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.
WBC usually normal to low (can see pancytopenia); minor LFT abnormalities are fairly common Routine Labs
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) Cultures
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 Serologic Testing
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