STDs – Etiology and Symptoms

1. STDs – Etiology and Symptoms HPV Gonorrhea Genital Herpes Chlamydia Trichomoniasis Hepatitis B Syphilis AIDS

2. HPV • Double-stranded DNA virus that belongs to the Papovaviridae family • Small and non-enveloped virions • Over 100 characterized types • Genital types have specific tropism (affinity) for genital skin and mucosa. • Very limited animal models and no widely available system for in vitro cultivation • Infection is identified by the detection of HPV DNA or capsid protein. Types are distinguished by different DNA sequences (>10% difference) at L1 capsid (surface) protein.

3. HPV, cont’d • Genital HPV types are generally characterized in terms of their oncogenic potential (ability to cause cervical cancer). • Low-risk types • Associated with genital warts and benign or low-grade cervical cell changes (mild Pap test abnormalities). • Most visible genital warts are caused by HPV types 6 and 11. • Recurrent respiratory papillomatosis, a rare condition, is usually associated with HPV types 6 and 11. • High-risk types • Associated with low grade cervical cell changes, high-grade cervical cell changes that are precursors to cancer (moderate to severe Pap test abnormalities), and, in rare cases, anogenital (i.e., cervix, vulva, anus, and penis) cancers. • HPV types 16 and 18 account for more than half of HPV types found in anogenital cancers. • Most women infected with high-risk HPV types have normal Pap test results and never develop precancerous (high-grade) cervical cell changes or cervical cancer.

4. HPV Symptoms • In most cases genital HPV infection is transient and has no clinical manifestations or sequelae. • Clinical manifestations of genital HPV infection include: • Genital warts • Cervical cell abnormalities • Anogenital squamous cell cancers • Recurrent respiratory papillomatosis • The two most common clinically significant manifestations of genital HPV infection are: • Genital warts that are visualized without magnification • Cervical cell abnormalities that are detected by Pap test screening (with or without HPV DNA testing) or colposcopy

5. Vulvar Warts Source: Reprinted with permission of Gordon D. Davis, MD.

6. Penile Warts Source: Cincinnati STD/HIV Prevention Training Center

7. Gonorrhea • Microbiology • Etiologic agent is Neisseria gonorrhoeae • Gram-negative intracellular diplococcus, oxidase-positive, utilizes glucose, but not sucrose, maltose, or lactose. Infects mucus-secreting epithelial cells. • Divides by binary fission (every 20-30 minutes) • Pathology • N. gonorrhoeae attaches to different types of mucus-secreting epithelial cells via a number of structures located on the surface of gonococci. • N. gonorrhoeae has ability to alter these surface structures, which helps the organism evade an effective host response. • N. gonorrhoeae employs several mechanisms to disarm the complement system, which may result in a survival advantage in the human host.

8. Clinical Symptoms • Urogenital, pharyngeal, and rectal infections in males and females • Conjunctivitis in adults and neonates. • If untreated, gonorrhea is a major cause of pelvic inflammatory disease (PID), tubal infertility, ectopic pregnancy, and chronic pelvic pain.

9. Cervicitis/Urethritis • Cervicitis (50% of women have no symptoms) • Symptoms: may be nonspecific such as abnormal vaginal discharge, intermenstrual bleeding, dysuria, lower abdominal pain, or dyspareunia • Clinical findings: may exhibit mucopurulent or purulent cervical discharge and easily induced cervical bleeding • Incubation period unclear, but symptoms may occur within 10 days of infection • Urethritis (most women asymptomatic) • Symptoms: dysuria (difficulty in urination) • 40%-60% of women with cervical gonococcal infection may have urethral infection

10. Clinical Manifestations Gonococcal Cervicitis Source: CDC/NCHSTP/Division of STD Prevention, STD Clinical Slides

11. Urethritis/Epididymitis • Urethritis • Most male patients develop overt, symptomatic urethritis. • Symptoms: typically purulent or mucopurulent urethral discharge often accompanied by dysuria • Clinical presentation: purulent or mucopurulent urethral discharge is common, but discharge may be clear or cloudy • Asymptomatic (unrecognized) infection may occur in approximately 10% of male cases. Asymptomatic gonorrhea may act as a reservoir in the community that perpetuates transmission from men to women. • Incubation period: usually 1-14 days for symptomatic disease. Most become symptomatic in 2-5 days after exposure. • Epididymitis • Symptoms: unilateral testicular pain and swelling • Infrequent, but most common local complication of gonorrhea infection in males • Usually associated with overt or subclinical urethritis • Can result in infertility due to blockage

12. Gonococcal Urethritis: Purulent Discharge Source: Seattle STD/HIV Prevention Training Center at the University of Washington: Connie Celum and Walter Stamm

13. Swollen or Tender Testicles (Epididymitis) Source: Seattle STD/HIV Prevention Training Center at the University of Washington

14. HSV – Herpes Simplex Virus • Genital herpes is a recurrent, lifelong viral infection. • Two HSV serotypes – HSV-1 & HSV-2; most genital symptoms due to HSV-2, but also possible with HSV-1 • 50% or more of new cases are asymptomatic or unrecognized.

15. Epidemiology Transmission • HSV-2 is transmitted sexually and perinatally. • Most sexual transmission occurs while source case is asymptomatic. • Efficiency of sexual transmission is greater from men to women than from women to men.

16. Transmission, cont’d • Likelihood of transmission to others declines with increased duration of infection. • Incubation period after acquisition is 2-12 days (average is 4 days). • Genital HSV-2 infection facilitates both acquisition and transmission of HIV infection.

17. HSV - Etiology • HSV-1 and HSV-2 are members of the human herpes viruses (herpetoviridae) that includes EBV and CMV. • HSV-1 and HSV-2 are double-stranded DNA viruses surrounded by an envelope of lipid glycoprotein. • 50% DNA homology exists between HSV-1 and HSV-2. • All members of this species establish latent infection in specific target cells (for HSV, this would be CNS cells, specifically, ganglia of peripheral nerves). • Infection persists despite the host immune response, often with recurrent disease.

18. Etiology, cont’d • The virus remains latent indefinitely. • Precipitation of viral replication due multiple known and unknown factors (eg., trauma, fever, stress) • The re-activated virus may cause a cutaneous outbreak of herpetic lesions. • Up to 90% of persons seropositive for HSV-2 antibody have no clinical history of anogenital herpes outbreaks.

19. Signs and Symptoms • First outbreak characterized by multiple lesions that are more severe, last longer, and have higher titers of virus than recurrent infections • Lesion progression: • papules  vesicles  pustules  ulcers  crusts  healed • Illness lasts 2-4 weeks • Often associated with systemic symptoms including fever, headache, malaise

20. Signs and Symptoms, cont’d • Local symptoms include pain, itching, dysuria, vaginal or urethral discharge, and tender inguinal lymph node swelling • Numerous, bilateral painful genital lesions; last an average of 11-12 days • Median duration of viral shedding (from the onset of lesions to the last positive culture) is ~12 days • HSV cervicitis occurs in most primary HSV-2 (~90%) and primary HSV-1 (~70%) infections

21. HSV Diagnosis • Clinical diagnosis is insensitive and nonspecific. Lesions may or may not be present, must be confirmed as to origin • Clinical diagnosis should be confirmed by lab testing: • Virologic tests (viral culture from lesions) • Type-specific serologic tests (to differentiate between HSV 1 and HSV 2) • Acyclovir (antiviral) = Recommended therapy (no cure, but decreases symptom duration and quantity of viral shedding)

22. Clinical Manifestations Herpes: Genitalis Clinical Periurethal Lesions on Vestibule Source: Cincinnati STD/HIV Prevention Training Center

23. Clinical Manifestations Herpes: Primary Complex Source: Cincinnati STD/HIV Prevention Training Center

24. Chlamydia • C. trachomatis is an obligate intracellular bacterium with a Gram-negative-like cell wall. • C. trachomatis infects columnar epithelial cells of cervix or urethra • C. trachomatis survives by replication that results in the death of the cell. (Alternative modes of replication and persistence of organisms are important research topics.) • Chlamydia takes 2 forms in the cycle: elementary body (EB) and reticulate body (RB). Life cycle ~ 72 hrs

26. Clinical Manifestations Men Women Infants Clinical Syndromes Caused by C. trachomatis

27. Clinical Manifestations C. trachomatis Infection in Men • Urethritis– • Majority (>50%) asymptomatic • Symptoms/signs if present: mucoid or clear urethral discharge, dysuria • Incubation period unknown (probably 5-10 days in symptomatic infection) • Epididymitis • Reiter’s Syndrome

28. C.trachomatis Urethritis: Mucoid Discharge Source: Seattle STD/HIV Prevention Training Center at the University of Washington/UW HSCER Slide Bank

29. Clinical Manifestations Swollen or tender testicles (epididymitis) Source: Seattle STD/HIV Prevention Training Center at the University of Washington

30. Clinical Manifestations C. trachomatis Infections in Women • Cervicitis • Majority (70%-80%) are asymptomatic • Local signs of infection, when present, include: • Mucopurulent endocervical discharge • Edematous cervical ectopy with erythema and friability • Urethritis • Usually asymptomatic • Signs/symptoms, when present, include dysuria, frequency, pyuria

31. Sequelae, female • Pelvic Inflammatory Disease (PID)–an acute clinical syndrome associated with ascending spread of microorganisms from the vagina or cervix to the endometrium, fallopian tubes, ovaries, and contiguous structures. • PID is defined as any combination of endometritis, salpingitis, tubo-ovarian abscess, or pelvic peritonitis. • Signs and symptoms when present: lower abdominal pain, cervical motion tenderness, and uterine tenderness on pelvic exam. • A substantial proportion of chlamydia-associated PID is clinically silent, but still results in tubal scarring which may lead to infertility and ectopic pregnancy. • It is estimated that up to 40% of women with untreated C. trachomatis infection will develop PID. Of those with PID, 20% will become infertile, 18% will experience debilitating chronic pelvic pain, and 9% will have a life-threatening ectopic pregnancy. • Endometritis (inflammation of the endometrium) • Salpingitis (inflammation of the fallopian tubes) • Perihepatitis (Fitz-Hugh-Curtis syndrome)

32. Clinical Manifestations Normal Cervix Source: STD/HIV Prevention Training Center at the University of Washington/Claire E. Stevens

33. Clinical Manifestations Chlamydial Cervicitis Source: STD/HIV Prevention Training Center at the University of Washington/Connie Celum and Walter Stamm

34. Clinical Manifestations Normal Human Fallopian Tube Tissue Source: Patton, D.L. University of Washington, Seattle, Washington

35. Clinical Manifestations C. trachomatis Infection (PID) Source: Patton, D.L. University of Washington, Seattle, Washington

36. Clinical Manifestations Acute Salpingitis Source: Cincinnati STD/HIV Prevention Training Center

37. Trichomonis vaginalis • Protozoan parasite • Anaerobic, lack mitochondria, must adhere to host epithelium to survive • No cyst enclosed form, but may survive 1-2 hrs on moist surfaces (thus, toilet seat transfer possible, but not likely)

38. Trichomonas vaginalis resides in the female lower genital tract and the male urethra and prostate   , where it replicates by binary fission   .  The parasite does not appear to have a cyst form, and does not survive well in the external environment.  Trichomonas vaginalis is transmitted among humans, its only known host, primarily by sexual intercourse   .

39. Symptoms - Female • Often asymptomatic • When symptomatic – • Foul smelling or frothy green discharge from the vagina, vaginal itching or redness. • Other symptoms can include painful sexual intercourse, lower abdominal discomfort, and the urge to urinate. • Much more common in women than in men; transmitted male to female, female to female (vulvar contact); 5-28 days post exposure

40. Symptoms - Male • Often asymptomatic • May have painful urination, discharge from urethra • Symptoms (and transmission) less in males than in females • Female to male transmission most likely

41. Sequelae • Untreated female, may lead to abdominal pain, PID, pregnancy complication • Untreated male, may lead to epididymitis, prostatitis, infertility • Treated – no complications

42. Diagnosis and Treatment • Verified only by presence of parasite • Microscopic observation diagnostic, but relatively imprecise. Can be cultured in vitro to verify in cases of low parasite numbers • Treatment = Metronidazole (although resistance has been reported in literature) • No host immunity possible, therefore re-infection problematic • Increases risks of HIV transmission by increasing numbers of lymphocytes in genital tract (these cells are susceptible to HIV infection). Effusion in relation to this parasite may also increase rates of HIV shedding

43. AIDS • Single Stranded RNA virus • Incapable of long-term survival outside the host • Encapsulated virus – host specific

44. Figure 14.AIDS_01

46. AIDS Timecourse

49. Syphilis - Treponema pallidum on darkfield

50. Syphilis – Signs and symptoms • Chancre – appearing at site of infection • 1o, 2o, 3o • Treated – Curable • Untreated – May lead to dementia and death