This document discusses Brucellosis, a zoonotic disease caused by bacteria from the Brucella genus. It notes that Brucellosis is endemic in many parts of the world, with six main species that can infect different animal hosts. The most common cause of human infection is B. melitensis from goats and sheep. Transmission occurs through contact with infected animals or consumption of unpasteurized dairy. Clinical presentation in humans is non-specific with fever being the most common symptom. Diagnosis involves blood cultures, serology or PCR. Treatment consists of a combination of doxycycline and rifampin or streptomycin for 6 weeks. Control relies on vaccination of livestock and pasteurization

1. DR. Sobia Khalid
Infectious Diseases

2.  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

3.  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.

4.  Gm - ve cocci, coccobacilli, bacilli.
 Strict aerobic, nonmotile, nonspore forming.
 B. ovis, B. abortus --CO2 supplementation.
 Grow in regular media -- prolonged incubation
> 4 weeks.

5.  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.

6.  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.

7. Entry to the body
Macrophage activation Polymorph migration &
Phagocytosis
Intracelluar multiplication
RES organs
Blood
Any organ
Lymphatics

8.  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

9.  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.

10. Clinical Manifestations
Acute
(8wks)
Undulant
(<52 wks)
Chronic
(>52wks)
Age Children,
young adults
Young adults > 40 yrs
Arthralgia + + + + + + + +
High fever 95% 50-70% No
Hepatomegaly 66% 50% Occasional
Splenomegaly 50-70% < 40% Rare
Psychiatric No Occasional Frequent
Ocular
(uveitis)
No 1-2% 5-10%

11.  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).

12.  Skeletal 20-60% :
 arthritis, spondylitis, osteomyelitis.
 sacroiliitis - most common.
 athritis - oligoarticular : hip, knee & ankles.
Joint asp. - monocytosis, culture +ve in 50 %

13.  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%

14.  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

15.  Genitourinary
 Epidydemoorchitis
 Pyonephrosis (rare)
 Cutaneous
 Nonspecific
 Hematologic
 Anemia
 Leukopenia
 Thrombocytopenia

16.  History of animal contact is pivotal
 In endemic area, it should be in the
DDx of any nonspecific febrile illness

17.  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

18.  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

19. IgM
S

20.  AGG = IgG + IgM
 2ME = IgG

21.  Preantibiotic era
 Mortality 2% mainly endocarditis
 Morbidity
 High with B. melitensis
 Nerve deafness
 Spinal cord damage

22.  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

23. Drugs against Brucella
 Tetracyclines
 Aminoglycosides
 Streptomycin since 1947
 Gentamicin
 Netilmicin
 Rifampicin
 Quinolones - ciprofloxacin
 ?3rd generation cephalosporins

24. 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

25. 10
100
1000
10000
1 2 3 4 5 6
Weeks
Titer
IgG
IgM
Untreated Brucellosis

26. 10
100
1000
10000
1 2 3 4 5 6 7
Months
Titer
IgG
IgM
Treated Brucellosis
Treatment

27. Relapse
Predictors of Relapse
Male sex
Inadequate antibiotic therapy.
Positive culture on initial disease
Thrombocytopenia
Ariza, et al: CID 20:1241, 1995