Genomics for antimicrobial resistance surveillance to support infection prevention and control in health-care facilities.

Integration of genomic technologies into routine antimicrobial resistance (AMR) surveillance in health-care facilities has the potential to generate rapid, actionable information for patient management and inform infection prevention and control measures in near real time. However, substantial challenges limit the implementation of genomics for AMR surveillance in clinical settings. Through a workshop series and online consultation, international experts from across the AMR and pathogen genomics fields convened to review the evidence base underpinning the use of genomics for AMR surveillance in a range of settings. Here, we summarise the identified challenges and potential benefits of genomic AMR surveillance in health-care settings, and outline the recommendations of the working group to realise this potential. These recommendations include the definition of viable and cost-effective use cases for genomic AMR surveillance, strengthening training competencies (particularly in bioinformatics), and building capacity at local, national, and regional levels using hub and spoke models.

Whole genome sequencing of multidrug resistant Enterobacterales identified in children and their household members within Siem Reap, Cambodia.

Objectives: To explore the association of recent hospitalization and asymptomatic carriage of multidrug-resistant Enterobacterales (MDRE) and determine the prevailing strains and antibiotic resistance genes in Siem Reap, Cambodia using WGS. Methods: In this cross-sectional study, faecal samples were collected from two arms: a hospital-associated arm consisted of recently hospitalized children (2-14 years), with their family members; and a community-associated arm comprising children in the matching age group and their family members with no recent hospitalization. Forty-two families in each study arm were recruited, with 376 enrolled participants (169 adults and 207 children) and 290 stool specimens collected from participants. The DNA of ESBL- and carbapenemase-producing Enterobacterales cultured from the faecal samples was subject to WGS on the Illumina NovaSeq platform. Results: Of the 290 stool specimens, 277 Escherichia coli isolates and 130 Klebsiella spp. were identified on CHROMagar ESBL and KPC plates. The DNA of 276 E. coli (one isolate failed quality control test), 89 Klebsiella pneumoniae, 40 Klebsiella quasipneumoniae and 1 Klebsiella variicola was sequenced. CTX-M-15 was the most common ESBL gene found in E. coli (n = 104, 38%), K. pneumoniae (n = 50, 56%) and K. quasipneumoniae (n = 16, 40%). The prevalence of bacterial lineages and ESBL genes was not associated with any specific arm. Conclusions: Our results demonstrate that MDRE is likely to be endemic within the Siem Reap community. ESBL genes, specifically blaCTX-M, can be found in almost all E. coli commensals, indicating that these genes are continuously propagated in the community through various unknown channels at present.

Epidemiology of Extended-Spectrum Beta-Lactamase and Carbapenemase-Producing Enterobacterales in the Greater Mekong Subregion: A Systematic-Review and Meta-Analysis of Risk Factors Associated With Extended-Spectrum Beta-Lactamase and Carbapenemase Isolation.

Background: Despite the rapid spread of extended-spectrum beta-lactamase (ESBL) producing-Enterobacterales (ESBL-E) and carbapenemase-producing Enterobacterales (CPE), little is known about the extent of their prevalence in the Greater Mekong Subregion (GMS). In this systematic review, we aimed to determine the epidemiology of ESBL-E and CPE in clinically significant Enterobacterales: Escherichia coli and Klebsiella pneumoniae from the GMS (comprising of Cambodia, Laos, Myanmar, Thailand, Vietnam and Yunnan province and Guangxi Zhuang region of China). Methods: Following a list of search terms adapted to subject headings, we systematically searched databases: Medline, EMBASE, Scopus and Web of Science for articles published on and before October 20th, 2020. The search string consisted of the bacterial names, methods involved in detecting drug-resistance phenotype and genotype, GMS countries, and ESBL and carbapenemase detection as the outcomes. Meta-analyses of the association between the isolation of ESBL from human clinical and non-clinical specimens were performed using the "METAN" function in STATA 14. Results: One hundred and thirty-nine studies were included from a total of 1,513 identified studies. Despite the heterogeneity in study methods, analyzing the prevalence proportions on log-linear model scale for ESBL producing-E. coli showed a trend that increased by 13.2% (95%CI: 6.1-20.2) in clinical blood specimens, 8.1% (95%CI: 1.7-14.4) in all clinical specimens and 17.7% (95%CI: 4.9-30.4) increase in carriage specimens. Under the log-linear model assumption, no significant trend over time was found for ESBL producing K. pneumoniae and ESBL-E specimens. CPE was reported in clinical studies and carriage studies past 2010, however a trend could not be determined because of the small dataset. Twelve studies were included in the meta-analysis of risk factors associated with isolation of ESBL. Recent antibiotic exposure was the most studied variable and showed a significant positive association with ESBL-E isolation (pooled OR: 2.9, 95%CI: 2.3-3.8) followed by chronic kidney disease (pooled OR: 4.7, 95%CI: 1.8-11.9), and other co-morbidities (pooled OR: 1.6, 95%CI: 1.2-2.9). Conclusion: Data from GMS is heterogeneous with significant data-gaps, especially in community settings from Laos, Myanmar, Cambodia and Yunnan and Guangxi provinces of China. Collaborative work standardizing the methodology of studies will aid in better monitoring, surveillance and evaluation of interventions across the GMS.

Duration and determinants of delayed tuberculosis diagnosis and treatment in high-burden countries: a mixed-methods systematic review and meta-analysis.

BACKGROUND: Thirty countries with the highest tuberculosis (TB) burden bear 87% of the world's TB cases. Delayed diagnosis and treatment are detrimental to TB prognosis and sustain TB transmission in the community, making TB elimination a great challenge, especially in these countries. Our objective was to elucidate the duration and determinants of delayed diagnosis and treatment of pulmonary TB in high TB-burden countries. METHODS: We conducted a systematic review and meta-analysis of quantitative and qualitative studies by searching four databases for literature published between 2008 and 2018 following PRISMA guidelines. We performed a narrative synthesis of the covariates significantly associated with patient, health system, treatment, and total delays. The pooled median duration of delay and effect sizes of covariates were estimated using random-effects meta-analyses. We identified key qualitative themes using thematic analysis. RESULTS: This review included 124 articles from 14 low- and lower-middle-income countries (LIC and LMIC) and five upper-middle-income countries (UMIC). The pooled median duration of delays (in days) were-patient delay (LIC/LMIC: 28 (95% CI 20-30); UMIC: 10 (95% CI 10-20), health system delay (LIC/LMIC: 14 (95% CI 2-28); UMIC: 4 (95% CI 2-4), and treatment delay (LIC/LMIC: 14 (95% CI 3-84); UMIC: 0 (95% CI 0-1). There was consistent evidence that being female and rural residence was associated with longer patient delay. Patient delay was also associated with other individual, interpersonal, and community risk factors such as poor TB knowledge, long chains of care-seeking through private/multiple providers, perceived stigma, financial insecurities, and poor access to healthcare. Organizational and policy factors mediated health system and treatment delays. These factors included the lack of resources and complex administrative procedures and systems at the health facilities. We identified data gaps in 11 high-burden countries. CONCLUSIONS: This review presented the duration of delays and detailed the determinants of delayed TB diagnosis and treatment in high-burden countries. The gaps identified could be addressed through tailored approaches, education, and at a higher level, through health system strengthening and provision of universal health coverage to reduce delays and improve access to TB diagnosis and care. PROSPERO registration: CRD42018107237.

Detection of colonisation by extended-spectrum beta-lactamase or carbapenemase producing Enterobacterales from frozen stool specimens.

OBJECTIVE: To determine the impact of pre-culture ultra-low temperature (ULT, - 80 °C) storage of human stool specimens on recovery of Extended-Spectrum Beta-Lactamase (ESBL) or Carbapenemase (CPM) producing Enterobacterales. RESULTS: Twenty stool specimens from a community-based household colonisation study in Cambodia were cultured fresh and after 4-5 days and ~ 6 months of ULT storage (as a slurry in tryptone soya broth-10% glycerol). Presumptive ESBL- and CPM-Escherichia coli isolates were detected in 19/20 (95%) and 1/20 (5%) freshly cultured specimens, respectively. The specimens yielded identical results when re-cultured after ULT storage at both time points. Detection of presumptive ESBL- and CPM-Klebsiella / Enterobacter / Citrobacter group was less frequent and slightly less stable over time. Comparison of antimicrobial susceptibility test profiles between pairs of E. coli and K. pneumoniae isolates from the two frozen culture time points revealed concordance in only 13/28 (46%) pairs, indicating likely colonisation by multiple strains. In conclusion, ULT storage of human stool specimens prior to culture appears to be an acceptable method for managing laboratory workflow in culture-based ESBL / CPM Enterobacterales colonisation studies in high prevalence settings.

YouTube as source of information on 2019 novel coronavirus outbreak: a cross sectional study of English and Mandarin content.

BACKGROUND: The current 2019 novel coronavirus outbreak is rapidly evolving. YouTube has been recognized as a popular source of information in previous disease outbreaks. We analyzed the content on YouTube about n-CoV in English and Mandarin languages. METHODS: YouTube was searched using the terms '2019 novel coronavirus', 'Wuhan virus' and '' (Mandarin for Wuhan virus) on 1st and 2nd February 2020. First 50 videos in each group were analyzed. Videos in other languages, duplicate videos, those without an audio and duration >15 min were excluded .72 videos in English and 42 in Mandarin were reviewed. 2 reviewers classified the videos as useful, misleading or news based on pre specified criterion. Inter-observer agreement was evaluated with kappa coefficient. Modified DISCERN index for reliability and medical information and content index (MICI) score were used for content analysis. RESULTS: These videos attracted cumulative 21,288,856 views. 67% of English and 50% Mandarin videos had useful information. The viewership of misleading Mandarin videos was higher than the useful ones. WHO accounted for only 4% of useful videos. Mean DISCERN score for reliability was 3.12/5 and 3.25/5 for English and Mandarin videos respectively. Mean cumulative MICI score of useful videos was low (6.71/25 for English and 6.28/25 for Mandarin). CONCLUSIONS: YouTube viewership during 2019 n-CoV outbreak is higher than previous outbreaks. The medical content of videos is suboptimal International health agencies are underrepresented. Given its popularity, YouTube should be considered as important platform for information dissemination.

Prevalence of MDR organism (MDRO) carriage in children and their household members in Siem Reap Province, Cambodia.

BACKGROUND: The rising incidence of infections caused by MDR organisms (MDROs) poses a significant public health threat. However, little has been reported regarding community MDRO carriage in low- and middle-income countries. METHODS: We conducted a cross-sectional study in Siem Reap, Cambodia comparing hospital-associated households, in which an index child (age: 2-14 years) had been hospitalized for at least 48 h in the preceding 2-4 weeks, with matched community households on the same street, in which no other child had a recent history of hospitalization. Participants were interviewed using a survey questionnaire and tested for carriage of MRSA, ESBL-producing Enterobacterales (ESBL-E) and carbapenemase-producing Enterobacterales (CPE) by culture followed by antibiotic susceptibility testing. We used logistic regression analysis to analyse associations between collected variables and MDRO carriage. RESULTS: Forty-two pairs of households including 376 participants with 376 nasal swabs and 290 stool specimens were included in final analysis. MRSA was isolated from 26 specimens (6.9%). ESBL-producing Escherichia coli was detected in 269 specimens (92.8%) whereas ESBL-producing Klebsiella pneumoniae was isolated from 128 specimens (44.1%), of which 123 (42.4%) were co-colonized with ESBL-producing E. coli. Six (2.1%) specimens tested positive for CPE (4 E. coli and 2 K. pneumoniae). The prevalence ratios for MRSA, ESBL-producing E. coli and ESBL-producing K. pneumoniae carriage did not differ significantly in hospital-associated households and hospitalized children compared with their counterparts. CONCLUSIONS: The high prevalence of ESBL-E across both household types suggests that MDRO reservoirs are common in the community. Ongoing genomic analyses will help to understand the epidemiology and course of MDRO spread.

Community involvement in the development and implementation of chronic condition programmes across the continuum of care in high- and upper-middle income countries: A systematic review.

BACKGROUND: Community involvement is an important component of health programme development and implementation, including those focused on chronic condition treatment and management. Yet, few studies explore the manifestations of community involvement in chronic care programmes. Our review aims to examine the evidence on how communities are involved in planning and implementing chronic condition programmes in high and upper-middle income countries. METHODS: Eligible studies included those that involved the community in the planning, implementation, monitoring and evaluation of health services, policy or health interventions. We searched Medline, Embase, Global Health, Scopus, and LILACs from 2000 to 2016, independently screened articles for inclusion, conducted data extraction, and assessed studies for risk of bias. RESULTS: 27,232 records were identified and after screening, 32 met inclusion criteria. We conducted a narrative synthesis to report on the forms and processes of community involvement used across mental health programmes and contrast this with the paucity of evidence on comparable programmes addressing other chronic conditions. Challenges reported included user factors, organisational factors, and social challenges such as stigma. CONCLUSION: Our review adds to the evidence supporting community involvement in chronic condition management and the processes that contribute to successful and sustainable involvement. We report on a model, derived from inductive analysis, that considers social and cultural components, organisational factors and stakeholder relationships as underpinning the development of community interventions across the care continuum.

A systematic review of community nursing interventions focusing on improving outcomes for individuals exhibiting risk factors of cardiovascular disease.

OBJECTIVE: To examine the role of community-based nursing interventions in improving outcomes for community-dwelling individuals exhibiting risk factors of cardiovascular disease (CVD). DESIGN: A systematic review and narrative synthesis. DATA SOURCES: Seven electronic databases (MEDLINE, CINAHL, Global Health, LILACS, Africa-Wide Information, IMEMR, and WPRIM) were searched from inception to 16 March 2018. REVIEW METHODS: This review included outcomes from studies that were led by or delivered primarily by nurses for individuals exhibiting risk factors of CVD in community settings. At least two independent reviewers performed study selection, data extraction and risk of bias. RESULTS: 46 studies met the eligibility criteria. Community nursing interventions were found to be effective in improving clinical outcomes of symptom control, symptom awareness, symptom management, and social outcomes. Effective interventions were found to be facilitated by a community-centric approach, participant empowerment, reinforcement strategies, a targeted approach towards underserved populations, and home visits. These resulted in positive outcomes such as significant reductions in HbA1c for diabetic patients, attainment of blood pressure targets for hypertensive patients and greater improvement in self-reported dietary intake for patients with hyperlipidaemia. CONCLUSION: Community-based nurse-led interventions can result in positive outcomes for patients with risk factors of CVD. However, the success of such interventions needs to be facilitated by appropriate funding, thoughtful intervention design and training opportunities for nurses. IMPACT: Community-based nursing interventions are largely effective in improving clinical and social outcomes for community-dwelling individuals with risk factors of CVD.

The role of community-based nursing interventions in improving outcomes for individuals with cardiovascular disease: A systematic review.

OBJECTIVE: To examine the role of community-based nursing interventions in improving outcomes for community-dwelling individuals with cardiovascular disease. DESIGN: A systematic review and narrative synthesis. DATA SOURCES: Seven electronic databases (MEDLINE, CINAHL, Global Health, LILACS, Africa-Wide Information, IMEMR and WPRIM) were searched from inception to 16 March 2018 without language restrictions. REVIEW METHODS: We included studies evaluating the outcomes of interventions led by, or primarily delivered by, nurses for individuals with cardiovascular disease in community settings. Study selection, data extraction and risk of bias assessments were performed by at least two independent reviewers. RESULTS: Twenty-eight studies met the inclusion criteria and were included in this review. Community-based nursing interventions improved outcomes in four key areas: (1) self-care, (2) health, (3) healthcare utilisation, and (4) quality of care. Significant improvements were reported in patients' knowledge and ability to self-manage, severity of disease, functional status, quality of life, risk of death, hospital readmission days, emergency department visits, healthcare costs and satisfaction with care. Facilitators to intervention effectiveness included the use of an individualised approach, multidisciplinary approach, specially trained nurses, family involvement and the home setting. Conversely, barriers to intervention success included limitations in nurses' time and skills, ineffective interdisciplinary collaboration and insufficient intervention intensity. CONCLUSIONS: The overall evidence is positive regarding the role of community-based nursing interventions in improving outcomes for individuals with cardiovascular disease. However, this review highlights the need for more robust research establishing definitive relationships between different types of interventions and outcomes as well as evaluating the cost-effectiveness of these interventions to aid the development of sustainable policy solutions.

Delayed diagnosis and treatment of pulmonary tuberculosis in high-burden countries: a systematic review protocol.

INTRODUCTION: Countries identified to bear the highest tuberculosis (TB) incidence account for approximately 85% of the global TB burden. TB is curable, yet nearly 40% of TB cases remained undiagnosed hence delaying treatment and perpetuating transmission. This systematic review aimed to review current evidence on factors associated with delayed diagnosis and treatment of TB in the high TB-burden countries. METHODS AND ANALYSIS: This systematic review will incorporate qualitative and observational study designs published between 2008 and 2018. Articles will be retrieved from major databases including PubMed, EMBASE, CINAHL and PsycINFO. Reference lists of key articles, including relevant systematic reviews and meta-analysis, will be screened for additional studies. Two independent reviewers will screen and select studies, extract data and assess the quality and risk of bias of each study. Study-specific estimates will be pooled by meta-analysis, and effect sizes will be presented as OR and their 95% CI. Levels of heterogeneity will be evaluated using chi-square statistic Q and I2. Publication bias will be assessed using forest plots and Egger's tests. Qualitative findings and sample quotes will be extracted. Textual references to the topics of interest will be retrieved and categorised using qualitative thematic analysis. We will triangulate quantitative and qualitative findings for a complete understanding of the reasons for delayed TB diagnosis and treatment. Results will be presented by geographical region. ETHICS AND DISSEMINATION: This study will be conducted based on published data. This systematic review may provide insights into the reasons for delayed TB diagnosis in high-burden countries. These findings will also inform future research and key stakeholders in developing interventions to reach these undiagnosed cases effectively. Findings from this review will be published in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42018107237.

Community participation in health services development, implementation, and evaluation: A systematic review of empowerment, health, community, and process outcomes.

BACKGROUND: Community participation is widely believed to be beneficial to the development, implementation and evaluation of health services. However, many challenges to successful and sustainable community involvement remain. Importantly, there is little evidence on the effect of community participation in terms of outcomes at both the community and individual level. Our systematic review seeks to examine the evidence on outcomes of community participation in high and upper-middle income countries. METHODS AND FINDINGS: This review was developed according to PRISMA guidelines. Eligible studies included those that involved the community, service users, consumers, households, patients, public and their representatives in the development, implementation, and evaluation of health services, policy or interventions. We searched the following databases from January 2000 to September 2016: Medline, Embase, Global Health, Scopus, and LILACs. We independently screened articles for inclusion, conducted data extraction, and assessed studies for risk of bias. No language restrictions were made. 27,232 records were identified, with 23,468 after removal of duplicates. Following titles and abstracts screening, 49 met the inclusion criteria for this review. A narrative synthesis of the findings was conducted. Outcomes were categorised as process outcomes, community outcomes, health outcomes, empowerment and stakeholder perspectives. Our review reports a breadth of evidence that community involvement has a positive impact on health, particularly when substantiated by strong organisational and community processes. This is in line with the notion that participatory approaches and positive outcomes including community empowerment and health improvements do not occur in a linear progression, but instead consists of complex processes influenced by an array of social and cultural factors. CONCLUSION: This review adds to the evidence base supporting the effectiveness of community participation in yielding positive outcomes at the organizational, community and individual level. TRIAL REGISTRATION: Prospero record number: CRD42016048244.

Health Care Providers' Perceptions of Responsibilities and Resources to Reduce Type 2 Diabetes Risk After Gestational Diabetes Mellitus.

IN BRIEF Gestational diabetes mellitus (GDM) increases the risk for type 2 diabetes. This qualitative study aimed to evaluate health care providers' perceptions of care responsibilities and resources related to reducing type 2 diabetes risk among women with previous GDM in Singapore. Health care providers acknowledged a shared responsibility. They felt that they had less understanding of compliance with long-term maintenance of lifestyle change, exacerbated further by fragmentation of follow-up care. The application of more integrated patient-centered care models, combined with greater health literacy, is urgently required in this area.

Mapping infectious disease hospital surge threats to lessons learnt in Singapore: a systems analysis and development of a framework to inform how to DECIDE on planning and response strategies.

BACKGROUND: Hospital usage and service demand during an Infectious Disease (ID) outbreak can tax the health system in different ways. Herein we conceptualize hospital surge elements, and lessons learnt from such events, to help build appropriately matched responses to future ID surge threats. METHODS: We used the Interpretive Descriptive qualitative approach. Interviews (n = 35) were conducted with governance and public health specialists; hospital based staff; and General Practitioners. Key policy literature in tandem with the interview data were used to iteratively generate a Hospital ID Surge framework. We anchored our narrative account within this framework, which is used to structure our analysis. RESULTS: A spectrum of surge threats from combinations of capacity (for crowding) and capability (for treatment complexity) demands were identified. Starting with the Pyramid scenario, or an influx of high screening rates flooding Emergency Departments, alongside fewer and manageable admissions; the Reverse-Pyramid occurs when few cases are screened and admitted but those that are, are complex; during a 'Black' scenario, the system is overburdened by both crowding and complexity. The Singapore hospital system is highly adapted to crowding, functioning remarkably well at constant near-full capacity in Peacetime and resilient to Endemic surges. We catalogue 26 strategies from lessons learnt relating to staffing, space, supplies and systems, crystalizing institutional memory. The DECIDE model advocates linking these strategies to types of surge threats and offers a step-by-step guide for coordinating outbreak planning and response. CONCLUSIONS: Lack of a shared definition and decision making of surge threats had rendered the procedures somewhat duplicative. This burden was paradoxically exacerbated by a health system that highly prizes planning and forward thinking, but worked largely in silo until an ID crisis hit. Many such lessons can be put into play to further strengthen our current hospital governance and adapted to more diverse settings.