Microbiology of Sexually Transmitted Infections

Microbiology of Sexually Transmitted Infections

1. Microbiology of Sexually Transmitted Infections Dr. Hany Lotfy Ass. Professor of Medical Microbiology and Immunology Sulaiman Al Rajhi University

2. OUTLINE Epidemiology of STIs. Causative agents of STIs. Bacterial causes of STIs. Chlamydia. Gonorrhea. Syphilis. Chancroid. Viral causes. Herpes Simplex Virus (HSV-II). Human papillomavirus (HPV). Hepatitis B virus. Human immunodeficiency virus (HIV). Protozoal causes. Trichomonas. Ecto -parasite: Scabies. Pubic louse. Quiz. Photo Gallery.

3. STIs or STDs? STIs: Infections acquired through sexual intercourse (may be symptomatic or asymptomatic) STDs: Symptomatic disease acquired after STI. STI is the most commonly used term because it applies to both symptomatic and asymptomatic infections Previously known as Venereal Diseases ( VDs).

4. STIs May be caused by bacteria, viruses, protozoa, or parasites. Some are curable, some are not. Mother-to-child transmission of STIs can result in stillbirth, neonatal death, low-birth weight, prematurity , sepsis, neonatal conjunctivitis, systemic infections, and congenital deformities. If left untreated, STIs can cause infertility , cancer and sometimes, death.

5. Epidemiology of STIs STIs are very common. The reasons for this increase include : Increasing density and mobility of human populations. The c hanges in human sexual behavior. The absence of vaccines for almost all STIs, except for the HBV and HPV. More than 1 million STIs are acquired every day worldwide. World : ~ 3.2 million teenagers are infected with STIs each year. USA: Most of the STIs diagnosed in the US occur among people under 25 years. About 25 % of US population acquired single STI by the age 35. There are 22.4 million new cases of STI in the US every year. The medical costs for these new cases are $17 billion.

6. Incident cases of Chlamydia , Gonorrhea, Trichomoniasis and Syphilis in 2020

7. Rates of reported Chlamydia cases by age group and sex in the United States, 2021 Age Distribution of STIs

8. Why this high prevalence? Absence of religious faith. Multiple sexual partners. U nprotected sex. Use of oral contraceptives. Limited access to health care. Practitioners don’t ask questions about patients’ sexual behaviors. Some infections have no obvious symptoms. Difficulty talking to partner.

9. Determinants of STIs prevalence

10. I. Bacterial infections Chlamydia. Gonorrhea. Non-Gonococcal Urethritis (NGU). Syphilis. Chancroid .

11. 1. Chlamydiasis Caused by: Chlamydia trachomatis. Obligatory intracellular organism, has a specific life cycle. Prevalence: The most common bacterial STI in the US. 2-3 million new cases per year. Transmission: Penile-vaginal , oral-genital, oral-anal, or genital-anal contact; can also be spread by fingers from one body site to another. Symptoms: In majority of cases, none. Women: mild irritation, itching , dysuria, slight vaginal discharge. Men: urethral discharge, burning urination.

12. The life cycle of Chlamydia . ( Black circle: elementary body; White circle: reticulate body)

13. Women: Pelvic Inflammatory Disease (PID) Infection spreads from cervix → fallopian tubes → ovaries. Scar tissue from PID can block fallopian tubes and causes infertility or ectopic pregnancy. Men: Epididymitis or urethritis. Both sexes: Reiter’s syndrome (reactive arthritis + urethritis + conjunctivitis). Complications:

14. Diagnosis: 1. Specimens: Scrapings from urogenital tract, urethral, cervical exudates etc. 2. Microscopic examination: Chlamydia can not be stained by Gram stain. Inclusion bodies in the scraped cells are detected with Giemsa stain . 3. Tissue Culture: On McCoy cells, typical cytoplasmic inclusions. Yolk sac of embryonated egg. 4. Serological tests: Detection of chlamydial Ag in a specimen (Direct immunofluorescence). Detection of anti-Chlamydia antibodies (IgM and I gG) in serum ( ELISA). 5. Molecular: PCR.

15. Treatment: 7-day treatment of doxycycline OR one dose of azithromycin. All exposed sexual partners should be treated. Patients should abstain from sexual intercourse until 7 days after their partner has completed treatment.

16. 2. Gonorrhea Caused by: Neisseria gonorrheae (Gram-negative diplococci ). Prevalence: ~700,000 new cases / year in US. Transmission: Penile-vaginal, oral-genital, oral-anal, or genital-anal. Symptoms: Male: Early: Profuse penile discharge, burning urination. Late: Morning drop. Female: Usually go undetected. M ild discharge, Burning urination.

17. Complications: Women: PID: more severe than Chlamydial infection. Ectopic pregnancy. Infertility. Men: Prostatitis, epididymitis. Possible sterility due to scar tissue in epididymis. Both sexes: Disseminated Gonorrhea: Can spread through blood (2 % of cases), causing fever, arthritis, synovitis, endocarditis, pharyngitis, meningitis. Ophthalmia neonatorum : Blindness in infants of infected mothers.

18. Lab Diagnosis : Clinically. Sample: urethral discharge, or cervical swab. Gram stain: Pus cells with Gram-negative intracellular and extracellular diplococci. Culture: on chocolate agar, or selective media ( Thayer-Martin). PCR.

19. Treatment: Often, Chlamydia accompanies gonorrhea infection, [dual therapy of 2 antibiotic regimens will treat both infections ]. Ceftriaxone + Doxycycline . Antimicrobial resistance of N. gonorrheae to antibiotics (azithromycin) has increased rapidly in recent years. All exposed sexual partners should be treated . Patients should abstain from sexual intercourse until 7 days after their partner has completed treatment.

20. 3. Non- Gonococcal Urethritis = Any urethral inflammation not caused by gonorrhea Etiology: A. Infection: Chlamydia trachomatis. Ureaplasma urealyticum . Mycoplasma. Trichomonas vaginalis. Gardenerella vaginalis. Viral: herpes simplex virus, Adenovirus. B . Non-infectious: Allergic reactions to vaginal secretions. Irritation from soaps, contraceptives, or deodorant sprays. Traumatic: catheter. Symptoms : Men: penile discharge, burning urination. 1/3 of patients can develop Reiter syndrome. Women: Mild itching, burning urination, vaginal discharge of pus and PID.

21. 4. Syphilis Caused by: Treponema pallidum. Prevalence: ~700,000 new cases / year in US. Transmission: Penile-vaginal, oral-genital, oral-anal, or genital-anal contact Symptoms: 1. Primary syphilis : P ainless sore (chancre) Women: on inner vaginal walls or cervix, labia… Men: glans of penis, shaft, or scrotum Other sites: on lips or tongue or in rectum/anus.

22. 2. Secondary syphilis: Skin rash. Often on palms, soles: not itching. Person may feel flu-like symptoms . Generalized lymphadenopathy. If not treated, symptoms will subside, but disease is not eliminated. 3. Latent syphilis: No symptoms; no longer contagious after 1 year of latent stage (except pregnant woman to fetus – at all stages). 4. Tertiary syphilis ( Gumma ): Severe symptoms anywhere; such as heart, blindness, paralysis, liver damage, mental disturbance, death.

23. Diagnosis: 1. Sample : Exudate from 1ry chancer or LN. Not stained by Gram. Organisms on microscopy using dark field microscope. Could be stained by Fontana’s stain. Stained with fluorescein-labelled anti-treponemal Ab, and examined by fluorescent microscope. Treponema by Fontana’s stain Treponema by dark field microscope

24. 2. Serology: Non-specific (Non- treponemal ) tests: Venereal Disease Research Laboratory (VDRL). Rapid Plasma Reagin (RPR). Specific ( Treponemal ) Test: Fluorescent Treponemal Antibody (FTA). Treponema pallidum Haemagglutination (TPHA). Treponema pallidum Immobilization (TPI).

25. Treatment: Penicillin. All exposed sexual partners should be treated. Treated patients need blood tests at 3-month intervals to make sure they are free of bacterium.

26. 5. Chancroid (Soft Sore) Caused by Haemophilus ducreyi. Diagnosis is usually clinically: Painful non-indurated genital ulcers and local lymphadenitis. Extra-genital lesions can occur. Gram-stained smears of aspirates: large numbers of short Gram-negative rods in chains, often described as having a ‘school of fish’ appearance, within or outside polymorphs . Treatment: macrolide (e.g. erythromycin or azithromycin ) or ceftriaxone.

27. II. Viral infections Herpes Simplex Virus (HSV-II). Human papillomavirus (HPV). Hepatitis B virus. Human immunodeficiency virus (HIV).

28. Caused by: Herpes simplex virus ( HSV-2): HSV-1 is usually oral herpes (cold sores), but can infect genitals . HSV-2 usually causes genital lesions, but can also infect the mouth. Prevalence: > 45 million Americans have genital herpes. Transmission: Genital herpes: penile-vaginal, oral-genital, oral-anal, or genital-anal contact. Oral herpes: through kissing, or oral-genital contact. Herpes sores are highly contagious, need to avoid contact between lesions and someone else’s body. 1. Herpes Simplex

29. Latency and reactivation: After 1ry lesions heal, virus enters up nerve fibers and stays latent in nerve cells in the sacral ganglia in the spinal cord. Flare-ups occur when virus moves back down along fibers to genitals or lips. Triggering factors: Stress , anxiety, depression, acidic food, UV light, fever, poor nutrition, fatigue… Symptoms during recurrent attacks tend to be milder than 1ry episode, heal more quickly.

30. Complications: Women: Increased incidence of cervical cancer (women with herpes should get Pap smears every 6-12 months). Newborn: Newborn baby can be infected by passage through birth canal → severe systemic infection or death. Ocular herpes of neonate. Both sexes: Ocular herpes. Aseptic meningitis or encephalitis.

31. Clinical presentation. Skin biopsy/scrapping and Giemsa smear. Serological tests. PCR . Viral culture. Diagnosis:

32. Treatment : Antiviral drugs which reduce viral shedding and the duration and severity of outbreaks: Acyclovir (Zovirax®). Valacyclovir (Valtrex ® ). Famiclovir ( Famvir ® ).

33. 2. Genital warts Etiology: Human papilloma virus (HPV). Ano -genital warts caused by HPV is called Condyloma accuminata . There are over 100 HPV strains, ~1/2 cause genital infections. Transmission: Penile-vaginal, oral-genital, oral-anal, or genital-anal contact. Condoms don’t prevent transmission of viral infections on vulva, base of penis, scrotum, and other genital areas not covered by condoms. HPV is most commonly transmitted by people who are asymptomatic.

34. Symptoms: Most people are unaware that they are infected. In women: usually appear on the lower vaginal opening, labia, inner vaginal walls and cervix. In men , usually on shaft of penis, scrotum. Both sexes: can also occur on anus, perineum.

35. Consequences : Certain strains of HPV are associated with cancers of the cervix, vagina, vulva, urethra, penis and anus. HPV infections account for 85-90% of risk for development of cervical cancer. Risk of HPV-induced cervical cancer is minimal if regular Pap testing and treatment of precancerous lesions is done.

36. LSIL: Low grade Squamous Intraepithelial Lesion HSIL: High grade Squamous Intraepithelial Lesion CIN: Cervical intraepithelial neoplasia

37. HPV strains associated with cancer: The most cancer-causing HPV strains include types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59 and 68. Types 16 and 18 are most commonly associated with development of cancer, together accounting for about 70% of invasive cervical cancers. However, not all infections with HPV 16 or 18 do progress to cancer. In addition, HPV 16 is strongly associated with anal cancer and throat cancer .

38. Prevention ( vaccine): Most health officials believe vaccination before puberty is best, before teens become sexually active. Cervarix : Vaccine against 2 strains of HPV (16 , and 18 ). Gardasil 4: Vaccine against 4 strains of HPV (6, 11, 16, and 18 ). Gardasil 9: Vaccine against 9 strains of HPV (6, 11, 16, 18, 31, 33, 45, 52, and 58). Treatment : Visible warts are removed by either cryotherapy (freezing) or chemical cauterization. Larger warts may require minor surgery to remove.

39. 4. Hepatitis B (HBV) Hepatitis B can cause liver damage and is considered the most general and severe liver disease worldwide. Transmission: Sexual contact * Sharing needles Mother-to-child

40. Symptoms: Jaundice. Fatigue. Abdominal and joint pain. Nausea. Loss of appetite. About 30% of persons have no signs or symptoms.

41. If left untreated … Transmission to sex partners and newborns. Cirrhosis. Liver failure. Liver cancer.

42. Vaccine: HBsAg . High risk people (HCWs, injection drug users, sexually active people with multiple sex partners, etc.) should be immunized. CDC recommends that children be immunized for Hepatitis B. 3 injections given over 6 months. Prevention:

43. 5. Human immunodeficiency virus (HIV) Virology: Retrovirus. HIV-1, and HIV-2. HIV-1 is more virulent, and causes most cases in US. HIV-2 exists along with HIV-1 in some African countries.

44. HIV = a retrovirus HIV mainly infects cells bearing the CD4 glycoprotein on the cell surface, and also requires chemokine co-receptors, CCR5 and CXCR4 Therefore, HIV infection leaves the body vulnerable to a variety of opportunistic infections and cancers. HIV becomes AIDS when: HIV is present, and CD4 T-cell count is <200 cells/microliter of blood (Normal: 600 - 1,200 cells/microliter) CD4 T cell under attack by HIV

45. Diagnoses of HIV Infection among Adults and Adolescents, by Transmission Category, 2014–2018—United States

46. AIDS: Transmission HIV in body fluids: Blood, semen, vaginal secretions, breast milk. NOTE: Saliva, urine, tears: the concentration of virus (if any) is too low to transmit infection. Can be transmitted: Through vaginal or anal intercourse or oral-genital contact. Through contaminated blood (needles, blood transfusion). From mother to fetus before or during birth, or after through breastfeeding. Likelihood of transmission during sexual contact: Depends on infected person’s viral load. Is greater when HIV is transmitted directly into blood, (through small tears in rectal tissues or vaginal walls).

47. Women are more easily infected from heterosexual intercourse with HIV+ partner than men Semen contains higher concentration of HIV than vaginal fluids. Female mucosal surface is exposed to HIV in ejaculate longer than a man’s penis is exposed to HIV in vaginal secretions. Larger mucosal surface area is exposed in vagina than on the penis. Female mucosal surface is exposed to greater potential trauma than the penis and can cause small tears that allow virus to enter. Some women have unprotected receptive anal intercourse (the single most risky behavior in terms of HIV infection for both men and women).

48. AIDS : symptoms & complications F lu-like symptoms. Periodically repeating fevers, night sweats, weight loss. Opportunistic infections: Oral candidiasis. Life-threatening pneumonia caused by Pneumocystis jirovecii . Others: TB, encephalitis, toxoplasmosis, CMV, Cryptococcus. Cancers: lymphomas, Kaposi’s sarcoma.

49. Treatment

50. The search for HIV vaccine Several disappointing attempts have been made to develop a vaccine against HIV. Many challenges confront vaccine researchers: New infections emerge all the time (1.7 million new case every year). Absence of ideal animal model for research. HIV virus reproduces and mutates too fast for antibodies to be effective . Its genetic diversity is greater than any other pathogen known to date. There are different subtypes of HIV spread around the world. The virus is able to “hide” inside cells that are apparently free of infection, suppressing immune responses at an early stage of the disease . There are no human models showing a cure for HIV. Ethical consideration.

51. III. Protozoa (Trichomoniasis) Primarily spread through sexual contact. Symptoms (women): Vaginitis, with white or yellow-green discharge, frothy, with unpleasant odor. Irritated vaginal and vulval tissues. In pregnant women, can lead to PROM & preterm delivery. Symptoms (men): Frequently asymptomatic. May have frequent or painful urination or slight urethral discharge .

52. Flagellated, motile protozoa on wet mount of vaginal secretion. Vaginal pH > 4.5 Diagnosis confirmed by microscopy. Other FDA approved test: OSOM Trichomonas Rapid Test. Treatment : Metronidazole or Tinidazole . Diagnosis

53. IV. Ecto -parasitic infections P arasites that live on the outer skin surfaces. Two common STIs caused by ecto -parasites: 1) Pubic lice. 2) Scabies.

54. 1. Pubic lice Caused by: biting louse called Phthirius pubis. Transmission: during sexual contact. Lice can live away from the body for as long as 1 day, can drop off onto underclothes, bedsheets, etc . Eggs deposited by female louse can survive for several days. Therefore, it is possible to get pubic lice by sleeping in someone’s bed or wearing someone’s clothes.

55. Symptoms: Itching (not relieved by scratching). Self-diagnosis is possible by locating a louse on a pubic hair. Treatment: Shaving. P ermethrin (1%) applied to all affected areas and all areas with hair (genitals, axilla, scalp, even eyebrows ). Boil all exposed clothes and bedding.

56. 2. Scabies Caused by: M ite called Sarcoptes scabiei . Too small to be seen by naked eye. Prevalence: worldwide. Transmission: as pubic lice… By close physical contact, both sexual and non-sexual. Can be transferred on clothing or bedding. Risk group: S exually active people, school children, prisoners, nursing home residents, and homeless people.

57. Symptoms: Small vesicles, red rash. Intense itching . Favorite sites of infestation: webs and sides of fingers, wrists, abdomen, genitals, buttocks, and breasts. Treatment: Permethrin (5%) lotion or cream applied at bedtime, then washed off after 8 hours. Wash all clothes and bedding that were exposed.

58. Still Think You Are Not At Risk???

59. Prevention of STI Dissemination STI dissemination can be reduced by: Stay faithful: Monogamy with one partner. Behavior modification: limiting partners . Barriers: condoms use. Screening of risk groups, pregnant women, and their partners. Health education and risk reduction counseling. Partner notification . Treating all infections. Vaccination: HBV, HPV.

60. QUIZ

61. Case 1 A 19-year-old woman presents for the evaluation of pelvic pain. The pain has progressively worsened over the past week. She has also been having some burning with urination and a vaginal discharge. She is sexually active, has had four lifetime partners, takes oral contraceptive pills, and occasionally uses condoms. On examination, she appears in no acute distress and does not have a fever. Her abdomen is soft with moderate lower abdominal tenderness. On pelvic examination, she is noted to have a yellow cervical discharge and significant cervical motion tenderness. No uterine or adnexal masses are palpated, but mild tenderness is also noted. A Gram stain of the cervical discharge reveals only multiple polymorphonuclear leukocytes.

62. Case 2 A 28-year-old stockbroker takes his vacation, spending two weeks at a ski resort in Colorado. During his stay at the resort, he meets and becomes intimately involved with a 25-year-old woman. They engage in vaginal intercourse several times and agree to keep in touch after returning to their respective hometowns and jobs. A few days after returning to his office, the stockbroker develops painful sores on the shaft of his penis. He also experiences low grade fever , headache, malaise, myalgia, and inguinal lymphadenopathy. He is so busy at his office that he is determined not to seek medical help unless his condition becomes overtly dangerous. As a matter of fact, his symptoms clear up after two weeks and starts to feel far better. However, he has some awareness of sexually transmitted diseases and is a bit worried about what happened because he realizes that it might be connected to his behavior at the ski resort. During a rather difficult phone call to the young women with whom he was intimate, he learns that she has had past episodes of similar genital lesions and experienced an outbreak of active lesions herself right after returning from the ski resort.

63. What is the most likely causative agent? What may happen if the man fails to seek treatment? Mention any 4 possible precipitating factors. What is the complication that may happen for his partner? How can she check for this complication? Is there a cure for this disease?

64. Clinical Cases Gallery

65. Chlamydia PID

66. Gonorrhea

67. Syphilis

68. Herpes simplex-1 and 2

69. Genital Herpes

70. Genital warts ( HPV )

71. Chancroid