1. GONORRHEA GONORRHEA Dr. Hani Masaadeh MD, Ph.D

2. What Is Gonorrhea? Gonorrhea is a sexually transmitted infection (STI). It’s caused by infection with the bacterium Neisseria gonorrhoeae. It tends to infect warm, moist areas of the body, including the: urethra (the tube that drains urine from the urinary bladder) eyes throat vagina Anus female reproductive tract (the fallopian tubes, cervix, and uterus)

3. MORPHOLOGY:  Gram negative diplococci with adjacent sides concave, being typically kidney shaped.  They are usually found with in the polymorphs.  They possess pili on their surface.

4. 4GONORRHEA Gram-negative diplococcus (Neisseria gonorrhoeae) Causes a variety of illnesses and is usually transmitted through sexual intercourse Vertical transmission is uncommon Risk of transmission is higher from males to females (50% per contact)

5. Properties : Neisseriae are gram-negative diplococci ( Bean shaped). Oxidase-positive; i.e., they possess the enzyme cytochrome c and produce oxidase. They are cultured on "chocolate" agar N. gonorrhoeae is maltose non fermenter Some of N. gonorrhoeae produce beta lactamases. Humans are only reservoir, not part of normal flora

6. Gonococci are very sensitive to heating or drying. Cultures must be plated rapidly. N. gonorrhoeae grows rapidly producing small, raised, grey or translucent colonies after overnight incubation. Non motile. Causes disease only in humans. Killed by drying that’s why transmitted sexually.

7. CULTURE & CULTURAL CHARACTERISTICS:  Gonococci are fastidious organisms do not grow on ordinary culture media.  They are aerobic but may grow anaerobically also.  The optimum temperature for growth is 35-36°C & optimum pH is 7.2-7.6.  It is essential to provide 5-10% CO2.

8. Media used: a) Non selective media: Chocolate agar, Mueller-Hinton agar. Mueller-Hinton agar. b) Selective media: Thayer Martin medium with antibiotics (Vancomycin, Colistin & Nystatin.

9. Colony morphology: Colonies are small, round, translucent, convex or slightly umbonate with finely granular surface & lobate margins.

10. Biochemical reactions: 1) Oxidase test: Positive 2) Ferments only glucose but not maltose. but not maltose.

12. The endotoxin of N. gonorrhoeae is a lipooligosaccharide (LOS). N.gonorrhoea has no capsule N. gonorrhoeae causes gonorrhea,neonatal conjunctivitis (ophthalmia neonatorum) and pelvic inflammatory disease (PID).

13. Pathogenecity: The virulence factors are. 1. Pili. Most important virulence factors. Piliated gonococci are usually virulent, whereas non piliated strains are avirulent. 2. Two virulence factors in the cell wall a. Lipooligosaccharride (LOS) (a modified form of endotoxin). Endotoxin of gonococci is weaker than that of meningococci. b. Outer membrane proteins.(OMP).

14. OMP cause attachment of bacteria to epithelial cells of the urethra, rectum, cervix, pharynx, or conjunctiva, like pilli. 3. IgA protease. The main host defenses against gonococci are antibodies (IgA and IgG), complement, and neutrophils. IgA protease degrades one of these antibodies. Certain strains of gonococci cause disseminated infections. These gonococci resist killing by bacteria due to protein Porin A (OMP). It inactivates the C3b component of complement.

15. PILLI

16. Clinical Findings: Transmitted sexually both in males and females. Cause pyogenic infections. Females are usually asymptomatic. N. gonorrhea causes following infections. 1. Genitourinary tract infections ( Gonorrhea) 2. Disseminated infection via spread through blood stream. 3. Rectal infections.

17. 4. Pharyngitis 5. Ophthalmia neonatorum 1. Genitourinary tract infections : Gonorrhea in men has features of urethritis accompanied by dysuria and a purulent discharge. Epididymitis can occur. In women, infection is initially in the endocervix (cervicitis), causing a purulent vaginal discharge and intermenstrual bleeding.

18. The first noticeable symptom in men is often a burning or painful sensation during urination. Other symptoms may include: greater frequency or urgency of urination a pus-like discharge (or drip) from the penis (white, yellow, beige, or greenish) swelling or redness at the opening of the penis swelling or pain in the testicles a persistent sore throat Symptoms in Women discharge from the vagina pain or burning sensation while urinating the need to urinate more frequently sore throat pain upon engaging in sexual intercourse sharp pain in the lower abdomen fever

19. The most frequent complication is ascending infection to the uterine tubes (salpingitis) which can lead to sterility or ectopic pregnancy 2. Disseminated gonococcal infection(DGI): Commonly manifest as arthritis, synovitis, or skin pustules. Disseminated infection is the most common cause of septic arthritis in sexually active adults.

20. 3.Rectal infections: Prevalent in male homosexuals, are characterized by constipation, painful defecation, and purulent discharge. 4.Pharyngitis is contracted by oral-genital contact. The condition may mimic a mild viral or a streptococcal sore throat.

21. 5.Ophthalmia neonatorum is an infection of the conjunctiva acquired by a newborn during passage through the birth canal of an infected mother. If untreated, acute conjunctivitis may lead to blindness.

24. LABORATORY DIAGNOSIS: Specimens collected: A) In men: a) Acute infection- Urethral discharge b) Chronic infection- i) Morning drop ii) Discharge collected after prostatic massage iii) Centrifuged deposit of urine B) In women: i) Urethral discharge ii) Cervical swabs

25. 25 GONORRHEA

26. 26GONORRHEA Disseminated Gonococcal Infection (occurs in 1% to 2% of patients) Arthralgias Asymmetric polyarthritis Dermatitis Manifestations MANIFESTATIONS

27. 27GONORRHEA N. gonorrhoeae infects columnar or cubodial epithelium It attaches via pili and penetrates within 1-2 days There is a neutrophilic response which creates a purulent discharge

29. 29GONORRHEA Females infected with gonorrhea are usually symptomatic Symptoms usually include: Increased vaginal discharge Dysuria Variable amount of vaginal bleeding The classic sign of Mucopurulent Cervicitis is not always present… if present it is usually similar to that caused by other genitourinary pathogens CERVICITIS

30. 30GONORRHEA Symptoms include: Anal pain and pruritus Tenesmus Purulent discharge Rectal bleeding More common among men but occurs in up to 40% of women who have endocervical disease ANORECTAL

31. 31GONORRHEA Usually contracted by fellatio Typically asymptomatic May resolve spontaneously PHARYNGEAL GONOCOCCAL INFECTION

32. 32GONORRHEA Present in 10%-20% of gonococcal infections in women Risk factors for ascending infection include Age <20 yrs Prior PID Vaginal douching Bacterial vaginosis Symptoms range from: Minimal (lower abdominal tenderness) to Severe Pain PELVIC INFLAMMATORY DISEASE

33. 33GONORRHEA Culture of endocervical region Gold standard, used in all medico legal arenas Specimen acquisition is the key Swab should have a wire shaft and a synthetic fiber tip N. gonorrhoeae Avoid swabs with wooden shafts or cotton tips because they may be toxic to N. gonorrhoeae DIAGNOSIS

34. 34GONORRHEA Gram Stain Highly specific, less costly, quick Diagnostic if gram negative diplococci are seen within polymorphonuclear leukocytes DIAGNOSIS

35. Lab diagnosis : 1.In the male, the finding of numerous neutrophils containing gram negative diplococci in a smear of urethral exudate provides a diagnosis of gonococcal infection. 2.In the female a positive culture is also needed. 3.Culture: N. gonorrhoeae grows best under aerobic conditions, and most strains require CO2 also.

36. 36GONORRHEA DNA probes High sensitivity and specificity Concurrently test for N. gonorrhea and C. trachomatis C. trachomatis with a single specimen More widely used than cultures… and cost is similar DIAGNOSIS

37. 37GONORRHEA Ligase chain reaction (LCR) assays More expensive but also more convenient Can perform on urine samples or vaginal swabs Sensitivity of 95% and specificity of 98%-100% Tests’ performance in asymptomatic, low prevalence setting, is unknown Not to be used as a test of cure (Will identify nonviable gonococcal nucleic acid) DIAGNOSIS

38. 38 Sensitivity and specificity of tests for gonorrhea Method* Sensitivity (%) Specificity (%) Gram stain+ Endocervix Urethra (with symptoms) Urethra (no symptoms 40-60 95-98 40-60 95-100 90-95 GONORRHEA

39. 39GONORRHEA All recommended therapies are given as a single dose Should be given to symptomatic patients at the time of testing Enhances compliance profoundly: Reduces further transmission Reduces resistance TREATMENT

40. 40 Recommended treatment regimens for gonococcal infections*: cervicitis, urethritis, proctitis Preferred regimen Cefixime (Suprax), 400 mg PO in a single dose or Ceftriaxone sodium (Rocephin), 125 mg IM in a single dose or Ciprofloxacin (Cipro), 500 mg PO in a single dose or Ofloxacin (Floxin), 400 mg PO in a single dose plus Chlamydia coverage: Azithromycin (Zithromax), 1 g PO in a single dose or Doxycycline, 100 mg PO bid x 7 days

41. 41 Recommended treatment regimens for gonococcal infections*: pelvic inflammatory disease Preferred regimen (inpatient) Cefotetan disodium (Cefotan), 2 g IV q 12h or cefoxitin sodium (Mefoxin), 2 g IV q6h plus Chlamydia coverage: Doxycycline, 100 mg PO+ q12h x 14 days or Clindamycin (Cleocin Phosphate), 900 mg IV q8h plus Chlamydia coverage: Gentamicin (Garamycin), 2 mg/kg loading dose IM/IV followed by 1.5 mg/kg maintenance dose IV q8h, then doxycycline, 100 mg PO q12h to complete 14 days or clindamycin (Cleocin), 450 mg PO qid to complete 14 days

42. 42 Recommended treatment regimens for gonococcal infections*: pelvic inflammatory disease Outpatient Ofloxacin, 400 mg PO bid x 14 days plus Chlamydia coverage: Metronidazole, 500 mg PO bid x 14 days or Ceftriaxone sodium (Rocephin), 250 mg IM in a single dose Or Cefoxitin, 2 g IM with probenecid, 1 g PO, in a single dose (concurrently ) or Other parenteral 3 rd -generation cephalosporin (eg., ceftizoxime sodium [Cefizox], Cefotaxime sodium [Claforan]) plus Chlamydia coverage: Doxycycline, 100 mg PO q12 h x 14 days

43. 43GONORRHEA Tests of cure are not needed for uncomplicated gonococcal infections If patient fails to improve, a culture is required for antimicrobial susceptibility testing Infections identified after completion of treatment are said to be due to reinfection rather than treatment failure FOLLOW-UP

44. 44GONORRHEA Some experts advocate the testing of all sexually active teenagers twice a year (this is based on the frequent reinfection rates in this age group) FOLLOW-UP

45. 45GONORRHEA Patients should be encouraged to refer their sexual partners for testing and treatment Patients should be advised to abstain from sexual intercourse until they have fully completed therapy and are asymptomatic FOLLOW-UP

46. FemalesMales 50% risk of infection after single exposure20% risk of infection after single exposure Asymptomatic infections frequently not diagnosed Most initially symptomatic (95% acute) Major reservoir is asymptomatic carriage in females Genital infection primary site is cervix (cervicitis), but vagina, urethra, rectum can be colonized Genital infection generally restricted to urethra (urethritis) with purulent discharge and dysuria Ascending infections in 10-20% including salpingitis, tubo-ovarian abscesses, pelvic inflammatory disease (PID), chronic infections can lead to sterility Rare complications may include epididymitis, prostatitis, and periurethral abscesses Disseminated infections more common, including septicemia, infection of skin and joints (1-3%) Disseminated infections are very rare Can infect infant at delivery (conjunctivitis, opthalmia neonatorum) More common in homosexual/bisexual men than in heterosexual populatiuon Gonorrhea

47. Prevention The prevention of gonorrhea involves the use of safety measures and the immediate treatment of symptomatic patients and their contacts.

48. 48 High-gonorrhea, high poverty neighborhood

49. 49 Low-gonorrhea, high poverty neighborhood