Brucellosis is caused by various bacteria of the genus Brucella. Brucella occurs worldwide and is sensitive to heat and all common disinfectants. In humans, the infectious disease caused by B. melitensis is known as Malta fever. B. abortus causes Bang's disease (Morbus Bang).

Brucella melitensis and Brucella abortus are common in domestic and farm animals worldwide with regional differences. In 2018, an outbreak caused by B . melitensis was reported in a cattle herd in Upper Austria. B. suis (Biovar 2) is rarely detected in domestic pigs and humans in Europe. A disease outbreak was last detected in a breeding sow herd in Upper Austria in 2017. B. canis was first detected in Austria as a miscarriage pathogen in dogs in 2010 in a poodle breeding farm in Upper Austria.

Cattle, sheep, goats, wild boar, hare, dog. The pathogen reservoir of B. abortus is cattle, and longstanding control programs have eradicated the pathogen in our latitudes. In the USA, infected wild bison herds are occasionally found, and in developing countries this pathogen is more common in humans and animals. The species B. melitensis occurs primarily in sheep and goats in Mediterranean countries. Wild boar and brown hares act as reservoirs for Brucella suis Biovar 2.

Transmission to humans usually occurs through food containing Brucella (raw milk and products made from it) or through direct contact with infected animals and their excretions. Direct transmission from person to person is extremely rare (in individual cases through breastfeeding or blood transfusions). The risk of infection in Austria is very low.

Usually between 5 and 60 days

Up to 90 % of all infections are asymptomatic; they can only be assessed by the detection of specific antibodies in patients and are the expression of a successful immune response. In the initial phase of acute brucellosis, patients experience non-specific, flu-like symptoms such as fatigue, mild fever, headache and aching limbs, which do not stop after 7 to 10 days, as is usually the case with influenza. After a short, symptom-free interval, flu-like symptoms may re-occur, often with evening temperature rises up to 40 °C, combined with massive sweating (the temperature returns to normal in the morning); this is often associated with a drop in blood pressure and swelling of the liver, spleen and lymph nodes. These phases last up to 5 weeks. The disease can heal spontaneously without antibiotic treatment, but without therapy it can also lead to a chronic progression with recurrent episodes of fever. Chronic progressions of the disease can lead to complications in the nervous system and internal organs.

Treatment with antibiotics

Brucellosis in cattle, pigs, sheep and goats is a notifiable animal disease. Control is focused on the isolation and culling of infected animals.

Brucellosis is found only very sporadically as an infectious disease in humans. In 2022, seven laboratory-confirmed cases were reported to the Epidemiological Reporting System (EMS) (EMS, as of 20.02.2023). B . melitensis was isolated and confirmed in two cases, and Brucella-specific antibodies were detected in the other cases. Five cases are considered imported, and two cases are considered non-imported.

Due to the officially recognized brucellosis-free status of the Austrian cattle population as well as the sheep and goat population, foodstuffs are currently not tested for brucella in Austria. In 2021, no foodborne disease outbreak (LMbKA) caused by brucella was notified to the EMS in Austria (as of March 1, 2022). In each of 2019 and 2020, one outbreak caused by B. melitensis was reported, probably due to consumption of raw milk and sheep meat abroad.

Bovine brucellosis: In Austria, the cattle population has been officially recognized free of B. abortus (OBF) since 1999. In 2008, the bovine brucellosis testing ordinance came into force. Until 2012, area-wide surveillance of all milk-supplying cattle farms was carried out via tank milk testing, and blood tests were performed according to a risk-based sampling plan. Since 2013, bulk milk samples from milk-supplying farms have also been selected according to a risk-based sampling plan. In 2021, 1,270 bulk milk samples from 1,236 farms were tested. Serologically non-negative tank milk samples are verified using blood samples. From non-dairy cattle farms, 11,233 blood samples were tested using a risk-based sampling plan from 1,482 farms. No brucellosis was detected in any cattle herd; all 55,102 herds in Austria carry OBF status. Sheep and goat brucellosis: Austrian sheep and goat herds have been officially recognized free of B. melitensis (OBmF) since 2001. To maintain recognition of the status, annual proof must be provided that less than 0.2% of all sheep and goat herds are infected with B. melitensis. In 2021, 22,898 blood samples from 1,658 flocks were tested throughout the state using a risk-based sampling plan. There was no evidence of Brucella infection in sheep and goats, thus the 25,282 sheep and goat flocks carry OBmF status.

Direct transmission from person to person is extremely rare (in individual cases through breastfeeding or blood transfusions) and occurs only in exceptional cases. It has essentially only been observed in infants through the milk of infected mothers. Brucella can be transmitted directly through contact with diseased animals or indirectly through contaminated food. Bovine brucellosis is enzootic in the herd. It poses a risk to human health, particularly to those in direct contact (farmers, veterinarians, slaughterhouse staff). Raw milk (unpasteurised milk or products made from it, such as butter made from raw milk and raw milk cheese) and raw meat from infected animals pose the greatest risk of transmission. In addition to the gastrointestinal tract, the pathogen can be absorbed into the body by several other routes, including the conjunctiva, the respiratory tract and injured skin. After entering the body, brucella are taken up by cells of the monocyte-macrophage system and transported to the nearest lymph nodes. From the infested lymph nodes, the germs are disseminated first lymphogenically and then hematogenically, reaching most organs, especially the liver, spleen, and bone marrow. In the affected organs, inflammatory granulomas consisting of macrophages and lymphocytes can form due to the activation of specific T cells. From these inflammatory foci, the brucella can enter the bloodstream in spurts.

Symptoms

The incubation period of brucellosis is usually 1 to 2 months (incubation periods of 5 days to 150 days have been described in individual cases). Up to 90% of all infections are subclinical; they can only be identified by the detection of specific antibodies in the patient and are an expression of a successful immune response. In acute brucellosis, fatigue, mild fever, headache and pain in the limbs occur in the initial phase. After a short, symptom-free interval, flu-like symptoms may appear, which then do not stop after 7 to 10 days as is usual with influenza. Typical for brucellosis are evening temperature rises of up to 40 °C combined with massive sweating! The temperature returns to normal in the morning. This undulating fever is typical of brucellosis in humans. The phases last up to 5 weeks and are interrupted by remission periods of up to 2 weeks with greatly attenuated symptoms. The course of fever extends over 7-21 days and may be interrupted by 2- to 5-day fever-free intervals (undulating fever). Chronic courses of the disease can lead to complications in the nervous system and internal organs. The disease can be treated well with antibiotics.

The genus Brucella comprises 12 officially described species: Brucella abortus, Brucella suis, Brucella melitensis, Brucella canis, Brucella ovis, Brucella neotomae, Brucella ceti, Brucella pinnipedialis, Brucella microti, Brucella inopinata, Brucella papionis and Brucella vulpis.

In Austria, the cattle population has been officially free of B. abortus since 1999 and the sheep and goat populations have been officially free of B. melitensis since 2001, therefore the risk of infection in humans in Austria is very low. Most recently, an outbreak of disease caused by B. melitensis was detected in a cattle herd in Upper Austria in 2018.

Disease in domestic pigs caused by B. suis Biovar 2 is rarely reported in Europe. In Austria, porcine brucellosis was first detected in a breeding sow in Styria in the 1990s. In 2003, outbreaks occurred in several pig farms in the Waldviertel region of Lower Austria, and in 2004, an outbreak occurred in the Schärding district of Upper Austria. In 2017, an outbreak was detected in a multiplier farm in the district of Grießkirchen in Upper Austria with a total of 9 contact farms.

B. suis Biovar 2 is widespread in wild boar and brown hares in Europe and can be transmitted from these wild animals to domestic pigs and humans. In 228 wild boars shot in 2011/2012 from 8 districts in Upper Austria, Lower Austria and Burgenland, B. suis Biovar 2 was isolated from the head lymph nodes of 12 animals (5.2%). Secondary hosts of B. suis Biovar 2 are humans, cattle, rats, red foxes and roe deer. The red fox can serve as an indicator animal for the investigation and monitoring of brucellosis natural herds (B. suis, B. microti, B. vulpis). From June 2007 to July 2008, mandibular lymph nodes of 903 foxes from 37 districts (20 Lower Austrian, 5 Burgenland, 5 Upper Austrian and 7 Styrian districts) were examined, revealing B. suis natural herds in Lower Austria, Styria and Burgenland. While B. suis biovar 2 has only a low pathogenicity for humans (rare reports, patients with pre-existing diseases), B. suis biovar 1, which has so far only been detected in Europe in wild and domestic animals in Croatia, is highly pathogenic for humans.

B. microti is a newly described species that was first detected in diseased field mice in the Czech Republic in 2000 and repeatedly in foxes in Lower Austria in 2007. The pathogenic significance of this causative agent of murine brucellosis for other animals and humans is unclear. So far, this species has only been detected in wild animals in the Czech Republic, Austria and Hungary.

B. vulpis was officially described in 2016 as the twelfth Brucella species. This species has only been isolated in Austria so far. In 2008, this brucella species could be isolated from macroscopically unaltered mandibular lymph nodes of 2 foxes in the Lower Austrian district of Hollabrunn. The reservoir of this pathogen and the pathogenic significance for other animal species and humans is unclear.

B. canis was first detected in Austria as an abortive pathogen in dogs in 2010 in a poodle breed in Upper Austria and is also a zoonotic agent.

B. ovis, the causative agent of infectious epididymitis in rams, is not pathogenic for humans.

Transmission and symptoms

Epidemiologically significant massive shedding occurs particularly in abortions and infected normal births, but also with milk, urine, faeces and nasal secretions. Typical routes of infection are oral ingestion and transmission during mating. Infections via the skin, also by arthropods as vectors, must be considered.

Domestic pig: In endemic areas, the possibility of transmission of B. suis Biovar 2 from wild animals to domestic pigs is given, especially when domestic pigs are kept outdoors. However, the pathogen can also be introduced with contaminated green fodder, indirectly via carnivorous mammals such as the fox and the dog or carrion-eating birds, or by purchasing a chronically infected boar into a breeding sow herd. The unsafe disposal of animal by-products from killed wild boar and hares is also a risk factor for introduction into the farm animal population. Adherence to hygiene principles in hunting and game processing by hunters is the most important measure to prevent the introduction of the pathogen into domestic pig herds and transmission to humans.

Within a domestic pig herd, infection occurs particularly through contact with infected material such as abortions, afterbirths, body excrement and secretions, and during mating. The incubation period is very variable (a few days to several months). In the case of infection through the mating act of an infected boar, the first symptom that may occur after 5-8 weeks is frequent murmuring due to premature abortions. However, abortions are possible at any stage of gestation. In domestic pigs, a new outbreak in sows results in frequent abortions at all stages of gestation, birth of weak piglets, postpartum behavior, and uterine inflammation with possible small-boned changes. In boars, testicular swelling and inflammation may occur. In general, movement disorders may occur due to joint inflammation as well as abscessing changes in various organs. The disease with years of excretion of the pathogen can also proceed without clinical manifestations.

Cattle: Before the frequent abortions, the infection is usually asymptomatic except for a temporary increase in temperature. The animals remain pathogen excretors. Calcification in the 2^nd half of gestation is the most conspicuous symptom; no signs of the disease are usually observed before abortion. Subsequently, inflammation of the joints, tendon sheaths and bursa often occurs, more rarely clinically conspicuous inflammation of the udder (pathogen excretion!). After the abortion a cow can carry a normal calf again, a new calcification is possible as well as sterility after the first abortion. In bulls, testicular and epididymitis are observed. Bovine brucellosis is enzootic in the herd. Infections with B. abortus rarely occur in other animal species (sheep, goats, sheep, pigs). Their occurrence is usually explained by contact with infected cattle herds.

Sheepand goat: Sheep and goat brucellosis is caused by B. melitensis with its 3 biovars. The course is similar to bovine brucellosis. Animals often suffer abortions, birth of weak lambs and inflammatory changes, especially in the genital tract. In addition, mastitis, inflammation of the testicles and epididymis occur. In rams, brucellosis also occurs in the form of infectious unilateral and bilateral epididymitis accompanied by a deterioration in semen quality caused by Brucella ovis. Brucella is transmitted during mating and can lead to abortions in the dam. After renal colonization, excretion occurs in the urine.

Dog: Infected dogs show no fever and may remain bacteraemic for years. Serologic tests may be falsely negative despite bacteremia. Brucellosis may go undetected if clinical signs are absent or unrecognized (infertility, disorders of gravidity, iritis, spondylodiscitis, lymphadenitis, prostatitis, epididymitis).

Control/Prevention

Brucellosis of cattle, pigs, sheep and goats is a notifiable animal disease. Control focuses on the detection, isolation and eradication of infected animals and the control of animal movements to prevent the spread of the disease. Surveillance of disease-free status is carried out by serological testing.

Farmers, veterinarians, breeders and slaughterhouse staff must strictly observe the hygiene rules when handling infected animals. Persons on those farms which receive animals from the affected farm should also be informed about the nature of the disease and the existing risk of infection via animals, carcasses and slaughterhouse waste. In addition to the use of protective gloves, especially in obstetrics, thorough hand disinfection with an approved hand sanitizer and hand washing with soap and water are essential. Appropriate ointment protection may provide additional protection against transdermal infections. Clothing and shoes should be changed after barn work. Surface disinfection in animal stables is appropriate.

Human diagnostics

For the cultural detection of the pathogen, blood should be taken repeatedly, if possible before the start of antibiotic therapy; bone marrow, urine and other tissue samples are also suitable for the cultural detection of the pathogen. The isolated Brucella species are identified by molecular biology using multiplex PCR. Serological detection of specific antibodies is also diagnostic.

Diagnostics animal

For the detection of brucellosis in cases of abortion, the placenta is a particularly important sample material for diagnostics due to the high pathogen concentration. Due to the classification of certain brucella species as risk group 3 pathogens, cultivation and phenotyping may only be carried out in the safety level L3 laboratory, the Centre for Biological Safety at the National Reference Laboratory for Brucellosis in Mödling. The exact identification of the isolated Brucella species is carried out both phenotypically using conventional, bacteriological methods and molecularly using a species- and biovar-specific multiplex PCR. Direct tissue PCR allows rapid pathogen detection at the genus level. Serological detection of specific antibodies is also diagnostic.