BRUCELLOSIS

 Brucellosis is a zoonotic infection caused by the

bacterial genus Brucella.
 The bacteria are transmitted from animals to
humans by ingestion through infected food
products
 direct contact with an infected animal
 or inhalation of aerosols.
 Also known by various names…..
 Mediterranean fever, Malta fever, gastric
remittent fever, and undulant fever.
 Cont….
 Brucella organism are small aerobic intracellular
coccobacilli, localize in the reproductive organs of
host animals.
 They are shed in large numbers in the animal’s
urine
 milk,
 placental fluid, and other fluids.
 , 8 species have been identified. Out of which
following 4 have moderate-to-significant human
pathogenicity
 CONT…..
• Brucella melitensis (from sheep; highest pathogenicity)

• •Brucella suis (from pigs; high pathogenicity)

• •Brucella abortus (from cattle; moderate pathogenicity)

• •Brucella canis (from dogs; moderate pathogenicity

 CONT….
 only Domesticated animals are of particular
importance
 BRucellosis is also found in wild animals
 Humans have only a limited risk from wild
animals
CAUSE
more than 500,000 infections per year
worldwide.
 pathophysiology
Brucellae are aerobic gram-negative
coccobacilli that possess a unique ability to
invade both phagocytic and nonphagocytic
cells .
Brucella can gain entry into the human body
through breaks in the skin
 mucous membranes, conjunctivae,
 respiratory and gastrointestinal (GI) tracts.
 ETIOLOGY
• the 4 Brucella species….
• B melitensis is thought to be the most virulent
and causes the most severe and acute cases of
brucellosis; it is also the most prevalent
worldwide.
• B melitensis may be acquired via exposure to
animals or animal products
• BRUCELLA, abortus is more widely distributed
throughout the world than B melitensis is, but it
is less pathogenic for both animals and humans
 CONT…
 B suis has been the second most common cause of
brucellosis in North America..
 B canis infection has a disease course that is
indistinguishable from that of B abortus infection.
 It infection has an insidious onset, causes frequent
relapses, and does not commonly CAUSE
chronic brucellosis…
 Ingestion of unpasteurized goat milk and related dairy
products is the main route by which B melitensis is
transmitted to humans
 EPIDEMIOLOGY
 Brucellosis causes more than 500,000 infections per year worldwide
 The heaviest disease burden lies in countries of the Mediterranean and
Arabian COUNTRIES… and the disease is also common in India, Mexico,
South and Central America
 Brucellosis in the Mediterranean, chiefly due to B melitensis, incidence
in males in their mid-20s
 . A report from northern Saudi Arabia found that 60% of cases of
brucellosis occurred in individuals aged 13-40 years,
 whereas 21% occurred in those younger than 13 years,
 16% in those aged 40-60 yearsbrucellosis may be more common in
children in developing countries because of lack of pasteurization
 brucellosis may be more common in children in developing countries
because of lack of pasteurization
 Transmission to infants may occur through breastfeeding [9] or ingestion
of raw milk
 CONT…
Worldwide, brucellosis is more common in
males than in females.
Occupational exposure to animals likely plays
an important role in the enhanced
vulnerability of men to the development of
brucellosis…
 CLINACAL PRESENTATION

• HISTORY
Travel hx..
Occupational hx..
Dietry hx
Hx of animal exposure…
 Cont…
Endemic exposure
 A dietary history is especially helpful for diagnosing
brucellosis in individuals who live in or visit regions of
endemic disease.
 Unpasteurized dairy products, especially goat’s cheese,
frequently are implicated as sources of human infection.
 Raw or poorly cooked meats are also important sources
of infection in regions of endemic disease.
 Laboratory transmission of brucellosis may occur,
especially in regions of endemic disease
 transmission to infants via breastfeeding also common in
endemic areas…
 Con…
• Nonendemic exposure
areas of the world where brucellosis is
rare, the diagnosis may be missed even in
patients who manifest typical signs, such
as otherwise uncomplicated persistent
undulating fever…

A dietary history is important in regions

where the disease is not endemic because
the disease may be acquired through
ingestion of infected foods shipped from
regions of endemic disease.

 Ingestion of unpasteurized milk from

cows or goats enhances risk of
 CON…
• In nonendemic regions, physicians,
,pathologists, and laboratory personal
exposed to tissues from infected animals
(including humans) are at particular risk for
brucellosis……
 symptoms
 Fever is the most common symptom and sign of
brucellosis, occurring in 80-100% of cases.
 It is intermittent in 60% of patients with acute and
chronic brucellosis
 undulant in 60% of patients with subacute brucellosis
 . Fever can be associated with a relative bradycardia.
 Fever of unknown origin (FUO) is a common initial
diagnosis in patients in areas of low endemicity.
 It is associated with chills in almost 80% of cases
 CONT…
• Constitutional symptoms of brucellosis include
anorexia
• asthenia, fatigue, weakness, malaise, and weight loss
and are very common (> 90% of cases….
• Bone and joint symptoms include arthralgias, low back
pain, spine and joint pain, and, rarely, joint swelling.
• These symptoms affect as many as 55-80% of patients.
• Arthralgias may be diffuse or localized, with a
predilection for bone ends and the sacroiliac joint.
• Acute monoarticular arthritis is uncommon but may be
part of the presentation
 CONT…
 Neuropsychiatric symptoms of brucellosis are
common despite the rare involvement of the
nervous system.
 Headache, depression, and fatigue are the most
frequently reported neuropsychiatric symptoms.
 In patients with advanced disease who have
meningoencephalitis may include changes in
mental status, coma, neurologic deficit, rigidity,
or seizures.
 CONT…
• A significant percentage (approximately 50%) of patients
have gastrointestinal (GI) complaints,
• primarily dyspepsia,
• though abdominal pain from hepatic abscesses may occur.
• Hepatic abscesses should be suspected in patients with
signs of systemic toxicity and persistently elevated liver
enzymes.
• The abscess can serve as a source of bacteremic seeding.
• Spontaneous bacterial peritonitis secondary to brucellosis
infection has been reported
• . Constipation, diarrhea, and vomiting may occur…
 CONT…
• Genitourinary infections with brucellae have been
reported and include orchitis,
• urinary tract infection (UTI), and glomerulonephritis.
Frank renal failure or sepsis is rare.

• Neurologic symptoms of brucellosis can include

weakness, dizziness, unsteadiness of gait, and urinary
retention. Wi
• cranial nerve dysfunction may affect persons with
chronic central nervous system (CNS) involvement.
 CONT….
• Cough and dyspnea develop in up to 19% of persons with
brucellosis
• Pleuritic chest pain may affect patients with underlying
empyema.

• Endocarditis from brucellae is reported, with septic

embolization a common complication of this form of
brucellosis.
• Other cardiac complications, such as pulmonary edema or
dysrhythmias, are rare.
• Brucella endocarditis is the form most commonly
associated with fatalities
 CONT…
• With the chronic form of brucellosis, in which
the illness has lasted longer than 1 year
(undiagnosed and untreated brucellosis), an
afebrile pattern is typical, with a history of
myalgia, fatigue, depression, and arthralgias
• (chronic fatigue syndrome is the most important
disease in the differential diagnosis).
• The chronic form is primarily caused by B
melitensis and usually affects adults older than
30 years. The chronic form is rare
 classification
• Subclinical brucellosis

• Disease is usually asymptomatic,

• the diagnosis is usually established incidentally
after serologic screening of persons at high risk of
exposure.

• Culture data are usually unrevealing.

• Acute and subacute brucellosis

• Disease can be mild and self-limited

orfulminant with severe complications …
• Associated symptoms can develop 2-3
months before diagnosis in mild cases and 3-
12 months before diagnosis in severe cases.
 Usually, acute brucellosis occurs without focal abnormalities.

 Nonfocal weakness may be noted.

 The tissues overlying the spine or peripheral nerves may be tender to

percussion
 . Tenderness, swelling, or effusion of joints may be evident

 . In some instances, orchitis appears after a few days of illness.



• Some patients manifest constipation.

• Occasionally, abdominal tenderness suggests an acute abdomen.
• In some more severe cases, tender enlargement of the spleen may be
detected
• of bacterial endocarditis, a complication that is
rare in acute or subacute brucellosis than in
chronic brucellosis.
• Rarely, disease of the lungs or pleura is a feature
of acute brucellosis
• Meningismus, papilledema, mental status
changes, and long-tract signs are found in a small
fraction of cases of acute brucellosis as
manifestations of acute neurobrucellosis.
• brucellotic osteomyelitis with associated epidural
abscess
• Chronic brucellosis

• The diagnosis of chronic brucellosis is typically made after

symptoms have persisted for 1 year or more
• . Low-grade fevers and neuropsychiatric symptoms predominate.
• Results of serologic studies and cultures are often negative…witout
confirmatory evidence

• many authorities doubt the existence of chronic disease.

• Many patients have persistent disease caused by inadequate initial
therapy and underlying localized disease may be present.
• Localized and relapsing brucellosis

 Localized complications of brucellosis are typically observed in patients

with acute disease or chronic untreated infection.
 Osteoarticular, genitourinary, and hepatosplenic involvement are most
common…..

• Relapsing brucellosis may be difficult to distinguish from reinfection

• . Presenting symptoms typically reflect the initial disease; however, these
symptoms are more severe. Symptoms typically develop 2-3 months after
therapy completion
• . Culture results are typically positive,
• and serology may be difficult to interpret
• , but enzyme-linked immunoassay (ELISA) testing may be more helpful.
 Physical findings
• Physical findings in patients with brucellosis vary and
are nonspecific for the disease.

• most common findings is hepatosplenomegaly

• (or isolated hepatomegaly or splenomegaly).
• Right upper quadrant pain and jaundice may indicate
hepatic abscess.
• Generalized tenderness, rebound tenderness, and
sluggish or absent bowel sounds can be expected in
patients with peritonitis.
• Osteoarticular involvement is also common

• . Focal infection of bones or joints may present with

localized abnormal physical findings (eg, swelling,
tenderness, and limited motion) in the affected areas.
• Arthritis, joint effusions, or, in severe
cases,costovertebral angle tenderness may be
observed.
• Focal osteomyelitis of the vertebrae, tibia, and,
especially, the knee has also been associated with
brucellosis infection even in the absence of other
significant systemic symptoms.
• . Epididymo-orchitis has been described in
association with brucellosis; a tender, swollen
scrotum with erythema is present in these
patients.
• Urethritis has been reported.
• Endocarditis may present with new or changing
murmurs, and mycotic aneurysms of ventricles,
brain, and aorta have been observed.
• A pericardial rub is present in patients with
pericarditis
• Neurologic findings vary according to the presentation of neurologic
disease and may include the following:

• •Acute meningoencephalitis (most common neurologic manifestation) -

Depressed level of consciousness, meningeal irritation, cranial nerve
involvement, coma, seizure, and respiratory depression

• Meningitis – Nuchal rigidity, Kerning sign, and Brudzinski sign

• •Increased intracranial pressure (ICP) or brain abscess – Papilledema,

cranial nerve palsy, and focal neurologic deficits
• Peripheral polyradiculoneuropathy - Hypotonia and
areflexia in most cases, paraparesis, and an absence of
sensory involvement

• •Diffuse CNS involvement - Spasticity, hyperreflexia,

clonus, extensor plantar response, sensorineural
hearing loss, cranial nerve involvement, and cerebellar
signs
• Cutaneous manifestations develop in 5-10% of patients…
•
• Erythema nodosum, abscesses, and papulonodular eruptions (most common)

•
• Impetigo, psoriatic, eczematous,
•

• •Macular, maculopapular, and scarlatiniform rashes

• Vasculitic lesions (eg, petechiae, purpura, and thrombophlebitis

• •Cutaneous ulcerations
 Cont….
• Ocular findings can include the following :

• Uveitis

• Keratoconjunctivitis

• Iridocyclitis

• Nummular keratitis
• Optic neuritis
• Choroiditis
• cataracts
 complications
• osteoarticular
• Osteoarticular symptoms affect 20-60% of
patients with
• sacroiliitis is the most common (though rarer
in children).
• Spondylitis, arthritis, osteomyelitis, bursitis,
and tenosynovitis have been reported
• .
 CONT…..
Hepatobiliary complications include hepatitis, hepatic abscess, and
acute cholecystitis.
The rarely reported GI complications include ileitis, colitis, and
spontaneous peritonitis.

genitourinary complications orchitis or epididymo-orchitis.

Renal involvement is rare, although glomerulonephritis and

pyelonephritis have been reported

Infection in pregnant patients is rare and is associated with first-

trimester abortions.
 CONT
• Neurobrucellosis
• . Meningitis (1-2%) and, less commonly,
• papilledema, optic neuropathy, radiculopathy,
stroke, and intracranial hemorrhage may be
seen.

• Acute meningoencephalitis
 CONT….
• cardiovascular
• Worldwide, endocarditis occurs in less than 2% of
patients with brucellosis; however, in endemic
areas, it may affect 7-10% of patients. The aortic
valve is affected in 75% of patients, and 50% of
affected valves were previously healthy.
Endocarditis is responsible for most of the
mortality associated with brucella…
• pericarditis myocarditis,
 CONT…..
• Pulmonary complications are reported in 0.3-1%
of patients with brucellosis (less commonly in
children) and include pneumonia and pleural
effusion.
• Hematologic complications are not typically
associated with severe sequelae and resolve with
appropriate therapy. Reports of disseminated
intravascular coagulation (DIC) and the
hemophagocytic syndrome have been published.
Splenic abscess has been reported.
Splenic absess …..thyroid absess ….uvuetis aare less common
complications

DIFFERENTIAL DIAGNOSIS…

ABORTION COMPLICATIONS

ACUTE EPIDIDYMITIS

ANKYLOSING SPONDYLITIS
 CONT….
• Leptospirosis

• Lumbar (Intervertebral) Disk Disorders

• Malaria
• Spontaneous Bacterial Peritonitis (SBP)

• Thrombotic Thrombocytopenic Purpura (TTP)

• Tuberculosis (TB)

• Tuberculosis of the Genitourinary System

• Tularemia

• Meningitis
 CONT…
• Tularemia

• Typhoid Fever

• Urinary Tract Infection (UTI) in Males

• Viral Hepatitis
• Fever of unknown origin

• Malignancy (eg, lymphoma)

• Rickettsial diseases

• Sacroiliitis

• Vasculitis
• Viral Pneumonia
 workup
• A complete blood count (CBC). Leukocytosis is
rare in brucellosis
• , and a significant number of patients are
neutropenic.
• Anemia is reported in 75% of patients
(particularly with chronic infection)
• , thrombocytopenia is reported in 40%
(secondary to hepatosplenomegaly or from
immune thrombocytopenia),
• and pancytopenia is reported in 6% of patients.
 CONT…
• liver enzymes
• A slight elevation in liver enzyme levels is a very
common finding..
• Culture
• Diagnosis of brucellosis is definitive when Brucella
organisms are recovered from blood, bone marrow, or
other tissue.
• The sensitivity of blood cultures approximately 60%
• . bloodcultures are still advised for at least 4 weeks;
• bone marrow culture is thought to be the criterion
standard. Sensitivity is usually 80-90%.
 CONT…
• CSF analysis
• In patients with neurobrucellosis, analysis of CSF
reveals a mild-to-modest lymphocytic pleocytosis
of 88-98%.
• Protein levels are elevated in conjunction with
normal glucose levels.
• CSF cultures are positive for brucellosis less than
50% of the time, but antibody testing of the fluid
yields a diagnosis.
• CSF cultures are indicated for suggested
meningitis.
 CONT..
• athrocentesis
• arthrocentesis may occasionally be needed to exclude
septic arthritis.
• The joint aspirate demonstrates an exudative fluid with
low cell counts…
• serology tube agglutination test,, measures antibodies
against (LPS); it remains the most popular test tool for the
diagnosis of brucellosis.
• The 2-mercaptoethanol test detects immunoglobulin G
(IgG), and titers higher than 1:80 define active infection.
• A high IgG antibody titer or a titer that is higher after
treatment suggests persistent infection or relapse.
•
 CONT..
• The shortcomings of agglutination tests test
include potential cross-reactivity with IgM of
other organisms

• Prozone phenomenon may occur secondary to

hyperantigenemia,
• (ELISA) typically uses the cytoplasmic proteins
as antigens and measures IgM, IgG, and IgA, in
brucellosis relapse
 CONT…
• urinalysis and urine culture
• Helpful in urinary tract infection (UTI).
• The most likely finding is a sterile pyuria,
• . Urine cultures may be helpful;
 CONT…
• A chest radiograph should be obtained if
respiratory symptoms are present……usually
absent in brucellosis
• Findings include
• include hilar and paratracheal lymphadenopathy,
pulmonary nodules, pleural thickening, and
pleural effusion.

• Spinal radiographic findings in patients with

osteoarticular complications
 CONT…
• Echocardiography is used to evaluate for
possible endocarditis.
• ultrasonography to diagnose testicular
abscess from brucellosis has been reported
• Ct scan
• is often normal, it may reveal evidence of
acute or chronic Brucella leptomeningitis,
subarachnoid hemorrhage, or cerebral
abscess.
 CONT…
• .
• Bone marrow examination may reveal
erythrophagocytosis.
• Microangiopathic hemolytic anemia,
thrombocytopenic purpura, and Coombs-positive
hemolytic anemia have been reported in
brucellosis.

• Percutaneous liver biopsy may be needed in the

patient with liver granulomas …
•TREATMENT
 CONT…
• initial Supportive Care
• . potentially transmissible disease,
appropriate precautions (eg, gloves, mask,
and gown) should be used.
 Pharmacological
• Single drug regimens are not recommended
because of relapse rate as high as 50per…
• for acute brucellosis in adults and children older
than 8 years, the World Health Organization
(WHO) guidelines recommend the following:

• Doxycycline 100 mg PO twice daily plus rifampin

600-900 mg/day PO – Both drugs are to be given
for 6 weeks; this regimen is more convenient but
probably increases the risk of relapse.
• Doxycycline 100 mg PO twice daily for 6
weeks and streptomycin 1 g/day IM for 2-3
weeks – This regimen is believed to be more
effective, mainly in preventing relapse;
gentamicin can be used as a substitute for
streptomycin and has shown equal efficacy
• Ciprofloxacin-based regimens have shown
efficacy equal to that of doxycycline-based
regimens
 CONT…
 The regimen consisting of doxycycline for 6 weeks
plus streptomycin for 2-3 weeks was more
effective than one consisting of doxycycline plus
rifampicin for 6 weeks.
• The investigators also found that a regimen
consisting of a fluoroquinolone plus rifampicin for
6 weeks was as effective overall as doxycycline
plus rifampin (though the evidence for this
conclusion was of low quality) and was slightly
better tolerated.
 CONT…
brucellosis in children younger than 8 years, administration
of rifampin and TMP-SMZ for 6 weeks is the therapy of choice
The relapse rate appears to be approximately 5% or lower.
• Treatment of brucellosis in pregnant women is a
challenging problem
• TMP-SMZ has been effective in this population, either as
monotherapy or as part of combination therapy with
rifampin or gentamicin
• . The most common recommendation is for rifampin, either
alone or in combination with TMP-SMZ.
• It should be kept in mind that the use of TMP-SMZ by the
end of pregnancy is associated with kernicterus.
 CONT…
• In patients with spondylitis or sacroiliitis, doxycycline and rifampin
combined with an aminoglycoside (gentamicin) for the initial 2-3
weeks, followed by 6 weeks of rifampin and doxycycline, is usually
recommended.
• patients with nervous system infections typically require
combination therapy.
• Doxycycline is generally preferred to tetracyclines or
aminoglycosides because the latter are less likely to cross the
blood-brain barrier in adequate quantities
• . Many authorities prefer a 3-drug (doxycycline-streptomycin-
rifampin or doxycycline−TMP-SMZ−rifampin) regimen to a 2-drug
regimen
• . A brief course of adjunctive corticosteroid therapy has been used
to control the inflammatory process, but studies are limited.
 CONT..
• third-generation cephalosporins have been used
in Brucella meningitis
• patients with endocarditis require aggressive
therapy. Aminoglycoside therapy in conjunction
with doxycycline, rifampin, and TMP-SMZ for at
least 4 weeks, followed by at least 2-3 active
agents (without aminoglycosides) for another 8-
12 weeks, is preferred.
• the use of corticosteroids is reserved for
symptomatic Brucella meningitis.
 CONT
• Any additional drugs needed for symptomatic
treatment (eg, antipyretics, analgesics) must
be administered as well.
• the main roles of surgery in patients with
brucellosis lie in the treatment of endocarditis
and in the drainage of pyogenic joint effusions
or paraspinal abscesses.
 CONT….
• Diet and Activity
• No special diet is required for the treatment of
brucellosis.
• Discuss with patients the importance of
consuming pasteurized milk and milk products
and avoiding other possible sources of infection
• . Restriction of activity with bed rest appears to
confer benefit in the acute phase of brucellosis,
increasing the rate of recovery.
 prevention
• P
prevntion of brucellosis in humans depends on
eradication or control of the disease in animals

. Better handling of infected animals or animal

products is paramount

. Public awareness and education play major

roles in prevention.
 CONT….
• Consumption of unpasteurized milk and milk
products, as well as of raw or undercooked
meats should be avoided…
• Use of gloves ,,mask
• Immunization
 Long term monitoring
• outpatient care consists of completing the prescribed course of antibiotic
therapy
• treating any exposed patients
• , and avoiding contact with the initial source of infection
• . Care is continued until the infection is cured and laboratory findings
return to reference range
• s. Serologic studies and enzyme-linked immunosorbent assay (ELISA) can
be used to document patient response to therapy

• .c areful follow-up is essential for ensuring that the patient complies with
the full 6-week antibiotic regimen and for determining whether a relapse
has occurred
• . In some instances, the disease takes a relapsing and remitting course. In
such cases, triple-drug therapy may be undertaken for periods as long as 6
months or more.
 prognosis
• Prognosis
• The prognosis is generally excellent
• . Although initial the disease is easily curable,
with a low risk of relapse or chronic disease
• . However, the prognosis is poor in persons
who present with congestive heart failure due
to endocarditis, in whom mortality
approaches 85%.
 CONT…
• uncomplicated cases of acute brucellosis, fever,
malaise, and many other manifestations improve
rapidly with bed rest, whereas sustained physical
activity may prolong or worsen the degree of
illnes
• mortality in recognizably symptomatic acute or
chronic cases of brucellosis is very low, certainly
less than 5% and probably less than 2%. It is
usually the result of the rare instance of Brucella
endocarditis or is the result of severe CNS
involvement,
 CONT…
• the likelihood of recurrence is greater in individuals
who are not treated or who are inadequately treated
for acute brucellosis.
• However, recurrence is possible even in properly
treated patients who have had acute brucellosis.
• Addition of oral rifampicin to oral tetracycline may
reduce the recurrence risk for patients who are treated
with that combined therapy for acute brucellosis.

• Chronic brucellosis may continue to trouble patients

for as long as 25 years, but such cases are quite rare.
 THANKS
PRESENTED
BY
DR MOMINA JAHANGIR