Brucella abortus: Persistence, Duration, and Testing

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Overview

Brucella abortus is a Gram-negative, facultative intracellular bacterium responsible for brucellosis, a chronic zoonotic disease. It primarily affects cattle, bison, and elk, but can also infect humans through contact with infected animal fluids or consumption of unpasteurized dairy products. The organism’s ability to survive and replicate within host cells—especially macrophages—allows it to evade immune responses and persist in the body for months or even years.

Persistence and Duration in the Human Body

Acute Phase

Symptoms such as fever, night sweats, fatigue, and joint pain typically appear between two to four weeks after exposure. If untreated, this phase can last for several weeks.

Chronic Phase

Without appropriate antibiotic treatment, Brucella abortus may enter a chronic or latent phase. The bacterium can persist in host tissues for months to years, potentially leading to relapsing infections or long-term complications such as arthritis, spondylitis, or endocarditis.

Intracellular Survival

The bacterium’s residence in phagocytic cells like macrophages enables it to avoid immune detection and resist clearance. This intracellular lifestyle also reduces the effectiveness of many antibiotics, contributing to its prolonged survival within the host.

Mechanisms Behind Long-Term Persistence

Intracellular Survival and Evasion

  • After entering the host, Brucella abortus survives and replicates within macrophages.

  • It avoids destruction by preventing phagosome-lysosome fusion, thereby creating a protected environment inside cells.

  • This mechanism shields the bacterium from both immune attacks and some antibiotic treatments.

Immune Modulation

  • Brucella alters the host immune response by suppressing pro-inflammatory cytokines and impairing antigen presentation.

  • This leads to reduced immune activation and supports the establishment of chronic or low-level infections.

Granuloma Formation

  • In chronic cases, the immune system may form granulomas—localized inflammatory structures—in organs such as the liver, spleen, and bone marrow.

  • These granulomas can harbor viable bacteria for extended periods, potentially leading to relapse if immune control weakens or treatment is incomplete.

Duration With and Without Treatment

With Treatment

  • Treatment typically involves a combination of antibiotics, most commonly doxycycline and rifampin, administered for at least six weeks.

  • Despite appropriate therapy, relapse rates between 5 to 15 percent have been reported, particularly if the treatment course is not completed.

Without Treatment

  • If untreated, brucellosis can become chronic and persist indefinitely.

  • Long-term complications may include:

    • Endocarditis (inflammation of the heart lining)

    • Osteomyelitis (bone infection)

    • Neurobrucellosis (nervous system involvement)

Brucella abortus: Testing and Diagnosis

Accurate Diagnosis

Diagnosing Brucella abortus infection requires a combination of clinical history, exposure risk assessment, and laboratory testing. Due to its slow-growing and intracellular nature, diagnosis can be complex and may involve multiple types of tests.

1. Testing in Humans

A. Serological Tests

These tests detect antibodies produced in response to Brucella infection and are the most commonly used methods.

  • Standard Agglutination Test (SAT)
    Detects total antibodies (IgM and IgG). A titer of 1:160 or higher is typically considered positive in symptomatic individuals.

  • Enzyme-Linked Immunosorbent Assay (ELISA)
    Measures specific IgM and IgG antibodies, helping to distinguish between acute and chronic infection.

  • Coombs Anti-Brucella Test
    Identifies incomplete or "blocking" antibodies that may be missed by the SAT. Useful in chronic or relapsing cases.

  • Rose Bengal Test (RBT)
    A rapid, simple screening test commonly used in outbreak or field settings. It offers high sensitivity but lower specificity than confirmatory tests.

B. Culture

  • Blood, bone marrow, or tissue samples can be cultured to directly isolate the bacterium.

  • Cultures must be performed in a biosafety level 3 (BSL-3) laboratory due to the risk of lab-acquired infections.

  • Culturing is definitive but slow, often requiring several weeks for results.

C. Polymerase Chain Reaction (PCR)

  • PCR detects Brucella DNA in blood or tissue samples.

  • It is faster and highly specific but may not be widely available in all laboratories.

2. Testing in Animals (Especially Cattle)

A. Serological Tests

Used for herd surveillance and control programs.

  • Rose Bengal Test (RBT)
    A fast screening method for detecting antibodies in cattle. Positive results are typically confirmed with more specific tests.

  • Complement Fixation Test (CFT)
    Confirms RBT-positive results and detects antibodies that activate complement in the presence of Brucella antigen.

  • Milk Ring Test (MRT)
    Used in dairy cows to detect antibodies in milk. A blue ring at the cream layer indicates a positive result.

  • ELISA (Indirect or Competitive)
    Offers high sensitivity and specificity. Can be used for both surveillance and confirmatory purposes.

B. Bacteriological Culture

  • Tissue samples from lymph nodes, spleen, placenta, or aborted fetuses may be cultured.

  • Culturing requires a BSL-3 laboratory due to the zoonotic risk.

C. PCR

  • Increasingly used to detect Brucella DNA in animal fluids and tissues such as milk, blood, or placental material.

3. Public Health and Field Applications

  • In regions where brucellosis is endemic, rapid field tests such as the Rose Bengal Test are essential for early detection and containment.

  • Infected animals are typically culled to prevent spread within herds.

  • Individuals with high occupational exposure (e.g., veterinarians, slaughterhouse workers, laboratory personnel) may be regularly screened using serological tests and monitored through occupational health programs.

    Summary of Testing Methods

    Test Type

    Applicable to Humans

    Applicable to Animals

    Notes

    Rose Bengal Test (RBT)

    Yes

    Yes

    Quick screening; high sensitivity

    ELISA

    Yes

    Yes

    Differentiates acute (IgM) and chronic (IgG) stages

    Standard Agglutination Test

    Yes

    No

    Common confirmatory test in human cases

    Milk Ring Test (MRT)

    No

    Yes

    Used in dairy cows; detects antibodies in milk

    Complement Fixation Test

    No

    Yes

    Confirms RBT-positive animals

    Culture

    Yes

    Yes

    Gold standard; slow; requires high biosafety levels

    PCR

    Yes

    Yes

    Rapid and highly specific DNA detection

    References:

    The new global map of human brucellosis https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(06)70382-6/abstract

    Reemergence of Brucella abortus, Israel, 2021
    https://wwwnc.cdc.gov/eid/article/31/4/24-1003_article

    Brucellosis: A re-emerging zoonosis
    https://www.sciencedirect.com/science/article/abs/pii/S0378113509003058?via%3Dihub

    Interleukin-18 enhances a Th2 biased response and susceptibility to Leishmania mexicana in BALB/c mice
    https://www.sciencedirect.com/science/article/pii/S1286457908000907?via%3Dihub

    © 2000-2030 Sieglinde W. Alexander. All writings by Sieglinde W. Alexander have a fife year copy right. Library of Congress Card Number: LCN 00-192742 ISBN: 0-9703195-0-9 

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