BRUCELLOSIS

Historical Background
Malta Fever
Major health problem to British troops in Malta in the 19th and early
20th centuries.

Cases(1901-07)

Deaths

Navy

1705

30

Army

1947

55

Civil services

4627

489

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 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 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
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

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

Gm - ve cocci, coccobacilli, bacilli.

Strict aerobic, nonmotile, nonspore forming.
B. ovis, B. abortus --CO2 supplementation.
Grow in regular media -- prolonged
incubation > 4 weeks.

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
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
Entry to the body
Macrophage activation
Intracelluar multiplication
Lymphatics

RES organs
Blood
Any organ

Polymorph migration &

Phagocytosis

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

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 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%

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 Manifestations

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

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 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 Manifestations
Genitourinary
Epidydemoorchitis
Pyonephrosis (rare)

Cutaneous
Nonspecific

Hematologic
Anemia
Leukopenia
Thrombocytopenia

Diagnosis

History of animal contact is pivotal

In endemic area, it should be in the
DDx of any nonspecific febrile
illness

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

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

Prognosis
Preantibiotic era
Mortality 2% mainly endocarditis

Morbidity
High with B. melitensis
Nerve deafness
Spinal cord damage

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
Drugs against Brucella
Tetracyclines
Aminoglycosides
Streptomycin since 1947
Gentamicin
Netilmicin

Rifampicin
Quinolones - ciprofloxacin
?3rd generation cephalosporins

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

Relapse
Predictors of Relapse
Male sex
Inadequate antibiotic therapy.
Positive culture on initial disease
Thrombocytopenia

Ariza, et al: CID 20:1241, 1995