Brucellosis

Brucellosis is a disease caused by the bacteria 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).

Occurrence

Brucellosis is only found sporadically as a human infectious disease in Austria. In 2019, six laboratory-confirmed cases were reported. B. melitensis was confirmed in five cases. Three cases were reported as imported, two cases (one with Austrian nationality, one with Armenian nationality) are considered non-imported, and in the case of an Austrian patient born in former Yugoslavia, the place of infection is unknown.

In 2019, bulk samples of milk from cattle from 2,666 farms were analysed. Serologically non-negative bulk milk samples are verified using blood samples. From non-dairy cattle farms 10,060 cattle from 1,342 farms were tested according to a risk-based sampling plan. Based on serologically positive blood samples, seven cattle were diagnostically killed in 2019. Brucella melitensis was isolated from the udder lymph nodes of one serologically positive bovine from the Urfahr-Umgebung district in Upper Austria at the National Reference Laboratory for Brucellosis in Mödling. Genome analysis was used to prove an epidemiological link with an outbreak of the disease in 2018 in a cattle stock in the district of Rohrbach in Upper Austria. 22,063 blood samples of sheep and goats from 1,700 herds were tested in 2019 according to a risk-based sampling plan throughout Austria. No Brucella melitensis infection was detected in sheep and goats.

Transmission in humans

Direct transmission  between humans is extremely rare (in individual cases through breastfeeding or blood transfusions) and occurs only in exceptional cases. It has only been observed in infants through breastfeeding from infected mothers. Brucella can be transmitted directly through contact with infected animals or indirectly via contaminated food. Bovine brucellosis is enzootic in the herd. Raw milk (non-pasteurised milk or products made from it, such as butter from raw milk and raw milk cheese) and raw meat from infected animals are the greatest risk of transmission. In addition to the gastrointestinal tract, the pathogen can be absorbed into the body by several other routes, such as the conjunctiva, the respiratory tract and the injured skin. After entering the body, brucella are absorbed by cells of the monocyte-macrophage system and transported to the nearest lymph nodes. From affected lymph nodes, the bacteria are first disseminated lymphogenically and then hematogenically, reaching most organs, especially the liver, spleen and bone marrow. Inflammatory granulomas of macrophages and lymphocytes can form in the affected organs through activation of specific T cells. Brucella can enter the bloodstream in relapses from these inflammatory foci.

Symptoms in humans

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 recognised by the detection of specific antibodies in the patient and are a sign of a successful immune reaction. In acute brucellosis, fatigue, slight fever, headaches and aching limbs occur in the initial phase. After a short, symptom-free interval, flu-like symptoms may occur, but these do not disappear after 7 to 10 days as is usually the case with influenza. Body temperature rises up to 40 °C in the evening, combined with massive sweats. These are typical symptoms of brucellosis. Body temperature returns to normal again in the morning. This undulating fever is typical of human brucellosis. The phases last for up to 5 weeks and are interrupted by remission periods of up to 2 weeks with greatly alleviated symptoms. The course of the fever extends over 7-21 days and can be interrupted by 2 to 5-day fever-free intervals (undulating fever). In chronic cases, complications in the nervous system and internal organs can occur. The disease can be treated with antibiotics.

Diagnostics

For the detection of the pathogen via culture, blood should be taken repeatedly, if possible before starting antibiotic therapy; bone marrow, urine and other tissue samples are also suitable for cultivation of the pathogen. For the identification of the isolated brucella species molecular methods like multiplex PCR are used. The serological detection of specific antibodies is also a diagnostic measure.

Brucella infections in animals in Austria

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 bovine population has been officially free of B. abortus since 1999 and the ovine and caprine herds have been officially free of B. melitensis since 2001, therefore the risk of infection in humans in Austria is very low. The last recorded outbreak of B. melitensis in a bovine herd was in 2018 in Upper Austria.

Diseases in domestic pigs caused by B. suis biovar 2 are rarely reported in Europe. In Austria, porcine brucellosis was first detected in Styria in the 1990s in a breeding sow. Outbreaks occurred in 2003 in several pig farms in the Waldviertel region of Lower Austria and in 2004 in the district of Schärding in 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 holdings.

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

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

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

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

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

Animal transmission and symptoms

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

Domestic swine: In endemic areas, the possibility of transmission of B. suis biovar 2 from wildlife to domestic swine is particularly prevalent in the free range management of domestic swine. However, the pathogen can also be introduced into a breeding sow population with contaminated green fodder, indirectly via carnivorous mammals such as fox and dog or scavenging birds, or by purchasing a chronically infected boar. The unsafe disposal of animal by-products from killed wild boar and hares is also a risk factor for introducing the pathogen into the farm animal population. Compliance with hygiene principles during hunting and game processing by hunters is the most important measure to prevent the introduction of the disease into domestic pig populations and its transmission to humans.

Within a domestic pig population, infection occurs particularly through contact with infected material such as abortions, afterbirths, body exudates and secretions and during mating. The incubation period is highly variable (a few days to several months). In the case of an infection through mating with an infected boar, the first symptom after 5-8 weeks may be increased reproductive activity due to early abortions. However, miscarriages are possible at any stage of pregnancy. In domestic pigs, a new outbreak in sows leads to frequent abortions at all stages of pregnancy, birth of weak piglets, postpartum behaviour and uterine inflammation with possible small nodular changes. In boars, testicular swelling and inflammation may occur. In general, movement disorders due to inflammation of the joints and changes in various organs with abscesses can occur. The disease can also proceed without clinical manifestations but with years of shedding the pathogen.

Cattle: Before the frequently occurring miscarriages, the infection usually proceeds without symptoms except for a temporary increase in body temperature. The animals remain excretors of the pathogen. Calcifications in the second half of pregnancy are the most conspicuous symptom, no signs of the disease are usually observed before abortion. Subsequently, there is often inflammation of the joints, tendon sheaths and bursae, rarely clinically conspicuous mastitis (shedding of pathogens!). After abortion, a cow can certainly carry a normal calf again, a new calving is possible, so is sterility after the first abortion. In bulls, testicles and epididymitis are observed. Bovine brucellosis is enzootic in the herd. Infections with B. abortus rarely occur in other animal species (sheep, goat, sheep, pig). Their occurrence is usually explained by contact with infected herds of cattle.

Sheep and goat: Sheep and goat brucellosis is caused by B. melitensis and its three biovars. The disease progression is similar to that of bovine brucellosis. Animals often suffer from miscarriages, birth of weak lambs and inflammatory changes, especially of the reproductive system. Mastitis, inflammation of the testicles and epididymis also occur. In rams, brucellosis also occurs in the form of infectious unilateral and bilateral epididymitis accompanied by a deterioration in sperm quality caused by Brucella ovis. Brucella are transmitted during mating and can lead to abortions. After kidney colonisation, shedding takes place via urine.

Dog: Infected dogs show no fever and can remain bacteremic for years. Serological tests can be false negative despite bacteremia. Brucellosis can remain undetected if clinical symptoms are absent or not detected (infertility, pregnancy disorders, iritis, spondylodiscitis, lymphadenitis, prostatitis, epididymitis).

Diagnostics

For the detection of brucellosis in cases of abortion, the placenta is a particularly important sample material for diagnostics due to the high concentration of the pathogen. Due to the classification of certain brucella species as pathogens of risk group 3, cultivation and phenotyping may only be carried out in the laboratory of safety level L3, 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 multiplex PCR specific for species and biovars. PCR from direct tissue enables rapid pathogen detection at genus level. The serological detection of specific antibodies is also diagnostic.

Control/Preventive measures

Brucellosis in 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 pathogen. Serological tests are used to monitor the absence of the disease.

Farmers, veterinarians, animal breeders and slaughterhouse staff must comply with the strictest hygiene rules when handling infected animals. Persons on farms that are supplied with animals from an affected farm should also be informed about the disease and the 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 disinfectant and cleaning of hands with soap and water are absolutely necessary. A suitable ointment protection can provide additional protection against transdermal infections. Clothing and shoes must be changed after stable work. Surface disinfection in animal stables is appropriate.

Institute for Veterinary Investigations Mödling (National Reference Laboratory for Brucellosis)

Robert-Koch-Gasse 17
2340 Mödling

Tel.: +43 50 555-38112
E-mail: vetmed.moedlingno@Spam@agesno.Spam.at