Genus: Brucella
Causative agent of undulant fever. This disease is also called “Malta Fever” Undulant fever
can be also called “ Brucellosis”.
Species of genus Brucella:
Brucellae are characteristically located intracellularly.
Morphology
The typical m.o. are predominantly gram negative coccobacilli, and stain irregularly. They
are aerobic and nonmotile m.o.
Culture:
Brucellae are adapted to intracellular compartment of cells (fastidious). So, their
requirments are complex including a.a., sugars, salts, and vitamines. The best media used
for the cultivation of these m.o. are:
1. Trypticase soy agar.
2. Castaneda biphasic medium (broth & agar).
3. Blood agar & blood culture media.
4. MacConkey’s agar
5. Brucella selective medium
6. Thionine tryptose agar.
7. Serum dextrose agar.
7. Glucose dextrose agar.
The growth characteristics:
1. B. abortus requires 5-10% CO2 for growth, whereas the other species grow in air.
2. nonhaemolytic, slightly yellowish in young cultures but brownish in old ones .
3. Also, the colonies from young cultures the m.o. are capsultaed when stained are
vireulent, whereas from old culture the m.o. are uncapsulat-ed and are avirulent.
Biochemically:
a) Brucellae can utilize carbohydrates, but with no acid and gas production (not
fermenter),
b) H2S is produced only by B. abortus and B. suis, most species reduce nitrate to nitrite,
oxidase positive, and are sensitive to acid and heat
Antigenic Structure:
1. Two lipopolysaccharides antigens (A & M) are present in different proportions among the
different species.
2. Superficial L antigen resembles the Vi antigen (virulence) of Salmonella.
Pathogenesis & Pathology:
The common routes of infections in humans are:
1. Intestinal tract ( ingesion )
2. Mucous membrane ( droplet )
3. Skin (contact with infected animal or human ).
4. Conjunctiva (rare; airborne).
5. Breast milk (lactating woman).
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The m.o. progress from the portal of entery, via lymphatic channels and regional L.N., to
the thoracic duct and the bloodstream,
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distributes them to the parenchymatous organs.
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Granulomatous nodules that may develop into abscesses form in lymphatic tissue, liver,
spleen, bone marrow, and other parts of the RES. In such lesions the m.o. is
intracellularly.
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Osteomyelitis, meningitis,orchitis, arthritis, vertebral collapse or cholecystitis may occur
Histological reaction in brucellosis :
1. consists of proliferation of mononuclear cells, exudate of fbrin, coagulation necrosis,
and fibrosis. The granulomas consist of epithelioid and giant cells, with central necrosis
and peripheral fibrosis.
2. B. abortus usually causes mild disease without suppurative complications;
non-caseating granulomas of the RES are found.
3. B. melitensis infection is more acute, severe and causes granulomatous lesions.
4. These two species are common in Iraq.
5. erythritol (a growth factor for Brucella). The proliferation of m.o. in pregnant animals
leads to placentitis and abortion (economic loss). There is no erythritol in human .
Clinical Finding:
1) The I.P. Of brucellosis is 1- 6 weeks. The onset is insidious, with malaise, fever,
weakness, aches, and sweat.
2) The fever usually rises in the afternoon; its fall during the night is accompanied by
drenching sweat.
3) There may be GI and nervous symptoms. L.N. enlarge, and the spleen becomes palpable.
4) Hepatitis may be accompanied by jaundice.
5) Deep pain and disturbances of motion, particularly in vertebral bodies suggest
osteomyelitis. The manifestations may suside in weeks or months , although localized
lesions and symptoms may continue.
Following the initial infection, a chronic stage may develop; characterized by weakness,
aches and pains, low grade fever, nervousness or depression and other nonspecific
manifestations including psychoneurotic symptoms.
The diagnosis of “chronic brucellosis” is difficult to establish. Because
Brucellae usually can
not be isolated from such patients except in only 2% of them.
Diagnostic Laboratory Tests:
A. Specimens: Blood and biopsy material
B. Culture
C. Serology:
1) IgM antibody levels rise during the FIRST
week of acute illness, peak at 3 months,
and may persist during chronic disease.
Even with approperiate treatment, high
IgM may persist up to 2 years.
2) IgG antibody levels rise 3 weeks after
onset of acute disease, peak at 6- 8
weeks and remain high during chronic
disease.
3) IgA levels parallel the IgG levels; could be
blocking antibody .
The serological tests used for diagnosis of
brucellosis are:
1. Agglutination test (tube or slide); usig:
a. Heat-killed phenolized smooth
standerized brucella antigens.
b. Rose bengal antigens (stained red).
The significant titre = 1/160 or higher.
Cross reaction may occur with cholera
vaccine, S.typhi /paratyphi , or Yersinia.
a) 2. 2-Mercaptoethanol test; 2-ME can
destroy IgM and leaves IgG. This may be
used to differentiate between current
/recent brucellosis from previous /old
brucellosis.
b) Also, is useful in chronic active
brucellosis.
3. Blocking antibodies; These are IgA
antibodies that interfere with agglutination by
IgG & IgM and cause false negative result
(prozone phenomena).
4. Skin test (Brucellergen or Brucellin); it is
DHS reaction to I.D. Injection of a protein
brucella extract.
5. ELISA , RIA or Immunofluorescent ; for Ab
detection.
Immunity:
Resistance to subsequent attack may be produced. Both cellular and humoral immunities
are induced.
Treatment:
Combined anti-microbial drugs are used, taking in consideration that the m.o. is an
intracellular one:
1. Ampicillin or tetracycline with Streptomycin give good result. Cotrimoxazole may be
added.
2. Refampin with doxycycline gives 97% cure rate. Also, an aminoglycoside drug could be
added.
Treatment should be continued for at least 6 weeks and for bone or joint infections the
treatment continues for at least 8 weeks.
For neuro-Brucellosis chloramphenicol or ampicillin could be used with other drugs.
Epidemiology, Prevention & Control:
1. Brucellae are animal pathogens transmitted to humans accidentally.
2. Eradication of brucellosis in animals by immunization
3. Immunization of humans is experimental, but was attempted in individuals at high risk of
getting brucellosis.
4. Pasteurization of milk and milk products and reduction of occupational hazards are also
important steps.