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 names
Undulant fever Malta fever Gibraltar fever Mediterranean 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 H2S sensitivity 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 severe fever & acute monoarthritis (hip/knee),young child long 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 pain Osteomyelitis Septic Arthritis Minimal 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 epididymoorchitis 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

Laboratory

 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 Site Vertebrae Diskitis Body Canal compression Osteophyte Deformity Recovery Paravertebral abscess Psoas Abscess Lumbar Multiple,contigous Late Intact until late Rare Anterolateral Wedging uncommon Sclerosis Small well localized Rare Tuberculosis Dorso lumbar Contigous Early Morphology lost early common unusual Anterior wedging Variable Common,discrete loss,transverse process 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-streptomycinrifampin) than to doxycycline-rifampin.

Neurobrucellosis
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 trimethoprimsulfamethoxazole(TMP-SMX; 5 mg/kg of the

trimethoprim component twice daily) for four weeks

Thank you