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Syphilis. Bacteriology of Syphilis -Spiral shaped spirochete (Treponema pallidum) -gram negative, but does not have lipopolysaccharide (LPS) -helical,

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Presentation on theme: "Syphilis. Bacteriology of Syphilis -Spiral shaped spirochete (Treponema pallidum) -gram negative, but does not have lipopolysaccharide (LPS) -helical,"— Presentation transcript:

1 Syphilis

2 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)

3 Epidemiology of syphilis How common? 3 rd most common STD 2006: > 36,000 cases of syphilis Incidence of 1° & 2° syphilis highest in women aged and men aged : 63% of 1° & 2° syphilis infections involved MSM : syphilis rates increased greatest among men & women y/o



6 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

7 In case you were wondering NOT transmitted through contact with : Toilet seats Doorknobs Swimming pools Hot tubs or bathtubs Shared clothing Eating utensils

8 Pathogenesis of Syphilis


10 Virulence Factors of Syphilis Induces inflammatory response Adherence via membrane proteins Coats itself with fibronectin Secretes hyaluronidase Motility & corkscrew shape

11 Clinical Manifestations- Syphillis Primary Syphillis presents with a PAINLESS CHANCRE! 152.jpg

12 Painless Chancre of Syphillis Photo: jpg jpg

13 Clinical Manifestations- Syphillis Secondary Syphilis Presents with Disseminated Disease with constitutional symptoms, maculopapular rash (that includes the PALMS and SOLES), condylomata lata. Many treponemes are present in the condylomata lata 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?

14 Secondary Syphillis- Disseminated Disease

15 Disseminated Rash (maculopapular) of Secondary Syphillis jpg

16 Rash on Palms and Feet- Secondary Syphilis

17 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.

18 Gummas of Tertiary Syphilis 389.jpg

19 Argyll Robertson Pupil- Associated with Tertiary Syphilis. Argyll Robertson is the pupil that constricts with accommodation, but is not reactive to light. aka Prostitutes pupil- it accommodates but does not react. Ypaw/s1600/argyll+robertson+pupil jpg

20 Congenital Syphillis Babies born with syphillis (infected in utero). Saber shins, saddle nose, CN VIII Deafness, Hutchinsons teeth, mulbery molars.

21 Hutchinson Teeth of Congenital Syphillis (note notching).

22 Diagnosis Will not grow in culture Microscopy of exudates to look for organisms Darkfield Direct fluorescent antibody staining

23 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)

24 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

25 Chlamydia

26 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 cells ATP -Cell wall is unusual in that it lacks muramic acid -Cannot be cultured in nutrient broth media or on agar plates

27 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

28 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




32 Pathogenesis of Chlamydia

33 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

34 Chlamydia manifestations Chalamydia trachomatis causes reactive arthritis, conjunctivitis, nongonoccocal urethritis, and pelvic inflammatory disease (PID). _discharge/chlamydial_urethritis.jpg

35 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.

36 Chlamydia manifestations in Women rdam.jpg rdam.jpg &

37 Diagnosis and Treatment Doesnt 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)

38 Neisseria Gonorrhea

39 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

40 Epidemiology of Gonorrhea How common? 2 nd 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

41 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



44 Pathogenesis of N. Gonorrhea

45 Virulence Factors of N. Gonorrhea Pili Opa proteins Antigen variation/antigen phase variation Porins LOS IgA protease

46 Clinical Manifestations- N. gonorrhoeae Causes The STD Gonorrhea aka The Clap Septic Arthritis Neonatal Conjunctivitis PID Fitz-Hugh-Curtis Syndrome

47 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) jpg

48 Gonorrhea Clinical Manifestations qwh5W8jB53wNOJzDtwNPTioEo01TC

49 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 jpg

50 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

51 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

52 Review Questions

53 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

54 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

55 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

56 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, 3 rd ed, Ch.22- The Female Genital Tract

57 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 medical history? 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

58 Question 3 Explanation Answer: (E) This description is most suggestive of syphilitic aortitis, a complication of tertiary syphilis, with characteristic involvement of the thoracic aorta. Obliterative endarteritis is not a feature of other forms of vasculitis. High-titer doublestranded DNA antibodies are diagnostic of systemic lupus erythematosus, and a test result for P-ANCA is positive in various vasculitides, including microscopic polyangiitis. A high sedimentation rate is a nonspecific marker of inflammatory diseases. Ketonuria can occur in individuals with diabetic ketoacidosis. Source: Robbins & Cotran Review of Pathology, 3rd ed, Ch.11-Blood Vessels

59 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

60 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, 3 rd ed, Ch.20- The Kidney

61 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

62 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, 3 rd ed, Ch.8- Infectious Diseases

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