syphilis: 2nd time's a charm

Question 1

Congenital syphilis (CS, a severe mutilating form of the disease):
tranmission?? 
when most likely??
Fetal response to infection
detected when ??

Answer 1

via placenta at any time during pregnancy, but fetal infection in utero occurs most frequently with mother in early stage of infection.
-fetal response detected 18-20th wk of development when fetal immune system becomes operational.

Question 2

CS infected fetus mostly likely will be ??

Answer 2

stillborn (significant mortality).

if live birth: symptomatic, or Perinatal/infantile/early congenital form (asymptomatic, most)

Question 3

life birth CS: if Symptomatic newborns are??

Answer 3

• are often born premature and usually die shortly after birth.
• Manifest with hepatosplenomegaly, skeletal abnormalities, pneumonia, pemphigus syphiliticus (a bullous skin disease)

Question 4

Perinatal/infantile/early congenital form: most are born without clinical evidence of disease but would be ??

Answer 4

STORCH test positive

• inf. involves multiple organs with lesions present in virtually any organ (esp. skin, bone, CNS, liver, kidney).
• Symptoms appear before age 2 (usually 34m post birth), are similar to secondary syphilis in adults, and include: macpap., desquam. rash, condylomata lata, persistent mucopurulent rhinitis/AKA snuffles (infection of the nasal mucosa) and S&S consistent with lesions involving one or more organs

Question 5

CS: Latent period: ??

Answer 5

If the patient survives the first 6-12 months after birth, enters the latent period (usually 5-15 y), then late congenital syphilis occurs

Question 6

Late congenital form (aka stigmata): which occurs ?? after birth. Appearance is somewhat like ??

Answer 6

2-20 yrs

tertiary syphilis in adults

Question 7

Late congenital form: Stigmata AKA “Hutchinson‘s triad”

Answer 7

• VIIIth nerve deafness
• Corneal ulcers and opacities and Interstitial keratitis.
• Hutchinson‘s teeth (centrally notched and widely spaced, peg-shaped, upper central incisors).

Question 8

Late congenital form: Other Stigmata:

Answer 8

Parrot’s Frontal Bossing (skull), Bulldog jaw (prominent mandible), Higoumenakia sign (unilateral irregular enlargement of the sternoclavicular portion of the clavicle secondary to periostitis), Mulberry molars (6th year molars with multiple poorly developed cusps), Saddle nose (depression of nasal bridge due to destruction of the
nasal septum & palate - gumma), perforation of palate, saber shins (anterior tibial bowing), Clutton’s joints (due to inflammation of the knee joints).

Question 9

Late congenital form: Other Stigmata: 2

Answer 9

Skin rhagades (radial scars) plus petechiae, haemorrhagic vesicles, bullae (pemphygis syphiliticus), erythematous macular, papulosquamous, annular, or polymorphous eruptions, optic nerve atrophy, neurosyphilis (tabes dorsalis and general paresis may develop as in adults) but rarely CV involvement.

Question 10

syphilis dx: often on ??

culture??

Answer 10

clinical findings (S/S) and a history of sexual contact with
a known infected individual in conjunction with laboratory test
-The organism is extremely fastidious and cannot be cultured in vitro or in vivo.

Question 11

Diagnosis by microscopic detection of T. pallidum cells in the primary and/or secondary lesions (scrapings, lesion material, or exudate):

Answer 11

• not observable in the blood due to low level spirochetemia.
• Darkfield microscopy – Direct observation of the spirochete
• Fluorescent microscopic examination of specimens with DFA for Treponema pallidum (DFA-TP; a fluorescein-labeled-T. pallidum specific- monoclonal antibody)
• Used to dx 1o and 2o syphilis*

Question 12

how can T. pallidum be misdx??

Answer 12

If lesions are in mouth, mucous membranes, anus, etc., normal spirochetal flora may contaminate lesion material collected from the site leading to misdiagnose if the normal spirochetal flora are mistaken for T. pallidum

Question 13

Two types of antibodies are produced in response to infection that both are the basis of the serological assays for T. pallidum

Answer 13

Treponemal-specific and Non-treponemal-specific Ab

Question 14

Non-treponemal antibody tests (NTT) detect ??

Answer 14

Reagin (both IgM and IgG antibodies) in the serum of persons infected with T. pallidum. These antiphospholipid antibodies serologically/immunologically cross reacts with cardiolipin (a phospholipid extracted
from beef heart)

Question 15

Reagin (both IgM and IgG antibodies) used in these screening tests:

Answer 15

• Venereal Disease Research Lab (VDRL)
• Rapid Plasma Reagin (RPR)
• Enzyme Immunoassay (EIA) is replacing the VDRL/RPR tests.

Question 16

characteristics of NTT Reagin screening tests
when positive??
when do titers decline??
All 3 tests possess ??

Answer 16

• flocculation (agglutination) slide tests that are easy to perform, cheap, and widely used
• 100% positive by end 4 week after chancre first appears (during 1o syphilis). Titers peak during 2o stage, then may gradually decline and even become negative in late latent syphilis but can persist for years in untx persons.
• high sensitivity but low specificity

Question 17

Uses of screening tests:

Answer 17

To diagnose primary -> early latent syphilis.

• RPR (only) is routinely used to monitor efficacy of tx (In most pts after the initiation of effective tx, RPR usually reverts to negative or near-negative values in 1-2 y)
• VDRL (only) to dx neurosyphilis

Question 18

Treponemal-specific antibody tests detect the presence of ??

Used in ??

Answer 18

IgM and/or IgG antibodies (specific for a T. pallidum Ag) in the serum of persons infected with T. pallidum

confirming test for syphilis

Question 19

Treponemal-specific antibody tests include:

Answer 19

• Fluorescent Treponemal Antibody test after Absorption (FTA-Ab). Pt.’s adsorbed serum is mixed with non-viable pathogenic treponemes and then fluorescein-labeled-anti-human IgG is added, observed microscopically.
• Microhemagglutination assay for T. pallidum [MHA-TP] and hemagglutination assay for T. pallidum [TP-HA] /hemagglutination treponemal test for Syphilis [HATTS]
• Enzyme Immunoassay (EIA) is replacing other confirming tests.

Question 20

Treponemal-specific antibody tests are ??

Answer 20

highly specific, sensitive, reliable and are positive early in 1o syphilis

Question 21

Uses of (Treponemal-specific) confirming tests:

Answer 21

• confirm screening tests RPR, EIA + rxns (to rule out BFP)
• to dx neurosyphilis (FTA-ABS CSF), esp. if VDRL is neg
• Used to dx late latent or tertiary syphilis because the NTT results may be negative
• Not used to assess therapy because treponemal specific-Ab are present in all 3 stages of disease regardless of tx; Ab titers are unaffected by tx.

Question 22

Congenital syphilis is extremely difficult to dx and may incorporate ??

Answer 22

clinical findings with specialized serological tests and comparing infant and maternal antibody titers

Question 23

tx of choice for all stages and conditions of syphilis: ??

Answer 23

a long-acting Benzathine penicillin G administered IM.

Tx is based on stage of disease:

Question 24

length of Benzathine PCN G tx regimen is ??
Prognosis for 1o or 2o syphillis with tx?? w.out??
3o syphilis px?

Answer 24

extended in latter stages of the disease (e.g. late-
latent syphilis)
excellent w. tx, w.out: 33% of all pts with 2o syphillis will progress to late/3o syphilis and die. (Late/3o is notoriously refractory to abx therapy)
-In the absence of adequate treatment, pt may progress to further stages

Question 25

what is used in patients with hypersensitivity to penicillin??

Answer 25

Macrolide (erythromycin, azithromycin), Tetracyclines (tetracycline, doxycycline), and ceftriaxone
(but treatment failures occur)

Question 26

how does resistance develop to alternative T. pallidum abx??

Answer 26

An A → G mutation in the 23S ribosomal RNA genes confers azithromycin resistance in clinical strains in localities in the US and Europe.
-occurs by spontaneous mutation, not by spread of a single resistant strain.

Question 27

tx of Congenital syphilis:

Prognosis for a patient with congenital syphilis ??

Answer 27

tx the gravid female with benzathine penicillin for more than 1 month prior to birth is adequate for fetal infection if the appropriate serologic response is observed in the mother.
-Prognosis for a patient with congenital syphilis is poor unless treated early enough


Question 28

Jarisch-Herxheimer reactions:

Answer 28

-endotoxic shock-like response, probably the result of dead or dying
treponemes released into the peripheral blood
-Often occur during tx, warn pt!
-Occurs 2-12 (1 -4)h post initiation of tx.
-s/s include: fever, chills or rigors, malaise, headache, myalgia and tachycardia

Question 29

more Jarisch-Herxheimer reaction characteristics

Answer 29

• Rarely severe or fatal with syphilis tx
• response does not affect efficacy or tx course
• does not predict if tx will or will not be effective
• nature of tx (antibiotics or which antibiotic or even if using an arsenical) is irrelevant to if response occurs or not

Question 30

A more significant systemic response (Jarisch-Herxheimer reaction) occurs when treating persons in early stages of syphilis but response can result in ?? if person tx is in late stages of syphilis

Answer 30

CNS or cardiovascular damage

Question 31

The Jarisch-Herxheimer reaction in relapsing fever has been controlled anti-TNF-α antibodies??
For Syphilis:

Answer 31

-tx or prevented with NSAIDs for 24-48h starting with administration of
abx
-Severe reactions respond well to prednisone

Question 32

Syphilis Treatment follow-up is essential. Do serology (RPR) when ??

Answer 32

3, 6, 12, 24 months post treatment.

Expect declining antibody titers over a 1-2 year period following tx

Question 33

congenital syphilis px

Answer 33

Poor prognosis unless very early treatment. Untx: 25-50% mortality and 50% of survivors have serious sequelae (which may occur even with effective treatment)

Question 34

Sexually transmitted syphilis px

Answer 34

With tx prognosis is excellent.
Without: about 33% of all
syphilis patients develop 3o form of disease, with an associated elevated mortality

Question 35

syphilis Prevention and control:

Answer 35

-Reportable disease: Public health measures, Tracing contacts/tx of those contacts
-Individual measures:
1. limiting number of sexual partners and/or discriminate partner selection.
2. use of barrier contraception/using condoms (use of condoms reduces the rate of
transmission per incident contact)
-congenital syphilis: Prenatal testing of mother, if infected, tx infected mother and
child she is carrying