Spirochete Diseases - MLS 227 Lecture Notes PDF

Spirochete Diseases MLS 227 Chapter 21  Syphilis A sexually transmitted disease caused by the spirochete bacterium Treponema pallidum ss. Pallidum Aerobic spirochete bacteria, gram negative Corkscrew motility as a result of coiled flagella Most commonly acquired spi...

Spirochete Diseases MLS 227 Chapter 21  Syphilis A sexually transmitted disease caused by the spirochete bacterium Treponema pallidum ss. Pallidum Aerobic spirochete bacteria, gram negative Corkscrew motility as a result of coiled flagella Most commonly acquired spirochete infection Rapidly destroyed by heat, cold, and drying Direct contact with open lesion needed Transmission to fetus during pregnancy Blood borne transmissions are rare Causative organism Other Species: T. Pallidum ss. Pertenue: Yaws T. Pallidum ss. Carateum: pinta T. Pallidum ss. Endemium: nonvenereal syphillis  Clinical Manifestations of Syphilis Primary stage Development of chancre Secondary stage Generalized lymphadenopathy, malaise, fever, pharyngitis, rash Latent stage Asymptomatic Tertiary stage Gummatous, cardiovascular, neurosyphilis Stages of Disease - Incubation Transmitted by: - Sexual contact - Transfusion of fresh blood (rare) - Direct inoculation - Placental transfer Bacteria enters body, carried in blood, multiplies Average length = 3 weeks No clinical symptoms Serological tests are negative Stages of Disease- Primary Syphilis Lesions (Chancre) appears at site of inoculation Heals spontaneously in 3 to 6 weeks  Early in stage: - Seronegative, may observe spirochetes in fluid from lesions (Darkfield microscopy) - Repeated testing for Non-Treponemal antibodies – after third week - 90% have nonspecific Abs that remain for 6 months Stages of Disease – Secondary Syphillis 6- 8 weeks after appearance of chancre, signal spread of treponemes throughout body Rare cases have no symptoms until tertiary stage All serological tests are positive Characterised by: - Skin rashes and flu- like symptoms - Mucus patches (lesions) on mucus membranes. Very high number of treponemes in lesions. - Spontaneously heal in 2-6 weeks. Stage of Disease - Latency May last many years No signs of symptoms Remain infectious, can still pass infection through placental transfer Serological tests positive for specific antibodies Stages of Disease- Tertiary Syphilis Slowly progressive inflammatory disease that can produce clinical illness 2-40 years after initial infection Serological tests are positive for specific antibodies Gummatous syphillis (lesions in skin, bones, mucosa, muscles and organs) Neurosyphilis (CNS lesions = Blindness/insanity) Cardiovascular syphilis (Cardiac damage = death) Congenital syphilis Transmission of treponemes to the fetus occurs when pregnant woman has early-stage or latent syphilis Causes death in 10% of cases, up to 60% infected eventually develop neurosyphilis Live-born infants may be asymptomatic at birth but develop symptoms later (runny nose, skin rash, generalized lymphadenopathy, hepatosplenomegaly, jaundice, anemia, bone abnormalities, neurosyphilis)  Laboratory Diagnosis of Syphilis Direct detection Demonstration of treponemes in active lesions (fluids from lesions) Dark-field microscopy – difficult to perform, requires special training and microscope Fluorescent labeled antibody staining Serological tests Nontreponemal tests Treponemal tests  Nontreponemal Tests Detect antibody against cardiolipin (reagin), a lipid released from membranes of cells damaged as a result of the infection Venereal Disease Research Laboratory (VDRL) test Rapid plasma reagin (RPR) test Look for flocculation  VDRL Test Patient serum mixed on a slide with cardiolipin- lecithin-cholesterol antigen suspension Viewed under a light microscope for flocculation (Clumping of fine particles) Results compared to controls Reactive = medium to large clumps Weakly reactive = small clumps Nonreactive = no clumps or slight roughness - More sensitive than RPR, but more difficult to run as it requires finely detailed procedures. - Complement must be heat inactivated. - Mainly used for detection in CSF  RPR Test Patient serum mixed on a card with charcoal particles coated with cardiolipin antigen Observe for macroscopic flocculation  Treponemal Tests Detect antibody to T. pallidum Fluorescent treponemal absorption (FTA-ABS) T. pallidum particle agglutination (TP-PA) Automated immunoassays Enzyme-linked immunosorbent assay (ELISA) Chemiluminescent immunoassays (CLIA) Multiplex flow immunoassays (MFI) Typical Antibody Patterns in Syphilis Traditional Testing Algorithm for Syphilis  Special Diagnostic Areas Molecular testing for T. pallidum DNA Polymerase chain reaction (PCR) may be a sensitive alternative to dark-field microscopy in the future. Patient monitoring Perform nontreponemal antibody titers. Titers decline with successful treatment. Congenital syphilis Perform nontreponemal tests on mother and infant at birth and IgM-specific treponemal assays to confirm. Neurosyphilis Perform CSF VDRL or ELISA on cerebrospinal fluid. Treatment Effectively treated with antibiotics (e.g., penicillin and tetracycline) when detected in the early stages  Lyme Disease Caused by the spirochete bacterium Borrelia burgdorferi Transmitted by Ixodes ticks Main reservoir: the white- footed mouse Clinical Manifestations of Lyme Disease Stage 1 Localized rash bull’s eye rash Stage 2 Early dissemination Stage 3 Late dissemination with arthritis Two-Tiered Testing for Lyme Disease Western Blot Results for B. burgdorferi Antibodies Patient serum is incubated with a nitrocellulose membrane containing electrophoresed B. burdorferi antigens. Positive IgM results: 2 of 3 characteristic bands Positive IgG results: 5 of 10 characteristic bands  Leptospirosis Caused by Leptospira species A zoonotic infection associated with occupational and recreational activities Humans are exposed by mucous membrane contact with urine-contaminated water Causes febrile episode that can progress to severe disease involving renal, liver, pulmonary, and CNS. Laboratory testing IgM screening by ELISA and Leteral Flow Assay(LFA) Microscopic Agglutination Test (MAT) is the gold standard for confirmation.  Summary Three diseases caused by spirochete bacteria are syphilis, Lyme disease, and leptospirosis. Syphilis is caused by Treponema pallidum; untreated patients may progress through four clinical stages: Primary (chancre) Secondary (lymphadenopathy, skin rash, sore throat) Latent (asymptomatic) Tertiary (granulomatous inflammation, cardiovascular disease, neurosyphilis)  Direct detection of T. pallidum can be performed by dark- field microscopy, fluorescence microscopy, or PCR. Nontreponemal tests such as the VDRL and RPR detect antibody to cardiolipin, a lipid released from host cells damaged during the infection; these tests are sensitive but not specific for syphilis. Treponemal tests such as the FTA-ABS, TP-PA, and automated immunoassays are more specific because they detect antibodies to T. pallidum. Nontreponemal antibody titers decline in later stages of syphilis and during effective treatment; treponemal antibody titers appear earlier in primary syphilis and remain elevated for life.  In the traditional testing algorithm for syphilis, patient samples are screened with a nontreponemal test, and positive samples are confirmed with a treponemal test. Lyme disease is caused by Borrelia burgdorferi, which is transmitted by Ixodes ticks. The characteristic feature of Lyme disease is an expanding red rash that occurs at the site of the tick bite; the infection can disseminate through the body if undetected and untreated in the early stage, causing joint pain, nervous system abnormalities, and arthritis.  ELISA or IFA for antibodies to B. burgdorferi are used in the initial diagnosis of Lyme disease. Confirmation of positive results is done by Western blot or another EIA. Antibodies are not detected until 3 to 6 weeks after the tick bite. Leptospirosis is a zoonosis caused by exposure to water contaminated with animal urine containing leptospires. This febrile disease can progress to a severe illness that may involve renal or hepatic failure. The gold standard for confirmation of leptospirosis is the microscopic agglutination test (MAT).