Brucellosis  Dr.T.V.Rao MD      Dr.T.V.Rao MD   1
Brucellosis an Important   Zoonotic Disease          Dr.T.V.Rao MD    2
Brucellosis,• Brucellosis, also called Bangs disease,  Crimean fever, Gibraltar fever, Malta  fever, Maltese fever, Medite...
BrucellosisBrucellosis is a zoonotic infectiontransmitted to humans contactwith fluids from infected animals(sheep, cattle...
Zoonosis• Brucellosis: Disease of domestic  and wild animals (zoonosis):  Transmittable to humans. It has  different non-s...
Brucellosis in humans• Brucellosis in humans is usually  associated with the consumption of  unpasteurized milk and soft c...
Major Transmission of Brucellosis              Dr.T.V.Rao MD         7
Other names for BrucellosisUndulant feverMalta feverGibraltar feverMediterranean fever.            Dr.T.V.Rao MD      8
BacteriologyGm - ve cocci, coccobacilli, bacilli.Strict aerobic, nonmotile, nonspore forming.B. ovis, B. abortus --CO2 ...
Characteristics of Bacteria• Brucella spp are small gram-negative  aerobic coccobacilli lacking a capsule,  flagella, endo...
Identification of Bacteria• Other methods for the identification  and speciation of Brucella include:production of urease...
B. abortus                                                                                     B. abortus• Bacteria is exc...
Brucella melitensis*• Principal hosts - goats and sheep• Most pathogenic in humans• Sporadic cases in humans in the U.S.  ...
Brucella abortus•    Principal host - cattle•    Eradication of B.    abortus from cattle is    nearly complete in the    ...
Brucella suis• Principal host - swine• Since B. suis is  normally found in  pigs, wild hog (feral  swine) hunters are at  ...
Brucella canis• Principal host - dog• Individuals who are in  close contact with  dogs, or  breeders/veterinary  staff who...
EpidemiologyBrucellosis occurs worldwide; major endemic areas include countries of the Mediterranean basin, Arabian Gulf, ...
Methods of transmission• Direct inoculation through cuts and skin abrasions  from handling animal carcasses, placentas, or...
Incubation period• Acute or sub acute disease follows an incubation  period which can vary from 1 week to 6 or more  month...
Portals of entry• Oral entry - most common route  – Ingestion of contaminated animal products    (often raw milk or its de...
Clinical Manifestation•   Fever•   Night sweats•   Malaise•   Anorexia•   Arthralgia•   Fatigue•   Weight loss•   Depressi...
Clinical Manifestations• The presentation of brucellosis is characteristically variable• The onset may be insidious or abr...
Clinical featuresOften fits one of the three pattern:febrile illness resembling typhoid, less  severefever & acute monoart...
Physical ExaminationPhysical manifestations may be absent.• If present,Focal Features:Musculoskeletal painOsteomyelitisSep...
Systemic Infections with Brucellosis• Osteoarticular disease, especially sacroileitis — 20 to  30 percent and vertebral sp...
Complications and Brucella Endocarditis — 1 percent.Most cases of  endocarditis are left-sided, and about two-  thirds oc...
Differential Diagnosis•Tuberculosis•Toxoplasmosis•CMV•HIV infection          Dr.T.V.Rao MD   27
Chronic Brucellosis• Patients with undiagnosed and  untreated brucellosis can be  symptomatic for months. In  addition, pr...
Chronic Brucellosis• The presence of granulomatous  hepatitis, hepatic micro  abscesses, bone marrow  granulomas, and/or  ...
Relapse• About 10 percent of patients relapse after  therapy.• Most relapses occur within three months  following therapy ...
Laboratory Diagnosis        Dr.T.V.Rao MD   31
Dr.T.V.Rao MD   32
Investigations• Total counts-Normal/reduced• Thrombocytopenia• ESR/CRP-Normal/Increased• CSF/Body fluid analysis-Lymphocyt...
Serological Tests• Most serological studies for diagnosis of  Brucellosis are based on antibody detectionThese include:• S...
• Serology  – Main laboratory method of diagnosis  – Serum agglutination test - most widely used     • measures agglutinat...
Serum agglutination• It is generally agreed that a titer of  >1:160 in the presence of a compatible  illness supports the ...
ELISA• ELISA is probably the second most common  serologic method.• The sensitivity of the ELISA was 100 percent  when com...
PCR an Emerging Tool• Polymerase chain reaction (PCR) shows  promise for rapid diagnosis of Brucella  spp in human blood s...
Imaging• Patients with spine symptoms   MRI  examination to rule out spinal cord  compromise.• Plain radiographs, radionu...
Radiology of Spinecan 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:  – Doxycy...
TreatmentDrugs against Brucella• Tetracyclines• Aminoglycosides  – Streptomycin since 1947  – Gentamicin  – Netilmicin• Ri...
TreatmentAntibiotic TherapyThere are two major regimens:Regimen A: Doxycycline 100 mg orally twice daily for 6 weeks + Str...
Treatment• Regimen B:  Doxycycline 100 mg orally  twice daily plus  rifampin 600 to 900 mg (15  mg/kg) orally once daily f...
Focal Disease• Patients with focal disease have a  less favorable prognosis. In a study  of 530 patients (including 170  p...
Indications for Surgery• Endocarditis where valve replacement or valve  debridement is required• Drainage or excision of a...
Need for Surgery• Resection of mycotic aneurysms• Procurement of tissue for diagnostic  purposes• Chronic hepatosplenic su...
Osteoarticular Disease• Patients with Brucella spondylitis  appear to respond better to  doxycycline-streptomycin or a thr...
Neurobrucellosis• Doxycycline,• Rifampin• Trimethoprim-Sulphmethoxazole .• The duration of therapy is generally prolonged ...
Endocarditis• Antimicrobial therapy alone may be  attempted absence of heart failure,  valvular destruction, abscess, or a...
Needs longer duration of Treatment• Therapy is usually given for six  weeks to six months.• The aminoglycoside component i...
Relapse• Relapse should prompt assessment for a  focal lesion, especially hepatosplenic  abscess• Most relapses can be tre...
Pregnancy and Brucellosis• Premature labor and fetal wastage• Rifampin — 900 mg once daily for six  weeks• Rifampin — 900 ...
Prevention–Control of disease in domestic animals  • immunization using B. abortus strain 19    and B. melitensis strain R...
• Programme Created by Dr.T.V.Rao MDfor Medical and Paramedical Students in         the Developing World               • E...
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Brucellosis

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Brucellosis

  1. 1. Brucellosis Dr.T.V.Rao MD Dr.T.V.Rao MD 1
  2. 2. Brucellosis an Important Zoonotic Disease Dr.T.V.Rao MD 2
  3. 3. Brucellosis,• Brucellosis, also called Bangs 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
  4. 4. BrucellosisBrucellosis is a zoonotic infectiontransmitted to humans contactwith fluids from infected animals(sheep, cattle, goats, pigs, orother animals) derived foodproducts such as unpasteurizedmilk and cheese . The disease israrely, if ever, transmittedbetween humans.Dr.T.V.Rao MD 4
  5. 5. 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
  6. 6. 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
  7. 7. Major Transmission of Brucellosis Dr.T.V.Rao MD 7
  8. 8. Other names for BrucellosisUndulant feverMalta feverGibraltar feverMediterranean fever. Dr.T.V.Rao MD 8
  9. 9. 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
  10. 10. 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
  11. 11. 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 antisera Dr.T.V.Rao MD 11
  12. 12. B. abortus B. abortus• Bacteria is excreted in genital secretions (including semen), milk, colostrum. • Sources of Human Infection:• Survival time: Raw milk and products /Direct contact Cheese at 4oC: 180 days !!! Water at 25oC: 50 days • Portal of entry: oral mucosa, nasopharynx and conjunctivae, genital then X in regional lymph Meat and salted meat: 65 days node and spread to RES (nodes of udder, uterus, Manure at 12oC: 250 days !!!! erythritol...). Placentitis with endometritis. Fetus die with edema /congestion of lung, dissimenated• Widespread: Cattle, Bison, Elk, Deer, Moose, Horse, hemorrhages of epicardium and splenic capsule. Sheep, Goat, Swine, Donkey, Dogs, Birds, Hares, Fox, Rats, Bacteria in lung and digestive tract of the fetus. mice, Camels and Human. B. suis • Wild pigs, Rats, Swine. B. melitensis • Abortion,metritis, bursitis, spondylitis (Lumbar and sacral),• Goat (1886), Sheep, arthritis, orchitis, Cow (1905 in paralysis. Malta), Swine, Brucella canis Hares, Camels, Buffalo, Impala. • Brucella canis was first described as a cause of abortion in beagles in the USA • It was subsequently shown to infect dogs in many other countries, irrespective of breed Dr.T.V.Rao MD 12 • An occasional cause of brucellosis in humans
  13. 13. 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
  14. 14. 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
  15. 15. 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
  16. 16. 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 Dr.T.V.Rao MD 16 canis
  17. 17. EpidemiologyBrucellosis occurs worldwide; major endemic areas include countries of the Mediterranean basin, Arabian Gulf, the Indian subcontinent, and parts of Mexico, Central and South AmericaHuman 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
  18. 18. 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
  19. 19. 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
  20. 20. 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
  21. 21. Clinical Manifestation• Fever• Night sweats• Malaise• Anorexia• Arthralgia• Fatigue• Weight loss• Depression. Dr.T.V.Rao MD 21
  22. 22. Clinical Manifestations• The presentation of brucellosis is characteristically variable• The onset may be insidious or abrupt• Influenza-like with fever reaching 38 to 40oC – 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
  23. 23. Clinical featuresOften fits one of the three pattern:febrile illness resembling typhoid, less severefever & acute monoarthritis (hip/knee),young childlong lasting fever,LBA,hip pain,older man• Travel to an endemic area• Occupation• Consumption of unpasteurized milk Dr.T.V.Rao MD 23
  24. 24. Physical ExaminationPhysical manifestations may be absent.• If present,Focal Features:Musculoskeletal painOsteomyelitisSeptic ArthritisMinimal lymphadenopathyHepatosplenomegaly occasionally. Dr.T.V.Rao MD 24
  25. 25. 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
  26. 26. 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
  27. 27. Differential Diagnosis•Tuberculosis•Toxoplasmosis•CMV•HIV infection Dr.T.V.Rao MD 27
  28. 28. 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
  29. 29. 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
  30. 30. 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
  31. 31. Laboratory Diagnosis Dr.T.V.Rao MD 31
  32. 32. Dr.T.V.Rao MD 32
  33. 33. 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
  34. 34. Serological Tests• Most serological studies for diagnosis of Brucellosis are based on antibody detectionThese include:• Serum agglutination (standard tube agglutination)• ELISA Rose Bengal agglutination• Complement fixation• Indirect Coombs• Immunecapture-agglutination (Brucellacapt Dr.T.V.Rao MD 34
  35. 35. • 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
  36. 36. 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
  37. 37. 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
  38. 38. 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
  39. 39. 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
  40. 40. Radiology of Spinecan differentiate Tuberculosis from Brucellosis Dr.T.V.Rao MD 40
  41. 41. 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
  42. 42. TreatmentDrugs against Brucella• Tetracyclines• Aminoglycosides – Streptomycin since 1947 – Gentamicin – Netilmicin• Rifampicin• Quinolones - ciprofloxacin• ?3rd generation cephalosporins Dr.T.V.Rao MD 42
  43. 43. TreatmentAntibiotic TherapyThere 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
  44. 44. 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
  45. 45. 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
  46. 46. 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
  47. 47. 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
  48. 48. 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
  49. 49. 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
  50. 50. 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
  51. 51. 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
  52. 52. 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
  53. 53. 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
  54. 54. 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
  55. 55. • Programme Created by Dr.T.V.Rao MDfor Medical and Paramedical Students in the Developing World • Email • doctortvrao@gmail.com Dr.T.V.Rao MD 55
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