Brucellosis is an infectious disease caused by Brucella species. It is known by many other names, including remitting fever, undulant fever, Mediterranean fever, Maltese fever, Gibraltar fever, Crimean fever, goat fever, and Bang disease. The disease was described by George Cleghorn, a British army surgeon stationed on Minorca, in his 1751 work Observations on the Epidemical Diseases in Minorca from the Year 1744 to 1749. Brucellosis again came to the attention of medical officers of the British army on the island of Malta following the Crimean War. The genus Brucella is named for Major-General Sir David Bruce, who in 1886 led the Malta Fever Commission that identified Brucella melitensis as the organism responsible for the disease. In 1905, Sir Themistocles Zammit identified that infected goats transmitted brucellosis in their milk. 
Brucellosis is a zoonotic disease that can be caused by four different Brucella species in humans: B. suis, B. melitensis, B. abortus, and B. canis. Among these, B. melitensis is the most virulent, followed by B. suis. As few as 10 to 100 organisms can cause the disease in humans. All Brucella species are gram-negative, nonmotile, facultative intracellular coccobacilli. Brucella species do not form spores or toxins. The animal host of B. suis is swine; the hosts of B. melitensis are sheep and goats; the host of B. abortus is cattle; and the hosts of B. canis are dogs. 
The disease is transmitted from animals to humans by consumption of unpasteurized milk and dairy products, consumption of under-cooked meat, or skin penetration of those in contact with livestock. It is one of the most common laboratory-acquired bacterial infections in the United States. It also has been shown to be transmitted by inhalation of contaminated aerosols, conjunctival inoculation, blood transfusions, transplacentally from mother to fetus, and rarely from person to person. In 2010, 115 cases of brucellosis were diagnosed in the United States and reported to the Centers for Disease Control and Prevention. California and Texas were the states with the highest number of cases in 2010, and most cases in the United States are related to occupational exposure of those who work with animals. 
The incubation period may be as few as three days or as long as several weeks. When ingested, Brucella organisms are phagocytosed and enter the intestinal submucosa, where they are transported to lymphoid tissue by macrophages. Symptoms frequently last for several months, and chronic infections with brucellosis may last for years.
Symptoms include a headache, cyclical fever, migratory arthralgia, myalgia, hepatomegaly, splenomegaly, vomiting, diarrhea, abdominal pain, miscarriage, transaminitis, orchitis, epididymitis, endocarditis, meningoencephalitis, and anemia. Brucella has been shown to cause sacroiliitis, osteomyelitis, spondylodiscitis, septic arthritis, and epidural abscess. Hepatic abscesses and granulomas occur in some cases. Spontaneous bacterial peritonitis and infection of a ventriculo-peritoneal shunt have been reported. Respiratory symptoms including a cough, dyspnea, and pleurisy may occur; however, in most cases, chest radiography is normal, although focal abscesses, effusions, granulomas, and abscesses have occurred. Neurologic symptoms and Guillain-Barre syndrome have been associated with acute neurobrucellosis. Subarachnoid hemorrhage and myelitis also have been observed. Skin lesions such as maculopapular eruptions, erythema nodosum, abscesses, and panniculitis have been reported. Immune thrombocytopenic purpura has occurred. Death occurs in 2% of cases. Endocarditis rarely occurs; however, it is the most common cause of death from brucellosis. Aortic fistulas have also been documented. Patients have been reported to have particularly foul-smelling perspiration that has been described as similar to mold or wet hay. The physical examination is most often normal, although lymphadenopathy, splenomegaly, and hepatomegaly may be found.
Brucellosis may be diagnosed by blood cultures in tryptose medium; however, because of the slow-growing nature of Brucella, the cultures may take a week or more to become positive. Culture of bone marrow has a higher yield than blood cultures. Standard agglutination testing is the most common method of diagnosis in endemic areas. Indirect enzyme-linked immunosorbent assay (ELISA) and Rose Bengal testing also may be used. Laboratory testing on the patient may show anemia, leukopenia, or pancytopenia as well as elevated C-reactive protein, erythrocyte sedimentation rate, serum lactate dehydrogenase, alkaline phosphatase, and transaminases. Pedro Pons sign, erosion of the anterior superior aspect of lumbar vertebrae with osteophytosis, is associated with spondylodiscitis caused by Brucella. Disc space narrowing, bone destruction, and sclerosis may be seen on imaging in patients with spondylitis. Nonspecific hepatitis and granulomas may be observed on liver biopsy. 
Doxycycline is used in conjunction with either streptomycin, rifampin, gentamicin, or sulfamethoxazole/trimethoprim to treat brucellosis; because the bacteria resides within cells, several weeks of treatment are needed. Treating with a single antibiotic should be avoided, as there is a high rate of relapse when a combination regimen is not used. In children, a regimen of trimethoprim-sulfamethoxazole and rifampin for 4 to 6 weeks may be used, since children should not be treated with doxycycline. Pregnant women may be treated with rifampin during pregnancy, with trimethoprim-sulfamethoxazole added postpartum. The infected heart valves of patients with endocarditis may need to be replaced and repair of aortic and aortopulmonary fistulas have been performed. Surgical debridement and bone grafting of patients with spondylitis also have been performed. Dairy herds in the United States are tested for brucellosis yearly, and cows are vaccinated against the disease; accidental exposure to the cow vaccine has been shown to cause the disease in humans.
Although it may take time to obtain control of the symptoms, the prognosis for most patients with brucellosis is excellent. The overall risk of relapse is very low. however, in patients with comorbid disorders like heart or lung disease, the condition can be disabling. Unlike many other infection disorders, the condition tends to improve with physical activity rather than bed rest. The recovery usually takes 3-6 months. When recurrence does occur, it may be either local or systemic.
The majority of patients are managed as outpatients unless there are complications. Avoiding contact with the source of infection is important. To ensure the patient is responding to treatment, serological monitoring is required. Compliance with medical treatment is essential for full recovery.
Brucella species have been successfully developed into biological weapons by the United States and several countries, although it is not known to have been used in war. B. suis (agent US), B. melitensis (agent AM), and B. abortus (agent AB) were all researched by the United States for its biological warfare program; however, their lethality of less than 5% made them less than ideal for military leaders who were seeking lethal agents. Brucella is easily aerosolized and survives well after aerosolization. In the event of a biological attack or a laboratory accident involving a Brucella species, treatment with one of the antibiotic regimens mentioned above should be considered. Antibiotic prophylaxis is not generally recommended for exposure to endemic Brucella species, and prevention is best achieved by wearing appropriate protection when working with infected animals, adequately cooking meat products, and pasteurization of dairy products. Although vaccines are available for animals, there is no human vaccine to prevent Brucella infection.
Brucellosis is a common zoonotic disease that is transmitted to humans from ruminants. While the disease is on the decline, epidemiological surveillance is vital to detect any outbreak or local emergence in humans or animals. Expert evidence indicates that brucellosis is best managed by an interprofessional team of health care workers that includes an epidemiologist, an infectious disease consultant, internists, a pharmacist, and a nurse. (Level V)
Because the disease is acquired from wildlife, it is vital to educate the patient and family on avoidance of exposure. Since brucellosis can present with involvement of almost any organ system, high suspicion should be maintained. The medical laboratory is essential to help make the diagnosis of the disease. Once the infection is treated, the pharmacist should ensure that the patient remains compliant with drug therapy. In addition, if there is any evidence of recurrence, the patient should be referred to an internist for serological studies. Countless studies show that a multidisciplinary approach to brucellosis results in a complete cure within 4-6 months, with excellent outcomes. (Level V)
|||Głowacka P,Żakowska D,Naylor K,Niemcewicz M,Bielawska-Drózd A, Brucella - Virulence Factors, Pathogenesis and Treatment. Polish journal of microbiology. 2018 Jun 30 [PubMed PMID: 30015453]|
|||Hull NC,Schumaker BA, Comparisons of brucellosis between human and veterinary medicine. Infection ecology [PubMed PMID: 30083304]|
|||Bakri FG,AlQadiri HM,Adwan MH, The Highest Cited Papers in Brucellosis: Identification Using Two Databases and Review of the Papers' Major Findings. BioMed research international. 2018 [PubMed PMID: 29850587]|
|||Bukhari EE, Pediatric brucellosis. An update review for the new millennium. Saudi medical journal. 2018 Apr [PubMed PMID: 29619483]|
|||Brown VR,Bowen RA,Bosco-Lauth AM, Zoonotic pathogens from feral swine that pose a significant threat to public health. Transboundary and emerging diseases. 2018 Jun [PubMed PMID: 29388363]|
|||Craighead L,Meyer A,Chengat B,Musallam I,Akakpo J,Kone P,Guitian J,Häsler B, Brucellosis in West and Central Africa: A review of the current situation in a changing landscape of dairy cattle systems. Acta tropica. 2018 Mar [PubMed PMID: 29287761]|
|||Peck D,Bruce M, The economic efficiency and equity of government policies on brucellosis: comparative insights from Albania and the United States of America. Revue scientifique et technique (International Office of Epizootics). 2017 Apr [PubMed PMID: 28926008]|
|||Guzmán-Hernández RL,Contreras-Rodríguez A,Ávila-Calderón ED,Morales-García MR, [Brucellosis: a zoonosis of importance in Mexico]. Revista chilena de infectologia : organo oficial de la Sociedad Chilena de Infectologia. 2016 Dec [PubMed PMID: 28146190]|
|||Zamri-Saad M,Kamarudin MI, Control of animal brucellosis: The Malaysian experience. Asian Pacific journal of tropical medicine. 2016 Dec [PubMed PMID: 27955740]|
|||Meng F,Pan X,Tong W, Rifampicin versus streptomycin for brucellosis treatment in humans: A meta-analysis of randomized controlled trials. PloS one. 2018 [PubMed PMID: 29462155]|
|||Buttigieg SC,Savic S,Cauchi D,Lautier E,Canali M,Aragrande M, Brucellosis Control in Malta and Serbia: A One Health Evaluation. Frontiers in veterinary science. 2018 [PubMed PMID: 30018972]|
|||Mailles A,Garin-Bastuji B,Lavigne JP,Jay M,Sotto A,Maurin M,Pelloux I,O'Callaghan D,Mick V,Vaillant V,De Valk H, Human brucellosis in France in the 21st century: Results from national surveillance 2004-2013. Medecine et maladies infectieuses. 2016 Dec [PubMed PMID: 27717526]|
|||Arenas-Gamboa AM,Rossetti CA,Chaki SP,Garcia-Gonzalez DG,Adams LG,Ficht TA, Human Brucellosis and Adverse Pregnancy Outcomes. Current tropical medicine reports. 2016 Dec [PubMed PMID: 29226068]|
|||Jia B,Zhang F,Lu Y,Zhang W,Li J,Zhang Y,Ding J, The clinical features of 590 patients with brucellosis in Xinjiang, China with the emphasis on the treatment of complications. PLoS neglected tropical diseases. 2017 May [PubMed PMID: 28459811]|