Nik Noramalina Bt Rozik

Epidemiology
• World-wide zoonosis &most commonly seen in Mediterranean and middle east but Asian continent has also emerged
as significant focus.
• More in developing countries & practically eradicated in developed country
• One of the most common laboratory acquired infection (category B biological weapon)

Transmission
1. Contaminated sheep & goat milk
2. Direct contact with infected animals or their secretion through bruises and laceration on skin
3. Inhalation of infected aerosol: lab acquired
4. Conjunctival inoculation
Pathogenesis

Clinical picture
1. Incubation period : 1-4 weeks but can extend beyond several months
2. Onset: abrupt or insidious over several days to weeks
3. Can affect any organs
4. Most common presentation : fever (previously known as undulant fever) → one of leading cause of fever of unknown
origin
5. Myalgia, arthralgias, loss of appetite, chills, lymphadenopathy, HSM

Focal form More than half patient

When ONLY a specific organ involved

Relapse ➔ Define as reappearance of clinical sign symptoms with/ without positive culture
➔ Frequently occur within 6months after discontinuation of therapy & milder than initial attack
➔ Not due to emergence of abx resistance but due to poor compliance to therapy,inappropriate
abx use, microbial virulence factors & focal infection
Complication
Skeletal • Sacroiliitis in young
• Spondylitis & peripheral arthritis in older
GIT o Enteric fever: nausea, vomiting, diarrhoea & abdominal tenderness
o Spontaneous bacterial peritonitis
o Splenic abscess
Hepatobiliary • Hepatitis
• Liver abscess
• Granulomatous lesion
Nervous o Acute meningitis or meningoencephalitis
system o Chronic peripheral radiculoneuropathy
o Cranial nerve : 6th & 8th
 Nik Noramalina Bt Rozik

Respiratory •
Bronchitis, pneumonia, pleural effusion
•
Granuloma & solitary lung nodule
•
Abscess and cavitation
Haematology Anaemia, leukopenia, Leucocytosis, thrombocytopenia, thrombocytosis
o
Pancytopenia
o
DIVC
o
Massive bleeding or capillary leak: capillary hyperpermeability
o
Genitourinary Epididymoorchitis in male → scrotal pain & swelling, usually unilateral
•
•
Pyelonephritis in female
•
Renal,scrotal,testicular abcess
C VS IE
o
Myocarditis
o
Pericarditis
o
Mycotic aneurysm
o
Ocular •
Optic neuritis
•
Papilledema
•
Keratitis
•
Pan uveitis
Pregnancy •
Chronic infection lead to sterility & abortion (abortion is lesser in human)
→Human placenta do not produce erythritol contributor to abortion
→Presence of Anti Brucella in human amniotic fluid
• IUD,prem delivery
• LBW
Diagnosis
GOLD STANDARD: isolation of organism in cultures of blood,BM,CSF,pleural fluid ,synovial fluid,abcess,tissue or urine

Direct antigen detection 1. PCR targeting cell surface protein ( BCS p31(, periplasmic protein ( BP26) 16S rRNA
2. MALDITOF: need strict culture conditions and sample preparation to ensure correct
identification
Culture

Grew well on CBA incubated in 5-10% CO2,BHI & trypticase soy broth also support growth of
brucella
• Colony: small convex smooth gamma haemolytic, slightly yellow and opalescent
• Gram stain: small coccobacilli resembling grain of sand
• Ident: catalse,urease,oxidase: +
• + H2S
• Only grow in CO2
Serology Serum agglutination Detect antibodies toward B.abortus,B.melitensis& B.suis.
test (SAT) or SAT does not detect B.canis
microplate Defines as positive of titer at least 1:160
aglutination (MAT) • SAT can cross react with M immunoglobulin of Francisella and
V.cholera
• Labor intensive & time consuming
Indirect Coombs Detect non agglutinating Ab against Brucella cells in complicated &
chronic disease
ELISA,Brucellacapt 1. Patient serum added to microwell coated with antibodies against
human IgG,IgM,IgA .
2. Then stained killed Brucella cells are added and agllutination is
observed

Comparable to SAT
Negative result do not exclude disease
 Nik Noramalina Bt Rozik

IgG avidity Antibodies can persist long after recovery

(IgM can remain positive in low titres for months or even years)
(High level of IgG and IgA more than 6months is sign of chronic or
relapse)

Not always possible to distinguish active or past infection

High avidity: immune memory not new onset
Others Lateral flow dipstick for outbreak screening

Other lab investigations FBC, CRP,ESR

Liver function test

Treatment
Need antimicrobial that accumulate in phagocytosis
Monotherapy is not recommended due to treatment failure and
relapse but monotherapy of doxycycline or minocycline can be
considered in absence of focal disease and cost effective in
country with limited resources

• Strepto+ doxy is superior than doxy +rifampicin in term

of relapse and therapeutic failure
• TMP-SMX
o A/W higher rate of relapse • thus must be
combined with other agent
o Imp in children <8y due to dental complication
of doxy
• 3 drug combination including TMP SMX to treat difficult
case eg non responding ,relapse,focal disease

Antibiotic duration: depend on clinical response + CSF parameter return to normal

 Nik Noramalina Bt Rozik

Prevention
1. Secure food supplies
Do not consume undercooked meat or unpasteurized dairy products
2. Proper protection ( gloves,googles,gown,apron) in people handling animals
3. Vaccination of domestic cattle, sheep and goats
• B. abortus:S19,RB51 ,104M
• B.melitensis: REV1
• No human vaccine yet
4. Post prophylaxis exposure
• Rifampicin +doxycycline
• Doxycycline standard dose for 3 weeks
• If contraindication for doxy, TMP SMX