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Brucellosis By Dr : Rabie Fahmy Zahran. Tropical M. Consultant. Damietta Fever Hospital. Egypt.

Brucellosis. : 

Brucellosis. * Common classical zoonotic disease of worldwide distribution . * The genus Brucella consists of 7 species, four of which cause human brucellosis.

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Reservoir: Br. Melitensis → Goats , Sheep , camels. Most widespread Most virulent

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Br. Abortus → Cattle and camels . Reservoir: Less virulent

Br. Suis → Pig : 

Br. Suis → Pig Reservoir: Less virulent

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Br. Canis → Dogs Reservoir: Least common

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Sir David Bruce (1855-1931) British Army physician and microbiologist who discovered Micrococcus melitensis

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Bernhard Bang (1848-1932) Danish physician and veterinarian discovered Bacterium abortus could infect cattle, horses, sheep and goats

Alice Evans (1881- 1975) : 

Alice Evans (1881- 1975) American bacteriologist noted resemblance between B. melitensis & B. abortus 1918

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Causative organism

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Causative organism: Brucella sp. * small (0.4-0.8 ×0.5-1.5μm), * non motile. * non capsulated, * non spore forming , * gram –ve coccobacilli. * Aerobic , * facultative intracellular bacteria.

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Causative organism: * the nutritional requirements of the organism are complex. * All strains grow best in a medium enrich with animal serum and glucose& 5-10% carbon dioxide G-ve coccobacellus

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Biochemistry Oxidase + Nonfermentative Urease +\catalase + H2S produced by B. abortus and B. suis Speciated based on the ability to grow in the presence of the dyes basic fuchsin and thionine Causative organism:

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Brucella species — Colony Brucella suis cultur Brucella blood agar media Brucella, Mueller Hinton

Antigenic Structure and classification : 

Antigenic Structure and classification Two main antigen: A and M The three main Brucella differ from one another in the amount of the two main antigen they have in common : B.abortus : A:M=20:1 B.melitensis : A:M=1:20 B.suis : A:M=2:1 Causative organism:

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B. melitensis has the highest concentration of M and causes the most serious infections. Virulence factors Endotxin. Causative organism:

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Clinical significance: “The organism has a tropism for erythritol “ Animal fetal tissues and placenta, other than those in humans are rich in erythritol and therefore, the organisms often cause abortions in these animals.

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Causative organism: *Bacteria is excreted in : =genital secretions (including semen) =milk, =colostrum. * Survival time: Cheese at 4oC: 180 days !!! Water at 25oC: 50 days. Meat and salted meat: 65 days. Manure at 12oC: 250 days !!!!

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Killed by: * boiling, * pasteurization, * lactic acid, * strong salts. Not killed by freezing. Causative organism:

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Patho-physiology: * This bacterium has a unique ability of invading both phagocytic and non-phagocytic cells. * surviving in the intracellular environment by avoiding the immune system in different ways. * This is why brucellosis is a systemic disease and can involve almost every organ system.

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* After ingestion by the phagocyte, about 15- 30% of the organisms survive . Patho-physiology: * After replication in the endoplasmic reticulum, the brucellae are released with the help of hemolysins and induced cell necrosis. Susceptibility to intracellular killing differs among species, with B abortus readily killed and B melitensis rarely affected; this might explain the differences in patho-genicity and clinical manifestations in human infections.

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- Orally by ingestion of untreated milk & its products ,raw meat ,liver ,spleen & bone marrow [main route in non endemic areas] Mode of transmission - Skin , direct contact of abraded or intact skin with infected meat or animals common in veterinaries & slaughter men - Inhalation through direct contact with animals &pollution of the atmosphere in endemic areas mainly children , farm workers & lab. workers.

Mode of transmission : 

Mode of transmission -Conjunctiva, accidental splashing during animal vaccination with live attenuated vaccine. - Uncommon routes include blood transfusion& bone m.transpl. - Unproved routes, trnsplacental,sexual&breast milk feeding.

Slide 28: Brucellosis Case Definition

Slide 29: Probable case : a clinically compatible case that is epidemiologically linked to a confirmed case or that has supportive serology (i.e., Brucella agglutination titer of greater than or equal to 160 in one or more serum specimens obtained after onset of symptoms)

Slide 30: Confirmed case: a clinically compatible case that is laboratory confirmed

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Onset : may be sudden [1-2days] or gradual [1 week or more] It presents as febrile illness with or without localization. Divided into acute, chronic &with complications Clinical picture I.P: 1-3 weeks , may extend to several months. It may resemble other febrile illness [non specific] May be short and trivial without sequelae .

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Acute Brucellosis: Symptoms: Fever, Rigors, Sweating ,Headache & generalized body aches specially low backache. Less common, chest pain , abdominal pain, palpitation, constipation , confusion & night mares.

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Pattern of fever in : Cyprus fever/ Gibraltar fever/ Malta fever/ Rock fever/ Undulant fever

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Signs: May be lacking . Temp. is always high. Hepato-splenomegaly {Splenomegaly reflects severe infection] Lymphadenopathy , specially in Br. Abortus . Tender spines. Spondyolitis , bursitis, Osteomyelitis, epidydemo-orchitis , meningo -encephalitis & endocarditis may occur specially in Br. Meltensis . Rarely, erythematous rash or erythema nodosum may occur.

Signs(cont) : 

Signs(cont) Lassitude may be present and may continue after successful ttt . Full recovery is likely, in spite of the severity, by proper therapy. Relapse may occurs after ttt. precipitated by new infection, trauma, surgery or stress.

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N= 930, unless specified in ( ). * Anorexia, asthenia, fatigue, weakness, malaise ** Abdominal pain, constipation, diarrhea, vomiting *** Anxiety, confusional psychosis, depression, insomnia **** Paralysis, nuchal rigidity, papilledema

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Signs: Temp. may be normal. Patient may looks normal, or his appearance may reflect a serious disease . Moderate Splenomegaly may be in the minority of cases ,about 4 fingers, not reflecting the severity of infection & may persist after treatment. Chronic brucellosis: Symptoms: Onset is insidious ,Commonly there is a story of recurrent flu with lassitude ,headache , pain & sweat. Law backache is common. Long standing infection leads to depression.

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1 :Skeletal system (bones & joint) Occurs in about 10% of cases. a- Arthritis: - Reactive: mainly due to synovitis, tenosynovitis or bursitis. -Septic: either blood born or extension from osteomyelitis. Bruclla with Complications: Complications may occur with acute or chronic &may be the presentation.

Complications(con): : 

Complications(con): b- Spondyolitis : Average. age is 40 yrs, rare in children. May affect single or mult.sites,L4 is the common site. c- Osteomyelitis : Rare, affecting long bones femur, tibia, humrus .

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Spondylitis of lumber spine 4 due to Brucellosis

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Spondylitis with para vertebral soft tissue mass due to Brucellosis


SACROILIITIS In patients with sacroiliitis, the most commonly observed abnormalities are blurring of articular margins and widening of the sacroiliac spaces.

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2- Cardiovascular: Endocarditis , myocarditis , pericarditis, aortic root abscess, mycotic aneurysm & thrombophlibitis . 3-Neurobrucellosis: Uncommon but serious. Meningitis, meningoencphalitis. ,multiple cerebral or cerebellar abssces. ,rupture mycotic aneurysm, cranial n. lesions, Transient E.A. , hemiplegia, myelitis.

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4- Genitourinary: May be the presenting feature, include unilat.or bilat. epididymo-orchitis in children, prostatitis &seminal vesiculitis in adult males. Dysmeno.,ameno. Tubo-ovarian abscess,chronic.salpingitis & cervasitis in females. Acute nephritis , Acute pyelonephritis like features , renal calcification. renal abscess , cystitis & posterior urithritis may occur. Urine culture is +ve in about 50% of cases.

Slide 46: Epididymoorchitis clinical By ultrasound

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5-Respiratory: Common but usually mild. Rarely , hailer & paratracheal lymphadenopathy , pneumonia, lung abscess, solitary or multiple Shadows , pleural eff., empyema & mediastinitis may occur . 6-G.Intestinal: Usually mild ,rarely a presenting feature. hepatitis with mild jaundice. liver & splenic abscesses are rare. liver transam, alk. phos.,& bilirubin may be slightly raised.

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Hepatic Granuloma due to Brucellosis

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7- Ocular: Conjunctivitis [accidental], keratitis, ….. 8-Skin: Uncommon, cotact dermatitis & maculop . eruptions, erythema nodosum, purpura , 9-In pregnancy: In endemic areas, the outcome like in animals, normal deliv., abor., I.U.F. death, premat.deliv., ret.of placenta may occur 10-Other rare complications: Thyroiditis , adrenal insuff. may occur.

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Diagnosis: Depends on the presence of clinical features + +ve blood or tissue culture and/or detection of raised brucella agglutinins in the blood. Culture: +ve in about 50 -70% of cases . Bone marrow culture is thought to be the criterion standard, since the reticuloendothelial system holds a high concentration of the organism. Sensitivity is usually 80-90%.

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Standard aggl. Test: A titer of : 1/160 in non endemic areas 1/320 in endemic areas are significant. - False +ve in Tularaemia, cholera & E-Coli infection. -False –ve in prozone phenom. Diagnosis:

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Diagnosis: Prozone phenomenon may occur secondarily to hyperantigenemia, which might result in a false-negative results, so routine dilution of the serum beyond 1:320 would help to prevent such a problem.

Diagnosis: : 

Diagnosis: 2-ME-test(mercaptoethanol): more specific +ve. in chronic Br. Compl. fixation t., Radio-I-Assay,Coombs t., ELISA t.: -High IgM in acute infection. - High IgG in chronic infection. Blood picture: Non sp., but exclude pyogenic inf. &T.B.(leucopenia, relative lymphocytosis, pancytopenia [in up to 20% of cases]). CSF& Synovial fl. analysis , X-Ray, CT scan ,MRI , in complications

Slide 56: CSF evaluation in patients with neurobrucellosis reveals: * mild-to-modest lymphocytic pleocytosis in 88-98% of cases. *Protein levels are elevated. *normal glucose levels. Diagnosis:

Slide 57: Polymerase chain reaction (PCR) testing for brucellae is a recent advance with promising potential. It would allow for rapid and accurate diagnosis of infection with Brucella species Diagnosis:

Slide 58: Differential Diagnosis : Anklosing SpodiolitisCryptococcosis Hepatitis, Viral Histoplasmosis Infectious Mononucleosis Infective Endocarditis Influenza Leptospirosis Malaria TB. TB of the Genitourinary System Typhoid Fever Other Problems to be Considered: *Collagen vascular disease*Chronic fatigue syndrome

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Treatment. The optimum antibiotic therapy is still disputed . Different regimes . the most suitable is: A: Adult without complications: A course of 2-3 months is required. 1st Month: - Doxycycline orally 100 mg / 12 h. + - Streptomycin inj. 1 gm IM. daily for patients less than 45 y. in older 0.5 – 0.75 gm.(advised For 2-3 weeks only). 2nd-3rd Month: - Doxycycline orally 100 mg / 12 h. + - Rifampicin orally 600-900 mg / day.

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B: Children without complications: A course of 2-3 months of: - Rifampicin 10-20 mg/kgm b.wt.orally or i.v. - Co-Trimoxazole * Infants →6 months:8-10 mgm/kg oral or i.v. in 2 devided doses. * children under 40 kgm: 8 mgm /kg. /12 h. In serious infection , in endemic areas we can use Doxy. & Gentamicin or netilmicin. Treatment.

Treatment. : 

Treatment. C: Pregnancy : A course of 2-3 months of: Rifampicin + Co-Trimoxazole. N.B: streptomycin can be substituted with: - Netilmicin 4-6 mg / kg . /12 h. - Gentamycin 2-5 mg/kg .i.m. or inf. 3 dos.

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D : Endocarditis: 2-3 months of triple therapy. Aminoglycoside + Rifampicin + Doxycycline E : Meningitis: 2-3 months of triple therapy. Rifampicin must be used all the time . F : Renal impairment: 2-3 months of: Doxycycline + Rifampicin or Co-Trimoxazole. Treatment.

Note : 

Note Uncomplicated patients are treated as outpatient . Except - children. - pregnant women . Treatment.

Treatment. : 

Treatment. G :Hepatic patient : Compensated cirrhosis : *Fluorinated quinolones can be used in its normal dose for 6-8 ws. With monitoring of liver function. *Azithromycine in its normal daily dose for 6 days /then 6days rest/for 6-8 ws

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W.H.O. Recommendations: * Adult uncompl. Acute infection: Doxy. +Rifam. for at least 6 wks. *Complicated cases: Aminogl. + Doxy. + Rifam. *Children & in pregnancy: Rifam. + Co-Trimoxazole.

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Quinolone Therapy in Brucellosis: Ciprofloxacine in a dose of 750 mg 3 times daily for 1 month can be used . Not advised because of: High relapse, high resistance rates & cross resistance with other quinolones. It is kept for failure of other regeems or in cases of contraindication to drugs in the previous regimes.

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Consultations Infectious disease specialist. Cardiothoracic surgery specialist if Endocarditis is suspected or documented

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Diet No special diet is required

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Prognosis This disease is easily curable with a low risk of relapse or chronicity . The prognosis is poor in persons who present with congestive heart failure due to Endocarditis, with a mortality rate approaching 85%.

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Patient Education: Stress the importance of patient medical compliance to prevent persistent disease and clinical relapse.

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Strategies to Fight Brucella : 

Strategies to Fight Brucella Collaboration among laboratory, field and public health services Control the infection Test and slaughter method Quarantine Depopulation Vaccination Programme

Control the infection : 

Control the infection Source of Infection. Transmission of infection. Movement of animals. Natural service by bulls. Transmission by carnivores animals and through milk .

Test and slaughter method : 

Test and slaughter method No effective treatment, so diagnose, if +ve kill the animals until no reactor animal for three consecutive tests, carried out at three-month interval is found (Mathur et. al., 1974) Various diagnostic test, for untagged animal best test is SDTH test (Bercovich et al., 1992) Financial compensation to farmers

Vaccination Programme : 

Vaccination Programme Increases resistance and decreases the source of infection Different vaccine against the B. abortus are Live B. abortus Strain-19 vaccine Killed adjuvant B. abortus 45/20 vaccine B. abortus vaccine RB51 Make calfhood vaccination compulsory and avoid vaccination of adult animals

References : 

References CDC. Web site Imbaba Fever Hospital web site MD consult web site

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