Spirochetes Thin-walled Spiral rods Flexible Motile Having an axial filament under the outer memberane

Motility  Spirochetes are motile through the undulation of an axial filament that lies under the outer sheath.

Treponema  - Seen only by darkfield microscopy, silver impregnation, or immunofluorescence.  - No growth in bacteriologic media or in cell culture except nonpathogenic treponems which are part of the normal flora of human mucous membranes. Leptospira  Seen only by darkfield microscopy, silver impregnation, or immunofluorescence.  Growth in bacteriologic media Borrelia  - Larger than two others  Seen by Giemsa’s and other blood stains  Seen in the standard light microscope  Growth in bacteriologic media

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Treponema pallidum  Causes syphilis

Treponema pallidum pallidum (The bacterial agent of syphilis) Subspecies pallidum (not bejel, pinta, yaws).  A worldwide STD  The incidence is increasing

Transmission  From spirochete-containing lesions of the skin or mucous membranes  From pregnant women to their fetuses  Blood transfusion during early syphilis.

Antibodies  The antigenes of T. pallidum induce specific antibodies, which can be detected by immunofluorescence tests.  They also induce nonspecific antibodies (reagin), which can be detected by the flocculation of lipids (cardiolipin) extracted from normal mammalian tissues, eg. Beef heart.

Pathogenesis  No important toxins or enzymes.

Clinical finding  Primary stage  Secondary stage  Tertiary stage

Primary stage  Chancre  Chancre in 2 – 10 weeks (average 21 days) after exposure.  A single firm, painless, non itchy skin ulceration with a clean base and sharp borders between 0.3 and 3 cm in size. The ulcer heals spontaneously after 3 to 6 weeks without treatment, but spirochetes spread widely in tissues.

Secondary stage  Secondary syphilis occurs approximately 4 to 10 weeks after the primary infection.  Lesions as maculopapular rash or moist papules on skin and mucous membranes. Or organ involvement (meningitis, nephritis, hepatitis….). rich in spirochetes  Secondary lesions are rich in spirochetes and highly infectious but heal spontaneously.

Tertiary stage  One-third of early syphilis cases progress to cure without treatment.  Another third remain latent; i.e. no lesions appear, but positive serologic tests indicating continuing infections (Asymptomatic).  In the remainder, the disease progresses to the late, tertiary stage.

Tertiary stage - Granulomas (gummas) ( Gummas in skin, bones, central nervous system, cardiovascular lesions, e.g. aortitis, aneurysm). - Paralysis (also tabes and paresis), Blindness, Insanity, Death - In tertiary stage, the treponemes are very rare.

Congenital syphilis Fetus infection through transplacental passage after the third month of pregnancy.transplacental Unless treated promptly, multiple fetal abnormalities.

Congenital syphilis  Early congenital syphilis Occurs in children between 0 and 2 years old  Late congenital syphilis Late congenital syphilis Starts to occurs after 2 years old

Congenital syphilis  Early congenital syphilis - - Born premature - Active mucocutaneous syphilis - Enlargement of the liver, spleenliverspleen - Skeletal abnormalities - Pneumonia

 Symptoms can develop two weeks to three months after birth:  anemia  fever  rashes  skin sores  weak/hoarse crying sounds  yellowish skin (jaundice)

Late congenital syphilis Late congenital syphilis  Malformations and damage to:Bones Brain Brain (neurologic changes)EyesEars Teeth Teeth (Hutchinson's teeth)

Immunity  Immunityincomplete  Immunity to syphilis is incomplete: Antibodies are produced but not stop the progression of the disease. early syphilis can contract syphilis again  Patients with early syphilis treated can contract syphilis again. late syphilis resistant  Patients with late syphilis are relatively resistant to reinfection.

Laboratory diagnosis Microscopy - Microscopy darkfield immunofluorescence Demonstrating spirochetes by darkfield or immunofluorescence microscopy. - Nonspecific serologic tests - Specific serologic tests - Specific serologic tests

 Antibodies agains Treponema palidum: - Nonspecific reagin - Specific antitreponemal antibody  Nonspecific serologic tests - Nontreponemal antigens - Nontreponemal antigens (extracts of Cardiolipin from beef heart) react with “reagin” antibodies in serum samples from patients with syphilis. These antibodies are a mixture of IgG and IgM.

- VDRL (Venereal Disease Research Laboratory)/RPR (Rapid plasma reagin) (a simplified version of VDRL test) - The reagin antibody binds with the antigen (Antigen is composed of a complex of cardiolipin, lecithin and cholesterol particles with activated charcoal). - Flocculation or clumping - Flocculation or clumping of the particles is read as a positive test. The test can be quantitated by examining serial dilutions of serum.

The ASI RPR test is in an 8-minute

Nonspecific antibodies (cont.)  Detectable in the majority of patients at the time the primary syphilis and are always present in secondary syphilis.  False-positive reactions may occur (in hepatitis and infectious mononucleosis and autoimmune diseases).  So, positive results have to be confirmed by specific tests.

Specific serologic tests treponemal antigens  Using treponemal antigens  T. pallidum extracted from experimentally infected rabbits.  Reacts in FTA-ABS (fluorescent treponemal antibody absorbed) test or TPHA (treponema pallidum hemagglutination)  Specific antitreponemal antibodies arise within 2-3 weeks of syphilitic infection.

Specific serologic tests  Treponemal antibody tests are specific for treponematoses but: - expensive - remain positive after treatment

Treatment  Penicillin G (A single injection of benzathin penicillin G) can eradicate T pallidum and cure early syphilis.

Prevention  Administration of antibiotic after suspected exposure.  The presence of any sexually transmitted disease makes testing for syphilis mandatory.  No vaccine is available.

Borrelia  Borrelia species are irregular, loosly coiled spirochetes which stain with Giemsa’s and other stains.  Culturable in bacteriologic media containing serum or tissue extracts.  Transmitted by arthropods.  Cause 2 major disease: relapsing fever and lyme disease.

Borrelia recurrentis  Causing relapsing fever  During infection, the antigens of these organisms undergo variation.  As antibodies develop against one antigen, variants emerge and produce relapses of the illness repeating 3-10 times.  Transmission from person to person by human body louse.  Humans are the only hosts

Borrelia hermsii  Causing relapsing fever  During infection, the antigens of these organisms undergo variation.  Transmission to humans by ticks  Rodents and other small animals are the main reservoirs.  These borrelia are passed transovarially in the ticks.

Clinical finding  Cyclic Fever, chills, headaches  Multiple organ dysfunction

Lab Diagnosis - Microscopy (large spirochetes in stained smears of peripheral blood) - Culture in special media - Serological tests

Treatment & Prevention  Tetracycline may be beneficial early in the illness and may prevent relapses.  Avoidance of arthropod vectors

Borrelia burgdorferi  Causes Lyme disease  Transmission by tick bite (genus Ixodes)Ixodes  The main reservoirs: Mice and deer Incidence of Lyme Disease in the United States, Lyme disease is the most prevalent tick- borne illness in the United States.

Clinical finding  Early in disease  Early in disease: erythema chronicum migrans Fever, severe headache, myalgia, fatigue, depression, stiff neck, and a typical skin rash called ‘erythema chronicum migrans [ECM]’ If untreated, neurologic and cardiac abnormalities ensue weeks later and arthritis follows months to years later. Immune complexes are found in the affected joints.

Erythema migrans

Lab diagnosis  Serology: Detecting IgM antibodies by immunofluorescence tests or ELISA  Culture are not typically done.

Treatment & Prevention  Penicillin or Tetracycline  Prevention includes avoiding tick bites.

Leptospira  Tightly coiled, fine spirochetes that are not stained with dyes.  They are seen by darkfield microscopy.  They grow in bacteriologic media containing serum.

Leptospira interrogans  The causative of leptospirosis  Divided into serogroups (occurring in different animals and geographic locations)  Each serogroup is subdivided into serovars by response to agglutination tests.  Leptospira infects various animals including rats and other rodents, domestic livestock and household pets.

Transmission  Animals excrete leptospiras in urine, which contaminates water and soil.  Swimming in contaminated water or consuming food or drink results human infection.  Miners, farmers and people who work in sewers are at high risk.  Person-to-person transmission is rare.

Pathogenesis  Leptospira are ingested or pass through mucous membranes or skin.  They circulate in the blood and multiply in various organs.

Clinical finding  Fever  Dysfunction of the liver (jundice, hemmorrhage), kidneys (uremia), and central nervous system (aseptic meningitis)  Subclinical infection is common.  Serovar-specific immunity develops with infection.

Lab Diagnosis Clinical Diagnosis is based on history of exposure.  Serology: Marked rise in agglutinating antibodies.  Occasionally leptospira is isolated from blood and urine cultures.

Treatment & Prevention  Tetracycline  Prevention: - Avoiding contact with the contaminated environment. - Doxycycline in exposed persons.

Rickettsiae  Very short rods and barely visible in the light microscope  Gram-negative but poorly stain with gram stain

Rickettsiae  Non-motile coccobacillus  Obligate intracellular parasites, so normally must be grown in cell culture.  Against chlamydiae divide by binary division not by a distinctive intracellular cycle.

Transmission  They maintained in nature in certain arthropods: ticks, lice, fleas and mites  The exception to arthropod transmission is C. burnetii, transmitted by aerosol and inhaled into the lungs. epidemic typhus only in humans  All rickettsial diseases are zoonoses with the exception of epidemic typhus which occurs only in humans.

Coxiella burnetii  Q fever (inhalation, contact with the milk, urine, feces, vaginal mucus, or semen of infected animalsinhalation

R. prowazekii  Epidemic Typhus (by lice)  R. typhi  Murine or endemic typhus (by fleas, commonly rat flea)fleas  Orientia (formerly Rickettsia) tsutsugamushi  Scrub typhus (by mite)  Rickettsia rickettsii  Rocky mountain spotted fever (by ticks)

R. prowazekii  Growth in the louse's gut  Excretion in its feces.feces  Transmition to an uninfected human who scratches the louse bite (which itches) and rubs the feces into the wound.

R. prowazekii  The incubation period: 1-2 weeks.incubation period  R. prowazekii can remain viable and virulent in the dried louse feces for many days.  Typhus will eventually kill the louse, though the disease will remain viable for many weeks in the dead louse.

Clinical findings  Severe headache, a sustained high fever (39 °C, common to all forms of typhus), cough, rash, severe muscle pain, chills, falling blood pressure, stupor, sensitivity to light, and delirium.rashmuscle painchillsblood pressurestuporsensitivity to light delirium  A rash begins on the chest about five days after the fever appears, and spreads to the trunk and extremities.

Brill-Zinsser disease  A mild form of epidemic typhus  It occurs when the disease re-activates in a person who was previously infected.  More common in the elderly

R. typhi (Murine/Endemic typhus) By bite of certain fleas Rash and other manifestations are similar to epidemic typhus: High fever, severe headaches, a red rash, chills, myalgia, nausea, vomiting, and cough. myalgianauseavomiting

Typhus rashes

Laboratory diagnosis of rickettsial infections  A complete blood count (CBC) may show anemia and low platelets.CBC anemiaplatelets Other tests:  High level of typhus antibodiesantibodies  Low level of albuminalbumin  Low sodium levelsodium  Mild kidney failure  Mildly high liver enzymes

Laboratory diagnosis of rickettsial infections  Weil-Felix test: (based on a cross-reaction of proteus vulgaris with R. prowazekii, R. tsutsugamushi, R. ricketsii, …) Detection of antirickettsial antibodies by agglutination of the antigenes of OX strain of proteus vulgaris

Treatment  Mortality rate 10% to 60% in untreated cases  Close to zero if intracellular antibiotics, such as tetracycline. tetracycline  Can prevented by vaccination.  Intravenous fluids  Intravenous fluids and oxygen may be needed to stabilize the patient.oxygen