GeneHealth - Your precision medicine

Brucellosis

Disease Details

Family Health Simplified

Buy Membership

Description: Brucellosis is a highly contagious bacterial infection transmitted from animals to humans, primarily causing fever, joint pain, and fatigue.
Type: Brucellosis is an infectious disease caused by bacteria of the genus Brucella. It is not genetically transmitted; rather, it is typically acquired through direct contact with infected animals or consumption of contaminated animal products.
Signs And Symptoms: The symptoms are like those associated with many other febrile diseases, but with emphasis on muscular pain and night sweats. The duration of the disease can vary from a few weeks to many months or even years.
In the first stage of the disease, bacteremia occurs and leads to the classic triad of undulant fevers, sweating (often with a characteristic foul, moldy smell sometimes likened to wet hay), and migratory arthralgia and myalgia (joint and muscle pain). Blood tests characteristically reveal a low number of white blood cells and red blood cells, show some elevation of liver enzymes such as aspartate aminotransferase and alanine aminotransferase, and demonstrate positive Bengal rose and Huddleston reactions. Gastrointestinal symptoms occur in 70% of cases and include nausea, vomiting, decreased appetite, unintentional weight loss, abdominal pain, constipation, diarrhea, an enlarged liver, liver inflammation, liver abscess, and an enlarged spleen.This complex is, at least in Portugal, Israel, Syria, and Jordan, known as Malta fever. During episodes of Malta fever, melitococcemia (presence of brucellae in the blood) can usually be demonstrated by means of blood culture in tryptose medium or Albini medium. If untreated, the disease can give origin to focalizations or become chronic. The focalizations of brucellosis occur usually in bones and joints, and osteomyelitis or spondylodiscitis of the lumbar spine accompanied by sacroiliitis is very characteristic of this disease. Orchitis is also common in men.
The consequences of Brucella infection are highly variable and may include arthritis, spondylitis, thrombocytopenia, meningitis, uveitis, optic neuritis, endocarditis, and various neurological disorders collectively known as neurobrucellosis.
Prognosis: The mortality of the disease in 1909, as recorded in the British Army and Navy stationed in Malta, was 2%. The most frequent cause of death was endocarditis. Recent advances in antibiotics and surgery have been successful in preventing death due to endocarditis. Prevention of human brucellosis can be achieved by eradication of the disease in animals by vaccination and other veterinary control methods such as testing herds/flocks and slaughtering animals when infection is present. Currently, no effective vaccine is available for humans. Boiling milk before consumption, or before using it to produce other dairy products, is protective against transmission via ingestion. Changing traditional food habits of eating raw meat, liver, or bone marrow is necessary, but difficult to implement. Patients who have had brucellosis should probably be excluded indefinitely from donating blood or organs. Exposure of diagnostic laboratory personnel to Brucella organisms remains a problem in both endemic settings and when brucellosis is unknowingly imported by a patient. After appropriate risk assessment, staff with significant exposure should be offered postexposure prophylaxis and followed up serologically for 6 months.
Onset: The onset of brucellosis typically occurs within 5 days to 5 months after exposure to the Brucella bacteria, with most cases developing symptoms within 2 to 4 weeks. The term "nan" does not seem to relate to the disease directly; if you intended something specific, please provide more context. Symptoms can include fever, sweats, malaise, anorexia, headache, and muscle pain.
Prevalence: Brucellosis is a globally widespread zoonotic bacterial infection caused by the genus Brucella. Its prevalence varies significantly by region and is most common in areas with extensive livestock farming and less stringent animal health programs. High prevalence rates are noted in the Mediterranean, the Middle East, parts of Asia, South and Central America, and some sub-Saharan African nations. Human cases are often linked to occupational exposure or consumption of unpasteurized dairy products. Reliable global statistics are challenging to obtain due to underreporting and misdiagnosis, but it remains a significant public health issue in many developing countries.
Epidemiology: **Epidemiology of Brucellosis:**

Brucellosis is a zoonotic infection caused by the Brucella species. It is prevalent worldwide, particularly in regions with poor animal disease control programs. High-risk areas include the Mediterranean Basin, parts of Africa, the Middle East, South America, and Asia. The disease primarily affects those in close contact with livestock or wildlife, such as farmers, veterinarians, and abattoir workers. Human infection typically occurs through direct contact with infected animals, consumption of unpasteurized dairy products, or inhalation of airborne agents. Brucellosis remains underreported in many countries due to limited diagnostic capabilities and awareness.
Intractability: Brucellosis is generally not considered intractable. With appropriate antibiotic treatment, most patients recover fully. However, treatment can be prolonged, sometimes requiring multiple courses of antibiotics due to the potential for relapse. Early diagnosis and appropriate management are key to preventing complications and achieving a good outcome.
Disease Severity: Brucellosis, also known as undulant fever or Malta fever, varies in severity but is generally considered serious. The disease can cause a range of symptoms, including fever, sweats, malaise, anorexia, headache, and muscle pain. Chronic infection can result in complications such as arthritis, endocarditis, and neurobrucellosis. If not treated properly, brucellosis can lead to prolonged debilitation and, in rare cases, death.
Healthcare Professionals: Disease Ontology ID - DOID:11077
Pathophysiology: Brucellosis is an infectious disease caused by bacteria of the genus Brucella. These bacteria are primarily transmitted from animals to humans, commonly through the consumption of unpasteurized dairy products, direct contact with infected animals, or inhalation of aerosols.

Pathophysiology:
1. **Entry and Spread**: The Brucella bacteria enter the human body through mucous membranes, skin abrasions, or through the gastrointestinal tract. Once inside, they are phagocytosed by macrophages.
2. **Intracellular Survival**: Brucella bacteria have mechanisms to survive inside macrophages by preventing phagosome-lysosome fusion, thus avoiding destruction. They create a niche within the endoplasmic reticulum-derived replicative vacuoles.
3. **Dissemination**: The bacteria spread through the lymphatic system and bloodstream, leading to systemic infection.
4. **Granuloma Formation**: The immune response to the infection involves the formation of granulomas—structures composed of immune cells that attempt to contain the infection. This can occur in various organs, including the liver, spleen, bones, and joints.
5. **Chronic Inflammation**: The persistence of bacteria within immune cells can lead to chronic inflammation and symptoms such as recurrent fever, malaise, weight loss, and organ-specific issues depending on the sites of infection.

Understanding the pathophysiology of brucellosis is critical for diagnosing, managing, and treating the disease effectively. Early detection and appropriate antibiotic therapy are necessary to prevent complications.
Carrier Status: Brucellosis is not typically characterized by a chronic carrier status in humans. Once treated properly, individuals usually do not harbor the bacteria long-term. However, untreated or inadequately treated individuals can experience relapses. For animals, certain species can become chronic carriers, particularly livestock such as cattle, sheep, goats, and pigs. These animals can carry the bacteria and spread it, even if they appear healthy.
Mechanism: Brucellosis is a bacterial infection caused by various species of the genus Brucella. The mechanism of infection primarily involves the bacteria entering the host and invading the cells of the reticuloendothelial system. Here are the key mechanisms:

**General Mechanism:**
1. **Entry and Initial Infection:** Brucella species typically enter the host through mucosal surfaces, such as those in the respiratory tract, digestive tract, or through broken skin.
2. **Intracellular Survival:** Once inside the host, Brucella bacteria are phagocytosed by macrophages and other immune cells. Remarkably, these bacteria have developed mechanisms to survive and replicate within these cells.
3. **Systemic Spread:** Brucella spreads to various organs and tissues, such as the liver, spleen, and bone marrow, through the lymphatic system and blood circulation.

**Molecular Mechanisms:**
1. **Virulence Factors:** Brucella produces several virulence factors, including the type IV secretion system (T4SS), which is crucial for their ability to survive and replicate within host cells. The T4SS injects effector proteins into host cells, modulating host cell functions.
2. **Inhibition of Host Immune Responses:** Brucella can inhibit the apoptosis of infected macrophages, enabling prolonged bacterial survival and replication. It can also evade detection by the host immune system through various mechanisms, such as modifying its surface antigens.
3. **Modification of Intracellular Trafficking:** Brucella bacteria can alter the intracellular trafficking pathways within host cells, preventing phagosome-lysosome fusion, which would typically lead to bacterial degradation. They create a replication niche called the Brucella-containing vacuole (BCV).
4. **Adaptation to Nutrient Limitation:** The bacteria can adapt metabolically to the nutrient limitations of the intracellular environment. Genes related to amino acid and nucleotide synthesis are upregulated to facilitate survival.

Overall, the ability of Brucella to persist in a host is due to a combination of its intracellular lifestyle, immune evasion strategies, and sophisticated regulation of gene expression that allows it to adapt to various hostile environments within the host.
Treatment: Antibiotics such as tetracyclines, rifampicin, and the aminoglycosides streptomycin and gentamicin are effective against Brucella bacteria. However, the use of more than one antibiotic is needed for several weeks, because the bacteria incubate within cells.The gold standard treatment for adults is daily intramuscular injections of streptomycin 1 g for 14 days and oral doxycycline 100 mg twice daily for 45 days (concurrently). Gentamicin 5 mg/kg by intramuscular injection once daily for 7 days is an acceptable substitute when streptomycin is not available or contraindicated. Another widely used regimen is doxycycline plus rifampicin twice daily for at least 6 weeks. This regimen has the advantage of oral administration. A triple therapy of doxycycline, with rifampicin and co-trimoxazole, has been used successfully to treat neurobrucellosis. Doxycycline plus streptomycin regimen (for 2 to 3 weeks) is more effective than doxycycline plus rifampicin regimen (for 6 weeks).Doxycycline is able to cross the blood–brain barrier, but requires the addition of two other drugs to prevent relapse. Ciprofloxacin and co-trimoxazole therapy is associated with an unacceptably high rate of relapse. In brucellic endocarditis, surgery is required for an optimal outcome. Even with optimal antibrucellic therapy, relapses still occur in 5 to 10% of patients with Malta fever.
Compassionate Use Treatment: Compassionate use treatment for brucellosis may involve the administration of investigational drugs not yet approved by regulatory agencies for general use. These are typically provided to patients who have not responded to standard therapies and have a life-threatening condition.

Off-label or experimental treatments for brucellosis can include:
1. **Fluoroquinolones**: While not traditionally first-line treatments, fluoroquinolones like ciprofloxacin or levofloxacin may be used in some cases, especially in combinations with other antimicrobials.
2. **Rifampin-based combinations**: Sometimes used in combination with other antibiotics like doxycycline or gentamicin for more severe or complicated cases.
3. **Other aminoglycosides**: Besides streptomycin and gentamicin, other aminoglycosides might be used in experimental or off-label scenarios.
4. **Macrolides**: Antibiotics like azithromycin or clarithromycin may be explored in experimental treatments, although not typically first-line.

It's important to consult with infectious disease specialists when considering these options, as they require careful monitoring and assessment.
Lifestyle Recommendations: For managing brucellosis, here are some lifestyle recommendations:

1. **Rest and Hydration**: Ensure ample rest and stay well-hydrated to help your body combat the infection.
2. **Antibiotic Adherence**: Take antibiotics exactly as prescribed by your healthcare provider. Completing the full course is crucial to prevent relapse.
3. **Nutrition**: Maintain a well-balanced diet to boost your immune system.
4. **Avoid Dairy Products**: Refrain from consuming unpasteurized dairy products to prevent reinfection or worsening of symptoms.
5. **Hygiene Practices**: Practice good hand hygiene, especially when handling animals or animal products.
6. **Work Precautions**: If you work with livestock or in a laboratory setting, use appropriate protective measures such as gloves and masks.
7. **Regular Monitoring**: Keep regular follow-up appointments with your healthcare provider to monitor your condition.

These steps can help manage symptoms and reduce the risk of transmission.
Medication: The primary medications used to treat brucellosis include antibiotics such as doxycycline and rifampin, typically administered in combination for a duration of 6 weeks. Other antibiotic regimens may include combinations like doxycycline with streptomycin or gentamicin. The choice and duration of antibiotics can vary based on the severity and site of the infection.
Repurposable Drugs: There is emerging interest in repurposing drugs for the treatment of brucellosis. Some research has suggested that doxycycline, rifampin, and streptomycin or gentamicin, which are already part of traditional brucellosis treatment regimens, might benefit from being combined with newer drugs to enhance efficacy. Additionally, other antibiotics like fluoroquinolones (e.g., ciprofloxacin) and trimethoprim-sulfamethoxazole have been considered for potential off-label use. Clinical studies are ongoing to determine the efficacy and safety of these repurposed drugs.
Metabolites: Brucellosis is caused by bacteria of the genus Brucella, and it primarily affects livestock but can also infect humans. Notable metabolites produced during Brucella infection include erythritol, which can promote bacterial growth, and other compounds involved in the bacterium's intracellular survival mechanisms, such as cyclic β-1,2-glucans and 5'-guanosine monophosphate (5'-GMP). Analysis of these metabolites can help in understanding the pathophysiology of brucellosis and developing diagnostic or therapeutic strategies.
Nutraceuticals: For brucellosis, there is limited evidence on the effectiveness of nutraceuticals. The mainstay of treatment involves antibiotics such as doxycycline and rifampin. Research into using nanotechnology for brucellosis treatment is ongoing, with some studies exploring nanoparticle delivery systems to enhance the effectiveness of antibiotics and potentially reduce side effects. However, these approaches are still largely experimental.
Peptides: Brucellosis is a bacterial infection caused by the genus Brucella. While peptide-based vaccines and nanotechnology are not yet standard treatment or prevention approaches for brucellosis, research in these areas is ongoing. Peptide-based vaccines aim to stimulate immune responses using specific protein fragments, and nanotechnology offers potential for improved vaccine delivery and diagnostics. However, current management of brucellosis primarily involves antibiotics like doxycycline, rifampin, or streptomycin.