Brucellosis

• The most common zoonotic febrile illness seen in children and adults associated with consumption of
unpasteurized milk, exposure to cows, goats, pigs, or sheep, and inadvertent laboratory exposure during
handling of Brucella infected tissue or cultures. National (Saudi Arabia) seroprevalence (15%).
• Rarely, cases due to exposure to marine mammal (e.g., porpoise) Brucella species.
• Brucella melitensis (causes more severe infection) and B. abortus cause the bulk of human disease.
• Relapse rate, post-treatment, is 10 (5-15)%. Usually during the first 6 months after treatment.
• Mortality is low and usually due to cardiac presentations.

Classification:

• Small gram-negative aerobic intracellular coccobacilli, slow growing.

• Brucella melitensis: goats, sheep & camels (Middle East).
• Brucella abortus: Cattle.
• Brucella suis: Pigs.
• Brucella canis: dogs and Other Brucella species may also cause disease.

Clinical disease:

• Acute vs subacute vs chronic.

Acute: non-specific febrile syndrome, non-focal. Localized Diseases
Relapsing/Undulant: Malta fever: arthritis, back pain, sweats and Osteoarticular disease: (20-30%,
fatigue. especially sacroileitis). Commonest
Chronic: may be cyclic or localized. Neurological and psychiatric Genital: 6-8%.
presentations described. Neurologic: 3-5%.
• Fever occurs in 90%. Cardiac: 1-3%.
• Malodorous perspiration almost pathognomic but uncommon. Pulmonary: 1-2%.
Renal: <1%.
Physical Examinations:

• Hepatomegaly or splenomegaly: 33%.

• Lymphadenopathy: 10%.

Lab findings:

• Elevated ESR.
• leukopenia < 4000 cells/µl and relative lymphocytosis (50%).
2-Mercaptoethanol (2-ME)
• Mild hepatitis.


It causes cleavage of disulphide bonds
Diagnosis:
of IgM and loss of the agglutinin
Blood culture: activity. Thus the comparison of the
• Gold standard (Category B agent of bioterrorism). results in the absence or presence of
• Yield: In acute (40-90%). In chronic (5-20%). this agent is often used to distinguish

IgM from IgG activity and tend to
Bone marrow culture:
differentiate between early and
• Gold standard & higher yield (addition of 15-20%).
persistent infection in human
Serology: brucellosis.
• Positive serologic studies:
Serum Agglutination test: ≥ 1:640 in our country!
ELISA: preferred in chronic or complicated infection and CNS disease.
dilute serum up to 1:160; prozone effect can cause false negative results at low levels of dilution.
• All positive rapid serologies require confirmation with Brucella sp. specific agglutination

Real-time PCR:

• Sensitivity 50-100% and specificity 60-90%.

Imaging:

• CT or MRI: MRI is preferred for vertebral osteomyelitis.

Treatment:

Treatment:
• Doxycycline 100 mg po bid + Gentamicin 5 mg/kg IV once daily x 7 days.
• Doxycycline 100 mg po bid + Rifampin 600-900 mg po once daily (WHO Recommendation).
Duration:
• 6 weeks unless specified.
Non-Localizing
Systematic review and meta-analysis of randomized clinical trials in the treatment of human
Disease
brucellosis (2012)

• There were no significant differences between combined doxycycline-streptomycin and

combined doxycycline-gentamicin (OR = 1.89; CI95% = 0.81-4.39).
• Treatment with rifampicin and quinolones was similar to combined doxycycline-rifampicin
(OR = 1.23; CI95% = 0.63-2.40).
Treatment:
Spondylitis • Doxycycline 100 mg po bid + Rifampin 600–900 mg po q24h + once daily Gentamicin IV for
Sacroileitis first 7 days.
Arthritis • Ciprofloxacin 750 mg po bid + Rifampin 600-900 mg po once daily.
Osteomyelitis Duration:
• ≥ 3 months unless specified.
Treatment:
• TMP-SMX 5 mg/kg of TMP component po bid + Rifampin 600–900 mg po q24h.
Brucella during
Pregnancy:
Duration:
• 4 weeks.
Treatment:
• Doxycycline 100 mg IV/po bid + Rifampin 600-900 mg po once daily + Ceftriaxone 2 gm IV
Neurobrucellosis q12h.

Duration:
• ≥ 8 weeks up to 2 years. Continue until CSF is normal.
Treatment & Duration:
• Almost always need surgery
Endocarditis PLUS
• Antibiotics. 2-4 weeks of once daily Gentamicn 5 mg/kg IV + 6 weeks to 6 months of the
combination of Rifampin, Doxycycline and TMP-SMX.
Treatment & Duration:
Post-Exposure • Limited data and regimens often not well-tolerated:
prophylaxis • Doxycycline 100 mg po bid + Rifampin 600 mg po once daily for 3 weeks; if B. abortus
after laboratory strain RB51 (resistant to Rifampin): Doxycycline alone for 3 weeks.
exposure. • If Doxycycline not well-tolerated or employee is pregnant TMP/SMX-DS po bid with or
without Rifampin 600 mg po once daily x 3 weeks.

Treatment failures:
• 5-8%.

Brucellosis in Pregnancy:

• There was no apparent relationship between the magnitude of
the titer and the occurrence of bacteremia.
• Serum agglutinin titers ≥ 1:2560, compared with those < 1:2560,
were not significantly associated with the occurrence of
spontaneous abortion (P=0.5).
• Bacteremia is mentioned as a risk factor for spontaneous
abortion in the literature, but our study found no association
between maternal bacteremic status and spontaneous abortion.
 • Although the number of patients in this study was not large, we were still able to extract from our findings that
cotrimoxazole and rifampin appear to be safe agents for treating brucellosis in pregnant women, because there
were no specific drug-related adverse effects in the 36 newborns for whom there were follow up data.

Comments:

• Observational study reports higher frequency (p 0.026) of clearance of Brucella DNA from whole blood with
triple therapy: (Gentamicin or Streptomycin) + Doxycycline + Rifampin.
• Antibody testing of exposed personnel via State labs or CDC at 2, 4, 6 and 24 weeks; NOTE: poor antibody
response to B. abortus strain RB51.

Recommendations for safe laboratory practices to avoid exposure to Brucella spp.

1. When brucellosis is suspected, clinicians or forwarding laboratories should note on the laboratory submission:
"Suspect or rule out brucellosis."
2. Review laboratory containment methods and microbiologic procedures to ensure compliance with
recommendations in the Biosafety in Microbiological and Biomedical Laboratories, Fifth Edition.
3. Use primary barriers (ie, safety centrifuge cups, personal protective equipment, and Class II or higher
biological safety cabinets [BSCs]) for procedures with a high likelihood of producing droplet splashes or
aerosols.
4. Use secondary barriers: restrict access to the laboratory when work is being performed and maintain the
integrity of the laboratory air-handling system by keeping external doors and windows closed.
5. Avoid causing splashes or aerosols when performing procedures on unidentified isolates.
6. Prohibit sniffing of open culture plates to assist in the identification of isolates.
7. Manipulate isolates of small gram-negative or gram-variable rods initially inside a BSC.

References:
• Johns Hokpkin’s antibiotic guide.
• Sanford guide.
• Uptodate.
• Others.

Good Luck
Jweida