Modelling dynamics between free-living amoebae and bacteria.

Free-living amoebae (FLA) serve as hosts for a variety of endosymbionts, which are microorganisms that reside and multiply within the FLA. Some of these endosymbionts pose a pathogenic threat to humans, animals, or both. The symbiotic relationship with FLA not only offers these microorganisms protection but also enhances their survival outside their hosts and assists in their dispersal across diverse habitats, thereby escalating disease transmission. This review is intended to offer an exhaustive overview of the existing mathematical models that have been applied to understand the dynamics of FLA, especially concerning their interactions with bacteria. An extensive literature review was conducted across Google Scholar, PubMed, and Scopus databases to identify mathematical models that describe the dynamics of interactions between FLA and bacteria, as published in peer-reviewed scientific journals. The literature search revealed several FLA-bacteria model systems, including Pseudomonas aeruginosa, Pasteurella multocida, and Legionella spp. Although the published mathematical models account for significant system dynamics such as predator-prey relationships and non-linear growth rates, they generally overlook spatial and temporal heterogeneity in environmental conditions, such as temperature, and population diversity. Future mathematical models will need to incorporate these factors to enhance our understanding of FLA-bacteria dynamics and to provide valuable insights for future risk assessment and disease control measures.

Correction: Behavior-change interventions to improve antimicrobial stewardship in human health, animal health, and livestock agriculture: A systematic review.

[This corrects the article DOI: 10.1371/journal.pgph.0001526.].

Behavior-change interventions to improve antimicrobial stewardship in human health, animal health, and livestock agriculture: A systematic review.

Antimicrobial resistance (AMR) is an economic, food security, and global health threat accelerated by a multitude of factors including the overuse and misuse of antimicrobials in the human health, animal health, and agriculture sectors. Given the rapid emergence and spread of AMR and the relative lack of development of new antimicrobials or alternative therapies, there is a need to develop and implement non-pharmaceutical AMR mitigation policies and interventions that improve antimicrobial stewardship (AMS) practices across all sectors where antimicrobials are used. We conducted a systematic literature review per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to identify peer-reviewed studies that described behavior-change interventions that aimed to improve AMS and/or reduce inappropriate antimicrobial use (AMU) among human health, animal health, and livestock agriculture stakeholders. We identified 301 total publications- 11 in the animal health sector and 290 in the human health sector-and assessed described interventions using metrics across five thematic areas- (1) AMU, (2) adherence to clinical guidelines, (3) AMS, (4) AMR, and (5) clinical outcomes. The lack of studies describing the animal health sector precluded a meta-analysis. Variation across intervention type, study type, and outcome precluded a meta-analysis for studies describing the human health sector; however, a summary descriptive analysis was conducted. Among studies in the human health sector, 35.7% reported significant (p<0.05) pre- to post-intervention decreases in AMU, 73.7% reported significant improvements in adherence of antimicrobial therapies to clinical guidelines, 45% demonstrated significant improvements in AMS practices, 45.5% reported significant decreases in the proportion of isolates that were resistant to antibiotics or the proportion of patients with drug-resistant infections across 17 antimicrobial-organism combinations. Few studies reported significant changes in clinical outcomes. We did not identify any overarching intervention type nor characteristics associated with successful improvement in AMS, AMR, AMU, adherence, nor clinical outcomes.

A stochastic compartmental model to simulate intra- and inter-species influenza transmission in an indoor swine farm.

Common in swine production worldwide, influenza causes significant clinical disease and potential transmission to the workforce. Swine vaccines are not universally used in swine production, due to their limited efficacy because of continuously evolving influenza viruses. We evaluated the effects of vaccination, isolation of infected pigs, and changes to workforce routine (ensuring workers moved from younger pig batches to older pig batches). A Susceptible-Exposed-Infected-Recovered model was used to simulate stochastic influenza transmission during a single production cycle on an indoor hog growing unit containing 4000 pigs and two workers. The absence of control practices resulted in 3,957 pigs [0-3971] being infected and a 0.61 probability of workforce infection. Assuming incoming pigs had maternal-derived antibodies (MDAs), but no control measures were applied, the total number of infected pigs reduced to 1 [0-3958] and the probability of workforce infection was 0.25. Mass vaccination (40% efficacious) of incoming pigs also reduced the total number of infected pigs to 2362 [0-2374] or 0 [0-2364] in pigs assumed to not have MDAs and have MDAs, respectively. Changing the worker routine by starting with younger to older pig batches, reduced the number of infected pigs to 996 [0-1977] and the probability of workforce infection (0.22) in pigs without MDAs. In pigs with MDAs the total number of infected pigs was reduced to 0 [0-994] and the probability of workforce infection was 0.06. All other control practices alone, showed little improvement in reducing total infected pigs and the probability of workforce infection. Combining all control strategies reduced the total number of infected pigs to 0 or 1 with a minimal probability of workforce infection (<0.0002-0.01). These findings suggest that non-pharmaceutical interventions can reduce the impact of influenza on swine production and workers when efficacious vaccines are unavailable.

New York State dairy veterinarians' perceptions of antibiotic use and resistance: A qualitative interview study.

Antimicrobial resistance (AMR) limits the ability to prevent and treat infection, making AMR one of the foremost threats to human and animal health. Animal agriculture's large use of antibiotics in food animals is an important factor in AMR. As such, policies to reduce antibiotic use and combat AMR in animal agriculture in the United States (US) have been in place or are developed. One key to the success of these policies in the US is understanding how a major stakeholder - veterinarians treating dairy cattle - perceive the scale of antibiotic use, the threat of AMR and the utility of antibiotic use policies. We interviewed 9 dairy veterinarians in New York State and conducted an iterative thematic analysis of their responses, through which five themes were identified: 1. veterinarians' views of the frequency and reasons for antibiotic misuse, 2. their ideas on reducing antibiotic use, 3. perceptions of AMR within the dairy industry, 4. view of organic farming and how it relates to animal welfare, and 5. the impact of consumers' beliefs on the dairy industry. Participants viewed antibiotic overuse as largely due to farmers' concern for the welfare of their cattle and desire to treat ailments swiftly. Interviewees believed that it was possible to reduce antibiotic use through regulation, such as the Veterinary Feed Directive and improved herd management activities, such as better colostrum management, culture-based mastitis treatment, and improved housing conditions. They did not view the dairy industry as a significant contributor to AMR, particularly when compared to the human medical industry. Interviewees also offered their (unsolicited) opinion on organic dairy farming in the US and expressed frustration with the limited treatment options available in organic dairy farming and how this dynamic may potentially compromise animal welfare. Finally, they commented on the impact of consumers' beliefs on the dairy industry, expressing frustration with how misinformation about the dairy industry has led to consumer driven changes. As consumer beliefs have an impact on the dairy industry, this influence could be leveraged to further decrease antibiotic use. These findings can help guide future efforts in veterinarian-client communication and the development and implementation of effective policies in New York State. These results also highlight the need for more quantitative research on antibiotic use in the dairy industry, as without this data it will be difficult to ascertain the true impact of policy interventions.

Control of Brucella melitensis in endemic settings: A simulation study in the Nile Delta, Egypt.

Small ruminant brucellosis remains endemic in many low- and middle-income countries (LMICs), where it poses a major economic and public health burden. Lack of resources to support long-term vaccination, inherent characteristics of small ruminant production systems such as mixing of different flocks for grazing and limitations of the vaccines currently available, which can induce abortion in pregnant animals, have all hindered the effectiveness of control programmes. In the current study, the likely effect of different control scenarios on the seroprevalence of brucellosis among the small ruminant population in a hypothetical area of an endemic region was simulated using compartmental models. The model accounts for variability in transmission rates between villages and also simulates control scenarios that target villages with high seroprevalence. Our results show that vaccination of young replacement animals only can effectively reduce the prevalence of small ruminant brucellosis in endemic settings if a high vaccination coverage is achieved. On the other hand, test-and-slaughter alone is not a promising strategy for control of small ruminant brucellosis under husbandry practices typical of endemic low-resource settings. Furthermore, results show the potential success of some strategies requiring a relatively low overall vaccination coverage such as the vaccination of 50% of young replacements and 25% of adult animals each year. Control strategies selectively targeting high initial seroprevalence villages (p > 10%) did not decrease the overall seroprevalence to acceptable levels in most of the examined scenarios. Scenario analysis showed that the efficacy of the simulated control strategies can be improved mostly by decreasing the proportion of between-village trade and also by improving the performance of the used serological tests and increasing vaccine efficacy.

New York State dairy farmers' perceptions of antibiotic use and resistance: A qualitative interview study.

Antibiotic resistance is a global problem affecting both human and animal health. Ensuring the strategic and effective use of antibiotics is paramount to combatting the emergence and spread of resistance. This study explored New York State (NYS) dairy farmers' perceptions regarding antibiotic use in dairy farming and antibiotic resistance. Dairy farmers' perceptions were assessed through semi-structured, in-person interviews. Twenty interviews with farm owners and/or managers of 15 conventional and five USDA certified organic dairy farms with 40 to 2,300 lactating cows were conducted. Thematic analysis was used to assess, compare and contrast transcripts for farmers' characterization of their beliefs, values, and concerns. Conventional dairy farmers had a low level of concern about the possible impacts of on-farm antibiotic resistance on human health and believed their antibiotic use was already judicious. Generally, they believed their cattle's health would suffer if antibiotic use were further curtailed. Conventional farmers expressed frustration over the possibility of more stringent governmental, milk cooperative, buyer, or marketer requirements for antibiotic use and associated animal welfare in the future. They attributed expanding regulations in part to misinformed consumer preferences, that farmers felt were influenced by the marketing of organic dairy products. Organic dairy farmers were generally more concerned about issues related to antibiotic resistance than conventional farmers. Both conventional and organic farmers placed emphasis on disease prevention through herd health management rather than treatment. In conclusion, the conventional NYS dairy farmers in this study were skeptical of the need for and benefits of reduced antibiotic use on their dairy farms. Interventions for farmers, delivered by a trusted source such as a veterinarian, that provide training about proper antibiotic use practices and information of possible financial benefits of refining antibiotic use may hold promise.

The prevalence and risk factors for human Brucella species infection in a cross-sectional survey of a rural population in Punjab, India.

BACKGROUND: Brucellosis is an important neglected zoonosis. Effective cattle vaccines are available but are infrequently used in India, where rural households commonly own one or two cattle as sources of protein and income. We assessed the prevalence of infection and risk factors in humans. METHODS: We conducted a cross-sectional sero-survey in randomly selected individuals in 60 villages in Punjab. Infection prevalence was assessed by positive Rose Bengal testing or immunoglobulin G enzyme-linked immunosorbent assay. Risk factors were adjusted for potential confounding using multivariable analyses. RESULTS: Of the 1927 subjects who were approached, 93% agreed to participate. Age-standardised prevalence for Brucella infection was 2.24% (95% confidence interval [CI] 1.61 to 3.11). More than 60% of households kept cattle and 10% assisted with calving or abortions. Nearly all individuals consumed boiled cow/buffalo milk from their own or neighbours' cattle and 3.3% consumed goat's milk. There was a 2.18 times increased odds (95% CI 0.96 to 4.95) of infection with calving/abortions and a 4.26 times increased odds (95% CI 1.33 to 13.6) with goat's milk but not bovine milk consumption. CONCLUSIONS: An association with calving/abortions and goat's milk consumption was seen. Brucella vaccination of household livestock would reduce the risk to humans in such settings. Additional measures include biosecurity training around calving/abortions, education to boil all milk and for healthcare workers to test for brucellosis.

Rapidly assessing the risks of infectious diseases to wildlife species.

Predicting the likelihood of rare events is increasingly demanded by risk managers. A key challenge is dealing with different types of uncertainty, including epistemic uncertainties (lack of knowledge), stochasticity (inherent randomness) and natural variation. One potentially catastrophic event which is impacted by high levels of all three of these uncertainty types is the transmission of livestock pathogens to wildlife, particularly for endangered species. There is often a lack of basic information, e.g. about a given pathogen's presence in local livestock populations or the susceptibility of a given wildlife species to infection by the pathogen. We adapted the OIE (World Organisation for Animal Health) risk assessment framework to rapidly assess and prioritize the risks of livestock pathogens for wildlife, taking account of epistemic uncertainties, stochasticity, seasonal movement of animals and interaction between different species at different spatial and temporal scales. We demonstrate the approach using the endangered saiga antelope (Saiga tatarica tatarica) as a case study. We conclude that, in general, transmission events are likely to be rare and limited to small geographical areas; however, their impact could be high. Brucella spp. and foot-and-mouth disease virus are among those most likely to be transmitted from livestock to the Betpak-Dala saiga population.

The prevalence of Escherichia coli O157:H7 fecal shedding in feedlot pens is affected by the water-to-cattle ratio: A randomized controlled trial.

Escherichia coli O157:H7 fecal shedding in feedlot cattle is common and is a public health concern due to the risk of foodborne transmission that can result in severe, or even fatal, disease in people. Despite a large body of research, few practical and cost-effective farm-level interventions have been identified. In this study, a randomized controlled trial was conducted to assess the effect of reducing the level of water in automatically refilling water-troughs on fecal shedding of E. coli O157:H7 in feedlot cattle. Pens in a feedlot in the Texas Panhandle were randomly allocated as control (total number: 17) or intervention (total number: 18) pens. Fecal samples (2,759 in total) were collected both at baseline and three weeks after the intervention, and tested for the presence of E. coli O157:H7 using immunomagnetic bead separation and selective culture. There was a strong statistical association between sampling date and the likelihood of a fecal sample testing positive for E. coli O157:H7. Pen was also a strong predictor of fecal prevalence. Despite accounting for this high level of clustering, a statistically significant association between reduced water levels in the trough and increased prevalence of E. coli O157:H7 in the feces was observed (Odds Ratio = 1.6; 95% Confidence Interval: 1.2-2.0; Likelihood Ratio Test: p = 0.02). This is the first time that such an association has been reported, and suggests that increasing water-trough levels may be effective in reducing shedding of E. coli O157:H7 in cattle feces, although further work would be needed to test this hypothesis. Controlling E. coli O157:H7 fecal shedding at the pre-harvest level may lead to a reduced burden of human foodborne illness attributed to this pathogen in beef.

Saigas on the brink: Multidisciplinary analysis of the factors influencing mass mortality events.

In 2015, more than 200,000 saiga antelopes died in 3 weeks in central Kazakhstan. The proximate cause of death is confirmed as hemorrhagic septicemia caused by the bacterium Pasteurella multocida type B, based on multiple strands of evidence. Statistical modeling suggests that there was unusually high relative humidity and temperature in the days leading up to the mortality event; temperature and humidity anomalies were also observed in two previous similar events in the same region. The modeled influence of environmental covariates is consistent with known drivers of hemorrhagic septicemia. Given the saiga population's vulnerability to mass mortality and the likely exacerbation of climate-related and environmental stressors in the future, management of risks to population viability such as poaching and viral livestock disease is urgently needed, as well as robust ongoing veterinary surveillance. A multidisciplinary approach is needed to research mass mortality events under rapid environmental change.

Cross-Sectional Study of Toxoplasma gondii Infection in Pig Farms in England.

Ingestion of undercooked meat has been proposed as an important source of human Toxoplasma gondii infection. To ascertain the contribution of meat consumption to the risk of human infection, estimates of the prevalence of infection in meat-producing animals are required. A cross-sectional study was conducted to assess T. gondii infection in pigs raised in England, to identify risk factors for infection, and to compare performance of two serological tests: modified agglutination test (MAT) and enzyme-linked immunosorbent assay (ELISA). Blood samples from 2071 slaughter pigs originating from 131 farms were collected and 75 (3.6%) were found to be positive by MAT. Positive pigs originated from 24 farms. A subset of samples (n = 492) were tested using ELISA, and a significant disagreement (p < 0.001) was found between the two tests. An empirical Bayes approach was used to estimate the farm-level prevalence and the probability of each individual farm having at least one positive animal, considering the uncertainty arising from the sampling strategy and the imperfect test performance. The adjusted farm-level prevalence was 11.5% (95% credible interval of positive farms 8.4-16.0%). Two different criteria were used for classifying farms as infected: (1) ≥50% probability of having at least one infected pig (n = 5, 6.8%) and (2) ≥10% probability (n = 15, 20.5%). Data on putative risk factors were obtained for 73 farms. Using a 10% cutoff, the relative risk (RR) of infection was higher in farms where cats have direct access to pigs' food (RR = 2.6; p = 0.04), pigs have outdoor access (RR = 3.0; p = 0.04), and farms keeping ≤200 pigs (RR = 3.9; p = 0.02), with strong collinearity between the three variables. The findings suggest a low level of T. gondii infection in the farms studied, most of which are likely to send to slaughter batches comprising 100% uninfected pigs. These results provide key inputs to quantitatively assess the T. gondii risk posed by pork to consumers.

Policies and Livestock Systems Driving Brucellosis Re-emergence in Kazakhstan.

Brucellosis is a considerable public health and economic burden in many areas of the world including sub-Saharan Africa, the Middle East and former USSR countries. The collapse of the USSR has been cited as a driver for re-emergence of diseases including brucellosis, and human incidence rates in the former Soviet republics have been estimated as high as 88 per 100,000 per year. The aim of this paper is to examine the historical trends in brucellosis in Kazakhstan and to explore how livestock systems, veterinary services and control policies may have influenced them. In conclusion, a brucellosis epidemic most likely began before the collapse of the USSR and high livestock densities may have played an important role. Changes to the livestock systems in Kazakhstan, as well as other factors, are likely to have an impact on the success of brucellosis policies in the future. Incentives and practicalities of different policies in smallholder settings should be considered. However, the lack of reliable estimates of brucellosis prevalence and difficulties in understanding exactly how policy is being applied in Kazakhstan, which is a vast country with low population density, prevent firm conclusions from being drawn.

Seroprevalence of infectious diseases in saiga antelope (Saiga tatarica tatarica) in Kazakhstan 2012-2014.

286 serum samples were collected from three sub-populations of saiga in Kazakhstan (Betpakdala, Ustyurt and Volga-Ural) between 2012 and 2014, and were tested for the presence of antibodies to Brucella spp., bluetongue virus, peste des petits ruminants (PPR) virus, Akabane virus, Schmallenberg virus, Chlamydophila, Toxoplasma, Mycobacterium avium subspecies paratuberculosis and Coxiella burnetii (Q Fever). Seropositives to Coxiella burnetii of saiga were detected and the adjusted seroprevalence of Q Fever antibodies was 0.07 (95% confidence interval (CI): 0.03-0.10). Seropositives to Akabane virus were detected in all three populations and the adjusted seroprevalence values for this virus were very high (all were>0.13). Lower adjusted seroprevalence values were estimated for PPR Virus and Mycobacterium avium subsp. paratuberculosis (0.005 and 0.006). No seropositives for bluetongue, Toxoplasma, Brucella or Schmallenberg were detected.

Vaccination control programs for multiple livestock host species: an age-stratified, seasonal transmission model for brucellosis control in endemic settings.

BACKGROUND: Brucella melitensis causes production losses in ruminants and febrile disease in humans in Africa, Central Asia, the Middle East and elsewhere. Although traditionally understood to affect primarily sheep and goats, it is also the predominant Brucella species that affects cows in some endemic areas. Despite this, no licensed vaccine is available specifically for use against B. melitensis in cows. The mainstay of most control programs is vaccination of sheep and goats with a live vaccine, Rev-1. The aim of this study was to investigate how critical vaccination of cows might be, in order to control B. melitensis on a mixed sheep-and-cattle farm. METHODS: A dynamic, differential-equation, age-structured, seasonal model with births and deaths, was used to investigate whether vaccination of both sheep and cattle had an impact on time to elimination of brucellosis on an individual mixed species farm, when compared to vaccination of sheep only. The model was a Susceptible-Exposed-Infectious-Recovered-Susceptible (SEIRS) model with an additional compartment for Persistently Infected (PI) individuals. Transmission parameters were fit based on a nation-wide probabilistic seroprevalence survey in Jordan. RESULTS: The model predicted that it would take 3.5 years to eliminate brucellosis (to less than 0.5% of adult sheep seropositive as a result of infection) on a mixed-species B. melitensis-endemic farm with the median field-study seroprevalence, following vaccination of both sheep and cattle, assuming a vaccine effectiveness of 80%. Limiting the vaccination to sheep only, increased the time to 16.8 years. Sensitivity analysis showed that the finding that vaccination of cattle was of significant importance, was robust. Vaccine effectiveness had a strong influence on time to elimination. CONCLUSIONS: In the absence of further data, vaccination of cattle should be considered essential in Brucella-endemic settings where mixed small ruminant and cattle flocks predominate. Further evidence that Brucella melitensis predominates in cattle in Jordan, as opposed to Brucella abortus, is needed in order to validate this model. The results may be applicable to other mixed-species settings with similar livestock management practices. These methods may be applied to other pathogens affecting multiple livestock species or with seasonal transmission.

The risk of rinderpest re-introduction in post-eradication era.

In 2011, ten years after the last reported outbreak, the eradication of rinderpest was declared. However, as rinderpest virus stocks still exist, there remains a risk of rinderpest re-introduction. A semi-quantitative risk assessment was conducted to assess this risk, which was defined as the probability of at least one host becoming infected and infectious outside a laboratory anywhere in the world within a one-year period. Pathways leading to rinderpest re-introduction were: deliberate or accidental use of virus in laboratories, deliberate or accidental use of vaccines, host exposure to an environmental source of virus, and use of virus for anti-animal biological warfare. The probability of each pathway step occurring was estimated through expert opinion elicitation. The risk estimate was associated with a high degree of uncertainty. It was estimated to range from negligible to high, with the median being very low. The accidental use of laboratory virus stocks was the highest risk pathway. Reducing the number of virus stocks and restricting their use, as well as upgrading the laboratories to a higher biosafety level, would effectively decrease the maximum and median risks. Likewise, ensuring that remaining vaccine stocks are not used and are instead destroyed or relocated to a limited number of regional repositories would also have a major effect on these estimates. However, these measures are unlikely to eliminate the risk of rinderpest re-introduction so that maintaining response preparedness is essential.

Rinderpest virus sequestration and use in posteradication era.

After the 2011 declaration of rinderpest disease eradication, we surveyed 150 countries about rinderpest virus stocks. Forty-four laboratories in 35 countries held laboratory-attenuated strains, field strains, or diagnostic samples. Vaccine and reagent production and laboratory experiments continued. Rigorous standards are necessary to ensure that stocks are kept under safe conditions.