Spatial and phylogenetic patterns reveal hidden infection sources of Bacillus anthracis in an anthrax outbreak in Son La province, Vietnam.

Bacillus anthracis, the bacterial cause of anthrax, is a zoonosis affecting livestock and wildlife often spilling over into humans. In Vietnam, anthrax has been nationally reportable since 2015 with cases occurring annually, mostly in the northern provinces. In April 2022, an outbreak was reported in Son La province following the butchering of a water buffalo, Bubalus bubalis. A total of 137 humans from three villages were likely exposed to contaminated meat from the animal. Early epidemiological investigations suggested a single animal was involved in all exposures. Five B. anthracis isolates were recovered from human clinical cases along with one from the buffalo hide, another from associated maggots, and one from soil at the carcass site. The isolates were whole genome sequenced, allowing global, regional, and local molecular epidemiological analyses of the outbreak strains. All recovered B. anthracis belong to the A.Br.001/002 lineage based on canonical single nucleotide polymorphism analysis (canSNP). Although not previously identified in Vietnam, this lineage has been identified in the nearby countries of China, India, Indonesia, Thailand, as well as Australia. A twenty-five marker multi-locus variable number tandem repeat analysis (MLVA-25) was used to investigate the relationship between human, soil, and buffalo strains. Locally, four MLVA-25 genotypes were identified from the eight isolates. This level of genetic diversity is unusual for the limited geography and timing of cases and differs from past literature using MLVA-25. The coupled spatial and phylogenetic data suggest this outbreak originated from multiple, likely undetected, animal sources. These findings were further supported by local news reports that identified at least two additional buffalo deaths beyond the initial animal sampled in response to the human cases. Future outbreak response should include intensive surveillance for additional animal cases and additional molecular epidemiological traceback to identify pathogen sources.

Review of antibiotic prescriptions as part of antimicrobial stewardship programmes: results from a pilot implementation at two provincial-level hospitals in Viet Nam.

Objectives: To investigate the feasibility of retrospective prescription-based review and to describe the antibiotic prescribing patterns to provide information for an antimicrobial stewardship programme in Viet Nam. Methods: This study was conducted in two provincial-level hospitals between February and April 2020. Reviews were done by a clinical team consisting of leaders/senior doctors of each ward to assess the optimal level (optimal/adequate/suboptimal/inadequate/not assessable) of antibiotic prescriptions. Mixed-effect logistic regression at prescription level was used to explore factors associated with optimal antibiotic use. Results: The retrospective prescription-based review was accepted by study clinical wards with varied levels of participants. One hundred and eighty-three patients (326 prescriptions) in Hospital 1 and 200 patients (344 prescriptions) in Hospital 2 were included. One hundred and nineteen of the 326 (36.5%) antibiotic prescriptions in Hospital 1 and 51/344 (14.8%) antibiotic prescriptions in Hospital 2 were determined to be optimal by the review teams. The number of adequate antibiotic prescriptions were 179/326 (54.9%) and 178 (51.7%) in Hospital 1 and Hospital 2, respectively. The optimal level was lower for surgical prophylaxis antibiotics than for empirical therapy (OR = 0.06; 95% CI 0.01-0.45), higher in prescriptions in the ICU (OR = 12.00; 95% CI 3.52-40.92), higher in definitive antibiotic therapy (OR = 48.12; 95% CI 7.17-322.57) and higher in those with an indication recorded in medical records (OR = 3.46; 95% CI 1.13-10.62). Conclusions: This study provides evidence on the feasibility of retrospective prescription-based review, with adaption to the local situation. High and varying levels of optimal antibiotic prescriptions in clinical wards in hospitals were observed in Viet Nam.

Antimicrobial resistance patterns in bacteria causing febrile illness in Africa, South Asia, and Southeast Asia: a systematic review of published etiological studies from 1980-2015.

OBJECTIVE: In this study, we aimed to conduct a systematic review to characterize antimicrobial resistance (AMR) patterns for bacterial causes of febrile illness in Africa and Asia. METHODS: We included published literature from 1980-2015 based on data extracted from two recent systematic reviews of nonmalarial febrile illness from Africa, South Asia, and Southeast Asia. Selection criteria included articles with full bacterial identification and antimicrobial susceptibility testing (AST) results for key normally sterile site pathogen-drug combinations. Pooled proportions of resistant isolates were combined using random effects meta-analysis. Study data quality was graded using the Microbiology Investigation Criteria for Reporting Objectively (MICRO) framework. RESULTS: Of 3475 unique articles included in the previous reviews, 371 included the target pathogen-drug combinations. Salmonella enterica tested against ceftriaxone and ciprofloxacin were the two highest reported combinations (30,509 and 22,056 isolates, respectively). Pooled proportions of resistant isolates were high for third-generation cephalosporins for Klebsiella pneumoniae and Escherichia coli in all regions. The MICRO grading showed an overall lack of standardization. CONCLUSION: This review highlights a general increase in AMR reporting and in resistance over time. However, there were substantial problems with diagnostic microbiological data quality. Urgent strengthening of laboratory capacity, standardized testing, and reporting of AST results is required to improve AMR surveillance.

Assessing feasibility of establishing antimicrobial stewardship programmes in two provincial-level hospitals in Vietnam: an implementation research study.

OBJECTIVES: To investigate the feasibility of establishing hospital-based antimicrobial stewardship (AMS) programmes comprising action-planning, educational interventions and data feedback in two provincial-level hospitals in Viet Nam. DESIGN AND SETTING: This was an implementation research using participatory action process and existing resources from the Duke Antimicrobial Stewardship Outreach Network with local adjustments. A national stakeholder meeting and Strengths-Weaknesses-Opportunities-Threats (SWOT) analysis were conducted to identify gaps and potential interventions. PARTICIPANTS: Hospital AMS staff implemented activities throughout the study phases. Routinely collected patient data were analysed to support planning, implementation and evaluation. INTERVENTIONS: Hospitals were considered as a complex adaptive system and leveraged their unique characteristics and interconnections to develop 1-year plans containing core interventions (data use, educational training, prospective audit with feedback (PAF) and evaluations). OUTCOME MEASURES: We assessed feasibility using outputs from stakeholder meeting, SWOT analysis, baseline data, planning process and implementation. RESULTS: The stakeholder meeting identified three gaps for AMS at national level: supportive policies, AMS training and core competencies and collaboration. At the hospitals, AMS programmes took 1 year for planning due to lack of hospital-specific procedures and relevant staff competencies. Baseline data (January-December 2019) showed variations in antibiotic consumption: 951 days of therapy (DOT) per 1000 days present in the control and 496 in the intervention wards in hospital 1, and 737 and 714 in hospital 2, respectively. During 1-year implementation, clinical pharmacists audited 1890 antibiotic prescriptions in hospital 1 (June 2020-May 2021) and 1628 in hospital 2 (July 2020-July 2021), and will continue PAF in their daily work. CONCLUSION: Our data confirmed the need to contextualise AMS programmes in low-income and middle-income countries (LMICs) and demonstrated the usefulness of implementation research design in assessing programme feasibility. Developing staff competencies, using local data to stimulate actions and integrating programme activities in routine hospital work are key to success in LMICs.

Improving antimicrobial use through antimicrobial stewardship in a lower-middle income setting: a mixed-methods study in a network of acute-care hospitals in Viet Nam.

OBJECTIVES: This study aimed to analyse the current state of antimicrobial stewardship (AMS) in hospitals in Viet Nam, a lower-middle income country (LMIC), to identify factors determining success in AMS implementation and associated challenges to inform planning and design of future programmes. METHODS: We conducted a mixed-methods study in seven acute-care hospitals in the antimicrobial resistance (AMR) surveillance network in Viet Nam. Data collection included 7 focus group discussions, 40 in-depth interviews and a self-administered quantitative survey of staff on AMR and AMS programmes. We summarised qualitative data by reporting the most common themes according to the core AMS elements, and analysed quantitative data using proportions and a linear mixed-effects model. RESULTS: The findings reveal a complex picture of factors and actors involved in AMS implementation from the national level to the departmental and individual level within each hospital. The level of implementation varied, starting from the formation of an AMS committee, with or without active delivery of specific interventions. Development of treatment guidelines, pre-authorisation of antimicrobial drug classes, and post-prescription audit and feedback to doctors in selected clinical departments were the main interventions reported. A higher level of leadership support and commitment to AMS led to a higher level of engagement with AMS activities from the AMS team and effective collaboration between departments involved. CONCLUSION: Establishing country-specific guidelines on AMS staffing and adapting standards for AMS education and training from international resources are needed to support capacity building to implement AMS programmes effectively in LMICs such as Viet Nam.

Plans for Nationwide Serosurveillance Network in Vietnam.

In recent years, serosurveillance has gained momentum as a way of determining disease transmission and immunity in populations, particularly with respect to vaccine-preventable diseases. At the end of 2017, the Oxford University Clinical Research Unit and the National Institute of Hygiene and Epidemiology held a meeting in Vietnam with national policy makers, researchers, and international experts to discuss current seroepidemiologic projects in Vietnam and future needs and plans for nationwide serosurveillance. This report summarizes the meeting and the plans that were discussed to set up nationwide serosurveillance in Vietnam.

Burden of disease and economic impact of human Streptococcus suis infection in Viet Nam.

BACKGROUND: Streptococcus suis is a zoonotic disease mainly affecting men of working age and can result in death or long-term sequelae, including severe hearing loss and vestibular dysfunction. We aimed to quantify the burden of disease and economic impact of this infection in Viet Nam. METHODS: The annual disease incidence for the period 2011-2014 was estimated based on surveillance data using a multiple imputation approach. We calculated disease burden in disability-adjusted life years (DALYs) and economic costs using an incidence-based approach from a patient's perspective and including direct and indirect impacts of S. suis infection and its long-term sequelae. RESULTS: The estimated annual incidence rate was 0.318, 0.324, 0.255 and 0.249 cases per 100 000 population in 2011, 2012, 2013 and 2014, respectively. The corresponding DALYs lost were 1832, 1866, 1467 and 1437. The mean direct cost per episode was US$1635 (95% confidence interval 1352-1923). The annual direct cost was US$370 000-500 000 and the indirect cost was US$2.27-2.88 million in this time period. CONCLUSIONS: This study showed a large disease burden and high economic impact of S. suis infection and provides important data for disease monitoring and control.

A Systematic Review and Meta-analysis of Ventilator-associated Pneumonia in Adults in Asia: An Analysis of National Income Level on Incidence and Etiology.

Background: Ventilator-associated pneumonia (VAP) is the commonest hospital-acquired infection (HAI) in intensive care. In Asia, VAP is increasingly caused by resistant gram-negative organisms. Despite the global antimicrobial resistance crisis, the epidemiology of VAP is poorly documented in Asia. Methods: We systematically reviewed literature published on Ovid Medline, Embase Classic, and Embase from 1 January 1990 to 17 August 2017 to estimate incidence, prevalence, and etiology of VAP. We performed a meta-analysis to give pooled rates and rates by country income level. Results: Pooled incidence density of VAP was high in lower- and upper-middle-income countries and lower in high-income countries (18.5, 15.2, and 9.0 per 1000 ventilator-days, respectively). Acinetobacter baumannii (n = 3687 [26%]) and Pseudomonas aeruginosa (n = 3176 [22%]) were leading causes of VAP; Staphylococcus aureus caused 14% (n = 1999). Carbapenem resistance was common (57.1%). Conclusions: VAP remains a common cause of HAI, especially in low- and middle-income countries, and antibiotic resistance is high.

Excess direct hospital cost of treating adult patients with ventilator associated respiratory infection (VARI) in Vietnam.

INTRODUCTION: Ventilator associated respiratory infections (VARIs) are the most common hospital acquired infections in critical care worldwide. This work aims to estimate the total annual direct hospital cost of treating VARI throughout Vietnam. METHODS: A costing model was constructed to evaluate the excess cost of diagnostics and treatment of VARI in Vietnam. Model inputs included costs for extra lengths of stay, diagnostics, VARI incidence, utilisation of ventilators and antibiotic therapy. RESULTS: With the current VARI incidence rate of 21.7 episodes per 1000 ventilation-days, we estimated 34,428 VARI episodes in the 577 critical care units in Vietnam per year. The extra cost per VARI episode was $1,174.90 and the total annual excess cost was US$40.4 million. A 1% absolute reduction in VARI incidence density would save US$1.86 million annually. For each episode of VARI, the share of excess cost components was 45.1% for critical care unit stay and ventilation, 3.7% for diagnostics and 51.1% for extra antimicrobial treatment. CONCLUSIONS: At the current annual government health expenditure of US$117 per capita, VARI represents a substantial cost to the health service in Vietnam. Enhanced infection prevention and control and antimicrobial stewardship programmes should be implemented to reduce this.

Correction: Excess direct hospital cost of treating adult patients with ventilator associated respiratory infection (VARI) in Vietnam.

[This corrects the article DOI: 10.1371/journal.pone.0206760.].

Raw pig blood consumption and potential risk for Streptococcus suis infection, Vietnam.

We assessed consumption of raw pig blood, which is a risk factor for Streptococcus suis infection in Vietnam, by using a mix-method design. Factors associated with consumption included rural residency, age, sex, occupation, income, and marital status. We identified risk groups and practices and perceptions that should be targeted by communication programs.

Epidemiology, clinical manifestations, and outcomes of Streptococcus suis infection in humans.

Streptococcus suis, a bacterium that affects pigs, is a neglected pathogen that causes systemic disease in humans. We conducted a systematic review and meta-analysis to summarize global estimates of the epidemiology, clinical characteristics, and outcomes of this zoonosis. We searched main literature databases for all studies through December 2012 using the search term "streptococcus suis." The prevalence of S. suis infection is highest in Asia; the primary risk factors are occupational exposure and eating of contaminated food. The pooled proportions of case-patients with pig-related occupations and history of eating high-risk food were 38.1% and 37.3%, respectively. The main clinical syndrome was meningitis (pooled rate 68.0%), followed by sepsis, arthritis, endocarditis, and endophthalmitis. The pooled case-fatality rate was 12.8%. Sequelae included hearing loss (39.1%) and vestibular dysfunction (22.7%). Our analysis identified gaps in the literature, particularly in assessing risk factors and sequelae of this infection.