Antibiotic use plays a major role in the emerging public health crisis of antibiotic resistance. Although the majority of antibiotic use occurs in agricultural settings, relatively little attention has been paid to how antibiotic use in farm animals contributes to the overall problem of antibiotic resistance. The aim of this review is to summarize literature on the role of antibiotics in the development of resistance and its risk to human health. We searched multiple databases to identify major lines of argument supporting the role of agricultural antibiotic use in the development of resistance and to summarize existing regulatory and policy documents. Several lines of reasoning support the conclusion that agricultural antibiotics are associated with resistance, yet most public policy is based on expert opinion and consensus. Finally, we propose strategies to address current gaps in knowledge.
Zoonotic infectious diseases have been an important concern to humankind for more than 10,000 years. Today, approximately 75% of newly emerging infectious diseases (EIDs) are zoonoses that result from various anthropogenic, genetic, ecologic, socioeconomic, and climatic factors. These interrelated driving forces make it difficult to predict and to prevent zoonotic EIDs. Although significant improvements in environmental and medical surveillance, clinical diagnostic methods, and medical practices have been achieved in the recent years, zoonotic EIDs remain a major global concern, and such threats are expanding, especially in less developed regions. The current Ebola epidemic in West Africa is an extreme stark reminder of the role animal reservoirs play in public health and reinforces the urgent need for globally operationalizing a One Health approach. The complex nature of zoonotic diseases and the limited resources in developing countries are a reminder that the need for implementation of Global One Health in low-resource settings is crucial. The Veterinary Public Health and Biotechnology (VPH-Biotec) Global Consortium launched the International Congress on Pathogens at the Human-Animal Interface (ICOPHAI) in order to address important challenges and needs for capacity building. The inaugural ICOPHAI (Addis Ababa, Ethiopia, 2011) and the second congress (Porto de Galinhas, Brazil, 2013) were unique opportunities to share and discuss issues related to zoonotic infectious diseases worldwide. In addition to strong scientific reports in eight thematic areas that necessitate One Health implementation, the congress identified four key capacity-building needs: (1) development of adequate science-based risk management policies, (2) skilled-personnel capacity building, (3) accredited veterinary and public health diagnostic laboratories with a shared database, and (4) improved use of existing natural resources and implementation. The aim of this review is to highlight advances in key zoonotic disease areas and the One Health capacity needs.
Erythromycin and tylosin are commonly used in animal production, and such use is perceived to contribute to the overall antimicrobial resistance (AR) reservoirs. Quantitative measurements of this type of AR reservoir in microbial communities are required to understand AR ecology (e.g., emergence, persistence, and dissemination). We report here the development, validation, and use of six real-time PCR assays for quantifying six classes of erm genes (classes A through C, F, T, and X) that encode the major mechanism of resistance to macrolides-lincosamidesstreptogramin B (MLS B ). These real-time PCR assays were validated and used in quantifying the six erm classes in five types of samples, including those from bovine manure, swine manure, compost of swine manure, swine waste lagoons, and an Ekokan upflow biofilter system treating hog house effluents. The bovine manure samples were found to contain much smaller reservoirs of each of the six erm classes than the swine manure samples. Compared to the swine manure samples, the composted swine manure samples had substantially reduced erm gene abundances (by up to 7.3 logs), whereas the lagoon or the biofilter samples had similar erm gene abundances. These preliminary results suggest that the methods of manure storage and treatment probably have a substantial impact on the persistence and decline of MLS B resistance originating from food animals, thus likely affecting the dissemination of such resistance genes into the environment. The abundances of these erm genes appeared to be positively correlated with those of the tet genes determined previously among these samples. These real-time PCR assays provide a rapid, quantitative, and cultivation-independent measurement of six major classes of erm genes, which should be useful for ecological studies of AR.
The rapid emergence of antibiotic-resistant (ART) pathogens is a major threat to public health. While the surfacing of ART food-borne pathogens is alarming, the magnitude of the antibiotic resistance (AR) gene pool in food-borne commensal microbes is yet to be revealed. Incidence of ART commensals in selected retail food products was examined in this study. The presence of 10(2)-10(7) CFU of ART bacteria per gram of foods in many samples, particularly in ready-to-eat, 'healthy' food items, indicates that the ART bacteria are abundant in the food chain. AR-encoding genes were detected in ART isolates, and Streptococcus thermophilus was found to be a major host for AR genes in cheese microbiota. Lactococcus lactis and Leuconostoc sp. isolates were also found carrying AR genes. The data indicate that food could be an important avenue for ART bacterial evolution and dissemination. AR-encoding plasmids from several food-borne commensals were transmitted to Streptococcus mutans via natural gene transformation under laboratory conditions, suggesting the possible transfer of AR genes from food commensals to human residential bacteria via horizontal gene transfer.
We report here the development, validation, and use of three real-time PCR assays to quantify the abundance of the following three groups of tetracycline resistance genes: tet(A) and tet(C); tet(G); and tet genes encoding ribosomal protection proteins, including tet(M), tet(O), tetB(P), tet(Q), tet(S), tet(T), and tet(W). The assays were validated using known numbers of sample-derived tet gene templates added to microbiome DNA. These assays are both precise and accurate over at least 6 log tet gene copies. New tet gene variants were also identified from cloned tet amplicons as part of this study. The utility of these real-time PCR assays was demonstrated by quantifying the three tet gene groups present in bovine and swine manures, composts of swine manure, lagoons of hog house effluent, and samples from an Ekokan upflow biofilter system treating hog house effluent. The bovine manures were found to contain fewer copies of all three groups of tet genes than the swine manures. The composts of swine manures had substantially reduced tet gene abundance (up to 6 log), while lagoon storage or the upflow biofilter had little effect on tet gene abundance. These results suggest that the method of manure storage and treatment may have a substantial impact on the persistence and dissemination of tet genes in agricultural environments. These real-time PCR assays provide rapid, quantitative, cultivation-independent measurements of 10 major classes of tet genes, which should be useful for ecological studies of antibiotic resistance.
The purpose of this study was to evaluate the association between milk urea nitrogen (MUN) and fertility of dairy cows using field data. The data came from 24 dairy herds belonging to Ohio Dairy Herd Improvement Cooperative Inc. Reproductive data and MUN measurements from cows that calved between June 1998 and May 1999 and that had been bred at least once were included in the study. Survival analysis, using the Cox proportional hazards model, was performed and days from calving to conception or to the end of the study was used as the outcome. Cows that had not been reported pregnant during the study were considered censored. The mean of monthly MUN values of cows before conception (or the end of the study for censored cows) was used to reflect the MUN status of a cow. Animals were categorized into quartiles based on MUN values in these data. Parity, calving season, peak milk yield, number of services, and herd were included in the models as fixed effects. Cows with MUN levels below 10.0 were 2.4 times more likely and cows with MUN levels between 10.0 and 12.7 mg/dl were 1.4 times more likely to be confirmed pregnant than cows with MUN values above 15.4 mg/dl. Our results indicate that increasing MUN levels appear to be negatively related to dairy cow fertility and are associated with a lower risk of detectable pregnancy at herd checks. They also suggest that the levels of MUN that are adversely associated with fertility might be lower than reported earlier.
Our observation of a herd-level but not an individual cow-level association between ceftiofur use and isolation of E coli with reduced ceftriaxone susceptibility from fecal samples suggests that interventions to reduce the spread of antimicrobial resistance genes in agricultural animals will be most effective at the herd level.
Recently, bovine coronavirus (BCV) has been isolated from new cattle arrivals to feedlots, but the association between respiratory and enteric infections with BCV in feedlot cattle remains uncertain. Fecal and nasal swab samples from 85 Ohio Agricultural Research and Development Center (OARDC) feedlot cattle averaging 7 months of age were collected at arrival (0) and at 4, 7, 14, and 21 days postarrival (DPA). An antigen capture enzyme-linked immunosorbent assay (ELISA) was used to detect concurrent shedding of BCV in fecal and nasal samples. All samples ELISA positive for BCV were matched with an equal number of BCV ELISA-negative samples and analyzed by reverse transcription-polymerase chain reaction (RT-PCR) of the N gene. Paired sera were collected at arrival and 21 DPA and tested for antibodies to BCV using an indirect ELISA. Information on clinical signs, treatments provided, and cattle weights were collected. The overall rates of BCV nasal and fecal shedding were 48% (41/85) and 53% (45/85) by ELISA and 84% (71/85) and 96% (82/85) by RT-PCR, respectively. The peak of BCV nasal and fecal shedding occurred at 4 DPA. Thirty-two cattle (38%) showed concurrent enteric and nasal shedding detected by both tests. Eleven percent of cattle had antibody titers against BCV at 0 DPA and 91% of cattle seroconverted to BCV by 21 DPA. The BCV fecal and nasal shedding detected by ELISA and RT-PCR were statistically correlated with ELISA antibody seroconversion (P < 0.0001); however, BCV fecal and nasal shedding were not significantly related to clinical signs. Seroconversion to BCV was inversely related to average daily weight gains (P < 0.06). Twenty-eight respiratory and 7 enteric BCV strains were isolated from nasal and fetal samples of 32 cattle in HRT-18 cell cultures. These findings confirm the presence of enteric and respiratory BCV infections in feedlot calves. Further studies are needed to elucidate the differences between enteric and respiratory strains of BCV and their role in the bovine respiratory disease complex of feedlot cattle.
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