A Walk Through the Disease:

Syphilis“The Great Imitator”

(Black 622)

(1905- Present)(Black 621)

What causes the disease?

Treponema Pallidum (T. Pallidum)○ Spirochete (corkscrew shaped bacterium)○ Helical rods ○ 0.1 - 0.4 micrometers in diameter○ 5-20 micrometers in length

(Bergey, 30)

T. Pallidum● Consists of:

○ (Periplast)outer enveloping membrane - contouredto give between 4-14 spirals

● axial filament (flagella)composed of several fibrils● outer envelope is between 70-90 micrometers thick● fibrils stretched from one end of treponeme to the

other end and unwind in helical coils● flexible cell wall

(Monif,Giles,2008)

(Darkfield Micrograph, http://plaza.ufl.edu) (T. Pallidum http://microbiologyglossary.wikispaces.com)

T. Pallidum

● Tight, regular or irregular elongated spirals● Unicellular● Gram Negative● Contains a multilayered outer membrane “envelope”

○ is an obligate internal bacterium

(Bergey, 27)

T. Pallidum

T. Pallidum● Fragile bacteria - can only survive and reproduce in

a living host● Grows best at 34-35 degrees celsius ● Sensitivity to elevated temperatures

○ death of bacterium occurs at 40.5 degrees celsius

● Reproduce by way of Transverse Binary Fission○ Constriction of cytoplasm is across the plane○ Parent cell divides, and results in 2 equal daughter

cells (Journal of Clinical Investigation,2011)

T. pallidum (cont.) ● Host associated, pathogenic organism● Found in oral cavities, intestinal tracts, and genital areas

of humans (Bergey, 30)

● Cannot be cultured in a lab using routine culture materials (antimicrobe.org)

● Has one or more flagella inserted at each end of the periplasmic space and it runs throughout (Bergey, 30)

(Periplasmic Flagella, Google)

T. Pallidum (cont.)

○ Entire genome completely sequenced in 1998 (antimicrobe.org)

■ less than 1,000 genes (“Treponema Pallidum”, Microbytes)

■ 1,138,006 base pairs (antimicrobe.org)

○ Actively, motile ○ Fastidious growth requirements (Black, 621)

○ Doesn’t stain well with Gram’s method, stains best with silver impregnation technique

○ Anaerobic or microaerophilic○ Chemoorganotrophs○ Catalase and oxidase negative (Bergey, 30)

Diagnosis of the disease● Definitive method is visualizing the unique movement of

the spirochete using dark field microscopy● Blood tests:

○ Nontreponemal tests (VDRL and RPR)○ Treponemal tests (FTA-ABS, TP-PA, various EIAs

and chemiluminescence

(“Syphilis,” CDC Factsheet)

Transmission of Disease● Contact with active lesions through:

○ Sexual means○ Body fluids (saliva)○ Kissing

● Passed from mother to fetus

(Black, 620)

Congenital Syphilis● Treponemes cross the placenta, infecting the fetus (Black, 623)

● Many fetuses infected with syphilis are stillborn or die shortly after birth (Marieb, 1053)

● Those who survive may show the following symptoms: (Black 623)

(“Diagnosis,” Fac Medicine) (“TORCH infections”) ("Zakaźne Obrazki Å�adne.") (“Pathology and Laboratory Medicine”)

Congenital Syphilis (Cont.)

● If left untreated in pregnant women, syphilis results in infant death in up to 40% of cases

● The rates of infant death due to syphilis in 2012 were as follows:○ Whites- 2.1 cases per 100,000 live births○ Hispanics- 3.8 times higher with 7.9 cases per

100,000 live births○ Blacks- 14.1 times higher with 29.6 cases per

100,000 live births (“Syphilis,” CDC Factsheet)

Typical Case of Syphilis● Consists of Multiple Stages

○ Incubation period○ Primary stage○ Primary latent period○ Secondary stage○ Secondary latent stage○ Tertiary stage

(Black, 621-622)

Incubation Period● Occurs over a 2-3 week period after infection.● Log/Lag phase of growth

○ Organisms are multiplying and spreading throughout the body.

(Black, 621)

Primary Stage

(“Syphilis,” CDC images)

On average…● Occurs about 3 weeks after infection

○ Inflammatory response at original entry site○ Formation of first chancre○ Additional chancres appear

● After 4-6 weeks....○ Lesions spontaneously go away without scarring

(Black, 622)

Primary Latent Period● All external signs of disease disappear● Diagnostic blood tests appear positive● Organisms are spreading throughout the circulation

(Black, 622)

Secondary Stage

● Carrier is highly contagious!!● Symptoms can appear, disappear, and reappear many

times over a 5 year span● Symptoms include:

○ Copper colored rash○ Various pustular rashes and skin eruptions○ Cervical lesions○ Painful, whitish mucous patches in oral cavity

● Eventually lesions spontaneously heal again(Black, 622) images- (“Syphilis,” CDC images)

Secondary Latent Stage● All symptoms disappear● Diagnostic blood tests may appear negative● Stage can last a lifetime or a highly variable amount of

time. (May not occur at all)● Can remain in this stage or progress further

(Black, 622)

Tertiary Stage● Permanent damage occurs throughout various systems

of the body○ CNS, blood vessels, skeleton, and skin

● Damage is caused by formation of Gummas● Neurosyphilis

○ Thickening of meninges○ Ataxia○ Paresis

(Black, 622)

(“Dermatology online journal”)

Tertiary Stage (cont.)

(“Syphilis-Tertiary”) (“General Paralysis of the Insane”)

Treatment

● Benzathine benzylpenicillin (form of penicillin)○ also known as Benzathine penicillin G○ a cell envelope antibiotic

(Beta Lactam antibiotic) - containing a beta lactam ring nucleus(merckmanuals.com)

● Combination of:○ benzylpen - antibiotic○ benzathine - penicillin stabilizer

(cdc.gov)

Treatment (Cont’d)● Intramuscular injection of Benzathine Penicillin

(More common form of treatment)

○ single dose is used to treat primary and secondary stages

○ provides low concentrations of antibiotic over a period of 2-4 weeks after a single dose

(cdc.gov)

Treatment (Cont’d)● Acts to:

○ inhibit cell wall synthesis○ interrupting peptidoglycan synthesis○ prevents cross linkages

(merckmanuals.com)

● Treatment kills the bacterium○ preventing further damage○ cannot repair damage already done

(cdc.gov)

Treatment (Cont’d)● In addition to antibiotic treatment, it is extremely

important to:

● abstain from sexual contact when active chancresare presentas well as during course of treatment

● advise any and all sexual partners of possibleexposure, as to be tested/treated appropriately asa result of being infected

● non-compliance can result in infecting partners, as well as re-infecting yourself

(cdc.gov)

Treatment (Cont’d)

Benzathine Penicillin Intramuscular Injection (http://farm5.static.flickr.com)

Treatment (Cont’d)● Additional treatments include:

○ Amoxicillin (semi-synthetic penicillin) given orally 2x daily in addition to

○ Probenecid (uricosuric drug)-increases uric acid excretion in urine (when used to treat syphilis, it inhibits renalsecretion of both natural and semi-syntheticpenicillin)

● This course of treatment can be utilized at any stage(antimicrobe.org)

Treatment (Cont’d)● Recommended regimen to treat Neurosyphilis

○ Intramuscular injections of Benzathine Penicillin(every 4 hours for 10-14 days)

This aids in reaching treponemicidal levels in the cerebrospinal fluid of the central nervous system

● Although regimens may fail, and re-treatment may berequired especially in HIV infected patients

(antimicrobe.org)

Treatment (Cont’d)● Without adequate treatment:

○ Primary Stage Secondary Stage

○ Secondary Stage -symptoms will go away with or without treatment, but without will result in Tertiary Stage

● Tertiary Stage Neurosyphilis DEATH((“Syphilis,” CDC Factsheet))

Works citedBergey, D. H., and John G. Holt. "Chapter V: Groups within the Four Major Categories of

Bacteria." Bergey's Manual of Determinative Bacteriology. 9th ed. Baltimore: Williams

& Wilkins, 1994. 17-20. Print.

"β-Lactams." : Bacteria and Antibacterial Drugs: Merck Manual Professional. Web. 17 Nov. 2014.<http://www.merckmanuals.

com/professional/infectious_diseases/bacteria_and_antibacterial_drugs/β-lactams.html

Black, Jacquelyn G. Microbiology: Principles and Explorations. Hoboken, NJ: Wiley, 2012. Print.

"Dermatology Online Journal." Solitary Frontal Ulcer: A Syphilitic Gumma [eScholarship]. Web. 17 Nov. 2014. <https://escholarship.

org/uc/item/5gs4q6wz>.

"Diagnosis." Fac Medicine. Web. 17 Nov. 2014. <http://forum.facmedicine.com/threads/diagnosis.10468/>.

"General Paralysis of the Insane* and Psychiatry’s Only Nobel Prize «." Web. 17 Nov. 2014. <http://frontierpsychiatrist.co.uk/general-paralysis-

of-the-insane-and-psychiatrys-only-nobel-prize/>.

Monif, Gilles. Infectious Diseases in Obstetrics & Gynecology. New York: Informa Healthcare, 2008. Print.

Marieb, Elaine Nicpon, and Katja Hoehn. Human Anatomy & Physiology. Boston: Pearson, 2013. Print.

"Pathology & Laboratory Medicine." Tulane University. Web. 17 Nov. 2014. <http://tulane.edu/som/departments/pathology/lues2nathx.cfm>.

Works Cited (Cont.)

"Symptoms You Might Have Syphilis." YouTube. YouTube. Web. 17 Nov. 2014.

<https://www.youtube.com/watch?v=mfWO3s7Mv58>.

"Syphilis - CDC Fact Sheet." Centers for Disease Control and Prevention. Centers for Disease

Control and Prevention, 07 Jan. 2014. Web. 17 Nov. 2014.

<http://www.cdc.gov/std/syphilis/stdfact-syphilis-detailed.htm>.

"Syphilis - Images." Centers for Disease Control and Prevention. Centers for Disease Control and Prevention, 13 Sept. 2012. Web. 17 Nov.

2014. <http://www.cdc.gov/std/syphilis/images.htm>.

"Syphilis - Tertiary." . Causes, Symptoms, Treatment. Web. 17 Nov. 2014. <http://dxline.info/diseases/syphilis-tertiary#prettyPhoto>.

"Syphilis: using modern approaches to understand an old disease." Journal of Clinical Investigation 121.12 (2011): 4584-4592. Print.

Works Cited (Cont.)

"TORCH Infections." Table of Contents. Web. 17 Nov. 2014. <https://pedclerk.bsd.uchicago.edu/page/torch-infections>.

"Treponema Pallidum." MicrobiologyGlossary -. Web. 17 Nov. 2014. <http://microbiologyglossary.wikispaces.com/Treponema pallidum>.

"Treponema Pallidum (Syphilis)." - Infectious Disease and Antimicrobial Agents. Web. 17 Nov. 2014. <http://www.antimicrobe.org/new/b242.

asp>.

"Treponema Pallidum." Treponema Pallidum. Web. 16 Nov. 2014. <http://www.microbiologybytes.com/video/Tpallidum.html>.

"Treponema/ Syphilis Darkfield Video (CDC)." YouTube. YouTube. Web. 17 Nov. 2014.

<http://www.youtube.com/watch?v=Klsfl50lrMU>.

Works Cited (Cont.)"Periplasmic Flagella - Google Search." Periplasmic Flagella - Google Search. Web. 17 Nov. 2014. <https://www.google.com/search?

q=periplasmic flagella&biw=1366&bih=631&tbm=isch&imgil=oWMZ4M6HCp59mM%3A%3BNOe1xcXCL1pquM%3Bhttp%253A%252F%

252Fquizlet.com%252F12509809%252Fprokaryotic-cells-flash-cards%252F&source=iu&pf=m&fir=oWMZ4M6HCp59mM%3A%

2CNOe1xcXCL1pquM%2C_&usg=__GwSbX-

ou6g2lHrB9ocMZXMSLwfE=&ved=0CDwQyjc&ei=_BdpVMjBNI6xyATU4IHIAg#facrc=_&imgdii=_&imgrc=oWMZ4M6HCp59mM%3A;

NOe1xcXCL1pquM;http%3A%2F%2Fo.quizlet.com%2Fi%2FcmmS70zlGjMXRZAWJD4boQ_m.jpg;http%3A%2F%2Fquizlet.com%

2F12509809%2Fprokaryotic-cells-flash-cards%2F;240;87>.

"WebMD - Better Information. Better Health." WebMD. WebMD. Web. 16 Nov. 2014. <http://webmd.com/>.

Web. 16 Nov. 2014. <http://farm5.static.flickr.com/>.

"Zakaźne Obrazki �adne." Flashcards. Web. 17 Nov. 2014.

<http://quizlet.com/38739400/zakazne-obrazki-ladne-flash-cards/>.