Antibiotic resistance (ABR) is recognized as a One Health challenge because of the rapid emergence and dissemination of resistant bacteria and genes among humans, animals and the environment on a global scale. However, there is a paucity of research assessing ABR contemporaneously in humans, animals and the environment in low-resource settings. This critical review seeks to identify the extent of One Health research on ABR in low- and middle-income countries (LMICs). Existing research has highlighted hotspots for environmental contamination; food-animal production systems that are likely to harbour reservoirs or promote transmission of ABR as well as high and increasing human rates of colonization with ABR commensal bacteria such as However, very few studies have integrated all three components of the One Health spectrum to understand the dynamics of transmission and the prevalence of community-acquired resistance in humans and animals. Microbiological, epidemiological and social science research is needed at community and population levels across the One Health spectrum in order to fill the large gaps in knowledge of ABR in low-resource settings.

BackgroundUnsafe water supplies continue to raise public health concerns, especially in urban areas in low resource countries. To understand the extent of public health risk attributed to supply water in Dhaka city, Bangladesh, Escherichia coli isolated from tap water samples collected from different locations of the city were characterized for their antibiotic resistance, pathogenic properties and genetic diversity.Methodology/Principal FindingsA total of 233 E. coli isolates obtained from 175 tap water samples were analysed for susceptibility to 16 different antibiotics and for the presence of genes associated with virulence and antibiotic resistance. Nearly 36% (n = 84) of the isolates were multi-drug(≥3 classes of antibiotics) resistant (MDR) and 26% (n = 22) of these were positive for extended spectrum β-lactamase (ESBL). Of the 22 ESBL-producers, 20 were positive for bla CTX-M-15, 7 for bla OXA-1-group (all had bla OXA-47) and 2 for bla CMY-2. Quinolone resistance genes, qnrS and qnrB were detected in 6 and 2 isolates, respectively. Around 7% (n = 16) of the isolates carried virulence gene(s) characteristic of pathogenic E. coli; 11 of these contained lt and/or st and thus belonged to enterotoxigenic E. coli and 5 contained bfp and eae and thus belonged to enteropathogenic E. coli. All MDR isolates carried multiple plasmids (2 to 8) of varying sizes ranging from 1.2 to >120 MDa. Ampicillin and ceftriaxone resistance were co-transferred in conjugative plasmids of 70 to 100 MDa in size, while ampicillin, trimethoprim-sulfamethoxazole and tetracycline resistance were co-transferred in conjugative plasmids of 50 to 90 MDa. Pulsed-field gel electrophoresis analysis revealed diverse genetic fingerprints of pathogenic isolates.SignificanceMulti-drug resistant E. coli are wide spread in public water supply in Dhaka city, Bangladesh. Transmission of resistant bacteria and plasmids through supply water pose serious threats to public health in urban areas.

Background: There is increasing concern around the use of antibiotics in animal food production and the risk of transmission of antimicrobial resistance within the food chain. In many low and middle-income countries, including Bangladesh, the commercial poultry sector comprises small-scale producers who are dependent on credit from poultry dealers to buy day-old chicks and poultry feed. The same dealers also supply and promote antibiotics. The credit system is reliant upon informal relationships among multiple actors as part of social capital. This paper aims to describe dependencies and relationships between different actors within unregulated broiler poultry production systems to understand the social and contextual determinants of antibiotic use in low-resource settings. Methods: We used a cross-sectional qualitative design including in-depth interviews among purposefully selected commercial poultry farmers (n = 10), poultry dealers (n = 5), sales representatives of livestock pharmaceutical companies (n = 3) and the local government livestock officer as a key-informant (n = 1). We describe the food production cycle and practices relating to credit purchases and sales using social capital theory. Findings: Poultry dealers provide credit and information for small-scale poultry farmers to initiate and operate their business. In return for credit, farmers are obliged to buy poultry feed and medicine from their dealer and sell their market-ready poultry to that same dealer. All farms applied multiple antibiotics to poultry throughout the production cycle, including banned antibiotics such as colistin sulfate. The relationship between dealers and poultry farmers is reciprocal but mostly regulated by the dealers. Dealers were the main influencers of decision-making by farmers, particularly around antibiotic use as an integral part of the production cycle risk management. Our findings suggest that strategies to improve antibiotic stewardship and responsible use should exploit the patron-client relationship which provides the social and information network for small-scale farmers. Masud et al. Antibiotic Use in Poultry Production Conclusion: Social capital theory can be applied to the patron-client relationship observed among poultry farmers and dealers in Bangladesh to identify influences on decision making and antibiotic use. Within unregulated food production systems, strategies to promote the prudent use of antibiotics should target commercial feed producers and livestock pharmaceutical manufacturers as a first step in developing a sustainable poultry value chain.

Antimicrobial resistance is a growing public health challenge that is expected to disproportionately burden lower-and middle-income countries (LMICs) in the coming decades. Although the contributions of human and veterinary antibiotic misuse to this crisis are well-recognized, environmental transmission (via water, soil, or food contaminated with human and animal feces) has been given less attention as a global driver of antimicrobial resistance (AMR), especially in urban informal settlements in LMICs, commonly known as "shantytowns" or "slums." These settlements may be unique hotspots for environmental AMR transmission given: 1) the high density of humans, livestock, and vermin living in close proximity; 2) frequent antibiotic misuse; and 3) insufficient drinking water, drainage, and sanitation infrastructure. Here, we highlight the need for strategies to disrupt environmental AMR transmission in urban informal settlements. We propose that water and waste infrastructure improvements tailored to these settings should be evaluated for their effectiveness in limiting environmental AMR dissemination, lowering the community-level burden of antimicrobial-resistant infections, and preventing antibiotic misuse. We also suggest that additional research is directed towards developing economic and legal incentives for evaluating and implementing water and waste infrastructure in these settings. Given that almost 90% of urban population growth will occur in regions predicted to be most burdened by the AMR crisis, there is an urgent need to build effective, evidence-based policies that could influence massive investments in the built urban environment in LMICs over the next few decades. Urban informal settlements are densely populated residential areas characterized by insufficient access to improved water and sanitation services, households constructed of non-durable material, insufficient living area, insecure residential status, and high participation in the informal economy 1-3. Four of the five largest slums in the world are in Asian and African LMICs, and in some countries, over 50% of the urban population resides in these types of settlements (e.g., Bangladesh, Kenya, Ethiopia) 1. Population densities are difficult to measure in urban informal settlements but they are estimated to exceed 125,000 persons/square km in multiple major LMIC cities, including Hyderabad

Background Antimicrobial resistance (AMR) has become an emerging issue in the developing countries as well as in Bangladesh. AMR is aggravated by irrational use of antimicrobials in a largely unregulated pluralistic health system. This review presents a 'snap shot' of the current situation including existing policies and practices to address AMR, and the challenges and barriers associated with their implementation. Methods A systematic approach was adopted for identifying, screening, and selecting relevant literature on AMR situation in Bangladesh. We used Google Scholar, Pubmed, and Biomed Central databases for searching peer-reviewed literature in human, animal and environment sectors during January 2010-August 2019, and Google for grey materials from the institutional and journal websites. Two members of the study team independently reviewed these documents for inclusion in the analysis. We used a 'mixed studies review' method for synthesizing evidences from different studies. Result Of the final 47 articles, 35 were primary research, nine laboratory-based research, two review papers and one situation analysis report. Nineteen articles on human health dealt with prescribing and/or use of antimicrobials, five on self-medication, two on non-compliance of dosage, and 10 on the sensitivity and resistance patterns of antibiotics. Four papers focused on the use of antimicrobials in food animals and seven on environmental

Multidrug-resistant Escherichia coli infections are a growing public health concern. This study analyzed the possibility of contamination of commercial poultry meat (broiler and free-range) with pathogenic and or multi-resistant E. coli in retail chain poultry meat markets in India. We analyzed 168 E. coli isolates from broiler and free-range retail poultry (meat/ceca) sampled over a wide geographical area, for their antimicrobial sensitivity, phylogenetic groupings, virulence determinants, extended-spectrum-β-lactamase (ESBL) genotypes, fingerprinting by Enterobacterial Repetitive Intergenic Consensus (ERIC) PCR and genetic relatedness to human pathogenic E. coli using whole genome sequencing (WGS). The prevalence rates of ESBL producing E. coli among broiler chicken were: meat 46%; ceca 40%. Whereas, those for free range chicken were: meat 15%; ceca 30%. E. coli from broiler and free-range chicken exhibited varied prevalence rates for multi-drug resistance (meat 68%; ceca 64% and meat 8%; ceca 26%, respectively) and extraintestinal pathogenic E. coli (ExPEC) contamination (5 and 0%, respectively). WGS analysis confirmed two globally emergent human pathogenic lineages of E. coli, namely the ST131 (H30-Rx subclone) and ST117 among our poultry E. coli isolates. These results suggest that commercial poultry meat is not only an indirect public health risk by being a possible carrier of non-pathogenic multi-drug resistant (MDR)-E. coli, but could as well be the carrier of human E. coli pathotypes. Further, the free-range chicken appears to carry low risk of contamination with antimicrobial resistant and extraintestinal pathogenic E. coli (ExPEC). Overall, these observations reinforce the understanding that poultry meat in the retail chain could possibly be contaminated by MDR and/or pathogenic E. coli.

The growth inhibitory effect of a mixture of trans, trans conjugated linoleic acid isomers (t, t CLA) was investigated in a human breast cancer cell line, MCF-7, with references to c9, t11 CLA, t10, c12 CLA, and linoleic acid. The t, t CLA treatment effectively induced a cytotoxic effect in a time-dependent (0-6 days) and concentration-dependent (0-40 microM) manner, as compared to the reference and control treatments. The apoptotic parameters were measured on cells treated with 40 microM t, t CLA for 4 days. The occurrence of the characteristic morphological changes and DNA fragmentation confirmed apoptosis. The t, t CLA treatment led to an increase in the level of p53 tumor suppressor protein and Bax protein, but suppressed the expression of Bcl-2 protein. In addition, cytochrome c was released from the mitochondria into the cytosol, and the activation of caspase-3 led to the cleavage of poly(ADP-ribose) polymerase (PARP). Moreover, the composition of the linoleic and arachidonic acids was decreased in cellular membranes. These findings suggest that incorporation of t, t CLA in the membrane induces a mitochondria-mediated apoptosis that can enhance the antiproliferative effect of t, t CLA in MCF-7 cells.

Resistance to carbapenem antibiotics through the production of New Delhi metallo-␤-lactamase-1 (NDM-1) constitutes an emerging challenge in the treatment of bacterial infections. To monitor the possible source of the spread of these organisms in Dhaka, Bangladesh, we conducted a comparative analysis of wastewater samples from hospital-adjacent areas (HAR) and from community areas (COM), as well as public tap water samples, for the occurrence and characteristics of NDM-1-producing bacteria. Of 72 HAR samples tested, 51 (71%) samples were positive for NDM-1-producing bacteria, as evidenced by phenotypic tests and the presence of the bla NDM-1 gene, compared to 5 of 41 (12.1%) samples from COM samples (P Ͻ 0.001). All tap water samples were negative for NDM-1-producing bacteria. Klebsiella pneumoniae (44%) was the predominant bacterial species among bla NDM-1 -positive isolates, followed by Escherichia coli (29%), Acinetobacter spp. (15%), and Enterobacter spp. (9%). These bacteria were also positive for one or more other antibiotic resistance genes, including bla CTX-M-1 (80%), bla CTX-M-15 (63%), bla TEM (76%), bla SHV (33%), bla CMY-2 (16%), bla OXA-48-like (2%), bla OXA-1 (53%), and bla OXA-47-like (60%) genes. Around 40% of the isolates contained a qnr gene, while 50% had 16S rRNA methylase genes. The majority of isolates hosted multiple plasmids, and plasmids of 30 to 50 MDa carrying bla NDM-1 were self-transmissible. Our results highlight a number of issues related to the characteristics and source of spread of multidrug-resistant bacteria as a potential public health threat. In view of the existing practice of discharging untreated liquid waste into the environment, hospitals in Dhaka city contribute to the potential dissemination of NDM-1-producing bacteria into the community.IMPORTANCE Infections caused by carbapenemase-producing Enterobacteriaceae are extremely difficult to manage due to their marked resistance to a wide range of antibiotics. NDM-1 is the most recently described carbapenemase, and the bla NDM-1 gene, which encodes NDM-1, is located on self-transmissible plasmids that also carry a considerable number of other antibiotic resistance genes. The present study shows a high prevalence of NDM-1-producing organisms in the wastewater samples from hospitaladjacent areas as a potential source for the spread of these organisms to community areas in Dhaka, Bangladesh. The study also examines the characteristics of the isolates and their potential to horizontally transmit the resistance determinants. The significance of our research is in identifying the mode of spread of multiple-antibiotic-resistant organisms, which will allow the development of containment measures, leading to broader impacts in reducing their spread to the community.