Brucellosis is a zoonotic disease spread primarily via ingestion of unpasteurized milk from infected animals. It is also known as undulant fever, Malta fever, and Mediterranean fever.

The causative agents, Brucella, are small, Gram-negative, nonmotile, nonspore-forming, rod-shaped (coccobacilli) bacteria. They function as facultative intracellular parasites, and can cause lifelong chronic disease. Four species infect humans: B. abortus, B. canis, B. melitensis, and B. suis. B. abortus is less virulent than B. melitensis and is primarily a disease of cattle. B. canis affects dogs. B. melitensis is the most virulent and invasive species; it usually infects goats and occasionally sheep. B. suis is of intermediate virulence and chiefly infects pigs. Symptoms include profuse sweating and joint and muscle pain. Brucellosis has been recognized in animals and humans since the early 20th century.Park. K., Park's textbook of preventive and social medicine, 23rd edition. Page 290-91

Signs and symptoms

Symptoms of brucellosis are described as flu-like, often consisting of fever, chills, anorexia, headaches, vomiting, diarrhea, abdominal pain, joint and muscle aches, and malaise.

Brucellosis can result in sacroiliitis, miscarriage, osteomyelitis, spondylodiscitis, septic arthritis, orchitis, and epidural abscesses. Neurological symptoms (neurobrucellosis) and endocarditis are rare complications of brucellosis; however, endocarditis is the most common cause of death from brucellosis.

Cause

Brucellosis in humans is usually associated with consumption of unpasteurized milk and soft cheeses made from the milk of infected animals—often goats—infected with B. melitensis, and with occupational exposure of laboratory workers, veterinarians, and slaughterhouse workers. These infected animals may be healthy and asymptomatic. Some vaccines used in livestock, most notably B. abortus strain 19, also cause disease in humans if accidentally injected. Brucellosis induces inconstant fevers, miscarriage, sweating, weakness, anemia, headaches, depression, and muscular and bodily pain. The other strains, B. suis and B. canis, cause infection in pigs and dogs, respectively.

Overall findings support that brucellosis poses an occupational risk to goat farmers with specific areas of concern including weak awareness of disease transmission to humans and lack of knowledge on specific safe farm practices such as quarantine practices.

Wildlife reservoirs and zoonotic transmission Brucellosis affects both domestic and wildlife species, with the latter serving as significant reservoirs that contribute to disease persistence and transmission. Notably, bison, elk, wild boars, and deer have been identified as carriers, particularly in North America and Europe Humans can contract the disease through direct handling of infected animals, aerosol exposure, or consumption of undercooked game meat. Additionally, the wildlife trade has been implicated in the geographical spread of brucellosis, as the movement and sale of infected animals, particularly in unregulated markets, introduce the bacteria into new ecosystems, increasing disease risks for both humans and animals. Reports from Central Asia and sub-Saharan Africa highlight cases where wildlife trafficking has facilitated brucellosis outbreaks in non-endemic regions.

Transmission through hunting and game meat consumption Hunters and individuals who consume wild game face an elevated risk of brucellosis exposure due to direct contact with infected animals and inadequate meat preparation. Transmission can occur during field-dressing or handling of infected carcasses, as Brucella bacteria can enter the body through skin abrasions, mucous membranes, or inhalation of aerosolized pathogens. Additionally, the consumption of undercooked or improperly handled wild game meat remains a significant risk factor, particularly in regions where game animals constitute a primary food source. Implementing protective measures, such as the use of personal protective equipment (PPE) during handling and ensuring thorough cooking of game meat, is essential to mitigating the risk of brucellosis transmission within hunting communities.

Diagnosis

The diagnosis of brucellosis relies on: Demonstration of the agent: blood cultures in tryptose broth, bone marrow cultures. The growth of brucellae is extremely slow (they can take up to two months to grow), and the culture poses a risk to laboratory personnel due to the high infectivity of brucellae. Demonstration of antibodies against the agent, either with the classic Huddleson, Wright, and/or Bengal Rose reactions, either with ELISA or the 2-mercaptoethanol assay for IgM antibodies associated with chronic disease Histologic evidence of granulomatous hepatitis on hepatic biopsy Radiologic alterations in infected vertebrae: the Pedro Pons sign (preferential erosion of the anterosuperior corner of lumbar vertebrae) and marked osteophytosis are suspicious of brucellic spondylitis. Definite diagnosis of brucellosis requires the isolation of the organism from the blood, body fluids, or tissues, but serological methods may be the only tests available in many settings. Positive blood culture yield ranges between 40 and 70% and is less commonly positive for B. abortus than B. melitensis or B. suis. Identification of specific antibodies against bacterial lipopolysaccharide and other antigens can be detected by the standard agglutination test (SAT), rose Bengal, 2-mercaptoethanol (2-ME), antihuman globulin (Coombs') and indirect enzyme-linked immunosorbent assay (ELISA). SAT is the most commonly used serology in endemic areas. An agglutination titre greater than 1:160 is considered significant in nonendemic areas and greater than 1:320 in endemic areas.

Due to the similarity of the O polysaccharide of Brucella to that of various other Gram-negative bacteria (e.g. Francisella tularensis, Escherichia coli, Salmonella urbana, Yersinia enterocolitica, Vibrio cholerae, and Stenotrophomonas maltophilia), the appearance of cross-reactions of class M immunoglobulins may occur.Brucellosis. Louisiana Department of Health, Office of Public Health, Infectious Disease Epidemiology Section, 20 Apr. 2005, https://ldh.la.gov/assets/oph/Center-PHCH/Center-CH/infectious-epi/BT/btmanual/Brucellosis.pdf The inability to diagnose B. canis by SAT due to lack of cross-reaction is another drawback. False-negative SAT may be caused by the presence of blocking antibodies (the prozone phenomenon) in the α2-globulin (IgA) and in the α-globulin (IgG) fractions.

Dipstick assays are new and promising, based on the binding of Brucella IgM antibodies, and are simple, accurate, and rapid. ELISA typically uses cytoplasmic proteins as antigens. It measures IgM, IgG, and IgA with better sensitivity and specificity than the SAT in most recent comparative studies. The commercial Brucellacapt test, a single-step immunocapture assay for the detection of total anti-Brucella antibodies, is an increasingly used adjunctive test when resources permit. PCR is fast and should be specific. Many varieties of PCR have been developed (e.g., nested PCR, real-time PCR, and PCR-ELISA) and found to have superior specificity and sensitivity in detecting both primary infection and relapse after treatment. Unfortunately, these are not standardized for routine use, and some centres have reported persistent PCR positivity after clinically successful treatment, fuelling the controversy about the existence of prolonged chronic brucellosis.

Other laboratory findings include normal peripheral white cell count, and occasional leucopenia with relative lymphocytosis. The serum biochemical profiles are commonly normal.

Prevention

Prevention of human brucellosis depends largely on controlling infection in animals and reducing exposure to contaminated animal products and animal tissues. Common public health measures include pasteurization of milk, avoidance of raw dairy products, use of protective clothing when handling potentially infected animals or animal tissues, and biosafety precautions in laboratories.

In areas where brucellosis is endemic in livestock, prevention strategies may include animal vaccination, testing, surveillance, movement control, and culling of infected herds where feasible. People at increased occupational risk, including veterinarians, farmers, slaughterhouse workers, hunters, and laboratory personnel, are advised to use personal protective equipment and avoid unprotected contact with placentas, fetuses, blood, and other potentially infectious materials. There is no widely available human vaccine for brucellosis, so prevention in humans relies primarily on food safety, occupational precautions, and control of the disease in animal populations.

Livestock vaccination and disease surveillance Vaccination is the most effective method for controlling brucellosis in livestock. In cattle, the most common vaccines are Brucella abortus strain 19 and RB51, while for goats and sheep, B. melitensis Rev-1 is used. Other methods include regular serological screening, and the culling of infected animals helps prevent the spread of disease. In many countries, mandatory vaccination programs and test-and-slaughter policies have been shown to significantly reduce brucellosis incidence in livestock populations.

Food safety and pasteurization Brucellosis is commonly transmitted to humans through the consumption of unpasteurized dairy products, particularly raw milk and cheese. Pasteurization is one of the most effective methods to eliminate Brucella with many countries implementing it while hosting public educational campaigns to discourage the consumption of raw dairy.

Wildlife reservoirs and disease control Wild animals, including bison, elk, wild boars, and deer, serve as natural reservoirs for Brucella. Spillover infections from wildlife to livestock pose ongoing challenges, particularly in regions with dairy farms. Control measures include restricted feeding areas, selective culling, and experimental wildlife vaccination programs. Hunters and individuals handling game meat are advised to wear protective gloves and cook meat thoroughly to prevent infection.

Occupational safety and laboratory precautions Brucellosis poses an occupational hazard for veterinarians, farmers, slaughterhouse workers, and laboratory personnel who handle infected animals or biological specimens. Common preventive measures include the use of personal protective equipment (PPE), proper ventilation in slaughterhouses, and adherence to laboratory biosafety protocols. Accidental exposure in laboratory settings can occur through aerosolized bacteria or direct contact with infected samples, necessitating post-exposure antibiotic prophylaxis.

Public health education and community awareness Educational initiatives are essential to reducing brucellosis transmission, particularly in rural communities where unpasteurized dairy products remain widely consumed. Public health campaigns emphasize the importance of basic knowledge of brucellosis disease and transmission, safe food handling, and vaccination compliance.

International disease control efforts and One Health integration Brucellosis control relies on a One Health approach integrating human, animal, and environmental health. Global organizations, including the World Health Organization (WHO), Food and Agriculture Organization (FAO), World Organisation for Animal Health (WOAH), and the United Nations Environment Programme (UNEP), advocate for integrated strategies to manage health threats across humans, animals, plants, and the environment, to prevent prevent future pandemics. Collaborative efforts to identify risk factors enhances outbreak surveillance, livestock vaccination programs, and food safety regulations such as mandatory pasteurization, ensuring a sustainable and comprehensive approach disease management.