Brucellosis is a zoonotic infectious disease, meaning it is transmitted from animals to humans. It is caused by bacteria belonging to the genus Brucella. It is a systemic disease that can affect various organs and tissues, leading to a wide range of symptoms.

Causative Agent (Bacteria)
The main Brucella species that cause disease in humans are:

• Brucella melitensis: Primarily found in sheep and goats (most common and severe cause of human brucellosis worldwide).

• Brucella abortus: Primarily found in cattle.

• Brucella suis: Primarily found in pigs.

• Brucella canis: Primarily found in dogs (less common cause of human disease).
  Brucella are small, Gram-negative, facultative intracellular coccobacilli. Being intracellular means they can survive and multiply within host cells (like macrophages), which helps them evade the host immune system and contributes to the chronic nature of the disease.

Reservoirs (Where the Bacteria Live)
The primary reservoirs are domestic animals:

• Sheep

• Goats

• Cattle

• Pigs

• Dogs
  Wild animals (e.g., bison, elk, deer, caribou, wild boar) can also be reservoirs.

Modes of Transmission to Humans
Humans are usually infected through direct or indirect contact with infected animals or their contaminated products.

1. Ingestion of Contaminated Food Products:

   • This is the most common route.

   • Consumption of unpasteurized (raw) milk and dairy products (e.g., cheese, butter, ice cream) made from milk of infected animals.

   • Consumption of undercooked meat from infected animals (less common).

2. Direct Contact with Infected Animals or Their Tissues/Secretions:

   • Through breaks in the skin or mucous membranes (eyes, mouth).

   • Exposure to blood, placenta, fetuses, urine, or other tissues of infected animals.

   • High risk for farmers, veterinarians, slaughterhouse workers, abattoir workers, and livestock handlers.

3. Inhalation of Aerosolized Bacteria:

   • Breathing in airborne particles containing Brucella bacteria.

   • Can occur in stables, abattoirs, laboratories (where cultures are handled), or during procedures like assisting with animal births.

4. Accidental Inoculation:

   • Needle-stick injuries in veterinarians or laboratory workers.

   • Splashing contaminated material into the eyes.
     Human-to-human transmission is very rare but has been documented through sexual contact, breastfeeding from an infected mother, blood transfusions, and tissue transplantation.

Incubation Period
Typically ranges from 1 week to 2 months, but can be longer (several months).

Pathogenesis (How it Causes Disease)

• Brucella bacteria enter the body through the skin, mucous membranes, gastrointestinal tract, or respiratory tract.

• They are taken up by phagocytic cells (macrophages and neutrophils) and transported to regional lymph nodes.

• From the lymph nodes, they can spread via the bloodstream (bacteremia) to various organs and tissues, particularly those rich in the reticuloendothelial system (liver, spleen, bone marrow, lymph nodes).

• Their ability to survive and replicate within macrophages allows them to evade host defenses and establish chronic infection.

• Granulomas (collections of immune cells) may form in affected tissues.

Clinical Manifestations (Signs and Symptoms)
Symptoms are often non-specific and can vary greatly in onset (acute or insidious) and severity. The classic symptom is an “undulant” fever (rising and falling fever, often higher in the afternoons/evenings).

• General Symptoms:

  • Fever (often undulant, intermittent, or remittent)

  • Profuse sweating (especially at night, often with a characteristic “malty” or “wet hay” odor)

  • Malaise, fatigue, weakness

  • Anorexia (loss of appetite), weight loss

  • Headache

  • Myalgia (muscle pain), arthralgia (joint pain)

• Focal Complications (due to localization of infection in specific organs):

  • Musculoskeletal: Most common focal complication.

    • Arthritis (inflammation of joints, often large weight-bearing joints like hips, knees, sacroiliac joints).

    • Spondylitis (inflammation of the vertebrae, especially lumbar spine), discitis.

    • Osteomyelitis (bone infection).

    • Sacroiliitis.

  • Genitourinary:

    • Orchitis (inflammation of the testes), epididymitis.

    • Prostatitis.

    • Less commonly, pyelonephritis, glomerulonephritis.

    • Miscarriage in pregnant women (though Brucella is not a major cause of abortion in humans as it is in animals).

  • Hepatosplenic:

    • Hepatomegaly (enlarged liver), splenomegaly (enlarged spleen).

    • Elevated liver enzymes.

    • Granulomatous hepatitis.

  • Neurological (Neurobrucellosis): Can be severe.

    • Meningitis, meningoencephalitis.

    • Radiculopathy, myelitis.

    • Cranial nerve palsies.

    • Peripheral neuropathy.

    • Psychiatric symptoms (depression, psychosis).

  • Cardiovascular:

    • Endocarditis (inflammation of the inner lining of the heart, especially heart valves) – most common cause of death in brucellosis.

    • Myocarditis, pericarditis.

  • Respiratory: Less common.

    • Pneumonia, bronchitis, lung abscesses, pleural effusion.

  • Cutaneous (Skin):

    • Various rashes (maculopapular, erythematous), nodules, abscesses.

  • Hematological:

    • Anemia, leukopenia, thrombocytopenia, pancytopenia.

• Chronic Brucellosis: Symptoms persisting for more than one year. May include chronic fatigue, aches, pains, depression, and focal complications. Relapses are common if treatment is inadequate.

Diagnosis
Diagnosis can be challenging due to non-specific symptoms. A high index of suspicion is needed, especially in individuals with relevant occupational exposure or history of consuming unpasteurized dairy products.

• 1. Serological Tests (Detection of Antibodies): Most common diagnostic method.

  • Standard Agglutination Test (SAT) / Serum Agglutination Test (Wright test): Detects IgM and IgG antibodies. A titer of ≥1:160 is often considered significant in non-endemic areas, or a fourfold rise in titer in paired sera.

  • ELISA (Enzyme-Linked Immunosorbent Assay): Can detect specific IgM and IgG antibodies, useful for distinguishing acute from chronic infection and for monitoring treatment response.

  • Rose Bengal Plate Test (RBPT): A rapid screening test.

  • 2-Mercaptoethanol (2-ME) test: Helps differentiate IgM from IgG (IgM is inactivated by 2-ME).

• 2. Culture (Isolation of Brucella bacteria): Gold standard for diagnosis, but can be difficult and slow-growing. Requires specialized media and biosafety precautions (risk of laboratory-acquired infection).

  • Specimens: Blood (especially during febrile episodes), bone marrow (higher yield), cerebrospinal fluid (CSF), synovial fluid, tissue biopsies.

• 3. Polymerase Chain Reaction (PCR): Detects Brucella DNA. Rapid and sensitive, can be performed on various clinical samples. Increasingly used.

• 4. Other Tests:

  • Complete Blood Count (CBC): May show anemia, leukopenia, or thrombocytopenia.

  • Erythrocyte Sedimentation Rate (ESR) and C-Reactive Protein (CRP): Often elevated.

  • Liver function tests: May be abnormal.

  • Imaging (X-rays, CT, MRI, ultrasound): Useful for identifying focal complications (e.g., spondylitis, abscesses, endocarditis).

Treatment
The goals of treatment are to relieve symptoms, prevent complications, and prevent relapse. Brucella are intracellular pathogens, so prolonged combination antibiotic therapy is required.

• Recommended Regimens (WHO and others):

  • First-line (for uncomplicated adult brucellosis):

    • Doxycycline (100 mg twice daily for 6 weeks) PLUS Streptomycin (1 g daily intramuscularly for 2-3 weeks)

    • OR Doxycycline (100 mg twice daily for 6 weeks) PLUS Rifampicin (600-900 mg daily for 6 weeks) – Rifampicin regimen is often preferred due to oral administration, but relapse rates might be slightly higher.

  • Alternative Regimens / Specific Situations:

    • Trimethoprim-sulfamethoxazole (TMP-SMX) can be used in combination, especially in individuals or where tetracyclines are contraindicated (e.g., younger individuals, though risks/benefits need careful consideration).

    • For focal complications like spondylitis or neurobrucellosis, treatment is usually longer (e.g., 3-6 months or more) and may involve three drugs.

    • For endocarditis, combination therapy including an aminoglycoside and surgical valve replacement may be necessary.

• Important Considerations:

  • Adherence to the full course of treatment is crucial to prevent relapse.

  • Monitoring for side effects of antibiotics.

  • Follow-up is necessary to assess treatment response and detect relapse.

Prevention and Control
Focuses on controlling the disease in animal reservoirs and preventing human exposure.

• 1. Animal Health Measures:

  • Vaccination of susceptible animals (cattle, sheep, goats).

  • Test-and-slaughter programs for infected animals.

  • Good animal husbandry and hygiene practices on farms.

  • Control of animal movement.

• 2. Food Safety Measures:

  • Pasteurization of milk and dairy products: This is the single most effective measure for preventing foodborne brucellosis.

  • Thorough cooking of meat.

• 3. Occupational Safety Measures:

  • For farmers, veterinarians, abattoir workers:

    • Use of Personal Protective Equipment (PPE) when handling animals or their tissues (gloves, aprons, masks, eye protection).

    • Good personal hygiene (handwashing).

    • Safe handling and disposal of animal placentas, aborted fetuses, and other contaminated materials.

    • Care during obstetric procedures in animals.

  • For laboratory workers:

    • Adherence to strict biosafety level 3 (BSL-3) precautions when handling Brucella cultures.

• 4. Public Health Education:

  • Educating the public about the risks of consuming unpasteurized dairy products and raw/undercooked meat.

  • Awareness among high-risk occupational groups.

Prognosis
With appropriate and timely antibiotic treatment, the prognosis for acute brucellosis is generally good, and most individuals recover fully. However, delays in diagnosis or inadequate treatment can lead to chronic illness, debilitating focal complications, and relapses. Endocarditis is the most serious complication and can be fatal if not managed aggressively. Neurobrucellosis can also have long-term neurological sequelae.