Brucellosis is a zoonotic bacterial infection caused by Brucella species—gram-negative, facultative intracellular pathogens that primarily affect livestock, including cattle (Brucella abortus), sheep and goats (Brucella melitensis), pigs (Brucella suis), and, less commonly, dogs (Brucella canis). These bacteria are highly infectious and can survive within host cells, evading the immune system and complicating treatment. The disease is endemic in many parts of the world, particularly in regions with limited veterinary infrastructure and inadequate public health resources.
Transmission to humans occurs through direct contact with infected animals, exposure to animal secretions such as blood, urine, vaginal discharges, or aborted fetuses, and the ingestion of unpasteurized dairy products such as raw milk, cheese, or butter. Occupational exposure is common among farmers, veterinarians, slaughterhouse workers, and laboratory personnel.
In humans, brucellosis typically manifests as a prolonged febrile illness, often referred to as undulant fever due to its characteristic pattern of recurring fevers. Other common symptoms include fatigue, malaise, sweats, anorexia, and musculoskeletal pain, particularly in the joints and lower back. If untreated, the disease can become chronic, leading to complications such as arthritis, endocarditis, spondylitis, and neurobrucellosis. Diagnosis is often delayed due to the non-specific nature of symptoms and the need for specialized laboratory tests.
Treatment typically involves combination antibiotic therapy to prevent relapse. The World Health Organization recommends a dual regimen of doxycycline and rifampicin for a minimum of six weeks. In some cases, alternative combinations such as doxycycline with streptomycin or gentamicin may be used, especially in severe or complicated cases. Control and prevention efforts focus on reducing infection in animal populations through vaccination programs, test-and-slaughter strategies, and improved biosecurity measures.
History of Brucellosis
Brucellosis was first described in the late 19th century. The disease was initially identified by British physician Sir David Bruce in 1887 during his work on Mediterranean fever. Early outbreaks were common where animal husbandry was widespread, especially in the Mediterranean region.
The link between human cases and infected animals became clear through research in the early 20th century. Pioneering work by microbiologists such as Themistocles Zammit in 1905 demonstrated that humans contracted the disease through the consumption of unpasteurized goat milk and contact with infected animals. Zammit’s identification of the goat as a primary reservoir was pivotal in understanding the transmission cycle and set the stage for future control measures.
Throughout the 1900s, brucellosis was recognized as a major occupational disease, especially among farmers, veterinarians, and slaughterhouse workers. The disease was prevalent in regions with extensive animal husbandry, particularly around the Mediterranean basin, Middle East, and Latin America. Efforts to curb human brucellosis began to gain traction in the mid-20th century with the widespread adoption of milk pasteurization and the introduction of livestock vaccination programs, especially in industrialized nations.
Causative Agents
The genus Brucella comprises several gram-negative, non-motile, facultative intracellular coccobacilli that are responsible for brucellosis in both animals and humans. These bacteria are uniquely adapted to survive and replicate within host phagocytic cells, especially macrophages, which allows them to evade the immune system and persist for extended periods. This intracellular lifestyle contributes to the chronic nature of the disease and complicates treatment.
The primary Brucella species that affect humans include:
- Brucella melitensis – Found in goats and sheep; it is the most virulent and invasive species for humans and is responsible for the majority of severe human cases worldwide.
- Brucella abortus – Primarily infects cattle; less virulent than B. melitensis, but still a significant cause of zoonotic infection.
- Brucella suis – Associated with pigs; capable of causing focal abscesses and more severe complications in humans.
- Brucella canis – Originates from dogs; infection in humans is rare and typically milder, but has been documented in immunocompromised individuals.
Other Brucella species, such as Brucella ovis and Brucella neotomae, affect animals but are not known to cause disease in humans. Recently identified marine species like Brucella ceti and Brucella pinnipedialis have been isolated from marine mammals and may have zoonotic potential, although confirmed human infections are rare.
These bacteria exhibit high infectivity and are able to withstand harsh environmental conditions for limited periods, especially in organic materials like aborted fetuses or contaminated dairy products.
Transmission of Brucellosis
Brucellosis spreads through several specific pathways involving animals and humans.
Routes of Infection
Brucella organisms can enter the human body through multiple portals, including mucosal membranes, abrasions in the skin, and the gastrointestinal and respiratory tracts. One of the most common infection routes is the ingestion of unpasteurized milk, cheese, or other dairy products contaminated with Brucella species. These products can contain high concentrations of viable bacteria, particularly when derived from infected animals.
Direct contact with infected animal secretions including blood, urine, vaginal discharge, aborted fetuses, and placental tissues, is another major transmission route, especially for individuals involved in livestock management or veterinary work. The risk increases significantly during animal birthing or abortion events due to the high bacterial load present in reproductive fluids.
Inhalation of aerosolized Brucella organisms poses a significant risk in certain occupational settings, such as laboratories (especially during specimen handling), slaughterhouses, and meat processing plants. Brucella species are highly infectious via the aerosol route; as few as 10–100 organisms can cause disease in humans, making brucellosis a notable biosafety concern and a Category B bioterrorism agent.
Though rare, sexual transmission between humans has been reported, supported by the presence of Brucella in semen. Vertical transmission from an infected mother to the fetus has also been documented, leading to miscarriage, intrauterine infection, or neonatal brucellosis in severe cases.
Zoonotic Transmission
Brucellosis is primarily a zoonotic disease, meaning it is naturally transmissible from vertebrate animals to humans. The primary animal reservoirs include cattle, sheep, goats, pigs, buffaloes, and camels, each typically infected by different Brucella species:
- Brucella abortus – predominantly infects cattle.
- Brucella melitensis – affects goats and sheep; considered the most virulent for humans.
- Brucella suis – infects pigs and can cause severe disease in humans.
- Brucella canis – primarily found in dogs, less commonly associated with human infection.
Occupational exposure is a critical factor in zoonotic transmission. Individuals working closely with animals such as farmers, veterinarians, livestock handlers, abattoir workers, and animal health technicians are at elevated risk. In some rural communities, entire households may be exposed if infected animals are housed near living quarters or if raw dairy is a dietary staple.
Wildlife reservoirs, such as elk, bison, and wild boar, can also harbor Brucella and contribute to disease persistence in areas where livestock and wildlife interact, complicating eradication efforts.
Risk Factors
Several key risk factors increase the likelihood of human brucellosis infection:
- Consumption of unpasteurized milk, cheese, or yogurt, especially in endemic regions.
- Assisting with livestock parturition or handling aborted materials without protective equipment.
- Occupational exposure to animal fluids, tissues, or carcasses.
- Inadequate use of personal protective equipment (PPE) such as gloves, aprons, and face masks during animal handling or laboratory procedures.
- Living in rural, agricultural, or nomadic communities, where close contact with livestock is common.
- Recreational hunting or processing of wild game, particularly feral pigs or deer.
Immunocompromised individuals, including those with HIV/AIDS, cancer, or on immunosuppressive medications, are more susceptible to severe or chronic brucellosis. Children and pregnant women are also considered vulnerable groups due to complications such as miscarriage or congenital infection.
Geographical Distribution
Brucellosis remains endemic in the Mediterranean basin, the Middle East, parts of Latin America, Central Asia, and sub-Saharan Africa.
In these regions, livestock management practices and limited pasteurization services promote bacterial persistence. Developed countries have reduced incidence through control programs and mandatory pasteurization.
Outbreaks still occur in areas with poor veterinary infrastructure. Travelers to endemic regions risk exposure, especially when consuming local dairy products or working with animals.
Signs and Symptoms
Brucellosis presents differently in humans and animals, with symptoms ranging from mild to severe. Certain complications may arise if the infection remains untreated, affecting multiple organ systems.
Symptoms in Humans
In humans, brucellosis typically manifests as a systemic febrile illness with a gradual onset. One of the hallmark features is undulant fever, characterized by a wave-like pattern of temperature spikes and remissions, often more pronounced in the evening. Other early symptoms include profuse night sweats, commonly described as having a pungent or moldy odor, malaise, arthralgia, myalgia, and headache. Patients frequently report fatigue that can persist long after resolution of the acute phase.
Appetite loss, weight loss, and gastrointestinal discomfort such as nausea or abdominal pain are also reported in some cases. Physical examination may reveal hepatosplenomegaly (enlarged liver and spleen), generalized lymphadenopathy, or tenderness in affected joints. The clinical picture varies significantly across stages:
- Acute brucellosis (less than 8 weeks) often presents with fever, sweating, and muscle pain.
- Subacute cases (8–12 weeks) may involve more systemic symptoms and organ involvement.
- Chronic brucellosis (over 12 weeks) typically includes relapsing fever, joint pain, fatigue, and depression, and is more difficult to treat.
Relapse may occur in up to 10% of treated patients, especially when therapy is inadequate or prematurely discontinued.
Symptoms in Animals
In animals, brucellosis mainly affects reproductive function, particularly in sexually mature livestock such as cattle, goats, sheep, pigs, and buffaloes. The most characteristic sign in female animals is late-term abortion, often followed by retained placenta or metritis, which can impair future fertility. These reproductive losses commonly occur during the first pregnancy after infection.
Male animals may develop orchitis, epididymitis, and testicular atrophy, leading to subfertility or sterility. In dairy herds, reduced milk yield and mastitis are frequent in infected females. Neonates may be weak or stillborn. Many infected animals, particularly in the chronic phase, may not show visible symptoms, contributing to silent transmission within herds. This asymptomatic nature makes routine serological surveillance crucial for disease control. The disease can persist in lymphatic tissues and reproductive organs, allowing intermittent shedding of bacteria through milk, urine, semen, and placental fluids.
Complications
Complications of brucellosis, especially in humans, can be diverse and severe, reflecting the pathogen’s capacity to infect multiple organ systems. They are more likely to develop in chronic or inadequately treated cases. One of the most frequent complications is osteoarticular involvement, reported in up to 60% of cases. This includes arthritis, most often affecting large joints like the knees and hips; sacroiliitis, presenting with low back or pelvic pain; and spondylitis, which can lead to vertebral collapse or spinal cord compression if untreated. Radiographic imaging is often required for diagnosis.
Endocarditis, although rare (1–2% of cases), is the leading cause of brucellosis-related mortality. It usually affects individuals with pre-existing valvular heart disease and often necessitates surgical intervention alongside antibiotics.
Neurological complications, termed neurobrucellosis, can present as meningitis, encephalitis, myelitis, or radiculopathy. Symptoms may include headache, neck stiffness, altered mental status, or cranial nerve involvement. Neurobrucellosis requires prolonged antibiotic therapy and may leave lasting neurological deficits if treatment is delayed.
Other complications include:
- Hepatic and splenic abscesses
- Genitourinary involvement, such as epididymo-orchitis
- Pulmonary manifestations, including pneumonia or pleural effusion
- Hematologic abnormalities, such as anemia, thrombocytopenia, and leukopenia
- Hematopoietic organ infiltration, leading to bone marrow suppression
In pregnant women, brucellosis has been associated with spontaneous abortion, preterm labor, and fetal death, making early diagnosis and treatment critical during pregnancy. Vertical transmission to the fetus, although rare, has been reported.
In animals, complications primarily impact fertility and productivity. Chronic reproductive disorders may render valuable breeding stock unfit for reproduction. Systemic dissemination of Brucella can lead to chronic inflammation in multiple organs, exacerbating economic losses. Additionally, zoonotic transmission from animals to humans poses an ongoing public health concern, especially in endemic regions with poor veterinary infrastructure.
Diagnosis of Brucellosis
Diagnosing brucellosis requires a combination of clinical insights and laboratory evidence. Accurate assessment and ruling out other diseases with similar symptoms are vital for targeted treatment.
Clinical Evaluation
Clinical evaluation focuses on identifying symptoms like fever, night sweats, fatigue, and joint pain. These symptoms typically appear gradually and may persist for weeks or months before presentation. Brucellosis may manifest as acute, subacute, or chronic illness, depending on the duration and severity of the infection.
A comprehensive patient history is critical in guiding diagnostic suspicion. Key factors include occupational exposure to livestock or wild animals, particularly in veterinarians, abattoir workers, farmers, and laboratory personnel. A history of consuming unpasteurized dairy products, such as raw milk or soft cheeses, is also a major risk factor, especially in endemic areas. Physical examination may reveal hepatosplenomegaly, generalized lymphadenopathy, arthritis, or epididymo-orchitis in males. In rare cases, neurologic signs or cardiovascular symptoms may point toward more severe forms such as neurobrucellosis or endocarditis. However, because these signs are not unique to brucellosis, laboratory testing is essential for confirmation.
Laboratory Testing
Laboratory confirmation remains the definitive step in diagnosing brucellosis. Serological testing is the most commonly used diagnostic approach, especially in resource-limited settings. The Rose Bengal Test (RBT) serves as a rapid screening tool, while the Standard Agglutination Test (SAT) and ELISA (Enzyme-Linked Immunosorbent Assay) provide more quantitative antibody titers and can distinguish between acute and chronic infection. IgM and IgG levels are used to determine the stage of infection.
Blood cultures are considered the gold standard for diagnosis, as they allow direct identification of Brucella species. However, their sensitivity is variable and often low in chronic infections due to intermittent bacteremia. Cultures typically require 2–4 weeks of incubation due to the slow-growing nature of Brucella. Modern automated blood culture systems have improved detection rates and turnaround times.
Polymerase Chain Reaction (PCR)-based methods are increasingly used in reference laboratories for rapid, specific detection of Brucella DNA. PCR is especially useful in cases where culture is negative or delayed, such as in neurobrucellosis or focal infections. Additional investigations may include liver and renal function tests, complete blood count (often showing anemia or leukopenia), and inflammatory markers like ESR and CRP to assess systemic involvement. In complicated cases, imaging studies (e.g., MRI or CT) may be required to detect organ involvement such as spondylitis or abscesses.
Differential Diagnosis
Due to its nonspecific clinical presentation, brucellosis must be distinguished from a variety of diseases with similar signs and symptoms. These include tuberculosis, malaria, typhoid fever, infective endocarditis, rheumatic diseases (such as rheumatoid arthritis or systemic lupus erythematosus), leptospirosis, and mononucleosis. Chronic brucellosis may also mimic undiagnosed fevers of unknown origin (FUO), leading to diagnostic delays.
Occupational and dietary history, along with laboratory findings such as positive serology or blood culture are needed in differentiating brucellosis from these conditions. Misdiagnosis may result in inappropriate antimicrobial therapy or unnecessary immunosuppressive treatment in cases mistaken for autoimmune disorders. Therefore, clinicians in endemic areas are advised to maintain a high index of suspicion and utilize both clinical judgment and laboratory resources to reach an accurate diagnosis.
Treatment and Management
Effective management of brucellosis relies on targeted antibiotic regimens and supportive care measures. The treatment plan must be followed carefully to avoid complications and reduce relapse risk.
Antibiotic Therapy
Brucellosis is treated primarily with antibiotics that penetrate intracellularly. The World Health Organization recommends a dual antibiotic regimen to reduce relapse and ensure adequate intracellular activity. The most widely used combination consists of doxycycline (100 mg twice daily) and rifampin (600–900 mg once daily), administered over a six-week period. This regimen is effective for uncomplicated cases and is well-tolerated by most adult patients. In children, pregnant women, or patients with specific contraindications, alternatives such as trimethoprim-sulfamethoxazole may be considered under medical supervision.
In more severe or complicated forms of brucellosis—such as neurobrucellosis, spondylitis, or endocarditis—a more aggressive approach is required. In such cases, aminoglycosides like streptomycin (1 g daily intramuscularly for 14–21 days) or gentamicin (5 mg/kg daily for 7–10 days) are added to the doxycycline-based regimen to enhance bactericidal activity. These combination therapies help prevent treatment failure, which is often associated with monotherapy or premature discontinuation of antibiotics. Tailoring the choice of antibiotics also depends on patient factors such as liver function, pregnancy status, medication interactions, and local antibiotic resistance patterns.
Supportive Care
Supportive care addresses symptoms and prevents complications during antibiotic treatment. Symptomatic management includes the use of nonsteroidal anti-inflammatory drugs (NSAIDs) or acetaminophen to alleviate fever, headaches, and musculoskeletal pain, which are common in both acute and chronic brucellosis. In cases involving significant fatigue or systemic symptoms, bed rest and reduced physical activity are advised during the acute phase of illness.
Adequate hydration, nutritional support, and patient education are also key aspects of supportive management. In patients with chronic brucellosis or joint involvement, physical therapy may be required to restore mobility and prevent long-term disability. Regular clinical monitoring is essential, particularly for patients on extended antibiotic therapy. Liver function tests, renal panels, and complete blood counts should be checked periodically to detect potential drug-related toxicities, especially with rifampin or aminoglycoside use. Patients should be counseled to report any new or worsening symptoms, such as vision changes, hearing loss, or persistent fevers, as these may indicate complications or therapeutic failure.
Duration of Treatment
The standard duration of treatment for uncomplicated brucellosis is six weeks, as shorter regimens have been associated with higher relapse rates. This treatment window ensures sufficient time to eliminate intracellular bacteria and reduce the risk of persistent infection. In localized or complicated infections, such as osteoarticular brucellosis, neurobrucellosis, or infective endocarditis, therapy may be extended to 8–12 weeks or longer, depending on clinical response and the site of infection.
Relapse occurs in up to 10% of cases, often due to incomplete treatment or suboptimal drug choices. Therefore, it is critical to complete the full course of therapy even if symptoms resolve early. In relapsed cases, re-treatment using a different or prolonged antibiotic regimen may be necessary, often including an injectable agent. Long-term follow-up, including physical examination and laboratory testing, is recommended for at least six months after completion of therapy to ensure full recovery and to identify late complications.
Prevention and Control
Effective prevention and control of brucellosis focus on interrupting transmission from animals to humans and limiting disease spread within livestock populations. This requires coordinated vaccination, public health policies, and strict handling protocols.
Vaccination Programmes
Vaccination of livestock remains one of the most effective and widely adopted strategies for controlling the spread of brucellosis, particularly in endemic regions where eradication is not yet feasible. The primary goal of these vaccination programs is to reduce infection rates within animal populations, thereby limiting the risk of transmission to humans.
In cattle, two main vaccines are commonly used: the Brucella abortus strain S19 and the RB51 strain. The S19 vaccine, a live attenuated strain developed in the early 20th century, has historically been the standard for preventing brucellosis in young female calves. While highly effective, it can cause persistent antibody responses that interfere with serological diagnostic tests, making it difficult to distinguish between vaccinated and naturally infected animals. To address this, the RB51 vaccine, also a live attenuated strain but lacking the O-side chain of lipopolysaccharide (a major antigenic determinant), was developed. RB51 is less likely to cause false positives in serological testing and has become the preferred option in many countries for vaccinating adult cattle, especially where test-and-slaughter programs are in place.
For small ruminants such as goats and sheep, the Rev-1 vaccine is used primarily to protect against Brucella melitensis, the most virulent Brucella species for humans. The Rev-1 strain is typically administered via conjunctival or subcutaneous routes, usually to female animals before breeding age to avoid complications such as abortion. Like S19, it is a live attenuated vaccine and may induce temporary shedding of the organism in milk, which must be managed to prevent human exposure.
To ensure effective disease control, vaccination coverage must be high and consistently maintained across entire herds or flocks. National and regional veterinary authorities often conduct mass vaccination campaigns on an annual or biannual basis, particularly in rural or high-risk areas.
Despite the success of animal vaccination, human vaccination is not practiced due to the live nature of current vaccines and associated safety concerns, including the potential for adverse effects.
Public Health Strategies
- Early detection through laboratory confirmation of suspected cases helps prevent outbreaks and cross-species transmission.
- Mandatory notification of human and animal brucellosis cases allows for centralized tracking and rapid response by health authorities.
- Educational outreach programs target high-risk populations, including farmers, veterinarians, slaughterhouse workers, and rural communities.
- Instruction on recognizing early symptoms and seeking medical care contributes to better outcomes in human cases.
- Movement control policies restrict the transport of animals from endemic or infected areas to prevent geographic spread.
- Slaughter of infected or exposed herds, although economically challenging, is often necessary to eliminate disease reservoirs.
- Enhancing food safety standards, especially through widespread pasteurization of dairy products, is a critical preventive measure.
- Public campaigns may promote the boiling of milk and thorough cooking of meat in areas lacking formal food regulation.
Safe Handling Practices
- Individuals handling livestock should wear personal protective equipment (PPE), including gloves, masks, goggles, and coveralls.
- High-risk activities such as assisting with animal births, necropsies, or handling reproductive fluids should be conducted with extreme caution.
- Contaminated materials such as aborted fetuses, placental tissues, and bedding should be disposed of using incineration or deep burial.
- Farm and veterinary tools, instruments, and surfaces must be cleaned and disinfected regularly with approved biocidal agents.
- Isolation of sick or recently aborted animals helps contain potential spread within the herd or flock.
- Handwashing and sanitation facilities should be readily available in animal handling environments to reduce cross-contamination.
- Workers should avoid consuming raw or unpasteurized milk, cheese, or other dairy products sourced from potentially infected animals.
- Public and occupational training on hygienic practices is essential in veterinary clinics, abattoirs, and livestock farms.
- Implementation of workplace biosafety protocols helps protect at-risk professionals such as lab technicians and animal health workers.
Economic and Social Impact
Brucellosis significantly affects both animal industries and public health systems. The economic losses in livestock sectors are substantial, while human cases impose costs on healthcare and productivity.
Effects on Livestock Industry
Brucellosis causes decreased milk production, abortions, and infertility in infected animals. These outcomes reduce herd productivity and breeding efficiency. The disease necessitates costly testing, vaccination programs, and culling of infected animals, further increasing expenses.
In many regions, trade restrictions are applied to herds or countries with brucellosis outbreaks. This limits market access and lowers income for farmers and exporters. Small-scale farmers often suffer disproportionately due to fewer resources to manage the disease.
State and national agricultural economies can experience notable declines due to livestock productivity loss and increased control costs. Key economic impacts include:
- Reduced animal reproduction and lifespan
- Loss of milk, meat, and wool production
- Expenses related to diagnostics and control measures
Public Health Burden
Brucellosis is a zoonotic disease, leading to chronic illness in humans such as undulant fever, joint pain, and fatigue. It can require prolonged antibiotic treatment, which raises healthcare costs significantly.
Affected individuals often face lost wages due to long recovery times or disability. The disease predominantly impacts rural populations who work closely with livestock. This creates a social burden by limiting workforce productivity in agricultural communities.
Public health systems must invest in surveillance, diagnosis, and education programs to reduce transmission. The lack of awareness or resources in endemic regions further complicates containment efforts. Healthcare expenses and social disruption due to brucellosis highlight its ongoing public health challenge.