Treponema is a gram-negative, microaerophilicMicroaerophilicHelicobacter spirochete. Owing to its very thin structure, it is not easily seen on Gram stainGram stainKlebsiella, but can be visualized using dark-field microscopy. This spirochete contains endoflagella, which allow for a characteristic corkscrew movement. The bacteriaBacteriaBacteria 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 are able to avoid immune recognitionImmune RecognitionYaws, Bejel, and Pinta and phagocytosisPhagocytosisThe 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 by forming a protective coating with fibronectinFibronectinGlycoproteins found on the surfaces of cells, particularly in fibrillar structures. The proteins are lost or reduced when these cells undergo viral or chemical transformation. They are highly susceptible to proteolysis and are substrates for activated blood coagulation factor VIII. The forms present in plasma are called cold-insoluble globulins.Connective Tissue: Histology. Humans are the only reservoirReservoirAnimate 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 and transmission is through human-to-human contact. The most common species involved in human disease is Treponema pallidum subspecies pallidum, which is the causative agent of syphilisSyphilisSyphilis 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. Other clinically relevant species include T. pallidum pertenue, T. pallidum endemicum, and T. carateum. These are the causative organisms for yawsYawsA systemic non-venereal infection of the tropics caused by treponema pallidum subspecies pertenue.Yaws, Bejel, and Pinta, bejelBejelYaws, 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, and pintaPintaAn 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, respectively.
Gram-negative bacteriaBacteriaBacteria 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: Most bacteriaBacteriaBacteria 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 can be classified according to a lab procedure called Gram stainingGram stainingBacteriology. BacteriaBacteriaBacteria 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 with cell walls that have a thin layer of peptidoglycanPeptidoglycanPenicillins do not retain the crystal violet stain utilized in Gram stainingGram stainingBacteriology. These bacteriaBacteriaBacteria 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 do, however, retain the safranin counterstain and thus appear as pinkish-red on the stain, making them gram negativeGram negativeBacteria which lose crystal violet stain but are stained pink when treated by gram’s method.Yersinia spp./Yersiniosis. These bacteriaBacteriaBacteria 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 can be further classified according to morphology (diplococci, curved rods, bacilliBacilliShigella, and coccobacilli) and their ability to grow in the presence of oxygen (aerobic versus anaerobic). The bacteriaBacteriaBacteria 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 can be more narrowly identified by growing them on specific media (triple sugar ironTriple sugar ironShigella (TSITSIShigella) agar) where their enzymesEnzymesEnzymes 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 can be identified (ureaseUreaseAn enzyme that catalyzes the conversion of urea and water to carbon dioxide and ammonia.Nocardia/Nocardiosis, oxidaseOxidaseNeisseria) and their ability to ferment lactose can be tested.
* Stains poorly on Gram stainGram stainKlebsiella ** PleomorphicPleomorphicBacteroides rod/coccobacillus
*** Require special transport media
Spirochete (spiralSpiralComputed tomography where there is continuous x-ray exposure to the patient while being transported in a spiral or helical pattern through the beam of irradiation. This provides improved three-dimensional contrast and spatial resolution compared to conventional computed tomography, where data is obtained and computed from individual sequential exposures.Computed Tomography (CT) shaped)
3 flagellaFlagellaA whiplike motility appendage present on the surface cells. Prokaryote flagella are composed of a protein called flagellin. Bacteria can have a single flagellum, a tuft at one pole, or multiple flagella covering the entire surface. In eukaryotes, flagella are threadlike protoplasmic extensions used to propel flagellates and sperm. Flagella have the same basic structure as cilia but are longer in proportion to the cell bearing them and present in much smaller numbers.Helicobacter originate from each end.
The pathogenic species are morphologically and antigenically indistinguishable.
Treponema pallidum spirochetes in a sample using a modified Steiner silver stainSilver stainThe use of silver, usually silver nitrate, as a reagent for producing contrast or coloration in tissue specimens.Legionella/Legionellosis
Image: “Treponema pallidum 01” by Dr. Edwin P. Ewing, Jr. License: Public Domain
A tissue sample showing numerous thin, spiral-shaped Treponema carateum.
T. pallidum subspecies pallidum (syphilisSyphilisSyphilis 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)
T. pallidum subspecies endemicum (bejelBejelYaws, 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)
T. pallidum subspecies pertenue (yawsYawsA systemic non-venereal infection of the tropics caused by treponema pallidum subspecies pertenue.Yaws, Bejel, and Pinta)
T. carateum (pintaPintaAn 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)
Pathogenesis of Treponema infectionsInfectionsInvasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases.Chronic Granulomatous Disease The pathogen adheres to the skinSkinThe 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 mucosal membranes, leading to the production of hyaluronidaseHyaluronidaseBacteroides which allows for tissue invasion. The pathogen coats itself in the host’s fibronectinFibronectinGlycoproteins found on the surfaces of cells, particularly in fibrillar structures. The proteins are lost or reduced when these cells undergo viral or chemical transformation. They are highly susceptible to proteolysis and are substrates for activated blood coagulation factor VIII. The forms present in plasma are called cold-insoluble globulins.Connective Tissue: Histology, which prevents its phagocytosisPhagocytosisThe 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 and recognition by the immune systemImmune systemThe 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. Consequently, the pathogen disseminates through the bloodstream. A host immune response ultimately occurs, which causes disease manifestations.
Humans are the only reservoirReservoirAnimate 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.
Transmission is human-to-human:
Sexual contact (syphilisSyphilisSyphilis 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)
Vertical (syphilisSyphilisSyphilis 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)
Contact with infected lesions (yawsYawsA systemic non-venereal infection of the tropics caused by treponema pallidum subspecies pertenue.Yaws, Bejel, and Pinta, bejelBejelYaws, 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, and pintaPintaAn 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)
VirulenceVirulenceThe 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
Able to move in thick substances (e.g., connective tissueConnective tissueConnective tissues originate from embryonic mesenchyme and are present throughout the body except inside the brain and spinal cord. The main function of connective tissues is to provide structural support to organs. Connective tissues consist of cells and an extracellular matrix.Connective Tissue: Histology)
Assists with dissemination
FibronectinFibronectinGlycoproteins found on the surfaces of cells, particularly in fibrillar structures. The proteins are lost or reduced when these cells undergo viral or chemical transformation. They are highly susceptible to proteolysis and are substrates for activated blood coagulation factor VIII. The forms present in plasma are called cold-insoluble globulins.Connective Tissue: Histology
SyphilisSyphilisSyphilis 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
The most common treponemal disease caused by T. pallidum pallidum:
Table: SyphilisSyphilisSyphilis 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
CongenitalCongenitalChorioretinitissyphilisSyphilisSyphilis 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
Transmission
Sexual contact
SkinSkinThe 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 disseminated rashRashRocky Mountain Spotted Fever
PatientsPatientsIndividuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures.Clinician–Patient Relationship are not contagious at this stage
Placental, during the first trimester
Symptoms
Localized disease:
Painless chancreChancreThe primary sore of syphilis, a painless indurated, eroded papule, occurring at the site of entry of the infection.Syphilis
Painless buboesBuboesChancroid after chancreChancreThe primary sore of syphilis, a painless indurated, eroded papule, occurring at the site of entry of the infection.Syphilis resolution
LymphadenopathyLymphadenopathyLymphadenopathy 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
NeurosyphilisNeurosyphilisInfections of the central nervous system caused by treponema pallidum which present with a variety of clinical syndromes. The initial phase of infection usually causes a mild or asymptomatic meningeal reaction. The meningovascular form may present acutely as brain infarction. The infection may also remain subclinical for several years. Late syndromes include general paresis; tabes dorsalis; meningeal syphilis; syphilitic optic atrophy; and spinal syphilis. General paresis is characterized by progressive dementia; dysarthria; tremor; myoclonus; seizures; and argyll-robertson pupils.Syphilis:
Tabes dorsalisTabes dorsalisParenchymatous neurosyphilis marked by slowly progressive degeneration of the posterior columns, posterior roots, and ganglia of the spinal cord. The condition tends to present 15 to 20 years after the initial infection and is characterized by lightning-like pains in the lower extremities, urinary incontinence; ataxia; severely impaired position and vibratory sense, abnormal gait, optic atrophy; Argyll-Robertson pupils, hypotonia, hyperreflexia, and trophic joint degeneration.Syphilis
MeningitisMeningitisMeningitis 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 or meningoencephalitisMeningoencephalitisEncephalitis
Stroke
Saddle noseNoseThe nose is the human body’s primary organ of smell and functions as part of the upper respiratory system. The nose may be best known for inhaling oxygen and exhaling carbon dioxide, but it also contributes to other important functions, such as tasting. The anatomy of the nose can be divided into the external nose and the nasal cavity. Nose and Nasal Cavity: Anatomy
Hutchinson’s teethTeethNormally, an adult has 32 teeth: 16 maxillary and 16 mandibular. These teeth are divided into 4 quadrants with 8 teeth each. Each quadrant consists of 2 incisors (dentes incisivi), 1 canine (dens caninus), 2 premolars (dentes premolares), and 3 molars (dentes molares). Teeth are composed of enamel, dentin, and dental cement.Teeth: Anatomy
Mulberry molarsMolarsThe most posterior teeth on either side of the jaw, totaling eight in the deciduous dentition (2 on each side, upper and lower), and usually 12 in the permanent dentition (three on each side, upper and lower). They are grinding teeth, having large crowns and broad chewing surfaces.Teeth: Anatomy
Nasal discharge
Short maxillaMaxillaOne of a pair of irregularly shaped bones that form the upper jaw. A maxillary bone provides tooth sockets for the superior teeth, forms part of the orbit, and contains the maxillary sinus.Skull: Anatomy
Diagnosis
RPR
VDRL
FTA-ABS
Dark-field microscopy
MHA-TP
PCRPCRPolymerase 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) of CSF (neurosyphilisNeurosyphilisInfections of the central nervous system caused by treponema pallidum which present with a variety of clinical syndromes. The initial phase of infection usually causes a mild or asymptomatic meningeal reaction. The meningovascular form may present acutely as brain infarction. The infection may also remain subclinical for several years. Late syndromes include general paresis; tabes dorsalis; meningeal syphilis; syphilitic optic atrophy; and spinal syphilis. General paresis is characterized by progressive dementia; dysarthria; tremor; myoclonus; seizures; and argyll-robertson pupils.Syphilis)
Management
Penicillin GPenicillin GA penicillin derivative commonly used in the form of its sodium or potassium salts in the treatment of a variety of infections. It is effective against most gram-positive bacteria and against gram-negative cocci. It has also been used as an experimental convulsant because of its actions on gamma-aminobutyric acid mediated synaptic transmission.Penicillins
CeftriaxoneCeftriaxoneA broad-spectrum cephalosporin antibiotic and cefotaxime derivative with a very long half-life and high penetrability to meninges, eyes and inner ears.Cephalosporins
Doxycycline
Prevention
Safe sexSexThe totality of characteristics of reproductive structure, functions, phenotype, and genotype, differentiating the male from the female organism.Gender Dysphoria practices
Mothers are tested and treated during pregnancyPregnancyThe 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.
CN: cranial nerve
VDRL: Venereal Disease ResearchResearchCritical and exhaustive investigation or experimentation, having for its aim the discovery of new facts and their correct interpretation, the revision of accepted conclusions, theories, or laws in the light of newly discovered facts, or the practical application of such new or revised conclusions, theories, or laws.Conflict of Interest Laboratories test
RPR: rapid plasmaPlasmaThe residual portion of blood that is left after removal of blood cells by centrifugation without prior blood coagulation.Transfusion Products reagin test
FTA-ABS: fluorescent treponemal antibody absorptionAbsorptionAbsorption involves the uptake of nutrient molecules and their transfer from the lumen of the GI tract across the enterocytes and into the interstitial space, where they can be taken up in the venous or lymphatic circulation.Digestion and Absorption test
MHA-TP: microhemagglutination test
PCRPCRPolymerase 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): polymerase chain reactionPolymerase chain reactionPolymerase 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)
CSF: cerebrospinal fluidCerebrospinal FluidA watery fluid that is continuously produced in the choroid plexus and circulates around the surface of the brain; spinal cord; and in the cerebral ventricles.Ventricular System: Anatomy
Primary, painless chancreChancreThe primary sore of syphilis, a painless indurated, eroded papule, occurring at the site of entry of the infection.Syphilis of syphilisSyphilisSyphilis 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 (Treponema pallidum pallidum infection)
The less-common species of Treponema and their diseases are summarized below:
Table: Less-common species of Treponema and their diseases
Disease
YawsYawsA systemic non-venereal infection of the tropics caused by treponema pallidum subspecies pertenue.Yaws, Bejel, and Pinta
BejelBejelYaws, 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 (endemic syphilisSyphilisSyphilis 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)
PintaPintaAn 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
Associated species
T. pallidum pertenue
T. pallidum endemicum
T. carateum
Transmission
Human-to-human
Direct contact with skinSkinThe 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 lesions
Human-to-human
Direct contact with mucosal lesions
Utensils
Human-to-human
Direct contact with skinSkinThe 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 lesions
Predominant locations
Tropical regions:
Africa
South America
India
Indonesia
Pacific Islands
Desert regions:
Middle East
Central and South Africa
Tropical regions: Central and South America
Primary demographic
Children
Children
Adults
Clinical manifestations
Primary phase: painless, yellow papillomaPapillomaA circumscribed benign epithelial tumor projecting from the surrounding surface; more precisely, a benign epithelial neoplasm consisting of villous or arborescent outgrowths of fibrovascular stroma covered by neoplastic cells.Cowden Syndrome lesion on lower extremities Secondary phase:
Solitary or disseminated papilloma-like skinSkinThe 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 lesions
Destructive bone lesionsBone LesionsMultiple Myeloma and skinSkinThe 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 ulcerations, particularly those of the face
Primary phase: small, primary papulePapuleElevated lesion < 1 cm in diameterGeneralized and Localized Rashes on the oral mucosaOral mucosaLining of the oral cavity, including mucosa on the gums; the palate; the lip; the cheek; floor of the mouth; and other structures. The mucosa is generally a nonkeratinized stratified squamous epithelium covering muscle, bone, or glands but can show varying degree of keratinization at specific locations.Stomatitis Secondary phase:
Plaques on mucous membranes and skinSkinThe 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
Lesions become condylomatous before eventually healing.
PeriostitisPeriostitisInflammation of the periosteum. The condition is generally chronic, and is marked by tenderness and swelling of the bone and an aching pain. Acute periostitis is due to infection, is characterized by diffuse suppuration, severe pain, and constitutional symptoms, and usually results in necrosis.Reactive Arthritis
Tertiary phase:
Gummas
Destructive bone lesionsBone LesionsMultiple Myeloma and skinSkinThe 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 ulcerations, particularly those of the face
Primary phase:
Initial small, red, pruritic papules
Commonly on lower extremities
Secondary phase: diffuse, flat skinSkinThe 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 lesions (pintidsPintidsYaws, Bejel, and Pinta)
Tertiary phase:
SkinSkinThe 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 discoloration
AtrophyAtrophyDecrease in the size of a cell, tissue, organ, or multiple organs, associated with a variety of pathological conditions such as abnormal cellular changes, ischemia, malnutrition, or hormonal changes.Cellular Adaptation
Diagnosis
Since these treponemal species are morphologically indistinguishable, the diagnosis is based on:
Clinical manifestations
Geographic region
Demographics
Supporting evidence:
VDRL
FTA-ABS
Management
Penicillin GPenicillin GA penicillin derivative commonly used in the form of its sodium or potassium salts in the treatment of a variety of infections. It is effective against most gram-positive bacteria and against gram-negative cocci. It has also been used as an experimental convulsant because of its actions on gamma-aminobutyric acid mediated synaptic transmission.Penicillins
AzithromycinAzithromycinA 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
VDRL: Venereal Disease ResearchResearchCritical and exhaustive investigation or experimentation, having for its aim the discovery of new facts and their correct interpretation, the revision of accepted conclusions, theories, or laws in the light of newly discovered facts, or the practical application of such new or revised conclusions, theories, or laws.Conflict of Interest Laboratories test
FTA-ABS: fluorescent treponemal antibody absorptionAbsorptionAbsorption involves the uptake of nutrient molecules and their transfer from the lumen of the GI tract across the enterocytes and into the interstitial space, where they can be taken up in the venous or lymphatic circulation.Digestion and Absorption test
Cutaneous manifestation of yawsYawsA systemic non-venereal infection of the tropics caused by treponema pallidum subspecies pertenue.Yaws, Bejel, and Pinta (A) A patient with lesions on the face due to Treponema pallidum pertenue (B) Resolution of the lesions after treatment with penicillinPenicillinRheumatic Fever
Image: “YawsYawsA systemic non-venereal infection of the tropics caused by treponema pallidum subspecies pertenue.Yaws, Bejel, and Pinta treatment” by PLOS. License: CC BY 2.5
Cutaneous manifestation of yawsYawsA systemic non-venereal infection of the tropics caused by treponema pallidum subspecies pertenue.Yaws, Bejel, and Pinta Juxta-articular skinSkinThe 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 lesions and nodules on the elbow resulting from a Treponema pallidum pertenue infection
Image: “YawsYawsA systemic non-venereal infection of the tropics caused by treponema pallidum subspecies pertenue.Yaws, Bejel, and Pinta 01” by Dr. Peter Perine. License: Public Domain
Mucocutaneous lesions of bejelBejelYaws, 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 (endemic syphilisSyphilisSyphilis 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) A: An oral lesion of primary bejelBejelYaws, 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 resulting from Treponema pallidum endemicumTreponema Pallidum EndemicumYaws, Bejel, and Pinta infection B: Chronic skinSkinThe 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 lesion of secondary bejelBejelYaws, 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
Image: “Endemic treponemal diseases” by Marks M, Solomon AW, Mabey DC. License: CC BY 4.0
Gummatous lesions in late-stage bejelBejelYaws, 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 (Treponema pallidum endemicumTreponema Pallidum EndemicumYaws, Bejel, and Pinta infection)
Image: “Infiltration of skinSkinThe 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 due to endemic syphilisSyphilisSyphilis 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” by Alireza Abdolrasouli, Adam Croucher, Yahya Hemmati, and David Mabey. License: Public Domain
Cutaneous lesions of pintaPintaAn 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 (Treponema carateum infection) (A) Erythematous plaquePlaquePrimary Skin Lesions of early pintaPintaAn 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 (B) SkinSkinThe 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 discoloration of late pintaPintaAn 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
Image: “Endemic treponemal diseases” by Marks M, Solomon AW, Mabey DC. License: CC BY 4.0
Spirochetes are gram negativeGram negativeBacteria which lose crystal violet stain but are stained pink when treated by gram’s method.Yersinia spp./Yersiniosis, spiralSpiralComputed tomography where there is continuous x-ray exposure to the patient while being transported in a spiral or helical pattern through the beam of irradiation. This provides improved three-dimensional contrast and spatial resolution compared to conventional computed tomography, where data is obtained and computed from individual sequential exposures.Computed Tomography (CT) shaped, and motile. The following table briefly compares some clinically relevant spirochetes:
Table: Comparison of clinically relevant spirochetes
Organism
Treponema pallidum pallidum
Other T. pallidum subspecies
Treponema carateum
BorreliaBorreliaBorrelia are gram-negative microaerophilic spirochetes. Owing to their small size, they are not easily seen on Gram stain but can be visualized using dark-field microscopy, Giemsa, or Wright stain. Spirochetes are motile and move in a characteristic spinning fashion due to axial filaments in the periplasmic space. Borrelia burgdorfi
LeptospiraLeptospiraLeptospira is a spiral or question mark-shaped, gram-negative spirochete with hook-shaped ends. The disease, leptospirosis, is a zoonosis, infecting animals. Rodents are the most important reservoir. Bacteria shed in the urine of rodents and other animals can be transmitted to humans via contaminated water. Leptospira/Leptospirosis interrogans
VirulenceVirulenceThe 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
FibronectinFibronectinGlycoproteins found on the surfaces of cells, particularly in fibrillar structures. The proteins are lost or reduced when these cells undergo viral or chemical transformation. They are highly susceptible to proteolysis and are substrates for activated blood coagulation factor VIII. The forms present in plasma are called cold-insoluble globulins.Connective Tissue: Histology coating
FibronectinFibronectinGlycoproteins found on the surfaces of cells, particularly in fibrillar structures. The proteins are lost or reduced when these cells undergo viral or chemical transformation. They are highly susceptible to proteolysis and are substrates for activated blood coagulation factor VIII. The forms present in plasma are called cold-insoluble globulins.Connective Tissue: Histology coating
FibronectinFibronectinGlycoproteins found on the surfaces of cells, particularly in fibrillar structures. The proteins are lost or reduced when these cells undergo viral or chemical transformation. They are highly susceptible to proteolysis and are substrates for activated blood coagulation factor VIII. The forms present in plasma are called cold-insoluble globulins.Connective Tissue: Histology coating
Antigenic variation
Osp regulation
Antigenic variation
LPS
HemolysinsHemolysinsProteins 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 enzymesEnzymesEnzymes 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
ReservoirReservoirAnimate 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 animalsAnimalsUnicellular 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 animalsAnimalsUnicellular 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
SyphilisSyphilisSyphilis 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
YawsYawsA systemic non-venereal infection of the tropics caused by treponema pallidum subspecies pertenue.Yaws, Bejel, and Pinta
BejelBejelYaws, 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
PintaPintaAn 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 diseaseLyme diseaseLyme 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 feverFeverFever 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
LeptospirosisLeptospirosisLeptospira 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
ELISAELISAAn 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
ELISAELISAAn 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
PCRPCRPolymerase 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 GPenicillin GA penicillin derivative commonly used in the form of its sodium or potassium salts in the treatment of a variety of infections. It is effective against most gram-positive bacteria and against gram-negative cocci. It has also been used as an experimental convulsant because of its actions on gamma-aminobutyric acid mediated synaptic transmission.Penicillins
CeftriaxoneCeftriaxoneA 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 GPenicillin GA penicillin derivative commonly used in the form of its sodium or potassium salts in the treatment of a variety of infections. It is effective against most gram-positive bacteria and against gram-negative cocci. It has also been used as an experimental convulsant because of its actions on gamma-aminobutyric acid mediated synaptic transmission.Penicillins
AzithromycinAzithromycinA 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 GPenicillin GA penicillin derivative commonly used in the form of its sodium or potassium salts in the treatment of a variety of infections. It is effective against most gram-positive bacteria and against gram-negative cocci. It has also been used as an experimental convulsant because of its actions on gamma-aminobutyric acid mediated synaptic transmission.Penicillins
AzithromycinAzithromycinA 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
AmoxicillinAmoxicillinA broad-spectrum semisynthetic antibiotic similar to ampicillin except that its resistance to gastric acid permits higher serum levels with oral administration.Penicillins
CeftriaxoneCeftriaxoneA broad-spectrum cephalosporin antibiotic and cefotaxime derivative with a very long half-life and high penetrability to meninges, eyes and inner ears.Cephalosporins
Penicillin GPenicillin GA penicillin derivative commonly used in the form of its sodium or potassium salts in the treatment of a variety of infections. It is effective against most gram-positive bacteria and against gram-negative cocci. It has also been used as an experimental convulsant because of its actions on gamma-aminobutyric acid mediated synaptic transmission.Penicillins
Doxycycline
Penicillin GPenicillin GA penicillin derivative commonly used in the form of its sodium or potassium salts in the treatment of a variety of infections. It is effective against most gram-positive bacteria and against gram-negative cocci. It has also been used as an experimental convulsant because of its actions on gamma-aminobutyric acid mediated synaptic transmission.Penicillins
Doxycycline
Osp: outer surface protein
LPS: lipopolysaccharideLipopolysaccharideLipid-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
FTA-ABS: fluorescent treponemal antibody absorptionAbsorptionAbsorption involves the uptake of nutrient molecules and their transfer from the lumen of the GI tract across the enterocytes and into the interstitial space, where they can be taken up in the venous or lymphatic circulation.Digestion and Absorption
ELISAELISAAn 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: enzyme-linked immunosorbent assay
PCRPCRPolymerase 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): polymerase chain reactionPolymerase chain reactionPolymerase 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)
Visual comparison of spirochetes on electron micrograph: thick spirals of Treponema
Image: “Treponema pallidum” by Dr. David Cox. License: Public Domain
Visual comparison of spirochetes on electron micrograph: BorreliaBorreliaBorrelia are gram-negative microaerophilic spirochetes. Owing to their small size, they are not easily seen on Gram stain but can be visualized using dark-field microscopy, Giemsa, or Wright stain. Spirochetes are motile and move in a characteristic spinning fashion due to axial filaments in the periplasmic space. Borrelia, which are larger than Treponema
Image: “Lyme diseaseLyme diseaseLyme 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 parasite BorreliaBorreliaBorrelia are gram-negative microaerophilic spirochetes. Owing to their small size, they are not easily seen on Gram stain but can be visualized using dark-field microscopy, Giemsa, or Wright stain. Spirochetes are motile and move in a characteristic spinning fashion due to axial filaments in the periplasmic space. Borrelia burgdorferi” by Claudia Molins. License: Public Domain
Visual comparison of spirochetes on electron micrograph: hooked ends of LeptospiraLeptospiraLeptospira is a spiral or question mark-shaped, gram-negative spirochete with hook-shaped ends. The disease, leptospirosis, is a zoonosis, infecting animals. Rodents are the most important reservoir. Bacteria shed in the urine of rodents and other animals can be transmitted to humans via contaminated water. Leptospira/Leptospirosis
Image: “A filtration-based technique for simultaneous SEM and TEM sample preparation for the rapid detection of pathogens” by Beniac DR, Siemens CG, Wright CJ, Booth TF. License: CC BY 3.0, edited by Lecturio.
Gladwin, M., & Trattler, B. (2008). Clinical microbiology made ridiculously simple (4th edition). Miami: MedMaster.
Radolf, J.D. (1996). Treponema. In: Baron S., (Ed.), Medical Microbiology. (4th edition). Galveston (TX): University of Texas Medical Branch at Galveston. Available from: https://www.ncbi.nlm.nih.gov/books/NBK7716/
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