By Dr.Sujith

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 namesUndulant 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 blueuse 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 transmissionDirect 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 Period1 week to several months

Clinical ManifestationFeverNight sweatsMalaiseAnorexiaArthralgia FatigueWeight lossDepression.

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 areaOccupationConsumption of unpasteurized milk

Physical ExaminationPhysical 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 percentOther 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

DifferentialsTuberculosisToxoplasmosisCMVHIV 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

RelapseAbout 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

Laboratory

Total counts-Normal/reducedThrombocytopeniaESR/CRP-Normal/IncreasedCSF/Body fluid analysis-Lymphocytosis,low

glucoce levels,elevated ADABiopsied samples of lymph node,liver-non

caseating granuloma without acid fast bacilli.

CulturesPolymerase 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 TestsMost 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 agglutinationIt 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.

ELISAELISA 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 fluidIn 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.

ImagingPatients with spine symptoms MRI

examination to rule out spinal cord compromise.

Plain radiographs, radionuclide bone scintigraphy, CT scanning, and joint sonography.

Radiology of SpineBrucellosis Tuberculosis

Site Lumbar Dorso lumbarVertebrae Multiple,contigous ContigousDiskitis Late EarlyBody Intact until late Morphology lost earlyCanal compression Rare commonOsteophyte Anterolateral unusualDeformity Wedging uncommon Anterior wedgingRecovery Sclerosis VariableParavertebral 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.

TreatmentAntibiotic 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 DiseasePatients 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 SurgeryEndocarditis where valve replacement or

valve debridement is required Drainage or excision of abscesses,

especially those that have not responded to antimicrobials

Spinal epidural abscessRemoval of infected foreign bodies, eg,

pacemaker wires, prosthetic joints

Resection of mycotic aneurysmsProcurement of tissue for diagnostic

purposesChronic hepatosplenic suppurative

brucellosis may require surgery in addition to antibiotics to achieve cure

Osteoarticular DiseasePatients with Brucella spondylitis appear

to respond better to doxycycline-streptomycin or a three-drug regimen (doxycycline-streptomycin-rifampin) than to doxycycline-rifampin.

NeurobrucellosisDoxycycline, RifampinTrimethoprim-sulfamethoxazole . The duration of therapy is generally

prolonged individualized according to clinical signs and symptoms

Continued until cerebrospinal fluid parameters have returned to normal

EndocarditisAntimicrobial 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

RelapseRelapse 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.

PregnancyPremature 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

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