Brucella

• Humans are accidental hosts

• Acquire this zoonosis from direct contact with an

infected animal or consumption of products of an
infected animal (food borne, eg.: consumption of
unpasteurized dairy products.

• Other names are: Malta Fever, Undulant Fever,

Mediterranean Fever, Rock Fever of Gibraltar, Gastric
Fever
Etiology
 Brucella
• Gram Negative coccobacillus
• Aerobic, non-spore forming, non-motile
• Fastidious in their growth
• Can be grown in blood and chocolate agar
 Epidemiology
• Rare in industrialized country however Brucellosis is
the second most important zoonotic disease in the
world after rabies
• Endemic in many parts of the world
• Endemic in some Asian countries including Sri Lanka,
India, China, Pakistan, Mongolia, and Nepal
• ≈500,000 new cases annually
• 10-30% childhood brucellosis
• B. militensis is the most prevalent species carried by
goats, sheeps, camel and buffalo.

• A history of travel to endemic regions, consumption

of exotic foods or unpasteurized dairy products or
occupational exposure to infected animals might be a
clue.
Pathogenesis
Transmission:
• Consumption of unpasteurized dairy products,
undercooked meat
• Occupational exposures through handling of aborted
fetus or placenta of infected animals
• Mucous membrane or abraded skin contact with infected
tissues
• Inhalation of contaminated aerosol during the processing
of the animal products
Pathogenesis

Major virulence factor: LPS

Taken by local tissue lymphocytes,

Enter the circulation via regional lymph nodes

seed throughout the body with tropism for RES

 Course
• Latent Infection
• Acute (<2 months)
• Subacute (2-12 months)
• Chronic relapsing course (>one year) with severe
complications.
 Clinical Features
• Acute or Insidious
• Incubation period: 2-4 weeks
• Fever (>75 % case); pattern varies
• Arthralgia (80%), Myalgia, Headache, Malaise (68%) ,
Night sweats (72%)
• Weight loss
• Abdominal pain, Diarrhoea, Vomiting
• Rash
• Cough and pharyngitis
• Depression
• Arthritis: monoarthritis (commonly, knee or hip joint in
children and sacroiliac joint in adolescents)
• Occult bacteremia
• hepatic (50%) and spleen enlargement (29%)
• hepatic and splenic abscess may develop
 Serious manifestation/
Complications
• Osteomyelitis/Sacroilitis/Spondylitis
– Child may refuse to walk, radiological apperance may
be normal

• Genitourinary: Epididymo-orchitis, prostatis, testicular

abscess, cystitis, glomerulonephritis

• CVS: Endocarditis
• Neurological Complication:
– Meningitis
– Vasculitis
– Abscess, hemorrhage

• Hemolytic complications: microangiopathic hemolytic

anemia, thrombotic microangiopathy and autoimmune
hemolytic anemia
• GI: Ileitis/colitis/Spontaneous bacterial peritonitis

• Hepatobiliary: Abscess/ Epitheloid granuloma/necrosis

• In pregnants, associated with increased risk of

spontaneous abriton
 Congenital Brucellosis
• Variable symptoms
– Premature delivery
– Low birth weight
– Fever
– Failure to thrive
– Jaundice
– Hepatomegaly
– Splenomegaly
• Abortion risk unclear
 Investigations
• CBC: thrombocytopenia, leukopenia, anemia or
pancytopenia
• LFT: elevated liver enzymes
• USG: hepatosplenomegaly
• Blood C/S
• Bone marrow culture
 Diagnosis
• Blood Culture, Bone marrow culture or other tissue
culture
– Isolation may require upto 4 weeks
– However low yield, insensitive and positive in inly minority of
case
• Bone marrow culture superior in patients who have
recieved previous antimicrobial therapy
• ELISA
• Agglutination test
• Antibodies generated 2-4 weeks after infection
• Serologic test to detect antibodies against B.
abortus, B. militensis and B. suis (not against B. canis)
• No single titer is diagnostic, but most patients with
acute infections have titers ≥ 160
• Low titers initially, 4 fold increase in titers drawn ≥ 2
weeks apart
• Active infection: both IgM and IgG present
• Serum agglutination measures both hence treatment
of serum with 2-mercaptoethanol to measure IgG
alone
• IgG titers decrease with effective therapy, 2 negative
test after treatment indicates favourable response
False positive results
• Yersinia enterocolitica
• Francisella tularensis
• Vibrio cholerae

False negative results

• the prozone effect can give false-negative results in the
presence of high titers of antibody.
• To avoid this issue, serum that is being tested should be
diluted to ≥1 : 320
• The enzyme immunoassay should only be used for
1. Complicated cases
2. Suspected chronic brucellosis
3. Reinfection

• Polymerase chain reaction assays have been developed

but are not available in most clinical laboratories.
 Differential Diagnois

Brucellosis as differential diagnosis of fever of unknown

origin in endemic areas

• Tularemia • Coccidioidomycosis.
• Cat-scratch disease Infections
• Malaria • Mycobacterium
• Typhoid fever
tuberculosis, atypical
• Histoplasmosis
mycobacteria
• Blastomycosis • Rickettsiae
• Yersinia
 Treatment
• Because of the risk of relapse with monotherapy,
combination therapy is generally recommended.
Age/ Antimicrobial Dose Route Duration
Conditions agents

≥ 8 years Doxycycline 4.4 mg/kg/day divided PO ≥6 wk

twice daily;
max 200 mg/day
Plus
Rifampin 15-20 mg/kg/day in 1 or PO ≥6 wk
2 divided doses; max
600-900 mg/day
Alternative
Doxycycline 4.4 mg/kg/day divided PO ≥6 wk
twice daily;
max 200 mg/day
Streptomycin or 20-40 mg/kg/day in 2-4 IM 2-3 wk
divided doses;
max 1 g/day
Gentamicin 6-7.5 mg/kg/day in 3 IM/IV 1-2 wks
divided doses
Age/ Antimicrobial Dose Route Duration
Conditions agents
<8 year TMP-SMX TMP (10 mg/kg/day; max PO ≥6 wk
480 mg/day) and SMX (50
mg/kg/day; max 2.4 g/day)
Plus
Rifampin 15-20 mg/kg/day in 1 or 2 PO ≥6 wk
divided doses; max 600-
900 mg/day
Meningitis, Doxycycline 4.4 mg/kg/day divided PO ≥4-6 mo
osteomyeliti twice daily;
s/ max 200 mg/day
spondylitis
endocarditi Plus
s Gentamicin 6-7.5 mg/kg/day in 3 IV 1-2 wks
divided doses
Plus
Rifampin 15-20 mg/kg/day in 1 or 2 PO ≥4-6 mo
divided doses; max 600-
900 mg/day
 Course
• Relapse in approximately 5–15% of cases
• Antimicrobial resistance is rare.
• Relapse is confirmed by isolation of Brucella within
weeks to months after therapy has ended.
• Prolonged treatment is the key to preventing disease
relapse, and steps should be taken to assure compliance
with the long courses of therapy needed to achieve
eradication.
 Prognosis
• The primary indication of clinical response is slow
• The prognosis after therapy is excellent
• Patients should be followed clinically and serologically for 1-2
yr.
• Since the institution of specific therapy, most deaths are a
result of specific organ system involvement (e.g., endocarditis)
in complicated cases.
• Mprecipitate a Jarisch-Herxheimer– like reaction, presumably
because of a large antigen load
 Prevention
• Prevention of brucellosis depends on effective

eradication of the organism from livestock.

• Pasteurization of milk and dairy products for human

consumption
• No vaccine currently exists
• Education of the public continues to have a prominent

role in prevention of brucellosis.

 Reference
• Nelson Text Book of Pediatrics, 21st edition

• Brucellosis in humans and animals.

WHO/CDS/EPR/2006.7
Thank you