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