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BRUCELLOSIS

BRUCELLOSIS. Dr. Indumathi Consultant Microbiologist Gokula Metropolis Clinical Laboratory. GRAM NEGATIVE COCCOBACILLI (PARVO BACTERIA). BORDETELLA, BRUCELLA, YERSENIA, PASTEURELLA, FRANCESELLA HAEMOPHILUS, MORAXELLA, GARDENERELLA HACEK. Historical Background. Malta Fever

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BRUCELLOSIS

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  1. BRUCELLOSIS Dr. Indumathi Consultant Microbiologist Gokula Metropolis Clinical Laboratory

  2. GRAM NEGATIVE COCCOBACILLI(PARVO BACTERIA) • BORDETELLA, BRUCELLA, YERSENIA, PASTEURELLA, FRANCESELLA • HAEMOPHILUS, MORAXELLA, GARDENERELLA • HACEK

  3. Historical Background • Malta Fever • Major health problem to British troops in Malta in the 19th and early 20th centuries.

  4. HISTORICAL BACKGROUND • MEDITERRANEAN FEVER • UNDULANT FEVER • MALTA FEVER

  5. Historical Background • 1860 J.A. Maraston; assistant surgeon in the British Army in Malta -- first accurate description “Mediterranian Gastric Remittent Fever” • David Bruce (1855-1931) -1883 sent to Malta to provide medical care to the troops. - 1887 isolated “micrococcus” from spleens of 4 soldiers died of the disease.

  6. Historical Background What is the source? “Mediterranean Fever Commission” 1904

  7. Historical Background • 1905 ZAMMIT;MALTESE PHYSICIAN - GOATS: SOURCE OF INFECTION. : GOATS’ MILK • 1897 E. BANG;DANISH VETERINARIAN -INTRACELULAR PATHOGEN CAUSING ABORTION IN CATTLE NAMED “BACILLUS ABORTUS”. • 1918 A.EVANS;AMERICAN MICROBIOLOGIST BACILLUS ABORTUS AND MICROCOCCUS MELITENSIS & NAMED IT BACTERIACEAE.

  8. Historical Background • 1920 Meyer and Shaw suggested BRUCELLA • 1914 Mohler isolated organism from liver & spleen of Pigs--B.suis. • 1957 B. neotome, 1963 B. ovis, 1966 B. canis

  9. Epidemiology • Worldwide zoonosis • Only 17 countries declared brucellosis free1986 • Six species 1. B.abortus - mainly cattle 2. B.melitensis - sheeps & goats 3. B.suis - pigs 4. B. canis - dogs 5. B. ovis - sheep (not human pathogen) 6. B. neotomae - desert wood rat (not human pathogen) • B. melitensis -- most common worldwide

  10. Epidemiology • ENDEMIC DISEASE :Saudi Arabia, Iran, Iraq • MOSTLY B. MELITENSIS & B. ABORTUS. • NO CLEAR FIGURES ABOUT INCIDENCE & PREVALENCE. • INCIDENCE : 5.4 PER 1000 PER YEAR. • PREVALENCE : 8.6 - 38 % - SOME REGIONS.

  11. Bacteriology • GRAM NEGATIVE COCCI, COCCOBACILLI, • STRICT AEROBIC, NONMOTILE, NONSPORE FORMING. • 3 SPECIES: • B.MELITENSIS : GOATS • B.ABORTUS : CATTLE • B.SUIS : PIGS

  12. BACTERIOLOGY • FACULTATIVE INTRACELLULAR • STRICT AEROBES/FASTIDIOUS • 5-10% CARBONDIOXIDE : FOR B.ABORTUS • SLOW GROWTH ON ORDINARY MEDIA • ENRICHED MEDIUM : GLUCOSE/SERUM/ • TRYPTICASE SOY BROTH/AGAR

  13. BIOCHEMICAL REACTIONS • NO FERMENTATION OF SUGARS • OXIDATIVE • OXIDASE AND UREASE POSITIVE • IMVIC : ----

  14. SPECIES DIFFERENTIATION

  15. Transmission • ZOONOSIS AFFECTING DOMESTIC ANIMALS. • CONCENTRATED IN MILK, URINE, GENITAL ORGANS. ROUTES OF TRANSMISSION • ORAL: UNPASTEURISED MILK & PRODUCTS RAW MILK OR MEET. • RESPIRATORY: LAB WORKERS. • SKIN: ACCIDENTAL PENETRATION OR ABRASION • - AT RISK FARMERS & VETERINARIANS. • OTHER ROUTES: CONJUNCTIVAL, BLOOD TRANSFUSION, TRANSPLACENTAL, ? PERSON TO PERSON.

  16. Pathogenesis Entry to the body Macrophage activation Polymorph migration & Phagocytosis Intracelluar multiplication Lymphatics RES organs Blood Any organ

  17. VIRULENCE FACTORS • RESISTS PHAGOCYTOSIS : • LOW M.W. MOLECULES INHIBIT FUSION OF LYSOSOMES/PHAGOSOMES • ABILITY TO SURVIVE INTRACELLULARLY : PROLONGED PERSISTANCE

  18. Pathogenesis • CELL MEDIATED IMMUNITY ALSO ACTIVATED WITH GRANULOMA FORMATION (MAINLY WITH B. ABORTUS) • HUMORAL ANTIBODY RESPONSE OF LITTLE IMPORTANCE • MAIN WAY OF BODY CONTROL OF THE INFECTION IS THROUGH COMMITTED T-LYMPHOCYTES PRODUCING LYMPHOKINES (- INTERFERON) WHICH ACTIVATE MACROPHAGE KILLING • PYOGENIC INFECTION MORE WITH B. MELITENSIS AND B. SUIS

  19. Clinical Manifestations • INCUBATION PERIOD: VARIABLE 2- 8 WKS. • PRESENTATION: ACUTE 50% & INSIDIOUS 50% • SX & SIGNS NOT SPECIFIC. • CAN AFFECT ANY ORGAN. • COMMON NONSPECIFIC SX: - FEVER WITH RIGORS. - SWEATS, MALAISE, ANOREXIA. - HEADACHE, BACK PAIN.

  20. Clinical Manifestations

  21. Clinical Manifestations • GIT 70% : ANOREXIA, ABD. PAIN, VOMITING, DIARRHEA,CONTIPATION, HEPATOSPLENOMEGALY. • LIVER : INVOLVED IN MOST CASES BUT LFTS NORMAL OR MILDLY ABNORMAL. • GRANULOMAS (B. ABORTUS). • HEPATITIS (B.MELITENSIS). • ABSCESSES (B.SUIS).

  22. Clinical Manifestations • SKELETAL 20-60% : • ARTHRITIS, SPONDYLITIS, OSTEOMYELITIS. • SACROILIITIS - MOST COMMON. • ATHRITIS - OLIGOARTICULAR : HIP, KNEE & ANKLES. JOINT ASP. - MONOCYTOSIS, CULTURE +VE IN 50 %

  23. CLINICAL MANIFESTATIONS • NEUROLOGIC • MENINGITIS, ENCEPHALITIS, RADICULOPATHY & PERIPHERAL NEUROPATHY, INTRACEREBRAL ABSCESSES • MENINGITIS • ACUTE OR CHRONIC • NECK RIGIDITY < 50% • CSF • LYMPHOCYTIC PLEOCYTOSIS • (N) OR LOW SUGAR • INCREASE PROTEIN • CULTURE +VE < 50% • AGGLUTINATION +VE IN >95%

  24. CLINICAL MANIFESTATIONS • CARDIOVASCULAR • ENDOCARDITIS 2% (MAJOR CAUSE OF MORTALITY) • RX: VALVE REPLACEMENT AND ANTIBIOTICS • PERICARDITIS & MYOCARDITIS • PULMONARY • INHALATION OR HEMATOGENOUS • CAUSE ANY CHEST SYNDROME • RARELY BRUCELLA ISOLATED FROM SPUTUM

  25. Clinical Manifestations • GENITOURINARY • EPIDYDEMOORCHITIS • PYONEPHROSIS (RARE) • CUTANEOUS • NONSPECIFIC • HEMATOLOGIC • ANEMIA • LEUKOPENIA • THROMBOCYTOPENIA

  26. DIAGNOSIS • HISTORY OF ANIMAL CONTACT IS PIVOTAL • IN ENDEMIC AREA, IT SHOULD BE IN THE DD OF ANY NONSPECIFIC FEBRILE ILLNESS

  27. Diagnosis • LABORATORY • WBC (N) OR . MONOCYTOSIS • SPECIMENS: BLOOD • BONE MARROW • BLOOD CULTURES : CASTANEDA’S • SLOW GROWTH = 4 WEEKS • NEW AUTOMATED SYSTEM BATEC IDENTIFIES HE ORGANISM 4-8 DAYS • MORE RECENT (BACT/ALERT) - 2.8 DAYS • PCR

  28. Diagnosis • SEROLOGY • STANDARD AGGLUTINATION TEST – (SAT DIAGNOSTIC ?? 1 : 160 - NON ENDEMIC 1 : 320 - ENDEMIC AREA • SAT - FALSE NEGATIVE • PROZONE • BLOCKING ANTIBODIES • OTHER TESTS: COOMBS, ELISA, CFT,

  29. Brucella Antibodies • AGG = IgG + IgM • 2ME = IgG • DETECTING INFECTED ANIMALS: • MILK RING TEST ; MILK + BACTERIAL SUSPENSION (STAINED) : BLUE RING ABOVE CREAM LINE

  30. Prognosis • Preantibiotic era • Mortality 2% mainly endocarditis • Morbidity • High with B. melitensis • Nerve deafness • Spinal cord damage

  31. Prevention • CONTROL OF DISEASE IN DOMESTIC ANIMALS • IMMUNIZATION USING • B. ABORTUS STRAIN S19 • ROUTINE PASTEURIZATION OF MILK • IN LABS STRICT BIOSAFETY PRECAUTIONS

  32. Treatment DRUGS AGAINST BRUCELLA • TETRACYCLINES • AMINOGLYCOSIDES • STREPTOMYCIN SINCE 1947 • GENTAMICIN • NETILMICIN • RIFAMPICIN • QUINOLONES - CIPROFLOXACIN

  33. Treatment Drugs against Brucella • Treatment for uncomplicated Brucellosis • Stremptomycin + Doxycycline for 6 weeks • ? TMP/SMX + Doxycycline for 6 weeks • WHO recommendation 1986 • Rifampicin + Doxycycline for 6 weeks • Treatment of complicated Brucellosis • Endocarditis, meningitis • No uniform agreement • Usually 3 antibrucella drugs for 3 months

  34. Untreated Brucellosis

  35. Treated Brucellosis Treatment

  36. Relapse PREDICTORS OF RELAPSE MALE SEX INADEQUATE ANTIBIOTIC THERAPY. POSITIVE CULTURE ON INITIAL DISEASE THROMBOCYTOPENIA Ariza, et al: CID 20:1241, 1995

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