1
??????????? ? ????? ?? ???? ?????? ???? ????
2
????? ???

• ????? ? ????? ??????? ??????? ??????? ? ????? ??
  ???? ???.
•    ???? ???? ??????? ?? ????? ???.
• ?????? ???? ???? ??????? ?? ????? ????? ?? ????
  ???.
• ??? ????? ??????? ????? ???? ?? ??? ???.
• ???? ????? ??????? ?? ????? ???.
• ??? ??? ?????? ?????? ?? ????? ??????? ?? ????
  ?????.
•   ????? ? ????? ?????? ? ??? ??? ???? ?????? ??
  ?? ??? ???.
• ??????? ?????? ?????? ? ?????? ?? ??? ???.
• ??????? ???? ?? ????? ?? ? ??? ???? ??? ?????? ??
  ????? ???.

3
?????

• ???????? ????? ?? ?????? ???? ??? ? ??? ?? ??????
  ??? ????? ??? ????? ? ??????? (??????) ??? ?? ??
  ???? ???? ??? ??? ?? ????? ???? ?? ??? ? ??
  ???????? ????? ???? ??????? ?????? ?????? ??????
  ? ?? ?????? ?????? ???? ????? ??? ?????? ??? ?
  ?????? ? ???? ??? ? ?? ???? .
• ???? ??? ???????
• 1 ) ?? ??? ??? ???? ?? ? ?????? ?? ?? ????? ???
  ??????? ?????? ?? ??? ? ??????? ???? ???? ??? ?
  ???? ???? ???? ????? ?? ????.
• 2 ) ?????? ?? ? ???? ??? ????? ?? ???? ????? ??
  ???? ?? ?????? ??????? ????? ?? ??? ? ?? ????? ??
  ????? ?????? ???.

4

• 3 ) ??? ??? ?????? ???? ???? ??? ? ???? ??? ??
  ????? ? ?? ??? ???? ??? ?? ?????? ????? ???? ????
  ???? ?????.
• 4 ) ???? ???? ?????? ?? ??? ??? ?? ????? ????
  ????? ??? ?????? ?? ????? ????? ? ?? ???? ?????
  ????? ?????? ? ?? ??? ??????? ???? ? ????
  ???????? ? ???????? ? ???? ??? ??????? ?? ?? ???
  ?? ????.
• 5 ) ???? ?? ???? ??? ??????? ???? ??????? ?? ???
  ??????? ???? ??? ????? ? ??????? ?? ???????
  ????????? ? ???? ???? ?? ?? ?? ????? ???? .

5

• ????? ??? ??? ?? ??? ??? ?? ?? ??? ??? ????????
  (Bioterrorism) ? ????? ??? ????? ??? ?? ?????? ??
  ? ?????? ???? ??? ???????? ? ?????? ?? ????? ???
  ????? ??? ???????? (Biowarfare) ??????? ???
  ?????. ??? ????? ??? ???? ???? ????? ?? ?? ???
  ???? ????? ?? ??????? ??? ??? ?? ???? ???? ???
  ????.

6
The Many Names of Brucellosis

• Human Disease
• Malta Fever
• Undulant Fever
• Mediterranean Fever
• Rock Fever of Gibraltar
• Gastric Fever

• Animal Disease
• Bangs Disease
• Enzootic Abortion
• Epizootic Abortion
• Slinking of Calves
• Ram Epididymitis
• Contagious Abortion

7
Professor FEG Cox. The Wellcome Trust,
Illustrated History of Tropical Diseases
Sir David Bruce (1855-1931)

• British Army physician and microbiologist who
  discovered Micrococcus melitensis

8
???? ????

• ?????? ?? ????? ??? ??? ????? ????? ????? ? ???
  ??????? ????? ?? ???? ????? ? ?????? ?? ?????.
  ??? ?? ?? ???? ??? ??? ?? ???? ??? Brucella
  Broth ?? ???? 37 ???? ????????? ? 7/6 H P??
  ??? ?????? ??? ?? ??????. ???? ??? ?????? ?? ????
  ??? ????? ?????? ?? ???? ????? ??? ???? ????? ???
  ?????? ?? ???? ?? ???????? ??? ?? ????. ????? ???
  ?????? ???? ? ?????? ?????? ?? ???? ???? ??? ???
  ? ???? ???????? ??????.
• ???? ???? ?? ?????? ?? ?? ??? ?????? ???? ??????
  ???????? ???? ?? ???? ??????? ??
• ?????? ????????
• ?????? ???????
• ?????? ?????
• ????? ?????? ???? ??? ???? ??? ???????? ???? ???
  ? ?? ????? ? ???? ???? ??
• ?????? ?? ?? ???? ????? ??? ????? ???????
  ??????? ????? ????? ?? ???????? ????? ???
  ??????????.

9
???? ????

• ???? ??? ?????? ???????? ?? ???? ?? ???? ?? ???
  ?? ????? ?? ??? ??? ?? ??? 10 ???? ?? ???? ????
  ?? ?? ??? ? ?? ????? ? ???? ??? ?? ???? ????
  ?????? ? ?? ???? ??? ??? ??? ???? ??? ?? ????
  ?????? ???? ??? ?? ???? ?? ????? ??? ?????
  ????????? ? ??? ??? ???? ?????? ????? ?? ?? ??
  ??? ??? ???? ????? ???? ?? ????.
• ??? ???????? ?? ?? ????? 60 ???? ????????? ?? ??
  ??? ?????? ?? ???? 1 ?? ??? 15 ????? ?? ???
  ?????? ??? ?? ????? ???????? ?? ??? ?? ????
  ??????.
• ??? ????? ?? ????? ???? ??? ???? ?????? ????
  ????? ???? ?? ????? ??????????? ???? ???? ???
  ?????? ?? ?? ???? ? ???????? ?????? ?? ???????
  ????? ?? ??????? ????? ????? ????? ?? ???? ????
  ???? ???? ??????? ? ?? ?? ??? ?????? ?? ??? ?????
  ?? ???? ???? ?? ??????? ???????? ? ??? ????? ??
  ???? ???? ???? ?????? ?????? ?? ????? ??? ????
  ???? ????? ????? ??? ????????? ? ???? ??????
  ????????? ????? ??????? ??????.

10
(No Transcript)
11
Human Disease

• Can affect any organ or organ system
• All patients have a cyclical fever
• Variability in clinical signs
• Acute, sub acute, chronic
• Headache, weakness, arthralgia, depression,
  weight loss, fatigue, liver dysfunction.Triad
  of Dx in most ptFever Arthralgia/ArthritisHSM

12

• Acute (lt8 weeks from illness onset)
• symptomatic, nonspecific, and flu-like, including
  fever, sweats, malaise, anorexia, headache,
  myalgia, and back pain
• Sub acute (lt1 yr. from illness onset)
• symptoms include undulant fevers, arthritis, and
  epididymorchitis in young males. malaise
  fatigue

13

• Chronic (gt1 yr. from onset)
• symptoms may include chronic fatigue-like
  syndrome, depressive episodes

14
Human Disease

• 20-60 of cases
• Osteoarticular complications
• Arthritis, spondylitis, osteomyelitis
• The most common of it is sacroilietisgt
  hipgtkneegtankle
• Hepatomegaly may occur
• Gastrointestinal complications
• nausea, vomiting, anorexia, weight loss, and
  abdominal discomfort
• 2-20 of cases
• Genitourinary involvement
• Orchitis and epididymitis most common

15
Human Disease

• Neurological
• Depression, mental fatigue
• CNS (lt2)
• SAH, TIA, Meningitis, Meningoencephalitis,
  encephalitis, Brain Abscess, subdural empyema
• PNS
• Mono neuropathy. Autonomic poly neuropathy, poly
  radiculoneuritis
• Spinal involvement
• Cardiovascular
• Endocarditis(B. melitensis) resulting in death(
  lt2)

16
Human Disease

• Chronic brucellosis is hard to define
• Length, type and response to treatment variable
• Localized infection
• Blood donations of infected should not be
  accepted
• Children FTT, anorexia
• Congenital infection transplacental, nursing

17
Signs and symptoms of patients with brucellosis by B. melitensis Trujillo I, Zavala A, Miranda C Brucellosis Infectious Disease Clinics of North America Vol. 8, No. 1, 225-242 Signs and symptoms of patients with brucellosis by B. melitensis Trujillo I, Zavala A, Miranda C Brucellosis Infectious Disease Clinics of North America Vol. 8, No. 1, 225-242
Signs and symptoms percentage
Fever 100.0
Sweating 95.8
Headache 83.3
Arthralgia 81.2
Muscle pain 81.2
Weakness 77.0
Anorexia 75.0
Weight loss 58.3
Arthritis 52.0
Constipation 31.2
Diarrhea 20.8
Vomiting 14.5
Splenomegaly 12.5
Hepatomegaly 10.5
Epistaxis 2.0
18
Iran

• Increasing from 1359-1368(most in 1368
  170/100000 90000 cases)
• After that decreasing(1376- 31/ 100000- 26000
  cases)
• Spring summer
• 15-45 y/o(gt 80 lt 40 y/o)
• Endemicity
• ??? 60
• Severe Lorestan, Ilam, Hamedan( gt 225/100000)
• Intermediate Chahar mahal, Markazi, Kermanshah
• The most prevalent B. melitensis

19
(No Transcript)
20
?????- ?????- ??????- ????????? ????
21
(No Transcript)
22
(No Transcript)
23
(No Transcript)
24
(No Transcript)
25
(No Transcript)
26
(No Transcript)
27
???? ????? ???? ?????? ?? ???? ?? ????? ?????
1386-1376
28
???? ????? ???? ?????? ?? ???? ?? ????? ?????
1389-1376
29
??? ?????

• ???? ?????? ?????? ?????? 5 ?? 60 ??? ? ????? ???
  1 ?? 2 ??? ? ????? ??? ??? ???.(3-1 ????)
• ?? ??? ??? ?? ?????? ?? ?????? ????? ????????
  ??? ????? ????????? ???? ?????? ???? ??? ??? ????
  ???????? ?? ????? ??? ??? ? ??????? ???? ?? ????.
  ???? ??? ????? ?? ????? ???????? ?? ???? ?????
  ??? ????? ????? ?? ?? 4-3 ???? ?? ?? ???? ??????
  ???? ?????? ? ?? ??? 8-6 ???? ????? ???? ???
  ???????? ??? ????? ????? ?? ??? ?? ???? ? ??????
  ????? ???? ?? ??? ??? ?? ????? ?? ????? ????????
  ?? ???? ???? ? ??? ????? ???? ????? ???????? ???
  ????? ?? ????? ?? ?????? ?????? ???????? ???
  ??????? ?? ????? ???? ?? ???????? ???? ??? ??
  ???? ????? ???? ???????? ??? ???? ???? ?? ??
  ????.
• ??? ?????? ???? ??? ?? ???? ?????? ??? ??????
  (??? ????????)? ??????? ??? ? ??? ???? ??????
  ????? (????????)? ??????? ??? ?????? ???????
  ????? ??????? ???? ?? ????? ????? ?????? ????
  ???.

30
??? ?????

• ????? ???? ????? ???????? ???? 12 ????? ????? ??
  ????? ?? ??????? ??? ???. ????? ??????? ??? ??
  30-10 ???? ?????? ???? ?? ?????.
• ??? ????? ?? ?? ??? ?? ?????? ? ?? ?? ????? ?? ??
  ?????? ? ??? ?? ???????? ?? ??? ?????? ????? ??
  ????? ???? ????? ? ?? ???? ???? ??? ??? ?????? ??
  ????? ?? ???? ?? ????? ??? ???? ???. ??? ????
  ???? ?? ??? ??? ??????? ?????? ???????? ???? ??
  15 ????? ?? ??? ?? ?? ???? ????? ?? ???? ? ?????
  ??? ???? ?? ?????? ???? ?? ???? 2 ??????.
• ??? ?????? ?? ???? ???? ???? ???? ???? ? ?? ?? ??
  ???? ??? ????? ?????? ?? ????? ?? ?? ???? ?????
  ???? ?????? ??????. ?? ??? ???? ??????? ?????? ??
  ??? ????? ?? ?????? ??????? ?????????? ???? ?????
  ? ?????? ????? ?? ???? ? ??? ??????? ?????? ?????
  ??????? ??????? ???? 500000 ???? ?? ?? ??????
  ????? ????? ? ???? ????????? ???????? ???? ??????
  ??????.

31
???? ?????

• ?????? ???????? ???? ?? ?? ???? ????? ????? ???
  ???? ???? ??? 19-15 ???? ??????? ????? ?? ????
  ???? ??? ???? ?? ???? ??? ?????? ?? ???????? ????
  ????? ? ???? ?????? ?? ???????? ?? ?????? ??????
  ?? ???? ??????? ???? ??? ????? ????? ???? ??
  ????????? ??????? ? ?????? ?????? ?? ????? ????
  ?????? ??? ?? ???? ??? ???? ? ??? ?? ?????? ?????
  ???? ????? ???? ????? ?? ???? ???? ????? ????
  ????? ??????? ?? ??? ?????? ? ??? ????? ?????? ??
  ???? ???.
• ??? ?????? ????? ?? ???? ?? ??? ???? ? ??
  ??????? ?????? ???? ??? ??? ?? ?? ????? ??????
  ??????? ? ?????? ????? ?? ?????? ????????? ????
  ???? ?? ????? ????? ???????? ?? ????? ??? ????
  ???.

32
???? ?????

• ??? ?????? ?? ????? ?? ?????? ???? ????????
  ?????? ?????? ?????? ??????? ? ??? ?? ?????????
  ??? ??????? ?? ????.
• ?? ??????? ?????? ? ??????? ????? ???? ???? ????
  ? ???? ????? ????? ?? ?? ???? ?? ???? ??? ????
  ????? (?? ???? ???? ??? ???? ???) ??? ??????
  ??????? ?? ???? ???? ?????? ? ?????? ? ???? ???
  ????.
• ????????? ? ?????????? ?? ?? ?????? ??? ?????
  ???????? ???? ?? ???? ?? ??? ????? ?????? ?????
  ??? ???? ???? ??? ?? ?????? ?? ?????? ?????? ??
  ???? ????? ???? ?? ???? ??? ?????? ???? ?????.
• ?????? ??? ???????? ?????? ???? ?? ???? ??? ???
  ?????????? ????? ???? ? ????? ???? ???.

33
???? ?????

• ?? ??? ???? ? ??????? ?? ?? ???? ??? ?????? ?
  ?????? ????? ??? ?? ??? ???? ?? ????? ?????? ???
  ??? ? ????? ?? ?? ?? ?????? ??? ??????? ???????
  ?? ????? ???? ??????? ? ?????? ??? ??? ????? ??
  ???? ? ???? ?????? ????? ??? ??? ?? ?????? ????
  ?????? ???? ???? ????? ????? ?? ??????? ??? ??
  ????. ???? ???? ?????? ?? ????? ??? ???????
  ??????? ? ?? ????? ????? ??? ???? ???? ?? ?
  ?????? ?? ????? ??? ???? ?????? ? ?? ??? ?????
  ????? ???? ????? ???? ?? ??? ?? ???? ????? ??????
  ?????? ????? ???.
• ?? ??????? ??????? ????? ???? ?????? ????? ??
  ???? ?? ???? 5 ?? 1 ?? 6 ?? 1 ? ????? ???????
  ??????? ???? ???? ?? ?????????? ????? ?????? ???
  ??? ?? ???? ??? ?? ??? ??????? ??? ???? ?? ?? ???
  ???? ??? ??? ??? ? ???? ?? ????? ?? ??????? ??
  ????? ?? ????? ?????? ?? ???? ????? ? ????? ???
  ???? ??? ????? ????? ????.

34
???? ?????

• ?? ??? ???? ??????? ??????? ?? ??????? ??????
  ????? ?? ??????? ???????? ?? ? ??????? ???? ??
  ???? ? ?????? ????????? ???????? ???? ?????? ??
  ??? ???? ??????.
• ?? ???? ????? ????? ??????? ????? ?? ??????? ??
  ????????? ???????? ? ?????? ?? ?? ??????? ???
  ???? ????????? ????? ??????? ???????? ?????
  ?????? ? ???? ?? ???? ?? ????? ????? ?????? ??? ?
  ???? ? ??? ?????? ????? ? ??? ????? ????? ??
  ??????? ????. ??? ?????? ?? ????? ???? ?? ????
  ???????? ???
• ??? ?? ???? ?? ????? ?????? ??????? ?? ??? ??
  ??????? ?? ??? ??? ???? ????? ????? ??? ????? ???
  ???? ???? ?? ?????? ?? ??????? ???? ?? ????
  ??????? ??? ?? ??? ????? ??????? ???? ????? ???
  ?? ??? ??????? ?????? ??????????? ????? ???? ????
  ? ?? ?? ??? ???? ???? ????? ?????? ? ??? ?????
  ??????.

35
(No Transcript)
36
??? ??? ?????? ???????? ?? ?????

• 1) ????? ?? ??? ??? ?? ????? ????????? ? ??? ??
  ??
• 2 ) ???? ?????? ???? ???? ???? ? ???? ???????
• 3 ) ????? ?????? ????? ?? ?? ??? ???? ???? ????
• 4 ) ???? ?????? ?? ??????? ???? ????? ??? ???????
  (??????? ??????? ???)
• 5 ) ???? ?????? ?? ???? ?????? ?????? ???? ?????
  ??????? ??? ???
• 6 ) ?? ???? ?????? ??? (??????) ????? ?? ???? ???
  ? ?????
• 7 ) ?? ????? ???? ?? ????? ???????? ?? ???? ????
  ???? ????
• 8 ) ?? ???? ???? ? ??? ??? ??? ????? ??????
  ???????
• 9 ) ????? ?? ??? ????? ???? ? ?????? ???? ???? ??
  ??? ?? ??????? ???????? (Congenital) ? ????
  ?????? ???.
• ?? ??????? ??????? ?????? ??????? ?? ??? ????? ?
  ?? ????? ???? ?????? ?????? ?? ???? ???? ?????
  (Food-borne) ?? ???? ?? ???.

37

• Consumers of unpasteurized dairy products are
  also at risk

38
????? ? ?????? ???? ?????? ?????? ? ???? ??????
?????

• ????? ???? ?????? ?? ??????????? ???? ???? ??????
  ? . . . ????? ?? ???.
• ?????? ?? ???? ?????? ?????? ?????? ????? ????
  ??? ?????? ?????? ???? ??????? ?????? ???? ???
  ??????? ? ???? ????? ?? ???.

39
????? ????????????

• ?????
• ????? ?????? ????? ?? ?????? ???????????? ??
  ????? ?????? ????? ?? ???? ? ?? ??????? ??? ?????
  ??????
• ?????
• ???? ????? ????? ???? ????
• ????
• ???? ????? ?? ?????? ?? ?? ????????? ???? ???.
• ????? ???????

40
(No Transcript)
41
??????? ? ?????
42
??????? ????? ?? ????? ??? ?????? ????? ???? 

• 1 ) ??????? ??????? ?????? ?? ??????? ?? ????????
  ???? ? ??????? ???? ?? ???? ???????
• 2 ) ??????????? ??????? ???? ?????
• 3 ) ????? ?????? ?? ???? ?????? ? ??? ??? ???????
  ?? ?? ?? ????? ?? ???? ??? ? ?? ????? ????? ??
  ???? ????
• 4 ) ????????? ???? ??????
• 5 ) ??? ???? ?? ???? ??????? ???? ???? ??? ??? ??
  ???? ??? ?????? ??????? ?? ?????? ???? ????? ?
  ???? ?????? ?? ???? ??? ????
• 6 ) ????? ???????? ? ?????? ???? ? ??? ??? ??
  ???? ?? ????? ?????? ????? ??? ????? ????? ????
  ?? ??????? ? ??? ??? ??????? ??
• 7 ) ???? ???? ??? ??? ????????? ? ???????? ?
  ????? ??? ??? ???? ?? ????? ??? ??? ??? ?????
  ???? ?? ?????? ????? ????? ?? ????

43
(No Transcript)
44
?????? ?? ??????? ?? ?? ? ??????
45
??????? ?????? ?? ????? ?????????? ?????? ?????
????? ? ??????? ?? ???? ?????

• ????? ????? ? ????? ??????? ??????? ????? ??????
  ?? ????? ?????? ????? ??? ?? ???? ?? ????? ??????
  ???? ???? ????? ????? ? ?? ???? ??? ??????
  ??????? ??????? ???? ????? ??? ? ?????? ?? ???
  ????? ???? ????.

46
Diagnosis
47
Diagnosis in Humans

• Isolation of organism
• Blood, bone marrow, other tissues
• Serum agglutination test
• Fourfold or greater rise in titer
• Samples 2 weeks apart
• Immunofluorescence of organism in clinical
  specimen
• PCR

48
Diagnosis

• No single titer of Brucella antibodies is always
  "diagnostic" however, most cases of active
  infection have titers higher than 1160
• False-negative reactions in the SAT can result
  from a prozone phenomenon
• False-positive reactions occasionally result from
  cross-reactions with antibodies to Yersinia,
  cholera, or tularemia

49
Diagnosis

• False-negative and false-positive reactions can
  be avoided by routinely diluting the serum beyond
  1320.
• Very rarely, the presence of so-called blocking
  antibodies yields a negative reaction, blocking
  substances can be identified by the Coombs test
  or a blocking assay.
• When agglutination tests are equivocal, the
  Brucella enzyme-linked immunosorbent assay can be
  definitive

50
???? ????? ????? ??? 2ME ???? ?????? ???? ??
????? ??????? ???.
51

• Adults
• Rifampin (600-900 mg/d fasting in the morning 1
  hr before or 2 hrs after meal single dose or
  divided Q 8-12 h) Doxycyclin(100 mg) for 8 wks
• Tetracycline (500 mg Q6h) for 8 wks
  Streptomycin(1 gr IM) or Gentamycin (3-5 mg IM)/d
  for 2-3 wks
• Rif Co-Trimoxazole (2 tab Q 8-12 h) for 8 wks

52
?????
53

• Children
• Rif (10 mg / kg) Co- Trimoxazole(8 mg
  trimetoprim/ kg in 2 divided doses)for 8 wks
• gt 8 y/o
• Doxycycline Gentamicin
• Doxycycline Rifampin
• Pregnancy
• As adults except in first last month

54
??????? ??????? ?? ????? ??????? ?? ?????? ?????
? ??????? ??? ?????

• ?????? ???? ????? ????? ???? ??????? ???? ???
  ?????????? ? . . . ?????? ???? ?????? ?? ?????
  ?????? ? ?????? ?????? ?? ?????? ?????? ? ????
  ????? ??????? ?????? ??????? ????.

55
???? ??????? ??????

• ???????? ?? ?? ????? ??? ??? ???? ??? ?????? ????
  ????? ???
• ?? ????? ???? ???? ???? ???? ????? ?? ?????? ???
  ? ??????? ??? ??? ????????? ?? ??? ??? ????? ???
  ???? ?? ????? ??????. ??????? ??? ???? ????? ??
  ???? ?? ??????? ?? ??? ???? ???? ? ?? ????? ????
  ???? ??? ?????? ?? ??? ???? ??? ????? ?? ??? ???
  ???? ???? ???????? ???? ????????? ????? ???????
  ??????.

56
(No Transcript)