Epidemiological and Clinical Features of Three Clustered Cases Co‐Infected with Lyme Disease and Rickettsioses

Lyme disease and rickettsioses are two common diseases in China. However, the concomitant occurrence of both diseases in a single individual has been reported infrequently in literature. We reported three related female patients admitted at Beijing Ditan Hospital from October to December 2010. They had similar epidemiological histories. At the beginning, they only got a single diagnosis, respectively, but after specific screenings, the final diagnoses were made. Because arthropods can harbour more than one disease‐causing agent, patients can be infected with more than one pathogen at the same time, so the possibility of co‐infection could be higher than what was thought previously. These observations suggested that clinicians should enhance the complete screening of arthropod‐related infectious diseases so as to make an accurate diagnosis and to avoid diagnostic errors.     

The sero‐epidemiology of Coxiella burnetii (Q fever) across livestock species and herding contexts in Laikipia County,Kenya

Coxiella burnetii, the causative agent of Query fever (Q fever), is among the most highly infectious zoonotic pathogens transmitted among livestock, with chronic effects challenging to veterinary and medical detection and care systems. Transmission among domestic livestock species can vary regionally due to herd management practices that determine which livestock species are raised, whether or not livestock are in contact with wildlife, and the susceptibility of these livestock to infection. To explore how different livestock management practices are associated with the risk of infection in multispecies environments, we carried out a comparative study of three types of herd management systems in the central Kenyan county of Laikipia: agro‐commercial, mixed conservancy/commercial, and smallholder ranches. We tested C. burnetii antibody seroprevalence in four common livestock species. Across all management types, the highest seroprevalence was in camels (20%), followed by goats (18%), sheep (13%), and cattle (6%). We observed a lower odds of testing seropositive for young compared to adult animals (adjusted OR = 0.44 [95% CI 0.24, 0.76]), and for males compared to females (adjusted OR = 0.52 [95% CI 0.33, 0.80]). Animals from mixed conservancy/commercial and smallholder operations had a higher odds of testing seropositive compared to animals from agro‐commercial ranches (adjusted OR = 5.17 [95% CI 2.71, 10.44] and adjusted OR = 2.21 [95% CI 1.17, 4.43] respectively). These data suggest that herd management practices might affect the transmission dynamics of C. burnetiiin arid African ecosystems like those seen in Kenya where several transmission modes are possible, risk of drought has promoted new livestock species such as camels, and multiple wildlife species may co‐occur with livestock on the landscape. Further longitudinal studies are needed to disentangle the mechanisms underlying these patterns, and further explore transmission patterns between wildlife, domestic animal, and human populations.     

The Effectiveness of Coxiella burnetii Vaccines in Occupationally Exposed Populations: A Systematic Review and Meta‐Analysis

To estimate the effect of vaccination in preventing acute Q fever in individuals occupationally exposed to Coxiella burnetii, a systematic review and meta‐analysis were undertaken in controlled trials and observational studies. Publications were obtained through a scoping study of English and non‐English articles, and those reporting a commercially licensed or licensable vaccine compared with an unvaccinated or placebo control group were included in the review. Two authors performed independent assessment of risk of systematic error and data extraction. One controlled trial and five cohort publications met the inclusion criteria. All trials used a Henzerling phase I vaccine. A random‐effects meta‐analysis estimated significant protection in abattoir workers (RR = 0.07; 95% confidence interval [CI] 0.02–0.22) compared with the control individuals. In individuals with rare or sporadic contact with the abattoir, a significant benefit of vaccination was also found (RR = 0.06; 95% CI 0–0.93). Overall, the vaccine effectively prevented acute Q fever in individuals responsible for handling animals or their products and those working in the abattoir but not directly exposed to animals (RR = 0.06; 95% CI 0.02–0.18). Caution must be taken when interpreting the effect of C. burnetii vaccination as significant heterogeneity amongst publications was observed. A meta‐regression found no significant univariate associations. This may reflect the uncertainty provided by reported data in the cohort publications. Potential systematic biases were present in the publications, and evidence included may not be sufficiently robust to extrapolate the effect of vaccination on occupationally exposed groups beyond the population of abattoir employees in Australia where all included studies occurred.     

The devil is in the details—Host disease and co‐infections are associated with zoonotic pathogen carriage in Norway rats (Rattus norvegicus)

Traditionally, zoonotic pathogen ecology studies in wildlife have focused on the interplay among hosts, their demographic characteristics and their pathogens. But pathogen ecology is also influenced by factors that traverse the hierarchical scale of biological organization, ranging from within‐host factors at the molecular, cellular and organ levels, all the way to the host population within a larger environment. The influence of host disease and co‐infections on zoonotic pathogen carriage in hosts is important because these factors may be key to a more holistic understanding of pathogen ecology in wildlife hosts, which are a major source of emerging infectious diseases in humans. Using wild Norway rats (Rattus norvegicus) as a model species, the purpose of this study was to investigate how host disease and co‐infections impact the carriage of zoonotic pathogens. Following a systematic trap and removal study, we tested the rats for the presence of two potentially zoonotic bacterial pathogens (Bartonella tribocorum and Leptospira interrogans) and assessed them for host disease not attributable to these bacteria (i.e., nematode parasites, and macroscopic and microscopic lesions). We fitted multilevel multivariable logistic regression models with pathogen status as the outcome, lesions and parasites as predictor variables and city block as a random effect. Rats had significantly increased odds of being infected with B. tribocorum if they had a concurrent nematode infection in one or more organ systems. Rats with bite wounds, any macroscopic lesion, cardiomyopathy or tracheitis had significantly increased odds of being infected with L. interrogans. These results suggest that host disease may have an important role in the ecology and epidemiology of rat‐associated zoonotic pathogens. Our multiscale approach to assessing complex intrahost factors in relation to zoonotic pathogen carriage may be applicable to future studies in rats and other wildlife hosts.     

Use of a Dose–Response Model to Study Temporal Trends in Spatial Exposure to Coxiella burnetii: Analysis of a Multiyear Outbreak of Q Fever

The Netherlands underwent a large Q fever outbreak between 2007 and 2009. In this paper, we study spatial and temporal Coxiella burnetii exposure trends during this large outbreak as well as validate outcomes against other published studies and provide evidence to support hypotheses on the causes of the outbreak. To achieve this, we develop a framework using a dose–response model to translate acute Q fever case incidence into exposure estimates. More specifically, we incorporate a geostatistical model that accounts for spatial and temporal correlation of exposure estimates from a human Q fever dose–response model to quantify exposure trends during the outbreak. The 2051 cases, with the corresponding age, gender and residential addresses, reside in the region with the highest attack rates during the outbreak in the Netherlands between 2006 and 2009. We conclude that the multiyear outbreak in the Netherlands is caused by sustained release of infectious bacteria from the same sources, which suggests that earlier implementation of interventions may have prevented many of the cases. The model predicts the risk of infection and acute symptomatic Q fever from multiple exposure sources during a multiple‐year outbreak providing a robust, evidence‐based methodology to support decision‐making and intervention design.     

Zinc Oxide Therapy Increases Prevalence and Persistence of Methicillin‐Resistant Staphylococcus aureus in Pigs: A Randomized Controlled Trial

There is concern that therapeutic use of zinc oxide (ZnO) in swine production may select for methicillin‐resistant Staphylococcus aureus (MRSA) due to co‐location of the zinc resistance gene (czrC) and methicillin resistance gene (mecA) within the staphylococcal cassette chromosome mec (SCCmec). The objective of this investigation was to determine whether MRSA carriage in pigs is influenced by exposure to therapeutic doses of in‐feed ZnO (3000 mg/kg) when compared to the recommended dietary levels (100 mg/kg). A randomized controlled trial was completed using 110 pigs that were naturally colonized with czrC‐positive MRSA. The pigs were followed from birth to weaning (21 d), at which point they were randomized into 8 pens and exposed to either a control feed (100 mg ZnO/kg feed; n = 49 pigs) or a treatment feed (3000 mg ZnO/kg feed; n = 50 pigs); neither feed contained additional antimicrobials. MRSA carriage was monitored weekly in each group for 4 weeks post‐weaning. The prevalence of MRSA was significantly higher in the treatment group at 1‐week (OR = 18.1; P < 0.01) and 2 weeks (OR = 3.01; P = 0.01) post‐weaning when compared to the control group, but there was no difference later in the nursery phase. Persistent MRSA carriage (testing positive ≥2 times post‐weaning) was observed in 2% (1/49) of control pigs and 22% (11/50) of treated pigs (P < 0.01). All MRSA isolates (spa types t034 and t3075) carried czrC and showed uniform resistance to zinc. These findings demonstrate that the prevalence and persistence of MRSA in nursery pigs can be affected by high levels of in‐feed ZnO in the absence of antibiotics.     

A dose titration study into the effects of diazepam or midazolam on the propofol dose requirements for induction of general anaesthesia in client owned dogs,premedicated with methadone and acepromazine

ObjectiveTo assess the effect of a benzodiazepine co–induction on propofol dose requirement for induction of anaesthesia in healthy dogs, to describe any differences between midazolam and diazepam and to determine an optimal benzodiazepine dose for co–induction.Study designProspective, randomised, blinded placebo controlled clinical trial.AnimalsNinety client owned dogs (ASA I–III, median body mass 21.5kg (IQR 10–33)) presented for anaesthesia for a variety of procedures.MethodsDogs were randomised to receive saline 0.1 mL kg^?1, midazolam or diazepam at 0.2, 0.3, 0.4 or 0.5 mg kg^?1. All dogs received 0.01 mg kg^?1 acepromazine and 0.2 mg kg^?1 methadone intravenously (IV). Fifteen minutes later, sedation was assessed and scored prior to anaesthetic induction. Propofol, 1 mg kg^?1, was administered IV, followed by the treatment drug. Further propofol was administered until endotracheal intubation was possible. Recorded data included patient signalment, sedation score, propofol dosage and any adverse reactions.ResultsMidazolam (all groups combined) significantly reduced propofol dose requirement compared to saline (p < 0.001) and diazepam (p = 0.008). Midazolam (0.4 mg kg^?1) significantly reduced propofol dose requirement (p = 0.014) compared to saline, however other doses failed to reach statistical significance. Diazepam did not significantly reduce propofol dose requirement compared to saline (p = 0.089). Dogs weighing <5 kg, regardless of treatment group, required a greater propofol dose than those weighing 5–40 kg (p = 0.002) and those >40 kg (p = 0.008). Dogs which were profoundly sedated required less propofol than those which were mildly sedated (p < 0.001) and adequately sedated (p = 0.003).Conclusions and clinical relevanceMidazolam (0.4 mg kg^?1) given IV after 1 mg kg^?1 of propofol significantly reduced the further propofol dose required for intubation compared to saline. At the investigated doses, diazepam did not have significant propofol dose sparing effects.     

Differential gene expression of Eph‐ephrin A1 and LEPR‐LEP with high or low number of embryos in pigs during implantation

The objective of this study was to ascertain whether mRNA and protein expressions of implantation‐related genes (erythropoietin‐producing hepatocellular receptor–ligand A1, Eph‐ephrin A1 and leptin receptor–leptin, LEPR‐LEP) differed between pigs with high and low number of embryos, and whether these differences in gene expression might affect embryo implantation. Experimental pig groups (n = 24) for high and low number of embryos were prepared by altering the number of eggs ovulated in pre‐pubertal gilts treated with 1.5 × (High) or 1.0 × (Low) PG600 ([400 IU PMSG + 200 IU hCG]/dose, AKZO‐NOBEL). Gilts expressing oestrus were artificially inseminated twice and maintained in breeding and gestation until the reproductive tract was collected on day 22 of pregnancy. At slaughter, the reproductive tracts from each pregnant gilt from each treatment were immediately processed to collect samples for RNA and protein analysis. Within each gilt, three conceptus points were sampled, one from each horn and then a random conceptus within the tract. At each conceptus point, endometrial attachment site, chorion–allantois and embryo were collected and immediately frozen in liquid nitrogen. Number of corpus luteum (CL) (35.4 vs. 12.6) and total embryo number (18.8 vs. 10.2) were greater in the high‐embryo compared to the low‐embryo group, respectively (p < .05). Real‐time qPCR results showed that Eph‐ephrin A1 mRNA expression was less in the high‐embryo (p < .05) compared to the low‐embryo group. In addition, Western blotting analysis indicated that Eph‐ephrin A1 and LEP protein expression at endometrial attachment site in high‐embryo was less (p < .05) compared to low‐embryo group. It was also noted that mRNA expression of Eph‐ephrin A1 and LEPR‐LEP was greater in pregnant than non‐pregnant gilts (p < .05). Moreover, mRNA expression of Eph‐ephrin A1 (p < .05) and LEPR‐LEP was greatest at endometrial attachment site among all three tissues. There was a positive correlation between expressions of Eph‐ephrin A1, LEPR‐LEP and embryo length with the correlation coefficient 0.31–0.59. For Eph‐ephrin A1, the highest correlation coefficient appeared between Eph A1 expression and normal embryo number, between ephrin A1 expression and embryo length. For LEPR‐LEP, the highest correlation coefficient appeared between LEPR‐LEP expression and ovary weight (0.79 for both, p < .05), followed by embryo length and weight. The results of this study suggest that low expression of Eph‐ephrin A1 and LEPR‐LEP is somehow related to increased embryo number during implantation and that endometrial attachment site might be the main target tissue of these gene products. Yet, the increased expression of Eph‐ephrin A1 and LEPR‐LEP appeared associated with increased embryo growth (length and weight) and ovary weight, Eph‐ephrin A1 and LEPR‐LEP might play roles in the regulation of embryo implantation in pigs.     

A comparison in dogs of medetomidine,with or without MK‐467, and the combination acepromazine‐butorphanol as premedication prior to anaesthesia induced by propofol and maintained with isoflurane

ObjectiveTo compare the haemodynamic effects of three premedicant regimens during propofol-induced isoflurane anaesthesia.Study designProspective, randomized cross-over study.AnimalsEight healthy purpose-bred beagles aged 4 years and weighing mean 13.6 ± SD 1.9 kg.MethodsThe dogs were instrumented whilst under isoflurane anaesthesia prior to each experiment, then allowed to recover for 60 minutes. Each dog was treated with three different premedications given intravenously (IV): medetomidine 10 μg kg^?1 (MED), medetomidine 10 μg kg^?1 with MK-467 250 μg kg^?1 (MMK), or acepromazine 0.01 mg kg^?1 with butorphanol 0.3 mg kg^?1 (AB). Anaesthesia was induced 20 minutes later with propofol and maintained with isoflurane in oxygen for 60 minutes. Heart rate (HR), cardiac output, arterial blood pressures (ABP), central venous pressure (CVP), respiratory rate, inspired oxygen fraction, rectal temperature (RT) and bispectral index (BIS) were measured and arterial and venous blood gases analyzed. Cardiac index (CI), systemic vascular resistance index (SVRI), oxygen delivery index (DO₂I), systemic oxygen consumption index (VO₂I) and oxygen extraction (EO₂) were calculated. Times to extubation, righting, sternal recumbency and walking were recorded. The differences between treatment groups were evaluated with repeated measures analysis of covariance.ResultsHR, CI, DO₂I and BIS were significantly lower with MED than with MMK. ABP, CVP, SVRI, EO₂, RT and arterial lactate were significantly higher with MED than with MMK and AB. HR and ABP were significantly higher with MMK than with AB. However, CVP, CI, SVRI, DO₂I, VO₂I, EO₂, T, BIS and blood lactate did not differ significantly between MMK and AB. The times to extubation, righting, sternal recumbency and walking were significantly shorter with MMK than with MED and AB.Conclusions and clinical relevanceMK-467 attenuates certain cardiovascular effects of medetomidine in dogs anaesthetized with isoflurane. The cardiovascular effects of MMK are very similar to those of AB.     

Preliminary insights into the occurrence of similar clones of extended‐spectrum beta‐lactamase‐producing bacteria in humans,animals and the environment in Tanzania: A systematic review and meta‐analysis between 2005 and 2016

The emergence and spread of extended‐spectrum beta‐lactamase producing Enterobacteriaceae (ESBL‐PE) are complex and of the public health concern across the globe. This review aimed at assessing the ESBL‐PE clones circulating in humans, animals and the environment to provide evidence‐based insights for combating ESBL‐PE using One Health approach. Systematic search from Medline/PubMed, Google Scholar and African Journals Online was carried out and retrieved nine eligible articles (of 131) based on phenotypic and genotypic detection of ESBL‐PE between 2005 and 2016 in Tanzania. Analysis was performed using STATA 11.0 software to delineate the prevalence of ESBL‐PE, phenotypic resistance profiles and clones circulating in the three interfaces. The overall prevalence of ESBL‐PE in the three interfaces was 22.6% (95% CI: 21.1–24.2) with the predominance of Escherichia coli (E. coli) strains (51.6%). The majority of ESBL‐PE were resistant to the commonly used antimicrobials such as trimethoprim–sulfamethoxazole and tetracycline/doxycycline, 38%–55% were resistant to ciprofloxacin and all were sensitive to meropenem/imipenem. ESBL‐PE infections were more associated with deaths compared to non‐ESBL‐PE infections. Strikingly, E. coli ST38, ST131 and ST2852 were found to intersect variably across the three interfaces. The predominant allele, bla_{CTX‐M‐15,} was found mostly in the conjugative IncF plasmids connoting transmission potential. The high prevalence of ESBL‐PE and shared clones across the three interfaces, including the global E. coli ST131 clone, indicates wide and inter‐compartmental spread that calls for One Health genomic‐driven studies to track the resistome flow.     

The cardiopulmonary effects of a peripheral alpha‐2‐adrenoceptor antagonist,MK‐467, in dogs sedated with a combination of medetomidine and butorphanol

ObjectiveTo compare the cardiopulmonary effects of intravenous (IV) and intramuscular (IM) medetomidine and butorphanol with or without MK-467.Study designProspective, randomized experimental cross-over.AnimalsEight purpose–bred beagles (two females, six males), 3–4 years old and weighing 14.5 ±1.6 kg (mean ± SD).MethodsAll dogs received four different treatments as follows: medetomidine 20 μg kg^?1 and butorphanol tartrate 0.1 mg kg^?1 IV and IM (MB), and MB combined with MK-467,500 μg kg^?1 (MBMK) IV and IM. Heart rate (HR), arterial blood pressures (SAP, MAP, DAP), central venous pressure (CVP), cardiac output, respiratory rate (f_R), rectal temperature (RT) were measured and arterial blood samples were obtained for gas analysis at baseline and at 3, 10, 20, 30, 45 and 60 minutes after drug administration. The cardiac index (CI), systemic vascular resistance index (SVRI) and oxygen delivery index (DO₂I) were calculated. After the follow-up period atipamezole 50 μg kg^?1 IM was given to reverse sedation.ResultsHR, CI and DO₂I were significantly higher with MBMK after both IV and IM administration. Similarly, SAP, MAP, DAP, CVP, SVRI and RT were significantly lower after MBMK than with MB. There were no differences in f_R between treatments, but arterial partial pressure of oxygen decreased transiently after all treatments. Recoveries were uneventful following atipamezole administration after all treatments.Conclusions and clinical relevanceMK-467 attenuated the cardiovascular effects of a medetomidine-butorphanol combination after IV and IM administration.     

The Use of Direct‐Fed Microbials to Reduce Shedding of Escherichia coli O157 in Beef Cattle: A Systematic Review and Meta‐analysis

Human illness due to infections with Escherichia coli O157 is a serious health concern. Infection occurs through direct contact with infected animals or their faeces, through contaminated food or water and/or through person‐to‐person transmission. A reduction in faecal E. coli O157 shedding in cattle might reduce the burden of human infections. We used systematic review and meta‐analysis to assess the efficacy of direct‐fed microbials (DFM), compared with placebo or no treatment, fed during the pre‐harvest stage of production in reducing faecal E. coli O157 shedding in beef cattle during field trials. Four electronic databases, Nebraska Beef Reports and review article reference lists were searched. A total of 16 publications assessing faecal shedding at the end of the trial and/or throughout the trial period were included. The majority of publicly disseminated trials evaluated the prevalence of E. coli O157 faecal shedding; only two evaluated the concentration of organisms in faeces. The prevalence of faecal E. coli O157 shedding in cattle is significantly reduced by DFM treatments (summary effect size for all DFM – OR = 0.46; CI = 0.36–0.60). The DFM combination Lactobacillus acidophilus (NP51) and Propionibacterium freudenreichii (NP24) was more efficacious in reducing the prevalence of faecal E. coli O157 shedding at the time of harvest and throughout the trial period compared with the group of other DFM, although this difference was not statistically significant. Furthermore, we found that the combination [NP51 and NP24] treatment was more efficacious in reducing the prevalence of faecal E. coli O157 shedding at the time of harvest and throughout the trial period when fed at the dose of 10⁹ CFU/animal/day than any lesser amount, although this difference was not statistically significant. Feeding beef cattle DFM during the pre‐harvest stage of production reduces the prevalence of E. coli O157 faecal shedding and might effectively reduce human infections.     

Attribution of human infections with Shiga toxin‐producing Escherichia coli (STEC) to livestock sources and identification of source‐specific risk factors,The Netherlands (2010–2014)

Shiga toxin‐producing Escherichia coli (STEC) is a zoonotic pathogen of public health concern whose sources and transmission routes are difficult to trace. Using a combined source attribution and case–control analysis, we determined the relative contributions of four putative livestock sources (cattle, small ruminants, pigs, poultry) to human STEC infections and their associated dietary, animal contact, temporal and socio‐econo‐demographic risk factors in the Netherlands in 2010/2011–2014. Dutch source data were supplemented with those from other European countries with similar STEC epidemiology. Human STEC infections were attributed to sources using both the modified Dutch model (mDM) and the modified Hald model (mHM) supplied with the same O‐serotyping data. Cattle accounted for 48.6% (mDM) and 53.1% (mHM) of the 1,183 human cases attributed, followed by small ruminants (mDM: 23.5%; mHM: 25.4%), pigs (mDM: 12.5%; mHM: 5.7%) and poultry (mDM: 2.7%; mHM: 3.1%), whereas the sources of the remaining 12.8% of cases could not be attributed. Of the top five O‐serotypes infecting humans, O157, O26, O91 and O103 were mainly attributed to cattle (61%–75%) and O146 to small ruminants (71%–77%). Significant risk factors for human STEC infection as a whole were the consumption of beef, raw/undercooked meat or cured meat/cold cuts. For cattle‐attributed STEC infections, specific risk factors were consuming raw meat spreads and beef. Consuming raw/undercooked or minced meat were risk factors for STEC infections attributed to small ruminants. For STEC infections attributed to pigs, only consuming raw/undercooked meat was significant. Consuming minced meat, raw/undercooked meat or cured meat/cold cuts were associated with poultry‐attributed STEC infections. Consuming raw vegetables was protective for all STEC infections. We concluded that domestic ruminants account for approximately three‐quarters of reported human STEC infections, whereas pigs and poultry play a minor role and that risk factors for human STEC infection vary according to the attributed source.