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Brucellosis Dr.T.V.Rao MD Dr.T.V.Rao MD 1

Brucellosis an Important Zoonotic Disease :

Brucellosis an Important Zoonotic Disease Dr.T.V.Rao MD 2


Brucellosis, Brucellosis, also called Bang's disease, Crimean fever, Gibraltar fever, Malta fever, Maltese fever, Mediterranean fever, rock fever, or undulant fever, is a highly contagious zoonosis caused by ingestion of unsterilized milk or meat from infected animals or close contact with their secretions. Dr.T.V.Rao MD 3

Brucellosis :

Brucellosis 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 . Dr.T.V.Rao MD 4


Zoonosis Brucellosis : Disease of domestic and wild animals (zoonosis): Transmittable to humans. It has different non-specific symptoms and signs “ 1886, Bruce isolated Brucella Melitensis from spleens of malta fever victims. Dr.T.V.Rao MD 5

Brucellosis in humans :

Brucellosis in humans Brucellosis in humans is usually associated with the consumption of unpasteurized milk and soft cheeses made from the milk of infected animals, primarily goats, infected with Brucella melitensis and with occupational exposure of laboratory workers, veterinarians, and slaughterhouse workers. Dr.T.V.Rao MD 6

Major Transmission of Brucellosis :

Major Transmission of Brucellosis Dr.T.V.Rao MD 7

Other names for Brucellosis :

Other names for Brucellosis Undulant fever Malta fever Gibraltar fever Mediterranean fever . Dr.T.V.Rao MD 8


Bacteriology Gm - ve cocci, coccobacilli, bacilli. Strict aerobic, nonmotile, nonspore forming. B. ovis, B. abortus --CO2 supplementation. Grow in regular media -- prolonged incubation > 4 weeks. Dr.T.V.Rao MD 9

Characteristics of Bacteria :

Characteristics of Bacteria 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 . Dr.T.V.Rao MD 10

Identification of Bacteria :

Identification of Bacteria 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 antiser a Dr.T.V.Rao MD 11

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Brucella melitensis*:

Brucella melitensis* Principal hosts - goats and sheep Most pathogenic in humans Sporadic cases in humans in the U.S. occur related to consumption of unpasteurized dairy products from countries where the disease is present. Dr.T.V.Rao MD 13

Brucella abortus:

Brucella abortus Principal host - cattle Eradication of B. abortus from cattle is nearly complete in the U.S., but the disease still occurs in some wild bison and elk herds in the western U.S. Dr.T.V.Rao MD 14

Brucella suis:

Brucella suis Principal host - swine Since B. suis is normally found in pigs, wild hog (feral swine) hunters are at risk of becoming infected when they field dress infected pigs. Dr.T.V.Rao MD 15

Brucella canis:

Brucella canis Principal host - dog Individuals who are in close contact with dogs, or breeders/veterinary staff who assist with birthing are at risk of becoming infected. CDC does not currently perform serological testing for Brucella canis Dr.T.V.Rao MD 16


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. 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 . Dr.T.V.Rao MD 17

Methods of transmission:

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 Dr.T.V.Rao MD 18

Incubation period:

Incubation period Acute or sub acute disease follows an incubation period which can vary from 1 week to 6 or more months . In most patients for whom the time of exposure can be identified, the incubation period is between 2 and 6 weeks The length of the incubation period may be influenced by many factors virulence of the infecting strain size of the inoculum route of infection resistance of the host Dr.T.V.Rao MD 19

Portals of entry:

Portals of entry Oral entry - most common route Ingestion of contaminated animal products (often raw milk or its derivatives) contact with contaminated fingers Aerosols Inhalation of bacteria Contamination of the conjunctivae Percutaneous infection through skin abrasions or by accidental inoculation Dr.T.V.Rao MD 20

Clinical Manifestation:

Clinical Manifestation Fever Night sweats Malaise Anorexia Arthralgia Fatigue Weight loss Depression . Dr.T.V.Rao MD 21

Clinical Manifestations:

Clinical Manifestations The presentation of brucellosis is characteristically variable The onset may be insidious or abrupt Influenza-like with fever reaching 38 to 40 o C Limb and back pains are unusually severe, night sweating and fatigue are marked. Anorexia, weakness, severe fatigue and loss of weight, depression Headache The leukocyte count tends to be normal or reduced, with a relative lymphocytosis Relative leukopenia On physical examination, splenomegaly may be the only finding. Dr.T.V.Rao MD 22

Clinical features :

Clinical features 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 Dr.T.V.Rao MD 23

Physical Examination:

Physical Examination Physical manifestations may be absent. If present, Focal Features: Musculoskeletal pain Osteomyelitis Septic Arthritis Minimal lymphadenopathy Hepatosplenomegaly occasionally . Dr.T.V.Rao MD 24

Systemic Infections with Brucellosis :

Systemic Infections with Brucellosis 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 Dr.T.V.Rao MD 25

Complications and Brucella :

Complications and Brucella 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 Dr.T.V.Rao MD 26

Differential Diagnosis:

Differential Diagnosis Tuberculosis Toxoplasmosis CMV HIV infection Dr.T.V.Rao MD 27

Chronic Brucellosis :

Chronic Brucellosis Patients with undiagnosed and untreated brucellosis can be symptomatic for months. In addition, previously treated patients may present with relapsed infection. Dr.T.V.Rao MD 28

Chronic Brucellosis :

Chronic Brucellosis The presence of granulomatous hepatitis, hepatic micro abscesses, bone marrow granulomas, and/or hemophagocytosis should prompt further diagnostic evaluation for brucellosis. Relapse — About 10 percent of patients relapse after therapy Dr.T.V.Rao MD 29


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 Dr.T.V.Rao MD 30

Laboratory Diagnosis:

Laboratory Diagnosis Dr.T.V.Rao MD 31

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Investigations :

Investigations Total counts-Normal/reduced Thrombocytopenia ESR/CRP-Normal/Increased CSF/Body fluid analysis-Lymphocytosis, low glucose levels, elevated ADA Biopsied samples of lymph node, liver-non caveating granuloma without acid fast bacilli. Dr.T.V.Rao MD 33

Serological Tests:

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 Dr.T.V.Rao MD 34

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Serology Main laboratory method of diagnosis Serum agglutination test - most widely used measures agglutination for IgG, IgM, IgA 2ME - break sulf-hydrile bonds in IgM polymer - no agglutination which level is diagnostic ?? 1 : 160 - non endemic area 1 : 320 - endemic area SAT - false negative Prozone Blocking antibodies Other tests : coombs, ELISA, CFT, FTA Dr.T.V.Rao MD 35

Serum agglutination:

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. Dr.T.V.Rao MD 36


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 Dr.T.V.Rao MD 37

PCR an Emerging Tool:

PCR an Emerging Tool 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 Dr.T.V.Rao MD 38


Imaging Patients with spine symptoms MRI examination to rule out spinal cord compromise. Plain radiographs, radionuclide bone scintigraphy, CT scanning, and joint sonography . Dr.T.V.Rao MD 39

Radiology of Spine can differentiate Tuberculosis from Brucellosis:

Radiology of Spine can differentiate Tuberculosis from Brucellosis Dr.T.V.Rao MD 40


Management The World Health Organization recommends the following for adults and children older than 8 years : Doxycycline 100 mg PO bid and rifampin 600-900 mg/d PO : Both drugs are to be given for 6 weeks (more convenient but probably increases the risk of relapse). Doxycycline 100 mg PO bid for 6 weeks and streptomycin 1 g/d IM daily for 2-3 weeks: This regimen is believed to be more effective, mainly in preventing relapse. Dr.T.V.Rao MD 41


Treatment Drugs against Brucella Tetracycline's Aminoglycosides Streptomycin since 1947 Gentamicin Netilmicin Rifampicin Quinolones - ciprofloxacin ?3rd generation cephalosporins Dr.T.V.Rao MD 42


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 Dr.T.V.Rao MD 43


Treatment Regimen B: Doxycycline 100 mg orally twice daily plus rifampin 600 to 900 mg (15 mg/kg) orally once daily for six weeks . Dr.T.V.Rao MD 44

Focal Disease:

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. Dr.T.V.Rao MD 45

Indications for Surgery:

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 Dr.T.V.Rao MD 46

Need for Surgery :

Need for Surgery Resection of mycotic aneurysms Procurement of tissue for diagnostic purposes Chronic hepatosplenic suppurative brucellosis may require surgery in addition to antibiotics to achieve cure Dr.T.V.Rao MD 47

Osteoarticular Disease:

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. Dr.T.V.Rao MD 48


Neurobrucellosis Doxycycline, Rifampin Trimethoprim-Sulphmethoxazole . The duration of therapy is generally prolonged individualized according to clinical signs and symptoms Continued until cerebrospinal fluid parameters have returned to normal Dr.T.V.Rao MD 49


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-Sulphmethoxazole . Dr.T.V.Rao MD 50

Needs longer duration of Treatment :

Needs longer duration of Treatment 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 Dr.T.V.Rao MD 51


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. Dr.T.V.Rao MD 52

Pregnancy and Brucellosis :

Pregnancy and Brucellosis Premature labor and fetal wastage Rifampin — 900 mg once daily for six weeks Rifampin — 900 mg once daily plus trimethoprim-Sulphmethoxazole(TMP-SMX; 5 mg/kg of the trimethoprim component twice daily) for four weeks Dr.T.V.Rao MD 53


Prevention Control of disease in domestic animals immunization using B. abortus strain 19 and B. melitensis strain Rev 1 Routine pasteurization of milk In labs strict biosafety precautions Dr.T.V.Rao MD 54

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