Spirochetes

• Spirochetes


  Large heterogenous group of spiral, motile bacteria
• Spirochete families


  • Spirochaeteceae
  • Leptospiraceae
• Spirochaeteceae genera


  • Borrelia
  • Treponema
• Leptospiraceae genera


  • Leptospira
• Spirochetes


  • Long slender, helically coiled, spiral or corkscrew shaped bacilli
  • Reproduce by transverse fission
  • Propel through the liquid environment using locomotion, rotation, and flexion
• Treponema species that cause disease in humans

  • T. pallidum
  • T. carateum
• T. pallidum


  • Transmitted through venereal contact
  • Predominantly seen in adults
  • Three subspecies: pallidum (syphilis), pertenue (yaws), endemicum (bejel)
  • Thin (0.2um), 6-20 um in length with 10-13 coils
  • Corkscrew motility with an undulating central flexion
• T. carateum


  • Transmitted through direct contact
  • Common among children 15 years old and below
  • Common in Spanish speaking countries- warm humid weather
• Spirochetes fail to stain / poorly stain with Gram and Giemsa stains
• Staining procedures have limited usefulness in characterizations of spirochetes
• Spirochetes


  • Mostly anaerobic but human pathogenic species are microaerophilic
  • Have flagella and motile even in a viscous solution
  • Easily destroyed by heat, cold or desiccation, chemicals like arsenicals and penicillin
• Syphilis


  • Man is the only natural reservoir
  • Transmission is by direct contact with active lesions, primarily through sexual contact
  • Primary lesion is intrarectal, perianal, or oral in 10–20% of cases
  • Vertical transmission (i.e., transplacental route) across the placenta may result when either a latently infected female becomes pregnant or when a pregnant woman becomes infected
• Diagnostics: Immunofluorescent stain or dark-field illumination is used to demonstrate spirals
• Syphilis progression


  • Multiply locally at the site of entry and some spread to nearby lymph nodes and then reach the bloodstream
  • Often multiply first in the external genitalia
  • Spread to neighboring soft tissue and eventually the lymph nodes
• Primary stage of syphilis

  • Development of chancre at the site of inoculation
  • Painless, firm, and smooth
  • Heals with little or no scarring
  • Found in the external genitalia
  • Occurs at a median of 3 weeks
  • May be absent for some
  • Regional lymphadenopathy
  • Early invasions of the blood
• Secondary stage of syphilis

  • Red maculopapular rash anywhere on the body, esp. hands and feet
  • Moist condylomas (warts) in the anogenital region, axillae, and mouth
  • Number of spirochetes reaches upper limit in primary and secondary stage
• Period of latency in syphilis

  • Follows secondary stage
  • Number of spirochetes rapidly decline
  • Patient shows no manifestations of the infection
  • Early latent period: may see episodes of relapse in the first 4 years of this period
  • Late latent period: relapses do not occur
  • Positive serologic test for syphilis
• Tertiary syphilis


  • Very hard to detect spirochetes in patient's tissues
  • Most serious manifestations in the cardiovascular system or CNS
  • Cardiovascular syphilis: Presents as aortic aneurysm, aortitis and even aortic valve aneurysm
  • Syphilitic gummas: Involve skin, skeletal system, and mucocutaneous
  • Meningovascular syphilis: Occurs 5–10 years after initial infection, clinically presents as seizures, stroke, and aphasia
  • Congenital syphilis: Passed from the mother to the fetus during the primary, secondary, or latent stage that may lead to miscarriage or stillbirth
• Obliterative endarteritis


  • Histologic hallmark of syphilis, whatever organ involved or whatever stage of the disease
  • Defined as a concentric endothelial and fibroblastic proliferation with an accompanying mononuclear cell infiltrate lush in plasma cells
• Diagnostics for syphilis


  • Detection is either by direct visualization of the organisms in material from lesions or indirectly by immunologic methods
  • Etiologic agents of human treponematosis cannot be isolated by routine culture techniques
  • Drying and elevation of the temperature to 42°C kill the spirochete rapidly
  • Cerebral spinal fluid is useful for the Venereal Disease Research Laboratory
• Non-treponemal tests for syphilis

  • Used to screen for disease and to monitor the course of post-treatment
  • Standard tests include VDRL, RPR, USR, TRUST
  • Widely available leading themselves to automation with the ease of performance in large numbers and have a low cost
  • Drawbacks: not very sensitive in early syphilis and false positive results can happen and the possibility of a pro-zone phenomenon
  • Can give quantitative results using serial 2-fold dilutions
  • Quantitative results (titers) are valuable in finding a diagnosis and in evaluating the effect of treatment
• Treponemal tests for syphilis

  • Detect the presence of antibodies to treponemal antigens
  • Used to confirm a positive non-treponemal screening test or infection in the face of a negative non-treponemal test in late or latent disease
  • T. pallidum-particle agglutination (TP-PA) test may be the most applied treponemal test in the US
  • Treponemal test will detect the presence of antibodies in the body whether the patient has been infected before and is not cured or presently has an active infection
• Treatment of syphilis

  • Benzathine penicillin G is the treatment of choice
  • Single injection of 2.4 million units intramuscularly if the patient has been ill for <1 year, 2 or more injections if ill for >1 year
  • Jarisch-Herxheimer reaction: pronounced worsening in the clinical course brought about by exposure of the patient to the toxic products of dead or dying treponemes, may be seen upon treatment of venereal syphilis patients
• Prevention of syphilis

  • Abstinence / safe sex
  • Detect patients sick of syphilis quickly
  • Public health office should trace the source and treat the patient, female sex workers need to be treated
• Yaws


  • Chronic non-venereal disease of the skin and bones caused by T. pallidum pertenue
  • Similar genetically and morphologically to T. pallidum
  • Distributed in the tropics
  • Often affects prepubescent to adolescent persons
  • Presents as papules turning into wart-like lesions on the lower limbs as time progresses
• Bejel


  • Non-venereal lesion caused by T. pallidum endemicum
  • Transmitted by direct contact with active lesions, contaminated fingers, or contaminated eating/drinking utensils
  • Found in hot areas of the Middle East, Africa, and India
  • Presents as mucous patches, condyloma lata, angular stomatitis, generalized LAD, and painful osteoperiostitis
• Pinta


  • Ulcerative skin disease caused by T. carateum
  • Endemic in rural tropical Central and South America
  • Primary papule or plaque → Secondary lesions or pintids → Hypopigmentation and skin atrophy or hyperkeratosis
• Syphilis, Yaws, Bejel, and Pinta can be treated with Penicillin since all are currently susceptible to this antibiotic
• Borella clades

  • Lyme borreliosis group
  • Relapsing fever group
• Borella


  • Multiple pathogenic and non-pathogenic species
  • Microaerophilic, helically coiled bacteria that stain well with Giemsa dyes
  • Human pathogenic species are transmitted through arthropod vectors (lice, ticks)
  • Form irregular spirals, 10-30μm long and 0.3μm wide
  • Highly flexible and move both by rotation and by twisting
  • Exhibit a characteristic motility pattern

  
• ateum


  Endemic in rural tropical Central and South America
• Progression of ateum


  Primary papule or plaque → Secondary lesions or pintids → Hypopigmentation and skin atrophy or hyperkeratosis
• Borella


  Multiple pathogenic and non-pathogenic species from 2 clades: Lyme borreliosis group and Relapsing fever group
• Borella


  • Microaerophilic, helically coiled bacteria that stain well with Giemsa dyes
  • Human pathogenic species are transmitted through arthropod vectors (lice, ticks)
  • Form irregular spirals, 10-30μm long and 0.3μm wide
  • Highly flexible and move both by rotation and by twisting
  • Exhibit a host of immunogenic proteins on their outer membrane surfaces
  • Many species can be grown on artificial media

  
• Relapsing fever


  Divided into 2 entities: Epidemic louse-borne relapsing fever and Endemic tick-borne relapsing fever
• Relapsing fever reservoirs


  • Rat
  • Ornithodoros spp. ticks
• Relapsing fever transmission


  In the tick, Borrelia spp. may be transmitted transovarially from 1 generation to the next
• Clinical manifestation of relapsing fever

  1. Sudden onset with chills and fever persisting for 3–5 days and then declines, leaving the patient weak

  2. Afebrile period lasts 4–10 days followed by a 2nd attack of chills, fever, intense headache, and body malaise

  3. 3–10 occurrences show diminishing severity

  4. Organisms are present in the blood during the febrile stage, while absent during the afebrile period
• Relapsing fever disease course

  • Relapsing course of the disease is encouraged by the multiplication of such antigenic variants against which the host must then develop new antibodies
  • During febrile episodes, there is bacterial proliferation in the blood and the body produces antibodies against bacterial antigens
  • Antigens get damaged and removed from the bloodstream causing lysis of the fever
  • Borrelia changes its antigenic structure, escaping detection restarting the cycle of fever, lysis and resurgence
  • Cycle repeats 3 to 10 times before the body develops full knowledge of the antigenic variation of the bacteria
• Fatal cases of relapsing fever show lavish spirochetes in the spleen and liver, necrotic foci in solid organs, and hemorrhage in the kidneys and GIT