Purpose of Review Brucellosis is a neglected, zoonotic disease of nearly worldwide distribution. Despite brucellosis being recognized as a reproductive disease in animals, it has been historically known as a flu-like illness in humans with little or no significant role in maternal or newborn health. This review focuses on what is currently known relative to the epidemiology of brucellosis in human pregnancy as well as new insights of placental immunology. Recent Findings New evidence suggests that maternal infection poses a significant risk factor for adverse pregnancy outcomes including increased risk for miscarriage during the first and second trimester of gestation, preterm delivery, and vertical transmission to the fetus. Adverse pregnancy outcomes were not associated with any specific clinical sign. However, prompt diagnosis and treatment significantly decreased the risk of miscarriage or any other adverse effect. Summary Brucellosis during pregnancy should be considered a significant risk factor for adverse pregnancy outcomes in humans. The identification of the mechanism behind bacterial tropism should prove powerful for the development of new countermeasures to prevent these detrimental effects. Increased awareness concerning brucellosis in pregnant women, its transmission, and prevention measures should be considered as a pressing need.

B . melitensis is considered the most virulent of the Brucella species, and a need exists for an improved laboratory animal model of infection that mimics natural transmission and disease. Guinea pigs are highly susceptible to infection with Brucella spp. and develop a disease syndrome that mimics natural disease after aerosol inoculation. Intratracheal inoculation is a targeted means of generating aerosols that offer advantages over aerosol chamber delivery. To establish this delivery method, female, Hartley guinea pigs were infected via intratracheal inoculation with PBS or 16M B . melitensis at low dose (10 1 to 10 3 ) or high dose (10 6 to 10 8 ) and monitored for 30 days for signs of disease. Guinea pigs in the high dose groups developed fever between 12–17 days post-inoculation. Bacteria were recovered from the spleen, liver, lymph nodes, lung, and uterus at 30-days post-inoculation and demonstrated dose dependent mean increases in colonization and pathologic changes consistent with human brucellosis. To study the kinetics of extrapulmonary dissemination, guinea pigs were inoculated with 10 7 CFU and euthanized at 2-hours post inoculation and at weekly intervals for 3 weeks. 5.8x10 5 to 4.2x10 6 CFU were recovered from the lung 2 hours post-inoculation indicating intratracheal inoculation is an efficient means of infecting guinea pigs. Starting at 1-week post inoculation bacteria were recovered from the aforementioned organs with time dependent mean increases in colonization. This data demonstrates that guinea pigs develop a disease syndrome that models the human manifestation of brucellosis, which makes the guinea pig a valuable model for pathogenesis studies.

Brucellosis is a zoonosis of nearly worldwide distribution. The disease is considered to be endemic in most of the developing countries with a substantial impact on both human and animal health as well as on the economy. The aim of this scoping review is to provide an overview of the brucellosis status in Colombia and the factors associated with its persistence, to highlight the strengths and gaps of the adopted countermeasures and to supply evidence to policy-makers on the best approaches to mitigate the disease burden. Due to the presence of brucellosis in several susceptible production livestock systems scattered throughout the country, a plan for its control, prevention and eradication was established almost 20 years ago. However, despite extensive efforts, brucellosis prevalence has fluctuated over the years without any trend of decreasing. The restricted budget allocated for brucellosis control is a limiting factor for the success of the program. For instance, the absence of indemnities for farmers results in infected animals remaining on farms which potentially increases the risk of disease spread. Likewise, disease surveillance is restricted to Brucella abortus and excludes other Brucella species of importance, such as B. melitensis and B. suis. The countermeasures are mostly focused on cattle and only a few actions are in place for the management of brucellosis in other livestock species. In humans, cases of brucellosis are annually diagnosed, although the disease remains highly underreported. High impact educational and training programs are required to address the disease in a comprehensive manner, including vulnerable groups, such as traditional smallholders and low-productivity regions, as well as other stakeholders, such as healthcare and veterinary authorities. Important financial investments based on sustained cooperation between governmental institutions, industry, and farmers are important for developing affordable and effective strategies to control the disease.

Canine brucellosis, caused by Brucella canis , is a disease of dogs and represents a public health concern as it can be transmitted to humans. Canine brucellosis is on the rise in the United States and there is currently no vaccine for use in dogs. Mice have been extensively utilized to investigate host-pathogen interactions and vaccine candidates for smooth Brucella species and could serve a similar role for studying B . canis . However, comparatively little is known about B . canis infection in mice. The objective of this study was to characterize the kinetics of colonization and pathogenicity of B . canis in mice in order to evaluate the mouse as a model for studying this pathogen. C57BL/6 mice were inoculated intraperitoneally with 10 5 , 10 7 , or 10 9 CFU of Brucella canis RM6/66 and euthanized 1-, 2-, 4-, 6-, 9-, and 12-weeks post-inoculation. B . canis induced splenomegaly in mice infected with 10 9 CFU at 1- and 2 weeks post-inoculation while no gross lesions were observed in other dose groups. Infection at the two higher doses resulted in dose-dependent granulomatous hepatitis and histiocytic infiltration of the spleen and mesenteric lymph nodes by 1–2 weeks. B . canis was cultured from the liver, spleen, uterus, bone marrow, lung, and kidney in all groups with colonization declining at a slow but steady rate throughout the experiment. Clearance was achieved by 9 weeks 10 5 CFU group and by 12 weeks in the 10 7 CFU group, while B . canis persisted in the spleen until 12 weeks in the highest dose group. Although B . canis does not demonstrate significant replication in C57BL/6 mice, it has the ability to establish an infection, induce splenomegaly, and persist for several weeks in multiple organs. Moreover, 1 x 10 7 CFU appears to be a suitable challenge dose for investigating vaccine safety.

La adaptación de los medios de comunicación tradicionales a los nuevos soportes digitales y su interfaz, lejos de constituir un mero ajuste técnico, ha contribuido a una paulatina transformación de los propios medios y sus audiencias. En una muestra integrada por los diarios de información general y de pago líderes en los 28 países de la UE, y mediante el análisis de 17 indicadores distribuidos en cuatro categorías, este artículo busca identificar las transformaciones que la implantación de los soportes digitales han provocado en las principales cabeceras de la prensa europea. En términos generales, los resultados de la investigación señalan que la mayoría de los diarios no sólo han logrado mantener su liderazgo en la Red, sino que en algunos casos también se está alumbrando un incipiente conjunto de medios globales a partir de medios nacionales preexistentes. Los soportes digitales y móviles también han favorecido la aparición de nuevos hábitos de consumo, caracterizados por una lectura más esporádica y superficial por parte de los usuarios, y han configurado una audiencia que ya en muchos casos es multisoporte, y donde los dispositivos digitales aportan ya la mayoría de lectores a muchos medios. Asimismo, las nuevas ventanas de acceso a la información –buscadores, redes sociales, etc.– generadas por Internet, también están contribuyendo decisivamente al cambio de las rutinas y las formas de trabajo de los propios mediosThe adaptation of traditional newspapers to new digital media and its interface, far from being a mere technical transformation, has contributed to a gradual change in the media themselves and their audiences. With a sample including the top general information pay newspaper in each of the 28 countries of the European Union, this research has carried out an analysis using 17 indicators divided in 4 categories. The aim is to identify the transformations that the implementation of digital media have brought to the top European newspapers. In general terms, the results show that most dailies have managed to keep their leadership also in online environment. Moreover, an emerging group of global media is growing up, based in preexisting national media. Digital and mobile media have contributed to the appearance of new consumption habits as well, where users read more superficially and sporadically. The audience uses several formats at a time, and digital devices already bring the biggest amount of users to many media. The Internet-created new information windows –search engines, social networks, etc. –are also contributing to the change in professional work routine

As a natural host species for Brucella melitensis, pregnant sheep offer an ideal model to evaluate vaccine candidates for safety. B. melitensis strain Rev. 1 has been used almost exclusively to prevent brucellosis in small ruminants, but it causes abortions when given to pregnant animals. To evaluate the comparative safety of the candidate Brucella melitensis 16MΔvjbR, pregnant sheep (n = 6) were vaccinated subcutaneously with 1 × 1010 CFU/ml of 16MΔvjbR or 1 × 109 CFU/ml Rev. 1 at a highly susceptible stage of gestation (approximately 70 days). 16MΔvjbR resulted in only 1 abortion (1 of 6) compared with 4 of 6 (66.7%) abortions in the Rev. 1 cohort. The placenta was evaluated by culture to determine if vaccination resulted in colonization. As another measure of safety, effects of B. melitensis on the fetus/offspring (vertical transmission) was evaluated by culture and histopathology of fetal tissues to determine if vaccination prevented infection of the fetus. Vaccination with 16MΔvjbR resulted in less vertical transmission than Rev. 1. To determine if vaccination was efficacious and could reduce tissue colonization in sheep, the same cohort of sheep were challenged 5 weeks postpartum by conjunctival inoculation with 1 × 107 CFU/ml B. melitensis. Protection was similar between Rev. 1 and 16MΔvjbR, with no statistical difference in colonization in the target organs. Overall, the 16MΔvjbR vaccine was considered safer than Rev. 1 based on a reduced number of abortions and limited infection in the offspring. Future experiments are needed to further refine the vaccine dose to increase the safety margin and to evaluate protection in pregnant ewes. IMPORTANCE Brucellosis is one of the most commonly reported zoonotic disease with a worldwide distribution. Of the 12 Brucella species, Brucella melitensis is considered the most virulent and causes reproductive failure (abortions/stillbirths) in small ruminants, which can spread the disease to other animals or to humans. Vaccination of small ruminants is a key measure used to protect both human and animal health. However, the commercially available live-attenuated vaccine for Brucella melitensis Rev. 1 retains virulence and can cause disease in animals and humans. In order to evaluate the safety and efficacy in sheep, we vaccinated pregnant sheep with 16MΔvjbR. Our results indicate that 16MΔvjbR was safer for use during pregnancy, provided a similar level of protection as Rev. 1, and could be considered an improved candidate for future vaccine trials.

Reproductive failure is the hallmark of brucellosis in animals. An uncommon but important complication in pregnant women who become acutely infected with Brucella melitensis is spontaneous pregnancy loss or vertical transmission to the fetus. Unfortunately, the mechanism behind reproductive failure is still obscure, partially due to the lack of a proper study model. Recently, it was demonstrated that intratracheal inoculation (IT) of non-pregnant guinea pigs would replicate features of clinical disease in humans. To determine if IT would induce reproductive disease, guinea pigs were infected at mid-gestation and monitored them daily for fever and abortions. Fever developed between day 14 to 18 post-inoculation and by 3-weeks post-inoculation, 75% of pregnant guinea pigs experienced stillbirths or spontaneous abortions mimicking natural disease. Next, to investigate the guinea pig as a model for evaluating vaccine efficacy during pregnancy, non-pregnant guinea pigs were vaccinated with S19, 16MΔvjbR + Quil-A, or 100 μl PBS + Quil-A. Guinea pigs were bred and vaccinated guinea pigs were challenged at mid-gestation with B. melitensis IT and monitored for fever and abortions. Vaccination with both vaccines prevented fever and protected against abortion. Together, this study indicates that pregnant guinea pigs are an appropriate animal model to study reproductive disease and offer an improved model to evaluate the ability of vaccine candidates to protect against a serious manifestation of disease.

HighlightsVaccination with Brucella abortus S19 or S19ΔvjbR in pregnant swine did not induce abortion, stillbirths or a reduction in litter size.Gross and histopathological evaluation did not demonstrate any local or systemic side effect associated with either vaccine.At the time of the delivery, there was no evidence of the presence of either vaccine strains in the fetuses, placentas or sows.Both vaccine candidates are safe for use in pregnant swine.