Borrelia

Borrelia

Borrelia are gram-negative microaerophilic Microaerophilic Helicobacter spirochetes Spirochetes An order of slender, flexuous, helically coiled bacteria, with one or more complete turns in the helix. Treponema. Owing to their small size, they are not easily seen on Gram stain Gram stain Klebsiella but can be visualized using dark-field microscopy Dark-field microscopy Treponema, Giemsa, or Wright stain. Spirochetes Spirochetes An order of slender, flexuous, helically coiled bacteria, with one or more complete turns in the helix. Treponema are motile and move in a characteristic spinning fashion due to axial Axial Computed Tomography (CT) filaments in the periplasmic space. The ability of Borrelia to express different repertoires of surface 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 allows for bacterial transmission and evasion of the host 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. Borrelia utilizes Ixodes ticks Ticks Blood-sucking acarid parasites of the order ixodida comprising two families: the softbacked ticks (argasidae) and hardbacked ticks (ixodidae). Ticks are larger than their relatives, the mites. They penetrate the skin of their host by means of highly specialized, hooked mouth parts and feed on its blood. Ticks attack all groups of terrestrial vertebrates. In humans they are responsible for many tick-borne diseases, including the transmission of rocky mountain spotted fever; tularemia; babesiosis; african swine fever; and relapsing fever. Coxiella/Q Fever, Ornithodoros ticks Ticks Blood-sucking acarid parasites of the order ixodida comprising two families: the softbacked ticks (argasidae) and hardbacked ticks (ixodidae). Ticks are larger than their relatives, the mites. They penetrate the skin of their host by means of highly specialized, hooked mouth parts and feed on its blood. Ticks attack all groups of terrestrial vertebrates. In humans they are responsible for many tick-borne diseases, including the transmission of rocky mountain spotted fever; tularemia; babesiosis; african swine fever; and relapsing fever. Coxiella/Q Fever, and the human body louse Human Body Louse Epidemic Typhus as vectors, and the resulting diseases include Lyme disease Lyme disease Lyme disease is a tick-borne infection caused by the gram-negative spirochete Borrelia burgdorferi. Lyme disease is transmitted by the black-legged Ixodes tick (known as a deer tick), which is only found in specific geographic regions. Patient presentation can vary depending on the stage of the disease and may include a characteristic erythema migrans rash. Lyme Disease and relapsing 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.

Last updated: Sep 8, 2022

Editorial responsibility: Stanley Oiseth, Lindsay Jones, Evelin Maza

Contents

General Characteristics of Borrelia

Pathogenesis

Diseases Caused by Borrelia

Comparison of Spirochetes

References

General Characteristics of Borrelia

Basic features of Borrelia species

Gram-negative, corkscrew-shaped spirochetes Spirochetes An order of slender, flexuous, helically coiled bacteria, with one or more complete turns in the helix. Treponema
Larger than Treponema Treponema Treponema is a gram-negative, microaerophilic spirochete. Owing to its very thin structure, it is not easily seen on Gram stain, but can be visualized using dark-field microscopy. This spirochete contains endoflagella, which allow for a characteristic corkscrew movement. Treponema species
Visualization:
- Dark-field microscopy Dark-field microscopy Treponema
- Wright or Giemsa stain
- Difficult to visualize using Gram stain Gram stain Klebsiella
Microaerophilic Microaerophilic Helicobacter
Surrounded by an additional phospholipid-rich outer membrane and few exposed 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
Difficult to culture on ordinary media; Barbour-Stoenner-Kelly (BSK) medium is commonly used.

Dark field microscopy of borrelia burgdorferi — Dark-field microscopy of *Borrelia burgdorferi*
Image: “Borrelia burgdorferi (CDC-PHIL-6631) lores” by CDC. License: Public Domain

Clinically relevant species

Lyme disease Lyme disease Lyme disease is a tick-borne infection caused by the gram-negative spirochete Borrelia burgdorferi. Lyme disease is transmitted by the black-legged Ixodes tick (known as a deer tick), which is only found in specific geographic regions. Patient presentation can vary depending on the stage of the disease and may include a characteristic erythema migrans rash. Lyme Disease:
- B. burgdorferi
- B. afzelii
- B. garinii
Relapsing 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:
- Tick-borne disease is associated with multiple species and includes:
  - B. hermsii
  - B. turicatae
  - B. miyamotoi
  - B. hispanica
  - B. duttoni
  - B. persica
- Louse-borne: B. recurrentis

Pathogenesis

Reservoirs

Rodents
Birds
Bats
White-tailed deer
Humans (B. recurrentis)

Transmission

Ticks Ticks Blood-sucking acarid parasites of the order ixodida comprising two families: the softbacked ticks (argasidae) and hardbacked ticks (ixodidae). Ticks are larger than their relatives, the mites. They penetrate the skin of their host by means of highly specialized, hooked mouth parts and feed on its blood. Ticks attack all groups of terrestrial vertebrates. In humans they are responsible for many tick-borne diseases, including the transmission of rocky mountain spotted fever; tularemia; babesiosis; african swine fever; and relapsing fever. Coxiella/Q Fever
- Occurs through saliva Saliva The clear, viscous fluid secreted by the salivary glands and mucous glands of the mouth. It contains mucins, water, organic salts, and ptyalin. Salivary Glands: Anatomy injection during feeding
- Ticks Ticks Blood-sucking acarid parasites of the order ixodida comprising two families: the softbacked ticks (argasidae) and hardbacked ticks (ixodidae). Ticks are larger than their relatives, the mites. They penetrate the skin of their host by means of highly specialized, hooked mouth parts and feed on its blood. Ticks attack all groups of terrestrial vertebrates. In humans they are responsible for many tick-borne diseases, including the transmission of rocky mountain spotted fever; tularemia; babesiosis; african swine fever; and relapsing fever. Coxiella/Q Fever are usually very small and the bite is often unnoticed.
- Longer attachment is associated with a higher risk of transmission.
- Associated species
  - Ixodes scapularis (deer tick)
  - Ornithodoros
Louse
- Species: Pediculus humanus corporis Pediculus Humanus Corporis Epidemic Typhus ( human body louse Human Body Louse Epidemic Typhus)
  - Lives on clothing
  - Only feeds on humans
- B. recurrentis is introduced when the louse is crushed by humans.
  - Can enter through breaks in the 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 or conjunctivae (from rubbing eyes)
  - Not transmitted from louse saliva Saliva The clear, viscous fluid secreted by the salivary glands and mucous glands of the mouth. It contains mucins, water, organic salts, and ptyalin. Salivary Glands: Anatomy or feces

Virulence Virulence The degree of pathogenicity within a group or species of microorganisms or viruses as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. The pathogenic capacity of an organism is determined by its virulence factors. Proteus

Motility Motility The motor activity of the gastrointestinal tract. Gastrointestinal Motility
- Possess numerous axial Axial Computed Tomography (CT) filaments
  - Thin endoflagella in the periplasmic space
  - Allows them to move in a spinning fashion
- Propels the organism through blood and extracellular matrix Extracellular matrix A meshwork-like substance found within the extracellular space and in association with the basement membrane of the cell surface. It promotes cellular proliferation and provides a supporting structure to which cells or cell lysates in culture dishes adhere. Hypertrophic and Keloid Scars
- Allows escape Escape With constant immune mechanisms holding unstable tumor cells in equilibrium, tumor-cell variants may emerge. These cancer cells may express fewer antigens on their surfaces or lose their MHC class I expression.Variants may also protect themselves from T-cell attack via expression of IC molecules on their surfaces, like normal cells.Creation of an immunosuppressive state in the microenvironment is another way to grow without immunologic interference. Cancer Immunotherapy from phagocytosis Phagocytosis The engulfing and degradation of microorganisms; other cells that are dead, dying, or pathogenic; and foreign particles by phagocytic cells (phagocytes). Innate Immunity: Phagocytes and Antigen Presentation
Outer surface 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 (Osps)
- Surface lipoproteins Lipoproteins Lipid-protein complexes involved in the transportation and metabolism of lipids in the body. They are spherical particles consisting of a hydrophobic core of triglycerides and cholesterol esters surrounded by a layer of hydrophilic free cholesterol; phospholipids; and apolipoproteins. Lipoproteins are classified by their varying buoyant density and sizes. Lipid Metabolism can be up- or down-regulated to facilitate transmission.
- OspA
  - Responsible for attachment to the midgut Midgut Development of the Abdominal Organs of ticks Ticks Blood-sucking acarid parasites of the order ixodida comprising two families: the softbacked ticks (argasidae) and hardbacked ticks (ixodidae). Ticks are larger than their relatives, the mites. They penetrate the skin of their host by means of highly specialized, hooked mouth parts and feed on its blood. Ticks attack all groups of terrestrial vertebrates. In humans they are responsible for many tick-borne diseases, including the transmission of rocky mountain spotted fever; tularemia; babesiosis; african swine fever; and relapsing fever. Coxiella/Q Fever
  - Down-regulation Down-Regulation A negative regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (gene expression regulation), mRNAs, and proteins. Pharmacokinetics and Pharmacodynamics results in detachment and transfer to the saliva Saliva The clear, viscous fluid secreted by the salivary glands and mucous glands of the mouth. It contains mucins, water, organic salts, and ptyalin. Salivary Glands: Anatomy of ticks Ticks Blood-sucking acarid parasites of the order ixodida comprising two families: the softbacked ticks (argasidae) and hardbacked ticks (ixodidae). Ticks are larger than their relatives, the mites. They penetrate the skin of their host by means of highly specialized, hooked mouth parts and feed on its blood. Ticks attack all groups of terrestrial vertebrates. In humans they are responsible for many tick-borne diseases, including the transmission of rocky mountain spotted fever; tularemia; babesiosis; african swine fever; and relapsing fever. Coxiella/Q Fever.
- OspC
  - Allows invasion through the host 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
  - Important for the use of plasminogen Plasminogen Precursor of plasmin (fibrinolysin). It is a single-chain beta-globulin of molecular weight 80-90, 000 found mostly in association with fibrinogen in plasma; plasminogen activators change it to fibrinolysin. It is used in wound debriding and has been investigated as a thrombolytic agent. Hemostasis
    - Digests fibrin Fibrin A protein derived from fibrinogen in the presence of thrombin, which forms part of the blood clot. Rapidly Progressive Glomerulonephritis and glycoproteins Glycoproteins Conjugated protein-carbohydrate compounds including mucins, mucoid, and amyloid glycoproteins. Basics of Carbohydrates
    - Assists movement through extracellular matrix Extracellular matrix A meshwork-like substance found within the extracellular space and in association with the basement membrane of the cell surface. It promotes cellular proliferation and provides a supporting structure to which cells or cell lysates in culture dishes adhere. Hypertrophic and Keloid Scars
Variable Variable Variables represent information about something that can change. The design of the measurement scales, or of the methods for obtaining information, will determine the data gathered and the characteristics of that data. As a result, a variable can be qualitative or quantitative, and may be further classified into subgroups. Types of Variables major 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 (VMPs) provide antigenic variation.
- Borrelia are able to change major antigens on their surface.
- Allows the 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 to evade the adaptive immune response Adaptive immune response Immune responses against pathogens are divided into the innate and adaptive immune response systems. The adaptive immune response, also called the acquired immune system, consists of 2 main mechanisms: the humoral- and cellular-mediated immune responses. Adaptive Immune Response of the host
Endo- and exotoxins Exotoxins Toxins produced, especially by bacterial or fungal cells, and released into the culture medium or environment. Bacteriology are generally not produced; symptoms are due to the 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 of the host.

Axial filaments of borrelia — Axial filaments of Borrelia:
Axial filaments are made up of multiple periplasmic flagella (bottom picture). This allows the spirochete (top picture) to move in a spinning fashion.
Image by Lecturio. License: CC BY-NC-SA 4.0

At-risk populations

Tick-borne diseases:
- Hikers
- Campers
- Woodworkers
Louse-borne diseases:
- Refugees
- Homeless

Diseases Caused by Borrelia

The following diseases are caused by Borrelia:

Table: Diseases caused by *Borrelia*
Disease	Lyme disease Lyme disease Lyme disease is a tick-borne infection caused by the gram-negative spirochete Borrelia burgdorferi. Lyme disease is transmitted by the black-legged Ixodes tick (known as a deer tick), which is only found in specific geographic regions. Patient presentation can vary depending on the stage of the disease and may include a characteristic erythema migrans rash. Lyme Disease	Relapsing 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
Associated species	B. burgdorferi (United States) B. afzelii and B. garinii (Europe)	B. hermsii, B. turicatae, B. miyamotoi ( TBRF TBRF Relapsing Fever) B. recurrentis ( LBRF LBRF Relapsing Fever)
Clinical manifestations	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, myalgias Myalgias Painful sensation in the muscles. Tick-borne Encephalitis Virus, 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 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: erythema Erythema Redness of the skin produced by congestion of the capillaries. This condition may result from a variety of disease processes. Chalazion chronicum migrans	Recurrent fever Recurrent Fever Fever, myalgias Myalgias Painful sensation in the muscles. Tick-borne Encephalitis Virus, arthralgia Arthralgia Pain in the joint. Rheumatic Fever, 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, delirium Delirium Delirium is a medical condition characterized by acute disturbances in attention and awareness. Symptoms may fluctuate during the course of a day and involve memory deficits and disorientation. Delirium 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: macular or purpuric rash Rash Rocky Mountain Spotted Fever on trunk and extremities, erythema Erythema Redness of the skin produced by congestion of the capillaries. This condition may result from a variety of disease processes. Chalazion multiforme
Complications	Neurological: Bell’s palsy Palsy paralysis of an area of the body, thus incapable of voluntary movement Cranial Nerve Palsies, 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, meningoradiculitis Meningoradiculitis Lyme Disease, encephalomyelitis Cardiac: 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, AV block AV block Atrioventricular (AV) block is a bradyarrhythmia caused by delay, or interruption, in the electrical conduction between the atria and the ventricles. Atrioventricular block occurs due to either anatomic or functional impairment, and is classified into 3 types. Atrioventricular block (AV block) Musculoskeletal: migratory polyarthritis Migratory Polyarthritis Rheumatic Fever	Neurological: Bell’s palsy Palsy paralysis of an area of the body, thus incapable of voluntary movement Cranial Nerve Palsies, 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, myelitis Myelitis Inflammation of the spinal cord. Relatively common etiologies include infections; autoimmune diseases; spinal cord; and ischemia. Clinical features generally include weakness, sensory loss, localized pain, incontinence, and other signs of autonomic dysfunction. Relapsing Fever Cardiac: 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 Pulmonary: ARDS Hematologic: 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, hemoptysis Hemoptysis Hemoptysis is defined as the expectoration of blood originating in the lower respiratory tract. Hemoptysis is a consequence of another disease process and can be classified as either life threatening or non-life threatening. Hemoptysis can result in significant morbidity and mortality due to both drowning (reduced gas exchange as the lungs fill with blood) and hemorrhagic shock. Hemoptysis, epistaxis Epistaxis Bleeding from the nose. Granulomatosis with Polyangiitis
Diagnosis	Clinical, supported using 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 and Western blot	Clinical, dark-field microscopy Dark-field microscopy Treponema, Giemsa stain, or Wright stain of blood smear Blood smear Myeloperoxidase Deficiency
Management	Doxycycline 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 for severe disease	Doxycycline, penicillin Penicillin Rheumatic Fever G Severe disease: penicillin Penicillin Rheumatic Fever G, 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
Prevention	↓ tick exposure → protective clothing, repellents, remove ticks Ticks Blood-sucking acarid parasites of the order ixodida comprising two families: the softbacked ticks (argasidae) and hardbacked ticks (ixodidae). Ticks are larger than their relatives, the mites. They penetrate the skin of their host by means of highly specialized, hooked mouth parts and feed on its blood. Ticks attack all groups of terrestrial vertebrates. In humans they are responsible for many tick-borne diseases, including the transmission of rocky mountain spotted fever; tularemia; babesiosis; african swine fever; and relapsing fever. Coxiella/Q Fever PEP PEP A monocarboxylic acid anion derived from selective deprotonation of the carboxy group of phosphoenolpyruvic acid. It is a metabolic intermediate in glycolysis; gluconeogenesis; and other pathways. Glycolysis: doxycycline for those in ↑ risk areas	TBRF TBRF Relapsing Fever: ↓ tick exposure → sealing floors in houses, avoid rodents, tick repellents Tick Repellents Ehrlichiosis and Anaplasmosis LBRF LBRF Relapsing Fever: ↓ louse exposure → improved hygiene, ↓ crowding, washing clothes PEP PEP A monocarboxylic acid anion derived from selective deprotonation of the carboxy group of phosphoenolpyruvic acid. It is a metabolic intermediate in glycolysis; gluconeogenesis; and other pathways. Glycolysis: doxycycline for those in ↑ risk areas

TBRF: tick-borne relapsing fever

LBRF: louse-borne relapsing fever

AV: atrioventricular

ARDS: acute respiratory distress syndrome

ELISA: enzyme-linked immunosorbent assay

PEP: post-exposure prophylaxis

Classic erythema migrans rash of borrelia burgdorferi — Classic erythema migrans rash of *Borrelia burgdorferi*
Image: “Diagnostic challenges of early Lyme disease: lessons from a community case series” by Aucott J, Morrison C, Munoz B, Rowe PC, Schwarzwalder A, West SK. License: CC BY 2.0

Comparison of Spirochetes

Spirochetes Spirochetes An order of slender, flexuous, helically coiled bacteria, with one or more complete turns in the helix. Treponema are gram negative Gram negative Bacteria which lose crystal violet stain but are stained pink when treated by gram’s method. Yersinia spp./Yersiniosis, spiral shaped Spiral shaped Treponema, and motile. The following table briefly compares some clinically relevant spirochetes Spirochetes An order of slender, flexuous, helically coiled bacteria, with one or more complete turns in the helix. Treponema:

Table: Comparison of clinically relevant spirochetes Spirochetes An order of slender, flexuous, helically coiled bacteria, with one or more complete turns in the helix. Treponema
Organism	Treponema pallidum Treponema pallidum The causative agent of venereal and non-venereal syphilis as well as yaws. Treponema pallidum	Other T. pallidum subspecies	Treponema carateum Treponema carateum Treponema	Borrelia burgdorfi	Borrelia recurrentis	Leptospira interrogans Leptospira interrogans A genus of question mark-shaped bacteria spirochetes which is found in freshwater that is contaminated by animal urine. It causes leptospirosis. Leptospira/Leptospirosis
Micro	Microaero Not seen using Gram or Giemsa stain	Microaero Not seen using Gram or Giemsa stain	Microaero Not seen using Gram or Giemsa stain	Microaero Seen using Giemsa and Wright stain	Microaero Seen using Giemsa and Wright stain	Aerobic Hooked ends
Virulence Virulence The degree of pathogenicity within a group or species of microorganisms or viruses as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. The pathogenic capacity of an organism is determined by its virulence factors. Proteus	Hyaluronidase Hyaluronidase Bacteroides Fibronectin coating Fibronectin coating Treponema	Hyaluronidase Hyaluronidase Bacteroides Fibronectin coating Fibronectin coating Treponema	Hyaluronidase Hyaluronidase Bacteroides Fibronectin coating Fibronectin coating Treponema	Antigenic variation Osp regulation	Antigenic variation	LPS 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 Complement regulators and enzymes Enzymes Enzymes are complex protein biocatalysts that accelerate chemical reactions without being consumed by them. Due to the body’s constant metabolic needs, the absence of enzymes would make life unsustainable, as reactions would occur too slowly without these molecules. Basics of Enzymes
Reservoir Reservoir Animate or inanimate sources which normally harbor disease-causing organisms and thus serve as potential sources of disease outbreaks. Reservoirs are distinguished from vectors (disease vectors) and carriers, which are agents of disease transmission rather than continuing sources of potential disease outbreaks. Humans may serve both as disease reservoirs and carriers. Escherichia coli	Humans	Humans	Humans	Rodents Deer	Humans	Wild 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 Livestock Domesticated 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
Transmission	Sexual contact	P2P contact	P2P contact	Ixodes tick	Louse	Direct contact with animal tissue or fluids
Clinical	Syphilis Syphilis Syphilis is a bacterial infection caused by the spirochete Treponema pallidum pallidum (T. p. pallidum), which is usually spread through sexual contact. Syphilis has 4 clinical stages: primary, secondary, latent, and tertiary. Syphilis	Yaws Yaws A systemic non-venereal infection of the tropics caused by treponema pallidum subspecies pertenue. Yaws, Bejel, and Pinta Bejel Bejel Yaws, bejel, and pinta are endemic, nonvenereal treponematoses. The causative organisms are Treponema pallidum pertenue (yaws), T. pallidum endemicum (bejel), and T. carateum (pinta). These treponematoses are generally transmitted by direct skin-to-skin contact with infected skin lesions. Yaws, Bejel, and Pinta	Pinta Pinta An infectious disease of the skin caused by treponema carateum that occurs only in the Western hemisphere. Age of onset is between 10 and 20 years of age. This condition is characterized by marked changes in the skin color and is believed to be transmitted by direct person-to-person contact. Yaws, Bejel, and Pinta	Lyme disease Lyme disease Lyme disease is a tick-borne infection caused by the gram-negative spirochete Borrelia burgdorferi. Lyme disease is transmitted by the black-legged Ixodes tick (known as a deer tick), which is only found in specific geographic regions. Patient presentation can vary depending on the stage of the disease and may include a characteristic erythema migrans rash. Lyme Disease	Relapsing 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	Leptospirosis Leptospirosis Leptospira is a spiral or question mark-shaped, gram-negative spirochete with hook-shaped ends. The major clinical species is Leptospira interrogans, which causes a mild flu-like illness in a majority of cases. The manifestations are biphasic, with Leptospira found in the blood initially. Leptospira/Leptospirosis Weil’s disease Weil’s disease Leptospira/Leptospirosis
Diagnosis	VDRL VDRL Treponema FTA-ABS Direct visualization	Clinical VDRL VDRL Treponema FTA-ABS	Clinical VDRL VDRL Treponema FTA-ABS	Clinical 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 Western blot	Blood-smear analysis	Blood culture Urine culture Urine culture Urinary Tract Infections (UTIs) 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 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)
Management	Penicillin Penicillin Rheumatic Fever G 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 Doxycycline	Penicillin Penicillin Rheumatic Fever G 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	Penicillin Penicillin Rheumatic Fever G 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	Doxycycline Amoxicillin Amoxicillin A broad-spectrum semisynthetic antibiotic similar to ampicillin except that its resistance to gastric acid permits higher serum levels with oral administration. Penicillins 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	Penicillin Penicillin Rheumatic Fever G Doxycycline	Penicillin Penicillin Rheumatic Fever G Doxycycline

Osp: outer surface protein

LPS: lipopolysaccharide

P2P: person-to-person

Microaero: microaerophilic

VDRL: Venereal Disease Research Laboratory test

FTA-ABS: fluorescent treponemal antibody absorption

ELISA: enzyme-linked immunosorbent assay

PCR: polymerase chain reaction

Thick spirals of treponema — Visual comparison of spirochetes on electron micrograph: thick spirals of *Treponema*
Image: “Treponema pallidum” by Dr. David Cox. License: Public Domain

Borrelia — Visual comparison of spirochetes on electron micrograph: thick spirals of *Treponema*
Image: “Treponema pallidum” by Dr. David Cox. License: Public Domain

References

Barbour, A.G. (2020). Clinical features, diagnosis, and management of relapsing fever. In Mitty, J. (Ed.), Uptodate. Retrieved December 21, 2020, from https://www.uptodate.com/contents/clinical-features-diagnosis-and-management-of-relapsing-fever
Barbour, A.G.(2020). Microbiology, pathogenesis, and epidemiology of relapsing fever. In Mitty, J. (Ed.), Uptodate. Retrieved December 22, 2020, from https://www.uptodate.com/contents/microbiology-pathogenesis-and-epidemiology-of-relapsing-fever
Barbour, A.G. (2020). Microbiology of Lyme disease. In Mitty, J. (Ed.), Uptodate. Retrieved December 22, 2020, from https://www.uptodate.com/contents/microbiology-of-lyme-disease
Gladwin, M., & Trattler, B. (2008). Clinical microbiology made ridiculously simple (4th edition). Miami: MedMaster

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