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Syphilis. -Spiral shaped spirochete (Treponema pallidum) -gram negative, but does not have lipopolysaccharide (LPS) -helical, thin (0.1 to 0.2 um), and long -flagella are inserted into the periplasm and give it motility -sensitive to drying, chemicals, and heat (as low as 42 degrees celsius).

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bacteriology of syphilis

-Spiral shaped spirochete (Treponema pallidum)

-gram negative, but does not have lipopolysaccharide (LPS)

-helical, thin (0.1 to 0.2 um), and long

-flagella are inserted into the periplasm and give it motility

-sensitive to drying, chemicals, and heat (as low as 42 degrees celsius)

Bacteriology of Syphilis
epidemiology of syphilis
Epidemiology of syphilis

How common?3rd most common STD

2006: > 36,000 cases of syphilis

Incidence of 1° & 2° syphilis highest in women aged 20-24 and men aged 35-39

2008: 63% of 1° & 2° syphilis infections involved MSM

2004-2008: syphilis rates increased greatest among men & women 15-24 y/o

more on syphilis
More on Syphilis

How do we spread it?Sexual contact: vaginal, oral, or anal

Spreads P-to-P via direct contact with a sore

Sore locations: external genitals, vagina, anus, rectum, lips, & mouth

Also, congenital infxn via transplacental transmission

Usually any time >20wks gestation

Spirochetes are capable of crossing placenta

The culprit?Treponema pallidum

in case you were wondering
In case you were wondering......

NOT transmitted through contact with:

Toilet seats

Doorknobs

Swimming pools

Hot tubs or bathtubs

Shared clothing

Eating utensils

virulence factors of syphilis
Virulence Factors of Syphilis
  • Induces inflammatory response
  • Adherence via membrane proteins
  • Coats itself with fibronectin
  • Secretes hyaluronidase
  • Motility & corkscrew shape
clinical manifestations syphillis
Clinical Manifestations- Syphillis

Primary Syphillis presents with a

PAINLESS CHANCRE!

http://img.medscape.com/pi/emed/ckb/infectious_diseases/211212-229461-152.jpg

painless chancre of syphillis
Painless Chancre of Syphillis

Photo: http://img.medscape.com/pi/emed/ckb/infectious_diseases/211212-1641801-229461-1949497.jpg

clinical manifestations syphillis1
Clinical Manifestations- Syphillis
  • Secondary Syphilis
  • Presents with Disseminated Disease with constitutional symptoms, maculopapular rash (that includes the PALMS and SOLES), condylomatalata.
  • Many treponemes are present in the condylomatalata of Secondary Syphilis (Treponemes and may be visualized through DARKFIELD MICROSCOPY.
    • “Teeming with spirochetes!”
  • Remember:
    • “Secondary Syphillis = Systemic”
    • Question: What other Disease presents with rash that includes the hands and feet?
secondary syphillis disseminated disease
Secondary Syphillis- Disseminated Disease

http://img.medscape.com/pi/emed/ckb/infectious_diseases/211212-229461-293.jpg

disseminated rash maculopapular of secondary syphillis
Disseminated Rash (maculopapular) of Secondary Syphillis

http://img.medscape.com/pi/emed/ckb/infectious_diseases/211212-1641801-229461-1949512.jpg

rash on palms and feet secondary syphilis
Rash on Palms and Feet- Secondary Syphilis

http://img.medscape.com/pi/emed/ckb/infectious_diseases/211212-229461-549.jpg

tertiary syphillis
Tertiary Syphillis
  • Gummas (chronic granulomas), aortitis (vasa vasorum destruction), neurosyphilis (tabes dorsalis), Argyll Robertson pupil.
  • NEUROSYPHILLIS has many manifestations
  • Signs: broad-based ataxia, positive Romberg, Charcot joint, stroke without hypertension.
gummas of tertiary syphilis
Gummas of Tertiary Syphilis

http://img.medscape.com/pi/emed/ckb/infectious_diseases/211212-229461-389.jpg

argyll robertson pupil associated with tertiary syphilis
Argyll Robertson Pupil- Associated with Tertiary Syphilis.
  • Argyll Robertson is the pupil that constricts with accommodation, but is not reactive to light.
  • aka “Prostitute’s pupil- it accommodates but does not react.”

http://1.bp.blogspot.com/_o3UvLBdaDQc/TGZa6gZOhsI/AAAAAAAAAAc/3GnIcWzYpaw/s1600/argyll+robertson+pupil-762395.jpg

congenital syphillis
Congenital Syphillis
  • Babies born with syphillis (infected in utero).
  • Saber shins, saddle nose, CN VIII Deafness, Hutchinson’s teeth, mulbery molars.

http://img.medscape.com/pi/emed/ckb/infectious_diseases/211212-229461-594.jpg

hutchinson teeth of congenital syphillis note notching
Hutchinson Teeth of Congenital Syphillis (note notching).

http://img.medscape.com/pi/emed/ckb/infectious_diseases/211212-229461-611.jpg

diagnosis
Diagnosis
  • Will not grow in culture
  • Microscopy of exudates to look for organisms
    • Darkfield
    • Direct fluorescent antibody staining
diagnosis1
Diagnosis
  • Serology
    • To detect antibodies to cardiolipin (nonspecific)
      • VDRL- (Venereal Disease Research Laboratory Test)
      • RPR- (Rapid Plasma Reagin) Test
    • Then test for treponemal antibodies
      • FTA-ABS (fluorescent treponemal antibody absorption)
      • MHA-TP- (microhemagglutination assay for treponema)
treatment
Treatment
  • DOC is Penicillin G
  • Can also use Ceftriaxone
  • If allergic to penicillin, can use Erythromycin or Doxycycline
  • Follow up at 3, 6, and 12 months with VDRL or RPR
bacteriology of chlamydia

-Obligate intracellular gram-negative bacteria

-pleomorphic and non-motile

-small in size (0.25 to 0.8 um in diameter), and have small chromosomes (1 – 1.2 megabases)

-”Energy Parasites”: Auxotropic for amino acids, and use host cell’s ATP

-Cell wall is unusual in that it lacks muramic acid

-Cannot be cultured in nutrient broth media or on agar plates

Bacteriology of Chlamydia
epidemiology of chlamydia
Epidemiology of Chlamydia

How common?#1 reported STD in U.S.

Highest infxn rates in Native & African Americans

2010: 1,307,893 reported infxns from 50 states

Many unreported cases d/t lack of sxs in many individuals

An estimated 2.8 million infxns occur in U.S. per year

Worldwide, an estimated 90 million new cases each year

Esp high infxn risk for sexually active teen girls d/t immaturity of cervix being more susceptible to infxn

epidemiology cont d
Epidemiology Cont'd

How do I get it?Vaginal, oral, or anal sex

Also transmitted during childbirth

More sexual partners = higher risk

Urethra = most common site for infxn in both men & women

Chlamydia trachomatis = MCC of acute urethral syndrome in women & MCC of nonspecific urethritis (NSU) in men

The leading preventable cause of infertility worldwide

N. gonorrhoeae coexists in 45% of cases

virulence factors of chlamydia
Virulence Factors of Chlamydia
  • Intracellular organism
  • Downregulates MHC-I
  • LPS
  • Prevent fusion of endosome with lysosome
  • Able to go into a persistent state
  • Nutrient up-take
  • Type 3 secretion system
chlamydia manifestations
Chlamydia manifestations
  • Chalamydia trachomatis causes reactive arthritis, conjunctivitis, nongonoccocal urethritis, and pelvic inflammatory disease (PID).

http://mshc.org.au/dnn/Portals/6/images/making_diag/urethral_discharge/ngu_discharge/chlamydial_urethritis.jpg

chlamydia in men
Chlamydia in men
  • Urethritis
  • Painful urination
  • Burning sensation upon urination
  • Discharge from penis
  • Red, inflamed urethra
  • Chlamydia is picked up easier in men because it is more noticeable.
chlamydia manifestations in women
Chlamydia manifestations in Women

http://www.sharinginhealth.ca/images/Chlamydia_trachomatis_speculum_SOA_Amsterdam.jpg & http://www.mdguidelines.com/images/Illustrations/pel_in_d.jpg

diagnosis and treatment
Diagnosis and Treatment
  • Doesn’t gram stain well but can gram stain urethral discharge to rule out gonorrhea
  • Fluorescent stained smear
  • Positive leukocyte esterase test on first-void urine
  • NAAT
  • Treatment-
    • Azithromycin (single dose) or Doxycycline (costs less, twice daily for 1 week)
bacteriology for n gonorrhea

-a facultative intracellular gram-negative diplococci,

-humans are the only reservoir

-Ferment glucose, but do not ferment maltose

-No polysaccharide capsule

-produce IgA proteases

Bacteriology for N. Gonorrhea
epidemiology of gonorrhea
Epidemiology of Gonorrhea

How common? 2nd most common venereal disease

2009: 301,174 reported cases

However, in U.S., it's estimated that >700,000 new infxns occur each year

Highest rates in sexually active teens, young adults, MSM, Hispanics & AAs

Worldwide, an estimated 62 million new cases each year

W/highest rates in sub-Saharan Africa, southeast Asia, the Caribbean, & Latin America

more gonorrhea epidemiology
More Gonorrhea Epidemiology

How are we spreading it?Contact w/infected penis, vagina, mouth, or anus

Pregnant female can transmit infxn to baby during delivery as well

Bacteria multiplies easily in warm, moist areas

Urethra = MC site for gonococcal infxn in both men & women

N. gonorrhoeae = MCC of septic arthritis in urban populations

Can lead to disseminated gonococcemia

More common in young women d/t C6-C9 deficiency

virulence factors of n gonorrhea
Virulence Factors of N. Gonorrhea
  • Pili
  • Opa proteins
  • Antigen variation/antigen phase variation
  • Porins
  • LOS
  • IgA protease
clinical manifestations n gonorrhoeae
Clinical Manifestations- N. gonorrhoeae
  • Causes
    • The STD Gonorrhea
      • aka “The Clap”
    • Septic Arthritis
    • Neonatal Conjunctivitis
    • PID
    • Fitz-Hugh-Curtis Syndrome
gonorrhea clinical manifestations
Gonorrhea Clinical Manifestations
  • Burning and pain while urinating
  • Increased urinary frequency or urgency
  • Discharge from the penis (white, yellow, or green in color)
  • Red or swollen opening of penis (urethra)
  • Tender or swollen testicles
  • Sore throat (gonococcal pharyngitis)

http://images.icanhascheezburger.com/completestore/2009/5/23/128875824687097628.jpg

gonorrhea clinical manifestations1
Gonorrhea Clinical Manifestations

http://stdpictures.org/_wp/wp-content/gallery/gonorrhea/male-gonorrhea.jpg

http://t0.gstatic.com/images?q=tbn:ANd9GcSMM3PMnX_rpuhUHUD4bg_Z6Ed3h9yqwh5W8jB53wNOJzDtwNPTioEo01TC

fitz hugh curtis syndrome
Fitz-Hugh-Curtis Syndrome
  • Fitz-Hugh-Curtis Syndrome is a complication of Pelvic Inflammatory Disease and can occur due to both Chlamydia and Gonorrhea
  • Note “Violin-String” appearance of chronic adhesions/fibrosis

http://img.medscape.com/pi/emed/ckb/obstetrics_gynecology/252558-1336972-256448-1810608.jpg

diagnosis2
Diagnosis
  • Nucleic acid amplification test (NAAT)- most sensitive
  • Culture on Thayer-Martin agar or chocolate agar
  • Gram stain male urethral specimens-shows intracellular gram negative diplococci
treatment1
Treatment
  • Current Recommendations:
    • Ceftriaxone or Cefixime PLUS Azithromycin or Doxycycline (for chlamydia infection)
  • Penicillin was the DOC but resistance to it and fluoroquinolones is growing
    • Mutation of fluoroquinolone binding sites on bacterial DNA gyrase and topoisomerase
    • Increased activity of efflux pumps or decreased membrane permeability
slide53

Q1: A 32y/o businessman comes into your office.  He was well until yesterday, when he admits he experienced dysuria accompanied by yellowish urethral discharge. He also admits that he had intercourse with a prostitute 5 nights ago. You perform a gram stain on a specimen of the discharge and see gram-negative diplococci within neutrophils.  Given this characteristic finding, you know right away that the most likely cause of this infection is?

  •             A: Neisseria gonorrhoeae
  •             B. Proteus mirabilis
  • C. Klebsiella pneumoniae
  •             D. Chlamydia trachomatis
  •             E. Treponema pallidum
question 1 explanation
Question 1 Explanation
  • Answer: (A).Neisseriae are gram-negative, oxidase-positive cocci that resemble paired kidney beans.  N. gonorrhoeae causes gonorrhea, neonatal conjunctivitis, & PID. Gonorrhea in men is characterized primarily by urethritis accompanied by dysuria and a purulent discharge. In women, infection is located primarily in the endocervix, causing a purulent vaginal discharge and intermenstrual bleeding (cervicitis).  The most common complication in women is ascending infection into the uterine tubes, causing salpingitis/PID, which can result in sterility or ectopic pregnancy.  Disseminated infections commonly manifest as arthritis, tenosynovitis, or pustules.  In men, the finding of gram-negative diplococci within PMNs is sufficient for diagnosis. In women, the use of gram stain alone can be difficult to interpret, so cultures should be done additionally.
  • T. pallidum is a spirochete, which is a thin-walled, flexible, spiral-shaped, motile rod. They are so thin that they are seen only by darkfield microscopy, silver impregnation, or immunofluorescence.
  • Chlamydiae are obligate intracellular bacteria, and thus, the gram stain is not useful. In men, C. trachomatis is a common cause of NGU, which may progress to epididymitis, prostatitis, or proctitis. In women, cervicitis develops and may progress to PID or salpingitis.
  • Source: Ex Master USMLE -style Question Bank
slide55

Q2: A 30-year-old, sexually active woman has had a mucopurulent vaginal discharge for 1 week. On pelvic examination, the cervix appears reddened around the os, but no erosions or mass lesions are present. A Pap smear shows numerous neutrophils, but no dysplastic cells. A cervical biopsy specimen shows marked follicular cervicitis. Which of the following infectious agents is most likely to produce these findings?

  • A. Chlamydia trachomatis
  • B. Candida albicans
  • C. Gardnerella vaginalis
  • D. HPV
  • E. Neisseria gonorrhoeae
  • F. Trichomonas vaginalis
question 2 explanation
Question 2 Explanation
  • Answer: (A)The redness of the cervix, the inflammatory cells in the cervical discharge, and the biopsy findings indicate that the patient has cervicitis. Chlamydia trachomatis is the most common cause of cervicitis in sexually active women. Candidiasis, gonorrhea, and trichomoniasis also are common. Candidiasis often produces a scant, white, curdlike vaginal discharge; gonorrhea may have an associated urethritis; and Trichomonas may produce a profuse homogeneous, frothy, and adherent yellow or green vaginal discharge. Gardnerella is found in bacterial vaginosis, a common condition caused by overgrowth of bacteria. Gardnerella infection produces a moderate, homogeneous, low-viscosity, adherent vaginal discharge that is white or gray and has a characteristic “fishy” odor; “clue” cells are seen on a wet mount. Herpetic infections are more likely to manifest as clear vesicles on the skin in the perineal region. Infection with human papillomavirus is associated with condylomata, dysplasias, and carcinoma.
  • Source: Robbins & Cotran Review of Pathology, 3rd ed, Ch.22- The Female Genital Tract
slide57

Q3:  A 73-year-old man who has had progressive dementia for the past 6 years dies of bronchopneumonia. Autopsy shows that the thoracic aorta has a dilated root and arch, giving the intimal surface a “tree-bark” appearance. Microscopic examination of the aorta shows an obliterative endarteritis of the vasa vasorum. Which of the following laboratory findings is most likely to be recorded in this patient's medicalhistory?

  •        A. High double-stranded DNA titer       B. P-ANCA positive 1:1024       C. Sedimentation rate 105 mm/hr       D. Ketonuria 4+       E. Antibodies against Treponema pallidum
question 3 explanation
Question 3 Explanation
  • Answer:  (E) This description is most suggestive of syphiliticaortitis, a complication of tertiary syphilis, with characteristicinvolvement of the thoracic aorta. Obliterative endarteritis is not afeature of other forms of vasculitis. High-titer doublestranded DNAantibodies are diagnostic of systemic lupus erythematosus, and a testresult for P-ANCA is positive in various vasculitides, includingmicroscopic polyangiitis. A high sedimentation rate is a nonspecificmarker of inflammatory diseases. Ketonuria can occur in individualswith diabetic ketoacidosis.
  • Source: Robbins & Cotran Review of Pathology, 3rd ed, Ch.11-Blood Vessels
slide59

Q4:  A sexually active, 26-year-old man has had pain on urination for the past 4 days. On physical examination, there are no lesions on the penis. He is afebrile. Urinalysis shows no blood, ketones, protein, or glucose. Microscopic examination of the urine shows few WBCs and no casts or crystals. What infectious agent is most likely to produce these findings?

  •                 A. Chlamydia trachomatis
  •                 B. Mycobacterium tuberculosis
  •                 C. Herpes simplex virus
  •                 D. Candida albicans
  • E. Treponema pallidum
question 4 explanation
Question 4 Explanation
  • Answer: (A)This patient has urethritis. The most common cause of nongonococcal urethritis in men is Chlamydia trachomatis. The condition is a nuisance; however, the behavior that led to the infection can place the patient at risk of other sexually transmitted diseases. Tuberculosis of the urinary tract is uncommon. Herpes simplex can produce painful vesicles on the skin. Candida infections typically occur in immunocompromised patients or in patients receiving long-term antibiotic therapy. A syphilitic chancre on the penis is an indicator of Treponema pallidum infection.
  • Source: Robbins & Cotran Review of Pathology, 3rd ed, Ch.20- The Kidney
slide61

Q5: A 20-year-old man who has multiple sexual partners and does not use barrier precautions comes to the physician complaining of a nontender ulcer on the penis that has been present for 1 week. On physical examination, the 0.6-cm lesion has a firm, erythematous base and sharply demarcated borders. The lesion is scraped, and darkfield examination is positive for spirochetes consistent with Treponema pallidum. Which of the following is most likely to be seen microscopically in the biopsy specimen?

  • A. Granulomatous inflammation with suppuration
  • B. Granulomatous inflammation with caseation
  • C. Acute inflammation with abscess formation
  • D. Perivascular inflammation with plasma cells
  • E. Gummatous inflammation
question 5 explanation
Question 5 Explanation
  • Answer:(D) Syphilitic chancres occur in the primary stage of syphilis and are characterized by lymphoplasmacytic infiltrates and by an obliterative endarteritis. Similar lesions also may appear with secondary syphilitic mucocutaneous lesions. Suppurative granulomas are typical of cat-scratch disease. Caseating granulomatous inflammation is more characteristic of tuberculosis or fungal infections. Acute inflammation with abscess formation is characteristic of bacterial infections such as gonorrhea. Gummatous inflammation can be seen in adults with tertiary syphilis or in congenital syphilis.
  • Source: Robbins & Cotran Review of Pathology, 3rd ed, Ch.8-Infectious Diseases