Brucellosis is a
zoonosis
A zoonosis (; plural zoonoses) or zoonotic disease is an infectious disease of humans caused by a pathogen (an infectious agent, such as a virus, bacterium, parasite, fungi, or prion) that can jump from a non-human vertebrate to a human. When ...
spread primarily via ingestion of
unpasteurized milk from infected animals. It is also known as undulant fever, Malta fever, and Mediterranean fever.
The bacteria causing this disease, ''
Brucella
''Brucella'' is a genus of Gram-negative bacterium, bacteria, named after David Bruce (microbiologist), David Bruce (1855–1931). They are small (0.5 to 0.7 by 0.6 to 1.5 μm), non-Bacterial capsule, encapsulated, non-motile, facultatively ...
'', are small,
Gram-negative
Gram-negative bacteria are bacteria that, unlike gram-positive bacteria, do not retain the crystal violet stain used in the Gram staining method of bacterial differentiation. Their defining characteristic is that their cell envelope consists ...
, nonmotile, nonspore-forming, rod-shaped (
coccobacilli) bacteria. They function as
facultative intracellular parasites, causing
chronic disease
A chronic condition (also known as chronic disease or chronic illness) is a health condition or disease that is persistent or otherwise long-lasting in its effects or a disease that comes with time. The term ''chronic'' is often applied when the ...
, which usually persists for life. 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
A joint or articulation (or articular surface) is the connection made between bones, ossicles, or other hard structures in the body which link an animal's skeletal system into a functional whole.Saladin, Ken. Anatomy & Physiology. 7th ed. McGraw- ...
and
muscle pain. Brucellosis has been recognized in animals and humans since the early 20th century.
Signs and symptoms

The symptoms are like those associated with many other
febrile diseases, but with emphasis on muscular pain and night sweats. The duration of the disease can vary from a few weeks to many months or even years.
In the first stage of the disease,
bacteremia
Bloodstream infections (BSIs) are infections of blood caused by blood-borne pathogens. The detection of microbes in the blood (most commonly accomplished by blood cultures) is always abnormal. A bloodstream infection is different from sepsis, wh ...
occurs and leads to the classic triad of undulant fevers, sweating (often with a characteristic foul, moldy smell sometimes likened to wet hay), and migratory
arthralgia
Arthralgia () literally means ' joint pain'. Specifically, arthralgia is a symptom of injury, infection, illness (in particular arthritis), or an allergic reaction to medication
Medication (also called medicament, medicine, pharmaceuti ...
and
myalgia
Myalgia or muscle pain is a painful sensation evolving from muscle tissue. It is a symptom of many diseases. The most common cause of acute myalgia is the overuse of a muscle or group of muscles; another likely cause is viral infection, espec ...
(joint and muscle pain). Blood tests characteristically reveal a
low number of white blood cells and
red blood cells
Red blood cells (RBCs), referred to as erythrocytes (, with -''cyte'' translated as 'cell' in modern usage) in academia and medical publishing, also known as red cells, erythroid cells, and rarely haematids, are the most common type of blood cel ...
, show some elevation of
liver enzymes such as
aspartate aminotransferase and
alanine aminotransferase, and demonstrate positive Bengal rose and Huddleston reactions. Gastrointestinal symptoms occur in 70% of cases and include
nausea
Nausea is a diffuse sensation of unease and discomfort, sometimes perceived as an urge to vomit. It can be a debilitating symptom if prolonged and has been described as placing discomfort on the chest, abdomen, or back of the throat.
Over 30 d ...
,
vomiting
Vomiting (also known as emesis, puking and throwing up) is the forceful expulsion of the contents of one's stomach through the mouth and sometimes the nose.
Vomiting can be the result of ailments like food poisoning, gastroenteritis, pre ...
,
decreased appetite
Anorexia is a medical term for a loss of appetite. While the term outside of the scientific literature is often used interchangeably with anorexia nervosa, many possible causes exist for a loss of appetite, some of which may be harmless, while o ...
, unintentional weight loss, abdominal pain,
constipation
Constipation is a bowel dysfunction that makes bowel movements infrequent or hard to pass. The Human feces, stool is often hard and dry. Other symptoms may include abdominal pain, bloating, and feeling as if one has not completely passed the ...
,
diarrhea
Diarrhea (American English), also spelled diarrhoea or diarrhœa (British English), is the condition of having at least three loose, liquid, or watery bowel movements in a day. It often lasts for a few days and can result in dehydration d ...
,
an enlarged liver,
liver inflammation,
liver abscess
A liver abscess is a mass filled with pus inside the liver. Common causes are abdominal conditions such as appendicitis or diverticulitis due to haematogenous spread through the portal vein. It can also develop as a complication of a liver injury.
...
, and
an enlarged spleen.
This complex is, at least in Portugal, Israel, Syria, Iran, and Jordan, known as Malta fever. During episodes of Malta fever, melitococcemia (presence of brucellae in the blood) can usually be demonstrated using blood culture in tryptose medium or Albini medium. If untreated, the disease can give rise to focalizations or become chronic. The focalizations of brucellosis usually occur in bones and joints, and
osteomyelitis
Osteomyelitis (OM) is the infectious inflammation of bone marrow. Symptoms may include pain in a specific bone with overlying redness, fever, and weakness. The feet, spine, and hips are the most commonly involved bones in adults.
The cause is ...
or
spondylodiscitis
Spondylodiscitis is a combination of discitis (inflammation of one or more intervertebral disc spaces) and spondylitis (inflammation of one or more vertebrae), the latter generally involving the areas adjacent to the intervertebral disc space.
...
of the lumbar spine, accompanied by
sacroiliitis, is very characteristic of this disease.
Orchitis
Orchitis is inflammation of the testicles. It can also involve swelling, pains, and frequent infection, particularly of the epididymis, as in epididymitis. The term is from the Ancient Greek ὄρχις meaning "testicle"; same root as ''orchid ...
is also common in men.
The consequences of ''Brucella'' infection are highly variable and may include
arthritis
Arthritis is a general medical term used to describe a disorder that affects joints. Symptoms generally include joint pain and stiffness. Other symptoms may include redness, warmth, Joint effusion, swelling, and decreased range of motion of ...
,
spondylitis
Spondylitis is an inflammation of the vertebrae. It is a form of spondylopathy. In many cases, spondylitis involves one or more vertebral joints, as well, which itself is called spondylarthritis.
__TOC__
Types
Pott disease is a tuberculous d ...
,
thrombocytopenia
In hematology, thrombocytopenia is a condition characterized by abnormally low levels of platelets (also known as thrombocytes) in the blood. Low levels of platelets in turn may lead to prolonged or excessive bleeding. It is the most common coag ...
,
meningitis
Meningitis is acute or chronic inflammation of the protective membranes covering the brain and spinal cord, collectively called the meninges. The most common symptoms are fever, intense headache, vomiting and neck stiffness and occasion ...
,
uveitis
Uveitis () is inflammation of the uvea, the pigmented layer of the eye between the inner retina and the outer fibrous layer composed of the sclera and cornea. The uvea consists of the middle layer of pigmented vascular structures of the eye and ...
,
optic neuritis
Optic neuritis (ON) is a debilitating condition that is defined as inflammation of cranial nerve II which results in disruption of the neurologic pathways that allow visual sensory information received by the retina to be able to be transmitted to ...
,
endocarditis
Endocarditis is an inflammation of the inner layer of the heart, the endocardium. It usually involves the heart valves. Other structures that may be involved include the interventricular septum, the chordae tendineae, the mural endocardium, o ...
, and various neurological disorders collectively known as neurobrucellosis.
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
fever
Fever or pyrexia in humans is a symptom of an anti-infection defense mechanism that appears with Human body temperature, body temperature exceeding the normal range caused by an increase in the body's temperature Human body temperature#Fever, s ...
s, miscarriage, sweating, weakness,
anemia
Anemia (also spelt anaemia in British English) is a blood disorder in which the blood has a reduced ability to carry oxygen. This can be due to a lower than normal number of red blood cells, a reduction in the amount of hemoglobin availabl ...
,
headache
A headache, also known as cephalalgia, is the symptom of pain in the face, head, or neck. It can occur as a migraine, tension-type headache, or cluster headache. There is an increased risk of Depression (mood), depression in those with severe ...
s,
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
A quarantine is a restriction on the movement of people, animals, and goods which is intended to prevent the spread of disease or pests. It is often used in connection to disease and illness, preventing the movement of those who may have bee ...
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
Personal protective equipment (PPE) is protective clothing, helmets, goggles, or other garments or equipment designed to protect the wearer's body from injury or infection. The hazards addressed by protective equipment include physical, elect ...
(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
An antibody (Ab) or immunoglobulin (Ig) is a large, Y-shaped protein belonging to the immunoglobulin superfamily which is used by the immune system to identify and neutralize antigens such as bacteria and viruses, including those that caus ...
against bacterial
lipopolysaccharide
Lipopolysaccharide (LPS), now more commonly known as endotoxin, is a collective term for components of the outermost membrane of the cell envelope of gram-negative bacteria, such as '' E. coli'' and ''Salmonella'' with a common structural archit ...
and other
antigens
In immunology, an antigen (Ag) is a molecule, moiety, foreign particulate matter, or an allergen, such as pollen, that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune response.
An ...
can be detected by the standard agglutination test (
SAT
The SAT ( ) is a standardized test widely used for college admissions in the United States. Since its debut in 1926, its name and Test score, scoring have changed several times. For much of its history, it was called the Scholastic Aptitude Test ...
), rose Bengal, 2-mercaptoethanol (2-ME), antihuman
globulin (Coombs') and indirect enzyme-linked immunosorbent assay (
ELISA
The enzyme-linked immunosorbent assay (ELISA) (, ) is a commonly used analytical biochemistry assay, first described by Eva Engvall and Peter Perlmann in 1971. The assay is a solid-phase type of enzyme immunoassay (EIA) to detect the presence of ...
). SAT is the most commonly used
serology
Serology is the scientific study of Serum (blood), serum and other body fluids. In practice, the term usually refers to the medical diagnosis, diagnostic identification of Antibody, antibodies in the serum. Such antibodies are typically formed in r ...
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
Polysaccharides (), or polycarbohydrates, are the most abundant carbohydrates found in food. They are long-chain polymeric carbohydrates composed of monosaccharide units bound together by glycosidic linkages. This carbohydrate can react with wat ...
of ''Brucella'' to that of various other
Gram-negative bacteria
Gram-negative bacteria are bacteria that, unlike gram-positive bacteria, do not retain the Crystal violet, crystal violet stain used in the Gram staining method of bacterial differentiation. Their defining characteristic is that their cell envelo ...
(e.g. ''
Francisella tularensis
''Francisella tularensis'' is a pathogenic species of Gram-negative coccobacillus, an aerobic bacterium. It is nonspore-forming, nonmotile, and the causative agent of tularemia, the pneumonic form of which is often lethal without treatment. It i ...
'', ''
Escherichia coli
''Escherichia coli'' ( )Wells, J. C. (2000) Longman Pronunciation Dictionary. Harlow ngland Pearson Education Ltd. is a gram-negative, facultative anaerobic, rod-shaped, coliform bacterium of the genus '' Escherichia'' that is commonly fo ...
'', ''
Salmonella urbana'', ''
Yersinia enterocolitica'', ''
Vibrio cholerae
''Vibrio cholerae'' is a species of Gram-negative bacteria, Gram-negative, Facultative anaerobic organism, facultative anaerobe and Vibrio, comma-shaped bacteria. The bacteria naturally live in Brackish water, brackish or saltwater where they att ...
'', and ''
Stenotrophomonas maltophilia''), the appearance of cross-reactions of class M
immunoglobulin
An antibody (Ab) or immunoglobulin (Ig) is a large, Y-shaped protein belonging to the immunoglobulin superfamily which is used by the immune system to identify and neutralize antigens such as pathogenic bacteria, bacteria and viruses, includin ...
s may occur. 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
Leukopenia () is a decrease in the number of white blood cells (leukocytes). It places individuals at increased risk of infection as white blood cells are the body's primary defense against infections.
Signs and symptoms
Symptoms may include:
* sk ...
with relative
lymphocytosis. The serum biochemical profiles are commonly normal.
Prevention
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 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.
Treatment
Antibiotic
An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting pathogenic bacteria, bacterial infections, and antibiotic medications are widely used in the therapy ...
s such as
tetracycline
Tetracycline, sold under various brand names, is an antibiotic in the tetracyclines family of medications, used to treat a number of infections, including acne, cholera, brucellosis, plague, malaria, and syphilis. It is available in oral an ...
s,
rifampicin, and the
aminoglycoside
Aminoglycoside is a medicinal and bacteriologic category of traditional Gram-negative antibacterial medications that inhibit protein synthesis and contain as a portion of the molecule an amino-modified glycoside (sugar). The term can also refer ...
s
streptomycin
Streptomycin is an antibiotic medication used to treat a number of bacterial infections, including tuberculosis, Mycobacterium avium complex, ''Mycobacterium avium'' complex, endocarditis, brucellosis, Burkholderia infection, ''Burkholderia'' i ...
and
gentamicin
Gentamicin is an aminoglycoside antibiotic used to treat several types of bacterial infections. This may include bone infections, endocarditis, pelvic inflammatory disease, meningitis, pneumonia, urinary tract infections, and sepsis amo ...
are effective against ''Brucella'' bacteria. However, the use of more than one antibiotic is needed for several weeks, because the bacteria incubate within
cells.
The gold standard treatment for adults is daily
intramuscular injection
Intramuscular injection, often abbreviated IM, is the medical injection, injection of a substance into a muscle. In medicine, it is one of several methods for parenteral, parenteral administration of medications. Intramuscular injection may be ...
s of streptomycin 1 g for 14 days and oral
doxycycline
Doxycycline is a Broad-spectrum antibiotic, broad-spectrum antibiotic of the Tetracycline antibiotics, tetracycline class used in the treatment of infections caused by bacteria and certain parasites. It is used to treat pneumonia, bacterial p ...
100 mg twice daily for 45 days (concurrently). Gentamicin 5 mg/kg by intramuscular injection once daily for 7 days is an acceptable substitute when streptomycin is not available or contraindicated.
Another widely used regimen is doxycycline plus rifampicin twice daily for at least 6 weeks. This regimen has the advantage of oral administration. A triple therapy of doxycycline, with rifampicin and
co-trimoxazole, has been used successfully to treat neurobrucellosis.
Doxycycline plus streptomycin regimen (for 2 to 3 weeks) is more effective than doxycycline plus rifampicin regimen (for 6 weeks).
Doxycycline can cross the
blood–brain barrier
The blood–brain barrier (BBB) is a highly selective semipermeable membrane, semipermeable border of endothelium, endothelial cells that regulates the transfer of solutes and chemicals between the circulatory system and the central nervous system ...
, but requires the addition of two other drugs to prevent relapse.
Ciprofloxacin
Ciprofloxacin is a fluoroquinolone antibiotic used to treat a number of bacterial infections. This includes bone and joint infections, intra-abdominal infections, certain types of infectious diarrhea, respiratory tract infections, skin ...
and co-trimoxazole therapy are associated with an unacceptably high rate of relapse. In brucellic
endocarditis
Endocarditis is an inflammation of the inner layer of the heart, the endocardium. It usually involves the heart valves. Other structures that may be involved include the interventricular septum, the chordae tendineae, the mural endocardium, o ...
, surgery is required for an optimal outcome. Even with optimal antibrucellic therapy, relapses still occur in 5 to 10% of patients with Malta fever.
Prognosis
The mortality of the disease in 1909, as recorded in the British Army and Navy stationed in Malta, was 2%. The most frequent cause of death was
endocarditis
Endocarditis is an inflammation of the inner layer of the heart, the endocardium. It usually involves the heart valves. Other structures that may be involved include the interventricular septum, the chordae tendineae, the mural endocardium, o ...
. Recent advances in
antibiotics
An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting pathogenic bacteria, bacterial infections, and antibiotic medications are widely used in the therapy ...
and surgery have been successful in preventing death due to endocarditis. Prevention of human brucellosis can be achieved by eradication of the disease in animals by vaccination and other veterinary control methods, such as testing herds/flocks and slaughtering animals when infection is present. Currently, no effective vaccine is available for humans. Boiling milk before consumption, or before using it to produce other dairy products, is protective against transmission via ingestion. Changing the traditional food habits of eating raw meat, liver, or bone marrow is necessary, but difficult to implement. Patients who have had brucellosis should probably be excluded indefinitely from donating blood or organs. Exposure of diagnostic laboratory personnel to ''Brucella'' organisms remains a problem in both endemic settings and when brucellosis is unknowingly imported by a patient. After appropriate risk assessment, staff with significant exposure should be offered postexposure prophylaxis and followed up serologically for 6 months.
Epidemiology
Argentina
According to a study published in 2002, an estimated 10–13% of farm animals were infected with ''Brucella'' species. Annual losses from the disease were calculated at around
US$
The United States dollar (Currency symbol, symbol: Dollar sign, $; ISO 4217, currency code: USD) is the official currency of the United States and International use of the U.S. dollar, several other countries. The Coinage Act of 1792 introdu ...
60 million. Since 1932,
government agencies
A government agency or state agency, sometimes an appointed commission, is a permanent or semi-permanent organization in the machinery of government (bureaucracy) that is responsible for the oversight and administration of specific functions, ...
have undertaken efforts to contain the disease. , all cattle aged 3–8 months must receive the ''Brucella abortus'' strain 19 vaccine.
Australia
Australia
Australia, officially the Commonwealth of Australia, is a country comprising mainland Australia, the mainland of the Australia (continent), Australian continent, the island of Tasmania and list of islands of Australia, numerous smaller isl ...
is free of cattle brucellosis, although it occurred in the past. Brucellosis of sheep or goats has never been reported. Brucellosis of pigs does occur. Feral pigs are the typical source of human infections.
Canada
On 19 September 1985, the
Canadian government
The Government of Canada (), formally His Majesty's Government (), is the body responsible for the federal administration of Canada. The term ''Government of Canada'' refers specifically to the executive, which includes ministers of the Crown ( ...
declared its cattle population brucellosis-free. Brucellosis ring testing of milk and cream, and testing of cattle to be slaughtered, ended on 1 April 1999. Monitoring continues through testing at auction markets, through standard disease-reporting procedures, and testing of cattle being qualified for export to countries other than the United States.
China
An outbreak infecting humans took place in
Lanzhou
Lanzhou is the capital and largest city of Gansu province in northwestern China. Located on the banks of the Yellow River, it is a key regional transportation hub, connecting areas further west by rail to the eastern half of the country. His ...
in 2019 after the Lanzhou Biopharmaceutical Plant, which was involved in vaccine production, accidentally pumped out the bacteria into the atmosphere in exhaust air due to use of expired disinfectant.
According to Georgios Pappas, an infectious-disease specialist and author of a report published in the journal ''
Clinical Infectious Diseases'',
the result was “possibly the largest laboratory accident in the history of infectious diseases.” According to Pappas, out of nearly 70,000 people tested, more than 10,000 were seropositive, citing figures compiled by the provincial health authorities in Lanzhou’s Gansu province. Pappas also states that Chinese documents show that more than 3,000 people living near the plant applied for compensation, an indication of at least a mild illness.
Europe
Malta
Until the early 20th century, the disease was
endemic
Endemism is the state of a species being found only in a single defined geographic location, such as an island, state, nation, country or other defined zone; organisms that are indigenous to a place are not endemic to it if they are also foun ...
in Malta to the point of it being referred to as "Maltese fever". Since 2005, due to a strict regimen of certification of milk animals and widespread use of pasteurization, the illness has been eradicated from Malta.
Republic of Ireland
Ireland
Ireland (, ; ; Ulster Scots dialect, Ulster-Scots: ) is an island in the North Atlantic Ocean, in Northwestern Europe. Geopolitically, the island is divided between the Republic of Ireland (officially Names of the Irish state, named Irelan ...
was declared free of brucellosis on 1 July 2009. It had troubled the country's farmers and veterinarians for several decades.
The
Irish government
The Government of Ireland () is the executive authority of Ireland, headed by the , the head of government. The government – also known as the cabinet – is composed of ministers, each of whom must be a member of the , which consists of ...
submitted an application to the
European Commission
The European Commission (EC) is the primary Executive (government), executive arm of the European Union (EU). It operates as a cabinet government, with a number of European Commissioner, members of the Commission (directorial system, informall ...
, which verified that Ireland had been liberated.
Brendan Smith, Ireland's then
Minister for Agriculture, Food and the Marine, said the elimination of brucellosis was "a landmark in the history of disease eradication in Ireland".
Ireland's
Department of Agriculture, Food and the Marine
The Department of Agriculture, Food, Fisheries and the Marine () is a Department of State (Ireland), department of the Government of Ireland. According to the department, its mission is to "lead the sustainable development of a competitive, cons ...
intends to reduce its brucellosis eradication programme now that eradication has been confirmed.
UK
Mainland Britain has been free of brucellosis since 1979, although there have been episodic reintroductions since.
[Monitoring brucellosis in Great Britain]
3 September 2020 ''veterinary-practice.com'', accessed 18 September 2020 The last outbreak of brucellosis in Great Britain was in cattle in Cornwall in 2004.
[ Northern Ireland was declared officially brucellosis-free in 2015.][
]
New Zealand
Brucellosis in New Zealand
New Zealand () is an island country in the southwestern Pacific Ocean. It consists of two main landmasses—the North Island () and the South Island ()—and List of islands of New Zealand, over 600 smaller islands. It is the List of isla ...
is limited to sheep (''B. ovis''). The country is free of all other species of ''Brucella''.
United States
Dairy herds in the U.S. are tested at least once a year to be certified brucellosis-free with the ''Brucella'' milk ring test. Cows confirmed to be infected are often killed. In the United States, veterinarian
A veterinarian (vet) or veterinary surgeon is a medical professional who practices veterinary medicine. They manage a wide range of health conditions and injuries in non-human animals. Along with this, veterinarians also play a role in animal r ...
s are required to vaccinate
A vaccine is a biological preparation that provides active acquired immunity to a particular infectious or malignant disease. The safety and effectiveness of vaccines has been widely studied and verified. A vaccine typically contains an age ...
all young stock, to further reduce the chance of zoonotic
A zoonosis (; plural zoonoses) or zoonotic disease is an infectious disease of humans caused by a pathogen (an infectious agent, such as a virus, bacterium, parasite, fungi, or prion) that can jump from a non-human vertebrate to a human. When h ...
transmission. This vaccination is usually referred to as a "calfhood" vaccination. Most cattle receive a tattoo in one of their ears, serving as proof of their vaccination status. This tattoo also includes the last digit of the year they were born.
The first state–federal cooperative efforts towards eradication of brucellosis caused by ''B. abortus'' in the U.S. began in 1934.
Brucellosis was originally imported to North America with non-native domestic cattle (''Bos taurus''), which transmitted the disease to wild bison
A bison (: bison) is a large bovine in the genus ''Bison'' (from Greek, meaning 'wild ox') within the tribe Bovini. Two extant taxon, extant and numerous extinction, extinct species are recognised.
Of the two surviving species, the American ...
(''Bison bison'') and elk (''Cervus canadensis''). No records exist of brucellosis in ungulates native to America until the early 19th century.
History
Brucellosis first came to the attention of British
British may refer to:
Peoples, culture, and language
* British people, nationals or natives of the United Kingdom, British Overseas Territories and Crown Dependencies.
* British national identity, the characteristics of British people and culture ...
medical officers in the 1850s in Malta during the Crimean War
The Crimean War was fought between the Russian Empire and an alliance of the Ottoman Empire, the Second French Empire, the United Kingdom of Great Britain and Ireland, and the Kingdom of Sardinia (1720–1861), Kingdom of Sardinia-Piedmont fro ...
, and was referred to as Malta Fever. Jeffery Allen Marston (1831–1911) described his case of the disease in 1861. The causal relationship between organism and disease was first established in 1887 by David Bruce. Bruce considered the agent spherical and classified it as a coccus
Bacterial cellular morphologies are the shapes that are characteristic of various types of bacteria and often key to their identification. Their direct examination under a light microscope enables the classification of these bacteria (and archaea ...
.
In 1897, Danish veterinarian
A veterinarian (vet) or veterinary surgeon is a medical professional who practices veterinary medicine. They manage a wide range of health conditions and injuries in non-human animals. Along with this, veterinarians also play a role in animal r ...
Bernhard Bang
Bernhard Lauritz Frederik Bang (7 June 1848 – 22 June 1932), was a Danish veterinarian. He discovered Brucella abortus in 1897, which came to be known as ''Bang's bacillus''. Bang's bacillus was the cause of the contagious ''Bang's disease'' (n ...
isolated a bacillus
''Bacillus'', from Latin "bacillus", meaning "little staff, wand", is a genus of Gram-positive, rod-shaped bacteria, a member of the phylum ''Bacillota'', with 266 named species. The term is also used to describe the shape (rod) of other so-sh ...
as the agent of heightened spontaneous abortion in cows, and the name "Bang's disease" was assigned to this condition. Bang considered the organism rod-shaped and classified it as a bacillus
''Bacillus'', from Latin "bacillus", meaning "little staff, wand", is a genus of Gram-positive, rod-shaped bacteria, a member of the phylum ''Bacillota'', with 266 named species. The term is also used to describe the shape (rod) of other so-sh ...
. At the time, no one knew that this bacillus had anything to do with the causative agent of Malta fever.
Maltese scientist and archaeologist Themistocles Zammit identified unpasteurized goat milk as the major etiologic factor of undulant fever in June 1905.
In the late 1910s, American bacteriologist Alice C. Evans was studying the Bang bacillus and gradually realized that it was virtually indistinguishable from the Bruce coccus. The short-rod versus oblong-round morphologic borderline explained the leveling of the erstwhile bacillus/coccus distinction (that is, these "two" pathogens were not a coccus versus a bacillus but rather were one coccobacillus
Bacterial cellular morphologies are the shapes that are characteristic of various types of bacteria and often key to their identification. Their direct examination under a light microscope enables the classification of these bacteria (and archae ...
). The Bang bacillus was already known to be enzootic in American dairy cattle, which showed itself in the regularity with which herds experienced contagious abortion. Having made the discovery that the bacteria were certainly nearly identical and perhaps totally so, Evans then wondered why Malta fever was not widely diagnosed or reported in the United States. She began to wonder whether many cases of vaguely defined febrile illnesses were in fact caused by the drinking of raw (unpasteurized) milk. During the 1920s, this hypothesis was vindicated. Such illnesses ranged from undiagnosed and untreated gastrointestinal upset to misdiagnosed febrile and painful versions, some even fatal. This advance in bacteriological science sparked extensive changes in the American dairy industry to improve food safety
Food safety (or food hygiene) is used as a scientific method/discipline describing handling, food processing, preparation, and food storage, storage of food in ways that prevent foodborne illness. The occurrence of two or more cases of a simi ...
. The changes included making pasteurization
In food processing, pasteurization (American and British English spelling differences#-ise, -ize (-isation, -ization), also pasteurisation) is a process of food preservation in which packaged foods (e.g., milk and fruit juices) are treated wi ...
standard and greatly tightening the standards of cleanliness in milkhouses on dairy farms. The expense prompted delay and skepticism in the industry, but the new hygiene rules eventually became the norm. Although these measures have sometimes struck people as overdone in the decades since, being unhygienic at milking time or in the milkhouse, or drinking raw milk, is not a safe alternative.
In the decades after Evans's work, this genus, which received the name ''Brucella
''Brucella'' is a genus of Gram-negative bacterium, bacteria, named after David Bruce (microbiologist), David Bruce (1855–1931). They are small (0.5 to 0.7 by 0.6 to 1.5 μm), non-Bacterial capsule, encapsulated, non-motile, facultatively ...
'' in honor of Bruce, was found to contain several species with varying virulence. The name "brucellosis" gradually replaced the 19th-century names Mediterranean fever and Malta fever.
Neurobrucellosis, a neurological involvement in brucellosis, was first described in 1879. In the late 19th century, its symptoms were described in more detail by M. Louis Hughes, a Surgeon-Captain of the Royal Army Medical Corps
The Royal Army Medical Corps (RAMC) was a specialist corps in the British Army which provided medical services to all Army personnel and their families, in war and in peace.
On 15 November 2024, the corps was amalgamated with the Royal Army De ...
stationed in Malta who isolated ''brucella'' organisms from a patient with meningo-encephalitis. In 1989, neurologists in Saudi Arabia made significant contributions to the medical literature involving neurobrucellosis.
These obsolete names have previously been applied to brucellosis:
Biological warfare
''Brucella'' species had been weaponized by several advanced countries by the mid-20th century. In 1954, ''B. suis'' became the first agent weaponized by the United States at its Pine Bluff Arsenal near Pine Bluff, Arkansas
Pine Bluff, officially the City of Pine Bluff, is the List of municipalities in Arkansas, tenth-most populous city in the U.S. state of Arkansas and the county seat of Jefferson County, Arkansas, Jefferson County. The population of the city wa ...
. ''Brucella'' species survive well in aerosols and resist drying. ''Brucella'' and all other remaining biological weapons in the U.S. arsenal were destroyed in 1971–72 when the American offensive biological warfare program was discontinued by order of President Richard Nixon
Richard Milhous Nixon (January 9, 1913April 22, 1994) was the 37th president of the United States, serving from 1969 until Resignation of Richard Nixon, his resignation in 1974. A member of the Republican Party (United States), Republican ...
.
The experimental American bacteriological warfare program focused on three agents of the ''Brucella'' group:
* Porcine brucellosis (agent US)
* Bovine brucellosis (agent AA)
* Caprine brucellosis (agent AM)
Agent US was in advanced development by the end of World War II
World War II or the Second World War (1 September 1939 – 2 September 1945) was a World war, global conflict between two coalitions: the Allies of World War II, Allies and the Axis powers. World War II by country, Nearly all of the wo ...
. When the United States Air Force
The United States Air Force (USAF) is the Air force, air service branch of the United States Department of Defense. It is one of the six United States Armed Forces and one of the eight uniformed services of the United States. Tracing its ori ...
(USAF) wanted a biological warfare capability, the Chemical Corps offered Agent US in the M114 bomblet, based on the four-pound bursting bomblet developed for spreading anthrax
Anthrax is an infection caused by the bacterium '' Bacillus anthracis'' or ''Bacillus cereus'' biovar ''anthracis''. Infection typically occurs by contact with the skin, inhalation, or intestinal absorption. Symptom onset occurs between one ...
during World War II. Though the capability was developed, operational testing indicated the weapon was less than desirable, and the USAF designed it as an interim capability until it could eventually be replaced by a more effective biological weapon.
The main drawback of using the M114 with Agent US was that it acted mainly as an incapacitating agent, whereas the USAF administration wanted deadly weapons. The stability of M114 in storage was too low to allow for storing it at forward air bases, and the logistical requirements to neutralize a target were far higher than originally planned. Ultimately, this would have required too much logistical support to be practical in the field.
Agents US and AA had a median infective dose of 500 organisms/person, and for Agent AM, it was 300 organisms/person. The incubation time was believed to be about 2 weeks, with a duration of infection of several months. The lethality estimate was, based on epidemiological information, 1 to 2
per cent. Agent AM was believed to be a somewhat more virulent disease, with a fatality rate of 3 per cent being expected.
Other animals
Species infecting domestic livestock are '' B. abortus'' (cattle, bison, and elk), '' B. canis'' (dogs), '' B. melitensis'' (goats and sheep), '' B. ovis'' (sheep), and '' B. suis'' (caribou and pigs). ''Brucella'' species have also been isolated from several marine mammal species (cetaceans and pinnipeds).
Cattle
'' B. abortus'' is the principal cause of brucellosis in cattle. The bacteria are shed from an infected animal at or around the time of calving or abortion
Abortion is the early termination of a pregnancy by removal or expulsion of an embryo or fetus. Abortions that occur without intervention are known as miscarriages or "spontaneous abortions", and occur in roughly 30–40% of all pregnan ...
. Once exposed, the likelihood of an animal becoming infected is variable, depending on age, pregnancy status, and other intrinsic factors of the animal, as well as the number of bacteria to which the animal was exposed. The most common clinical signs of cattle infected with ''B. abortus'' are high incidences of abortions, arthritic joints, and retained placenta
The placenta (: placentas or placentae) is a temporary embryonic and later fetal organ that begins developing from the blastocyst shortly after implantation. It plays critical roles in facilitating nutrient, gas, and waste exchange between ...
.
The two main causes for spontaneous abortion in animals are erythritol
Erythritol (, ) is an organic compound, the naturally occurring achiral meso four-carbon sugar alcohol (or polyol). It is the reduced form of either D- or L- erythrose and one of the two reduced forms of erythrulose. It is used as a food ad ...
, which can promote infections in the fetus and placenta,, and the lack of anti-''Brucella'' activity in the amniotic fluid. Males can also harbor the bacteria in their reproductive tracts, namely seminal vesicle
The seminal vesicles (also called vesicular glands or seminal glands) are a pair of convoluted tubular accessory glands that lie behind the urinary bladder of male mammals. They secrete fluid that largely composes the semen.
The vesicles are 5 ...
s, ampullae, testicle
A testicle or testis ( testes) is the gonad in all male bilaterians, including humans, and is Homology (biology), homologous to the ovary in females. Its primary functions are the production of sperm and the secretion of Androgen, androgens, p ...
s, and epididymis
The epididymis (; : epididymides or ) is an elongated tubular genital organ attached to the posterior side of each one of the two male reproductive glands, the testicles. It is a single, narrow, tightly coiled tube in adult humans, in length; ...
es.
Dogs
The causative agent of brucellosis in dog
The dog (''Canis familiaris'' or ''Canis lupus familiaris'') is a domesticated descendant of the gray wolf. Also called the domestic dog, it was selectively bred from a population of wolves during the Late Pleistocene by hunter-gatherers. ...
s, '' B. canis'', is transmitted to other dogs through breeding and contact with aborted fetuses. Brucellosis can occur in humans who come in contact with infected aborted tissue or semen. The bacteria in dogs normally infect the genitals and lymphatic system
The lymphatic system, or lymphoid system, is an organ system in vertebrates that is part of the immune system and complementary to the circulatory system. It consists of a large network of lymphatic vessels, lymph nodes, lymphoid organs, lympha ...
, but can also spread to the eyes, kidney
In humans, the kidneys are two reddish-brown bean-shaped blood-filtering organ (anatomy), organs that are a multilobar, multipapillary form of mammalian kidneys, usually without signs of external lobulation. They are located on the left and rig ...
s, and intervertebral disc
An intervertebral disc (British English), also spelled intervertebral disk (American English), lies between adjacent vertebrae in the vertebral column. Each disc forms a fibrocartilaginous joint (a symphysis), to allow slight movement of the ver ...
s. Brucellosis in the intervertebral disc is one possible cause of discospondylitis. Symptoms of brucellosis in dogs include abortion in female dogs and scrotal inflammation and orchitis
Orchitis is inflammation of the testicles. It can also involve swelling, pains, and frequent infection, particularly of the epididymis, as in epididymitis. The term is from the Ancient Greek ὄρχις meaning "testicle"; same root as ''orchid ...
in males. Fever is uncommon. Infection of the eye can cause uveitis
Uveitis () is inflammation of the uvea, the pigmented layer of the eye between the inner retina and the outer fibrous layer composed of the sclera and cornea. The uvea consists of the middle layer of pigmented vascular structures of the eye and ...
, and infection of the intervertebral disc can cause pain or weakness. Blood testing of the dogs prior to breeding can prevent the spread of this disease. It is treated with antibiotics, as with humans, but it is difficult to cure.
Aquatic wildlife
Brucellosis in cetaceans is caused by the bacterium '' B. ceti''. First discovered in the aborted fetus of a bottlenose dolphin
The bottlenose dolphin is a toothed whale in the genus ''Tursiops''. They are common, cosmopolitan members of the family Delphinidae, the family of oceanic dolphins. Molecular studies show the genus contains three species: the common bot ...
, the structure of ''B. ceti'' is similar to ''Brucella'' in land animals. ''B. ceti'' is commonly detected in two suborders of cetaceans, the Mysticeti
Baleen whales (), also known as whalebone whales, are marine mammals of the parvorder Mysticeti in the infraorder Cetacea (whales, dolphins and porpoises), which use baleen plates (or "whalebone") in their mouths to sieve plankton from the wate ...
and Odontoceti
The toothed whales (also called odontocetes, systematic name Odontoceti) are a parvorder of cetaceans that includes dolphins, porpoises, and all other whales with teeth, such as beaked whales and the sperm whales. 73 species of toothed whales ar ...
. The Mysticeti include four families of baleen whales, filter-feeders, and the Odontoceti include two families of toothed cetaceans ranging from dolphins to sperm whales. ''B. ceti'' is believed to transfer from animal to animal through sexual intercourse, maternal feeding, aborted fetuses, placental issues, from mother to fetus, or through fish reservoirs. Brucellosis is a reproductive disease, so it has an extreme negative impact on the population dynamics of a species. This becomes a greater issue when the already low population numbers of cetaceans are taken into consideration. ''B. ceti'' has been identified in four of the 14 cetacean families, but the antibodies have been detected in seven of the families. This indicates that ''B. ceti'' is common amongst cetacean families and populations. Only a small percentage of exposed individuals become ill or die. However, particular species apparently are more likely to become infected by ''B. ceti''. The harbor porpoise, striped dolphin, white-sided dolphin, bottlenose dolphin, and common dolphin have the highest frequency of infection amongst odontocetes. In the mysticetes families, the northern minke whale is by far the most infected species. Dolphins and porpoises are more likely to be infected than cetaceans such as whales. Concerning sex and age biases, the infections do not seem influenced by an individual's age or sex. Although fatal to cetaceans, ''B. ceti'' has a low infection rate for humans.
Terrestrial wildlife
The disease in its various strains can infect multiple wildlife species, including elk (''Cervus canadensis''), bison (''Bison bison''), African buffalo (''Syncerus caffer''), European wild boar (''Sus scrofa''), caribou (''Rangifer tarandus''), moose (''Alces alces''), and marine mammals (see section on aquatic wildlife above). While some regions use vaccines to prevent the spread of brucellosis between infected and uninfected wildlife populations, no suitable brucellosis vaccine for terrestrial wildlife has been developed. This gap in medicinal knowledge creates more pressure for management practices that reduce spread of the disease.
Wild bison and elk in the greater Yellowstone
Yellowstone National Park is a List of national parks of the United States, national park of the United States located in the northwest corner of Wyoming, with small portions extending into Montana and Idaho. It was established by the 42nd U ...
area are the last remaining reservoir of ''B. abortus'' in the US. The recent transmission of brucellosis from elk back to cattle in Idaho and Wyoming illustrates how the area, as the last remaining reservoir in the United States, may adversely affect the livestock industry. Eliminating brucellosis from this area is a challenge, as many viewpoints exist on how to manage diseased wildlife. However, the Wyoming Game and Fish Department has recently begun to protect scavengers (particularly coyote
The coyote (''Canis latrans''), also known as the American jackal, prairie wolf, or brush wolf, is a species of canis, canine native to North America. It is smaller than its close relative, the Wolf, gray wolf, and slightly smaller than the c ...
s and red fox
The red fox (''Vulpes vulpes'') is the largest of the true foxes and one of the most widely distributed members of the order Carnivora, being present across the entire Northern Hemisphere including most of North America, Europe and Asia, plus ...
) on elk feedgrounds, because they act as sustainable, no-cost, biological control agents by removing infected elk fetuses quickly.
The National Elk Refuge in Jackson, Wyoming, asserts that the intensity of the winter feeding program affects the spread of brucellosis more than the population size of elk and bison. Since concentrating animals around food plots accelerates spread of the disease, management strategies to reduce herd density and increase dispersion could limit its spread.
See also
* Brucella suis
References
Further reading
WHO fact sheet on brucellosis
Brucella
genomes and related information a
PATRIC
a Bioinformatics Resource Center funded b
NIAID
from Centers for Disease Control
The Centers for Disease Control and Prevention (CDC) is the national public health agency of the United States. It is a United States federal agency under the Department of Health and Human Services (HHS), and is headquartered in Atlanta, ...
* – re high rate of brucellosis in humans in ancient Pompeii
Brucellosis
factsheet from European Centre for Disease Prevention and Control
The European Centre for Disease Prevention and Control (ECDC) is an agency of the European Union (EU) whose mission is to strengthen Europe's defences against infectious diseases. It covers a wide spectrum of activities, such as: surveillance, e ...
{{Authority control
Animal bacterial diseases
Bacterium-related cutaneous conditions
Biological agents
Bovine diseases
Dog diseases
Occupational diseases
Sheep and goat diseases
Zoonoses
Zoonotic bacterial diseases