Brucellosis remains a neglected disease in the developing world: a call for interdisciplinary action.

BACKGROUND: Brucellosis is an endemic zoonotic disease in most of the developing world that causes devastating losses to the livestock industry and small-scale livestock holders. Infected animals exhibit clinical signs that are of economic significance to stakeholders and include reduced fertility, abortion, poor weight gain, lost draught power, and a substantial decline in milk production. In humans, brucellosis typically manifests as a variety of non-specific clinical signs. Chronicity and recurring febrile conditions, as well as devastating complications in pregnant women are common sequelae. DISCUSSION: In regions where the disease is endemic, brucellosis has far-reaching and deleterious effects on humans and animals alike. Deeply entrenched social misconceptions and fear of government intervention contribute to this disease continuing to smolder unchecked in most of the developing world, thereby limiting economic growth and inhibiting access to international markets. The losses in livestock productivity compromise food security and lead to shifts in the cognitive competency of the working generation, influence the propagation of gender inequality, and cause profound emotional suffering in farmers whose herds are affected. The acute and chronic symptoms of the disease in humans can result in a significant loss of workdays and a decline in the socioeconomic status of infected persons and their families from the associated loss of income. The burden of the disease to society includes significant human healthcare costs for diagnosis and treatment, and non-healthcare costs such as public education efforts to reduce disease transmission. CONCLUSION: Brucellosis places significant burdens on the human healthcare system and limits the economic growth of individuals, communities, and nations where such development is especially important to diminish the prevalence of poverty. The implementation of public policy focused on mitigating the socioeconomic effects of brucellosis in human and animal populations is desperately needed. When developing a plan to mitigate the associated consequences, it is vital to consider both the abstract and quantifiable effects. This requires an interdisciplinary and collaborative, or One Health, approach that consists of public education, the development of an infrastructure for disease surveillance and reporting in both veterinary and medical fields, and campaigns for control in livestock and wildlife species.

Identification of Brucella spp. in feral swine (Sus scrofa) at abattoirs in Texas, USA.

Various tissues, nasal swabs, urine and blood samples were collected from 376 feral swine at two federally inspected abattoirs in Texas during six separate sampling periods in 2015. Samples were tested for Brucella spp. by culture and serology. Brucella spp. were cultured from 13.0% of feral swine, and antibodies were detected in 9.8%. Only 32.7% of culture-positive feral swine were also antibody positive, and 43.2% of antibody-positive feral swine were culture positive. Approximately, the same number of males (14.0%) and females (12.1%) were culture positive, and slightly more males (10.5%) than females (8.7%) were antibody positive. Our results indicate that serology likely underestimates the prevalence of feral swine infected, and that those who come in contact with feral swine should be aware of the symptoms of infection with Brucella spp. to ensure prompt treatment.

Peripheral neuroblastomas in dogs: a case series.

The peripheral neuroblastic tumours (PNTs) include neuroblastoma, ganglioneuroblastoma and ganglioneuromas. These subtypes reflect a spectrum of differentiation of progenitor cells of the sympathetic nervous system from tumours with predominant undifferentiated neuroblasts to those consisting of neuronal cell bodies that are well differentiated. Peripheral neuroblastoma is a tumour composed of neuroblastic cells with no or limited neuronal differentiation. In dogs, peripheral neuroblastoma is rare. The present report documents nine cases of canine peripheral neuroblastoma, the majority occurring as large masses in the craniodorsal abdominal cavity of young dogs (mean age of 3 years at diagnosis). Microscopically, all of the masses consisted of round to oval cells with a scant cytoplasm and hyperchromatic nuclei. Homer-Wright rosettes and pseudorosettes were evident in three of the nine cases. Neoplastic cells were immunoreactive in varying degrees to S100, neuron-specific enolase, synaptophysin, chromogranin A, tyrosine hydroxylase (one case) and were negative for vimentin, cytokeratin, CD3 and CD79a, indicating a neurogenic nature. Four of the nine cases occurred in Labrador retrievers (44%) and two (22%) in boxers, suggesting a possible breed predisposition.

Extended safety and efficacy studies of the attenuated Brucella vaccine candidates 16 M(Delta)vjbR and S19(Delta)vjbR in the immunocompromised IRF-1-/- mouse model.

The global distribution of brucellosis and high incidence in certain areas of the world warrant the development of a safer and efficacious vaccine. For the past 10 years, we have focused our attention on the development of a safer, but still highly protective, live attenuated vaccine for human and animal use. We have demonstrated the safety and protective efficacy of the vaccine candidates 16 MΔvjbR and S19ΔvjbR against homologous and heterologous challenge in multiple immunocompetent animal models, including mice and deer. In the present study, we conducted a series of experiments to determine the safety of the vaccine candidates in interferon regulatory factor-1-knockout (IRF-1(-/-)) mice. IRF-1(-/-) mice infected with either wild-type Brucella melitensis 16 M or the vaccine strain Brucella abortus S19 succumb to the disease within the first 3 weeks of infection, which is characterized by a marked granulomatous and neutrophilic inflammatory response that principally targets the spleen and liver. In contrast, IRF-1(-/-) mice inoculated with either the 16 MΔvjbR or S19ΔvjbR vaccine do not show any clinical or major pathological changes associated with vaccination. Additionally, when 16 MΔvjbR- or S19ΔvjbR-vaccinated mice are challenged with wild-type Brucella melitensis 16M, the degree of colonization in multiple organs, along with associated pathological changes, is significantly reduced. These findings not only demonstrate the safety and protective efficacy of the vjbR mutant in an immunocompromised mouse model but also suggest the participation of lesser-known mechanisms in protective immunity against brucellosis.

Sclerosing cholangitis in baboons (Papio spp) resembling primary sclerosing cholangitis of humans.

Primary sclerosing cholangitis is a chronic and progressive cholestatic liver disease that has been extensively documented in the human literature. Although it shares many features in common with chronic lymphocytic cholangitis in cats, primary sclerosing cholangitis has never been reported in a nonhuman primate. Primary sclerosing cholangitis is characterized by the presence of intrahepatic and/or extrahepatic inflammation and concentric fibrosis of bile ducts, eventually leading to cirrhosis and hepatic failure. The pathogenesis and cause remain unknown, but the disease likely involves a multifactorial mechanism with genetic- and immune-mediated components. The authors report 2 cases that histologically resemble the condition in humans; they consist of 2 adult male baboons with a clinical history of chronic elevated liver enzymes. In both cases, the liver was histologically characterized by thick bands of fibrosis and mild lymphoplasmacytic periportal cholangiohepatitis with concentric periductal fibrosis, resulting in atrophy and loss of bile ducts. Immunohistochemical analysis revealed positivity of hepatocytes to cytokeratin 7. Masson stain demonstrated marked biliary fibrosis. This is the first report that resembles sclerosing cholangitis in a nonhuman primate, and it suggests that the baboon may provide a useful animal model for this condition in humans.

Protective efficacy and safety of Brucella melitensis 16MΔmucR against intraperitoneal and aerosol challenge in BALB/c mice.

Brucellosis is a zoonosis of nearly worldwide distribution. Vaccination against this pathogen is an important control strategy to prevent the disease. Currently licensed vaccine strains used in animals are unacceptable for human use due to undesirable side effects and modest protection. Substantial progress has been made during the past 10 years toward the development of improved vaccines for brucellosis. In part, this has been achieved by the identification and characterization of live attenuated mutants that are safer in the host but still can stimulate an adequate immune response. In the present study, the identification and characterization of the mucR mutant (BMEI 1364) as a vaccine candidate for brucellosis was conducted. BALB/c mice were vaccinated intraperitoneally at a dose of 10(5) CFU with the mutant to evaluate safety and protective efficacy against intraperitoneal and aerosol challenge. All animals vaccinated with the vaccine candidate demonstrated a statistically significant degree of protection against both intraperitoneal and aerosol challenge. Safety was revealed by the absence of Brucella associated pathological changes, including splenomegaly, hepatomegaly, or granulomatous disease. These results suggest that the 16MΔmucR vaccine is safe, elicits a strong protective immunity, and should be considered as a promising vaccine candidate for human use.

Epithelioid haemangiosarcoma in the ocular tissue of horses.

Haemangiosarcomas (HSAs) are malignant tumours of endothelial cell origin. Epithelioid HSA is a variant of the histologically conventional HSA that has little or no morphological evidence of a vascular origin and has been reported rarely in domestic animals. The following report documents six cases of equine epithelioid HSA occurring in the ocular tissues of horses with a mean age of 19.8 years at the time of diagnosis. Microscopically, all of the lesions consisted of solid sheets or cords of epithelioid cells with rare narrow clefts or small spaces containing erythrocytes that were often the only feature indicating a vascular origin. On immunohistochemistry, the neoplastic cells expressed vimentin, CD31 and factor VIII-related antigen, but not cytokeratin, indicating an endothelial nature.

The Brucella abortus S19 DeltavjbR live vaccine candidate is safer than S19 and confers protection against wild-type challenge in BALB/c mice when delivered in a sustained-release vehicle.

Brucellosis is an important zoonotic disease of nearly worldwide distribution. Despite the availability of live vaccine strains for bovine (S19, RB51) and small ruminants (Rev-1), these vaccines have several drawbacks, including residual virulence for animals and humans. Safe and efficacious immunization systems are therefore needed to overcome these disadvantages. A vjbR knockout was generated in the S19 vaccine and investigated for its potential use as an improved vaccine candidate. Vaccination with a sustained-release vehicle to enhance vaccination efficacy was evaluated utilizing the live S19 DeltavjbR::Kan in encapsulated alginate microspheres containing a nonimmunogenic eggshell precursor protein of the parasite Fasciola hepatica (vitelline protein B). BALB/c mice were immunized intraperitoneally with either encapsulated or nonencapsulated S19 DeltavjbR::Kan at a dose of 1 x 10(5) CFU per animal to evaluate immunogenicity, safety, and protective efficacy. Humoral responses postvaccination indicate that the vaccine candidate was able to elicit an anti-Brucella-specific immunoglobulin G response even when the vaccine was administered in an encapsulated format. The safety was revealed by the absence of splenomegaly in mice that were inoculated with the mutant. Finally, a single dose with the encapsulated mutant conferred higher levels of protection compared to the nonencapsulated vaccine. These results suggest that S19 DeltavjbR::Kan is safer than S19, induces protection in mice, and should be considered as a vaccine candidate when administered in a sustained-release manner.

Aerosol infection of BALB/c mice with Brucella melitensis and Brucella abortus and protective efficacy against aerosol challenge.

Brucellosis is a zoonotic disease with a worldwide distribution that can be transmitted via intentional or accidental aerosol exposure. In order to engineer superior vaccine strains against Brucella species for use in animals as well as in humans, the possibility of challenge infection via aerosol needs to be considered to properly evaluate vaccine efficacy. In this study, we assessed the use of an aerosol chamber to infect deep lung tissue of mice to elicit systemic infections with either Brucella abortus or B. melitensis at various doses. The results reveal that B. abortus causes a chronic infection of lung tissue in BALB/c mice and peripheral organs at low doses. In contrast, B. melitensis infection diminishes more rapidly, and higher infectious doses are required to obtain infection rates in animals similar to those of B. abortus. Whether this difference translates to severity of human infection remains to be elucidated. Despite these differences, unmarked deletion mutants BADeltaasp24 and BMDeltaasp24 consistently confer superior protection to mice against homologous and heterologous aerosol challenge infection and should be considered viable candidates as vaccine strains against brucellosis.