Brucellosis is a highly contagious
zoonosis
A zoonosis (; plural zoonoses) or zoonotic disease is an infectious disease of humans caused by a pathogen (an infectious agent, such as a bacterium, virus, parasite or prion) that has jumped from a non-human (usually a vertebrate) to a human. ...
caused by ingestion of
unpasteurized
Pasteurization or pasteurisation is a process of food preservation in which packaged and non-packaged foods (such as milk and fruit juices) are treated with mild heat, usually to less than , to eliminate pathogens and extend shelf life.
Th ...
milk
Milk is a white liquid food produced by the mammary glands of mammals. It is the primary source of nutrition for young mammals (including breastfed human infants) before they are able to digestion, digest solid food. Immune factors and immune ...
or undercooked
meat
Meat is animal flesh that is eaten as food. Humans have hunted, farmed, and scavenged animals for meat since prehistoric times. The establishment of settlements in the Neolithic Revolution allowed the domestication of animals such as chic ...
from infected animals, or close contact with their secretions. 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 bacteria, named after David Bruce (1855–1931). They are small (0.5 to 0.7 by 0.6 to 1.5 µm), non encapsulated, non motile, facultatively intracellular coccobacilli.
''Brucella'' spp. are the caus ...
'', are small,
Gram-negative
Gram-negative bacteria are bacteria that do not retain the crystal violet stain used in the Gram staining method of bacterial differentiation. They are characterized by their cell envelopes, which are composed of a thin peptidoglycan cell wall ...
, nonmotile, nonspore-forming, rod-shaped (
coccobacilli) bacteria. They function as
facultative
{{wiktionary, facultative
Facultative means "optional" or "discretionary" (antonym '' obligate''), used mainly in biology in phrases such as:
* Facultative (FAC), facultative wetland (FACW), or facultative upland (FACU): wetland indicator statuses ...
intracellular parasites, causing
chronic disease
A chronic condition 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 course of the disease lasts for more than three m ...
, 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
Myalgia (also called muscle pain and muscle ache in layman's terms) is the medical term for muscle pain. Myalgia is a symptom of many diseases. The most common cause of acute myalgia is the overuse of a muscle or group of muscles; another like ...
. Brucellosis has been recognized in animals and humans since the early 20th century.
Signs and symptoms
![BrucellosisGraph](https://upload.wikimedia.org/wikipedia/commons/7/77/BrucellosisGraph.png)
The symptoms are like those associated with many other
febrile
Fever, also referred to as pyrexia, is defined as having a temperature above the normal range due to an increase in the body's temperature set point. There is not a single agreed-upon upper limit for normal temperature with sources using val ...
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 occurs and leads to the classic triad of undulant fevers, sweating (often with characteristic foul, moldy smell sometimes likened to wet hay), and migratory
arthralgia
Arthralgia (from Greek ''arthro-'', joint + ''-algos'', pain) literally means ''joint pain''. Specifically, arthralgia is a symptom of injury, infection, illness (in particular arthritis), or an allergic reaction to medication.
According to MeSH, ...
and
myalgia (joint and muscle pain). Blood tests characteristically reveal a
low number of white blood cells and
red blood cells, show some elevation of
liver enzyme
Liver function tests (LFTs or LFs), also referred to as a hepatic panel, are groups of blood tests that provide information about the state of a patient's liver. These tests include prothrombin time (PT/INR), activated partial thromboplastin tim ...
s such as
aspartate aminotransferase
Aspartate transaminase (AST) or aspartate aminotransferase, also known as AspAT/ASAT/AAT or (serum) glutamic oxaloacetic transaminase (GOT, SGOT), is a pyridoxal phosphate (PLP)-dependent transaminase enzyme () that was first described by Arthur ...
and
alanine aminotransferase
Alanine transaminase (ALT) is a transaminase enzyme (). It is also called alanine aminotransferase (ALT or ALAT) and was formerly called serum glutamate-pyruvate transaminase or serum glutamic-pyruvic transaminase (SGPT) and was first character ...
, 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. While not painful, it can be a debilitating symptom if prolonged and has been described as placing discomfort on the chest, abdomen, or back of the ...
,
vomiting
Vomiting (also known as emesis and throwing up) is the involuntary, 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, gastroenteri ...
,
decreased appetite
Anorexia is a medical term for a loss of appetite. While the term in non-scientific publications is often used interchangeably with anorexia nervosa, many possible causes exist for a loss of appetite, some of which may be harmless, while others ...
, unintentional weight loss, abdominal pain,
constipation
Constipation is a bowel dysfunction that makes bowel movements infrequent or hard to pass. The stool is often hard and dry. Other symptoms may include abdominal pain, bloating, and feeling as if one has not completely passed the bowel movement ...
,
diarrhea
Diarrhea, also spelled diarrhoea, is the condition of having at least three loose, liquid, or watery bowel movements each day. It often lasts for a few days and can result in dehydration due to fluid loss. Signs of dehydration often begin wi ...
,
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, and Jordan, known as Malta fever. During episodes of Malta fever, melitococcemia (presence of brucellae in the blood) can usually be demonstrated by means of blood culture in tryptose medium or Albini medium. If untreated, the disease can give origin to focalizations or become chronic. The focalizations of brucellosis occur usually in bones and joints, and
osteomyelitis
Osteomyelitis (OM) is an infection of bone. Symptoms may include pain in a specific bone with overlying redness, fever, and weakness. The long bones of the arms and legs are most commonly involved in children e.g. the femur and humerus, while the ...
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.
C ...
of the lumbar spine accompanied by
sacroiliitis
Sacroiliitis is inflammation within the sacroiliac joint. It is a feature of spondyloarthropathies, such as axial spondyloarthritis (including ankylosing spondylitis), psoriatic arthritis, reactive arthritis or arthritis related to inflammatory b ...
is very characteristic of this disease.
Orchitis
Orchitis is inflammation of the testes. 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''.
S ...
is also common in men.
The consequences of ''Brucella'' infection are highly variable and may include
arthritis,
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 dis ...
,
thrombocytopenia
Thrombocytopenia is a condition characterized by abnormally low levels of platelets, also known as thrombocytes, in the blood. It is the most common coagulation disorder among intensive care patients and is seen in a fifth of medical patients a ...
,
meningitis,
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 in ...
,
optic neuritis
Optic neuritis describes any condition that causes inflammation of the optic nerve; it may be associated with demyelinating diseases, or infectious or inflammatory processes.
It is also known as optic papillitis (when the head of the optic nerv ...
,
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, or the ...
, 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—primarily goats, infected with ''B. melitensis'' and with occupational exposure of laboratory workers, veterinarians, and slaughterhouse workers. Some vaccines used in livestock, most notably ''B. abortus'' strain 19, also cause disease in humans if accidentally injected. Brucellosis induces inconstant
fever
Fever, also referred to as pyrexia, is defined as having a body temperature, temperature above the human body temperature, normal range due to an increase in the body's temperature Human body temperature#Fever, set point. There is not a single ...
s, miscarriage, sweating, weakness,
anemia
Anemia or anaemia (British English) is a blood disorder in which the blood has a reduced ability to carry oxygen due to a lower than normal number of red blood cells, or a reduction in the amount of hemoglobin. When anemia comes on slowly, th ...
,
headache
Headache 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 in those with severe headaches.
Headaches can occur as a result ...
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
Employment is a relationship between two party (law), parties Regulation, regulating the provision of paid Labour (human activity), labour services. Usually based on a employment contract, contract, one party, the employer, which might be a co ...
risk
In simple terms, risk is the possibility of something bad happening. Risk involves uncertainty about the effects/implications of an activity with respect to something that humans value (such as health, well-being, wealth, property or the environme ...
to goat
farmer
A farmer is a person engaged in agriculture, raising living organisms for food or raw materials. The term usually applies to people who do some combination of raising field crops, orchards, vineyards, poultry, or other livestock. A farmer mig ...
s 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 been ...
practices.
Diagnosis
![Rose Bengal Deneyi](https://upload.wikimedia.org/wikipedia/commons/d/da/Rose_Bengal_Deneyi.jpg)
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 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), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of the ...
against bacterial
lipopolysaccharide
Lipopolysaccharides (LPS) are large molecules consisting of a lipid and a polysaccharide that are bacterial toxins. They are composed of an O-antigen, an outer core, and an inner core all joined by a covalent bond, and are found in the outer ...
and other
antigens 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 scoring have changed several times; originally called the Scholastic Aptitude Test, it was later called the Schol ...
), rose Bengal, 2-mercaptoethanol (2-ME), antihuman
globulin
The globulins are a family of globular proteins that have higher molecular weights than albumins and are insoluble in pure water but dissolve in dilute salt solutions. Some globulins are produced in the liver, while others are made by the immune ...
(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 uses a solid-phase type of enzyme immunoassay (EIA) to detect the presence ...
). 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 of ''Brucella'' to that of various other
Gram-negative bacteria
Gram-negative bacteria are bacteria that do not retain the crystal violet stain used in the Gram staining method of bacterial differentiation. They are characterized by their cell envelopes, which are composed of a thin peptidoglycan cell wall ...
(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 is ...
'', ''
Escherichia coli
''Escherichia coli'' (),Wells, J. C. (2000) Longman Pronunciation Dictionary. Harlow ngland Pearson Education Ltd. also known as ''E. coli'' (), is a Gram-negative, facultative anaerobic, rod-shaped, coliform bacterium of the genus ''Escher ...
'', ''
Salmonella urbana'', ''
Yersinia enterocolitica
''Yersinia enterocolitica'' is a Gram-negative, bacillus-shaped bacterium, belonging to the family Yersiniaceae. It is motile at temperatures of 22–29° C (72–84 °F), but becomes nonmotile at normal human body temperature. ''Y. enterocoliti ...
'', ''
Vibrio cholerae
''Vibrio cholerae'' is a species of Gram-negative, facultative anaerobe and comma-shaped bacteria. The bacteria naturally live in brackish or saltwater where they attach themselves easily to the chitin-containing shells of crabs, shrimps, and oth ...
'', and ''
Stenotrophomonas maltophilia''), the appearance of cross-reactions of class M
immunoglobulin
An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of the ...
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
The hook effect refers to the prozone phenomenon, also known as antibody excess or the Postzone phenomenon, also known as antigen excess. It is an immunology, immunologic phenomenon whereby the effectiveness of antibody, antibodies to form immune c ...
) 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, realtime 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 leukocytes (WBC). Found in the blood, they are the white blood cells, and are the body's primary defense against an infection. Thus the condition of leukopenia places individuals at increased risk of inf ...
with relative
lymphocytosis
Lymphocytosis is an increase in the number or proportion of lymphocytes in the blood. Absolute lymphocytosis is the condition where there is an increase in the lymphocyte count beyond the normal range while relative lymphocytosis refers to the cond ...
. The serum biochemical profiles are commonly normal.
Prevention
Surveillance using serological tests, as well as tests on milk such as the milk ring test, can be used for screening and play an important role in campaigns to eliminate the disease. Also, individual animal testing both for trade and for disease-control purposes is practiced. In endemic areas, vaccination is often used to reduce the incidence of infection. An
animal vaccine is available that uses modified live bacteria. The
World Organisation for Animal Health
The World Organisation for Animal Health (WOAH), formerly the (OIE), is an intergovernmental organization coordinating, supporting and promoting animal disease control.
Mission and status
The main objective of the WOAH is to control epizo ...
''Manual of Diagnostic Test and Vaccines for Terrestrial Animals'' provides detailed guidance on the production of vaccines. As the disease is closer to being eliminated, a test and eradication program is required to eliminate it.
The main way of preventing brucellosis is by using fastidious hygiene in producing raw milk products, or by
pasteurizing
Pasteurization or pasteurisation is a process of food preservation in which packaged and non-packaged foods (such as milk and fruit juices) are treated with mild heat, usually to less than , to eliminate pathogens and extend shelf life.
Th ...
all milk that is to be ingested by human beings, either in its unaltered form or as a derivative, such as
cheese
Cheese is a dairy product produced in wide ranges of flavors, textures, and forms by coagulation of the milk protein casein. It comprises proteins and fat from milk, usually the milk of cows, buffalo, goats, or sheep. During production, ...
.
Treatment
Antibiotic
An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting bacterial infections, and antibiotic medications are widely used in the treatment and prevention of ...
s such as
tetracycline
Tetracycline, sold under various brand names, is an oral antibiotic in the tetracyclines family of medications, used to treat a number of infections, including acne, cholera, brucellosis, plague, malaria, and syphilis.
Common side effects in ...
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, endocarditis, brucellosis, ''Burkholderia'' infection, plague, tularemia, and rat bite fever. F ...
and
gentamicin 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 injection of a substance into a muscle. In medicine, it is one of several methods for parenteral administration of medications. Intramuscular injection may be preferred because muscles have ...
s of streptomycin 1 g for 14 days and oral
doxycycline
Doxycycline is a broad-spectrum tetracycline class antibiotic used in the treatment of infections caused by bacteria and certain parasites. It is used to treat bacterial pneumonia, acne, chlamydia infections, Lyme disease, cholera, typhus, an ...
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 is able to cross the
blood–brain barrier, 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 inf ...
and co-trimoxazole therapy is 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, or the ...
, 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, or the ...
. 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 bacterial infections, and antibiotic medications are widely used in the treatment and prevention o ...
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 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 are infected with ''Brucella'' species. Annual losses from the disease were calculated at around $60 million. Since 1932,
government agencies
A government or state agency, sometimes an appointed commission, is a permanent or semi-permanent organization in the machinery of government that is responsible for the oversight and administration of specific functions, such as an administratio ...
have undertaken efforts to contain the disease. Currently, all cattle of ages 3–8 months must receive the ''Brucella abortus'' strain 19 vaccine.
Australia
Australia
Australia, officially the Commonwealth of Australia, is a Sovereign state, sovereign country comprising the mainland of the Australia (continent), Australian continent, the island of Tasmania, and numerous List of islands of Australia, sma ...
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 (french: gouvernement du Canada) is the body responsible for the federal administration of Canada. A constitutional monarchy, the Crown is the corporation sole, assuming distinct roles: the executive, as the ''Crown-in ...
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 through 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 Northwest 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. H ...
in 2020 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. The outbreak affected over 6,000 people.
Europe
Malta
Until the early 20th century, the disease was
endemic
Endemism is the state of a species being found 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 found elsew ...
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 ( ; ga, Éire ; Ulster Scots dialect, Ulster-Scots: ) is an island in the Atlantic Ocean, North Atlantic Ocean, in Northwestern Europe, north-western Europe. It is separated from Great Britain to its east by the North Channel (Grea ...
was declared free of brucellosis on 1 July 2009. The disease had troubled the country's farmers and veterinarians for several decades.
The
Irish government
The Government of Ireland ( ga, Rialtas na hÉireann) is the cabinet that exercises executive authority in Ireland.
The Constitution of Ireland vests executive authority in a government which is headed by the , the head of government. The gover ...
submitted an application to the
European Commission
The European Commission (EC) is the executive of the European Union (EU). It operates as a cabinet government, with 27 members of the Commission (informally known as "Commissioners") headed by a President. It includes an administrative body o ...
, which verified that Ireland had been liberated.
Brendan Smith, Ireland's then
Minister for Agriculture, Food and the Marine
The Minister for Agriculture, Food and the Marine ( ga, An tAire Talmhaíochta, Bia agus Mara) is a senior minister in the Government of Ireland and leads the Department of Agriculture, Food and the Marine. Historically, the agriculture portfol ...
, 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 and the Marine ( ga, An Roinn Talmhaíochta, Bia agus Mara) is a department of the Government of Ireland. According to the department, its mission is to "lead the sustainable development of a competitive, con ...
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 re-introductions 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 ( mi, Aotearoa ) is an island country in the southwestern Pacific Ocean. It consists of two main landmasses—the North Island () and the South Island ()—and over 700 smaller islands. It is the sixth-largest island count ...
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), also known as a veterinary surgeon or veterinary physician, 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, vet ...
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.[ ...]
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 bacterium, virus, parasite or prion) that has jumped from a non-human (usually a vertebrate) to a human. ...
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 (''Bison bison'') and elk
The elk (''Cervus canadensis''), also known as the wapiti, is one of the largest species within the deer family, Cervidae, and one of the largest terrestrial mammals in its native range of North America and Central and East Asia. The common ...
(''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.
** Britishness, the British identity and common culture
* British English, ...
medical officers in the 1850s in Malta during the Crimean War
The Crimean War, , was fought from October 1853 to February 1856 between Russia and an ultimately victorious alliance of the Ottoman Empire, France, the United Kingdom and Piedmont-Sardinia.
Geopolitical causes of the war included the ...
, and was referred to as Malta Fever. Jeffery Allen Marston (1831–1911) described his own 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
A coccus (plural cocci) is any bacterium or archaeon that has a spherical, ovoid, or generally round shape. Bacteria are categorized based on their shapes into three classes: cocci (spherical-shaped), bacillus (rod-shaped) and spiral ( of whi ...
.
In 1897, Danish
Danish may refer to:
* Something of, from, or related to the country of Denmark
People
* A national or citizen of Denmark, also called a "Dane," see Demographics of Denmark
* Culture of Denmark
* Danish people or Danes, people with a Danish a ...
veterinarian
A veterinarian (vet), also known as a veterinary surgeon or veterinary physician, 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, vet ...
Bernhard Bang isolated a bacillus
''Bacillus'' (Latin "stick") 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-shaped bacteria; and the plural ''Bacill ...
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'' (Latin "stick") 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-shaped bacteria; and the plural ''Bacill ...
. So at the time, no one knew that this bacillus had anything to do with the causative agent in Malta fever.
Maltese scientist and archaeologist Themistocles Zammit
Sir Themistocles "Temi" Zammit (or Żammit; 30 September 1864 – 2 November 1935) was a Maltese archaeologist and historian, professor of chemistry, medical doctor, researcher and writer. He served as Rector (1920–26) of the Royal Univer ...
identified unpasteurized
Pasteurization or pasteurisation is a process of food preservation in which packaged and non-packaged foods (such as milk and fruit juices) are treated with mild heat, usually to less than , to eliminate pathogens and extend shelf life.
Th ...
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
A coccobacillus (plural coccobacilli), or bacilluscocco, is a type of bacterium with a shape intermediate between cocci (spherical bacteria) and bacilli (rod-shaped bacteria). Coccobacilli, then, are very short rods which may be mistaken for coc ...
). The Bang bacillus was already known to be enzootic
Enzootic is the non-human equivalent of endemic and means, in a broad sense, "belonging to" or "native to", "characteristic of", or "prevalent in" a particular geography, race, field, area, or environment; native to an area or scope.
It also has ...
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. The changes included making pasteurization standard and greatly tightening the standards of cleanliness in milkhouses on dairy farms
A dairy is a business enterprise established for the harvesting or processing (or both) of animal milk – mostly from cows or buffaloes, but also from goats, sheep, horses, or camels – for human consumption. A dairy is typically located on ...
. 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, are 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 bacteria, named after David Bruce (1855–1931). They are small (0.5 to 0.7 by 0.6 to 1.5 µm), non encapsulated, non motile, facultatively intracellular coccobacilli.
''Brucella'' spp. are the caus ...
'' 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) is a specialist corps in the British Army which provides medical services to all Army personnel and their families, in war and in peace. The RAMC, the Royal Army Veterinary Corps, the Royal Army Dental Corps a ...
stationed in Malta who isolated ''brucella'' organisms from a patient with meningo-encephalitis. In 1989, neurologists
Neurology (from el, νεῦρον (neûron), "string, nerve" and the suffix -logia, "study of") is the branch of medicine dealing with the diagnosis and treatment of all categories of conditions and disease involving the brain, the spinal c ...
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 were 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
The Pine Bluff Arsenal is a United States Army installation in Jefferson County, Arkansas, about eight miles northwest of Pine Bluff and thirty miles southeast of Little Rock.
Pine Bluff Arsenal is one of nine Army installations in the United ...
near Pine Bluff, Arkansas
Pine Bluff is the eleventh-largest city in the state of Arkansas and the county seat of Jefferson County. It is the principal city of the Pine Bluff Metropolitan Statistical Area and part of the Little Rock-North Little Rock-Pine Bluff Combin ...
. ''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 to 1974. A member of the Republican Party, he previously served as a representative and senator from California and was ...
.
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, often abbreviated as WWII or WW2, was a world war that lasted from 1939 to 1945. It involved the vast majority of the world's countries—including all of the great powers—forming two opposin ...
. When the United States Air Force
The United States Air Force (USAF) is the air service branch of the United States Armed Forces, and is one of the eight uniformed services of the United States. Originally created on 1 August 1907, as a part of the United States Army Signal ...
(USAF) wanted a biological warfare capability, the Chemical Corps offered Agent US in the M114 bomblet
The M114 bomb was a four-pound U.S. anti-personnel bomb and biological cluster bomb sub-munition. The M114 was used in the M33 cluster bomb.
History
The M114 was a sub-munition for the M33 cluster bomb, as such, it was the first standardized U.S ...
, based on the four-pound bursting bomblet developed for spreading anthrax 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 weapons that were deadly. 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 was 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 termination of a pregnancy by removal or expulsion of an embryo or fetus. An abortion that occurs without intervention is known as a miscarriage or "spontaneous abortion"; these occur in approximately 30% to 40% of pregn ...
. 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 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 physically separate mater ...
.
The two main causes for spontaneous abortion in animals are erythritol
Erythritol is an organic compound, a four-carbon sugar alcohol (or polyol) with no optical activity, used as a food additive and sugar substitute. It is naturally occurring. It can be made from corn using enzymes and fermentation. Its formula i ...
, 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 two convoluted tubular glands that lie behind the urinary bladder of some male mammals. They secrete fluid that partly composes the semen.
The vesicles are 5 ...
s, ampullae
An ampulla (; ) was, in Ancient Rome, a small round vessel, usually made of glass and with two handles, used for sacred purposes. The word is used of these in archaeology, and of later flasks, often handle-less and much flatter, for holy water or ...
, testicle
A testicle or testis (plural testes) is the male reproductive gland or gonad in all bilaterians, including humans. It is homologous to the female ovary. The functions of the testes are to produce both sperm and androgens, primarily testoste ...
s, and epididymes.
Dogs
The causative agent of brucellosis in dog
The dog (''Canis familiaris'' or ''Canis lupus familiaris'') is a domesticated descendant of the wolf. Also called the domestic dog, it is derived from the extinct Pleistocene wolf, and the modern wolf is the dog's nearest living relative. Do ...
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, lymphatic or lymphoid o ...
, but can also spread to the eyes, kidney
The kidneys are two reddish-brown bean-shaped organs found in vertebrates. They are located on the left and right in the retroperitoneal space, and in adult humans are about in length. They receive blood from the paired renal arteries; blood ...
s, and intervertebral discs. Brucellosis in the intervertebral disc is one possible cause of discospondylitis. Symptoms of brucellosis in dogs include abortion in female dogs and scrotal
The scrotum or scrotal sac is an anatomical male reproductive structure located at the base of the penis that consists of a suspended dual-chambered sac of skin and smooth muscle. It is present in most terrestrial male mammals. The scrotum co ...
inflammation and orchitis
Orchitis is inflammation of the testes. 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''.
S ...
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 in ...
, 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 structure of ''B. ceti'' is similar to ''Brucella'' in land animals. ''B. ceti'' is commonly detected in two suborders of cetaceans, the Mysticeti and Odontoceti
The toothed whales (also called odontocetes, systematic name Odontoceti) are a parvorder of cetaceans that includes dolphins, porpoises, and all other whales possessing teeth, such as the beaked whales and sperm whales. Seventy-three species of ...
. The Mysticeti include four families of baleen whales
Baleen whales (systematic name Mysticeti), also known as whalebone whales, are a parvorder of carnivorous marine mammals of the infraorder Cetacea (whales, dolphins and porpoises) which use keratinaceous baleen plates (or "whalebone") in the ...
, 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 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 ondontocetes. 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. With regard to sex and age biases, the infections do not seem influenced by the age or sex of an individual. 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 an American national park located in the western United States, largely in the northwest corner of Wyoming and extending into Montana and Idaho. It was established by the 42nd U.S. Congress with the Yellowston ...
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'') is a species of canis, canine native to North America. It is smaller than its close relative, the wolf, and slightly smaller than the closely related eastern wolf and red wolf. It fills much of the same ecologica ...
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 (biology), order Carnivora, being present across the entire Northern Hemisphere including most of North America, Europe ...
) 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.
Effects on hunters
Hunters may be at additional risk for exposure to brucellosis due to increased contact with susceptible wildlife, including predators that may have fed on infected prey. Hunting dogs can also be at risk of infection.CDC - Hunters Risks - Animals That Can Put Hunters at Risk
/ref> Exposure can occur through contact with open wounds or by directly inhaling the bacteria while cleaning game. In some cases, consumption of undercooked game can result in exposure to the disease. Hunters can limit exposure while cleaning game through the use of precautionary barriers, including gloves and masks, and by washing tools rigorously after use. By ensuring that game is cooked thoroughly, hunters can protect themselves and others from ingesting the disease. Hunters should refer to local game officials and health departments to determine the risk of brucellosis exposure in their immediate area and to learn more about actions to reduce or avoid exposure.
See also
* Brucella suis
''Brucella suis'' is a bacterium that causes swine brucellosis, a zoonosis that affects pigs. The disease typically causes chronic inflammatory lesions in the reproductive organs of susceptible animals or orchitis, and may even affect joints and ...
References
Further reading
Fact sheet on Brucellosis from World Organisation for Animal Health
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, and is headquartered in Atlanta, Georgi ...
* – 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, ...
External links
{{Authority control
Zoonotic bacterial diseases
Bacterium-related cutaneous conditions
Animal bacterial diseases
Occupational diseases
Zoonoses
Dog diseases
Bovine diseases
Sheep and goat diseases
Biological weapons