Controlling Coxiella burnetii in naturally infected sheep, goats and cows, and public health implications: a scoping review.

Q fever is a worldwide zoonotic disease which domestic ruminants are the main source of infection for humans. This scoping review summarizes the control measures currently available to reduce Coxiella burnetii (Cb) infection in naturally infected sheep, goat and cattle herds. A total of 28 articles were included in the review. A lack of methodological standardization was noted in the articles analyzed. The results indicated that long-term vaccination in cows reduces bacterial excretion in milk and environmental contamination. In small ruminants, the results of vaccination in terms of efficacy are variable. In goats, there is a reduction in bacterial excretion, unlike in sheep, where a long-term vaccination program is necessary to reduce bacterial excretion. Moreover, the high persistence of viable Cb in the environment means that control measures for sheep are needed for several years. The use of antibiotics as a control measure in cows and sheep was not found to reduce excretion. However, the combination of vaccination with antibiotic therapy appears to have positive effects in small ruminants in terms of controlling outbreaks of Q fever. Hygiene and biosecurity measures are the basic means for controlling Cb infection on ruminant farms and ensuring public health.

Genome Mosaicism in Field Strains of Mycoplasma bovis as Footprints of In-Host Horizontal Chromosomal Transfer.

Horizontal gene transfer was long thought to be marginal in Mollicutes, but the capacity of some of these wall-less bacteria to exchange large chromosomal regions has been recently documented. Mycoplasma chromosomal transfer (MCT) is an unconventional mechanism that relies on the presence of a functional integrative conjugative element (ICE) in at least one partner and involves the horizontal acquisition of small and large chromosomal fragments from any part of the donor genome, which results in progenies composed of an infinite variety of mosaic genomes. The present study focuses on Mycoplasma bovis, an important pathogen of cattle responsible for major economic losses worldwide. By combining phylogenetic tree reconstructions and detailed comparative genome analyses of 36 isolates collected in Spain (2016 to 2018), we confirmed the mosaic nature of 16 field isolates and mapped chromosomal transfers exchanged between their hypothetical ancestors. This study provides evidence that MCT can take place in the field, most likely during coinfections by multiple strains. Because mobile genetic elements (MGEs) are classical contributors of genome plasticity, the presence of phages, insertion sequences (ISs), and ICEs was also investigated. Data revealed that these elements are widespread within the M. bovis species and evidenced classical horizontal transfer of phages and ICEs in addition to MCT. These events contribute to wide-genome diversity and reorganization within this species and may have a tremendous impact on diagnostic and disease control. IMPORTANCE Mycoplasma bovis is a major pathogen of cattle that has significant detrimental effects on economics and animal welfare in cattle rearing worldwide. Understanding the evolution and the adaptative potential of pathogenic mycoplasma species in the natural host is essential to combating them. In this study, we documented the occurrence of mycoplasma chromosomal transfer, an atypical mechanism of horizontal gene transfer, in field isolates of M. bovis that provide new insights into the evolution of this pathogenic species in their natural host. Although these events are expected to occur at low frequency, their impact is accountable for genome-wide variety and reorganization within M. bovis species, which may compromise both diagnostic and disease control.

Importance and Antimicrobial Resistance of Mycoplasma bovis in Clinical Respiratory Disease in Feedlot Calves.

Bovine respiratory disease (BRD) is an important viral and/or bacterial disease that mainly affects feedlot calves. The involvement of Mycoplasma bovis in BRD can lead to chronic pneumonia poorly responsive to antimicrobial treatment. Caseonecrotic bronchopneumonia is a pulmonary lesion typically associated with M. bovis. In Spain, M. bovis is widely distributed in the feedlots and circulating isolates are resistant to most antimicrobials in vitro. However, the role of this species in clinical respiratory disease of feedlot calves remains unknown. Furthermore, available data are relative to a fixed panel of antimicrobials commonly used to treat BRD, but not to the specific set of antimicrobials that have been used for treating each animal. This study examined 23 feedlot calves raised in southeast Spain (2016-2019) with clinical signs of respiratory disease unresponsive to treatment. The presence of M. bovis was investigated through bacteriology (culture and subsequent PCR), histopathology and immunohistochemistry. The pathogen was found in 86.9% (20/23) of the calves, mainly in the lungs (78.26%; 18/23). Immunohistochemistry revealed M. bovis antigens in 73.9% (17/23) of the calves in which caseonecrotic bronchopneumonia was the most frequent lesion (16/17). Minimum inhibitory concentration assays confirmed the resistance of a selection of 12 isolates to most of the antimicrobials specifically used for treating the animals in vivo. These results stress the importance of M. bovis in the BRD affecting feedlot calves in Spain.

PK/PD Analysis of Marbofloxacin by Monte Carlo Simulation against Mycoplasmaagalactiae in Plasma and Milk of Lactating Goats after IV, SC and SC-Long Acting Formulations Administration.

Contagious agalactia is a mycoplasmosis affecting small ruminants that have become an important issue in many countries. However, PK/PD studies of antibiotics to treat this problem in lactating goats affected by Mycoplasma (M.) agalactiae, the main CA-causing mycoplasma are almost non-existent. The aims of this study were to evaluate the plasma and milk disposition of marbofloxacin in lactating goats after intravenous (IV), subcutaneous (SC) and subcutaneous poloxamer P407 formulations with and without carboxy-methylcellulose (SC-P407-CMC and SC-P407) administration. Marbofloxacin concentrations were analysed by the High Performance Liquid Chromatography (HPLC) method. Minimum inhibitory concentrations (MIC) of M. agalactiae field isolates from mastitic goat's milk were used to calculate surrogate markers of efficacy. Terminal half-lives of marbofloxacin after IV, SC, SC-P407 and SC-P407-CMC administration were 7.12, 6.57, 13.92 and 12.19 h in plasma, and the half-lives of elimination of marbofloxacin in milk were 7.22, 7.16, 9.30 and 7.74 h after IV, SC, SC-P407 and SC-P407-CMC administration, respectively. Marbofloxacin penetration from the blood into the milk was extensive, with Area Under the Curve (AUCmilk/AUCplasma) ratios ranged 1.04-1.23, and maximum concentrations (Cmax-milk/Cmax-plasma) ratios ranged 0.72-1.20. The PK/PD surrogate markers of efficacy fAUC24/MIC and the Monte Carlo simulation show that marbofloxacin ratio (fAUC24/MIC > 125) using a 90% of target attainment rate (TAR) need a dose regimen between 8.4 mg/kg (SC) and 11.57 mg/kg (P407CMC) and should be adequate to treat contagious agalactia in lactating goats.

Mycoplasma bovis in Spanish Cattle Herds: Two Groups of Multiresistant Isolates Predominate, with One Remaining Susceptible to Fluoroquinolones.

Mycoplasma bovis is an important bovine pathogen causing pneumonia, mastitis, and arthritis and is responsible for major economic losses worldwide. In the absence of an efficient vaccine, control of M. bovis infections mainly relies on antimicrobial treatments, but resistance is reported in an increasing number of countries. To address the situation in Spain, M. bovis was searched in 436 samples collected from beef and dairy cattle (2016-2019) and 28% were positive. Single-locus typing using polC sequences further revealed that two subtypes ST2 and ST3, circulate in Spain both in beef and dairy cattle, regardless of the regions or the clinical signs. Monitoring of ST2 and ST3 isolates in a minimum inhibitory concentration (MIC) to a panel of antimicrobials revealed one major difference when using fluoroquinolones (FQL): ST2 is more susceptible than ST3. Accordingly, whole-genome sequencing (WGS) further identified mutations in the gyrA and parC regions, encoding quinolone resistance-determining regions (QRDR) only in ST3 isolates. This situation shows the capacity of ST3 to accumulate mutations in QRDR and might reflect the selective pressure imposed by the extensive use of these antimicrobials. MIC values and detection of mutations by WGS also showed that most Spanish isolates are resistant to macrolides, lincosamides, and tetracyclines. Valnemulin was the only one effective, at least in vitro, against both STs.

The Addition of Lactobacillus spp., Enrofloxacin or Doxycycline Negatively Affects the Viability of Mycoplasma bovis in Diluted Bovine Semen.

Mycoplasma bovis is an important etiologic agent of bovine mycoplasmosis in cattle. Different transmission routes have been described, including those related to reproduction. The presence of mycoplasma in semen has led to its appearance in infection-free areas through artificial insemination (AI). Semen was recently reported to be the initial source of two M. bovis mastitis outbreaks in two closed dairy herds in Finland. This questions the effectiveness of the antimicrobials currently used in semen extenders to control the pathogens in contaminated semen. They should be re-evaluated, or alternative measures to antimicrobials should be tested to obtain M. bovis-free semen. This in vitro study aimed to assess different strategies to reduce the risk of transmission of M. bovis through AI technologies. The viability of M. bovis (PG45, NCTC 10131) in bull semen diluted (DS) in a Tris-citrate-fructose solution was tested, after the addition of enrofloxacin, doxycycline or a Lactobacillus spp.-based probiotic. The data show the susceptibility of the pathogen to the addition of 0.125 µg/mL of enrofloxacin or 0.0625 µg/mL of doxycycline and to the addition of the probiotic at a concentration of 3.24 × 106 colony forming units (CFU)/mL or 3.24 × 108 CFU/mL in DS. The Tris-citrate-fructose medium negatively affected the viability of M. bovis, although this effect was lower than that observed after the addition of the probiotic and antimicrobials (p < 0.05). Our results may support new strategies for reducing the risk of M. bovis transmission through AI.

[Occupational exposure to influenza virus of the wild birds]. / Exposición ocupacional a los virus influenza de las aves silvestres.

Wild waterfowl are considered the main natural reservoir of influenza viruses and they have contributed to the reassortment of both pandemic viruses and viruses responsible for outbreaks of avian influenza in wild and domestic species. In order to determinate the factors involved, we reviewed the human cases of avian influenza related to the management of wild birds, the use of personal protective equipment, as well as the basis of surveillance programs of highly pathogenic avian influenza in wild birds in Spain. The direct transmission of influenza virus from wild birds to humans is a rare event. However, our epidemiological context is influenced by climate change and marked by the presence of migratory routes from territories where infection may be present. Thus and due to the clinical, economical and public health implications that such infections may have, the different groups exposed to wild birds (veterinarians, biologists, ornithologists, conservationists, field technicians, environmental officers, falconers, hunters, etc.) should know which are the possible sources of infection and how to handle the personal protective equipment. Besides, it is important that those groups know the current sanitary situation regarding avian influenza so they can consequently adapt their activities and employ proper protective measures, in addition to providing valuable information for surveillance programs.

Las aves acuáticas silvestres representan el principal reservorio natural de los virus influenza y han participado en el reordenamiento tanto de virus pandémicos como de los virus responsables de los brotes de gripe aviar en las especies domésticas y silvestres. Con el objetivo de conocer los determinantes implicados, en el presente trabajo se revisaron los casos humanos de influenza aviar asociados al manejo de avessilvestres y la utilización de los equipos de protección personal, así como las bases de la vigilancia de la influencia aviar altamente patógena en aves silvestres en España. Las evidencias existentes permiten concluir que la transmisión directa de virus influenza desde las aves silvestres al ser humano es un evento raro. No obstante, nuestro contexto epidemiológico se encuentra influido por el cambio climático y queda marcado por la presencia de rutas migratorias desde territorios donde la infección puede estar presente. Por ello, y ante las implicaciones clínicas, económicas y para la salud pública que dichas infecciones pueden tener, los diferentes colectivos expuestos a las aves silvestres (veterinarios, biólogos, ornitólogos, conservacionistas, técnicos de campo, agentes medioambientales, cetreros, cazadores, etc.) deberían conocer las posibles fuentes de contagio y manejar correctamente los equipos de protección personal. Al mismo tiempo, es importante que dichos grupos conozcan la situación sanitaria actualizada respecto a la influenza aviar, para adaptar sus actividades en consecuencia y poder aplicar las medidas de protección de forma proporcionada a la misma, amén de aportar una valiosa información para los programas de vigilancia.

Exposición ocupacional a los virus influenza de las aves silvestres / Occupational exposure to influenza virus of the wild birds

Las aves acuáticas silvestres representan el principal reservorio natural de los virus influenza y han participado en el reordenamiento tanto de virus pandémicos como de los virus responsables de los brotes de gripe aviar en las especies domésticas y silvestres. Con el objetivo de conocer los determinantes implicados, en el presente trabajo se revisaron los casos humanos de influenza aviar asociados al manejo de avessilvestres y la utilización de los equipos de protección personal, así como las bases de la vigilancia de la influencia aviar altamente patógena en aves silvestres en España. Las evidencias existentes permiten concluir que la transmisión directa de virus influenza desde las aves silvestres al ser humano es un evento raro. No obstante, nuestro contexto epidemiológico se encuentra influido por el cambio climático y queda marcado por la presencia de rutas migratorias desde territorios donde la infección puede estar presente. Por ello, y ante las implicaciones clínicas, económicas y para la salud pública que dichas infecciones pueden tener, los diferentes colectivos expuestos a las aves silvestres (veterinarios, biólogos, ornitólogos, conservacionistas, técnicos de campo, agentes medioambientales, cetreros, cazadores, etc.) deberían conocer las posibles fuentes de contagio y manejar correctamente los equipos de protección personal. Al mismo tiempo, es importante que dichos grupos conozcan la situación sanitaria actualizada respecto a la influenza aviar, para adaptar sus actividades en consecuencia y poder aplicar las medidas de protección de forma proporcionada a la misma, amén de aportar una valiosa información para los programas de vigilancia

Wild waterfowl are considered the main natural reservoir of influenza viruses and they have contributed to the reassortment of both pandemic viruses and viruses responsible for outbreaks of avian influenza in wild and domestic species. In order to determinate the factors involved, we reviewed the human cases of avian influenza related to the management of wild birds, the use of personal protective equipment, as well as the basis of surveillance programs of highly pathogenic avian influenza in wild birds in Spain. The direct transmission of influenza virus from wild birds to humans is a rare event. However, our epidemiological context is influenced by climate change and marked by the presence of migratory routes from territories where infection may be present. Thus and due to the clinical, economical and public health implications that such infections may have, the different groups exposed to wild birds (veterinarians, biologists, ornithologists, conservationists, field technicians, environmental officers, falconers, hunters, etc.) should know which are the possible sources of infection and how to handle the personal protective equipment. Besides, it is important that those groups know the current sanitary situation regarding avian influenza so they can consequently adapt their activities and employ proper protective measures, in addition to providing valuable information for surveillance programs

[Zoonoses and occupational health in the veterinary profession]. / Zoonosis y salud laboral en la profesión veterinaria.

The veterinary profession implies a greater risk of infection by zoonotic pathogens than the overall population. The aim of the present work was to evaluate the impact of zoonoses on the occupational health of veterinarians reviewing the published surveys addressing this subject. Following these inquiries, between 4% and 64.3% of the surveyed professionals acknowledge to have suffered at least one zoonotic disease, and dermatophytosis is the most frequently described zoonosis. In addition, from a qualitative point of view, it is necessary to highlight the occurrence of different diseases of important clinical seriousness and the existence of infections by antimicrobial-resistant pathogens. Due to the absence of updated studies in Spain, the present work reflects on the need to recognize the health determinants associated to the veterinary profession within the characteristics of our labour market. The available data suggest that the occurrence of zoonoses as occupational diseases is underestimated in Spain. Therefore, performing surveys on occupational health, documenting and publishing cases and reviewing the risks and the impact of zoonotic diseases on the veterinary profession would contribute to the description and notification of such diseases on behalf of the healthcare administration and would also become an essential tool in occupational risk prevention.

La profesión veterinaria presenta mayor riesgo de infección frente a agentes patógenos de carácter zoonósico que la población general. Con el objetivo de valorar el impacto de las zoonosis, el presente trabajo revisa las encuestas publicadas sobre salud laboral en la profesión veterinaria. En dichas encuestas, el rango de profesionales que refieren haber padecido al menos una zoonosis oscila entre el 4% y el 64,3%, siendo la dermatofitosis la zoonosis comunicada con mayor frecuencia. Además, desde el punto de vista cualitativo, cabe destacar la comunicación de diferentes procesos de especial gravedad clínica, así como la existencia documentada de infecciones por agentes patógenos resistentes a los antimicrobianos. Dada la ausencia de estudios actualizados en España, se reflexiona sobre la necesidad de conocer los determinantes de salud asociados a las características del mercado laboral de la profesión en nuestro entorno. Los datos existentes sugieren que la consideración legal de enfermedad profesional para las zoonosis se encuentra infraestimada en nuestro país. Por todo ello, la realización de encuestas de salud laboral, la documentación y publicación de los casos, así como la revisión de los riesgos y el impacto de las zoonosis en la profesión veterinaria, pueden contribuir a la calificación y notificación de dichas enfermedades por parte de la administración sanitaria, al tiempo que suponen una herramienta fundamental en el ámbito de la prevención de riesgos laborales.

Zoonosis y salud laboral en la profesión veterinaria / Zoonoses and occupational health in the veterinary profession

La profesión veterinaria presenta mayor riesgo de infección frente a agentes patógenos de carácter zoonósico que la población general. Con el objetivo de valorar el impacto de las zoonosis, el presente trabajo revisa las encuestas publicadas sobre salud laboral en la profesión veterinaria. En dichas encuestas, el rango de profesionales que refieren haber padecido al menos una zoonosis oscila entre el 4% y el 64,3%, siendo la dermatofitosis la zoonosis comunicada con mayor frecuencia. Además, desde el punto de vista cualitativo, cabe destacar la comunicación de diferentes procesos de especial gravedad clínica, así como la existencia documentada de infecciones por agentes patógenos resistentes a los antimicrobianos. Dada la ausencia de estudios actualizados en España, se reflexiona sobre la necesidad de conocer los determinantes de salud asociados a las características del mercado laboral de la profesión en nuestro entorno. Los datos existentes sugieren que la consideración legal de enfermedad profesional para las zoonosis se encuentra infraestimada en nuestro país. Por todo ello, la realización de encuestas de salud laboral, la documentación y publicación de los casos, así como la revisión de los riesgos y el impacto de las zoonosis en la profesión veterinaria, pueden contribuir a la calificación y notificación de dichas enfermedades por parte de la administración sanitaria, al tiempo que suponen una herramienta fundamental en el ámbito de la prevención de riesgos laborales

The veterinary profession implies a greater risk of infection by zoonotic pathogens than the overall population. The aim of the present work was to evaluate the impact of zoonoses on the occupational health of veterinarians reviewing the published surveys addressing this subject. Following these inquiries, between 4% and 64.3% of the surveyed professionals acknowledge to have suffered at least one zoonotic disease, and dermatophytosis is the most frequently described zoonosis. In addition, from a qualitative point of view, it is necessary to highlight the occurrence of different diseases of important clinical seriousness and the existence of infections by antimicrobial-resistant pathogens. Due to the absence of updated studies in Spain, the present work reflects on the need to recognize the health determinants associated to the veterinary profession within the characteristics of our labour market. The available data suggest that the occurrence of zoonoses as occupational diseases is underestimated in Spain. Therefore, performing surveys on occupational health, documenting and publishing cases and reviewing the risks and the impact of zoonotic diseases on the veterinary profession would contribute to the description and notification of such diseases on behalf of the healthcare administration and would also become an essential tool in occupational risk prevention