Sexually Transmitted Infections

1. Sexually Transmitted Infections Maggie Dougherty, MSII

2. Learning Objectives • High risk behavior • Papillomavirus • HBV • Retroviruses • HSV2 • Bacterial • Yeast

3. High-Risk Behavior • Having unprotected sex • Having multiple partners • Early age of sexual onset • Alcohol/illicit drug use • Trading sex for money/drugs • Having an STI

4. Viral STIs • Human papillomavirus • Hepatitis B • Herpes Simplex Virus 2 • Retroviruses

5. Human Papillomavirus • Papilloma = wart-like growth on the skin or mucous membrane • Papillomaviruses are double-stranded DNA viruses • Estimated that 75-80% of sexually active adults will acquire a genital tract HPV infection before the age of 50

6. Human Papillomavirus and Malignancy • HPV has been associated with the development of a variety of anogenital cancers, notably cervical cancer • 5.2% of cancers worldwide attributed to HPV infection • Over 40 HPV types • Split into “high-risk” and “low-risk” genotypes • HPV 16 and 18 are the most common genotypes seen in cancer • Viral oncogenes E6 and E7 act to immortalize epithelial cells

7. Prevention of Cervical Cancer • Pap smear • Mortality from cervical cancer plunged after screening was introduced • Of women with cervical cancer: • 50% have never had a Pap test • 15% have not been screened in the prior 5 years Sawaya GF. N Engl J Med. 2009 Dec 24;361(26):2503-5. Obstet Gynecol. 2009 Dec;114(6):1409-20.

8. Pap Smear

9. Prevention of Cervical Cancer • Vaccines • Gardasil • Recommended for females 11 through 26 years of age and males 9 through 26 years of age • Protects against HPV types 6, 11, 16, and 18 • Cervarix • Recommended for females 10 through 25 years of age • Protects against HPV types 16 and 18

10. Hepatitis B • Hepatitis = inflammation of the liver • Circular double-stranded DNA • One strand is incomplete • 5-10% develop chronic hepatitis

11. Hepatitis B • Transmitted through: • Sexual contact • Sharing needles • Contact with open wounds or blood • Vaccination • Hepatitis B surface antigen (HBsAg)

12. Hepatocellular Carcinoma • 90% of liver cancer • 4-5% of all human cancer • Most significant risk factors of HCC in the US: • Chronic hepatitis B or C infection • Heavy alcohol consumption • Diabetes mellitus (type 2) • Cigarette smoking • Family history of liver cancer

13. Human Immunodeficiency Virus • Responsible for the development of Acquired Immune Deficiency Syndrome (AIDS) • Being HIV positive is NOT the same as having AIDS • HIV/AIDS is a global pandemic • Brief history of HIV in the US: • A number of cases of Kaposi’s sarcoma and opportunistic infections in gay men and IV drug users catches the attention of the CDC in 1981 • Virus discovered in 1983 • Blood test developed in 1985 • AZT clinical trials in 1986

14. HIV/AIDS Pandemic

15. HIV/AIDS Pandemic

16. Transmission of HIV • Unprotected sexual contact • Direct blood contact • Needle sharing, blood transfusions, accidents in healthcare settings • Mother to baby • Before or during birth, in breast milk • Non-infectious bodily fluids: • Saliva • Sweat • Urine • Feces • Tears

17. HIV Life Cycle • Positive-stranded RNA virus • Entry of HIV into host cell requires two host proteins: • CD4 • Chemokine receptor (CCR5 or CXCR4) • Reverse transcription • Integration • Integrase • Provirus • Transcription • Assembly • Protease • Budding

18. Stages of HIV Infection • Acute infection • 50-70% of patients • Self-limited mononucleosis-like illness • Chronic phase/clinical latency • Asymptomatic • Large amounts of HIV-1 are produced at this time • Advanced HIV disease and AIDS

19. HIV Immunopathogenesis • Broad immunodeficiency with CD4 cell depletion • Mechanisms of CD4 cell depletion • Direct killing by virus • Killing of infected CD4 cells by cytotoxic lymphocytes • Decreased production (over time) • Changes to lymph node architecture • Apoptosis • HIV progression typically measured by T cell count and/or viral load

20. CD4 Cell Count and Viral Load in HIV

21. AIDS • HIV infection plus either/or: • An AIDS-defining complication • CD4 count < 200 copies/mL at least once • Risk of AIDS-defining complications varies with degree of immunodeficiency • Measured by the CD4 count

22. Treatment of HIV Infection • Highly active antiretroviral therapy (HAART) • A few different classes based on mechanism of action: • Nucleoside reverse transcriptase inhibitors • Non-nucleoside reverse transcriptase inhibitors • Protease inhibitors • Fusion inhibitors • Integrase inhibitors • CCR5 inhibitors • Major goal of therapy is to achieve an undetectable viral load within six months of initiation of treatment

23. Herpes Simplex Virus-2 • HSV-2 normally causes genital herpes • Can be spread whether infection is active or not • dsDNA virus

24. HSV-2 Latency • Herpes = from the Greek meaning “to creep” • Primary infection may be severe and last for three week • Recurrences from latent infection are common and may be mild • Latency is established in the neuron

25. Chlamydia • Caused by Chlamydia trachomatis • Gram-negative • Obligate intracellular pathogen • Most frequently reported bacterial STI in the US • Estimated 2.3 million US citizens ages 14-39 are infected • Transmission: • Vaginal, anal, and oral sex

26. Chlamydia • C. trachomatislacks mechanisms for the production of metabolic energy • Elementary bodies • Smaller • Condensed DNA • Infectious particle • Reticulate bodies • Larger (x2) • Intracellular • Dispersed DNA • Non-infectious

27. Clinical Manifestations of Chlamydia • 75% of infected women and 50% of infected men are asymptomatic • Symptoms appear 1-3 weeks after exposure

28. LymphogranulomaVenereum • Caused by Chlamydia trachomatis • Three stages • Primary infection • Genital ulcer or mucosal inflammatory reaction • Lesions spontaneously heal • Secondary infection • 2-6 weeks after primary infection • Infection extends to regional lymph nodes • Severe inflammation and invasive infection • Often systemic symptoms • Late LGV

29. Gonorrhea • Caused byNeisseriagonorrhoeae • Gram-negative diplococci

30. Pelvic Inflammatory DIsease • Caused by infection of the upper reproductive structures in women • Uterus, fallopian tubes, and ovaries • Inflammatory repair process leads to deposition of scar tissue • Narrowing of the lumen in the tubes or closing them completely • May lead to infertility • Chlamydia trachomatisand Neisseriagonnorrhoeaeare the top two leading causes of PID

31. Candidiasis • Vaginal yeast infection • May be sexually transmitted • Especially through oral-genital sexual contact • Not actually considered an STI • Usually caused by Candida albicans • Diploid fungus • Normally present in the vagina • Lactobacillus also normally present in the vagina • Produces acid • Disruption of bacteria-yeast balance can result in an overgrowth of yeast

32. Clinical Manifestations and Treatment of Vaginal Candidiasis • Clinical manifestations • Itching and irritation • Burning sensation • Redness and swelling • Vaginal pain and soreness • Thick, white, odor-free vaginal discharge • Miconazole • Topical • Inhibits synthesis of ergosterol • Component of the fungal cell wall

33. Summary • High-risk behavior is any activity that increases risk of contracting an STI • Some STIs may cause cancer • Important characteristics of HIV including reverse transcription, DNA integration, and immunosuppression • HAART has significantly improved life expectancy of HIV positive individuals • HSV-2 establishes latent infection in nerves • Chlamydia and gonorrhea may be asymptomatic, but can lead to PID and infertility • Vaginal yeast infections may a side effect of antibiotic use