CLASS: 10:00 – 11:00Scribe: Adam Baird

DATE: October 27, 2010Proof:

PROFESSOR: BenjaminSpirochetes and RickettsiaePage1 of 6

  1. SPIROCHETES AND RICKETTSIAE [S1]
  2. OBJECTIVES [S2]
  3. To review and discuss:
  4. Microbiological characteristics
  5. Epidemiology
  6. Virulence factors
  7. Associated diseases
  8. Laboratory detection
  9. Topics:
  10. Teponema pallidum
  11. Borrelia spp.
  12. Leptospira spp.
  13. Rickettsiae
  14. Ehrlichia spp.
  15. TREPONEMA PALLIDUM [S3]
  16. Treponema pallidum is one of the most important topics of this lecture
  17. Physiological characteristics of treponema pallidum:
  18. Motile spirals (5-15 micrometers)
  19. Has not been successfully cultured/subcultured on artificial media, but may multiply in rabbit epithelial cell cultures
  20. Very susceptible to environment conditions
  21. Does not stain with aniline dyes
  22. GRAPH: PRIMARY AND SECONDARY SYPHILIS [S4]
  23. This graph shows the rate (per 100,000 population) of primary and secondary syphilis.
  24. Notice that syphilis goes through a 10 year cycle
  25. Notice the male-female ratio. There used to be about the same amount of male and females effected (1989 – 1999). Cases of syphilis in males increased from 2000 – 2003 and have remained higher in males than in females (largely due to male-male sexual relations).
  26. To put these figures in perspective: There are about the same number of cases for syphilis and tuberculosis (about 4.5 – 5.0 per 100,000).
  27. FIGURE: PRIMARY AND SECONDARY SYPHILIS [S5]
  28. This figure shows the rates of primary and secondary syphilis by state.
  29. Notice that the darker color red indicates a higher number of syphilis cases.
  30. Birmingham used to be the “capital for syphilis” for many years. (The new “capital for syphilis” is Memphis.)
  31. FIGURE: SYPHILLIS P & S RATES AND CONGENITAL CASES (1999 – 2008) [S6]
  32. The state of Alabama had the third highest number of syphilis nationwide (2008).
  33. Notice that some counties in Alabama reported no cases of syphilis (2008).
  34. Jefferson County, though, had quite a large amount.
  35. Notice that the male and female rate of syphilis is about the same for both males and female (both are increasing from 2005 – 2008).
  36. Notice California’s statistics. Males in California had much higher rates than females in California.
  37. EPIDEMIOLOGY 2008 [S7]
  38. Alabama:
  39. 449 cases of syphilis in 2008
  40. Ranked 3rd with 9.7 cases of syphilis per 100,00 population
  41. National rate of 4.5
  42. 12 cases of congenital syphilis
  43. Ranked 7th with 19 cases of syphilis per 100,000 population
  44. National rate of 10.1
  45. STAGES OF SYPHILIS [S8]
  46. Stages of syphilis:
  47. Primary
  48. Chancre (a painless, hard ulcer) at site of inoculation
  49. Lasts 1 – 3 weeks
  50. Secondary
  51. Manifestations due to spirochete
  52. Infectious rash seen on various parts of the body, specifically the palms of the hands and soles of the feet
  53. Disseminated disease
  54. Lasts 2 – 8 weeks
  55. Typically resolves in a few days or up to 8 weeks.
  56. Latent
  57. Patient is still infected
  58. Unknown duration
  59. Tertiary
  60. Severe disease
  61. Lifelong infection
  62. More details will be discussed later in the lecture
  63. PRIMARY SYPHILIS [S9]
  64. Disease characteristics of primary syphilis:
  65. Chancre (a painless, hard ulcer) at site of inoculation; quickly erodes and becomes indurated
  66. Painless lesion (but tender to touch or examine; can become secondarily infected)
  67. Highly variable in HIV-infected patients
  68. Regional, non-tender adenopathy (swollen/enlarged lymph nodes, specifically in the area of the lesion)
  69. Heals spontaneously in 1 – 12 weeks (is usually healed in 3 – 6 weeks though)
  70. Not uncommon to have no lesions noted
  71. Not uncommon to have a small papule that is darkfield negative
  72. PICTURE: ORAL AND GENITAL CHANCRES [S10]
  73. Pictures of what some of the syphilis lesions or chancres can look like.
  74. Mainly oral lesions and genital lesions
  75. It’s difficult to examine oral lesions due to the normal flora in the mouth though
  76. CLINICAL MANIFESTATIONS OF SECONDARY SYPHILIS [S11]
  77. Disease characteristics of secondary syphilis:
  78. 90% of infected patients have rashes
  79. Mucous patches
  80. Chondyloma latum
  81. Constitutional symptoms (fever, malaise, pharyngitis, weight loss, arthralgias, etc.). Syphilis is known as the “great mimicker” because many of its symptoms can look like other infections, making it difficult to diagnose.
  82. Headache
  83. Meningismus (the triad of nuchal ridgidity, or “neck stiffness”, photophobia, and headache)
  84. Diplopia (double vision)
  85. Tinnitus (ringing or buzzing in the ears)
  86. Vertigo
  87. Glomerulonephritis (acute inflammation of the kidney) or nephritic syndrome
  88. Hepatitis
  89. Arthritis
  90. PICTURE: SKIN LESIONS OF SECONDARY SYPHILIS [S12]
  91. Pictures of secondary syphilis rashes.
  92. Notice the effected areas: palms of the hands, soles of the feet, etc.
  93. Rashes don’t necessarily “itch” just a skin rash.
  94. Condyloma lata (usually where “warm area” where “skin touches skin”, like perianal regions, under female breasts, etc.)
  95. TERTIARY SYPHILIS [S13]
  96. Very serious, dangerous
  97. Disease characteristics of tertiary syphilis:
  98. Cardiovascular trouble (aortitis, valve lesions)
  99. Benign tertiary (gumma formation)
  100. Central nervous system involvement
  101. Paresis (general paresis of the insane)
  102. Tabes doraslis (spinal cord)
  103. Meningovascular
  104. PICTURE: TERTIARY SYPHILIS “GUMMA” [S14]
  105. Pictures of gumma, a characteristic symptom of tertiary syphilis
  106. CONGENITAL SYPHILIS [S15]
  107. Disease characteristics of congenital syphilis:
  108. Transplacental (meaning that the infection crosses the placenta, from mother to child)
  109. “Snuffles” (child has difficulty breathing, “loud breathing”)
  110. Pneumonia
  111. Hepatitis
  112. Tooth malformation (Hutchinson’s incisors, Mulberry molars)
  113. 8th nerve palsy/deafness
  114. Saber shins due to persistent inflammation (curved shins)
  115. DIAGNOSIS OF SYHPILIS: DARKFIELD [S16]
  116. One way to diagnose syphilis:
  117. Darkfield Microscope
  118. Easiest way to diagnosis syphilis
  119. Removes unscattered light beams from the image, making the microscopic field around the specimen dark, making the specimen look lighter.
  120. Useful only if lesion is present
  121. Not useful for oral lesions
  122. Positive before serology tests
  123. NON-TREPONEMAL TESTS (RPR, VDRL) [S17]
  124. Another way to diagnose syphilis:
  125. Non-Treponemal Tests (Rapid Plasma Reagin, Venereal Disease Research Laboratory)
  126. Screeinng test (inexpensive, easy, and quick, but “false positive” results may occur)
  127. Cardiolipin (extracted from beef hearts), lecithin, cholesterol antigen
  128. Can be titered (rising titer indicates active disease, falling titer indicates adequate therapy)
  129. Reflects overall activity of syphilis (as opposed to past activity)
  130. Limitations (may become reactive in late primary syphilis, some patients who have been treated late in the course of syphilis may become “serofast” for life, and “false positive” results may occur, specifically in some autoimmune, viral, or acute febrile states)
  131. PICTURE: RPR NON-TREPONEMAL TEST [S18]
  132. Picture of RPR non-treponemal test
  133. 18 mm circles drawn on paper. Drop of cariolipin placed in each circle. Patient serum is then placed in each circle.
  134. Very standardized test. Well-controlled environment needed.
  135. This picture indicates positive results because of the “dark spots” inside the circles
  136. TREPONEMAL TESTS [S19]
  137. Picture of treponema pallidum particle agglutination (TPPA)
  138. TPPA is the follow-up test to RPR non-treponemal test.
  139. TPPA has true treponema antigens on gelatin particles.
  140. Patient’s serum is diluted (1:40, 1:80, 1:160, etc.) and mixed with “red-stained particles”. Wherever antibodies bind to the particles and hold them apart, they settle in the wells and give a “diffused pattern’ (positive). Whenever the antibodies don’t bind to the particles, they don’t hold them apart, and give a “button” or a “single spot” (negative).
  141. Notice that each well is marked positive or negative.
  142. FLUORESCENT TREPONEMAL ANTIGEN (FTA) TEST [S20]
  143. FTA test is a more labor-intensive test
  144. FTA tests become reactive earlier than RPR
  145. FTA test is really a confirmatory test of RPR results
  146. Organisms are grown within a rabbit, placed on a slide, and stained with the patient’s serum. Finally, fluorophore-labeled anti-treponeme antibody (to identify spirochete location) and fluorophone-labeled anti-human antibodies (to identify if the patient has anti-treponemal pallidum antibodies binding to the same spirochete) are added.
  147. Serofast for life; patient may show positive results even after primary syphilis exposure.
  148. BORRELIA CHARACTERISTICS [S21]
  149. Physiological characteristics of borrelia:
  150. Large spirochete (20 – 30 micrometers in length); much larger than syphilis
  151. Motile
  152. Stainable with aniline dyes (Giemsa)
  153. May be observed with conventional microscopy
  154. Cultivable in artificial media
  155. Relatively rare disease
  156. Found among campers in Colorado (especially those who stay in cabins where rodents may also reside)
  157. RELAPSING FEVER: B. RECURRENTIS & OTHERS [S22]
  158. Relapsing fever (borrelia recurrentis, etc.)is considered to be an endemic in Western US
  159. Transmission of relapsing fever (borrelia recurrentis, etc.):
  160. Ornithodoros (soft ticks on rodents, which are active but rarely seen)
  161. Pediculus (human body lice)
  162. Infected rats by contact with blood
  163. Disease characteristics of relapsing fever (borrelia recurrentis, etc.):
  164. Febrile bacteremia with chills and headache
  165. Common to have 3-10 recurrences
  166. Bacteria antigens usually change, escaping antibody control of the host
  167. Diagnosis of relapsing fever (borrelia recurrentis, etc.):
  168. Culture (rarely successful)
  169. Antibody detection
  170. Antigenic shifts confound diagnosis and serology
  171. LYME DISEASE: BORRELIA BURGDORFERI [S23]
  172. Agent identified in 1984
  173. Reported from over 40 states (not endemic in Alabama)
  174. Transmission of lyme disease (borrelia burgdorferi):
  175. Transmitted mainly by Ixodes ticks (deer tick)
  176. Reservoir in mice
  177. Commonly found in the area of US around the Great Lakes(see map)
  178. Disease characteristics of lyme disease (borrelia burgdorferi):
  179. Bloodstream invasion seeds tissue (nerve, heart, joints)
  180. Three distinct stages:
  181. Erythema chornicum migrans rash at site of tick bite
  182. Neural and heart problems (usually for several months)
  183. Joint problems (like arthritis, usually for several years)
  184. Diagnosis of lyme disease (borrelia burgdorferi)
  185. Antibody production (can be problematic though)
  186. PICTURE: ERYTHEMA CHRONICUM MIGRANS RASH [S24]
  187. Notice the erythema chronicum migrans rash (spreading rash), which is found in 60 – 80% of lyme disease (borrelia burgdorferi) cases.
  188. The rash is actually found in Alabama, even though lyme disease (borrelia burgdorferi) is not. It is commonly known as “southern tick-associated rash illness”.
  189. GRAPH: LYME DISEASE IN US [S25]
  190. Statistics given by CDC
  191. Delaware seems to have many cases of lyme disease (borrelia burgdorferi) each year.
  192. PICTURE: IXODIES TICK VECTOR FOR LYME DISEASE [S26]
  193. The larval stage is not infectious. Larval stage needs to feed on another organism (like a rodent) to become infectious. (Very tiny; unable to be seen without a microscope.)
  194. The nymph stage (though very tiny too) can be infectious though.
  195. Spring and summer is the transition time from the nymph stage to the tick stage. Ticks have a two year life cycle. They feed once, lay eggs, and then start the cycle again.
  196. LEPTOSPIRA [S27]
  197. Physiological characteristics of leptospira:
  198. Spirals (thin, tightly coiled; 10 – 20 micrometers)
  199. Obligate anaerobes
  200. Grow in artificial media supplemented by rabbit serum (Fletcher’s)
  201. May require 4 weeks
  202. Example: Leptospira interrogans parasitizes animals (and commonly found in rodent urine). See next slide.
  203. LEPTOSPIROSIS [S28]
  204. Epidemiology of leptospirosis:
  205. Parasitize animals that carry leptospirosis in their kidney (dogs, cats, pigs, livestock, etc.)
  206. Occasionally infect humans who come in contact with soil or water contaminated with urine
  207. Pathogenesis of leptospirosis:
  208. Entry through mucous membranes or breaks in skins; gain access to bloodstream, kidney, liver, CNS
  209. Disease characteristics of leptospirosis:
  210. Fever of unknown origin (FUO)
  211. Aseptic meningitis
  212. Jaundice
  213. Nephritis
  214. Weil’s disease (leptospirosis interrogans serovar icterohaemorrhagiae)
  215. Diagnosis of leptospirosis:
  216. Culture (blood, CSF, urine)
  217. Serology (how leptospirosis is mainly diagnosed)
  218. Darkfield examination
  219. RICKETTSIAE [S29]
  220. Not very common, but very serious (can be deadly)
  221. Physiological characteristics of rickettsiae:
  222. Obligate intracellular organisms
  223. Contain both RNA and DNA
  224. Cell walls are similar to gram-negative bacteria
  225. Stains with Giemsa
  226. Reproduce by binary fission
  227. Not routinely grown in diagnostic microbiology labs
  228. Quickly destroyed by heat, drying, and bactericidal chemicals
  229. Transmission of rickettsiae:
  230. Most transmitted to humans by arthropods (except coxiella)
  231. Diagnosis of rickettsiae:
  232. Serology
  233. Treatment of rickettsiae:
  234. Tetracycline
  235. RICKETTSIAE IN CYTOPLASM OF HOST CELL [S30]
  236. Picture of rickettsiae stained in the cytoplasm of host cell
  237. Notice the purple-stained rickettsiae inside the blue-stained cell
  238. RICKETTSIA PATHOLOGY [S31]
  239. Pathology of rickettsia:
  240. Organisms multiply in endothelium of small vessels (vasculitis)
  241. Cells swell and become necrotic (thromobose vessel)
  242. Disseminated Inravascular Coagulation
  243. Organism may replicate within phagocytic cell (can survive inside macrophages, etc.)
  244. CHART: SECLECTED RICKETTSIAL DISEASES OF US [S32]
  245. Chart showing some of the rickettsial disease commonly found in the US
  246. Rickettsia prowazekki (causing Louse-Borne Typhus) is relatively rare though
  247. Rickettsia rickettsii (causing Rocky Mountain Spotted Fever) is very dangerous (can be deadly). Unfortunately, it’s difficult to diagnose.
  248. Notice that coxiela burnetti (causing Q Fever) doesn’t have a vector, so it can spread rapidly.
  249. MACULAR RASH OF RMSF [S33]
  250. Picture of macular rash of Rocky Mountain Spotted Fever (RMSF)
  251. Disease characteristics of RMSF:
  252. 2 – 18% mortality rate (30% before antibiotics)
  253. About 50% have macular rash in first 3 days
  254. Treatment of RMSF:
  255. Treatment time is the most important factor
  256. Tetracycline-derivate treatment is best
  257. FIGURE: RMSF INCIDENCE (MILLION) [S34]
  258. Rocky Mountain Spotted Fever is actually found in other places than the Rocky Mountains
  259. Common in North Carolina, South Carolina, Oklahoma, Arkansas, Missouri
  260. PICTURE: EHRLICHIA CHAFEENSIS IN A MONOCYTE [S35]
  261. Notice the cells growing inside the cells in the blood
  262. Only 10 – 20% of the cases have the morula
  263. GRAPH: EHRLICHIA CHAFFEENSIS [S36]
  264. Graph showing the amount of ehrlichia chaffeensis.
  265. Notice that there were nearly 1200 cases in 2008.

[End 40:52 mins]