Download Spirochetes and Rickettsiae

CLASS: 10:00 – 11:00
DATE: October 27, 2010
PROFESSOR: Benjamin
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Spirochetes and Rickettsiae
Scribe: Adam Baird
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SPIROCHETES AND RICKETTSIAE [S1]
OBJECTIVES [S2]
a. To review and discuss:
1. Microbiological characteristics
2. Epidemiology
3. Virulence factors
4. Associated diseases
5. Laboratory detection
b. Topics:
1. Teponema pallidum
2. Borrelia spp.
3. Leptospira spp.
4. Rickettsiae
5. Ehrlichia spp.
TREPONEMA PALLIDUM [S3]
a. Treponema pallidum is one of the most important topics of this lecture
b. Physiological characteristics of treponema pallidum:
1. Motile spirals (5-15 micrometers)
2. Has not been successfully cultured/subcultured on artificial media, but may multiply in rabbit epithelial
cell cultures
3. Very susceptible to environment conditions
4. Does not stain with aniline dyes
GRAPH: PRIMARY AND SECONDARY SYPHILIS [S4]
a. This graph shows the rate (per 100,000 population) of primary and secondary syphilis.
b. Notice that syphilis goes through a 10 year cycle
c. 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).
d. 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).
FIGURE: PRIMARY AND SECONDARY SYPHILIS [S5]
a. This figure shows the rates of primary and secondary syphilis by state.
b. Notice that the darker color red indicates a higher number of syphilis cases.
c. Birmingham used to be the “capital for syphilis” for many years. (The new “capital for syphilis” is Memphis.)
FIGURE: SYPHILLIS P & S RATES AND CONGENITAL CASES (1999 – 2008) [S6]
a. The state of Alabama had the third highest number of syphilis nationwide (2008).
b. Notice that some counties in Alabama reported no cases of syphilis (2008).
c. Jefferson County, though, had quite a large amount.
d. Notice that the male and female rate of syphilis is about the same for both males and female (both are
increasing from 2005 – 2008).
e. Notice California’s statistics. Males in California had much higher rates than females in California.
EPIDEMIOLOGY 2008 [S7]
a. Alabama:
1. 449 cases of syphilis in 2008
a. Ranked 3rd with 9.7 cases of syphilis per 100,00 population
b. National rate of 4.5
2. 12 cases of congenital syphilis
a. Ranked 7th with 19 cases of syphilis per 100,000 population
b. National rate of 10.1
STAGES OF SYPHILIS [S8]
a. Stages of syphilis:
1. Primary
a. Chancre (a painless, hard ulcer) at site of inoculation
b. Lasts 1 – 3 weeks
2. Secondary
a. Manifestations due to spirochete
b. Infectious rash seen on various parts of the body, specifically the palms of the hands and
soles of the feet
CLASS: 10:00 – 11:00
DATE: October 27, 2010
PROFESSOR: Benjamin
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Scribe: Adam Baird
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Spirochetes and Rickettsiae
c. Disseminated disease
d. Lasts 2 – 8 weeks
e. Typically resolves in a few days or up to 8 weeks.
3. Latent
a. Patient is still infected
b. Unknown duration
4. Tertiary
a. Severe disease
b. Lifelong infection
c. More details will be discussed later in the lecture
PRIMARY SYPHILIS [S9]
a. Disease characteristics of primary syphilis:
1. Chancre (a painless, hard ulcer) at site of inoculation; quickly erodes and becomes indurated
2. Painless lesion (but tender to touch or examine; can become secondarily infected)
3. Highly variable in HIV-infected patients
4. Regional, non-tender adenopathy (swollen/enlarged lymph nodes, specifically in the area of the
lesion)
5. Heals spontaneously in 1 – 12 weeks (is usually healed in 3 – 6 weeks though)
6. Not uncommon to have no lesions noted
7. Not uncommon to have a small papule that is darkfield negative
PICTURE: ORAL AND GENITAL CHANCRES [S10]
a. Pictures of what some of the syphilis lesions or chancres can look like.
b. Mainly oral lesions and genital lesions
c. It’s difficult to examine oral lesions due to the normal flora in the mouth though
CLINICAL MANIFESTATIONS OF SECONDARY SYPHILIS [S11]
a. Disease characteristics of secondary syphilis:
1. 90% of infected patients have rashes
2. Mucous patches
3. Chondyloma latum
4. 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.
5. Headache
6. Meningismus (the triad of nuchal ridgidity, or “neck stiffness”, photophobia, and headache)
7. Diplopia (double vision)
8. Tinnitus (ringing or buzzing in the ears)
9. Vertigo
10. Glomerulonephritis (acute inflammation of the kidney) or nephritic syndrome
11. Hepatitis
12. Arthritis
b.
PICTURE: SKIN LESIONS OF SECONDARY SYPHILIS [S12]
a. Pictures of secondary syphilis rashes.
b. Notice the effected areas: palms of the hands, soles of the feet, etc.
c. Rashes don’t necessarily “itch” just a skin rash.
d. Condyloma lata (usually where “warm area” where “skin touches skin”, like perianal regions, under female
breasts, etc.)
e.
TERTIARY SYPHILIS [S13]
a. Very serious, dangerous
b. Disease characteristics of tertiary syphilis:
1. Cardiovascular trouble (aortitis, valve lesions)
2. Benign tertiary (gumma formation)
3. Central nervous system involvement
4. Paresis (general paresis of the insane)
5. Tabes doraslis (spinal cord)
6. Meningovascular
PICTURE: TERTIARY SYPHILIS “GUMMA” [S14]
a. Pictures of gumma, a characteristic symptom of tertiary syphilis
CLASS: 10:00 – 11:00
Scribe: Adam Baird
DATE: October 27, 2010
Proof:
PROFESSOR: Benjamin
Spirochetes and Rickettsiae
Page 3 of 6
b.
c.
XV.
CONGENITAL SYPHILIS [S15]
a. Disease characteristics of congenital syphilis:
1. Transplacental (meaning that the infection crosses the placenta, from mother to child)
2. “Snuffles” (child has difficulty breathing, “loud breathing”)
3. Pneumonia
4. Hepatitis
5. Tooth malformation (Hutchinson’s incisors, Mulberry molars)
6. 8th nerve palsy/deafness
7. Saber shins due to persistent inflammation (curved shins)
XVI.
DIAGNOSIS OF SYHPILIS: DARKFIELD [S16]
a. One way to diagnose syphilis:
1. Darkfield Microscope
a. Easiest way to diagnosis syphilis
b. Removes unscattered light beams from the image, making the microscopic field around the
specimen dark, making the specimen look lighter.
c. Useful only if lesion is present
d. Not useful for oral lesions
e. Positive before serology tests
XVII. NON-TREPONEMAL TESTS (RPR, VDRL) [S17]
a. Another way to diagnose syphilis:
1. Non-Treponemal Tests (Rapid Plasma Reagin, Venereal Disease Research Laboratory)
a. Screeinng test (inexpensive, easy, and quick, but “false positive” results may occur)
b. Cardiolipin (extracted from beef hearts), lecithin, cholesterol antigen
c. Can be titered (rising titer indicates active disease, falling titer indicates adequate therapy)
d. Reflects overall activity of syphilis (as opposed to past activity)
e. 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)
XVIII. PICTURE: RPR NON-TREPONEMAL TEST [S18]
a. Picture of RPR non-treponemal test
b. 18 mm circles drawn on paper. Drop of cariolipin placed in each circle. Patient serum is then placed in each
circle.
c. Very standardized test. Well-controlled environment needed.
d. This picture indicates positive results because of the “dark spots” inside the circles
XIX.
TREPONEMAL TESTS [S19]
a. Picture of treponema pallidum particle agglutination (TPPA)
b. TPPA is the follow-up test to RPR non-treponemal test.
c. TPPA has true treponema antigens on gelatin particles.
d. 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).
e. Notice that each well is marked positive or negative.
XX.
FLUORESCENT TREPONEMAL ANTIGEN (FTA) TEST [S20]
a. FTA test is a more labor-intensive test
b. FTA tests become reactive earlier than RPR
c. FTA test is really a confirmatory test of RPR results
d. 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 antihuman antibodies (to identify if the patient has anti-treponemal pallidum antibodies binding to the same
spirochete) are added.
e. Serofast for life; patient may show positive results even after primary syphilis exposure.
XXI.
BORRELIA CHARACTERISTICS [S21]
a. Physiological characteristics of borrelia:
1. Large spirochete (20 – 30 micrometers in length); much larger than syphilis
2. Motile
3. Stainable with aniline dyes (Giemsa)
CLASS: 10:00 – 11:00
Scribe: Adam Baird
DATE: October 27, 2010
Proof:
PROFESSOR: Benjamin
Spirochetes and Rickettsiae
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4. May be observed with conventional microscopy
5. Cultivable in artificial media
6. Relatively rare disease
7. Found among campers in Colorado (especially those who stay in cabins where rodents may also
reside)
XXII. RELAPSING FEVER: B. RECURRENTIS & OTHERS [S22]
a. Relapsing fever (borrelia recurrentis, etc.) is considered to be an endemic in Western US
b. Transmission of relapsing fever (borrelia recurrentis, etc.):
1. Ornithodoros (soft ticks on rodents, which are active but rarely seen)
2. Pediculus (human body lice)
3. Infected rats by contact with blood
c. Disease characteristics of relapsing fever (borrelia recurrentis, etc.):
1. Febrile bacteremia with chills and headache
2. Common to have 3-10 recurrences
3. Bacteria antigens usually change, escaping antibody control of the host
d. Diagnosis of relapsing fever (borrelia recurrentis, etc.):
1. Culture (rarely successful)
2. Antibody detection
3. Antigenic shifts confound diagnosis and serology
XXIII. LYME DISEASE: BORRELIA BURGDORFERI [S23]
a. Agent identified in 1984
b. Reported from over 40 states (not endemic in Alabama)
c. Transmission of lyme disease (borrelia burgdorferi):
1. Transmitted mainly by Ixodes ticks (deer tick)
2. Reservoir in mice
3. Commonly found in the area of US around the Great Lakes (see map)
d. Disease characteristics of lyme disease (borrelia burgdorferi):
1. Bloodstream invasion seeds tissue (nerve, heart, joints)
2. Three distinct stages:
a. Erythema chornicum migrans rash at site of tick bite
b. Neural and heart problems (usually for several months)
c. Joint problems (like arthritis, usually for several years)
e. Diagnosis of lyme disease (borrelia burgdorferi)
1. Antibody production (can be problematic though)
XXIV. PICTURE: ERYTHEMA CHRONICUM MIGRANS RASH [S24]
a. Notice the erythema chronicum migrans rash (spreading rash), which is found in 60 – 80% of lyme disease
(borrelia burgdorferi) cases.
b. 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”.
XXV. GRAPH: LYME DISEASE IN US [S25]
a. Statistics given by CDC
b. Delaware seems to have many cases of lyme disease (borrelia burgdorferi) each year.
XXVI. PICTURE: IXODIES TICK VECTOR FOR LYME DISEASE [S26]
a. 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.)
b. The nymph stage (though very tiny too) can be infectious though.
c. 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.
XXVII. LEPTOSPIRA [S27]
a. Physiological characteristics of leptospira:
1. Spirals (thin, tightly coiled; 10 – 20 micrometers)
2. Obligate anaerobes
3. Grow in artificial media supplemented by rabbit serum (Fletcher’s)
4. May require 4 weeks
b. Example: Leptospira interrogans parasitizes animals (and commonly found in rodent urine). See next slide.
XXVIII. LEPTOSPIROSIS [S28]
a. Epidemiology of leptospirosis:
1. Parasitize animals that carry leptospirosis in their kidney (dogs, cats, pigs, livestock, etc.)
2. Occasionally infect humans who come in contact with soil or water contaminated with urine
CLASS: 10:00 – 11:00
Scribe: Adam Baird
DATE: October 27, 2010
Proof:
PROFESSOR: Benjamin
Spirochetes and Rickettsiae
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b. Pathogenesis of leptospirosis:
1. Entry through mucous membranes or breaks in skins; gain access to bloodstream, kidney, liver, CNS
c. Disease characteristics of leptospirosis:
1. Fever of unknown origin (FUO)
2. Aseptic meningitis
3. Jaundice
4. Nephritis
5. Weil’s disease (leptospirosis interrogans serovar icterohaemorrhagiae)
d. Diagnosis of leptospirosis:
1. Culture (blood, CSF, urine)
2. Serology (how leptospirosis is mainly diagnosed)
3. Darkfield examination
XXIX. RICKETTSIAE [S29]
a. Not very common, but very serious (can be deadly)
b. Physiological characteristics of rickettsiae:
1. Obligate intracellular organisms
2. Contain both RNA and DNA
3. Cell walls are similar to gram-negative bacteria
4. Stains with Giemsa
5. Reproduce by binary fission
6. Not routinely grown in diagnostic microbiology labs
7. Quickly destroyed by heat, drying, and bactericidal chemicals
c. Transmission of rickettsiae:
1. Most transmitted to humans by arthropods (except coxiella)
d. Diagnosis of rickettsiae:
1. Serology
e. Treatment of rickettsiae:
1. Tetracycline
XXX. RICKETTSIAE IN CYTOPLASM OF HOST CELL [S30]
a. Picture of rickettsiae stained in the cytoplasm of host cell
b. Notice the purple-stained rickettsiae inside the blue-stained cell
XXXI. RICKETTSIA PATHOLOGY [S31]
a. Pathology of rickettsia:
1. Organisms multiply in endothelium of small vessels (vasculitis)
2. Cells swell and become necrotic (thromobose vessel)
3. Disseminated Inravascular Coagulation
4. Organism may replicate within phagocytic cell (can survive inside macrophages, etc.)
XXXII. CHART: SECLECTED RICKETTSIAL DISEASES OF US [S32]
a. Chart showing some of the rickettsial disease commonly found in the US
b. Rickettsia prowazekki (causing Louse-Borne Typhus) is relatively rare though
c. Rickettsia rickettsii (causing Rocky Mountain Spotted Fever) is very dangerous (can be deadly).
Unfortunately, it’s difficult to diagnose.
d. Notice that coxiela burnetti (causing Q Fever) doesn’t have a vector, so it can spread rapidly.
XXXIII. MACULAR RASH OF RMSF [S33]
a. Picture of macular rash of Rocky Mountain Spotted Fever (RMSF)
b. Disease characteristics of RMSF:
1. 2 – 18% mortality rate (30% before antibiotics)
2. About 50% have macular rash in first 3 days
c. Treatment of RMSF:
1. Treatment time is the most important factor
2. Tetracycline-derivate treatment is best
XXXIV. FIGURE: RMSF INCIDENCE (MILLION) [S34]
a. Rocky Mountain Spotted Fever is actually found in other places than the Rocky Mountains
b. Common in North Carolina, South Carolina, Oklahoma, Arkansas, Missouri
XXXV. PICTURE: EHRLICHIA CHAFEENSIS IN A MONOCYTE [S35]
a. Notice the cells growing inside the cells in the blood
b. Only 10 – 20% of the cases have the morula
XXXVI. GRAPH: EHRLICHIA CHAFFEENSIS [S36]
a. Graph showing the amount of ehrlichia chaffeensis.
CLASS: 10:00 – 11:00
DATE: October 27, 2010
PROFESSOR: Benjamin
Spirochetes and Rickettsiae
b. Notice that there were nearly 1200 cases in 2008.
[End 40:52 mins]
Scribe: Adam Baird
Proof:
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