Temporal dynamics of the fecal microbiome in female pigs from early life through estrus, parturition, and weaning of the first litter of piglets.

BACKGROUND: Age-associated changes in the gastrointestinal microbiome of young pigs have been robustly described; however, the temporal dynamics of the fecal microbiome of the female pig from early life to first parity are not well understood. Our objective was to describe microbiome and antimicrobial resistance dynamics of the fecal microbiome of breeding sows from early life through estrus, parturition and weaning of the first litter of piglets (i.e., from 3 to 53 weeks of age). RESULTS: Our analysis revealed that fecal bacterial populations in developing gilts undergo changes consistent with major maturation milestones. As the pigs progressed towards first estrus, the fecal bacteriome shifted from Rikenellaceae RC9 gut group- and UCG-002-dominated enterotypes to Treponema- and Clostridium sensu stricto 1-dominated enterotypes. After first estrus, the fecal bacteriome stabilized, with minimal changes in enterotype transition and associated microbial diversity from estrus to parturition and subsequent weaning of first litter piglets. Unlike bacterial communities, fecal fungal communities exhibited low diversity with high inter- and intra-pig variability and an increased relative abundance of certain taxa at parturition, including Candida spp. Counts of resistant fecal bacteria also fluctuated over time, and were highest in early life and subsequently abated as the pigs progressed to adulthood. CONCLUSIONS: This study provides insights into how the fecal microbial community and antimicrobial resistance in female pigs change from three weeks of age throughout their first breeding lifetime. The fecal bacteriome enterotypes and diversity are found to be age-driven and established by the time of first estrus, with minimal changes observed during subsequent physiological stages, such as parturition and lactation, when compared to the earlier age-related shifts. The use of pigs as a model for humans is well-established, however, further studies are needed to understand how our results compare to the human microbiome dynamics. Our findings suggest that the fecal microbiome exhibited consistent changes across individual pigs and became more diverse with age, which is a beneficial characteristic for an animal model system.

Effect of castration timing and weaning strategy on the taxonomic and functional profile of ruminal bacteria and archaea of beef calves.

BACKGROUND: Beef cattle experience several management challenges across their lifecycle. Castration and weaning, two major interventions in the early life of beef cattle, can have a substantial impact on animal performance. Despite the key role of the rumen microbiome on productive traits of beef cattle, the effect of castration timing and weaning strategy on this microbial community has not been formally described. We assessed the effect of four castration time windows (at birth, turnout, pre-weaning and weaning) and two weaning strategies (fence-line and truck transportation) on the rumen microbiome in a randomized controlled study with 32 male calves across 3 collection days (i.e., time points). Ruminal fluid samples were submitted to shotgun metagenomic sequencing and changes in the taxonomic (microbiota) and functional profile (metagenome) of the rumen microbiome were described. RESULTS: Using a comprehensive yet stringent taxonomic classification approach, we identified 10,238 unique taxa classified under 40 bacterial and 7 archaeal phyla across all samples. Castration timing had a limited long-term impact on the rumen microbiota and was not associated with changes in alpha and beta diversity. The interaction of collection day and weaning strategy was associated with changes in the rumen microbiota, which experienced a significant decrease in alpha diversity and shifts in beta diversity within 48 h post-weaning, especially in calves abruptly weaned by truck transportation. Calves weaned using a fence-line weaning strategy had lower relative abundance of Bacteroides, Lachnospira, Fibrobacter and Ruminococcus genera compared to calves weaned by truck transportation. Some genes involved in the hydrogenotrophic methanogenesis pathway (fwdB and fwdF) had higher relative abundance in fence-line-weaned calves post-weaning. The antimicrobial resistance gene tetW consistently represented more than 50% of the resistome across time, weaning and castration groups, without significant changes in relative abundance. CONCLUSIONS: Within the context of this study, castration timing had limited long-term effects on the rumen microbiota, while weaning strategy had short-term effects on the rumen microbiota and methane-associated metagenome, but not on the rumen resistome.

Evaluating variations in metabolic profiles during the dry period related to the time of hyperketonemia onset in dairy cows.

Hyperketonemia (HYK) in early lactation can have a different impact on health and productivity depending on the timing of HYK onset. While specific metabolites measured during the dry period may serve as biomarkers of HYK, the correlations between metabolites represent a challenge for the use of metabolic profiles dataset, and little has been explored on HYK. This exploratory cohort study aimed a) to characterize the correlations among metabolites measured during the late dry period in dairy cows, and b) to identify biomarkers in the late dry period associated with the onset of HYK at the first (wk1) and second (wk2) week of lactation. Individual blood samples from 440 Holstein dairy cows were collected at 21 ± 3 days before expected parturition. From each sample, 36 different metabolites were measured in serum and plasma. Hyperketonemia was diagnosed in wk1 and wk2 of lactation based on the blood concentration of beta-hydroxybutyrate (BHB > 1.2 mmol/L). Principal component analysis (PCA) was performed to reduce metabolites to a smaller number of uncorrelated components. Multivariable logistic regression models were applied to assess the associations between principal components (PC) and HYK at wk1 only (HYK+ wk1), wk2 only (HYK+ wk2), or both weeks (HYK+ wk1-2). The incidence of HYK was 16.2% in the first week, 13.0% in the second week, and 21.2% within the first two weeks of lactation. The results of PCA highlighted 10 PCs from which two were associated with HYK+ wk1 as compared with cows without HYK during the first two weeks of lactation (non-HYK); the PC a2 led by bilirubin and non-esterified fatty acids (OR = 1.29; 95%CI: 1.02-1.68), and the PC a5 led by alkaline phosphatase (ALP) and gamma-glutamyl transferase (GGT) (OR = 2.77; 95%CI: 1.61-4.97). There was no evidence of an association between any PC and HYK+ wk2 (vs. non-HYK cows). Cows with elevated PC a5 (led by ALP and GGT) in the dry period were 3.18 times more likely to be HYK+ wk1 than HYK+ wk2 (OR: 3.18, 95%CI: 1.34-8.73; P = 0.013). Overall, the main hypothesis generated by our exploratory study suggests that cows with biomarkers of liver dysfunction (ALP, GGT, bilirubin) assessed by PCA at 3 weeks before calving are more likely to develop HYK during the first week of lactation compared to the second week. In addition, results suggest that cows with HYK in both of the first two weeks of lactation had an overall metabolic disbalance during the onset of the late dry period, which based on PCs, encompass biomarkers related to glucogenic and ketogenic metabolic pathways as well as liver dysfunction and fatty liver. Further research is needed to determine the underlying mechanisms associated with the different adaptations between cows that develop HYK during the first and second week of lactation.

Age influences the temporal dynamics of microbiome and antimicrobial resistance genes among fecal bacteria in a cohort of production pigs.

BACKGROUND: The pig gastrointestinal tract hosts a diverse microbiome, which can serve to select and maintain a reservoir of antimicrobial resistance genes (ARG). Studies suggest that the types and quantities of antimicrobial resistance (AMR) in fecal bacteria change as the animal host ages, yet the temporal dynamics of AMR within communities of bacteria in pigs during a full production cycle remains largely unstudied. RESULTS: A longitudinal study was performed to evaluate the dynamics of fecal microbiome and AMR in a cohort of pigs during a production cycle; from birth to market age. Our data showed that piglet fecal microbial communities assemble rapidly after birth and become more diverse with age. Individual piglet fecal microbiomes progressed along similar trajectories with age-specific community types/enterotypes and showed a clear shift from E. coli/Shigella-, Fusobacteria-, Bacteroides-dominant enterotypes to Prevotella-, Megaspheara-, and Lactobacillus-dominated enterotypes with aging. Even when the fecal microbiome was the least diverse, the richness of ARGs, quantities of AMR gene copies, and counts of AMR fecal bacteria were highest in piglets at 2 days of age; subsequently, these declined over time, likely due to age-related competitive changes in the underlying microbiome. ARGs conferring resistance to metals and multi-compound/biocides were detected predominately at the earliest sampled ages. CONCLUSIONS: The fecal microbiome and resistome-along with evaluated descriptors of phenotypic antimicrobial susceptibility of fecal bacteria-among a cohort of pigs, demonstrated opposing trajectories in diversity primarily driven by the aging of pigs.

The impacts of viral infection and subsequent antimicrobials on the microbiome-resistome of growing pigs.

BACKGROUND: Antimicrobials are used in food-producing animals for purposes of preventing, controlling, and/or treating infections. In swine, a major driver of antimicrobial use is porcine reproductive and respiratory syndrome (PRRS), which is caused by a virus that predisposes infected animals to secondary bacterial infections. Numerous antimicrobial protocols are used to treat PRRS, but we have little insight into how these treatment schemes impact antimicrobial resistance (AMR) dynamics within the fecal microbiome of commercial swine. The aim of this study was to determine whether different PRRS-relevant antimicrobial treatment protocols were associated with differences in the fecal microbiome and resistome of growing pigs. To accomplish this, we used a metagenomics approach to characterize and compare the longitudinal wean-to-market resistome and microbiome of pigs challenged with PRRS virus and then exposed to different antimicrobial treatments, and a group of control pigs not challenged with PRRS virus and having minimal antimicrobial exposure. Genomic DNA was extracted from pen-level composite fecal samples from each treatment group and subjected to metagenomic sequencing and microbiome-resistome bioinformatic and statistical analysis. Microbiome-resistome profiles were compared over time and between treatment groups. RESULTS: Fecal microbiome and resistome compositions both changed significantly over time, with a dramatic and stereotypic shift between weaning and 9 days post-weaning (dpw). Antimicrobial resistance gene (ARG) richness and diversity were significantly higher at earlier time points, while microbiome richness and diversity were significantly lower. The post-weaning shift was characterized by transition from a Bacteroides-dominated enterotype to Lactobacillus- and Streptococcus-dominated enterotypes. Both the microbiome and resistome stabilized by 44 dpw, at which point the trajectory of microbiome-resistome maturation began to diverge slightly between the treatment groups, potentially due to physical clustering of the pigs. Challenge with PRRS virus seemed to correspond to the re-appearance of many very rare and low-abundance ARGs within the feces of challenged pigs. Despite very different antimicrobial exposures after challenge with PRRS virus, resistome composition remained largely similar between the treatment groups. Differences in ARG abundance between the groups were mostly driven by temporal changes in abundance that occurred prior to antimicrobial exposures, with the exception of ermG, which increased in the feces of treated pigs, and was significantly more abundant in the feces of these pigs compared to the pigs that did not receive post-PRRS antimicrobials. CONCLUSIONS: The fecal microbiome-resistome of growing pigs exhibited a stereotypic trajectory driven largely by weaning and physiologic aging of the pigs. Events such as viral illness, antimicrobial exposures, and physical grouping of the pigs exerted significant yet relatively minor influence over this trajectory. Therefore, the AMR profile of market-age pigs is the culmination of the life history of the individual pigs and the populations to which they belong. Disease status alone may be a significant driver of AMR in market-age pigs, and understanding the interaction between disease processes and antimicrobial exposures on the swine microbiome-resistome is crucial to developing effective, robust, and reproducible interventions to control AMR. Video Abstract.

A longitudinal investigation of the effects of age, dietary fiber type and level, and injectable antimicrobials on the fecal microbiome and antimicrobial resistance of finisher pigs.

Age and diet are among the factors that influence the community composition of the fecal microbiome. Additionally, antimicrobial use can alter the composition of bacterial communities. An 86-d study with finisher pigs aimed to evaluate age-related dynamics (day 98 to 177 of age), effects of types and levels of dietary fiber, and injectable antimicrobials on the fecal microbiome and antimicrobial resistance (AMR) was conducted. A total of 287 pigs, housed in 36 pens, with 7 to 8 pigs per pen, fed a corn grain and soybean meal-based basal diet, formulated to contain 8.7% neutral detergent fiber (NDF), were randomly assigned to one of three treatments: 1) basal diet with no supplement, 2) basal diet supplemented with 20% distillers dried grains with solubles (DDGS) formulated to contain 13.6% NDF, or 3) basal diet supplemented with 14.5% sugar beet pulp (SBP) formulated to contain 13.6% NDF. Five finisher pigs from each treatment group were selected randomly, and fecal samples were collected on days 98, 110, 144, and 177 of age. In addition, fecal samples were collected from pigs that were injected intramuscularly ceftiofur hydrochloride or penicillin G on days 1 and 3 along with pen-mate-untreated controls on day 1. Fecal samples were subjected to 16S rRNA amplicon-based microbiome analysis and culture methods to quantify the abundance of total AMR coliforms and enterococci populations. The alpha-diversity, such as species richness, increased with age, and the overall bacterial composition changed with age (P =0.001) and diet (P = 0.001). Diet-associated shifts in the specific bacterial taxa were observed. The richness, diversity, and evenness of bacterial taxa did not differ between pigs that were injected with ceftiofur vs. their untreated pen mates or by dietary treatments but differed in pigs that received penicillin G injection. Both antimicrobial treatments contributed to changes in the overall fecal bacterial composition at the genus level. Collectively, the data demonstrate that both age and the diet (control vs. DDGS-, control vs. SBP-, or DDGS- vs. SBP-based diets) were associated with the overall bacterial community composition, and the impact of age on variations in fecal microbiome composition was greater than the diet. Antibiotic treatment had minimal effect on bacterial diversity and relative abundance of taxa. Furthermore, diets and antimicrobial treatment had minimal impact on the overall counts of AMR coliforms and enterococci populations in feces.

Bacterial communities in the gut and the feces are strongly influenced by a number of factors, particularly the age of the animal and the diet. In addition, antibiotic administration routinely used to treat bacterial diseases can also affect the community composition. A study with finisher pigs was conducted to evaluate age-related changes, effects of types­distiller's dried grains with solubles (DGGS) or sugar beet pulp (SBP)­and levels of dietary fiber, and injectable antibiotics on the fecal bacterial composition and antibiotic resistance in fecal bacteria. Fecal samples were collected from five pigs in each of the three dietary treatment groups, control diet with no supplement or supplemented with DDGS or SBP, on days 98, 110, 144, and 177 of age and on days 1 and 3 after the first injection of antibiotics, ceftiofur or penicillin G. Samples were analyzed to identify the bacterial community composition and prevalence of antibiotic resistance in fecal bacteria. Data generated suggested that the overall bacterial composition changed with age and diet, and age appeared to have a greater impact than diet. Antibiotics had only a modest impact on the bacterial community and had minimum impact on antibiotic resistance of fecal bacteria.

The microbiome of common bedding materials before and after use on commercial dairy farms.

BACKGROUND: Bovine mastitis is one of the most economically important diseases affecting dairy cows. The choice of bedding material has been identified as an important risk factor contributing to the development of mastitis. However, few reports examine both the culturable and nonculturable microbial composition of commonly used bedding materials, i.e., the microbiome. Given the prevalence of nonculturable microbes in most environments, this information could be an important step to understanding whether and how the bedding microbiome acts as a risk factor for mastitis. Therefore, our objective was to characterize the microbiome composition and diversity of bedding material microbiomes, before and after use. METHODS: We collected 88 bedding samples from 44 dairy farms in the U.S. Unused (from storage pile) and used (out of stalls) bedding materials were collected from four bedding types: new sand (NSA), recycled manure solids (RMS), organic non-manure (ON) and recycled sand (RSA). Samples were analyzed using 16S rRNA sequencing of the V3-V4 region. RESULTS: The overall composition as well as the counts of several microbial taxa differed between bedding types, with Proteobacteria, Actinobacteria, Bacteroidetes and Firmicutes dominating across all types. Used bedding contained a significantly different microbial composition than unused bedding, but the magnitude of this difference varied by bedding type, with RMS bedding exhibiting the smallest difference. In addition, positive correlations were observed between 16S rRNA sequence counts of potential mastitis pathogens (bacterial genera) and corresponding bedding bacterial culture data. CONCLUSION: Our results strengthen the role of bedding as a potential source of mastitis pathogens. The consistent shift in the microbiome of all bedding types that occurred during use by dairy cows deserves further investigation to understand whether this shift promotes pathogen colonization and/or persistence, or whether it can differentially impact udder health outcomes. Future studies of bedding and udder health may be strengthened by including a microbiome component to the study design.

Modelling the antimicrobial pharmacodynamics for bacterial strains with versus without acquired resistance to fluoroquinolones or cephalosporins.

OBJECTIVES: Antimicrobial resistance threatens therapeutic options for human and animal bacterial diseases worldwide. Current antimicrobial treatment regimens were designed against bacterial strains that were fully susceptible to them. To expand the useable lifetime of existing antimicrobial drug classes by modifying treatment regimens, data are needed on the antimicrobial pharmacodynamics (PD) against strains with reduced susceptibility. In this study, we generated and mathematically modelled the PD of the fluoroquinolone ciprofloxacin and the cephalosporin ceftriaxone against non-typhoidal Salmonella enterica subsp. enterica strains with varying levels of acquired resistance. METHODS: We included Salmonella strains across categories of reduced susceptibility to fluoroquinolones or cephalosporins reported to date, including isolates from human infections, food-animal products sold in retail, and food-animal production. We generated PD data for each drug and strain via time-kill assay. Mathematical models were compared in their fit to represent the PD. The best-fit model's parameter values across the strain susceptibility categories were compared. RESULTS: The inhibitory baseline sigmoid Imax (or Emax) model was best fit for the PD of each antimicrobial against a majority of the strains. There were statistically significant differences in the PD parameter values across the strain susceptibility categories for each antimicrobial. CONCLUSION: The results demonstrate predictable multiparameter changes in the PD of these first-line antimicrobials depending on the Salmonella strain's susceptibility phenotype and specific genes conferring reduced susceptibility. The generated PD parameter estimates could be used to optimise treatment regimens against infections by strains with reduced susceptibility.

Faecal concentrations of ceftiofur metabolites in finisher pigs administered intramuscularly with ceftiofur.

The objective of this study was to determine the effects of dietary fibre level and source on faecal ceftiofur metabolites concentrations after intramuscular administration of therapeutic ceftiofur hydrochloride in finisher pigs. Pens of finisher pigs (n = 36), with an equal number of barrows and gilts, were randomly assigned to 1 of 3 dietary treatment groups: basal diet composed of corn grain and soy bean meal with no supplement and formulated to contain 8.7% neutral detergent fibre (NDF), supplemented with 20% distillers dried grains with solubles (a byproduct of the ethanol production from corn grain) formulated to contain 13.6% NDF, primarily insoluble fibre or supplemented with 14.5% sugar beet pulp formulated to contain 13.6% NDF. Faecal samples were collected 6-8 hr after ceftiofur injection from treated and untreated pen-mate pigs on days 1 and 3 of the 3-day treatment regimen. Faecal concentrations of ceftiofur metabolites, including the major metabolite, desfuroylceftiofur, were analysed by reverse-phase high pressure liquid chromatography with ultraviolet detection. Overall, the faecal concentrations of ceftiofur metabolites did not differ significantly between the dietary treatments. The mean concentrations of metabolites tended to be lower (p = .1) on day 3 compared to day 1 of the 3-day treatment regimen. Faecal concentrations of metabolites were not affected by the gender of the finisher pigs. The concentrations of ceftiofur metabolites in the faeces are likely reflective of the microbial activity in the hindgut. Our data suggest that the fibre level and source used in the study did not affect the faecal concentrations of ceftiofur metabolites.

Perception and Challenges of Preventive Measures of COVID-19 Among Nepalese Frontline Health Professionals: An Unexplored Realism.

Background: A new coronavirus causes COVID-19, a developing respiratory illness. Unfortunately, there is little information assessing healthcare workers' understanding of technology and preventative strategies during the Nepalese epidemic. Researchers from other subspecialties uncovered some mythical thoughts. As a result, we decided to put it to the test with healthcare personnel on the front lines. The research also looked at the problems experienced by frontline health care personnel (HCP) because of the COVID-19 strategic shift in work policy. Methods: Nepalese healthcare workers participated in web-based cross-sectional research. A pre-tested, structured questionnaire utilizing a Google form was used to get self-informed, digitally typed consent, and examine critical perspectives and problems with current technology and COVID-19 prevention efforts. Results: In total, 243 participants with mean age of 29.66 ± 7.61 years agreed to participate and were doctors (n = 27), health assistants (n = 2), medical intern doctors (n = 1), paramedical (n = 139), pharmacy (n = 1), and paramedical interns (n = 73) in this study. The calculated mean percentage score of knowledge on instruments and tools was 73.64 (SD ± 10.43) %, and perception on COVID-19 transmission and control was 70.06 (SD ± 18.30) %. At various levels, frontline health workers faced significant challenges, including the adoption of digital health technology. Conclusion: Frontline HCPs are anticipated to have updated knowledge from what the study has outlined. It is recommended to follow national guidelines. Policies should be put in place so that every frontline worker can demonstrate high standards in prevention, control, and equipment use that do not create misinformation among HCPs. Throughout, support for digital health materials and disease control methods for HCPs is essential.

Why has COVID-19 not hit the countries like Nepal yet?

Noble CORONA Virus (COVID-19) is an infectious disease similar form of pneumonia/ SARS-CoV-2- impacting globally. The fear of coronavirus looks pandemic, but its severity is uncertain. Nepal was one of the first nine countries outside of China to report a COVID-19 case. Also, its unpredictability of mode or range of surface, the lifespan of the virus, objects of transmission (a distance of air/air currents, living duration in air, humidity, duration on objects, surface). The first case was found in Wuhan in December 2019 in China. The purpose is to summarize the current information about COVID-19 and to explore in terms of why Nepal is not hitting severely, while other countries are on death toll? We summarized the published articles form the web sources and news, Academic Journals, Ministry of health and population Nepal, WHO/CDC update reports/guidelines, Google search engine. Thematic analysis is made to explore the situation. Although, Nepal has a lack of health services, testing kits, advance lab and protecting equipment (PPE), why COVID-19 does not hit Nepal than China, Europe and North America, it still tremendous uncertainty. Is lockdown, isolation, social distance and quarantine the best ways of prevention? The hypothesis is floating globally - do BCG vaccinated countries are safer than non-user OR due to not having enough kits to screen populations at risk for the virus - while lack of testing a big cause for missing case OR Nepalese have better immune systems? It has attracted global attention. We believe that the COVID-19 is still evolving and it is too early to predict of an outbreak in Nepal. The government needs to increase funding for local health departments, begin planning for future epidemics and be prepared to bolster the economy by supporting consumer spending the midst of a serious outbreak. COVID-19 is a serious health challenge for Nepal, but so far the number of death has been lower than was foretell. It is, therefore essential to carry out more scientific evidence to explore results. Nepalese health services need to maintain up than today and follow lockdown, isolation, social distance and an advance screening test kit through the country.

Can the use of older-generation beta-lactam antibiotics in livestock production over-select for beta-lactamases of greatest consequence for human medicine? An in vitro experimental model.

Though carbapenems are not licensed for use in food animals in the U.S., carbapenem resistance among Enterobacteriaceae has been identified in farm animals and their environments. The objective of our study was to determine the extent to which older-generation ß-lactam antibiotics approved for use in food animals in the U.S. might differentially select for resistance to antibiotics of critical importance to human health, such as carbapenems. Escherichia coli (E. coli) strains from humans, food animals, or the environment bearing a single ß-lactamase gene (n = 20 each) for blaTEM-1, blaCMY-2, and blaCTX-M-* or else blaKPC/IMP/NDM (due to limited availability, often in combination with other bla genes), were identified, along with 20 E. coli strains lacking any known beta-lactamase genes. Baseline estimates of intrinsic bacterial fitness were derived from the population growth curves. Effects of ampicillin (32 µg/mL), ceftriaxone (4 µg/mL) and meropenem (4 µg/mL) on each strain and resistance-group also were assessed. Further, in vitro batch cultures were prepared by mixing equal concentrations of 10 representative E. coli strains (two from each resistance gene group), and each mixture was incubated at 37°C for 24 hours in non-antibiotic cation-adjusted Mueller-Hinton II (CAMH-2) broth, ampicillin + CAMH-2 broth (at 2, 4, 8, 16, and 32 µg/mL) and ceftiofur + CAMH-2 broth (at 0.5, 1, 2, 4, and 8µg/mL). Relative and absolute abundance of resistance-groups were estimated phenotypically. Line plots of the raw data were generated, and non-linear Gompertz models and multilevel mixed-effect linear regression models were fitted to the data. The observed strain growth rate distributions were significantly different across the groups. AmpC strains (i.e., blaCMY-2) had distinctly less robust (p < 0.05) growth in ceftriaxone (4 µg/mL) compared to extended-spectrum beta-lactamase (ESBL) producers harboring blaCTX-M-*variants. With increasing beta-lactam antibiotic concentrations, relative proportions of ESBLs and CREs were over-represented in the mixed bacterial communities; importantly, this was more pronounced with ceftiofur than with ampicillin. These results indicate that aminopenicillins and extended-spectrum cephalosporins would be expected to propagate carbapenemase-producing Enterobacteriaceae in food animals if and when Enterobacteriaceae from human health care settings enter the food animal environment.

Nepal: country report on children's environmental health.

Although Nepal is a country rich in natural beauty, along with an abundance of natural resources, the children of this diverse nation still face several serious health issues arising from their own environment (water pollution, air pollution, chemical pollution, solid waste issues and drainage issues). Nepal also ranks as a highly vulnerable country to the adverse impacts of climate change. Children are more vulnerable to various infections for immunological, physiological and social reasons. Their inherent immunity diminishes within months after birth. There are risk factors for the development of various diseases, e.g. unsafe drinking water and lack of sanitation, which contribute to diarrheal diseases, trachoma, hookworm and amoebic dysentery; another risk factor is indoor air pollution. The infant mortality rate (IMR) is higher in rural areas with 55 per 1000 live births, compared to urban areas with 38 per 1000 live births. Likewise, the under-5-year-old mortality rate (MR) in rural areas is 64 and that in urban areas is 45 per 1000 live births. Around 12% of the population suffer from chronic respiratory diseases, according to a recent study exploring the situation in Kathmandu. Pneumonia is a leading cause of mortality among children under 5 years of age in Nepalese hospitals. Children under 5 are more prone to the ill effects of polluted environments because of their less well-developed immune system. In addition, the school environment is not sufficiently healthy due to the distribution of unsafe drinking water and poor sanitation supply systems. In Nepal, mainly in the 20 Terai districts, arsenic contamination of groundwater is a public health problem. Underground water is used as drinking water in those areas, but without purification - the estimate is that around 0.5 million people live at the risk of arsenic poisoning. Within a span of 200 km from north to south, the climate of Nepal varies from arctic to tropical. The annual average air pollution concentration is 5 times above the World Health Organization (WHO) air quality guidelines, which poses a serious health risk to hundreds of thousands of Nepalese people: 133 out of 1,000,000 deaths each year are related to air pollution. Dramatically, Kathmandu city is a silent killer to walk around due to air pollution, and its air quality is ranked as the worst out of 180 countries, according to the 2018 Environmental Performance Index. However, insufficient studies have been conducted to explore children's environmental health issues. It is therefore essential to carry out more scientific studies to explore the issues of children's environmental health as environmental health problems in children are serious in the Nepalese context.

Age Dependence of Antimicrobial Resistance Among Fecal Bacteria in Animals: A Scoping Review.

Introduction: A phenomenon of decreasing antimicrobial resistance (AMR) among fecal bacteria as food animals age has been noted in multiple field studies. We conducted a scoping review to summarize the extent, range, and nature of research activity and the data for the following question: "does AMR among enteric/fecal bacteria predictably shift as animals get older?". Methods: This review followed a scoping review methodology framework. Pertinent literature published up until November 2018 for all animals (except humans) was retrieved using keyword searches in two online databases, namely, PubMed® and the Web of Science™ Core Collection, without filtering publication date, geographic location, or language. Data were extracted from the included studies, summarized, and plotted. Study quality was also assessed using the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) guidelines for all included papers. Results: The publications with detailed relevant data (n = 62) in food animals, poultry, and dogs were identified. These included longitudinal studies (n = 32), cross-sectional studies of different age groups within one food animal production system or small-animal catchment area (n = 16), and experimental or diet trials (n = 14). A decline in host-level prevalence and/or within-host abundance of AMR among fecal bacteria in production beef, dairy cattle, and swine was reported in nearly two-thirds (65%) of the identified studies in different geographic locations from the 1970's to 2018. Mixed results, with AMR abundance among fecal bacteria either increasing or decreasing with age, have been reported in poultry (broiler chicken, layer, and grow-out turkey) and dogs. Conclusions: Quantitative synthesis of the data suggests that the age-dependent AMR phenomenon in cattle and swine is observed irrespective of geographic location and specific production practices. It is unclear whether the phenomenon predates or is related to antimicrobial drug use. However, almost 50% of the identified studies predate recent changes in antimicrobial drug use policy and regulations in food animals in the United States and elsewhere.

Variation in fluoroquinolone pharmacodynamic parameter values among isolates of two bacterial pathogens of bovine respiratory disease.

To design an antimicrobial treatment regimen for a bacterial disease, data on the drug pharmacodynamics (PD) against selected drug-susceptible strains of the pathogen are used. The regimen is applied across such strains in the field, assuming the PD parameter values remain the same. We used time-kill experiments and PD modeling to investigate the fluoroquinolone enrofloxacin PD against different isolates of two bovine respiratory disease pathogens: four Mannheimia haemolytica and three Pasteurella multocida isolates. The models were fitted as mixed-effects non-linear regression; the fixed-effects PD parameter values were estimated after accounting for random variation among experimental replicates. There was both inter- and intra- bacterial species variability in the PD parameters Hill-coefficient and Emax (maximal decline of bacterial growth rate), with more variable PD responses among M. haemolytica than among P. multocida isolates. Moreover, the Hill-coefficient was correlated to the isolate's maximal population growth rate in the absence of antimicrobial exposure (a.k.a. specific growth rate; Spearman's ρ = 0.98, p-value = 0.003, n = 6 isolates excluding one outlier). Thus, the strain's properties such as growth potential may impact its PD responses. This variability can have clinical implications. Modifying the treatment regimen depending on phenotypic properties of the pathogen strain causing disease may be a precision medicine approach.

Epidemiology, Impact and Control of Rabies in Nepal: A Systematic Review.

BACKGROUND: Rabies is a vaccine-preventable viral zoonosis belonging to the group of neglected tropical diseases. Exposure to a rabid animal may result in a fatal acute encephalitis if effective post-exposure prophylaxis is not provided. Rabies occurs worldwide, but its burden is disproportionately high in developing countries, including Nepal. We aimed to summarize current knowledge on the epidemiology, impact and control of rabies in Nepal. METHODS: We performed a systematic review of international and national scientific literature and searched grey literature through the World Health Organization Digital Library and the library of the National Zoonoses and Food Hygiene Research Centre, Nepal, and through searching Google and Google Scholar. Further data on animal and human rabies were obtained from the relevant Nepalese government agencies. Finally, we surveyed the archives of a Nepalese daily to obtain qualitative information on rabies in Nepal. FINDINGS: So far, only little original research has been conducted on the epidemiology and impact of rabies in Nepal. Per year, rabies is reported to kill about 100 livestock and 10-100 humans, while about 1,000 livestock and 35,000 humans are reported to receive rabies post-exposure prophylaxis. However, these estimates are very likely to be serious underestimations of the true rabies burden. Significant progress has been made in the production of cell culture-based anti-rabies vaccine and rabies immunoglobulin, but availability and supply remain a matter of concern, especially in remote areas. Different state and non-state actors have initiated rabies control activities over the years, but efforts typically remained focalized, of short duration and not harmonized. Communication and coordination between veterinary and human health authorities is limited at present, further complicating rabies control in Nepal. Important research gaps include the reporting biases for both human and animal rabies, the ecology of stray dog populations and the true contribution of the sylvatic cycle. INTERPRETATION: Better data are needed to unravel the true burden of animal and human rabies. More collaboration, both within the country and within the region, is needed to control rabies. To achieve these goals, high level political commitment is essential. We therefore propose to make rabies the model zoonosis for successful control in Nepal.

Cross-sectional serosurvey and associated factors of bluetongue virus antibodies presence in small ruminants of Nepal.

BACKGROUND: Bluetongue (BT) is an infectious, insect-borne viral disease primarily affecting sheep and occasionally cattle and goats. In Nepal, BT is an emerging disease of economic importance. The objective of this study was to estimate the seroprevalence of BT virus (BTV) in small ruminants of two eco-zones of Nepal, Hills and Terai, and to identify the factors associated with virus exposure. We conducted a cross-sectional serosurvey from March 2012 through February 2013 by sampling 318 small ruminants (184 sheep and 134 goats) from seven clusters (villages) of selected vulnerable communities of Chitwan (Terai) and Lamjung (Hills) Districts of Nepal. RESULTS: Of the 318 serum sample tested, 27.9% [95% confidence interval (CI): 23.1- 33.2] were positive for BTV antibodies (25.0% sheep and 31.3% goats). Bivariate analysis indicated a positive association between seroconversion to BTV and flock size, eco-zone, breed, and contact history with cattle. Additionally, in female sheep and goats, a history of abortion was positively associated with seropositivity to BTV. However, the final multivariable model, after controlling for clustering of animals within the villages, identified only history of abortion and breed as the factors significantly associated with BT seropositivity in female sheep and goats. Based on this model, female small ruminants having a history of abortion were more likely to be seropositive compared to those without such history [Odds Ratio (OR) = 46.14 (95% CI: 11.66- 182.5)]. Exotic breeds were more likely to be seropositive compared to indigenous breeds [OR = 9.04 (95% CI: 3.08- 24.46)] while the risk for BTV seropositivity was not significantly different between indigenous and cross breeds. CONCLUSIONS: Our results showed that nearly a quarter of small ruminants in two regions of Nepal were seropositive for BTV, indicating wide exposure of small ruminants to this pathogen. We identified history of abortion and breed as factors significantly associated with the seropositivity of BTV. We recommend that surveillance for BTV infection in Nepal be strengthened and that it would be valuable to enhance the education of farmers about the possible impacts of this disease.