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BRUCELLOSIS
Morning report 7/11/05
Andy Bomback
• Also called undulant,
Mediterranean, or Mata
fever, brucellosis is an
acute and chronic infection
of the reticuloendothelial
system
• gram negative facultative
intracellular coccobacilli
• 4 species: B. melitensis, B.
abortus, B. suis, B. canis
• Humans acquire
brucellosis from exposure
to infected animals (direct
contact with infected
animal parts) or
contaminated animal
products (unpasteurized
animal-milk products, such
as raw milk, soft cheese,
butter, and ice cream); the
disease is also spread by
inhalation of infected
aerosolized particles
in US, most cases occur in slaughterhouse workers,
farmers, veterinarians, and other animal handlers
(including micro lab personnel)
The disease also presents in US Hispanic populations
and is probably related to illegal importation of
unpasteurized dairy products from Mexico
Number of reported cases of human brucellosis in Hispanic and non-
Hispanic California residents, by year, 1973–1992
The relationship between the disease and individual socioeconomic status is
exemplified in the US, where programs to eradicate brucellosis have successfully
limited the annual incidence of the disease, which now predominantly occurs in CA
and TX (which account for >50% of US cases) with relatively high rates of
incidence in NC, IL, FL, WY, IA, and AZ.
• Country 1998 1999 2000 2001 2002 2003 • Azerbaijan 494 582 654 660 519 407
• Italy 1461 1324 1067 923 813 520
• Mexico 3550 2719 2171 3013 2851 3008
• Turkey 11,427 11,462 10,742 15,510 17,553 14,435
USA 79 82 87 136 125 93
What the Republicans don’t want
you to know about brucellosis!!!
Clinical picture
• Brucellosis is a well documented cause of FUO
with variable symptomatology – fever (can be
spiking and accompanied by rigors), sweats (often
malodorous), malaise, anorexia, fatigue, weight
loss, depression. Onset can be abrupt or insidious
– developing over several days to weeks. Despite
multiple patient complaints, the physical exam
findings (other than fever) are usually minimal to
none – can see minimal LAN and occasional HSM
Almost all organ systems can be
involved with brucellosis –
localization of disease can cause
focal symptoms or findings
• of 530 cases studies prospectively, 32%
developed a complication; major risk factor
for developing focal disease was duration of
symptoms > 30 days
• most common sites for localization:
o Osteoarticular, especially sacroiliitis (20-30%) and
peripheral arthritis
o GU, especially epididymoorchitis (2-40% males)
o Neurobrucellosis, usually presenting as meningitis
(1-2%)
o Endocarditis, left-sided and 2/3 on previously
damaged valves (1%); remains the principle cause
of mortality in the course of brucellosis and
typically requires immediate surgical valve
replacement
o Hepatic abscess (1%)
• Undiagnosed and
untreated
brucellosis can be
symptomatic for
months and some
previously treated
patients may
relapse
• In the 1950’s, a syndrome called “chronic brucellosis” – malaise, weakness, depression – was a relatively common diagnosis; these patients likely represent the current population receiving diagnoses of chronic fatigue syndrome or chronic Lyme disease
MED H
Diagnostic work-up
• Consider brucellosis in
patients with otherwise
unexplained chronic fever
and nonspecific
complaints, particularly if
there has been exposure to
Brucella by contact with
animal tissues or ingestion
of unpasteurized milk or
cheese.
Routine Labs
• WBC usually normal
to low (can see
pancytopenia); minor
LFT abnormalities are
fairly common
Cultures
• ideally, the diagnosis
is made by isolation of
the organism from
cultures of blood or
other sites (liver
biopsies, bone marrow
aspirates, pleural fluid,
CSF)
Serologic Testing • “classic” serologic testing for
brucellosis uses standard tube
agglutination testing. In
general, a single titer of
>1:160 in the presence of
compatible illness supports the
diagnosis; titers should be
repeated over the next 4-12
weeks, as a fourfold or greater
increase or decrease provides
even stronger evidence of the
diagnosis
• other diagnostic serologic tests: ELISA,
antibrucella Coombs, complement
fixation, Rose Bengal agglutination
P. C. freaking R.
• PCR identified 97% of fluid and tissue
samples in patients with focal complications
of brucellosis compared to only 29% by
culture – a combination of PCR-ELISA may
turn out to be the most sensitive and
specific method for diagnosis
Treatment • After ingestion, the majority of brucellae are
rapidly eliminated by phagolysosome fusion. Of
those bacteria, 15-30% survive in gradually
evolving brucellae-containing compartments, in
which rapid acidification takes place. How this
unique environment is formed is incompletely
understood, but it is responsible for limiting
antibiotic action and explains the discrepancy
between in vitro studies and in vivo events.
All monotherapies have
unacceptably high relapse
rate, so combination regimens
of antibiotics that can
penetrate macrophages and
act in the acidic intracellular
environment are necessary.
1986 WHO guidelines for the
treatment of brucellosis
• Regimen A:
doxycycline 100
mg PO bid for 6
weeks +
streptomycin 1 g
IM qd for the
first 14-21 days
• Regimen B:
doxycycline 100
mg PO bid +
rifampin 600 to
900 mg (15
mg/kg) PO qd for
6 weeks
• same relative efficacy
of both regimens
(including time to
defervescence and
relapse rate), but
regimen B is
obviously easier to
implement
• other drugs (used in
combination with
doxycycline and/or
rifampin): gentamicin,
ofloxacin,
ciprofloxacin, TMP-
SMX
Relapses
• Most relapses occur within 3 months of
stopping therapy and almost all within 6
months – rate of relapse is about 10%.
Relapses are often milder in severity than
the initial disease and can be treated with a
repeat course of the usual antibiotic regimen
Closing slide with picture of children
to elicit sympathy from the audience