wadsworth.org

Syphilis :An Ancient

Disease Revisited

HARVINDER KAUR LAKHBEER SINGH

LAB TECHNOLOGIST MIRCOBIOLOGY PPUM

Treponema pallidum – The Agent of SyphilisKINGDOM: BACTERIA

PHYLUM: SPIROCHAETAE

CLASS: SPIROCHAETES

ORDER: SPIROCHAETALES

FAMILY : SPIROCHAERACECAE

GENUS: TREPONEMA

1493 1526

?

- Origin of syphilis has not been agreed on by researchers1.Christopher Columbus and his crew brought it back with them from the “new world”.2. Syphilis was always present in the “old world” but it wasn’t yet identified as a separate disease from leprosy. Greece Lit3.Syphilis developed from the related diseases bejel and yaws.

1495

1500

Fernandez de Oviedo was the first personto mention the “American origin”

of syphilis

# of cases in Europe reach epidemic proportions

http://www.latinamericanstudies.org/columbus/older-columbus.gif

Christopher Columbus

The first reference to the “French sickness” is madeduring Charles VIII’s Italian campaign

1514

1530

The disease recieves the name syphilis from a poem entitled “Syphilis Sive

Morbus Gallicus” by Jerome Francastor

A complete description of the “French sickness” wagiven by Juan de Virgo

History

1996

the rising occurrence of syphilis aroundthe world causes hope of eradicating the disease

to lessen after being raised by the success of penicillin

1964-1965

so few cases that the medical and scientific community is prepared to

consider it eradicated

2001

rising of cases on the rise in western countriesWHO 12 MIL NEW CASES EVERY YEAR

http://nobelprize.org/nobel_prizes/medicine/laureates/1945/fleming-bio.html

1928

Sir Alexander Fleming discovers penicillin while working on the

influenza virus.

1905

Treponema Pallidum, the bacteria that causes syphilis is discovered on March 3

in Berlin by Chauvinand Hoffmann

Sir Alexander Fleming

•Transmission

–Sexual–Trans-placental/In Utero–Percutaneous following contact with infectious lesions–Blood Transfusion – very rare

• Infectious Dose: ~57 organisms• Incubation Period – 21 days (median)• 3 clinical stages of syphilis

• Primary:• Painless sore (chancre) at inoculation site

• Secondary:• Rash, Fever, Lymphadenopathy, Malaise

• Tertiary/Latent:• CNS invasion, organ damage

• “The physician that knows syphilis knows medicine.” – Sir William Osler 1Magnuson HJ, et al. Inoculation of syphilis in human volunteers. Medicine 1956;35:33-82

http://www.cdc.gov/std/syphilis/stdfact-syphilis.htm6

Laboratory Diagnosis

6-15 micrometer in length and 0.2 micrometer in width

obligate parasite, needs a host to conduct metabolic process and life cycle.

It thrives under in vitro conditions , O2 between 10 to 20 %- microaerophilic

Not only oxygen dependent it also prefers temp that is relative to human body

circular genome smaller compared to other prokaryotes

SYPHILIS DIAGNOSTIC TEST FALLS INTO FOUR CATEGORIES

(i) direct microscopic examination,

(ii) nontreponemal tests, used for screening;

(iii) treponemal tests that are confirmatory; and

(iv) Direct antigen detection tests currently used in research settings and as gold standards for test evaluation

Laboratory Diagnosis

The Uncommon Methods

Rabbit Infectivity Test (RIT) –High Sensitivity and Specificity –Long turn-around-time –Limited to research settings

Magnuson, H. J., H. Eagle, and R. Fleischman. 1948. The minimal infectious inoculum of Spirochaeta pallida (Nichols strain and a consideration of its rate of multiplication in vivo. Am. J. Syph. 32:1–18.

Dark Field Microscopy –Useful only during primary infection –Technician expertise required

Immunostaining –Direct fluorescent antibody or silver stain

IN THE MID 1960 the direct fluorescent antibody test ‘(DFA) was developed, later it was modified for use with monoclonal antibodies and tissues sections in the direct fluorescent antibody tissue test(DFAT-TP)

Kellogg, D. S., Jr., and S. M. Mothershed. 1969. Immunofluorescent detection of Treponema pallidum: a review. JAMA 107:938–941.

Polymerase Chain Reaction (PCR) PCR is now commercially available but not used routinely in diagnostic medical laboratories.

PCR is useful mainly in early acute disease

Emily L Ho et al. Syphilis: using modern approaches to understand an old disease, J Clin Invest, 2011

Laboratory Diagnosis of Syphilis The Common Methods

•Serology –Mainstay for syphilis testing

–Two classes of serologic tests •Non-treponemal

•TreponemalS Ratnam. The laboratory diagnosis of syphilis. Can J Infect Dis Med Microbiol 2005;16(1):45-51

Serologic Tests for Syphilis:

Non-Treponemal Assays

•Principle: –T. pallidum infection leads to the production of reagin •Reagin – Antibodies to substances released from cells damaged by T. pallidum –Reagin reacts with cardiolipin •Cardiolipin – a phospholipid component of certain eukaryotic and prokaryotic membranes •Examples of non-treponemal tests:

–Rapid Plasma Reagin (RPR) –Venereal Disease Research Laboratory (VDRL)

Falcone, V. H., G. W. Stout, and M. B. M. Moore. 1964. Evaluation of rapid plasma reagin (circle) card test. Public Health Rep. 79:491–495.

Portnoy, J., W. Carson, and C. A. Smith. 1957. Rapid plasma reagin test for syphilis. Public Health Rep. 72:761–766.

CAN BE USED IN FIELD

NON TREPONEMAL TEST :

LIMITATIONS

Neimeister, R. P., R. Teschemacher, I. J. Yankevitch, and J. Cocklin. 1975.Proficiency testing, trouble schooting and quality control for the RPR test.Am. J. Med. Technol. 41:13–17.

EIA (AUTOMATED ENZYME

IMMUNOASSAY)

Reverse Sequence Syphilis Screening

Performance and clinical data for the use of reverse sequence screening

MMWR February 11, 2011 / 60(05);133-137

JID 2011

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