Brucellosis is a zoonotic infection transmitted to humans contact with fluids from infected animals (sheep, cattle, goats, pigs, or other animals) derived food products such as unpasteurized milk and cheese . The disease is rarely, if ever, transmitted between humans.
Other names Undulant fever Malta feverGibraltar feverMediterranean fever.
Brucella spp are small gram-negative aerobic coccobacilli lacking a capsule, flagella, endospores, or native plasmids. Oxidase and catalase tests are positive for most members of the genus Brucella. Some species require CO2 enrichment for primary isolation in the laboratory.
Other methods for the identification and speciation of Brucella include: production of urease and H2Ssensitivity to dyes, basic fuchsin, thionin, and thionin blue use of specific antisera
Epidemiology Brucellosis occurs worldwide; major endemic areas include countries of the Mediterranean basin, Arabian Gulf, the Indian subcontinent, and parts of Mexico, Central and South America Human Infection:B. melitensis is the species that infects humans most frequently. The incubation period ranges from a few days to a few months. The disease is manifested as fever accompanied by a wide array of other symptoms.
Methods of transmission Direct inoculation through cuts and skin abrasions from handling animal carcasses, placentas, or contact with animal vaginal secretions Direct conjunctival inoculation Inhalation of infectious aerosols Ingestion of contaminated food such as raw milk, cheese made from unpasteurized (raw) milk, or raw meat Venereal transmission has been suggested, but the data are not conclusive
Incubation Period 1 week to several months
Clinical Manifestation Fever Night sweats Malaise Anorexia Arthralgia Fatigue Weight loss Depression.
Patients may have a multitude of complaints without objective findings except fever.
Often fits one of the three pattern:febrile illness resembling typhoid,less severefever & acute monoarthritis (hip/knee),young childlong lasting fever,LBA,hip pain,older man Travel to an endemic area Occupation Consumption of unpasteurized milk
Physical Examination Physical manifestations may be absent. If present,Focal Features:Musculoskeletal painOsteomyelitisSeptic ArthritisMinimal lymphadenopathy Hepatosplenomegaly ocacsionally.
Osteoarticular disease, especially sacroileitis — 20 to 30 percent and vertebral spondylitis. Large joints are affected most commonly in children Genitourinary disease, especially epididymo- orchitis — 2 to 40 percent of males Neurobrucellosis, usually presenting as meningitis — 1 to 2 percent. Less common neurologic complications include papilledema, optic neuropathy, radiculopathy, stroke, and intracerebral hemorrhage
Endocarditis — 1 percent.Most cases of endocarditis are left-sided, and about two-thirds occur on previously damaged valves. Hepatic abscess — 1 percent Other less common complications include pneumonitis, pleural effusion, empyema,, or abscess involving the spleen, thyroid, or epidural space, uveitis. A few cases of Brucella infection involving prosthetic devices such as pacemaker wires and prosthetic joints have been reported
Differentials Tuberculosis Toxoplasmosis CMV HIV infection
Patients with undiagnosed and untreated brucellosis can be symptomatic for months. In addition, previously treated patients may present with relapsed infection.
The presence of granulomatous hepatitis, hepatic microabscesses, bone marrow granulomas, and/or hemophagocytosis should prompt further diagnostic evaluation for brucellosis. Relapse — About 10 percent of patients relapse after therapy
Relapse About 10 percent of patients relapse after therapy. Most relapses occur within three months following therapy and almost all occur within six months. Risk factors for relapse include inadequate initial therapy, duration of the initial illness of less than 10 days, male sex, bacteremia, and thrombocytopenia
Total counts-Normal/reduced Thrombocytopenia ESR/CRP-Normal/Increased CSF/Body fluid analysis-Lymphocytosis,low glucoce levels,elevated ADA Biopsied samples of lymph node,liver-non caseating granuloma without acid fast bacilli.
Cultures Polymerase chain reaction (PCR) shows promise for rapid diagnosis of Brucella spp in human blood specimens Positive PCR at the completion of treatment is not predictive of subsequent relapse PCR testing for fluid and tissue samples other than blood has also been described
Serological Tests Most serological studies for diagnosis of Brucellosis are based on antibody detection These include: Serum agglutination (standard tube agglutination) ELISA Rose Bengal agglutination Complement fixation Indirect Coombs Immunecapture-agglutination (Brucellacapt
Serum agglutination It is generally agreed that a titer of >1:160 in the presence of a compatible illness supports the diagnosis of brucellosis. Demonstration of a fourfold or greater increase or decrease in agglutinating antibodies over 4 to 12 weeks provides even stronger evidence for the diagnosis.
ELISA ELISA is probably the second most common serologic method. The sensitivity of the ELISA was 100 percent when compared with blood culture but only 44 percent compared with serologic tests other than ELISA The Specificity was >99 percent. In a study including 75 patients with brucellosis, five patients with positive ELISA had a negative tube agglutination test
Synovial fluid In the setting of Brucella arthritis, the synovial fluid white blood cell count does not generally exceed 15,000 cells/microL.
In brucellosis, lymphocytes frequently predominate (in contrast to septic arthritis due to other bacteria, in which polymorphonuclear leukocytes frequently predominate.
Imaging Patients with spine symptoms MRI examination to rule out spinal cord compromise. Plain radiographs, radionuclide bone scintigraphy, CT scanning, and joint sonography.
Radiology of Spine Brucellosis Tuberculosis Site Lumbar Dorso lumbar Vertebrae Multiple,contigous Contigous Diskitis Late Early Body Intact until late Morphology lost early Canal compression Rare common Osteophyte Anterolateral unusual Deformity Wedging uncommon Anterior wedging Recovery Sclerosis Variable Paravertebral abscess Small well localized Common,discrete loss,transverse process Psoas Abscess Rare More likely
Localized snowflake calcification in chronic hepatosplenic brucellosis only specific radiographic finding.
Treatment Antibiotic Therapy There are two major regimens:Regimen A: Doxycycline 100 mg orally twice daily for 6 weeks + Streptomycin 1 gram intramuscularly once daily for the first 14 to 21 days
Regimen B: Doxycycline 100 mg orally twice daily plus rifampin 600 to 900 mg (15 mg/kg) orally once daily for six weeks.
Focal Disease Patients with focal disease have a less favorable prognosis. In a study of 530 patients (including 170 patients with focal disease); those with focal disease had a greater likelihood of therapeutic failure, relapse, or death.
Indications for Surgery Endocarditis where valve replacement or valve debridement is required Drainage or excision of abscesses, especially those that have not responded to antimicrobials Spinal epidural abscess Removal of infected foreign bodies, eg, pacemaker wires, prosthetic joints
Resection of mycotic aneurysms Procurement of tissue for diagnostic purposes Chronic hepatosplenic suppurative brucellosis may require surgery in addition to antibiotics to achieve cure
Osteoarticular Disease Patients with Brucella spondylitis appear to respond better to doxycycline-streptomycin or a three-drug regimen (doxycycline-streptomycin- rifampin) than to doxycycline-rifampin.
Neurobrucel osis Doxycycline, Rifampin Trimethoprim-sulfamethoxazole . The duration of therapy is generally prolonged individualized according to clinical signs and symptoms Continued until cerebrospinal fluid parameters have returned to normal
Endocarditis Antimicrobial therapy alone may be attempted absence of heart failure, valvular destruction, abscess, or a prosthetic valve. A combination of three or four antimicrobials, eg, a tetracycline, rifampin, and an aminoglycoside plus or minus trimethoprim-sulfamethoxazole.
Therapy is usually given for six weeks to six months. The aminoglycoside component is usually administered for two to four weeks in an effort to avoid toxicity
Relapse Relapse should prompt assessment for a focal lesion, especially hepatosplenic abscess Most relapses can be treated successfully with a repeat course of a standard regimen. Should resistance or a second or third relapse occur, an alternative regimen should be devised.
Pregnancy Premature labor and fetal wastage Rifampin — 900 mg once daily for six weeks Rifampin — 900 mg once daily plus trimethoprim- sulfamethoxazole(TMP-SMX; 5 mg/kg of the trimethoprim component twice daily) for four weeks