCR result increased from 44.4% in May/June to 85.7% in December. HCWs with higher occupational risk (based on profession and working site), nurses, males, and those self-reporting COVID-19-like symptoms had significantly higher odds of seropositivity. CONCLUSIONS: This investigation provides insight into the burden of HCW infection in this local outbreak context and the antibody dynamics over time with an improved robust testing strategy. It also highlights the continued need for effective infection control measures particularly among HCWs with higher occupational risk.

Impact of the COVID-19 pandemic on the surveillance, prevention and control of antimicrobial resistance: a global survey.

OBJECTIVES: The COVID-19 pandemic has had a substantial impact on health systems. The WHO Antimicrobial Resistance (AMR) Surveillance and Quality Assessment Collaborating Centres Network conducted a survey to assess the effects of COVID-19 on AMR surveillance, prevention and control. METHODS: From October to December 2020, WHO Global Antimicrobial Resistance and Use Surveillance System (GLASS) national focal points completed a questionnaire, including Likert scales and open-ended questions. Data were descriptively analysed, income/regional differences were assessed and free-text questions were thematically analysed. RESULTS: Seventy-three countries across income levels participated. During the COVID-19 pandemic, 67% reported limited ability to work with AMR partnerships; decreases in funding were frequently reported by low- and middle-income countries (LMICs; P < 0.01). Reduced availability of nursing, medical and public health staff for AMR was reported by 71%, 69% and 64%, respectively, whereas 67% reported stable cleaning staff availability. The majority (58%) reported reduced reagents/consumables, particularly LMICs (P < 0.01). Decreased numbers of cultures, elective procedures, chronically ill admissions and outpatients and increased ICU admissions reported could bias AMR data. Reported overall infection prevention and control (IPC) improvement could decrease AMR rates, whereas increases in selected inappropriate IPC practices and antimicrobial prescribing could increase rates. Most did not yet have complete data on changing AMR rates due to COVID-19. CONCLUSIONS: This was the first survey to explore the global impact of COVID-19 on AMR among GLASS countries. Responses highlight important actions to help ensure that AMR remains a global health priority, including engaging with GLASS to facilitate reliable AMR surveillance data, seizing the opportunity to develop more sustainable IPC programmes, promoting integrated antibiotic stewardship guidance, leveraging increased laboratory capabilities and other system-strengthening efforts.

Infection prevention and control (IPC) implementation in low-resource settings: a qualitative analysis.

BACKGROUND: The coronavirus disease-2019 (COVID-19) pandemic has again demonstrated the critical role of effective infection prevention and control (IPC) implementation to combat infectious disease threats. Standards such as the World Health Organization (WHO) IPC minimum requirements offer a basis, but robust evidence on effective IPC implementation strategies in low-resource settings remains limited. We aimed to qualitatively assess IPC implementation themes in these settings. METHODS: Semi-structured interviews were conducted with IPC experts from low-resource settings, guided by a standardised questionnaire. Applying a qualitative inductive thematic analysis, IPC implementation examples from interview transcripts were coded, collated into sub-themes, grouped again into broad themes, and finally reviewed to ensure validity. Sub-themes appearing ≥ 3 times in data were highlighted as frequent IPC implementation themes and all findings were summarised descriptively. RESULTS: Interviews were conducted with IPC experts from 29 countries in six WHO regions. Frequent IPC implementation themes including the related critical actions to achieve the WHO IPC core components included: (1) To develop IPC programmes: continuous advocacy with leadership, initial external technical assistance, stepwise approach to build resources, use of catalysts, linkages with other programmes, role of national IPC associations and normative legal actions; (2) To develop guidelines: early planning for their operationalization, initial external technical assistance and local guideline adaption; (3) To establish training: attention to methods, fostering local leadership, and sustainable health system linkages such as developing an IPC career path; (4) To establish health care-associated (HAI) surveillance: feasible but high-impact pilots, multidisciplinary collaboration, mentorship, careful consideration of definitions and data quality, and "data for action"; (5) To implement multimodal strategies: clear communication to explain multimodal strategies, attention to certain elements, and feasible but high-impact pilots; (6) To develop monitoring, audit and feedback: feasible but high-impact pilots, attention to methods such as positive (not punitive) incentives and "data for action"; (7) To improve staffing and bed occupancy: participation of national actors to set standards and attention to methods such as use of data; and (8) To promote built environment: involvement of IPC professionals in facility construction, attention to multimodal strategy elements, and long-term advocacy. CONCLUSIONS: These IPC implementation themes offer important qualitative evidence for IPC professionals to consider.

Implementation of Automated Blood Culture With Quality Assurance in a Resource-Limited Setting.

Background: Blood cultures (BC) have a high clinical relevance and are a priority specimen for surveillance of antimicrobial resistance. Manual BC are still most frequently used in resource-limited settings. Data on automated BC performance in Africa are scarce. We implemented automated BC at a surveillance site of the African Network for improved Diagnostics, Epidemiology and Management of Common Infectious Agents (ANDEMIA). Methods: Between June 2017 and January 2018, pairs of automated BC (BacT/ALERT®FA Plus) and manual BC (brain-heart infusion broth) were compared at a University hospital in Bouaké, Côte d'Ivoire. BC were inoculated each with a target blood volume of 10 ml from the same venipuncture. Automated BC were incubated for up to 5 days, manual BC for up to 10 days. Terminal subcultures were performed for manual BC only. The two systems were compared regarding yield, contamination, and turnaround time. For quality assurance, isolates were retested in a German routine microbiological laboratory. Results: BC sampling was increased from on average 24 BC to 63 BC per month. A total of 337 matched pairs of BC were included. Automated BC was positive in 36.5%, manual BC in 24.0% (p-value < 0.01), proportion of contamination was 47.9 and 43.8%, respectively (p-value = 1.0). Turnaround time of positive BC was shortened by 2.5 days with automated compared to manual BC (p < 0.01). Most common detected pathogens in both systems were Klebsiella spp. (26.0%) and Staphylococcus aureus (18.2%). Most contaminants were members of the skin flora. Retesting of 162 isolates was concordant in 79.6% on family level. Conclusions: Implementing automated BC in a resource-limited setting is possible and improves microbiological diagnostic performance. Automated BC increased yield and shortened turnaround times. Regular training and mentorship of clinicians has to be intensified to increase number and quality of BC. Pre-analytical training to improve diagnostic stewardship is essential when implementing a new microbiological method. Retesting highlighted that manual identification and antimicrobial susceptibility testing can be of good quality and sustainable. The implementation of automated tools should be decided individually according to economic considerations, number of samples, stable supply chain of consumables, and technical sustainability.

The African Network for Improved Diagnostics, Epidemiology and Management of common infectious Agents.

BACKGROUND: In sub-Saharan Africa, acute respiratory infections (ARI), acute gastrointestinal infections (GI) and acute febrile disease of unknown cause (AFDUC) have a large disease burden, especially among children, while respective aetiologies often remain unresolved. The need for robust infectious disease surveillance to detect emerging pathogens along with common human pathogens has been highlighted by the ongoing novel coronavirus disease 2019 (COVID-19) pandemic. The African Network for Improved Diagnostics, Epidemiology and Management of Common Infectious Agents (ANDEMIA) is a sentinel surveillance study on the aetiology and clinical characteristics of ARI, GI and AFDUC in sub-Saharan Africa. METHODS: ANDEMIA includes 12 urban and rural health care facilities in four African countries (Côte d'Ivoire, Burkina Faso, Democratic Republic of the Congo and Republic of South Africa). It was piloted in 2018 in Côte d'Ivoire and the initial phase will run from 2019 to 2021. Case definitions for ARI, GI and AFDUC were established, as well as syndrome-specific sampling algorithms including the collection of blood, naso- and oropharyngeal swabs and stool. Samples are tested using comprehensive diagnostic protocols, ranging from classic bacteriology and antimicrobial resistance screening to multiplex real-time polymerase chain reaction (PCR) systems and High Throughput Sequencing. In March 2020, PCR testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and analysis of full genomic information was included in the study. Standardised questionnaires collect relevant clinical, demographic, socio-economic and behavioural data for epidemiologic analyses. Controls are enrolled over a 12-month period for a nested case-control study. Data will be assessed descriptively and aetiologies will be evaluated using a latent class analysis among cases. Among cases and controls, an integrated analytic approach using logistic regression and Bayesian estimation will be employed to improve the assessment of aetiology and associated risk factors. DISCUSSION: ANDEMIA aims to expand our understanding of ARI, GI and AFDUC aetiologies in sub-Saharan Africa using a comprehensive laboratory diagnostics strategy. It will foster early detection of emerging threats and continued monitoring of important common pathogens. The network collaboration will be strengthened and site diagnostic capacities will be reinforced to improve quality management and patient care.

COVID-19: cross-border contact tracing in Germany, February to April 2020.

IntroductionThe Robert Koch Institute (RKI) managed the exchange of cross-border contact tracing data between public health authorities (PHA) in Germany and abroad during the early COVID-19 pandemic.AimWe describe the extent of cross-border contact tracing and its challenges.MethodsWe analysed cross-border COVID-19 contact tracing events from 3 February to 5 April 2020 using information exchanged through the European Early Warning Response System and communication with International Health Regulation national focal points. We described events by PHA, number of contacts and exposure context.ResultsThe RKI processed 467 events, initiating contact to PHA 1,099 times (median = 1; interquartile range (IQR): 1-2) and sharing data on 5,099 contact persons. Of 327 (70%) events with known exposure context, the most commonly reported exposures were aircraft (n = 64; 20%), cruise ships (n = 24; 7%) and non-transport contexts (n = 210; 64%). Cruise ship and aircraft exposures generated more contacts with authorities (median = 10; IQR: 2-16, median = 4; IQR: 2-11) and more contact persons (median = 60; IQR: 9-269, median = 2; IQR: 1-3) than non-transport exposures (median = 1; IQR: 1-6 and median = 1; IQR: 1-2). The median time spent on contact tracing was highest for cruise ships: 5 days (IQR: 3-9).ConclusionIn the COVID-19 pandemic, cross-border contact tracing is considered a critical component of the outbreak response. While only a minority of international contact tracing activities were related to exposure events in transport, they contributed substantially to the workload. The numerous communications highlight the need for fast and efficient global outbreak communication channels between PHA.

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.

Implementation research for the prevention of antimicrobial resistance and healthcare-associated infections; 2017 Geneva infection prevention and control (IPC)-think tank (part 1).

Background: Around 5-15% of all hospital patients worldwide suffer from healthcare-associated infections (HAIs), and years of excessive antimicrobial use in human and animal medicine have created emerging antimicrobial resistance (AMR). A considerable amount of evidence-based measures have been published to address these challenges, but the largest challenge seems to be their implementation. Methods: In June 2017, a total of 42 experts convened at the Geneva IPC-Think Tank to discuss four domains in implementation science: 1) teaching implementation skills; 2) fostering implementation of IPC and antimicrobial stewardship (AMS) by policy making; 3) national/international actions to foster implementation skills; and 4) translational research bridging social sciences and clinical research in infection prevention and control (IPC) and AMR. Results: Although neglected in the past, implementation skills have become a priority in IPC and AMS. They should now be part of any curriculum in health care, and IPC career paths should be created. Guidelines and policies should be aligned with each other and evidence-based, each document providing a section on implementing elements of IPC and AMS in patient care. International organisations should be advocates for IPC and AMS, framing them as patient safety issues and emphasizing the importance of implementation skills. Healthcare authorities at the national level should adopt a similar approach and provide legal frameworks, guidelines, and resources to allow better implementation of patient safety measures in IPC and AMS. Rather than repeating effectiveness studies in every setting, we should invest in methods to improve the implementation of evidence-based measures in different healthcare contexts. For this, we need to encourage and financially support collaborations between social sciences and clinical IPC research. Conclusions: Experts of the 2017 Geneva Think Tank on IPC and AMS, CDC, and WHO agreed that sustained efforts on implementation of IPC and AMS strategies are required at international, country, and hospital management levels, to provide an adequate multimodal framework that addresses (not exclusively) leadership, resources, education and training for implementing IPC and AMS. Future strategies can build on this agreement to make strategies on IPC and AMS more effective.

Technology for the prevention of antimicrobial resistance and healthcare-associated infections; 2017 Geneva IPC-Think Tank (Part 2).

Background: The high burden of healthcare-associated infections (HAIs) and antimicrobial resistance (AMR) is partially due to excessive antimicrobial use both in human and animal medicine worldwide. How can technology help to overcome challenges in infection prevention and control (IPC) and to prevent HAI and emerging AMR? Methods: In June 2017, 42 international experts convened in Geneva, Switzerland to discuss four potential domains of technology in IPC and AMR: 1) role and potential contribution of microbiome research; 2) whole genome sequencing; 3) effectiveness and benefit of antimicrobial environmental surfaces; and 4) future research in hand hygiene. Results: Research on the microbiome could expand understanding of antimicrobial use and also the role of probiotics or even faecal transplantation for therapeutic purposes. Whole genome sequencing will provide new insights in modes of transmission of infectious diseases. Although it is a powerful tool for public health epidemiology, some challenges with interpretation and costs still need to be addressed. The effectiveness and cost-effectiveness of antimicrobially coated or treated environmental high-touch surfaces requires further research before they can be recommended for routine use. Hand hygiene implementation can be advanced, where technological enhancement of surveillance, technique and compliance are coupled with reminders for healthcare professionals. Conclusions: The four domains of technological innovation contribute to the prevention of HAI and AMR at different levels. Microbiome research may offer innovative concepts for future prevention, whole genome sequencing could detect new modes of transmission and become an additional tool for effective public health epidemiology, antimicrobial surfaces might help to decrease the environment as source of transmission but continue to raise more questions than answers, and technological innovation may have a role in improving surveillance approaches and supporting best practice in hand hygiene.

Factors associated with fatal cases of acute respiratory infection (ARI) among hospitalized patients in Guatemala.

BACKGROUND: Acute respiratory infection (ARI) is an important cause of mortality in children and adults. However, studies assessing risk factors for ARI-related deaths in low- and middle-income settings are limited. We describe ARI-related death and associated factors among children aged < 2 years and adults aged ≥18 years hospitalized with ARI in Guatemala. METHODS: We used respiratory illness surveillance data in Guatemala from 2007 to 2013. ARI was defined as evidence of acute infection and ≥ 1 sign/symptom of respiratory disease in hospitalized patients. Clinical, sociodemographic, and follow-up data were gathered. Nasopharyngeal/oropharyngeal swabs were collected from patients with ARI and tested for 6 respiratory viruses; urine was collected only from adults with ARI and tested for pneumococcal antigen. Blood cultures and chest radiographs were performed at the physician's discretion. Radiographs were interpreted per World Health Organization guidelines to classify endpoint pneumonia (i.e. suggestive of bacterial pneumonia). Multivariable logistic regression was used to compare characteristics of patients with fatal cases, including those who died in-hospital or were discharged in a moribund state, with those of patients with non-fatal cases. RESULTS: Among 4109 ARI cases identified in hospitalized children < 2 years old, 174 (4%) were fatal. Median age at admission was 4 and 6 months for children with fatal and non-fatal cases, respectively. Factors associated with fatality included low weight-for-age, low family income, heart disease, and endpoint pneumonia; breastfeeding and respiratory syncytial virus (RSV) detection were negatively associated with fatality. Among 1517 ARI cases identified in hospitalized adults ≥18 years, 181 (12%) episodes were fatal. Median age at admission was 57 years for adults with fatal and non-fatal cases. Low body mass index, male sex, kidney disease, and endpoint pneumonia were significantly more common among patients with fatal versus non-fatal cases. CONCLUSIONS: Our findings highlight some of the factors that must be addressed in order to reduce ARI-related mortality, including promotion of good nutrition, breastfeeding, management and prevention of chronic comorbidities, and poverty reduction. Although no specific pathogen increased risk for death, endpoint pneumonia was significantly associated with fatality, suggesting that the pneumococcal conjugate vaccine could contribute to future reductions in ARI-related mortality.

Control of Carbapenem-resistant Enterobacteriaceae, Acinetobacter baumannii, and Pseudomonas aeruginosa in Healthcare Facilities: A Systematic Review and Reanalysis of Quasi-experimental Studies.

Carbapenem-resistant Enterobacteriaceae (CRE), Acinetobacter baumannii (CRAB), and Pseudomonas aeruginosa (CRPsA) are a serious cause of healthcare-associated infections, although the evidence for their control remains uncertain. We conducted a systematic review and reanalysis to assess infection prevention and control (IPC) interventions on CRE-CRAB-CRPsA in inpatient healthcare facilities to inform World Health Organization guidelines. Six major databases and conference abstracts were searched. Before-and-after studies were reanalyzed as interrupted time series if possible. Effective practice and organization of care (EPOC) quality criteria were used. Seventy-six studies were identified, of which 17 (22%) were EPOC-compatible and interrupted time series analyses, assessing CRE (n = 11; 65%), CRAB (n = 5; 29%) and CRPsA (n = 3; 18%). IPC measures were often implemented using a multimodal approach (CRE: 10/11; CRAB: 4/5; CRPsA: 3/3). Among all CRE-CRAB-CRPsA EPOC studies, the most frequent intervention components included contact precautions (90%), active surveillance cultures (80%), monitoring, audit and feedback of measures (80%), patient isolation or cohorting (70%), hand hygiene (50%), and environmental cleaning (40%); nearly all studies with these interventions reported a significant reduction in slope and/or level. The quality of EPOC studies was very low to low.

Combating antibiotic resistance: a survey on the antibiotic-prescribing habits of dentists.

Adherence to clinical guidelines is recommended to promote appropriate antibiotic use in dentistry and address concerns about increasing antibiotic resistance. Guidelines for antibiotic prophylaxis before invasive dental procedures were updated in 2007 and 2015. In an effort to inform antibiotic stewardship efforts, a study was undertaken to assess the knowledge of antibiotic usage guidelines and antibiotic-prescribing practices among Minnesota dentists. During September 2015, a 22-question online survey was sent to the state dental association membership. Among 437 respondents, dentists reported a median of 4 antibiotic prophylaxis and 5 treatment prescriptions per month. Dentists reported prescribing antibiotics for prophylaxis before invasive dental procedures for patients with "high-risk conditions" (84%) and localized swelling (70%) as well as for a number of reasons that are not recommended by current guidelines, such as an upcoming vacation for the patient (38%), gingival pain (38%), legal concerns (24%), patient demand (22%), and failed local anesthesia (21%). Dentists defined high-risk conditions as a history of infective endocarditis (75%), prosthetic cardiac valve (70%), selected congenital heart disease (68%), cardiac transplantation with cardiac valvulopathy (4%), and primary care physician recommendation (59%). In addition, some dentists assigned a high-risk category to conditions that do not fall within current guideline recommendations, including prosthetic joints (39%), poorly controlled type 2 diabetes (27%), human immunodeficiency virus (18%), chronic kidney disease (13%), mitral valve prolapse (11%), all congenital heart disease (4%), and well-controlled type 2 diabetes (1%). Respondents indicated that common challenges to stewardship of antibiotic use included perceived conflicting provider guidelines (44%), conflicting scientific evidence (44%), or lack of information on antibiotic selection (19%) or risks (23%). Dentists reported greater antibiotic use than currently recommended by existing guidelines. Antibiotic stewardship efforts in dentistry should address challenges to guideline adherence.