Brucellosis is primarily a disease of animals such as cattle, swine, sheep and goats. Human infection can occur through consumption of infected raw milk, raw milk products or raw meat. Other means of infection include skin abrasions or inhalation of airborne manure particles. Brucellae are highly infectious agents, and without adequate laboratory precautions, staff who work with cultures and infected samples are at risk of infection themselves. There have also been case reports of sexual transmission of Brucellae, and it is important to note that Brucellae are considered to be potential agents used in bioterrorism.
The infecting agent is a member of the genus Brucella. The taxonomy of Brucellae is complicated and still subject to change. Initially there were six species, though with the advent of molecular techniques and the discovery of new species, the following system is currently in use:
- Brucella cetaceae
- Brucella melitensis - subdivided into:
- Brucella melitensis biovar Abortus
- Brucella melitensis biovar Canis
- Brucella melitensis biovar Melitensis
- Brucella melitensis biovar Neotomae
- Brucella melitensis biovar Ovis
- Brucella melitensis biovar Suis
- Brucella pinnipediae
Brucellosis exists worldwide, though is particularly prevalent in the Mediterranean, the Middle East, the Indian subcontinent, Central & South America and Mexico.
- Brucella melitensis biovar Abortus mainly causes infection in cattle though it can also infect other species such as buffalo, yaks and camels.
- Brucella melitensis biovar Melitensis occurs primarily in sheep and goats, though camels are also a reservoir in some areas. It has also been implicated in outbreaks in cattle, particularly in Israel.
- Brucella melitensis biovar Suis causes infection in pigs, and has been the cause of a number of abbattoir-related human cases. A strain of Brucella melitensis biovar Suis also exists in caribou & reindeer in the Arctic.
- Brucella melitensis biovar Canis causes infection in kennel-raised dogs and is a relatively rare cause of human infection.
- Brucella melitensis biovar Ovis causes infection in sheep, but not in humans.
- Brucella melitensis biovar Neotomae causes infection in desert wood rats but not humans.
- Brucella cetaceae and Brucella pinnipediae cause infection in marine mammals, and may cause human infection.
Human infection is usually due to B. melitensis biovar abortus, B. melitensis biovar melitensis,B. melitensis biovar suis and B. melitensis biovar canis.
Brucellosis is a systemic infection, and as such can manifest itself in many ways. The common clinical features of human brucellosis are depressingly non-specific consisting of fever, sweats, malaise, anorexia, back pain and headache. The incubation period is highly variable, ranging from 5-60 days, and symptoms can manifest themselves very quickly or take a much more insidious course of 2-4 weeks. In addition, patients may complain of depression, a bad taste in the mouth and unpleasant-smelling sweat. Clinical signs are few, but include splenomegaly or hepatomegaly in up to a third of cases and mild lymphadenopathy in 10-20% of cases. Untreated, brucellosis can continue for long periods, with an "undulant" fever pattern.
Due to its systemic nature, virtually any organ can be affected by brucellosis:
Depression is a relatively common feature of brucellosis, though direct infection of the nervous system is found in less than 5% of all cases. Manifestations include meningitis, encephalitis and brain & epidural abscesses. Meningitis is the most common neurological complication and may occur at any time during the course of infection.
Hepatobiliary infectionLiver involvement is common, and varies depending on the infecting organism. Brucella melitensis biovar Abortus can give rise to granulomas that can be difficult to distinguish from sarcoid. Brucella melitensis biovar Melitensis infection can give rise to spectrum of lesions ranging from small foci of necrosis throughout the liver parenchyma to diffuse nonspecific inflammation, and occasionally liver abscesses. Brucella melitensis biovar Suis has a tendency to cause suppurative splenic and hepatic abscesses.
Inhalation of Brucella spp. is common in abbatoirs and from inhalation of dried manure. Respiratory complications range from a flu-like syndrome with minimal chest X-ray changes to more severe problems such as pneumonia, bronchitis, lung abscesses and pleural effusion.
Renal complications are uncommon, though pyelonephritis, glomerulonephritis, IgA nephropathy and interstitial nephritis have all been reported. Orchitis occurs in approximately 20% of men with brucellosis. Salpingitis, cervicitis and pelvic abscesses have been reported in women with brucellosis. In animals, brucellosis is to all intents and purposes a sexually transmitted disease and causes spontaneous abortion. Whilst human abortion has also been observed, it has not been established whether this is specifically due to the organism or whether this is due to the incresed rate of foetal loss seen in any bacteraemic febrile illness during pregnancy.
Less than 5% of patients with brucellosis experience cutaneous involvement which can manifest as a papular, petechial or purpuric rash. Ulcers, vasculitides, and erythema nodosum have also been reported.
For brucellosis not complicated by endocarditis, neurological infection or suppurative abscess formation, treatment of choice is doxycycline plus rifampicin for 6 weeks. Shorter courses of antibiotics can lead to unacceptable relapse rates. Alternative therapy includes doxycycline plus streptomycin, trimethoprim-sulfamethoxazole plus gentamicin and ofloxacin plus rifampicin. In the case of endocarditis or neurobrucellosis, triple therapy is advocated, for example doxycycline plus trimethoprim-sulfamethoxazole plus rifampicin.
Diagnosishistory including any travel to enzootic areas, occupation, exposure to animals and ingestion of any high-risk animal products. Full blood count is often unremarkable, and a raised white cell count is not usually seen. C-reactive protein is useful as an indicator of disease progression and outcome. Erythrocyte sedimentation rate is variable and is of little diagnostic value.
The 'gold standard' diagnostic tool is isolation of brucellae from clinical specimens, especially blood and bone marrow. Isolation of brucellae from blood cultures can be problematic, and culture bottles should be incubated for at least 28 days to minimise the risk of missing a positive culture. Brucellae can be missed in automated blood culture systems due to a long doubling time coupled with slow release of carbon dioxide by the bacteria. Many automated systems rely on changes in CO2 concentration in blood culture bottles to detect positive cultures.
NB: If a laboratory culture is suspected to be a Brucella sp. appropriate precautions should be taken to prevent infection of those working with the organism. Once an organism is suspected to be a Brucella sp. the isolate should be sent to the reference laboratory for definitive identification and antibiotic susceptibility testing. An important pitfall to be aware of is that some Brucella isolates can be misidentified as Moraxella phenylpyruvica using commercially-available rapid identification systems. Brucellae are small non-motile non spore-forming gram negative coccobacilli. They grow aerobically, though some strains prefer a CO2 atmosphere. All strains are catalase positive, though oxidase and urease activity may be variable. Selective media containing inhibitory dyes such as basic fuchsin and thionin are used to help differentiate between different biovars.
Prevention and Prophylaxis
There are no licensed vaccines for use in humans, and preventative measures rely on eradication or control of disease in animals. Animal vaccines are available or being developed and utilise a number of different methods, including live attenuated strains, killed strains and subunit or DNA vaccines.