Carlos Alberto Rossetti

Although the concept of "One Health" was used in the past, it was formally formulated at the beginning of this Century to indicate that the health of humans, animals and plants are closely linked and interdependent with each other as well as with their shared environment (1). The concept also emphasizes that collaboration across disciplines contributes to addressing health challenges such as the prevention, detection, control and elimination of infectious diseases, increasing global health security.Brucellosis is a neglected zoonotic infectious disease in most developing countries (2). It causes chronic illness with a variety of non-specific clinical signs in humans (fever, malaise, fatigue and arthritis) and abortion, infertility and decreased milk production in animals. These clinical manifestations cause significant economic losses in livestock and pose a risk to public health. It is estimated that hundreds of thousands of new human brucellosis cases appear each year (3), while the livestock industry loses millions of dollars annually (4).Prevention measures and diagnostic tests are the best tools for preventing and controlling brucellosis, with vaccines and serological tests being the prototypes of these measures, respectively. However, despite a large amount of research in these topics, brucellosis vaccines are far from ideal, and no serological test by itself can identify a positive sample with enough specificity. Given the importance of improving these tools in creating a safe environment, these subjects are primarily addressed in our Research Topic.As mentioned earlier, no vaccine for humans is licensed and veterinary vaccines present several shortcomings. There are four brucellosis veterinary vaccines available:

La brucelosis es una enfermedad infecciosa crónica, zoonótica, de amplia distribución mundial causada por bacterias del género Brucella spp. En las especies animales susceptibles, el principal y muchas veces único signo clínico es el aborto. El aborto, además de producir pérdidas económicas en las explotaciones pecuarias, es el elemento más importante para que la enfermedad se disemine y perpetúe, generando también problemas en la salud pública. Sin embargo, es muy poco lo que se conoce acerca de los mecanismos moleculares que lo ocasionan. Brucella spp. muestra un especial tropismo por el útero gestante en el último tercio de la preñez, donde sobrevive y se reproduce en el interior de los trofoblastos. El alto número de bacterias dentro de los trofoblastos desencadena la apoptosis de las células infectadas por estrés del retículo endoplásmico. La destrucción masiva de trofoblastos resulta en una placentitis fibrino-necrótica, que dificulta el intercambio nutricional y gaseoso entre la madre y el feto, y la interrupción de la gestación se produce cuando los placentomas sobrevivientes no son suficientes para mantener activa la gestación. La interacción de Brucella con los trofoblastos no se ha estudiado en detalle, y muchos eventos de esa interacción, se infieren a partir de las observaciones en otros tipos celulares. En este artículo se describen los factores de virulencia de Brucella que intervienen en la adherencia, invasión y replicación intratrofoblástica de la bacteria, y las consecuencias locales que desencadena, y se discute la acción preventiva de la vacunación sobre el aborto. Finalmente se muestran varios modelos de estudio in vitro o ex vivo disponibles que no han sido explotados y que podrían brindar mayores datos sobre la patogenia molecular del aborto por Brucella.

Kalirin (gene: KALRN) is a Rho-GEF kinase linked to neurodegenerative diseases in humans. Unexpectedly, various polymorphisms in KALRN gene were previously associated with resistance to bacterial infections in ruminants. In this study, we evaluated the effect of the rs384223075 (RS-075) deletion in KALRN intron 5 on the occurrence of Mycobacterium bovis and Brucella abortus infections in cattle. We performed two separate case-control association analyses: one for bovine tuberculosis (bTB) using 308 Holstein and Jersey cows from three herds with prevalence between 5 and 15% for this infection; and another for brucellosis using 140 Holstein and beef crossbred cows from two herds with high prevalence for brucellosis (> 30%). In the bTB analysis, the RS-075 deletion frequency was higher among cases than controls (p = 0.0001), and the absence of the RS-075 deletion allele was associated with negative PPD-skin test results (p = 0.0009) at genotype level. On the contrary, RS-075 was not associated with Brucella spp. serological status (p = 0.72) but, unexpectedly, the deletion allele was more frequent among controls than cases in the beef crossbred herd (0.31 vs. 0.14, p = 0.02). In concordance with this observation, in vitro assays showed that the RS-075 deletion could be linked to an enhanced cellular response to bacterial antigens and unspecific stimulation in mononuclear cells derived from beef crossbred cows, specifically the reactive nitrogen species production (p = 0.008) and proliferation capacity (p = 0.018). This study is consistent with other reports that support an important role of the KALRN gene and its polymorphisms in the host response to intracellular pathogens.

Brucella melitensis and Brucella ovis are the primary etiological agents of brucellosis in small domestic ruminants. B. melitensis was first isolated in 1887 by David Bruce in Malta Island from spleens of four soldiers, while B. ovis was originally isolated in Australia and New Zealand in early 1950's from ovine abortion and rams epididymitis. Today, both agents are distributed worldwide: B. melitensis remains endemic and associated with an extensive negative impact on the productivity of flocks in -some regions, and B. ovis is still present in most sheep-raising regions in the world. Despite being species of the same bacterial genus, B. melitensis and B. ovis have extensive differences in their cultural and biochemical characteristics (smooth vs. rough colonial phases, serum and CO₂ dependence for in vitro growth, carbohydrate metabolism), host preference (female goat and sheep vs. rams), the outcome of infection (abortion vs. epididymitis), and their zoonotic potential. Some of these differences can be explained at the bacterial genomic level, but the role of the host genome in promoting or preventing interaction with pathogens is largely unknown. Diagnostic techniques and measures to prevent and control brucellosis in small ruminants vary, with B. melitensis having more available tools for detection and prevention than B. ovis. This review summarizes and analyzes current available information on: (1) the similarities and differences between these two etiological agents of brucellosis in small ruminants, (2) the outcomes after their interaction with different preferred hosts and current diagnostic methodologies, (3) the prevention and control measures, and (4) alerting animal producers about the disease and raise awareness in the research community for future innovative activities.