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Q fever is a zoonotic disease, resulting from infection with Coxiella burnetii . Infection in cattle can cause abortion and infertility, however, there is little epidemiological information regarding the disease in dairy cattle in Tanzania. Between July 2019 and October 2020, a serosurvey was conducted in six high dairy producing regions of Tanzania. Cattle sera were tested for antibodies to C. burnetii using an indirect enzyme-linked immunosorbent assay. A mixed effect logistic regression model identified risk factors associated with C. burnetii seropositivity. A total of 79 out of 2049 dairy cattle tested positive with an overall seroprevalence of 3.9% (95% CI 3.06-4.78) across the six regions with the highest seroprevalence in Tanga region (8.21%, 95% CI 6.0-10.89). Risk factors associated with seropositivity included: extensive feeding management (OR 2.77, 95% CI 1.25-3.77), and low precipitation below 1000 mm (OR 2.76, 95% 1.37-7.21). The disease seroprevalence is relatively low in the high dairy cattle producing regions of Tanzania. Due to the zoonotic potential of the disease, future efforts should employ a "One Health" approach to understand the epidemiology, and for interdisciplinary control to reduce the impacts on animal and human health.

Background: Coxiella burnetti can be transmitted to humans primarily through inhaling contaminated droplets released from infected animals or consumption of contaminated dairy products. Despite its zoonotic nature and the close association pastoralist communities have with their livestock, studies reporting simultaneous assessment of C. burnetti exposure and risk-factors among people and their livestock are scarce., Objective: This study therefore estimated the seroprevalence of Q-fever and associated risk factors of exposure in people and their livestock., Materials and Methods: We conducted a cross-sectional study in pastoralist communities in Marsabit County in northern Kenya. A total of 1,074 women and 225 children were enrolled and provided blood samples for Q-fever testing. Additionally, 1,876 goats, 322 sheep and 189 camels from the same households were sampled. A structured questionnaire was administered to collect individual- and household/herd-level data. Indirect IgG ELISA kits were used to test the samples., Results: Household-level seropositivity was 13.2% [95% CI: 11.2-15.3]; differences in seropositivity levels among women and children were statistically insignificant ( p = 0.8531). Lactating women had higher odds of exposure, odds ratio (OR) = 2.4 [1.3-5.3], while the odds of exposure among children increased with age OR = 1.1 [1.0-1.1]. Herd-level seroprevalence was 83.7% [81.7-85.6]. Seropositivity among goats was 74.7% [72.7-76.7], while that among sheep and camels was 56.8% [51.2-62.3] and 38.6% [31.6-45.9], respectively. Goats and sheep had a higher risk of exposure OR = 5.4 [3.7-7.3] and 2.6 [1.8-3.4], respectively relative to camels. There was no statistically significant association between Q-fever seropositivity and nutrition status in women, p = 0.900 and children, p = 1.000. We found no significant association between exposure in people and their livestock at household level (p = 0.724) despite high animal exposure levels, suggesting that Q-fever exposure in humans may be occurring at a scale larger than households., Conclusion: The one health approach used in this study revealed that Q-fever is endemic in this setting. Longitudinal studies of Q-fever burden and risk factors simultaneously assessed in human and animal populations as well as the socioeconomic impacts of the disease and further explore the role of environmental factors in Q-fever epidemiology are required. Such evidence may form the basis for designing Q-fever prevention and control strategies., Competing Interests: The authors declare no conflict of interest., (© 2022 The Author(s).)

Q fever infection in dairy herds is introduced through the transmission of the bacterium Coxiella burnetii , resulting in multiple detrimental effects such as reduction of lactation, abortions and chronic infection. Particularly in the UK, recent evidence suggests that the infection is endemic in dairy cattle. In this work, we investigate the dynamics of the disease with the aim to disentangle the relationship between the heterogeneity in the shedding routes and their effect on the environmental contamination. We develop a mathematical model for the transmission of Q fever within UK cattle herds by coupling the within-herd infection cycle of the disease with farm demographics and environmental effects, introduced by either the indoor or outdoor environment. Special focus is given on the mechanism of transmission in nulliparous heifers and multiparous cattle. We calibrate the model based on available knowledge on various epidemiological aspects of the disease and on data regarding farm demographics available in the UK DEFRA. The resulting model is able to reproduce the reported prevalence levels by field and in silico studies, as well as their evolution in time. In addition, it is built in an manner that allows the investigation of different housing techniques, farm management styles and a variety of interventions. Sensitivity analysis further reveals the parameters having the major effect in maintaining high prevalence levels of seropositive and shedding cattle. The present analysis aims also to indicate the gaps in the available data required to optimise the proposed model or future models that will developed on the basis of the one proposed herein. Finally, the developed model can serve as mathematical proof for the assessment of various interventions for controlling the dynamics of Q fever infection.

Livestock abortion is an important cause of productivity losses worldwide and many infectious causes of abortion are zoonotic pathogens that impact on human health. Little is known about the relative importance of infectious causes of livestock abortion in Africa, including in subsistence farming communities that are critically dependent on livestock for food, income, and wellbeing. We conducted a prospective cohort study of livestock abortion, supported by cross-sectional serosurveillance, to determine aetiologies of livestock abortions in livestock in Tanzania. This approach generated several important findings including detection of a Rift Valley fever virus outbreak in cattle; high prevalence of C. burnetii infection in livestock; and the first report of Neospora caninum, Toxoplasma gondii, and pestiviruses associated with livestock abortion in Tanzania. Our approach provides a model for abortion surveillance in resource-limited settings. Our findings add substantially to current knowledge in sub-Saharan Africa, providing important evidence from which to prioritise disease interventions., (© 2022. The Author(s).)

Environmental transmission of Chlamydia abortus as a result of enzootic disease or disease outbreaks and the threats posed by this pathogen has been previously reported, however a state-of-the-science review of these reports and the identification of future research priorities in this area is still lacking. This study provides an overview of the current knowledge of host-pathogen-environment interactions, addressing public health risks and identifying critical questions and research gaps. We performed a systematic PubMed and Web of Science search for publications related to Chlamydia abortus in the past four decades, and we reviewed and combined the evidence critically discussing and commenting the results. A total of 182 studies, 5 chapters of specific books and the "OIE terrestrial manual" were included in this review. There were substantial variations between the studies in topic addressed and experimental design. Overall, the literature largely supports the crucial role played by environmental exposure on the acquisition of zoonotic disease caused by Chlamydia abortus. We also identify the paucity of information related to interspecies transmission and pathogen adaptation in relation to environmental dissemination and zoonotic risk. This analysis further highlights the need for additional research given that environmental transmission represents a serious risk not only to susceptible patients (pregnant women and immunocompromised individuals), but also for other species including wildlife., (© 2022. The Author(s).)

Aims: The order Chlamydiales comprises a broad range of bacterial pathogens and endosymbionts, which infect a wide variety of host species. Within this order, members of the family Parachlamydiaceae, which includes Parachlamydia and Neochlamydia species, have been particularly associated with infections in both humans and cattle, including having a potential pathogenic role in cases of bovine abortion. While the route of transmission has yet to be defined, it has been hypothesised that asymptomatic carriage and contamination of the immediate environment may be a route of inter-animal transmission. We investigated the asymptomatic carriage of Chlamydia-related organisms in healthy cattle., Methods & Results: DNA was isolated from nasal and rectal swabs obtained from 38 healthy dairy heifers. A Chlamydiales sp. 16S rRNA qPCR was performed on each sample. A total of 18/38 nasal samples and all 38/38 rectal samples were identified as positive for Chlamydiales sp. Each positive sample was sequenced confirming the presence of DNA belonging to the Parachlamydiaceae., Conclusions: The presence of Parachlamydiaceae DNA in nasal and rectal swab samples of healthy cattle provides evidence for the asymptomatic carriage of parachlamydial organisms within cattle., Significance & Impact of the Study: The study provides evidence of potential routes of environmental contamination that could provide a route for inter-animal and animal transmission of Parachlamydiaceae., (© 2021 The Society for Applied Microbiology.)

Q fever is a bacterial disease that passes between animals and humans and causes disease in both. The disease has been associated with pregnancy complications including miscarriage. This study was undertaken to identify if Q fever exposure was correlated with miscarriage in 369 women attending a pregnancy support unit in Edinburgh. The women in the study were in two groups, the miscarriage group with 251 women who had experienced a miscarriage and a control group of 118 women who had not experienced miscarriage. Three women were found to be positive for Q fever antibodies, suggesting that they had previously been exposed to the infection and all of them were from the group who had experienced miscarriage. The study indicates that Q fever is relatively rare in women attending an urban Scottish hospital suggesting that the infection is not a major cause of miscarriage in this population. However, as Q fever antibodies could only be found in women within the miscarriage group, it suggests that the infection cannot be ruled out as a potential cause of miscarriage in individual cases., (© The authors.)

Chlamydia abortus , the aetiological agent of enzootic abortion of ewes, is a major cause of reproductive loss in small ruminants worldwide, accounting for significant economic losses to the farming industry. Disease can be managed through the use of commercial inactivated or live whole organism-based vaccines, although both have limitations particularly in terms of efficacy, safety and disease-associated outbreaks. Here we report a comparison of two experimental vaccines (chlamydial outer membrane complex (COMC) and octyl glucoside (OG)-COMC) based on detergent extracted outer membrane preparations of C. abortus and delivered as prime-boost immunisations, with the commercial live vaccine Cevac ® Chlamydia in a pregnant sheep challenge model. No abortions occurred in either experimental vaccine group, while a single abortion occurred in the commercial vaccine group. Bacterial shedding, as a measure of potential risk of transmission of infection to naïve animals, was lowest in the COMC vaccinated group, with reductions of 87.5%, 86.4% and 74% observed for the COMC, OG-COMC and live commercial vaccine groups, respectively, compared to the unvaccinated challenge control group. The results show that the COMC vaccine performed the best and is a safer efficacious alternative to the commercial vaccines. However, to improve commercial viability, future studies should optimise the antigen dose and number of inoculations required.

Coxiella burnetii is an obligate intracellular bacterium that causes Q fever, a zoonotic disease of public health importance. In northern Tanzania, Q fever is a known cause of human febrile illness, but little is known about its distribution in animal hosts. We used a quantitative real-time PCR (qPCR) targeting the insertion element IS1111 to determine the presence and prevalence of C. burnetii infections in small mammals trapped in 12 villages around Moshi Rural and Moshi Urban Districts, northern Tanzania. A total of 382 trapped small mammals of seven species were included in the study; Rattus rattus (n = 317), Mus musculus (n = 44), Mastomys natalensis (n = 8), Acomys wilson (n = 6), Mus minutoides (n = 3), Paraxerus flavovottis (n = 3) and Atelerix albiventris (n = 1). Overall, 12 (3.1%) of 382 (95% CI: 1.6-5.4) small mammal spleens were positive for C. burnetii DNA. Coxiella burnetii DNA was detected in five of seven of the small mammal species trapped; R. rattus (n = 7), M. musculus (n = 1), A. wilson (n = 2), P. flavovottis (n = 1) and A. albiventris (n = 1). Eleven (91.7%) of twelve (95% CI: 61.5-99.8) C. burnetii DNA positive small mammals were trapped within Moshi Urban District. These findings demonstrate that small mammals in Moshi, northern Tanzania are hosts of C. burnetii and may act as a source of C. burnetii infection to humans and other animals. This detection of C. burnetii infections in small mammals should motivate further studies into the contribution of small mammals to the transmission of C. burnetii to humans and animals in this region., (© 2020 The Authors Veterinary Medicine and Science Published by John Wiley & Sons Ltd.)

Chlamydia trachomatis is the most commonly diagnosed sexually transmitted infection in the UK, with over 200,000 positive diagnoses annually. The infection is thought to cause reproductive complications including problems in conceiving a pregnancy through to miscarriage and early or stillbirth. One potential reason Chlamydia may impact upon pregnancy is through disrupting the embryo implantation at the earliest stages of pregnancy is by altering the ability of specific cells that line the uterus called stromal cells to respond to the hormone progesterone, the hormone responsible for preparing the uterus for pregnancy. The results of this study showed that Chlamydial infection of these uterus lining stromal cells decreased the levels of specific progesterone sensitive markers which are associated with early embryo implantation, suggesting a loss of responsiveness to progesterone treatment. These changes were accompanied by a decrease in the levels of RNA for the progesterone receptor which is responsible for progesterone activity, suggesting that this is a potential mechanism through which Chlamydia could directly inhibit the effects of progesterone on uterine cells., Competing Interests: Nick Wheelhouse is an Associate Editor of Reproduction and Fertility. Nick Wheelhouse was not involved in the review or editorial process for this paper, on which he is listed as an author., (© 2021 The authors.)

Data are presented on the identification and partial characterisation of proteins comprising the chlamydial outer membrane complex (COMC) fraction of Chlamydia abortus (C. abortus)-the aetiological agent of ovine enzootic abortion. Inoculation with the COMC fraction is known to be highly effective in protecting sheep against experimental challenge and its constituent proteins are therefore of interest as potential vaccine candidates. Sodium N-lauroylsarcosine (sarkosyl) insoluble COMC proteins resolved by SDS-PAGE were interrogated by mass spectrometry using combined rapid monolithic column liquid chromatography and fast MS/MS scanning. Downstream database mining of processed tandem MS data revealed the presence of 67 proteins in total, including putative membrane associated proteins (n = 36), such as porins, polymorphic membrane proteins (Pmps), chaperonins and hypothetical membrane proteins, in addition to others (n = 22) that appear more likely to have originated from other subcellular compartments. Electrophoretic mobility data combined with detailed amino acid sequence information derived from secondary fragmentation spectra for 8 Pmps enabled peptides originating from protein cleavage fragments to be mapped to corresponding regions of parent precursor molecules yielding preliminary evidence in support of endogenous post-translational processing of outer membrane proteins in C. abortus. The data presented here will facilitate a deeper understanding of the pathogenesis of C. abortus infection and represent an important step towards the elucidation of the mechanisms of immunoprotection against C. abortus infection and the identification of potential target vaccine candidate antigens., Competing Interests: The authors have declared that no competing interests exist.

Background: Chlamydia trachomatis (C. trachomatis) is the most common bacterial sexually transmitted infection in the UK. Recent studies suggest that in addition to the genital tract, C. trachomatis is found in the throat and rectum, suggesting the number of infections is under-reported. There is an urgent need to study the impact of extending diagnosis to include extra-genital samples; however, there is a lack of evidence on the acceptability of asking young women to provide these samples., Method: A mixed methods single group feasibility study explored the acceptability of combined genital and extra-genital testing in young women aged 16-25 years consecutively attending a sexual health centre in Edinburgh, Scotland. Young women were asked to complete a self- administered anonymous questionnaire whether they would be willing to give self-taken throat and ano-rectal samples. Interviews with women (n = 20) willing to self-sample were conducted before and after self-sampling, and these explored the underlying reasons behind their decision, and feelings about the tests., Results: Of 500 women recruited to the study, 422 (84.4%) women provided sufficient data for analysis. From completed questionnaires, 86.3% of respondents reported willingness to self-sample from the throat. Willingness of ano-rectal self-sampling was lower (59.1%), particularly in women under 20 (< 20 years: 44.4%; ≥20 years, 68.2%). Willingness of ano-rectal self-sampling was higher in women who had more sexual partners in the last 6 months (0 partners, 48.3%, n = 14, 3 or more partners, 67.4%, n = 60) and in those who have previous experience of a positive test for a sexually transmitted infection (STI) (positive: 64.5%; negative: 57%). Interviewed women suggested that a lack of knowledge of STIs, embarrassment and lack of confidence in the ability to carry out the sampling were barriers towards acceptability., Conclusions: In this study, self-sampling of throat samples is largely acceptable; however, the acceptability of taking an ano-rectal sample for C. trachomatis testing in young women was lower in younger women. The study suggests further research to investigate the acceptability of extra-genital testing as an addition to routine C. trachomatis testing, and whether this increases detection and prevents infective sequelae for women.

Listeria monocytogenes is sporadically detected on a range of ready to eat fresh produce lines, such as spinach and rocket, and is a threat to public health. However, little is known about the diversity of L. monocytogenes present on fresh produce and their potential pathogenicity. In this work, fifteen Listeria monocytogenes isolates from the UK fresh produce supply chain were characterised using whole genome sequencing (WGS). Additionally, isolates were characterised based on their ability to form biofilm. Whole genome sequencing data was used to determine the sequence type of isolates based on multi-locus sequence typing (MLST), construct a core single nucleotide polymorphism (SNP) phylogeny and determine the presence of virulence and resistance associated genes. MLST revealed 9 distinct sequence types (STs) spanning 2 lineages (I & II) with one isolate belonging to the ST6 subtype, strains from which have been recently implicated in two large, food-associated L. monocytogenes outbreaks in South Africa and across Europe. Although most of the 15 isolates were different, comparison of core genome SNPs showed 4 pairs of 'indistinguishable' strains (<5 SNPs difference). Virulence profiling revealed that some isolates completely lacked the Listeria pathogenicity island-3 (LIPI-3) amongst other virulence factors. Investigation of the inlA gene showed that no strains in this study contained a premature stop codon (PMSC), an indicator of attenuated virulence. Assessment of biofilm production showed that isolates found in the fresh produce supply chain differ in their ability to form biofilm. This trait is considered important for L. monocytogenes to persist in environments associated with food production and processing. Overall the work indicates that a genetically diverse range of L. monocytogenes strains is present in the UK fresh produce supply chain and the virulence profiles found suggests that at least some of the strains are capable of causing human illness. Interestingly, the presence of some genetically indistinguishable isolates within the 15 isolates examined suggests that cross-contamination in the fresh produce environment does occur. These findings have useful implications in terms of food safety and for informing microbial surveillance programmes in the UK fresh produce supply chain., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Q fever is a bacterial worldwide zoonosis (except New Zealand) caused by the Gram-negative obligate intracellular bacterium Coxiella burnetii (C. burnetii). The bacterium has a large host range including arthropods, wildlife and companion animals and is frequently identified in human and livestock populations. In humans, the disease can occur as either a clinically acute or chronic aetiology, affecting mainly the lungs and liver in the acute disease, and heart valves when chronic. In livestock, Q fever is mainly asymptomatic; however, the infection can cause abortion, and the organism is shed in large quantities, where it can infect other livestock and humans. The presence of Q fever in Africa has been known for over 60 years, however while our knowledge of the transmission routes and risk of disease have been well established in many parts of the world, there is a significant paucity of knowledge across the African continent, where it remains a neglected zoonosis. Our limited knowledge of the disease across the African sub-continent have relied largely upon observational (sero) prevalence studies with limited focus on the molecular epidemiology of the disease. This review highlights the need for systematic studies to understand the routes of C. burnetii infection, and understand the disease burden and risk factors for clinical Q fever in both humans and livestock. With such knowledge gaps filled, the African continent could stand a better chance of eradicating Q fever through formulation and implementation of effective public health interventions., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Tubal ectopic pregnancies are a leading cause of global maternal morbidity and mortality. Previous infection with Chlamydia trachomatis is a major risk factor for tubal embryo implantation but the biological mechanism behind this association is unclear. Successful intra-uterine embryo implantation is associated with increased expression of endometrial "receptivity" integrins (cell adhesion molecules). We examined integrin expression in Fallopian tubes of women with previous C. trachomatis infection, in mice experimentally infected with C. trachomatis, in immortalised human oviductal epithelial cells (OE-E6/E7) and in an in vitro model of human embryo attachment (trophoblast spheroid-OE-E6/7 cell co-culture). Previous exposure with C. trachomatis increased Fallopian tube/oviduct integrin-subunit beta-1 (ITGB1) in women and mice compared to controls. C. trachomatis increased OE-E6/E7 cell ITGB1 expression and promoted trophoblast attachment to OE-E6/E7 cells which was negated by anti-ITGB1-antibody. We demonstrate that infection with C. trachomatis increases tubal ITGB1 expression, predisposing to tubal embryo attachment and ectopic pregnancy., (Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.)

Ethical behavior encompasses actions that benefit both self and society. This means that tackling antimicrobial resistance (AMR) becomes an ethical obligation, because the prospect of declining anti-infectives affects everyone. Without preventive action, loss of drugs that have saved lives over the past century, will condemn ourselves, people we know, and people we don't know, to unacceptable risk of untreatable infection. Policies aimed at extending antimicrobial life should be considered within an ethical framework, in order to balance the choice, range, and quality of drugs against stewardship activities. Conserving availability and effectiveness for future use should not compromise today's patients. Practices such as antimicrobial prophylaxis for healthy people 'at risk' should receive full debate. There are additional ethical considerations for AMR involving veterinary care, agriculture, and relevant bio-industries. Restrictions for farmers potentially threaten the quality and quantity of food production with economic consequences. Antibiotics for companion animals do not necessarily spare those used for humans. While low-income countries cannot afford much-needed drugs, pharmaceutical companies are reluctant to develop novel agents for short-term return only. Public demand encourages over-the-counter, internet, black market, and counterfeit drugs, all of which compromise international control. Prescribers themselves require educational support to balance therapeutic choice against collateral damage to both body and environment. Predicted mortality due to AMR provides justification for international co-operation, commitment and investment to support surveillance and stewardship along with development of novel antimicrobial drugs. Ethical arguments for, and against, control of antimicrobial resistance strategies are presented and discussed in this review.

To implement appropriate and effective disease control programs at the national level, up-to-date and unbiased information on disease frequency is needed. The aim of this study was to estimate the prevalence of selected endemic infectious diseases in the population of dairy herds in Great Britain. Bulk milk tank (BMT) samples from 225 randomly selected dairy farms, stratified by region and herd size, were tested for antibodies against bovine viral diarrhea virus (BVDV), bovine herpesvirus type 1, Mycobacterium avium ssp. paratuberculosis, Leptospira Hardjo, Salmonella spp., Coxiella burnetii, Fasciola hepatica, Neospora caninum, and Ostertagia ostertagi. Furthermore, the presence of BVDV, C. burnetii, and Chlamydia-like organisms was determined by PCR. The apparent herd prevalence was estimated as a weighted proportion of positive herds. The true prevalence was calculated when a test was used with known test characteristics for the cut-off value used. Among unvaccinated herds, the true prevalence of BMT antibodies against BVDV was estimated at 66% [95% confidence interval (CI): 56-77%], M. avium ssp. paratuberculosis 68% (95% CI: 59-77%), bovine herpesvirus type 1 62% (95% CI: 52-73%), Leptospira Hardjo 47% (95% CI: 34-60%), and Salmonella spp. 48% (95% CI: 39-56%). The apparent prevalence of BMT antibodies against C. burnetii was 80% (95% CI: 75-85%), F. hepatica 55% (95% CI: 48-62%), N. caninum 46% (95% CI: 38-54%), and O. ostertagi 95% (95% CI: 91-98%). The BVDV, C. burnetii, and Chlamydia-like antigens were detected in 5 (95% CI: 2-9%), 29 (95% CI: 21-36%), and 31% (95% CI: 24-38%) of herds, respectively. Our results show that dairy cows across GB are frequently exposed to the studied pathogens, which are endemic at high levels with some geographical variations. These prevalence estimates provide a much-needed basis to assess whether nationwide control programs for the studied pathogens are justified by their potential economic, environmental, and public health implications. Should surveillance and control programs be initiated, the estimates presented here are a baseline against which progress can be assessed., (The Authors. Published by the Federation of Animal Science Societies and Elsevier Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).)

Miscarriage affects ~20% of pregnancies and maternal infections account for ~15% of early miscarriages. Chlamydia trachomatis (Ct) has been associated with miscarriage but the underlying mechanisms are unknown. Successful implantation requires endometrial stromal cell (ESC) decidualisation. Maintenance of pregnancy requires angiogenesis, establishment of the correct cellular milieu and trophoblast invasion, all of which involve the action of chemokines. Our objective was to determine whether Ct infection impacts upon ESC decidualisation and chemokine secretion. Human primary ESC were decidualised in-vitro, infected with Ct serovar E, and changes in expression of genes of interest were measured using RT-PCR, proteomic array and ELISA. We demonstrate for the first time that Ct can infect and proliferate in ESC. Expression of the decidualisation marker prolactin was decreased in Ct-infected ESC at both mRNA and protein levels. Ct infection altered the chemokine profile of decidualised ESC as shown by proteomic array. Chemokines CXCL12 and CXCL16, important for trophoblast invasion, were analysed further and expression was reduced in infected decidualised cells at mRNA and protein levels. Our data indicate that Ct infection of ESC impairs decidualisation and alters chemokine release. These findings at least partially explain how Ct infection could result in adverse pregnancy outcomes.

This study investigated the pathogenesis of two variant strains (LLG and POS) of Chlamydia abortus, in comparison to a typical wild-type strain (S26/3) which is known to be responsible for late term abortion in small ruminants. Challenge with the three strains at mid-gestation resulted in similar pregnancy outcomes, with abortion occurring in approximately 50-60% of ewes with the mean gestational lengths also being similar. However, differences were observed in the severity of placental pathology, with infection appearing milder for strain LLG, which was reflected in the lower number of organisms shed in vaginal swabs post-partum and less gross pathology and organisms present in placental smears. Results for strain POS were somewhat different than LLG with a more focal restriction of infection observed. Post-abortion antibody responses revealed prominent differences in seropositivity to the major outer membrane protein (MOMP) present in elementary body (EB) preparations under denaturing conditions, most notably with anti-LLG and anti-POS convalescent sera where there was no or reduced detection of MOMP present in EBs derived from the three strains. These results and additional analysis of whole EB and chlamydial outer membrane complex preparations suggest that there are conformational differences in MOMP for the three strains. Overall, the results suggest that gross placental pathology and clinical outcome is not indicative of bacterial colonization and the severity of infection. The results also highlight potential conformational differences in MOMP epitopes that perhaps impact on disease diagnosis and the development of new vaccines.

Waddlia chondrophila is a Gram-negative intracellular bacterial organism that is related to classical chlamydial species and has been implicated as a cause of abortion in cattle. Despite an increasing number of observational studies linking W. chondrophila infection to cattle abortion, little direct experimental evidence exists. Given this paucity of direct evidence the current study was carried out to investigate whether experimental challenge of pregnant cattle with W. chondrophila would result in infection and abortion. Nine pregnant Friesian-Holstein heifers received 2 × 10 8 inclusion forming units (IFU) W. chondrophila intravenously on day 105-110 of pregnancy, while four negative-control animals underwent mock challenge. Only one of the challenged animals showed pathogen-associated lesions, with the organism being detected in the diseased placenta. Importantly, the organism was re-isolated and its identity confirmed by whole genome sequencing, confirming Koch's third and fourth postulates. However, while infection of the placenta was observed, the experimental challenge in this study did not confirm the abortifacient potential of the organism., Competing Interests: ES is the CEO and VF the lead in bacteriology at BioSellal which manufactures and supplies the commercial Waddlia chondrophila qPCR kit used during this study. The remaining authors declare no competing financial interests.

Climate change has the potential to impair livestock health, with consequences for animal welfare, productivity, greenhouse gas emissions, and human livelihoods and health. Modelling has an important role in assessing the impacts of climate change on livestock systems and the efficacy of potential adaptation strategies, to support decision making for more efficient, resilient and sustainable production. However, a coherent set of challenges and research priorities for modelling livestock health and pathogens under climate change has not previously been available. To identify such challenges and priorities, researchers from across Europe were engaged in a horizon-scanning study, involving workshop and questionnaire based exercises and focussed literature reviews. Eighteen key challenges were identified and grouped into six categories based on subject-specific and capacity building requirements. Across a number of challenges, the need for inventories relating model types to different applications (e.g. the pathogen species, region, scale of focus and purpose to which they can be applied) was identified, in order to identify gaps in capability in relation to the impacts of climate change on animal health. The need for collaboration and learning across disciplines was highlighted in several challenges, e.g. to better understand and model complex ecological interactions between pathogens, vectors, wildlife hosts and livestock in the context of climate change. Collaboration between socio-economic and biophysical disciplines was seen as important for better engagement with stakeholders and for improved modelling of the costs and benefits of poor livestock health. The need for more comprehensive validation of empirical relationships, for harmonising terminology and measurements, and for building capacity for under-researched nations, systems and health problems indicated the importance of joined up approaches across nations. The challenges and priorities identified can help focus the development of modelling capacity and future research structures in this vital field. Well-funded networks capable of managing the long-term development of shared resources are required in order to create a cohesive modelling community equipped to tackle the complex challenges of climate change., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Cationic host defence peptides (CHDP; also known as antimicrobial peptides) are key components of the immune response in the female reproductive tract. The role of the placental trophoblast in ovine host defence remains poorly understood. This study characterises expression of genes for cathelicidin and defensin peptides in primary ovine placental tissues, the ovine trophoblast cell line (AH-1) and in response to the TLR-4 ligand LPS, the abortifacient organism Waddlia chondrophila and 1α,25-dihydroxyvitamin D3. Using RT-PCR, expression of the CHDP SMAP-29, sBD-1 and sBD-2 was assessed in the AH-1 cell line in response to LPS, 1α,25-dihydroxyvitamin D3 exposure (a known stimulator of cathelicidin gene expression), or W. chondrophila infection. Expression of cathelicidin in the trophoblast compartment of the ovine placenta and in the ovine trophoblast cell line (AH-1) was also established. AH-1 cells did not upregulate expression of CHDP in response to LPS, but sBD-1 and sBD-2 expression was significantly increased in response to W. chondrophila infection. SMAP-29 expression was not altered by in vitro exposure to 1α,25-dihydroxyvitamin D3. This study demonstrates that the ovine trophoblast expresses cathelicidins, but does not upregulate expression of CHDP in response to LPS. Ovine trophoblasts are shown to differentially regulate expression of CHDP and lack a demonstrable vitamin D-mediated cathelicidin response., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Background: Waddlia chondrophila (W. chondrophila) is an emerging agent of respiratory and reproductive disease in humans and cattle. The organism is a member of the order Chlamydiales, and shares many similarities at the genome level and in growth studies with other well-characterised zoonotic chlamydial agents, such as Chlamydia abortus (C. abortus). The current study investigated the growth characteristics and innate immune responses of human and ruminant epithelial cells in response to infection with W. chondrophila., Methods: Human epithelial cells (HEp2) were infected with W. chondrophila for 24h. CXCL8 release was significantly elevated in each of the cell lines by active-infection with live W. chondrophila, but not by exposure to UV-killed organisms. Inhibition of either p38 or p42/44 MAPK significantly inhibited the stimulation of CXCL8 release in each of the cell lines. To determine the pattern recognition receptor through which CXCL8 release was stimulated, wild-type HEK293 cells which express no TLR2, TLR4, NOD2 and only negligible NOD1 were infected with live organisms. A significant increase in CXCL8 was observed., Conclusions/significance: W. chondrophila actively infects and replicates within both human and ruminant epithelial cells stimulating CXCL8 release. Release of CXCL8 is significantly inhibited by inhibition of either p38 or p42/44 MAPK indicating a role for this pathway in the innate immune response to W. chondrophila infection. W. chondrophila stimulation of CXCL8 secretion in HEK293 cells indicates that TLR2, TLR4, NOD2 and NOD1 receptors are not essential to the innate immune response to infection.

Background: Miscarriage is the spontaneous loss of a pregnancy before 12 weeks (early miscarriage) or from 12 to 24 weeks (late miscarriage) of gestation. Miscarriage occurs in one in five pregnancies and can have considerable physiological and psychological implications for the patient. It is also associated with significant health care costs. There is evidence that potentially preventable infections may account for up to 15% of early miscarriages and up to 66% of late miscarriages. However, the provision of associated screening and management algorithms is inconsistent for newly pregnant women. Here, we review recent population-based studies on infections that have been shown to be associated with miscarriage., Methods: Our aim was to examine where the current scientific focus lies with regards to the role of infection in miscarriage. Papers dating from June 2009 with key words 'miscarriage' and 'infection' or 'infections' were identified in PubMed (292 and 327 papers, respectively, on 2 June 2014). Relevant human studies (meta-analyses, case-control studies, cohort studies or case series) were included. Single case reports were excluded. The studies were scored based on the Newcastle - Ottawa Quality Assessment Scale., Results: The association of systemic infections with malaria, brucellosis, cytomegalovirus and human immunodeficiency virus, dengue fever, influenza virus and of vaginal infection with bacterial vaginosis, with increased risk of miscarriage has been demonstrated. Q fever, adeno-associated virus, Bocavirus, Hepatitis C and Mycoplasma genitalium infections do not appear to affect pregnancy outcome. The effects of Chlamydia trachomatis, Toxoplasma gondii, human papillomavirus, herpes simplex virus, parvovirus B19, Hepatitis B and polyomavirus BK infections remain controversial, as some studies indicate increased miscarriage risk and others show no increased risk. The latest data on rubella and syphilis indicate increased antenatal screening worldwide and a decrease in the frequency of their reported associations with pregnancy failure. Though various pathogens have been associated with miscarriage, the mechanism(s) of infection-induced miscarriage are not yet fully elucidated., Conclusions: Further research is required to clarify whether certain infections do increase miscarriage risk and whether screening of newly pregnant women for treatable infections would improve reproductive outcomes., (© The Author 2015. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology.)

Background: Waddlia chondrophila (W. chondrophila) is an emerging abortifacient organism which has been identified in the placentae of humans and cattle. The organism is a member of the order Chlamydiales, and shares many similarities at the genome level and in growth studies with other well-characterised zoonotic chlamydial abortifacients, such as Chlamydia abortus (C. abortus). This study investigates the growth of the organism and its effects upon pro-inflammatory cytokine expression in a ruminant placental cell line which we have previously utilised in a model of C. abortus pathogenicity., Methodology/principal Findings: Using qPCR, fluorescent immunocytochemistry and electron microscopy, we characterised the infection and growth of W. chondrophila within the ovine trophoblast AH-1 cell line. Inclusions were visible from 6 h post-infection (p.i.) and exponential growth of the organism could be observed over a 60 h time-course, with significant levels of host cell lysis being observed only after 36 h p.i. Expression of CXCL8, TNF-α, IL-1α and IL-1β were determined 24 h p.i. A statistically significant response in the expression of CXCL8, TNF-α and IL-1β could be observed following active infection with W. chondrophila. However a significant increase in IL-1β expression was also observed following the exposure of cells to UV-killed organisms, indicating the stimulation of multiple innate recognition pathways., Conclusions/significance: W. chondrophila infects and grows in the ruminant trophoblast AH-1 cell line exhibiting a complete chlamydial replicative cycle. Infection of the trophoblasts resulted in the expression of pro-inflammatory cytokines in a dose-dependent manner similar to that observed with C. abortus in previous studies, suggesting similarities in the pathogenesis of infection between the two organisms.

Background: Chlamydia pecorum is the causative agent of a number of acute diseases, but most often causes persistent, subclinical infection in ruminants, swine and birds. In this study, the genome sequences of three C. pecorum strains isolated from the faeces of a sheep with inapparent enteric infection (strain W73), from the synovial fluid of a sheep with polyarthritis (strain P787) and from a cervical swab taken from a cow with metritis (strain PV3056/3) were determined using Illumina/Solexa and Roche 454 genome sequencing., Results: Gene order and synteny was almost identical between C. pecorum strains and C. psittaci. Differences between C. pecorum and other chlamydiae occurred at a number of loci, including the plasticity zone, which contained a MAC/perforin domain protein, two copies of a >3400 amino acid putative cytotoxin gene and four (PV3056/3) or five (P787 and W73) genes encoding phospholipase D. Chlamydia pecorum contains an almost intact tryptophan biosynthesis operon encoding trpABCDFR and has the ability to sequester kynurenine from its host, however it lacks the genes folA, folKP and folB required for folate metabolism found in other chlamydiae. A total of 15 polymorphic membrane proteins were identified, belonging to six pmp families. Strains possess an intact type III secretion system composed of 18 structural genes and accessory proteins, however a number of putative inc effector proteins widely distributed in chlamydiae are absent from C. pecorum. Two genes encoding the hypothetical protein ORF663 and IncA contain variable numbers of repeat sequences that could be associated with persistence of infection., Conclusions: Genome sequencing of three C. pecorum strains, originating from animals with different disease manifestations, has identified differences in ORF663 and pseudogene content between strains and has identified genes and metabolic traits that may influence intracellular survival, pathogenicity and evasion of the host immune system.

Despite the availability of effective management and treatment strategies, Chlamydia abortus remains the single most frequently diagnosed cause of infectious ovine abortion (enzootic abortion of ewes, EAE) in the UK and one of the most significant causes of lamb mortality world-wide. In 2007, a survey of UK farmers, veterinarians and other farm animal holders was conducted to gather information on their perceptions of the risk of acquiring infection and the management practices employed to control the disease. The survey indicated that the preferred options for controlling EAE are either through vaccination and/or keeping flocks closed. However, further analysis of data indicates that implementation of these strategies does not provide a guarantee of exclusion of disease from flocks and thus further work is required to improve on current intervention strategies., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Lawsonia intracellularis is the etiological agent of proliferative enteropathy (PE), causing mild or acute hemorrhagic diarrhea in infected animals. Here we report the genome sequence of strain N343, isolated from a sow that died of hemorrhagic PE. N343 contains 24 single nucleotide polymorphisms and 90 indels compared to the reference strain PHE/MN1-00.