An estimation of total antimicrobial usage in humans and animals in Vietnam

Abstract: The accurate assessment of antimicrobial use (AMU) requires relating quantities of active ingredients (AAIs) with population denominators. These data can be used to prioritize potential sources of selective pressure for antimicrobial resistance and to establish reduction targets. Here, we estimated AMU in Vietnam (human population 93.4 M in 2015), and compared it with European Union (EU) data (population 511.5 M in 2014). We extrapolated AMU data on each key animal species and humans from different published sources to calculate overall AMU (in tonnes) in Vietnam. We then compared these data with published statistics on AMU in the European Union (EU). A total of 3838 t of antimicrobials were used in Vietnam, of which 2751 (71.7%) corresponded to animal use, and the remainder (1086 t; 28.3%) to human AMU. This equates to 261.7 mg and 247.3 mg per kg of human and animal biomass, compared with 122.0 mg and 151.5 mg in the EU. The greatest quantities of antimicrobials (in decreasing order) were used in pigs (41.7% of total use), humans (28.3%), aquaculture (21.9%) and chickens (4.8%). Combined AMU in other species accounted for < 1.5%. These results are approximate and highlight the need to conduct targeted surveys to improve country-level estimates of AMU

Состояние провоспалительного цитокинового звена у больных с нестабильной стенокарадией и сахарным диабетом 2-го типа в зависимости от функционального класса хронической сердечной недостаточности

Проанализировано состояние провоспалительного звена цитокинов у больных с нестабильной стенокардией (НС) и сопутствующим сахарным диабетом (СД) 2−го типа в зависимости от функционального класса хронической сердечной недостаточности (ХСН). Нарастание проявлений сердечной декомпенсации у больных с НС и СД 2−го типа ассоциируется с высокой активностью провоспалительного цитокинового звена, представленного фактором некроза опухолей−α и интерлейкином−6. Повышение функционального класса ХСН характеризуется увеличением инсулинорезистентности у больных с НС и СД 2−го типа.Проаналізовано стан прозапальної ланки цитокінів у хворих із нестабільною стенокардією (НС) та супутнім цукровим діабетом (ЦД) 2−го типу залежно від функціонального класу хронічної серцевої недостатності (ХСН). Наростання проявів серцевої декомпенсації у хворих із НС та СД 2−го типу асоціюється з високою активністю прозапальної цитокінової ланки, представленої фактором некрозу пухлин−α та інтерлейкіном−6. Підвищення функціонального класу ХСН характеризується зростанням інсулінорезистентності у хворих із НС та ЦД 2−го типу.The state of pro−inflammatory cytokines in patients with unstable angina (UA) and associated type 2 diabetes mellitus (DM) was analyzed depending on the functional class of chronic heart failure (CHF). The increase in manifestations of cardiac decompensation in patients with UA and type 2 DM is associated with high activity of pro−inflammatory cytokine level represented by tumor necrosis factor−β and interleukin−6. Increase of functional class of CHF is characterized by increased insulin resistance in patients with UA and type 2 DM

Limited contribution of non-intensive chicken farming to ESBL-producing Escherichia coli colonization in humans in Vietnam: an epidemiological and genomic analysis.

OBJECTIVES: To investigate the risk of colonization with ESBL-producing Escherichia coli (ESBL-Ec) in humans in Vietnam associated with non-intensive chicken farming. METHODS: Faecal samples from 204 randomly selected farmers and their chickens, and from 306 age- and sex-matched community-based individuals who did not raise poultry were collected. Antimicrobial usage in chickens and humans was assessed by medicine cabinet surveys. WGS was employed to obtain a high-resolution genomic comparison between ESBL-Ec isolated from humans and chickens. RESULTS: The adjusted prevalence of ESBL-Ec colonization was 20.0% (95% CI 10.8%-29.1%) and 35.2% (95% CI 30.4%-40.1%) in chicken farms and humans in Vietnam, respectively. Colonization with ESBL-Ec in humans was associated with antimicrobial usage (OR = 2.52, 95% CI = 1.08-5.87) but not with involvement in chicken farming. blaCTX-M-55 was the most common ESBL-encoding gene in strains isolated from chickens (74.4%) compared with blaCTX-M-27 in human strains (47.0%). In 3 of 204 (1.5%) of the farms, identical ESBL genes were detected in ESBL-Ec isolated from farmers and their chickens. Genomic similarity indicating recent sharing of ESBL-Ec between chickens and farmers was found in only one of these farms. CONCLUSIONS: The integration of epidemiological and genomic data in this study has demonstrated a limited contribution of non-intensive chicken farming to ESBL-Ec colonization in humans in Vietnam and further emphasizes the importance of reducing antimicrobial usage in both human and animal host reservoirs

New Variant of Multidrug-Resistant Salmonella enterica Serovar Typhimurium Associated with Invasive Disease in Immunocompromised Patients in Vietnam.

Nontyphoidal Salmonella (NTS), particularly Salmonella enterica serovar Typhimurium, is among the leading etiologic agents of bacterial enterocolitis globally and a well-characterized cause of invasive disease (iNTS) in sub-Saharan Africa. In contrast, S Typhimurium is poorly defined in Southeast Asia, a known hot spot for zoonotic disease with a recently described burden of iNTS disease. Here, we aimed to add insight into the epidemiology and potential impact of zoonotic transfer and antimicrobial resistance (AMR) in S Typhimurium associated with iNTS and enterocolitis in Vietnam. We performed whole-genome sequencing and phylogenetic reconstruction on 85 human (enterocolitis, carriage, and iNTS) and 113 animal S Typhimurium isolates isolated in Vietnam. We found limited evidence for the zoonotic transmission of S Typhimurium. However, we describe a chain of events where a pandemic monophasic variant of S Typhimurium (serovar I:4,[5],12:i:- sequence type 34 [ST34]) has been introduced into Vietnam, reacquired a phase 2 flagellum, and acquired an IncHI2 multidrug-resistant plasmid. Notably, these novel biphasic ST34 S Typhimurium variants were significantly associated with iNTS in Vietnamese HIV-infected patients. Our study represents the first characterization of novel iNTS organisms isolated outside sub-Saharan Africa and outlines a new pathway for the emergence of alternative Salmonella variants into susceptible human populations.IMPORTANCESalmonella Typhimurium is a major diarrheal pathogen and associated with invasive nontyphoid Salmonella (iNTS) disease in vulnerable populations. We present the first characterization of iNTS organisms in Southeast Asia and describe a different evolutionary trajectory from that of organisms causing iNTS in sub-Saharan Africa. In Vietnam, the globally distributed monophasic variant of Salmonella Typhimurium, the serovar I:4,[5],12:i:- ST34 clone, has reacquired a phase 2 flagellum and gained a multidrug-resistant plasmid to become associated with iNTS disease in HIV-infected patients. We document distinct communities of S Typhimurium and I:4,[5],12:i:- in animals and humans in Vietnam, despite the greater mixing of these host populations here. These data highlight the importance of whole-genome sequencing surveillance in a One Health context in understanding the evolution and spread of resistant bacterial infections

The baseline characteristics and interim analyses of the high-risk sentinel cohort of the Vietnam Initiative on Zoonotic InfectiONS (VIZIONS)

The Vietnam Initiative for Zoonotic Infections (VIZIONS) includes community-based 'high-risk sentinel cohort' (HRSC) studies investigating individuals at risk of zoonotic infection due to occupational or residential exposure to animals. A total of 852 HRSC members were recruited between March 2013 and August 2014 from three provinces (Ha Noi, Dak Lak, and Dong Thap). The most numerous group (72.8%) corresponded to individuals living on farms, followed by slaughterers (16.3%) and animal health workers (8.5%). Nasal/pharyngeal and rectal swabs were collected from HRSC members at recruitment and after notifying illness. Exposure to exotic animals (including wild pigs, porcupine, monkey, civet, bamboo rat and bat) was highest for the Dak Lak cohort (53.7%), followed by Ha Noi (13.7%) and Dong Thap (4.0%). A total of 26.8% of individuals reported consumption of raw blood over the previous year; 33.6% slaughterers reported no use of protective equipment at work. Over 686 person-years of observation, 213 episodes of suspect infectious disease were notified, equivalent of 0.35 reports per person-year. Responsive samples were collected from animals in the farm cohort. There was noticeable time and space clustering of disease episodes suggesting that the VIZIONS set up is also suitable for the formal epidemiological investigation of disease outbreaks

The Vietnam Initiative on Zoonotic Infections (VIZIONS): A Strategic Approach to Studying Emerging Zoonotic Infectious Diseases

The effect of newly emerging or re-emerging infectious diseases of zoonotic origin in human populations can be potentially catastrophic, and large-scale investigations of such diseases are highly challenging. The monitoring of emergence events is subject to ascertainment bias, whether at the level of species discovery, emerging disease events, or disease outbreaks in human populations. Disease surveillance is generally performed post hoc, driven by a response to recent events and by the availability of detection and identification technologies. Additionally, the inventory of pathogens that exist in mammalian and other reservoirs is incomplete, and identifying those with the potential to cause disease in humans is rarely possible in advance. A major step in understanding the burden and diversity of zoonotic infections, the local behavioral and demographic risks of infection, and the risk of emergence of these pathogens in human populations is to establish surveillance networks in populations that maintain regular contact with diverse animal populations, and to simultaneously characterize pathogen diversity in human and animal populations. Vietnam has been an epicenter of disease emergence over the last decade, and practices at the human/animal interface may facilitate the likelihood of spillover of zoonotic pathogens into humans. To tackle the scientific issues surrounding the origins and emergence of zoonotic infections in Vietnam, we have established The Vietnam Initiative on Zoonotic Infections (VIZIONS). This countrywide project, in which several international institutions collaborate with Vietnamese organizations, is combining clinical data, epidemiology, high-throughput sequencing, and social sciences to address relevant one-health questions. Here, we describe the primary aims of the project, the infrastructure established to address our scientific questions, and the current status of the project. Our principal objective is to develop an integrated approach to the surveillance of pathogens circulating in both human and animal populations and assess how frequently they are exchanged. This infrastructure will facilitate systematic investigations of pathogen ecology and evolution, enhance understanding of viral cross-species transmission events, and identify relevant risk factors and drivers of zoonotic disease emergence

Antimicrobial Resistance in Bacterial Poultry Pathogens: A Review

Antimicrobial resistance (AMR) is a global health threat, and antimicrobial usage and AMR in animal production is one of its contributing sources. Poultry is one of the most widespread types of meat consumed worldwide. Poultry flocks are often raised under intensive conditions using large amounts of antimicrobials to prevent and to treat disease, as well as for growth promotion. Antimicrobial resistant poultry pathogens may result in treatment failure, leading to economic losses, but also be a source of resistant bacteria/genes (including zoonotic bacteria) that may represent a risk to human health. Here we reviewed data on AMR in 12 poultry pathogens, including avian pathogenic Escherichia coli (APEC), Salmonella Pullorum/Gallinarum, Pasteurella multocida, Avibacterium paragallinarum, Gallibacterium anatis, Ornitobacterium rhinotracheale (ORT), Bordetella avium, Clostridium perfringens, Mycoplasma spp., Erysipelothrix rhusiopathiae, and Riemerella anatipestifer. A number of studies have demonstrated increases in resistance over time for S. Pullorum/Gallinarum, M. gallisepticum, and G. anatis. Among Enterobacteriaceae, APEC isolates displayed considerably higher levels of AMR compared with S. Pullorum/Gallinarum, with prevalence of resistance over &gt;80% for ampicillin, amoxicillin, tetracycline across studies. Among the Gram-negative, non-Enterobacteriaceae pathogens, ORT had the highest levels of phenotypic resistance with median levels of AMR against co-trimoxazole, enrofloxacin, gentamicin, amoxicillin, and ceftiofur all exceeding 50%. In contrast, levels of resistance among P. multocida isolates were less than 20% for all antimicrobials. The study highlights considerable disparities in methodologies, as well as in criteria for phenotypic antimicrobial susceptibility testing and result interpretation. It is necessary to increase efforts to harmonize testing practices, and to promote free access to data on AMR in order to improve treatment guidelines as well as to monitor the evolution of AMR in poultry bacterial pathogens

Integrated Interventions to Tackle Antimicrobial Usage in Animal Production Systems: The ViParc Project in Vietnam

Antimicrobial usage and antimicrobial resistance (AMR) in animal production is now recognized to be an important contributor to the global problem of AMR. Initiatives to curb indiscriminate antimicrobial use in animal production are currently being discussed in many low- and middle-income countries. Well-designed, scientifically sound interventions aimed to tackle excessive antimicrobial usage should provide scientists and policy makers with evidence of the highest quality to guide changes in policy and to formulate better targeted research initiatives. However, since large-scale interventions are costly, they require careful planning in order not to waste valuable resources. Here, we describe the components of the ViParc project (www.viparc.org), one of the first large-scale interventions of its kind to tackle excessive antimicrobial usage in Southeast Asian animal production systems. The project has been formulated as a “randomized before-and-after controlled study” targeting small-scale poultry farms in the Mekong Delta region of Vietnam. It aims to provide farmers with a locally-adapted veterinary support service to help them reduce their reliance on antimicrobials. ViParc has been developed in the backdrop of efforts by the Government of Vietnam to develop a National Action Plan to reduce Antimicrobials in Livestock and Aquaculture. Crucially, the project integrates socio-economic analyses that will provide insights into the drivers of antimicrobial usage, as well as an assessment of the cost-effectiveness of the proposed intervention. Information generated from ViParc should help the Government of Vietnam refine its policies to curb excessive antimicrobial usage in poultry production, while lessons from ViParc will help tackle excessive antimicrobial usage in other productions systems in Vietnam and in the broader Southeast Asian region

Antimicrobial Resistance in Bacterial Poultry Pathogens: A Review

Antimicrobial resistance (AMR) is a global health threat, and antimicrobial usage and AMR in animal production is one of its contributing sources. Poultry is one of the most widespread types of meat consumed worldwide. Poultry flocks are often raised under intensive conditions using large amounts of antimicrobials to prevent and to treat disease, as well as for growth promotion. Antimicrobial resistant poultry pathogens may result in treatment failure, leading to economic losses, but also be a source of resistant bacteria/genes (including zoonotic bacteria) that may represent a risk to human health. Here we reviewed data on AMR in 12 poultry pathogens, including avian pathogenic Escherichia coli (APEC), Salmonella Pullorum/Gallinarum, Pasteurella multocida, Avibacterium paragallinarum, Gallibacterium anatis, Ornitobacterium rhinotracheale (ORT), Bordetella avium, Clostridium perfringens, Mycoplasma spp., Erysipelothrix rhusiopathiae, and Riemerella anatipestifer. A number of studies have demonstrated increases in resistance over time for S. Pullorum/Gallinarum, M. gallisepticum, and G. anatis. Among Enterobacteriaceae, APEC isolates displayed considerably higher levels of AMR compared with S. Pullorum/Gallinarum, with prevalence of resistance over >80% for ampicillin, amoxicillin, tetracycline across studies. Among the Gram-negative, non-Enterobacteriaceae pathogens, ORT had the highest levels of phenotypic resistance with median levels of AMR against co-trimoxazole, enrofloxacin, gentamicin, amoxicillin, and ceftiofur all exceeding 50%. In contrast, levels of resistance among P. multocida isolates were less than 20% for all antimicrobials. The study highlights considerable disparities in methodologies, as well as in criteria for phenotypic antimicrobial susceptibility testing and result interpretation. It is necessary to increase efforts to harmonize testing practices, and to promote free access to data on AMR in order to improve treatment guidelines as well as to monitor the evolution of AMR in poultry bacterial pathogens

Antimicrobial Usage in Animal Production: A Review of the Literature with a Focus on Low- and Middle-Income Countries

Antimicrobial use (AMU) in animal production is a key contributor to antimicrobial resistance (AMR) worldwide. As consumption of animal protein and associated animal production is forecast to increase markedly over coming years in low- and middle-income countries (LMICs), accurate monitoring of AMU has become imperative. We summarized data from 89 scientific studies reporting AMU data in animal production published in English since 1998, identified through the &lsquo;ISI Web of Knowledge&rsquo; search engine. The aims were as follows: (a) to describe methodologies and metrics used to quantify AMU; (b) to summarize qualitative (on-farm prevalence of use) and quantitative (amounts of antimicrobial active principle) data, in order to identify food animal species at the highest risk of AMU; and (c) to highlight data gaps from LMICs. Only 17/89 (19.1%) studies were conducted in LMICs. Sixty (67.3%) reported quantitative data use, with &lsquo;daily doses per animal-time&rsquo; being the most common metric. AMU was greatest in chickens (138 doses/1000 animal-days [inter quartile range (IQR) 91.1&ndash;438.3]), followed by swine (40.2 [IQR 8.5&ndash;120.4]), and dairy cattle (10.0 [IQR 5.5&ndash;13.6]). However, per kg of meat produced, AMU was highest in swine, followed by chickens and cattle. Our review highlights a large deficit of data from LMICs, and provides a reference for comparison with further surveillance and research initiatives aiming to reduce AMU in animal production globally