Brucella/Brucellosis

General Characteristics of Brucella

General characteristics

• Gram-negative coccobacilli
• Facultative intracellular Facultative intracellular Yersinia spp./Yersiniosis
• Aerobic
• Requires carbon dioxide (CO₂)
• Non-motile
• Unencapsulated
• Non-spore forming
• Oxidase Oxidase Neisseria and urease Urease An enzyme that catalyzes the conversion of urea and water to carbon dioxide and ammonia. Nocardia/Nocardiosis positive
• Require enriched media for culture growth (Thayer-Martin medium)
  • Improved with blood or serum
  • Optimum temperature: 35–37°C (95–98.6°F)

Clinically relevant species

• B. melitensis
• B. abortus 
• B. suis 
• B. canis

Epidemiology and Risk Factors

Epidemiology

• Most common zoonotic infection worldwide and a significant public health problem in many developing countries:
  • Endemic areas: 
    • Mediterranean
    • Middle East 
    • Central Asia ASIA Spinal Cord Injuries 
    • China 
    • Mexico 
    • Central and South America
  • Rare in the United States, mostly seen in:
    • California
    • Florida
    • Texas
    • Virginia
• Prevalence Prevalence The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. Measures of Disease Frequency:
  • Worldwide: approximately 500,000 cases annually
  • United States: 100–200 cases annually
  • Increasing due to international tourism and migration
• Affects all age groups

Occupations at high risk

• Veterinarians 
• Dairy farmers 
• Shepherds
• Slaughterhouse workers
• Laboratory personnel

Pathogenesis

Reservoirs

• Sheep, goats, camels → B. melitensis
• Cattle → B. abortus
• Swine → B. suis
• Dogs → B. canis

Transmission

• Ingestion of unpasteurized animal products (most common)
• Skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions contact with mucous membranes of infected animal tissues or fluids 
• Inhalation of aerosolized particles (more common in laboratory workers)
• Rarely, human-to-human transmission

Virulence factors Virulence factors Those components of an organism that determine its capacity to cause disease but are not required for its viability per se. Two classes have been characterized: toxins, biological and surface adhesion molecules that affect the ability of the microorganism to invade and colonize a host. Haemophilus

• Lipopolysaccharide Lipopolysaccharide Lipid-containing polysaccharides which are endotoxins and important group-specific antigens. They are often derived from the cell wall of gram-negative bacteria and induce immunoglobulin secretion. The lipopolysaccharide molecule consists of three parts: lipid a, core polysaccharide, and o-specific chains (o antigens). When derived from Escherichia coli, lipopolysaccharides serve as polyclonal b-cell mitogens commonly used in laboratory immunology. Klebsiella (LPS)
  • Inhibits: 
    • Phagosomal fusion and lysosomal destruction → allows intracellular survival
    • Complement deposition
  • “Non-classical”
    • Less toxic than in other species of bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology
    • Weak immune system Immune system The body’s defense mechanism against foreign organisms or substances and deviant native cells. It includes the humoral immune response and the cell-mediated response and consists of a complex of interrelated cellular, molecular, and genetic components. Primary Lymphatic Organs inducer
• Superoxide dismutase Superoxide dismutase An oxidoreductase that catalyzes the reaction between superoxides and hydrogen to yield molecular oxygen and hydrogen peroxide. The enzyme protects the cell against dangerous levels of superoxide. Myeloperoxidase Deficiency and catalase Catalase An oxidoreductase that catalyzes the conversion of hydrogen peroxide to water and oxygen. It is present in many animal cells. A deficiency of this enzyme results in acatalasia. Nocardia/Nocardiosis: provides defense against oxidative burst activity → allows intracellular survival
• Type IV secretion Secretion Coagulation Studies system
  • Multi-protein complex
  • Allows Brucella to reach and replicate within a cell’s endoplasmic reticulum Endoplasmic reticulum A system of cisternae in the cytoplasm of many cells. In places the endoplasmic reticulum is continuous with the plasma membrane (cell membrane) or outer membrane of the nuclear envelope. If the outer surfaces of the endoplasmic reticulum membranes are coated with ribosomes, the endoplasmic reticulum is said to be rough-surfaced; otherwise it is said to be smooth-surfaced. The Cell: Organelles

Pathophysiology

• Bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology translocate across mucosal epithelium Epithelium The epithelium is a complex of specialized cellular organizations arranged into sheets and lining cavities and covering the surfaces of the body. The cells exhibit polarity, having an apical and a basal pole. Structures important for the epithelial integrity and function involve the basement membrane, the semipermeable sheet on which the cells rest, and interdigitations, as well as cellular junctions. Surface Epithelium: Histology.
• Engulfed by macrophages Macrophages The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood monocytes. Main types are peritoneal macrophages; alveolar macrophages; histiocytes; kupffer cells of the liver; and osteoclasts. They may further differentiate within chronic inflammatory lesions to epithelioid cells or may fuse to form foreign body giant cells or langhans giant cells. Innate Immunity: Phagocytes and Antigen Presentation
  • Approximately 10% of bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology survive.
  • Replication occurs in the endoplasmic reticulum Endoplasmic reticulum A system of cisternae in the cytoplasm of many cells. In places the endoplasmic reticulum is continuous with the plasma membrane (cell membrane) or outer membrane of the nuclear envelope. If the outer surfaces of the endoplasmic reticulum membranes are coated with ribosomes, the endoplasmic reticulum is said to be rough-surfaced; otherwise it is said to be smooth-surfaced. The Cell: Organelles.
• Transported to the lymphatic system Lymphatic system A system of organs and tissues that process and transport immune cells and lymph. Primary Lymphatic Organs → disseminate throughout the body
• Hemolysins Hemolysins Proteins from bacteria and fungi that are soluble enough to be secreted to target erythrocytes and insert into the membrane to form beta-barrel pores. Biosynthesis may be regulated by hemolysin factors. Leptospira/Leptospirosis allow for release of bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology from the macrophage → cell apoptosis Apoptosis A regulated cell death mechanism characterized by distinctive morphologic changes in the nucleus and cytoplasm, including the endonucleolytic cleavage of genomic DNA, at regularly spaced, internucleosomal sites, I.e., DNA fragmentation. It is genetically-programmed and serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. Ischemic Cell Damage → triggers an immune response
• Antigens are presented to T lymphocytes T lymphocytes Lymphocytes responsible for cell-mediated immunity. Two types have been identified – cytotoxic (t-lymphocytes, cytotoxic) and helper T-lymphocytes (t-lymphocytes, helper-inducer). They are formed when lymphocytes circulate through the thymus gland and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen. T cells: Types and Functions → cytokine production 
  • Activation of macrophages Macrophages The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood monocytes. Main types are peritoneal macrophages; alveolar macrophages; histiocytes; kupffer cells of the liver; and osteoclasts. They may further differentiate within chronic inflammatory lesions to epithelioid cells or may fuse to form foreign body giant cells or langhans giant cells. Innate Immunity: Phagocytes and Antigen Presentation → ↑ bactericidal Bactericidal Penicillins effect
  • Attracts more immune cells → granuloma formation
• Antibodies Antibodies Immunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution. Immunoglobulins: Types and Functions and natural killer cells Natural killer cells A specialized subset of T-lymphocytes that exhibit features of innate immunity similar to that of natural killer cells. They are reactive to glycolipids presented in the context of the major histocompatibility complex (MHC) class I-like molecule, CD1D antigen. Lymphocytes: Histology play a smaller role in the immune response.

Clinical Presentation

General signs and symptoms

• Average incubation Incubation The amount time between exposure to an infectious agent and becoming symptomatic. Rabies Virus period is 2–4 weeks.
• Symptoms:
  • “Undulant fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever” 
    • Comes in waves
    • Can vary in presentation
    • Persists 1‒5 weeks
  • Night sweats Night sweats Tuberculosis: associated with a strong, moldy odor
  • Malaise Malaise Tick-borne Encephalitis Virus
  • Arthralgias
  • Headache Headache The symptom of pain in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of headache disorders. Brain Abscess
  • Loss of appetite
  • Weight loss Weight loss Decrease in existing body weight. Bariatric Surgery
  • Symptoms may disappear and then return after weeks or months.
• Physical exam (nonspecific):
  • Hepatomegaly
  • Splenomegaly Splenomegaly Splenomegaly is pathologic enlargement of the spleen that is attributable to numerous causes, including infections, hemoglobinopathies, infiltrative processes, and outflow obstruction of the portal vein. Splenomegaly
  • Painful lymphadenopathy Lymphadenopathy Lymphadenopathy is lymph node enlargement (> 1 cm) and is benign and self-limited in most patients. Etiologies include malignancy, infection, and autoimmune disorders, as well as iatrogenic causes such as the use of certain medications. Generalized lymphadenopathy often indicates underlying systemic disease. Lymphadenopathy

Complications

• Osteoarticular (70% of patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship):
  • Arthritis Arthritis Acute or chronic inflammation of joints. Osteoarthritis
  • Sacroiliitis Sacroiliitis Inflammation of the sacroiliac joint. It is characterized by lower back pain, especially upon walking, fever, uveitis; psoriasis; and decreased range of motion. Many factors are associated with and cause sacroiliitis including infection; injury to spine, lower back, and pelvis; degenerative arthritis; and pregnancy. Ankylosing Spondylitis
  • Spondylitis
  • Osteomyelitis Osteomyelitis Osteomyelitis is an infection of the bone that results from the spread of microorganisms from the blood (hematogenous), nearby infected tissue, or open wounds (non-hematogenous). Infections are most commonly caused by Staphylococcus aureus. Osteomyelitis
• Genitourinary:
  • Orchitis Orchitis Inflammation of a testis. It has many features of epididymitis, such as swollen scrotum; pain; pyuria; and fever. It is usually related to infections in the urinary tract, which likely spread to the epididymis and then the testis through either the vas deferens or the lymphatics of the spermatic cord. Epididymitis and Orchitis
  • Epididymitis Epididymitis Epididymitis and orchitis are characterized by acute inflammation of the epididymis and the testicle, respectively, due to viral or bacterial infections. Patients typically present with gradually worsening testicular pain and scrotal swelling along with systemic symptoms such as fever, depending on severity. Epididymitis and Orchitis
  • Cystitis Cystitis Inflammation of the urinary bladder, either from bacterial or non-bacterial causes. Cystitis is usually associated with painful urination (dysuria), increased frequency, urgency, and suprapubic pain. Urinary Tract Infections (UTIs)
  • Interstitial nephritis and glomerulonephritis
  • ↑ Risk of spontaneous abortion Abortion Expulsion of the product of fertilization before completing the term of gestation and without deliberate interference. Spontaneous Abortion in pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care
• Neurobrucellosis:
  • Meningitis Meningitis Meningitis is inflammation of the meninges, the protective membranes of the brain, and spinal cord. The causes of meningitis are varied, with the most common being bacterial or viral infection. The classic presentation of meningitis is a triad of fever, altered mental status, and nuchal rigidity. Meningitis
  • Encephalitis Encephalitis Encephalitis is inflammation of the brain parenchyma caused by an infection, usually viral. Encephalitis may present with mild symptoms such as headache, fever, fatigue, and muscle and joint pain or with severe symptoms such as seizures, altered consciousness, and paralysis. Encephalitis
  • Neuritis
  • Brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification abscess Abscess Accumulation of purulent material in tissues, organs, or circumscribed spaces, usually associated with signs of infection. Chronic Granulomatous Disease
• Cardiovascular:
  • Endocarditis Endocarditis Endocarditis is an inflammatory disease involving the inner lining (endometrium) of the heart, most commonly affecting the cardiac valves. Both infectious and noninfectious etiologies lead to vegetations on the valve leaflets. Patients may present with nonspecific symptoms such as fever and fatigue. Endocarditis (main cause of death)
  • Myocarditis Myocarditis Myocarditis is an inflammatory disease of the myocardium, which may occur alone or in association with a systemic process. There are numerous etiologies of myocarditis, but all lead to inflammation and myocyte injury, most often leading to signs and symptoms of heart failure. Myocarditis
  • Pericarditis Pericarditis Pericarditis is an inflammation of the pericardium, often with fluid accumulation. It can be caused by infection (often viral), myocardial infarction, drugs, malignancies, metabolic disorders, autoimmune disorders, or trauma. Acute, subacute, and chronic forms exist. Pericarditis
• Pulmonary:
  • Bronchitis
  • Interstitial pneumonitis Pneumonitis Human Herpesvirus 6 and 7
  • Pneumonia Pneumonia Pneumonia or pulmonary inflammation is an acute or chronic inflammation of lung tissue. Causes include infection with bacteria, viruses, or fungi. In more rare cases, pneumonia can also be caused through toxic triggers through inhalation of toxic substances, immunological processes, or in the course of radiotherapy. Pneumonia
  • Pleural effusion Pleural Effusion Pleural effusion refers to the accumulation of fluid between the layers of the parietal and visceral pleura. Common causes of this condition include infection, malignancy, autoimmune disorders, or volume overload. Clinical manifestations include chest pain, cough, and dyspnea. Pleural Effusion
• Abdominal:
  • Cholecystitis Cholecystitis Cholecystitis is the inflammation of the gallbladder (GB) usually caused by the obstruction of the cystic duct (acute cholecystitis). Mechanical irritation by gallstones can also produce chronic GB inflammation. Cholecystitis is one of the most common complications of cholelithiasis but inflammation without gallstones can occur in a minority of patients. Cholecystitis
  • Hepatic abscess Abscess Accumulation of purulent material in tissues, organs, or circumscribed spaces, usually associated with signs of infection. Chronic Granulomatous Disease
  • Splenic abscess Splenic Abscess Imaging of the Spleen
  • Pancreatitis Pancreatitis Inflammation of the pancreas. Pancreatitis is classified as acute unless there are computed tomographic or endoscopic retrograde cholangiopancreatographic findings of chronic pancreatitis. The two most common forms of acute pancreatitis are alcoholic pancreatitis and gallstone pancreatitis. Acute Pancreatitis
  • Ileitis and colitis Colitis Inflammation of the colon section of the large intestine, usually with symptoms such as diarrhea (often with blood and mucus), abdominal pain, and fever. Pseudomembranous Colitis
• Ocular: uveitis Uveitis Uveitis is the inflammation of the uvea, the pigmented middle layer of the eye, which comprises the iris, ciliary body, and choroid. The condition is categorized based on the site of disease; anterior uveitis is the most common. Diseases of the Uvea
• Cutaneous: rash Rash Rocky Mountain Spotted Fever (varying presentation)

Relapse Relapse Relapsing Fever can occur in 4%–24% of patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship, usually within 1 year.

Diagnosis

Diagnostic algorithm

Diagnostic testing

• Culture
  • Definitive
  • Blood cultures are usually obtained in all patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship.
  • Bone marrow Bone marrow The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. Bone Marrow: Composition and Hematopoiesis is considered the gold standard (most sensitive).
  • Requires special culture techniques
• Serum tube agglutination test (SAT)
  • Measures antibodies Antibodies Immunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution. Immunoglobulins: Types and Functions against a Brucella antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination (smooth lipopolysaccharide Lipopolysaccharide Lipid-containing polysaccharides which are endotoxins and important group-specific antigens. They are often derived from the cell wall of gram-negative bacteria and induce immunoglobulin secretion. The lipopolysaccharide molecule consists of three parts: lipid a, core polysaccharide, and o-specific chains (o antigens). When derived from Escherichia coli, lipopolysaccharides serve as polyclonal b-cell mitogens commonly used in laboratory immunology. Klebsiella)
  • Evolution titers (fourfold increase in the titer between acute and convalescent serum obtained ≥ 2 weeks apart)
    • Provides a definitive diagnosis
    • Limited by the time required
  • Positive titers providing a presumptive diagnosis: 
    • > 1:160 outside endemic regions 
    • > 1:320 within endemic regions
  • Cannot be used for B. canis
• Enzyme-linked immunosorbent assay ( ELISA ELISA An immunoassay utilizing an antibody labeled with an enzyme marker such as horseradish peroxidase. While either the enzyme or the antibody is bound to an immunosorbent substrate, they both retain their biologic activity; the change in enzyme activity as a result of the enzyme-antibody-antigen reaction is proportional to the concentration of the antigen and can be measured spectrophotometrically or with the naked eye. Many variations of the method have been developed. St. Louis Encephalitis Virus)
  • Comparable sensitivity and specificity Sensitivity and Specificity Binary classification measures to assess test results. Sensitivity or recall rate is the proportion of true positives. Specificity is the probability of correctly determining the absence of a condition. Epidemiological Values of Diagnostic Tests to SAT
  • Tests for immunoglobulins Immunoglobulins Immunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution. Immunoglobulins: Types and Functions against cytoplasmic proteins Proteins Linear polypeptides that are synthesized on ribosomes and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of amino acids determines the shape the polypeptide will take, during protein folding, and the function of the protein. Energy Homeostasis
• Rose Bengal agglutination
  • Can be used as a screening Screening Preoperative Care tool
  • Rapid
• Polymerase chain reaction Polymerase chain reaction Polymerase chain reaction (PCR) is a technique that amplifies DNA fragments exponentially for analysis. The process is highly specific, allowing for the targeting of specific genomic sequences, even with minuscule sample amounts. The PCR cycles multiple times through 3 phases: denaturation of the template DNA, annealing of a specific primer to the individual DNA strands, and synthesis/elongation of new DNA molecules. Polymerase Chain Reaction (PCR) ( PCR PCR Polymerase chain reaction (PCR) is a technique that amplifies DNA fragments exponentially for analysis. The process is highly specific, allowing for the targeting of specific genomic sequences, even with minuscule sample amounts. The PCR cycles multiple times through 3 phases: denaturation of the template DNA, annealing of a specific primer to the individual DNA strands, and synthesis/elongation of new DNA molecules. Polymerase Chain Reaction (PCR))
  • Detects Brucella DNA DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA Types and Structure
  • Can provide a presumptive diagnosis

Additional workup

The testing performed is guided by the patient’s clinical presentation and any concerns for complications.

• Laboratory testing (nonspecific)
  • Complete blood count:
    • Anemia Anemia Anemia is a condition in which individuals have low Hb levels, which can arise from various causes. Anemia is accompanied by a reduced number of RBCs and may manifest with fatigue, shortness of breath, pallor, and weakness. Subtypes are classified by the size of RBCs, chronicity, and etiology. Anemia: Overview and Types 
    • Leukopenia with ↑ lymphocytes Lymphocytes Lymphocytes are heterogeneous WBCs involved in immune response. Lymphocytes develop from the bone marrow, starting from hematopoietic stem cells (HSCs) and progressing to common lymphoid progenitors (CLPs). B and T lymphocytes and natural killer (NK) cells arise from the lineage. Lymphocytes: Histology
    • Thrombocytopenia Thrombocytopenia Thrombocytopenia occurs when the platelet count is < 150,000 per microliter. The normal range for platelets is usually 150,000-450,000/µL of whole blood. Thrombocytopenia can be a result of decreased production, increased destruction, or splenic sequestration of platelets. Patients are often asymptomatic until platelet counts are < 50,000/µL. Thrombocytopenia
  • ↑ Liver function tests Liver function tests Liver function tests, also known as hepatic function panels, are one of the most commonly performed screening blood tests. Such tests are also used to detect, evaluate, and monitor acute and chronic liver diseases. Liver Function Tests 
  • Synovial fluid:
    • May be tested in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with arthritis Arthritis Acute or chronic inflammation of joints. Osteoarthritis
    • White blood cell (WBC) count ≤ 15,000 cells/µL
    • Culture will grow Brucella
  • CSF:
    • May be tested in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with neurologic involvement
    • 10‒200 WBC with mononuclear cell predominance
    • ↑ Protein
    • Antibody or agglutination testing may be done.
  • Urinalysis Urinalysis Examination of urine by chemical, physical, or microscopic means. Routine urinalysis usually includes performing chemical screening tests, determining specific gravity, observing any unusual color or odor, screening for bacteriuria, and examining the sediment microscopically. Urinary Tract Infections (UTIs) in Children
    • ↑ WBC
    • Brucella may be grown on culture.
• Imaging
  • Radiographs
    • Arthritis Arthritis Acute or chronic inflammation of joints. Osteoarthritis
    • Interstitial pneumonitis Pneumonitis Human Herpesvirus 6 and 7, pleural effusion Pleural Effusion Pleural effusion refers to the accumulation of fluid between the layers of the parietal and visceral pleura. Common causes of this condition include infection, malignancy, autoimmune disorders, or volume overload. Clinical manifestations include chest pain, cough, and dyspnea. Pleural Effusion, or pneumonia Pneumonia Pneumonia or pulmonary inflammation is an acute or chronic inflammation of lung tissue. Causes include infection with bacteria, viruses, or fungi. In more rare cases, pneumonia can also be caused through toxic triggers through inhalation of toxic substances, immunological processes, or in the course of radiotherapy. Pneumonia
  • Computerized tomography (CT)
    • Abscess Abscess Accumulation of purulent material in tissues, organs, or circumscribed spaces, usually associated with signs of infection. Chronic Granulomatous Disease
  • Magnetic resonance imaging (MRI)
    • Spondylitis
    • Osteomyelitis Osteomyelitis Osteomyelitis is an infection of the bone that results from the spread of microorganisms from the blood (hematogenous), nearby infected tissue, or open wounds (non-hematogenous). Infections are most commonly caused by Staphylococcus aureus. Osteomyelitis
  • Echocardiography Echocardiography Ultrasonic recording of the size, motion, and composition of the heart and surrounding tissues. The standard approach is transthoracic. Tricuspid Valve Atresia (TVA) 
    • Endocarditis Endocarditis Endocarditis is an inflammatory disease involving the inner lining (endometrium) of the heart, most commonly affecting the cardiac valves. Both infectious and noninfectious etiologies lead to vegetations on the valve leaflets. Patients may present with nonspecific symptoms such as fever and fatigue. Endocarditis
    • Myocarditis Myocarditis Myocarditis is an inflammatory disease of the myocardium, which may occur alone or in association with a systemic process. There are numerous etiologies of myocarditis, but all lead to inflammation and myocyte injury, most often leading to signs and symptoms of heart failure. Myocarditis

Management and Prevention

Management

• Antibiotics
  • Adults: doxycycline plus an aminoglycoside or rifampin Rifampin A semisynthetic antibiotic produced from streptomyces mediterranei. It has a broad antibacterial spectrum, including activity against several forms of Mycobacterium. In susceptible organisms it inhibits dna-dependent RNA polymerase activity by forming a stable complex with the enzyme. It thus suppresses the initiation of RNA synthesis. Rifampin is bactericidal, and acts on both intracellular and extracellular organisms. Epiglottitis
  • Children < 8 years: trimethoprim-sulfamethoxazole (TMP-SMX) plus rifampin Rifampin A semisynthetic antibiotic produced from streptomyces mediterranei. It has a broad antibacterial spectrum, including activity against several forms of Mycobacterium. In susceptible organisms it inhibits dna-dependent RNA polymerase activity by forming a stable complex with the enzyme. It thus suppresses the initiation of RNA synthesis. Rifampin is bactericidal, and acts on both intracellular and extracellular organisms. Epiglottitis
  • Neurobrucellosis: ceftriaxone Ceftriaxone A broad-spectrum cephalosporin antibiotic and cefotaxime derivative with a very long half-life and high penetrability to meninges, eyes and inner ears. Cephalosporins plus rifampin Rifampin A semisynthetic antibiotic produced from streptomyces mediterranei. It has a broad antibacterial spectrum, including activity against several forms of Mycobacterium. In susceptible organisms it inhibits dna-dependent RNA polymerase activity by forming a stable complex with the enzyme. It thus suppresses the initiation of RNA synthesis. Rifampin is bactericidal, and acts on both intracellular and extracellular organisms. Epiglottitis and doxycycline for 12 weeks
  • Endocarditis Endocarditis Endocarditis is an inflammatory disease involving the inner lining (endometrium) of the heart, most commonly affecting the cardiac valves. Both infectious and noninfectious etiologies lead to vegetations on the valve leaflets. Patients may present with nonspecific symptoms such as fever and fatigue. Endocarditis: aminoglycoside plus rifampin Rifampin A semisynthetic antibiotic produced from streptomyces mediterranei. It has a broad antibacterial spectrum, including activity against several forms of Mycobacterium. In susceptible organisms it inhibits dna-dependent RNA polymerase activity by forming a stable complex with the enzyme. It thus suppresses the initiation of RNA synthesis. Rifampin is bactericidal, and acts on both intracellular and extracellular organisms. Epiglottitis and doxycycline for 12 weeks
• 5%–15% of patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship relapse Relapse Relapsing Fever.
  • All patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship should have close clinical follow-up.
  • Repeat serologic studies for 1 year.
  • Treat relapse Relapse Relapsing Fever with a repeat course of the standard antibiotic regimen.
• Immunity lasts for only 2 years after the disease.

Prevention

• Brucellosis is a reportable disease.
• Post-exposure prophylaxis Prophylaxis Cephalosporins for high-risk patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship: doxycycline plus rifampin Rifampin A semisynthetic antibiotic produced from streptomyces mediterranei. It has a broad antibacterial spectrum, including activity against several forms of Mycobacterium. In susceptible organisms it inhibits dna-dependent RNA polymerase activity by forming a stable complex with the enzyme. It thus suppresses the initiation of RNA synthesis. Rifampin is bactericidal, and acts on both intracellular and extracellular organisms. Epiglottitis
• Avoid unpasteurized dairy products.
• Wear gloves, gowns, and goggles when handling animals Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, animalia was one of the kingdoms. Under the modern three domain model, animalia represents one of the many groups in the domain eukaryota. Cell Types: Eukaryotic versus Prokaryotic and carcasses.
• Vaccination Vaccination Vaccination is the administration of a substance to induce the immune system to develop protection against a disease. Unlike passive immunization, which involves the administration of pre-performed antibodies, active immunization constitutes the administration of a vaccine to stimulate the body to produce its own antibodies. Vaccination of livestock (do not give to humans, as can cause infection)

Comparison of Gram-negative Coccobacilli

Differential Diagnosis

• Malaria Malaria Malaria is an infectious parasitic disease affecting humans and other animals. Most commonly transmitted via the bite of a female Anopheles mosquito infected with microorganisms of the Plasmodium genus. Patients present with fever, chills, myalgia, headache, and diaphoresis. Plasmodium/Malaria: an infection due to Plasmodium Plasmodium A genus of protozoa that comprise the malaria parasites of mammals. Four species infect humans (although occasional infections with primate malarias may occur). These are plasmodium falciparum; plasmodium malariae; plasmodium ovale, and plasmodium vivax. Species causing infection in vertebrates other than man include: plasmodium berghei; plasmodium chabaudi; p. Vinckei, and plasmodium yoelii in rodents; p. Brasilianum, plasmodium cynomolgi; and plasmodium knowlesi in monkeys; and plasmodium gallinaceum in chickens. Antimalarial Drugs. Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship may present with periodic fever Periodic Fever Fever similar to brucellosis. Other symptoms include rigors Rigors Fever, night sweats Night sweats Tuberculosis, diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea, abdominal pain Abdominal Pain Acute Abdomen, seizure, hemolytic anemia Hemolytic Anemia Hemolytic anemia (HA) is the term given to a large group of anemias that are caused by the premature destruction/hemolysis of circulating red blood cells (RBCs). Hemolysis can occur within (intravascular hemolysis) or outside the blood vessels (extravascular hemolysis). Hemolytic Anemia, and splenomegaly Splenomegaly Splenomegaly is pathologic enlargement of the spleen that is attributable to numerous causes, including infections, hemoglobinopathies, infiltrative processes, and outflow obstruction of the portal vein. Splenomegaly. The diagnosis is confirmed by visualizing Plasmodium Plasmodium A genus of protozoa that comprise the malaria parasites of mammals. Four species infect humans (although occasional infections with primate malarias may occur). These are plasmodium falciparum; plasmodium malariae; plasmodium ovale, and plasmodium vivax. Species causing infection in vertebrates other than man include: plasmodium berghei; plasmodium chabaudi; p. Vinckei, and plasmodium yoelii in rodents; p. Brasilianum, plasmodium cynomolgi; and plasmodium knowlesi in monkeys; and plasmodium gallinaceum in chickens. Antimalarial Drugs on a peripheral smear and with rapid test detection of Plasmodium Plasmodium A genus of protozoa that comprise the malaria parasites of mammals. Four species infect humans (although occasional infections with primate malarias may occur). These are plasmodium falciparum; plasmodium malariae; plasmodium ovale, and plasmodium vivax. Species causing infection in vertebrates other than man include: plasmodium berghei; plasmodium chabaudi; p. Vinckei, and plasmodium yoelii in rodents; p. Brasilianum, plasmodium cynomolgi; and plasmodium knowlesi in monkeys; and plasmodium gallinaceum in chickens. Antimalarial Drugs antigens. Treatment with antimalarials depends on the species. 
• Tuberculosis Tuberculosis Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis complex bacteria. The bacteria usually attack the lungs but can also damage other parts of the body. Approximately 30% of people around the world are infected with this pathogen, with the majority harboring a latent infection. Tuberculosis spreads through the air when a person with active pulmonary infection coughs or sneezes. Tuberculosis: a mycobacterial infection, most commonly affecting the lungs Lungs Lungs are the main organs of the respiratory system. Lungs are paired viscera located in the thoracic cavity and are composed of spongy tissue. The primary function of the lungs is to oxygenate blood and eliminate CO2. Lungs: Anatomy. Symptoms include fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever, night sweats Night sweats Tuberculosis, weight loss Weight loss Decrease in existing body weight. Bariatric Surgery, malaise Malaise Tick-borne Encephalitis Virus, and cough. The diagnosis is made with a sputum smear and culture detecting acid-fast bacilli Acid-fast bacilli Mycobacterium. Treatment involves combination therapy with isoniazid Isoniazid Antibacterial agent used primarily as a tuberculostatic. It remains the treatment of choice for tuberculosis. Antimycobacterial Drugs, rifampin Rifampin A semisynthetic antibiotic produced from streptomyces mediterranei. It has a broad antibacterial spectrum, including activity against several forms of Mycobacterium. In susceptible organisms it inhibits dna-dependent RNA polymerase activity by forming a stable complex with the enzyme. It thus suppresses the initiation of RNA synthesis. Rifampin is bactericidal, and acts on both intracellular and extracellular organisms. Epiglottitis, pyrazinamide Pyrazinamide A pyrazine that is used therapeutically as an antitubercular agent. Antimycobacterial Drugs, and ethambutol Ethambutol An antitubercular agent that inhibits the transfer of mycolic acids into the cell wall of the tubercle Bacillus. It may also inhibit the synthesis of spermidine in mycobacteria. The action is usually bactericidal, and the drug can penetrate human cell membranes to exert its lethal effect. Antimycobacterial Drugs.
• Endocarditis Endocarditis Endocarditis is an inflammatory disease involving the inner lining (endometrium) of the heart, most commonly affecting the cardiac valves. Both infectious and noninfectious etiologies lead to vegetations on the valve leaflets. Patients may present with nonspecific symptoms such as fever and fatigue. Endocarditis: an inflammatory condition of the endocardium Endocardium The innermost layer of the heart, comprised of endothelial cells. Heart: Anatomy, usually due to an infection. The heart valves are typically affected. Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship present with fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever and a new heart murmur. Endocarditis Endocarditis Endocarditis is an inflammatory disease involving the inner lining (endometrium) of the heart, most commonly affecting the cardiac valves. Both infectious and noninfectious etiologies lead to vegetations on the valve leaflets. Patients may present with nonspecific symptoms such as fever and fatigue. Endocarditis is diagnosed with blood cultures and echocardiography Echocardiography Ultrasonic recording of the size, motion, and composition of the heart and surrounding tissues. The standard approach is transthoracic. Tricuspid Valve Atresia (TVA). Prolonged antibiotics are required for infectious causes, and surgery may be required.
• Typhoid Typhoid Typhoid (or enteric) fever is a severe, systemic bacterial infection classically caused by the facultative intracellular and Gram-negative bacilli Salmonella enterica serotype Typhi (S. Typhimurium, formerly S. typhi). S. paratyphi serotypes A, B, or C can cause a similar syndrome. Enteric Fever (Typhoid Fever) fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever: a systemic disease caused by Salmonella enterica Salmonella enterica A subgenus of Salmonella containing several medically important serotypes. The habitat for the majority of strains is warm-blooded animals. Salmonella serotype Typhi. Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship may have a high fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever, abdominal pain Abdominal Pain Acute Abdomen, and rose spots Rose spots Small, speckled, rose-colored exanthem most commonly on the lower chest/abdomen Enteric Fever (Typhoid Fever) ( rash Rash Rocky Mountain Spotted Fever) on the body. Unlike brucellosis, typhoid Typhoid Typhoid (or enteric) fever is a severe, systemic bacterial infection classically caused by the facultative intracellular and Gram-negative bacilli Salmonella enterica serotype Typhi (S. Typhimurium, formerly S. typhi). S. paratyphi serotypes A, B, or C can cause a similar syndrome. Enteric Fever (Typhoid Fever) predominantly manifests with gastrointestinal symptoms. The diagnosis is based on the clinical presentation and confirmed by culture. Antibiotics are used to treat typhoid Typhoid Typhoid (or enteric) fever is a severe, systemic bacterial infection classically caused by the facultative intracellular and Gram-negative bacilli Salmonella enterica serotype Typhi (S. Typhimurium, formerly S. typhi). S. paratyphi serotypes A, B, or C can cause a similar syndrome. Enteric Fever (Typhoid Fever) fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever, and include ceftriaxone Ceftriaxone A broad-spectrum cephalosporin antibiotic and cefotaxime derivative with a very long half-life and high penetrability to meninges, eyes and inner ears. Cephalosporins, fluoroquinolones Fluoroquinolones Fluoroquinolones are a group of broad-spectrum, bactericidal antibiotics inhibiting bacterial DNA replication. Fluoroquinolones cover gram-negative, anaerobic, and atypical organisms, as well as some gram-positive and multidrug-resistant (MDR) organisms. Fluoroquinolones, and azithromycin Azithromycin A semi-synthetic macrolide antibiotic structurally related to erythromycin. It has been used in the treatment of Mycobacterium avium intracellulare infections, toxoplasmosis, and cryptosporidiosis. Macrolides and Ketolides.
• Rheumatic fever Rheumatic fever Acute rheumatic fever (ARF) is an autoimmune inflammatory process that usually follows Streptococcal pharyngitis. Acute rheumatic fever usually occurs 2-4 weeks after an untreated infection and affects the heart, skin, joints, and nervous system. Rheumatic Fever: a nonsuppurative, inflammatory complication of streptococcal pharyngitis Streptococcal Pharyngitis Rheumatic Fever. The disease is rare in developed countries. Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship can have a high fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever, arthritis Arthritis Acute or chronic inflammation of joints. Osteoarthritis, pancarditis, and erythema marginatum Erythema Marginatum Rheumatic Fever, and often have preceding symptoms of sore throat Sore throat Pharyngitis is an inflammation of the back of the throat (pharynx). Pharyngitis is usually caused by an upper respiratory tract infection, which is viral in most cases. It typically results in a sore throat and fever. Other symptoms may include a runny nose, cough, headache, and hoarseness. Pharyngitis or skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions infection. Diagnosis is based on the clinical presentation, modified Jones criteria Jones Criteria Rheumatic Fever, and laboratory testing. Treatment includes aspirin Aspirin The prototypical analgesic used in the treatment of mild to moderate pain. It has anti-inflammatory and antipyretic properties and acts as an inhibitor of cyclooxygenase which results in the inhibition of the biosynthesis of prostaglandins. Aspirin also inhibits platelet aggregation and is used in the prevention of arterial and venous thrombosis. Nonsteroidal Antiinflammatory Drugs (NSAIDs), corticosteroids Corticosteroids Chorioretinitis, and antibiotics.