Lecture By Dr.Satti Moh'd Saleh

2. Overview
DR. SATTI MOHD SALLEH

3. Overview
Organism 
History 
Epidemiology 
Transmission 
Disease in Humans 
Disease in Animals 
Prevention and Control 
Actions to Take 
Center for Food Security and Public Health, Iowa
State University, 2008

5. Brucella spp.
Gram negative, coccobacilli bacteria 
Facultative, intracellular organism 
Environmental persistence 
Temperature, pH, humidity 
Frozen and aborted materials 
Multiple species 
Center for Food Security and Public Health, Iowa
State University, 2008

6. The Many Names of
Brucellosis
Human 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 
Center for Food Security and Public Health, Iowa
State University, 2008

7. Transmission to Humans
Conjunctiva or broken skin contacting 
infected tissues
Blood, urine, vaginal discharges, aborted 
fetuses, placentas
Ingestion 
Raw milk & unpasteurized dairy products 
Rarely through undercooked meat 
Center for Food Security and Public Health, Iowa
State University, 2008

8. 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 very rare 
Incubation varies 
5-21 days to three months 
Center for Food Security and Public Health, Iowa
State University, 2008

11. Human Disease
Can affect any organ or organ system 
All patients have a cyclical fever 
Variability in clinical signs 
Headache, weakness, 
arthralgia, depression,
weight loss, fatigue,
liver dysfunction
Center for Food Security and Public Health, Iowa
State University, 2008

12. 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 ○
Center for Food Security and Public Health, Iowa
State University, 2008

13. 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
Center for Food Security and Public Health, Iowa
State University, 2008

14. Human Disease
Congenitally infected infants 
Low birth weight 
Failure to thrive 
Jaundice 
Hepatomegaly 
Splenomegaly 
Respiratory difficulty 
General signs of sepsis (fever, vomiting) 
Asymptomatic 
Center for Food Security and Public Health, Iowa
State University, 2008

15. Differentials
Tuberculosis 
Toxoplasmosis 
CMV 
HIV infection 

16. Brucella spp.
Gram negative, coccobacilli bacteria 
Facultative, intracellular organism 
Environmental persistence 
Temperature, pH, humidity 
Frozen and aborted materials 
Multiple species 
Center for Food Security and Public Health, Iowa
State University, 2008

17. MOST HUMAN INFECTION
CAUSED BY:
BRUCELLA MELIENTESIS ( 3 bio 
Types) Sheep, Goat, Camel -
Brucella Abortus ( Cattle ) 9Bio Types - 
BRUCELLA SUIS– Pigs ( 5Bio types ) - 
Brucella CANIS – Dogs ( Rare ) 

18. B. melitensis
Latin America, Middle East, 
Mediterranean, eastern Europe,
Asia, and parts of Africa
Accounts for most human cases 
In the Mediterranean and Middle East 
Up to 78 cases/100,000 people/year ○
Arabic Peninsula 20% seroprevalence ○
Recent emergence in cattle on 
Middle Eastern intensive dairy farms
Center for Food Security and Public Health, Iowa
State University, 2008

19. Center for Food Security and Public Health, Iowa
State University, 2008

20. B. abortus
Worldwide 
Some countries have 
eradicated it
Notifiable disease 
in many countries
Poor surveillance and reporting 
due to lack of recognition
Fever of Unknown Origin (FUO) 
Center for Food Security and Public Health, Iowa
State University, 2008

21. B. suis
Biovars 1 and 3 
Worldwide problems where swine are raised 
Free 
United Kingdom, Canada 
Eradicated 
Holland, Denmark 
Low Incidence 
Middle East, North Africa ○
Center for Food Security and Public Health, Iowa
State University, 2008

22. B. canis
Poorly understood 
1-19% prevalence in 
United States
Rarely causes disease in 
humans
Center for Food Security and Public Health, Iowa
State University, 2008

23. intracellular Organisms – 
Incubation ; Weeks to Months

24. Human Acquire Infections
from
Ingesting Milk – 
Dairy Products ( Not Pasteurized )- 
Products of Abortion & Placenta 
(Infected Animals, Farmers, Veterinarian
Breast Milk ( Rare )- 
Sexual Transmission ( Rare )- 
Transfusion of Blood (Rare)- 
Only Raw Meat 

25. ---CLINICAL---
Recurrent Prolonged Fever- 
Undulating Patterns- 
A febrile Period- 
Relapse- 
Musculoskeletal Symptoms – 
Fever Mostly at Night- 
Profuse sweating- 
Anorexia, Lethargy ,Depressions- 
Neuropsychiatric Manifestations 

26. MeningoEncephalitis- 
5-10 % Orchitis- 
Dry cough- 
Epistaxis- 
Meletenesis more acute Onset 

27. Children 
( Fever, 
Joint pain 
single joint – 
Rule out RH -fever 

28. Suis ( Deep tissue Abscess )- 
10 % Lymphodenephathy) 
25 % Spleenomegally- 
Endocarditis less 1 % 

29. DIAGNOSIS
GENERAL 
Low WBC w/ Lymphophenia- Low 
platelets-
Low Hag- 
Low Alkaline Phosphates- 
Low Transeminates- 
ESR- 

30. CULTURE
Blood Culture 2/3 Meletenesis- 
1 Week to 3 Weeks to 6 Weeks- 
( Risk of Aerosol )- 
Bone marrow culture- 
Synovial fluid 

31. SEROLOGY

Standard Agglutination Test – 
Prozone Phenomenon ( False Negative 
)-
Increase Dilution – 1/640 – 
Fourfold Rise on Titer ( Acute & 
Convalescent Sample )-
Previous Exposure ( Low Titer )- 

32. SEROLOGY
Negative result does rule out - 
Antigen Used is Important- 
Mercaptoethanol 
( Dissociate 1gm ). 
Cross react -ve-Bacilli (Yersenia, Cholera)- 
EL Dipsticks- 
PCR ( DNA ) sensitive- 
Tissues ( Non Calcified Granuloma- 
Radiology ( differentiate from TB ) 
ISA –Specific IgG ,IGM Immuno essay- 

33. Imaging
Patients with spine symptoms MRI 
examination to rule out spinal cord
compromise.
Plain radiographs, radionuclide bone 
scintigraphy, CT scanning, and joint
sonography.

34. Radiology of Spine
Brucellosis Tuberculosis
Site Lumbar Dorso lumbar
Vertebrae Multiple,contigous Contigous
Disctis Late Early
Body Intact until late Morphology lost early
Canal compression Rare common
Epiphysitis Antero Superior (Pedro- General + Lower Disc
Pons’ –Sign ) region,Centre,subperiost
rial
Osteophyte Anterolateral Parrot beak unusual
Deformity Wedging uncommon Anterior wedging
Recovery Sclerosis Of whole body Variable
Paravertebral abscess Small well localized Common discrete
loss,transverse process
Psoas Abscess Rare More likely

36. Localized snowflake calcification in chronic 
hepatosplenic brucellosis only specific
radiographic finding.

38. TREATMENT

3 Questions Guide Management once 
Diagnosis has been made 
#- Is the disease acute less than 1 
month or Relapsing or Chronic more
than 6 months ###- Is there disease of
bone or joints?-?-
Has TB or other been Excluded?- 

39. MANAGEMENT

Adults =acute non focal disease, 
treatment 6 weeks.-
Patients with focal disease and or 
chronic disease. Treat for 3 months-
No mono therapy ,early relapse, 
Increase 30 %
Endocarditis 6 months 

40. ANTIBIOTICS
 At least 2 antibiotics
Suspicious of TB 
Treat both 
Do not take REFAMPICINE OR STREPTOMYCINE 
if TB not excluded
3. Gold Standard 
Doxycline (6 – 12 weeks 100 mg / BID 
Stripmycine 1G (2-3 weeks) 
4. Gentamycin 8 mg / kg may be substituted for 
streptomycin
Optimum duration ?? 
WHO – 14 days 

41. 5. Alternative 
Doxycycline 6 weeks 
+ or 
Rifampicin 3 months 
(relapse is 10 % compared to 5 % with 
doxystriptomycin)
6. Co-trimoxazole 
High dose (3 tabs / BID) S/E drug rash &anemia, 
supplement with folic acid
For adults (cotrimoxazole + doxycycline better than 
dcotrimoxazole + rifampicin)
Children (3 weeks rather than 6 weeks) 

42. Pregnant women
Rifampicin alone or + Co – trimoxazole 
(avoid or add folic acid in 1st trimester

43. Pregnancy
Premature labour and fetal wastage 
Rifampin — 900 mg once daily for six 
weeks
Rifampin — 900 mg once daily plus 
trimethoprim-sulfamethoxazole(TMP-SMX;
5 mg/kg of the trimethoprim component
twice daily) for four weeks

44. 8. Triple Theraphy 
Doxy + Rifampicin + gentamycine 
Superior to double treatment 
Use for all infection with complication ex. 
Spondylitis, meningitis,endocarditis
(may need volume replacement)
9. ? Ceftriaxone 

45.  Follow – up at 3 weeks
Encourage adherence to therapy 

Return of appetite 
Return of weight 
Investigation WBC, HB, ESR, 
PLATELETES

46.  Follow – up at 3 weeks
Encourage adherence to therapy 

Return of appetite 
Return of weight 
Investigation WBC, HB, ESR, 
PLATELETES

47.  Serology not very useful (variable
pattern for months or year)
Relapse – define as further episode as 
further episode 6months
Failure to adequate treatment 
Treatment for 3 months – include 
streptomycin (to ensure compliance)

48.  Chronic Brucellosis difficult to define
serologically
Exclude chronic fatigue syndrome 
Depression 
Malignancy 
Immunity not solid (repeated infection) 

49. 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

50. Resection of mycotic aneurysms 
Procurement of tissue for diagnostic 
purposes
Chronic hepatosplenic suppurative 
brucellosis may require surgery in addition
to antibiotics to achieve cure

51. 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.

52. Neurobrucellosis
Doxycycline, 
Rifampin 
Trimethoprim-sulfamethoxazole . 
The duration of therapy is generally 
prolonged individualized according to
clinical signs and symptoms
Continued until cerebrospinal fluid 
parameters have returned to normal

53.  Public health aspects
Education to people 
Commitment of all related deportation 
Control of infected hands flucks 
Animal vaccination 
For infected animal test & slaughter 
Financial compliment 

55. 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 
Center for Food Security and Public Health, Iowa
State University, 2008

56. 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
Center for Food Security and Public Health, Iowa
State University, 2008

57. Prevention and Control
B. suis, B. ovis, and B. canis 
Venereal transmission 
Separate females at birthing to reduce 
transmission on the farm or in kennel
Center for Food Security and Public Health, Iowa
State University, 2008

58. RB51
Approved for use February 1996 for calves 
Able to differentiate ―wild type‖ exposure 
from immunization
Lacks LPS-O antigen that causes antibody 
response on serologic or milk tests
Infectious to humans 
Serologically negative upon testing post- 
exposure
CDC registry of human exposures 
32 documented exposures as of 1998 
Center for Food Security and Public Health, Iowa
State University, 2008

59. U.S. Eradication Program
U.S. Department of Agriculture 
1934: Cooperative State-Federal Brucellosis 
Eradication Program
Removal of diseased cattle due to drought ○
1951: APHIS became involved 
1957: 124,000 positive herds 
Approach 
Test, slaughter, trace back, 
investigate, and vaccinate
Center for Food Security and Public Health, Iowa
State University, 2008

60. U.S. Eradication Program
Target date for eradication was 
December 31, 1998
Surveillance 
Brucellosis ring test 
Pooled milk ○
Market Cattle Identification 
Blood test, individual ○
Indemnity for whole herd depopulation 
$250 nonregistered cattle/bison 
$750 or 95% of value minus salvage value for 
registered cattle
Center for Food Security and Public Health, Iowa
State University, 2008

61. U.S. Eradication Program
Fiscal Year 2001 
4.7 million calves vaccinated 
9.9 million cattle tested under the Market 
Cattle Identification program
3 brucellosis herds depopulated 
Indemnity paid = $211,153 ○
An additional $47,700 for purchase of animals ○
or diagnostic purposes
Center for Food Security and Public Health, Iowa
State University, 2008

62. http://www.aphis.usda.gov/vs/nahps/brucellosis/status_rpt/figure11.jpg
Center for Food Security and Public Health, Iowa
State University, 2008

63. http://www.aphis.usda.gov/vs/nahps/brucellosis/status_rpt/figure05.jpg
Center for Food Security and Public Health, Iowa
State University, 2008

64. Brucella as
a Biological Weapon
Aerosolized B. melitensis 
City of 100,000 people 
Inhale 1,000 cells (2% decay per min) 
Case-fatality rate of 0.5% 
50% hospitalized for 7 days 
Outpatients required 14 visits ○
5% relapsed ○
Results 
82,500 cases requiring extended therapy 
413 deaths 
$477.7 million economic impact 
Center for Food Security and Public Health, Iowa
State University, 2008