Microbiology and epidemiology
Brucellae are slow-growing, small, aerobic, nonmotile, nonencapsulated, non–spore-
forming, gram-negative coccobacilli
Brucellosis is an enzootic infection (i.e. endemic in animals). Although six species of
Brucella are known, only four are important to humans: B. melitensis (goats, sheep and
camels), B. abortus (cattle), B. suis (pigs) and B. canis (dogs).B. ovis, neotomae and
recent isolates from marine mammals, tentatively named maris
More than 500,000 cases of brucellosis are reported yearly to the World Health
Organization from 100 countries
Alternative na me for brucella include : malta f., andulant f., Gibraltar fever, and
B. melitensis is enzootic in the Middle East, Africa, India, Central Asia and South
America. B. abortus is found in Africa, Asia and South America, and B. suis in South
B. melitensis causes the most severe disease; B. suis is often associated with abscess
Infected animals may excrete brucellae in their milk for long periods of time and human
infection is acquired by ingesting contaminated milk, cheese, yoghurt and butter.
Uncooked meat and offal may also spread infection. Animal urine, faeces, vaginal
discharge and uterine products may act as sources of infection through abraded skin or
via splashes and aerosols to the respiratory tract and conjunctiva.
After penetrating the epithelial cells of human skin, conjunctiva, pharynx, or lung,
Brucella organisms initially induce an exuberant polymorphonuclear neutrophil
response in the submucosa.
After ingestion of organisms by neutrophils and tissue macrophages, spread to
regional lymph nodes occurs. If host defenses within the lymph nodes are
overwhelmed, bacteremia follows.
The usual incubation period between infection and bacteremia is 1½ to 3 weeks.
Bacteremia is also accompanied by phagocytosis of free Brucella organisms by
neutrophils and localization of bacteria primarily to the spleen, liver, and bone
marrow, with the formation of granulomas.
If the inoculum is large and the patient receives no treatment, large granulomas
may form, suppurate, and serve as a source of persistent bacteremia with the
potential for multiorgan spread. The primary virulence factor of Brucella appears
to be cell wall lipopolysaccharide.
Brucellae are intracellular organisms that can survive for long periods within the
reticulo-endothelial system. This explains many of the features of clinical
brucellosis, including the chronicity of the disease and the tendency to relapse
even after adequate antimicrobial therapy.
Clinically, human brucellosis may be divided into subclinical illness, acute or
subacute disease, localized disease and complications, relapsing infection, and
chronic disease .
1. Subclinical Illness
Detected only by serologic testing, asymptomatic or clinically unrecognized human
brucellosis often occurs in high-risk groups, including slaughterhouse workers, farmers,
and veterinarians. More than 50% of abattoir workers and up to 33% of veterinarians
have high anti-Brucella antibody titers but no history of recognized clinical infection.
2. Acute and Subacute Disease
After an incubation period of several weeks or months, acute brucellosis may
occur as a mild, transient illness (with B. abortus or B. canis) or as an explosive,
toxic illness with the potential for multiple complications (with B. melitensis).
Approximately 50% of patients have an abrupt onset over days, whereas the
remainder has an insidious onset over weeks.
Symptoms in brucellosis are protean and nonspecific. More than 90% of patients
experience malaise, chills, sweats, fatigue, and weakness.
More than 50% of patients have myalgias, anorexia, and weight loss.
Fewer patients complain of arthralgias, cough, testicular pain, dysuria, ocular
pain, or visual blurring. Likewise, few localizing physical signs are apparent.
Fever, with temperatures often greater than 39.4° C (103° F), occurs in 95% of
patients. An undulating or intermittent fever pattern is unusual. A relative pulse
temperature deficit may occur.
Splenomegaly is present in 10 to 15%, and lymphadenopathy occurs in up to 14%
(axillary, cervical, and supraclavicular locations are most frequent, related to hand
wound or oropharyngeal routes of infection); hepatomegaly is less frequent.
Other laboratory findings in acute or subacute disease may include mild anemia,
lymphopenia or neutropenia (especially with bacteremia), lymphocytosis,
thrombocytopenia, or (rarely) pancytopenia. The majority of infected individuals
recover completely without sequelae if the diagnosis is appropriately made and
prompt therapy is initiated.
3. Localized Disease and Complications
Brucella organisms may localize in almost any organ but most commonly localize
in bone, joints, central nervous system (CNS), heart, lung, spleen, testes, liver,
gallbladder, kidney, prostate, and skin. Localized disease may occur
simultaneously at multiple sites. Localized complications most often appear in
association with a more chronic course of illness, although complications may
occur with acute disease caused by B. melitensis or B. suis.
4. Relapsing Infection
Up to 10% of patients with brucellosis experience relapses after antimicrobial
therapy. Relapses occur usually 3 to 6 months after completion of therapy but
may be seen up to 2 years after treatment.
Relapses are associated frequently with antimicrobial resistance as well as the
intracellular location of the organisms, which protects the bacteria from certain
antibiotics and host defense mechanisms.
Relapsing infection is difficult to distinguish from reinfection in high-risk groups
with continued exposure.
5. Chronic Disease
Disease with a duration of more than 1 year has been called chronic brucellosis.
A majority of patients classified as having chronic brucellosis really have
persistent disease caused by inadequate treatment of the initial episode, or they
have focal disease in bone, liver, or spleen.
About 20% of patients diagnosed as having chronic brucellosis complain of
persistent fatigue, malaise, and depression; in many aspects this condition
resembles the chronic fatigue syndrome.
These symptoms frequently are not associated with clinical, microbiologic, or
serologic evidence of active infection and may represent a preexisting
FOCAL complication OF BRUCELLOSIS
Suppurative arthritis; synovitis, bursitis
Paravertebral or psoas abscess
Central nervous system
Cranial nerve palsies
Intracranial or subarachnoid haemorrhage
Definitive diagnosis of brucellosis depends on the isolation of the organism. Blood
cultures are positive in 75-80% of infections caused by B. melitensis and 50% of those
caused by B. abortus.
The non-radiometric 'Bactec' system gives a good isolation rate, but if brucellosis is
suspected, prolonged incubation and blind subcultures are recommended.
Bone marrow culture should not be used routinely but may increase the diagnostic yield,
particularly if antibiotics have been given before specimens are taken.
CSF culture in neurobrucellosis is positive in about 30% of cases.
World-wide, the serum agglutination test is the serological technique most commonly
employed to detect brucellosis.
Agglutination should be carried out to a high dilution (at least 1/640) to avoid the
prozone phenomenon whereby non-agglutinating IgG and IgA molecules completely
block the agglutinating reaction.
Significant agglutination titres may persist for months or years after recovery and in
endemic areas a single titre of 1/320 or a fourfold rise in titre is needed to support a
diagnosis of acute infection.
The test usually takes several weeks to become positive but should eventually detect 95%
of acute infections. The pre-treatment of serum with 2-mercaptoethanol helps to
distinguish between IgG and IgM responses.
The enzyme-linked immunosorbent assay (ELISA) also identifies IgM and IgG
antibodies; IgM decreases rapidly within the first few months of illness.
Specialist laboratory techniques including the use of the anti-human globulin (Coombs)
test may be necessary to distinguish chronic disease from past inactive infection.
Aminoglycosides show synergistic activity with tetracyclines when used against
brucellae. Standard therapy therefore consists of doxycycline 100 mg 12-hourly
for 6 weeks, with streptomycin 1 g i.m(or new regimen that include gentamycine
3-5mg /kg) . daily for the first 2 weeks. The relapse rate with this treatment is
An alternative oral regimen consists of doxycycline 100 mg 12-hourly plus
rifampicin 900 mg (15 mg/kg) daily for 6 weeks, but failure and relapse rates are
higher, particularly with spondylitis. Rifampicin may antagonise doxycycline
activity by reducing serum levels through enzyme induction.
Chronic illness should be treated for a minimum of 3 months and many
authorities would extend this to 6 months, depending upon the condition of the
patient and the result of sequential serological tests.
The optimum therapy for neurobrucellosis is unknown, and there is no current
agreement on the combination or number of drugs to use. Treatment should
continue for at least 3 months, and longer if CSF pleocytosis persists.
the usual drug that is used is 3ed generation cephalosporine or doxicycline +
refampicn + cotrimoxazole
The control of human brucellosis is related directly to prevention programs in
domestic animals and avoiding unpasteurized milk and milk products. In
slaughterhouses, important means of prevention include careful wound dressing,
protective glasses and clothing, prohibition of raw meat ingestion, and the use of
previously infected (immune) individuals in high-risk areas.
Brucellosis appropriately treated within the first month of symptom onset is
curable. Acute brucellosis often produces severe weakness and fatigue, and
patients are frequently unable to work for up to 2 months.
Immunity to reinfection follows initial Brucella infection in the majority of
With early antimicrobial therapy, cases of chronic brucellosis or localized disease
and complications are rare.
Of patients who die of brucellosis, 84% have endocarditis involving a previously
abnormal aortic valve, often associated with severe congestive heart failure.
With best luck