Welcome to BRIDGING! A Greek-German Research and Innovation Programme
BRIDGING (BRucellosis IDendification in Greece aNd Germany) provides a unique and innovative Greek-German consortium in translational research in human brucellosis, taking advantage of expertise on the fields of molecular immunology, clinical microbiology, system biology and advanced diagnostics.
BRIDGING project aims to bring together Greek and German academic partners with experience and expertise in clinical and laboratory diagnosis and treatment of Brucellosis, with leading researchers in the field of immunology and industrial partners with experience in the development of novel diagnostic tools.
By applying a systems biology approach, we aim to provide an in-depth analysis of host response to Brucellosis in an endemic region of EU, in an effort a) to identify molecular targets for the development of new diagnostic assays and algorithms and b) to assess the effect of Brucella infection on human immunity and the potential epidemiological impacts.
Brucellosis: an important zoonosis worldwide
Brucellosis is the most common bacterial zoonotic disease worldwide, annually affecting more than 500,000 new individuals, an incidence that is definitely an underestimate given that brucellosis remains under-diagnosed and under-reported in several endemic countries, and an emerging zoonosis in EU countries.
Brucellosis is caused by facultative intracellular pathogens of the genus Brucella that have domestic animals, mainly goats, sheep and cows, as natural reservoirs. The disease is transmitted to humans by consumption of unpasteurized milk and dairy products or by occupational contact with infected animals. Additionally, Brucella is highly infectious through aerosol route, thus is considered as one of the most common laboratory-acquired pathogens and is also classified as category B agent on the biodefense list.
Human brucellosis causes high clinical morbidity and protean clinical manifestations, mimicking many infectious and non-infectious diseases, as any organ can be affected. Despite early diagnosis and prolonged combination therapy with antibiotics is associated with substantial residual disability. Up to 30% of patients develop chronic disease, which is characterized by atypical clinical picture, high frequency of focal complications (eg spondylitis), chronic fatigue syndrome and relapses.
A continuously re-emerging zoonosis
Despite the efforts in controlling Brucellosis in livestock in many developing countries, human brucellosis remains widespread and neglected in many areas, including southeastern Europe, the Mediterranean basin, Asia, Central and Latin America and Africa.
Greece has the highest reported incidence among EU countries, while the region of Eastern Macedonia and Thrace (REMTH) represents an endemic area. However, in recent years, new disease foci emerge, altering the epidemiology of the disease and enhancing the role of Brucella in travel and immigration-related infections. More specifically, brucellosis has been recently described in Germany in immigrants from endemic areas whereas the pathogen can be transferred through illegal food items.
For these reasons, and especially with the current refugee crisis, Brucellosis can be considered as an emerging zoonosis in EU countries, in which the alertness of the medical community regarding this disorder is minimal. The burden of the disease is not likely to minimize in the near future, since there exists no efficient vaccine for humans, and disease prevention depends on complex and costly animal control and eradication projects.
Brucella and host immunity interplay
Host protection against Brucella depends on cell-mediated immunity, involving mainly activated monocytes and T cells. On the other hand, Brucella has developed various stealthy strategies to evade innate and adaptive immune responses, aimed at establishment of an intracellular niche for long term survival and replication. Thus, Brucella can survive within monocytes/macrophages of the host subverting the normal mechanisms of bacterial killing, causing chronic or latent disease. In line with this, several studies have demonstrated that patients with chronic brucellosis display defective cell-mediated immunity (brucellosis-acquired cellular anergy) probably due to modulation of host cellular immunity by Brucella.
The timely and accurate diagnosis of different disease types/forms of human brucellosis, such as acute, chronic/relapsing, asymptomatic/subclinical, cured/resolved, continues to be challenging making the decision to “treat or not to treat” difficult in many cases. This is because of: a) the non-specific and atypical clinical features, b) the slow growth rate of Brucella in blood cultures and the reduced sensitivity of the method for detecting chronic cases c) the complexity of serodiagnosis of brucellosis, especially in people living in endemic regions, in high risk occupational groups (livestock workers and veterinarians) and in previously infected individuals, d) the long term persistence of brucellar DNA despite appropriate treatment and apparent recovery, making the interpretation of molecular diagnosis with PCR puzzling in many cases.
Integrated molecular data and methods that characterize different clinical types/forms of human brucellosis and the impact of Brucella on host immunity are missing today.
- Identify novel molecular targets for the diagnosis, stratification and epidemiologic surveillance of different types of human brucellosis
- Investigate the possible impact of brucellosis on population health by assessing the effect of Brucella on key host innate immune circuits
- Provide the principles of novel diagnostic assays for human brucellosis
- Increase medical community awareness on brucellosis and initiate a long-term co-operation between the partners of the project
