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BRUCELLOSIS. Hail M. Al-Abdely, M.D. Associate Consultant Infectious Diseases. Historical Background. Malta Fever Major health problem to British troops in Malta in the 19 th and early 20 th centuries. Historical Background.

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brucellosis
BRUCELLOSIS

Hail M. Al-Abdely, M.D.

Associate Consultant

Infectious Diseases

historical background
Historical Background
  • Malta Fever
    • Major health problem to British troops in Malta in the 19th and early 20th centuries.
historical background3
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.
historical background4
Historical Background
  • 1897 A.E. Wright ; pathologist in British army - developed agglutination test.

What is the source?

“Mediterranean Fever Commission” 1904

historical background5
Historical Background
  • 1905 Zammit;Maltese physician

- Goats were the source of infection.

  • 1897 E. Bang;Danish veterinarian

-described intracelular pathogen causing abortion in cattle named “Bacillus abortus”.

  • 1918 A. Evans;American microbiologist

-made the connection between Bacillus abortus and micrococcus melitensis & named it Bacteriaceae.

historical background6
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
epidemiology
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
epidemiology in saudi arabia
Epidemiology in Saudi Arabia
  • Endemic disease
  • Mostly B. melitensis & b. abortus.
  • No clear figures about incidence & prevalence.
  • Incidence : 5.4 per 1000 per year.
  • Prevalence : 8.6 - 38 % - some regions.
bacteriology
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.
bacteriology13
Bacteriology
  • Surface lipopolysccharide cell wall
    • smooth vs non-smooth.
    • determine virulence.
      • smooth LPS : B. melitensis,suis,abortus
      • Non-smooth LPS B.canis, ovis.
    • the basis for agglutination test.
transmission
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.

pathogenesis
Pathogenesis

Entry to the body

Macrophage activation

Polymorph migration & Phagocytosis

Intracelluar multiplication

Lymphatics

RES organs

Blood

Any organ

pathogenesis16
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
clinical manifestations
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.
clinical manifestations19
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).
clinical manifestations20
Clinical Manifestations
  • Skeletal 20-60% :
  • arthritis, spondylitis, osteomyelitis.
  • sacroiliitis - most common.
  • athritis - oligoarticular : hip, knee & ankles.

Joint asp. - monocytosis, culture +ve in 50 %

clinical manifestations21
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%
clinical manifestations22
Clinical Manifestations
  • Cardiovascular
    • Edocarditis 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
clinical manifestations23
Clinical Manifestations
  • Genitourinary
    • Epidydemoorchitis
    • Pyonephrosis (rare)
  • Cutaneous
    • Nonspecific
  • Hematologic
    • Anemia
    • Leukopenia
    • Thrombocytopenia
diagnosis
Diagnosis
  • History of animal contact is pivotal
  • In endemic area, it should be in the DDx of any nonspecific febrile illness
diagnosis25
Diagnosis
  • Laboratory
    • WBC (N) or . monocytosis
    • ESR of little help
    • Blood cultures
      • slow growth = 4 weeks
      • new automated system BATEC identifies he organism 4-8 days
      • more recent (BACT/ALERT) - 2.8 days
  • PCR
diagnosis26
Diagnosis
  • 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
slide27

S

IgM

brucella antibodies
Brucella Antibodies
  • AGG = IgG + IgM
  • 2ME = IgG
prognosis
Prognosis
  • Preantibiotic era
    • Mortality 2% mainly endocarditis
  • Morbidity
    • High with B. melitensis
    • Nerve deafness
    • Spinal cord damage
prevention
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
treatment
Treatment

Drugs against Brucella

  • Tetracyclines
  • Aminoglycosides
    • Streptomycin since 1947
    • Gentamicin
    • Netilmicin
  • Rifampicin
  • Quinolones - ciprofloxacin
  • ?3rd generation cephalosporins
treatment32
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
slide35

Relapse

Predictors of Relapse

Male sex

Inadequate antibiotic therapy.

Positive culture on initial disease

Thrombocytopenia

Ariza, et al: CID 20:1241, 1995