16. A current perspective on antimicrobial resistance in Southeast Asia
Abstract: Southeast Asia, a vibrant region that has recently undergone unprecedented economic development, is regarded as a global hotspot for the emergence and spread of antimicrobial resistance (AMR). Understanding AMR in Southeast Asia is crucial for assessing how to control AMR on an international scale. Here we (i) describe the current AMR situation in Southeast Asia, (ii) explore the mechanisms that make Southeast Asia a focal region for the emergence of AMR, and (iii) propose ways in which Southeast Asia could contribute to a global solution.
17. Antimicrobial resistance in bacterial poultry pathogens: a review
Abstract: 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.
18. Antimicrobial residues and resistance against critically important antimicrobials in non-typhoidal Salmonella from meat sold at wet markets and supermarkets in Vietnam
Abstract: Excessive antimicrobial usage and deficiencies in hygiene in meat production systems may result in undesirable human health hazards, such as the presence of antimicrobial drug residues and non-typhoidal Salmonella (NTS), including antimicrobial resistant (AMR) NTS. Recently, Vietnam has witnessed the emergence of integrated intensive animal production systems, coexisting with more traditional, locally-sourced wet markets. To date no systematic studies have been carried out to compare health hazards in beef, pork and chicken in different production systems. We aimed to: (1) estimate the prevalence of antimicrobial residues in beef, pork and chicken meat; (2) investigate the prevalence and levels of NTS contamination; and (3) investigate serovar distribution and AMR against critically important antimicrobials by animal species and type of retail (wet market vs. supermarket) in Vietnam. Fresh pork, beef and chicken meat samples (N = 357) sourced from wet markets and supermarkets in Ho Chi Minh City (HCMC), Hanoi and Dong Thap were screened for antimicrobial residues by PremiTest, and were further investigated by Charm II. Samples from HCMC (N = 113) were cultured using ISO 6579:2002/Amd 1:2007. NTS bacteria were quantified using a minimum probable number (MPN) technique. NTS isolates were assigned to serovar by Multilocus Sequence Typing (MLST), and were investigated for their phenotypic susceptibility against 32 antimicrobials. A total of 26 (7.3%) samples tested positive by PremiTest (9.5% beef, 4.1% pork and 8.4% chicken meat). Sulfonamides, tetracyclines and macrolides were detected by Charm in 3.1%, 2.8% and 2.0% samples, respectively. Overall, meat samples from wet markets had a higher prevalence of residues than those from supermarkets (9.6% vs. 2.6%) (p = 0.016). NTS were isolated from 68.4% samples from HCMC. Chicken samples from wet markets had by far the highest NTS counts (median 3.2 log MPN/g). NTS isolates displayed high levels of resistance against quinolones (52.2%) and β-lactams (49.6%), but low levels against 3rd generation cephalosporins (4.4%) and aminoglycosides (0.8%). The highest adjusted prevalence of multidrug resistance (MDR) corresponded to isolates from chicken meat and pork (OR 8.3 and 1.8, respectively) (baseline = beef). S. Kentucky was the most common serovar identified (11 from chicken, 1 from beef) and 91.7% isolates was MDR. 11/12 isolates corresponded to ST198, a worldwide-disseminated multi-resistant NTS clone. We recommend stepping up policy measures to promote responsible antimicrobial use in animal production, as well as awareness about withdrawal periods to limit the hazard of residues in animal products, and improving slaughtering/hygiene procedures to limit cross-contamination with NTS, particularly in poultry wet markets.
19. Antimicrobial usage in animal production: a review of the literature with a focus on low- and middle-income countries
Abstract: 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 ‘ISI Web of Knowledge’ 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 ‘daily doses per animal-time’ being the most common metric. AMU was greatest in chickens (138 doses/1000 animal-days [inter quartile range (IQR) 91.1–438.3]), followed by swine (40.2 [IQR 8.5–120.4]), and dairy cattle (10.0 [IQR 5.5–13.6]). 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.
20. Mortality, disease and associated antimicrobial use in commercial small-scale chicken flocks in the Mekong Delta of Vietnam
Abstract: Raising chickens in small-scale flocks following all-in-all-out management is common in the Mekong Delta of Vietnam. These flocks represent an intermediate category between backyard and intensive (industrial) farming systems. However, little is known about the occurrence and burden of disease and/or mortality in such flocks, and their potential association with antimicrobial usage (AMU). We investigated mortality, disease and weekly antimicrobial use (AMU) in 124 cycles of meat chicken flocks raised in 88 farms in the Mekong Delta of Vietnam (with a median cycle duration of 18 weeks [inter-quartile range IQR 17–20]). We visited each farm 4 times per cycle to review data collected weekly by the farmers on clinical signs, mortality, and AMU. The overall probability of disease and AMU were 0.31 (95% CI 0.29–0.32) and 0.26 (95% CI 0.24–0.28), respectively. The average weekly incidence of mortality was 2.6 (95% CI 2.2–3.0) per 100 birds. Both the probabilities of a flock experiencing disease and mortality, as well as of using antimicrobials decreased with theflock’s age. However, mortality peaked at the 5–10 week period. The only significant explanatory factors associated with presence of disease was the stage of production≥5 weeks (protective) (OR≤0.51). Factors independently associated with AMU (p< 0.05) were: (1) Number of chickens (log) (OR=1.46), (2) Stage of production≥5 weeks (OR≤0.67)(protective), (3) Cao Lanh district (OR=2.23), (4) Density of veterinary drug shops at commune level (log)(OR=1.58), and (5) Disease in flocks (OR=1.80). Factors independently associated with overall increased weekly incidence of mortality (p< 0.05) were: (1) High level of education attainment (secondary education or higher) (Hazard rate Ratio [HR]=1.70), (2) number of chickens (log) (HR=1.39), and (3) Stage of production > 5 weeks (HR≤2.14). In flocks reporting disease, AMU significantly reduced the incidence of mortality (HR=0.90). These results confirm an exceptionally high mortality in chicken flocks in the area, jeopardizing the profitability and sustainability of these small-scale farming systems. The data also suggest an association between nearby access to antimicrobials and AMU, and a high correlation of AMU over consecutive cycles. The atomized farming landscape of the Mekong Delta, the high incidence of disease and mortality, and the unrestricted and easy access to antimicrobials present major challenges to the implementation of policies aimed at AMU reductions.
21. Assessment of drivers of antimicrobial usage in poultry farms in the Mekong Delta of Vietnam: A combined participatory epidemiology and Q-sorting approach
Abstract: In the Mekong Delta of Vietnam, poultry farmers use high amounts of antimicrobials, but little is known about the drivers that influence this usage. We aimed to identify these drivers using a novel approach that combined participatory epidemiology (PE) and Q-sorting (a methodology that allows the analysis of the subjectivity of individuals facing a common phenomenon). A total of 26 semi-structured collective interviews were conducted with 125 farmers representative of the most common farming systems in the area (chickens, meat ducks, and mobile grazing ducks), as well as with 73 farmers’ advisors [veterinarians, veterinary drug shop owners, and government veterinarians/commune animal health workers (CAHWs)] in five districts of Dong Thap province (Mekong Delta). Through these interviews, 46 statements related to the antimicrobials’ perceived reliability, costs, and impact on flock health were created. These statements were then investigated on 54 individuals (28 farmers and 26 farmers’ advisors) using Q-sorting interviews. Farmers generally indicated a higher propensity for antimicrobial usage (AMU) should their flocks encounter bacterial infections (75.0–78.6%) compared with viral infections (8.3–66.7%). The most trusted sources of advice to farmers were, in decreasing order: government veterinarian/CAHWs, their own knowledge/experience, veterinary drug shop owners, and sales persons from pharmaceutical and feed companies. The highest peak of AMU took place in the early phase of the production cycle. Farmers and their advisors showed considerable heterogeneity of attitudes with regards to AMU, with, respectively, four and three discourses representing their views on AMU. Overall, farmers regarded the cost of AMU cheaper than other disease management practices implemented on their farms. However, they also believed that even though these measures were more expensive, they would also lead to more effective disease prevention. A key recommendation from this finding would be for the veterinary authorities to implement long-term sustainable training programs aiming at reducing farmers’ reliance on antimicrobials.
22. The affordability of antimicrobials for animals and humans at retail in Vietnam: A call for revising pricing policies
23. Assessing antimicrobial misuse in small-scale chicken farms in Vietnam from an observational study
Background: Antimicrobials are used by poultry farmers in Vietnam as a tool to treat and prevent infectious diseases. We aimed to determine the fraction of disease episodes likely to remain untreated due to the administration of antimicrobials on non-susceptible pathogens in chicken flocks in the Mekong Delta of Vietnam. Weekly data on antimicrobial use and clinical signs were collected from 88 randomly chosen chicken flocks over 124 full production cycles (i.e. time between restocking flocks with day-old chicks and sale for slaughter). A naïve Bayes model was trained to infer the probabilities of disease episodes having been caused by each of 24 pathogens, given the observed clinical sign profile, and expert knowledge on their relative incidence.
Results: A total of 224 disease episodes were observed, of which 44.8% were attributed to viruses (95% CI 31.1–58.4%), 54.6% (CI 40.4–68.7%) to bacteria, and 0.6% (CI 0–1.7%) to a protozoan (Eimeria spp.). Antimicrobials were more frequently administered on weeks with disease than on weeks without disease (43.3% vs. 17.8%; p < 0.001). A median of 2 [IQR 0–4] antimicrobials were used by episode. The choice of specific antimicrobials was independent on whether the flocks had disease clinical signs or not. Antimicrobials were not used in 30.3% of the episodes. The overall probability that episodes were not effectively treated was 74.2, and 53.7% when discounting cases where the inferred aetiology is viral. Considering only episodes where antimicrobials were given, these probabilities were 57.4 and 23.8% respectively.
Conclusions: This study highlights untargeted use of antimicrobials on small-scale Vietnamese chicken farms, as well as the limitations of antimicrobials as effective tools to control infectious diseases.
24. High-resolution monitoring of antimicrobial consumption in Vietnamese small-scale chicken farms highlights discrepancies between metrics
Abstract: Chicken is, among farmed species, the target of the highest levels of antimicrobial use (AMU). There are considerable knowledge gaps on how and when antimicrobials are used in commercial small-scale chicken farms. These shortcomings arise from cross-sectional study designs and poor record keeping practiced by many such farmers. Furthermore, there is a large diversity of AMU metrics, and it is not clear how these metrics relate to each other. We performed a longitudinal study on a cohort of small-scale chicken farms (n = 102) in the Mekong Delta (Vietnam), an area regarded as a hotspot of AMU, from October 2016 to May 2018. We collected data on all medicine products administered to 203 flocks with the following aims: (1) to describe types and quantities of antimicrobial active ingredients (AAIs) used; (2) to describe critical time points of AMU; and (3) to compare AMU using three quantitative metrics: (a) weight of AAIs related to bird weight at the time of treatment (mg/kg at treatment); (b) weight of AAIs related to weight of birds sold (mg/kg sold); and (c) “treatment incidence” (TI), or the number of daily doses per kilogram of live chicken [Vietnamese animal daily dose (ADDvetVN)] per 1,000 days. Antimicrobials contained in commercial feed, administered by injection (n = N = 6), or antimicrobials for human medicine (n = N = 16) were excluded. A total of 236 products were identified, containing 42 different AAIs. A total of 76.2% products contained AAIs of “critical importance” according to the World Health Organization (WHO). On average, chickens consumed 791.8 (SEM ±16.7) mg/kg at treatment, 323.4 (SEM ±11.3) mg/kg sold, and the TI was 382.6 (SEM ±5.5) per 1,000 days. AMU was more common early in the production cycle and was highly skewed, with the upper 25% quantile of flocks accounting for 60.7% of total AMU. The observed discrepancies between weight- and dose-based metrics were explained by differences in the strength of AAIs, mortality levels, and the timing of administration. Results suggest that in small-scale chicken production, AMU reduction efforts should preferentially target the early (brooding) period, which is when birds are most likely to be exposed to antimicrobials, whilst restricting access to antimicrobials of critical importance for human medicine.
25. Characterisation of gastrointestinal helminths and their impact in commercial small-scale chicken flocks in the Mekong Delta of Vietnam
Abstract: Commercial small-scale chicken farms managed as all-in-all-out but operating with low standards of hygiene/biosecurity are increasingly common in Vietnam. These conditions facilitate the transmission of gastrointestinal helminths. However, there are no published data on helminths in these systems. We aimed (1) to determine the prevalence/burden of gastrointestinal helminths in small-scale commercial flocks in the Mekong Delta region and (2) to investigate the association between worm burdens and birds’ weight and disease status. Randomly selected chickens (n = 120) from ‘normal’ flocks were investigated at the end of their production cycle (~ 18 weeks), as well as 90 chickens from ‘diseased’ flocks with signs of respiratory and/or severe disease. The gastrointestinal tract of chickens was dissected and all visible helminths were identified and counted. A total of 54.2% and 54.4% normal and diseased chickens contained helminths. Among colonised birds, the diseased ones harboured a higher mass of helminth worms than normal (healthy) birds (3.8 ± SD 8.6 g vs. 1.9 ± SD 6.3 g, respectively). Eight species were identified, including nematodes (Ascaridia galli, Cheilospirura hamulosa and Heterakis gallinarum), cestodes (Hymenolepis, Raillietina cesticillus, Raillietina echinobothrida, Raillietina tetragona) and one trematode (Echinostomatidae). Heterakis gallinarum was the most prevalent helminth (43.3% and 42.2% in normal and sick chickens, respectively), followed by A. galli (26.7% and 41.1%). Colonised chickens weighed 101.5 g less than non-colonised birds. Colonisation was higher during the rainy months (May–November) for both H. gallinarum and A. galli. Anthelminthic usage was not associated with reduced helminth burdens. We recommend upgrading cleaning and disinfection and limiting access to ranging areas to control helminths in small-scale chicken flocks.
26. Antimicrobial residues, non-typhoidal Salmonella, Vibrio spp. and associated microbiological hazards in retail shrimps purchased in Ho Chi Minh city (Vietnam)
Abstract: We investigated antimicrobial residues, non-typhoidal Salmonella (NTS), Vibrio spp. and their associated antimicrobial resistance (AMR), in shrimps locally purchased in Ho Chi Minh City (Vietnam). In addition, we investigated the relationship between AMR in NTS, Vibrio spp. and antimicrobial residue in the same sample. A total of 40 samples of shrimp heads/shells from different retail sources was cultured using ISO 6579–1:2017 (NTS) and ISO/TS 21872–1:2007 (Vibrio spp.). Phenotypic antimicrobial susceptibility was investigated using Vitek (NTS, 34 antimicrobials) and disk diffusion (Vibrio spp., 12 antimicrobials). A total of 9 (22.5%) samples contained antimicrobial residue, including tetracyclines, fluoroquinolones, sulfonamides and macrolides (in 7.5%, 7.5%, 2.5% and 2.5% of samples, respectively). Shrimp samples from supermarkets had a higher prevalence of antimicrobial residue than those purchased in street markets (50% vs. 13.3%) (p = 0.049). A total of 30 (75%) samples were contaminated with NTS. All samples contained Vibrio spp., with V. parahaemolyticus being most common (87.5% samples). A total of 58.9% NTS isolates were multidrug resistant. With regards to the highest priority, critically important antimicrobials, the highest resistance corresponded to quinolones (14.4–47.8%), followed by 3rd and 4th generation cephalosporins (3.3–7.8%). Vibrio spp. isolates were characterised by their high resistance against ampicillin (82.7%) and 3rd generation cephalosporins (8.3–16.5%). Extended Spectrum Beta-Lactamase (ESBL) activity was detected in 28.1% V. parahaemolyticus isolates. Half of ESBL-positive V. parahaemolyticus strains harboured blaCTX-M1. We found an association between the presence of residues and the number of resistances for NTS (p = 0.075) and Vibrio spp. isolates (p = 0.093) from the same sample. These findings suggest that the presence of residues may contribute to the selection of AMR in foodborne pathogens in shrimps. Authorities should strengthen policies aiming at restricting inappropriate antimicrobial usage in shrimp farming, and step up monitoring of antimicrobial residues and food-borne pathogens at retail in Vietnam.
27. Labelling and quality of antimicrobial products used in chicken flocks in the Mekong Delta of Vietnam
Background: The Mekong Delta of Vietnam is a hotspot of antimicrobial use (AMU), but there is no information on the quality of the labelling and strength of antimicro‐bial products used in poultry production.
Methods: Based on a large random sample of farms, we identified the 20 most used antimicrobial products in the area, and investigated their antimicrobial active ingredient (AAI) content by UPLC‐MS/MS (91 analytical tests).
Results: Only 17/59 (28.8%) batches contained all AAIs within 10% of the declared strength. Worryingly, 65.0% products provided in their label preparation guidelines for both therapeutic and prophylactic use. Withdrawal times for both meat and eggs were stated in 8/20 (40%) products.
Conclusion: Results highlight deficiencies in quality and labelling contents that undermine authorities’ efforts to discourage inappropriate use of antimicrobials.
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