II. Epidemiology

  1. US Incidence <100 cases per year (0.34/100,000)

III. Causes

  1. Brucella abortus (cows)
  2. Brucella suis (pigs)
  3. Brucella melitensis (goats, camels)
  4. Brucella canis (dogs)

IV. Pathophysiology

  1. Facultative intracellular Parasite
    1. Releases endotoxin when dies
  2. Infective dose: 10-100 organisms
  3. Incubation: 5-60 days

V. Transmission

  1. Zoonosis from animal exposure or infected animal products
    1. Tissue from Sheep in U.S.
    2. Unpasteurized milk
    3. Cow, pig, goat or sheep exposure
  2. Vaccine exposure
  3. No transmission person to person
  4. Enters via mucus membranes, broken skin, or inhalation

VI. Risk Factors

  1. Veterinarians
  2. Farm workers
  3. Meat processing plants
  4. Travel or residence in endemic region
    1. Mediterranean
    2. India
    3. North Africa, East Africa
    4. Central Asia, South Asia

VII. Symptoms

  1. Intermittent Fevers
    1. Undulating fever
    2. Temperature peaks in evening to 101-104
  2. Arthralgia especially sacroileitis (20-30%, up to 90% in some studies)
  3. Weakness
  4. Lassitude
  5. Weight loss
  6. Headache
  7. Sweating
  8. Chills

VIII. Signs

  1. Hepatosplenomegaly (20-30%)
  2. Cervical or Inguinal Lymphadenopathy (12-20%)
  3. Orchitis or Epididymitis (2-40%)
  4. Purpura (5%)

X. Complications

  1. Meningitis
  2. Endocarditis

XI. Labs

  1. Culture (Slow growing, fastidious organism)
    1. Blood Culture (70% sensitive in acute illness)
    2. Discharge Culture
    3. Bone Marrow Aspirate (90% sensitive in acute illness)
  2. Complete Blood Count
    1. Thrombocytopenia
    2. Granulopenia
    3. Leukopenia with relative Lymphocytosis
    4. Anemia
  3. Brucella Serology
  4. Brucella PCR
  5. Liver Function Tests (elevated in 30-60%)
  6. Bone Marrow Biopsy show Granuloma

XII. Management: Non-localized

  1. Precautions
    1. Risk of relapse in 10% of cases
    2. See other references for neurobrucellosis and endocarditis
  2. Age <8 years old or pregnancy
    1. TMP-SMZ 5 mg/kg of TMP orally twice daily for 6 weeks AND
    2. Rifampin 15-20 mg/kg up to 600-900 mg orally daily for 6 weeks
  3. Age >8 years old and adults
    1. Doxycycline 100 mg orally twice daily for 6 weeks AND
    2. Gentamicin 5 mg/kg IV daily for 7 days AND
    3. Consider Rifampin 15-20 mg/kg up to 600-900 mg orally daily for 6 weeks
      1. May be used in place of Gentamicin
      2. For Spondyloarthropathy or Arthritis, use all 3 agents, with Rifampin with Doxycycline for 3 months
      3. When combined with Doxycyline and Gentamicin improves clearance rates without relapse
        1. Vrioni (2014) Antimicrob Agents Chemother 58:7541-4 [PubMed]

XIII. Prevention

  1. See other references for Post-exposure Prophylaxis

XIV. Course

  1. Weeks to months

XV. Prognosis

  1. Case Fatality <5% treated

XVI. References

  1. (2016) Sanford Guide to Antibiotics, IOS app accessed 4/14/2016
  2. (1998) Medical Management of Biological Casualties
    1. U.S. Army Medical Research Institute of ID

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Definition (NCI_CDISC) Any bacterial organism that can be assigned to the species Brucella melitensis.
Definition (NCI) A species of aerobic, Gram-negative, coccobacilli shaped bacteria assigned to the phylum Proteobacteria. This species is nonmotile, non-spore forming, catalase, oxidase and urease positive, reduces nitrates, does not produce hydrogen sulfide, grows in both basic fuchsin and thionine, and is negative for Tiblisi and Weybridge phage lysis. B. melitensis is found in goats and sheep and is pathogenic to these species as well as causes brucellosis in humans.
Definition (MSH) A species of the genus BRUCELLA whose natural hosts are sheep and goats. Other mammals, including humans, may be infected. In general, these organisms tend to be more virulent for laboratory animals than BRUCELLA ABORTUS and may cause fatal infections.
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SnomedCT 72829003
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Japanese マルタ熱菌, マルタネツキン
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Czech Brucella melitensis
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English Brucella melitensis (Hughes 1893) Meyer and Shaw 1920 (Approved Lists 1980) emend. Verger et al. 1985, Brucella melitensis (Hughes 1893) Meyer and Shaw 1920 (Approved Lists 1980), brucella melitensis, Brucella melitensis, BRUCELLA MELITENSIS, Streptococcus Miletensis, Micrococcus melitensis, Brucella melitensis (organism)
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Norwegian Brucella melitensis
Spanish Micrococcus melitensis, Brucella melitensis (organismo), Brucella melitensis
Portuguese Micrococcus melitensis, Brucella melitensis
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Ontology: Brucellosis (C0006309)

Definition (MSHFRE) Infection provoquée par des bactéries du genre Brucella impliquant surtout le système réticulo-endothélial. Maladie caractérisée par fièvre, affaiblissement, malaise et amaigrissement.
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Definition (MSH) Infection caused by bacteria of the genus BRUCELLA mainly involving the MONONUCLEAR PHAGOCYTE SYSTEM. This condition is characterized by fever, weakness, malaise, and weight loss.
Concepts Disease or Syndrome (T047)
MSH D002006
ICD9 023.9, 023
ICD10 A23 , A23.9
SnomedCT 111804008, 186310006, 187304000, 154296006, 75702008
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English Brucelloses, Fevers, Undulant, Malta Fever, Undulant Fever, Undulant Fevers, Fever, Malta, BRUCELLOSIS, Fever, Undulant, Brucellosis, unspecified, [X]Brucellosis, unspecified, Brucellosis due to Brucella sp., Brucellosis due to Brucella sp. (disorder), brucellosis (diagnosis), brucellosis, Brucella infections, Unspecified brucellosis, Brucellosis NOS, undulant fever, Brucellosis [Disease/Finding], mediterranean fever, rock fever, cyprus fever, brucelloses, fever mediterranean, malta fever, fever malta, Fever, Gibraltar, Cyprus Fever, Fevers, Rock, Gibraltar Fever, Fever, Cyprus, Fever, Rock, Cyprus Fevers, Fevers, Cyprus, Rock Fever, Rock Fevers, Brucellosis NOS (disorder), [X]Brucellosis, unspecified (disorder), Brucellosis due to Brucella species, Brucellosis due to Brucella species (disorder), Infection due to Brucella, Malta fever, Undulant fever, Mediterranean fever, Brucellosis (disorder), Cyprus fever, Gibraltar fever, Rock fever, Gibraltar; fever, Malta; fever, fever; Cyprus, fever; Gibraltar, fever; Malta, infection; Brucella, Brucella; infection, Bruce, Brucellosis, NOS, Brucellosis
Italian Infezioni da brucella, Brucellosi non specificata, Febbre mediterranea, Febbre maltese, Febbre ondulante, Brucellosi
Dutch niet-gespecificeerde brucellose, mediterrane koorts, brucellose, niet-gespecificeerd, Brucella; infectie, Gibraltar; koorts, Malta; koorts, infectie; Brucella, koorts; Cyprus, koorts; Gibraltar, koorts; Malta, Brucellose, niet gespecificeerd, Brucella-infecties, brucellose, Brucellose, Brucellosis, Febris undulans, Malta-koorts
French Brucellose non précisée, Brucellose, non précisée, Infections à Brucella, Brucellose, Fièvre méditerranéenne, Fièvre ondulante, Mélitococcie, Fièvre de Malte
German unspezifische Brucellose, Brucellose, unspezifisch, Mittelmeerfieber, Malta-Fieber, Brucellose, nicht naeher bezeichnet, Brucella-Infektionen, Brucellose, Febris undulans, Maltafieber
Portuguese Febre mediterrânica, Febre ondulante, Brucelose NE, Brucelose Pulmonar, Infecções a Brucella, Brucelose, Febre de Malta, Febre Ondulante
Spanish Fiebre mediterránea, Fiebre ondulante, Brucelosis no especificada, [X]brucelosis, no especificada (trastorno), brucelosis causada por especies de Brucella (trastorno), brucelosis, SAI (trastorno), brucelosis causada por especies de Brucella, brucelosis, SAI, [X]brucelosis, no especificada, Brucelosis Pulmonar, brucelosis (trastorno), brucelosis, fiebre de Malta, fiebre del Mediterráneo, fiebre mediterránea, fiebre ondulante, Infecciones por brucella, Brucelosis, Fiebre de Malta, Fiebre Ondulante
Japanese ブルセラ症、詳細不明, 詳細不明のブルセラ症, ブルセラ感染, ブルセラショウ, ブルセラショウショウサイフメイ, ブルセラカンセン, チチュウカイネツ, ハジョウネツ, ショウサイフメイノブルセラショウ, マルタネツ, ブルセラ症, 地中海熱, マルタ熱, 波状熱
Swedish Brucellos
Czech brucelóza, Brucelózy, Febris undulans, Blíže neurčená brucelóza, Brucelóza, Brucelóza, blíže neurčená, Maltská horečka, Středozemní horečka, maltská horečka, vlnitá horečka
Finnish Bruselloosi
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Hungarian Brucella fertőzések, brucellosis, nem meghatározott, Mediterrán láz, nem meghatározott brucellosis, Febris undulans, Brucellosis, Máltai láz
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Concepts Bacterium (T007)
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SnomedCT 186307004, 48317004
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French Brucella melitensis biovar suis, Brucella suis
Japanese ブタ流産菌ブルセラ症, ブタリュウザンキンブルセラショウ
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English Brucella melitensis bv. Suis, Brucella melitensis (Hughes 1893) Meyer and Shaw 1920 (Approved Lists 1980) emend. Verger et al. 1985, biovar Suis, Brucella suis Huddleson 1929 (Approved Lists 1980), Brucella suis, BRUCELLA SUIS, Brucella melitensis biovar suis, Brucella melitensis biov suis, Brucella suis (organism)
Czech Brucella suis
Finnish Brucella suis
Italian Brucella melitensis biovar suis, Brucella suis
Polish Brucella suis
Hungarian Brucella suis
Norwegian Brucella suis, Brucella melitensis biovar suis
Spanish Brucella melitensis, biovariedad suis, Brucella suis (organismo), Brucella suis
German Brucella suis
Dutch Brucella suis
Portuguese Brucella suis