Brucellosis

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Brucellosis rabiezahran@gawab.com 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. rabiezahran@gawab.com

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Reservoir: Br. Melitensis → Goats , Sheep , camels. Most widespread Most virulent rabiezahran@gawab.com

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Br. Abortus → Cattle and camels . Reservoir: Less virulent rabiezahran@gawab.com

Br. Suis → Pig : 

Br. Suis → Pig Reservoir: Less virulent rabiezahran@gawab.com

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Br. Canis → Dogs Reservoir: Least common rabiezahran@gawab.com

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Sir David Bruce (1855-1931) British Army physician and microbiologist who discovered Micrococcus melitensis rabiezahran@gawab.com

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

Alice Evans (1881- 1975) : 

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

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Causative organism rabiezahran@gawab.com

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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. rabiezahran@gawab.com

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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 rabiezahran@gawab.com

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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: rabiezahran@gawab.com

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Brucella species — Colony Brucella suis cultur Brucella blood agar media Brucella, Mueller Hinton rabiezahran@gawab.com

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: rabiezahran@gawab.com

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

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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. rabiezahran@gawab.com

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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 !!!! rabiezahran@gawab.com

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

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Pathophysiology: rabiezahran@gawab.com

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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. rabiezahran@gawab.com

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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. rabiezahran@gawab.com

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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. rabiezahran@gawab.com

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. rabiezahran@gawab.com

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rabiezahran@gawab.com Brucellosis Case Definition

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rabiezahran@gawab.com 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)

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rabiezahran@gawab.com 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 . rabiezahran@gawab.com

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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. rabiezahran@gawab.com

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Pattern of fever in : Cyprus fever/ Gibraltar fever/ Malta fever/ Rock fever/ Undulant fever rabiezahran@gawab.com

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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. rabiezahran@gawab.com

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. rabiezahran@gawab.com

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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 rabiezahran@gawab.com

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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. rabiezahran@gawab.com

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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. rabiezahran@gawab.com

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 . rabiezahran@gawab.com

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Spondylitis of lumber spine 4 due to Brucellosis rabiezahran@gawab.com

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Spondylitis with para vertebral soft tissue mass due to Brucellosis rabiezahran@gawab.com

SACROILIITIS : 

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

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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. rabiezahran@gawab.com

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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. rabiezahran@gawab.com

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rabiezahran@gawab.com 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. rabiezahran@gawab.com

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Hepatic Granuloma due to Brucellosis rabiezahran@gawab.com

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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. rabiezahran@gawab.com

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Diagnosis rabiezahran@gawab.com

CLINICAL DIAGNOSIS : 

CLINICAL DIAGNOSIS rabiezahran@gawab.com

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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%. rabiezahran@gawab.com

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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. rabiezahran@gawab.com 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. rabiezahran@gawab.com

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 rabiezahran@gawab.com

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rabiezahran@gawab.com 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:

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rabiezahran@gawab.com 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:

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rabiezahran@gawab.com 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 rabiezahran@gawab.com

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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. rabiezahran@gawab.com

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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. rabiezahran@gawab.com

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. rabiezahran@gawab.com

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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. rabiezahran@gawab.com

Note : 

Note Uncomplicated patients are treated as outpatient . Except - children. - pregnant women . rabiezahran@gawab.com 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 rabiezahran@gawab.com

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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. rabiezahran@gawab.com

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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. rabiezahran@gawab.com

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Consultations Infectious disease specialist. Cardiothoracic surgery specialist if Endocarditis is suspected or documented rabiezahran@gawab.com

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Diet No special diet is required rabiezahran@gawab.com

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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%. rabiezahran@gawab.com

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

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Prevention rabiezahran@gawab.com

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 rabiezahran@gawab.com

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 . rabiezahran@gawab.com

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 rabiezahran@gawab.com

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 rabiezahran@gawab.com

References : 

References CDC. Web site Imbaba Fever Hospital web site MD consult web site Emedicine.com rabiezahran@gawab.com

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THANK YOU rabiezahran@gawab.com

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