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Fundamentals on transmission, disease manifestations,diagnosis and preventive aspects have been mentioned.

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  1. 1. Genus BRUCELLA Dr.P.Sreenivasulu Reddy MD., Professor of Microbiology NARAYANA MEDICAL COLLEGE Nellore-1 Andhra Pradesh INDIA
  2. 2. Many Names of BrucellosisHuman Disease Animal Disease Malta Fever  Bang’s Disease Undulant Fever  Enzootic Abortion Mediterranean Fever  Epizootic Abortion Rock Fever of Gibraltar  Slinking of Calves Gastric Fever  Ram Epididymitis  Contagious Abortion
  3. 3. Sir William Burnett (1779-1861)•Physician General tothe British Navy•Differentiated thevarious feversaffecting soldiers
  4. 4. Jeffery Allen Marston•Contracted Malta fever.•Described his owncase in great detail.
  5. 5. Sir David Bruce (1855-1931)•British Army physicianand microbiologist•Discovered Micrococcusmelitensis (July 9, 1887)
  6. 6. Bernhard Bang (1848-1932)•Danish physician andveterinarian•Discovered Bacteriumabortus (1897) couldinfect cattle, horses,sheep and goats.
  7. 7.  Alice Evans, American bacteriologist  Credited with linking the organisms  Similar morphology and pathology between:  Bang’s Bacterium abortus  Bruce’s Micrococcus melitensis Nomenclature today credited to Sir David Bruce  Brucella abortus and Brucella melitensis.
  8. 8. Morphological ProfileBrucella spp. are small,Gram-negative, non-motile,non-spore-forming,coccobacilli .Intracellular microbescausing chronic disease.
  9. 9. Cultural charactersAerobe.Best medium is TrypticaseSoya Agar with selectiveagents(Polymyxin,Cyclohexamide).Small,moist,translucent andglistening colonies after 3 ormore days of incubation.
  10. 10. Species Biovar/ Natural Host Human Serovar PathogenB. abortus 1-6, 9 cattle yesB.melitensis 1-3 goats, sheep yesB. suis 1, 3 swine yes 2 hares yes 4 reindeer, caribou yes 5 rodents yesB. canis none Dogs yesB. ovis none Sheep noB. neotomae none Desert wood rat noB. maris (?) marine mammals ?
  11. 11. Biochemical reactions Catalase and Oxidase positive. Nitrates are reduced. Rapidly positive for urease. Negative for IMViC reactions. Susceptibility Killed at 600 C in 10 minutes Pasteurization of milk . Survival is long in refrigerated milk, ice creams and cheese.
  12. 12. Transmission to Humans Conjunctiva or broken skin on contact with infected tissues  Blood, urine, vaginal discharges, aborted fetuses, placentas Ingestion  Raw milk & unpasteurized dairy products (Cheese)  Rarely through undercooked meat
  13. 13. Transmission to Humans Inhalation of infectious aerosols  Pens, stables, slaughter houses Inoculation with vaccines  B. abortus strain 19, RB-51  B. melitensis Rev-1  Conjunctival splashes, injection Person-to-person transmission is rare Incubation varies  5 days to three months
  14. 14. Transmission in Animals Ingestion / contact with infected tissues or body fluids  Mucous membranes, injections Venereal  Swine, sheep, goats, dogs  Fomites
  15. 15. Who is at Risk? Occupational Disease  Cattle ranchers/dairy farmers  Veterinarians  Abattoir workers  Meat inspectors  Lab workers Hunters Travelers Consumers of unpasteurized dairy products
  16. 16. Pathogenecity and Immunity Followed by EntryIngested by PMN and not killed (super oxide dismutase ,LPS and nucleotide substance). Spread to local LN, multiply and spread to blood. Reaches to RES (Spleen,Liver,BM,LN).Resist phagocytosis (production of AMP/GMP and TNF Inhibits the phagolysosome fusion). Spread (CNS,Heart,Joints,Respiratory,Skin,GU system) Host response leads to granuloma formation and necrosis.
  17. 17. B. abortus (Contagious/ Infectious abortion) Worldwide Some countries have eradicated it Notifiable disease in many countries abortions, arthritic joints.  Fever of Unknown Origin (FUO) Main causes for spontaneous abortion in animals are erythritol, which can promote infections in the fetus and placenta and lack of anti-Brucella antibody in amniotic fluid.
  18. 18. B. canis Poorly understood 1-19% prevalence in United States contact with aborted fetuses and semen. Rarely causes disease in humans.
  19. 19. B. suis Biovars 1 and 3  Worldwide problem. Free  United Kingdom, Canada Eradicated  Holland, Denmark Low Incidence  Middle East, North Africa
  20. 20. Human Disease Can affect any organ or system All patients have a cyclical fever  Headache, weakness, arthralgia, depression, weight loss, fatigue, liver dysfunction
  21. 21. Human Disease 20-60% of cases  Osteoarticular complications  Arthritis, spondylitis, osteomyelitis Hepatomegaly may occur Gastrointestinal complications 2-20% of cases  Genitourinary involvement  Orchitis and epididymitis most common
  22. 22. Human Disease Neurological  Depression, mental fatigue Cardiovascular  Endocarditis resulting in death Chronic brucellosis is hard to define  Length, type and response to treatment variable  Localized infection Blood donations of infected persons should not be accepted
  23. 23. Human Disease Congenitally infected infants  Low birth weight  Failure to thrive  Jaundice  Hepatomegaly  Splenomegaly  Respiratory difficulty  General signs of sepsis (fever, vomiting)  Asymptomatic
  24. 24. Chronic brucellosis:It is hard to define- Length, type and response to treatment variableThe localized form:-Bones and joints.-Lumbar spondylodiscitis, sacroiliitis is typical.-Orchitis also frequent.
  25. 25. Sequelae are highly variable- Granulomatous hepatitis,- Arthritis, spondylitis,- Anaemia, leukopenia,thrombocytopenia,- Meningitis, uveitis, optic neuritis,- Endocarditis. Granuloma of Liver
  26. 26. Diagnosis in Humans Isolation of organism  Blood, bone marrow, other tissues Serum agglutination test  Four-fold or greater rise in titer  Samples 2 weeks apart Immunofluorescence Method  Organisms in clinical specimens PCR
  27. 27. Blood cultures in trypticasesoya broth (Castaneda’smethod): Biphasic medium.Sample inoculated bottle has tobe tilted to flow the broth oversolid medium and keep it uprightposition at 370C.The growth of brucellae isextremely slow.Bone marrow cultures are moresensitive than blood.
  28. 28. Demonstration of IgM , IgG and Ig A ELISA is the best method. Standard tube agglutination test: Anti -O-polysaccharide of LPS. Killed strains of B. abortus as antigen. Not useful for B.canis. Modified Tube agglutination test: 2- mercaptoethanol is added to serum before testing which causes disruption of IgM and only IgG are detected. . Problems with TA test: Prozone phenomenon, Presence of blocking or non-agglutinating antibodies. False positives with cholera, tularemia,yersinia or vaccination Contd…..
  29. 29. Castaneda strip test: Strip with colored brucella antigen. Onaddition of patients serum, if antibodies are present, preventsthe flow of serum.Brucellin Skin test: Delayed hypersensitivity.Molecular techniques: PCRRadiology: Alterations in infected vertebrae; Pedro Pons sign ( erosion of antero-superior corner of lumbar vertebrae) and marked osteophytosis are suspecious of brucellicspondylitis.
  30. 30. Diagnosis in AnimalsCulture of urine and Milk.Rapid latex agglutination test,Rose Bengal card test. (Rose Bengal + B.abortus +Sodium azide) Contd….
  31. 31. Milk Ring Test: Frequently used test.A drop of colored brucella antigen(B.abortus/B.melitensis with hematoxylin) is added tomilk in a test tube, incubated in a water bath at700C for 40-50 minutes.Positive: Blue ring at the top leaving the milkunstained.Negative: No ring. Milk remains uniformly blue.
  32. 32. Treatment of Choice Combination therapy has the best efficacy  Doxycycline for 6 weeks in combination with Streptomycin for 2-3 weeks or Rifampin for 6 weeks CNS cases to treat for 6-9 months.  Same for endocarditis cases plus surgical replacement of valves.
  33. 33. Prognosis May last days, months, or years Recovery is common Disability is often pronounced About 5% of treated cases relapse  Failure to complete the treatment regimen  Sequestered infection requiring surgical drainage Case-fatality rate: <2% ( untreated)  Endocarditis caused by B. melitensis
  34. 34. Prevention and Control Education about risk of transmission  Farmer, veterinarian, abattoir worker, butcher, consumer, hunter, public Wear proper attire if dealing with infected animals/ tissues  Gloves, masks, goggles Avoid consumption of raw dairy products
  35. 35. Prevention and Control Immunize in areas of high prevalence  Young goats and sheep with Rev-1  Calves with RB51  No human vaccine Eradicate reservoir  Identify, segregate, and / or cull infected animals