BRUCELLA

Brucella

Brucella is a genus of small, gram-negative, facultative intracellular bacteria that cause brucellosis, a zoonotic infection transmitted to humans from infected animals or animal products. The disease can affect various organs and systems, leading to a range of clinical manifestations, often with a chronic course. The most common species associated with human infections are Brucella melitensis, Brucella abortus, Brucella suis, and Brucella canis.

Microscopic Appearance

• Small, gram-negative coccobacilli.

• Non-motile and non-spore-forming.

• Usually appear singly or in pairs.

• Difficult to visualize with standard Gram staining, often requiring longer staining times.

Virulence Factors

• Lipopolysaccharide (LPS):

  • Brucella's LPS has a modified structure compared to other gram-negative bacteria, which helps it evade the host's immune system and contributes to its ability to cause chronic infections.

• Type IV Secretion System (VirB):

  • A complex that allows Brucella to inject effector proteins into host cells, facilitating intracellular survival and replication within macrophages.

• Intracellular Survival:

  • Brucella can survive and replicate within host macrophages by avoiding lysosomal degradation, enabling it to evade the immune response and establish chronic infections.

• BCV (Brucella-containing vacuole):

  • The bacteria survive within a specialized vacuole that resists fusion with lysosomes, allowing it to replicate and persist within host cells.

Pathogenesis

• Transmission:

  • Humans are typically infected through direct contact with infected animals (e.g., cattle, goats, pigs, dogs), consumption of unpasteurized dairy products, or inhalation of aerosols.

  • The bacteria enter through mucous membranes, cuts, or inhalation, then travel to regional lymph nodes and spread hematogenously to multiple organs.

• Intracellular Survival:

  • Once inside the host, Brucella localizes within macrophages, where it evades the immune response and multiplies within the BCV.

• Chronic Infection:

  • The ability of Brucella to establish chronic infections is linked to its capacity to survive in macrophages, leading to prolonged and recurrent clinical symptoms.

Clinical Manifestations

• Acute Brucellosis:

  • Symptoms typically develop 2-4 weeks after exposure and include fever (often undulant or relapsing), sweating, malaise, fatigue, anorexia, headache, and arthralgia.

  • The fever may be intermittent or continuous, often accompanied by drenching night sweats with a characteristic "wet hay" odor.

• Chronic Brucellosis:

  • If untreated, the disease can progress to a chronic form with persistent or recurrent symptoms, including fatigue, depression, and joint pain.

  • Focal infections may develop, affecting the liver (hepatitis), spleen, bones (osteomyelitis), joints (arthritis), and the genitourinary system (orchitis, epididymitis).

• Complications:

  • Endocarditis, though rare, is the most serious complication and can be fatal if not promptly treated.

  • Neurological involvement (neurobrucellosis) can present with meningoencephalitis, radiculopathy, or peripheral neuropathy.

Lab Diagnosis

• Culture:

  • Blood culture is the gold standard for diagnosing brucellosis, but it requires prolonged incubation (up to 4 weeks) due to the slow-growing nature of Brucella.

  • Cultures from other sites (e.g., bone marrow, liver) may be necessary in focal disease.

  • Stamps’s method- modified zeihl neelson method

    Brucella organisms stain red against a blue background

  • Basal media- tryptose soy agar (TSA)

• Serology:

  • The standard tube agglutination test (SAT) detects antibodies against Brucella and is commonly used for diagnosis. A fourfold rise in antibody titers between acute and convalescent sera is diagnostic.

  • Enzyme-linked immunosorbent assay (ELISA) can detect both IgM and IgG antibodies, providing information on the stage of infection.

• PCR:

  • Polymerase chain reaction (PCR) is used to detect Brucella DNA in blood or tissue samples, offering rapid and sensitive diagnosis.

• Microscopy:

  • Direct examination of clinical specimens is generally not useful due to the small size and intracellular location of the bacteria.

Treatment

• Antibiotics:

  • Combination therapy is recommended to prevent relapse:

    • Doxycycline (6 weeks) combined with rifampin (6 weeks) is the most common regimen.

    • An alternative is doxycycline combined with streptomycin (2-3 weeks) or gentamicin (7-10 days) for more severe cases.

  • Treatment duration varies depending on the severity and presence of focal complications.

• Management of Complications:

  • Prolonged or additional antibiotic therapy may be required for focal complications like osteomyelitis or endocarditis.

  • Surgical intervention may be necessary for endocarditis or abscesses.

• Prevention:

  • Avoiding unpasteurized dairy products and ensuring proper handling of animal products are key preventive measures.

  • Vaccination of livestock is used in endemic areas to reduce the incidence of animal-to-human transmission.

  • Occupational safety measures, such as protective clothing and equipment, are important for those working in high-risk environments (e.g., slaughterhouses, laboratories)