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Gonorrhoea
Introduction
• Infection with Sexually Acquired Bacterial Pathogen
 Neisseria gonorrhoeae
• Dates back over 2000 years
• Hippocrates: acute gonorrhea as “Strangury”
 Obtained from the “Pleasures of Venus”
• Galen (A.D. 130) confused discharge with semen
 Flow of seed
Introduction
• Humans as the sole natural host
• Neisser [1879] described the Causative agent
• Leistikow & Loffler [1882] cultivated Gonococcus
Introduction CDC Fact Sheet
• The second most commonly occurring reportable STI
• Approx. 820,000 new gonococcal infections occur each year
• 570,000 of them are among young people 15-24 years of age
• In 2017, 555,608 cases of gonorrhea were reported
Introduction Fact Sheet
Introduction Fact Sheet
Introduction Fact Sheet
Introduction
• Acquired at multiple mucosal sites
 Lower genital tract
o Urethra, Cervix, Bartholin’s & Skene’s glands
 Anorectal canal
 Pharynx & conjunctivae
• May spread to the Upper Genital Tract, Uterine Tubes, & Abdominal Cavity,
as well as Other Systemic Sites
Transmission
• Relies on sexual networks
The Core, High-risk Population
Medium-risk Group
Members’ Partners
• MUSIC
• Men to Partners:
 N. gonorrhoeae attaches to sperm
 Transmitted through ejaculates
• Women to Partners:
 Cervicovaginal microbiota secrete Sialiadases
 Desialylate N. gonorrhoeae lipooligosaccharide [LOS] to enable efficient
transmission from women to men
Pathogenesis factors
• Surface structures
• Adhesion, Invasion & Immune Evasion
 Type IV pili
• Cellular adherence to Epithelial Surface
• Twitching motility
• Immune Evasion
Antigenic Variation & Phase Variation
Adherence to the epithelial surface & subsequent pilus retraction bring the
gonococci close to the cell surface
Pathogenesis factors
• Surface structures
• Adhesion, Invasion & Immune Evasion
 Opacity (Opa) proteins
• Interact with carcinoembryonic antigen-related cell adhesion molecule [CEACAM]
• Heparin sulfate proteoglycans [HSPG]
• Immune Evasion
Antigenic Variation & Phase Variation
Pathogenesis factors
• Surface structures
• Adhesion, Invasion & Immune Evasion
 Major outer membrane protein porin
• Binds C4b-binding protein & Factor H
• Suppresses neutrophil oxidative burst & neutrophil apoptosis
Pathogenesis factors
• Surface structures
• Adhesion, Invasion & Immune Evasion
 LOS
• Similar LPS
• Activation of inflammatory transcription factors
Release of cytokines & chemokines
Pathogenesis factors
 Efflux Pump
• Protect from Antimicrobials & Fatty acid stress
 Membrane Transporters
• Allow to co-opt nutrients from the surrounding environment
 Transcriptional Regulators
• Respond to changing growth requirements, oxidative stress, DNA & protein damage &
antimicrobials
 Protective enzymes
• Detoxify various ROS
Pathogenesis factors – Summary
Transcriptional Regulatory Factors
Establishment of infection
OMVs: Outer Membrane Vesicles , NOD: Nucleotide-binding Oligomerization Domain-containing Protein, TLR: Toll Like
Receptor, HSP: Heptose-1,7-bisphosphate, TIFA: TRAF-interacting Protein With FHA Domain-containing Protein A
Immune Evasion
 Prevents Complement Activation, Opsonization & Bacterial Killing
 Modulates the Activities of Macrophages, DCs & Neutrophils
 Modulates T Cell Function & Varies its Surface Components
Complement Activation
Regulation of Complement
Immune Evasion
 Prevents Complement Activation, Opsonization & Bacterial Killing
Sialylates its lipooligosaccharide
Binds host Factor H, Factor I & C4b-binding protein
Immune Evasion
 Modulates the Activities of Macrophages, DCs & Neutrophils
Prevents PMN granules from releasing their contents at the plasma membrane or into phagosomes
TGFβ is inhibitory for Th1 and Th2 cells
IL-10 inhibits the activity of Th1 cells, NK cells, & macrophages
PD-L1 counteract T cell-activating signals
Immune Evasion
 Modulates T Cell Function & Varies its Surface Components
Clinical Aspects
Neonates
• Exposed to infected exudate during vaginal delivery
 Ophthalmia neonatorum [Purulent Conjunctivitis]
 Scalp abscesses
 Disseminated disease
Clinical Aspects
Prepubertal Children
• Occurs typically via sexual abuse
 Can occur in Pharynx, Rectum, & most commonly Vagina
 Purulent Vaginal Discharge
 Vaginitis
 Erythematous, Swollen Vulva
Clinical Aspects
Adolescents & Adults
• Either symptomatic or asymptomatic
• In Males
• Urethritis
• In Females
• Cervicitis, Urethritis, PID, Menometrorrhagia,
Dyspareunia
• In Either Sex
• Dysuria , Proctitis, Pharyngitis, & DGI
Complications
• In Males
• Epididymitis, Prostatitis, Seminal Vesiculitis, Infection of Cowper & Tyson Glands
• In Females
• Acute Endometritis, Salpingitis, Tuboovarian Abscess, Peritonitis, Perihepatitis
• Ectopic pregnancy [6 – 10 fold risk]
• Infertility [3% to 21% risk]
• In Either Sex
• Disseminated Gonococcal Infection
Disseminated Gonococcal Infection
• Two Common Classifications
• Tenosynovitis – Dermatitis Syndrome [Most Common]
• Suppurative Arthritis Syndrome
• Fever, Chills
• Arthralgia
• Skin Lesions
• Hemorrhagic or vesiculopapular lesions
• Painful
• On palmar & plantar surfaces
Disseminated Gonococcal Infection
• Less Common
• Endocarditis
• Pericarditis,
• Meningitis
Diagnosis
• Appropriate Sexual History
 The five “P”s :
1. Partners
2. Practices
3. Protection from STDs
4. Past history of STDs
5. Prevention of pregnancy
Areas that you should openly discuss with your patients
Diagnosis
 Dialogue With Patient
ℚ Are you currently sexually active? (Are you having sex?)
ℚ If no, have you ever been sexually active?
ℚ In recent months, how many sex partners have you had?
ℚ In the past 12 months, how many sex partners have you had?
ℚ Are your sex partners men, women, or both?
ℚ If a patient answers “both” repeat first two questions for each specific
gender.
Partners
Diagnosis
 Dialogue With Patient
ℚ What kind of sexual contact do you have or have you had?
ℚ Genital (penis in the vagina)?
ℚ Anal (penis in the anus)?
ℚ Oral (mouth on penis, vagina, or anus)?
Practices
Diagnosis
 Dialogue With Patient
ℚ Do you and your partner(s) use any protection against STDs?
ℚ If not, could you tell me the reason?
ℚ If so, what kind of protection do you use?
ℚ How often do you use this protection?
ℚ If “sometimes,” in what situations or with whom do you use protection?
ProtectionfromSTDs
Diagnosis
 Dialogue With Patient
ℚ Have you ever been diagnosed with an STD? When? How were you treated?
ℚ Have you had any recurring symptoms or diagnoses?
ℚ Have you ever been tested for HIV, or other STDs? Would you like to be tested?
ℚ Has your current partner or any former partners ever been diagnosed or
treated for an STD? Were you tested for the same STD(s)?
ℚ If yes, when were you tested? What was the diagnosis? How was it treated?
PastHistoryofSTDs
Diagnosis
 Dialogue With Patient
ℚ Are you currently trying to conceive or father a child?
ℚ Are you concerned about getting pregnant or getting your partner pregnant?
ℚ Are you using contraception or practicing any form of birth control? Do you
need any information on birth control?
Questions should be gender appropriate
PreventionofPregnancy
Diagnosis
 Dialogue With Patient
ℚ What other things about your sexual health and sexual practices should we
discuss to help ensure your good health?
ℚ What other concerns or questions regarding your sexual health or sexual
practices would you like to discuss?
 Thank the patient for being open and honest and praise any
protective practices
 Ensure that this information is kept in strict confidence
CompletingtheHistory
Laboratory Diagnosis
• Specimens
• Genital Specimens
• In females
• Endocervical swab/discharge
• Vaginal Swab/discharge
• In males
• Urethral swab/discharge in males
• Urine (First Voided)
• Non Genital Specimens
• Rectal, Pharynx, & Conjunctival swab
• Body Fluids from Arthritic Joints
Laboratory Diagnosis
Laboratory Diagnosis
• Transport of Specimens
• Stuart’s Medium
Specimens should be collected with Dacron or Rayon swabs because
Calcium alginate may be toxic to gonococci
Laboratory Diagnosis
• Methods
• Gram Stain
• Gram Negative Intracellular Diplococci
• Sensitivity:
• Urethral Smear: 90%
• Endocervical Smear: 50-70%
• Specificity:
• Urethral Smear: 95%
• Endocervical Smear: 90%
Laboratory Diagnosis
• Methods
• Culture
• Culture Media:
• Chocolate Agar
• Thayer-Martin
• Martin Lewis
• New York City
• GC agar
• Culture Conditions:
• 35°C to 37°C
• CO2 (3% to 7%)
Convex, 1-2mm, Moist, Transparent ( Dew Drop)
Laboratory Diagnosis
• Methods
• Identification
• Gram Negative Cocci
• Catalase: Positive
• Oxidase: Positive
• Ferment: Only Glucose
[Glucose+Maltose by N. meningitidis]
• Chromogenic enzyme substrate
• DIF
• Coagglutination tests
• Neuclic Acid Test
Laboratory Diagnosis
Laboratory Diagnosis
• Methods
• Non Culture Methods
 NAAT
 DNA probe system (AccuProbe, Gen-Probe, USA)
 PCR
 Ligase chain reaction
 Strand displacement amplification system
 Nucleic acid sequence-based amplification
Treatment
Treatment
• Uncomplicated Gonococcal Infections
Recommended Regimen
Ceftriaxone 250 mg in a single intramuscular dose
PLUS Azithromycin 1 g orally in a single dose or Doxycycline 100 mg orally twice
daily for 7 days
Alternative Regimens
Cefixime 400 mg in a single oral dose
PLUS Azithromycin 1 g orally in a single dose or Doxycycline 100 mg orally twice
daily for 7 days
Treatment
• Complicated Gonococcal Infections
48
• Counseling and Education
 Nature of the disease
 Transmission
 Treatment and follow-up
 Risk reduction
• Management of Sex Partners
Prevention
Remember…
Its your health. Protect yourself.

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Gonorrhoea

  • 2. Introduction • Infection with Sexually Acquired Bacterial Pathogen  Neisseria gonorrhoeae • Dates back over 2000 years • Hippocrates: acute gonorrhea as “Strangury”  Obtained from the “Pleasures of Venus” • Galen (A.D. 130) confused discharge with semen  Flow of seed
  • 3. Introduction • Humans as the sole natural host • Neisser [1879] described the Causative agent • Leistikow & Loffler [1882] cultivated Gonococcus
  • 4. Introduction CDC Fact Sheet • The second most commonly occurring reportable STI • Approx. 820,000 new gonococcal infections occur each year • 570,000 of them are among young people 15-24 years of age • In 2017, 555,608 cases of gonorrhea were reported
  • 8. Introduction • Acquired at multiple mucosal sites  Lower genital tract o Urethra, Cervix, Bartholin’s & Skene’s glands  Anorectal canal  Pharynx & conjunctivae • May spread to the Upper Genital Tract, Uterine Tubes, & Abdominal Cavity, as well as Other Systemic Sites
  • 9. Transmission • Relies on sexual networks The Core, High-risk Population Medium-risk Group Members’ Partners • MUSIC • Men to Partners:  N. gonorrhoeae attaches to sperm  Transmitted through ejaculates • Women to Partners:  Cervicovaginal microbiota secrete Sialiadases  Desialylate N. gonorrhoeae lipooligosaccharide [LOS] to enable efficient transmission from women to men
  • 10. Pathogenesis factors • Surface structures • Adhesion, Invasion & Immune Evasion  Type IV pili • Cellular adherence to Epithelial Surface • Twitching motility • Immune Evasion Antigenic Variation & Phase Variation Adherence to the epithelial surface & subsequent pilus retraction bring the gonococci close to the cell surface
  • 11. Pathogenesis factors • Surface structures • Adhesion, Invasion & Immune Evasion  Opacity (Opa) proteins • Interact with carcinoembryonic antigen-related cell adhesion molecule [CEACAM] • Heparin sulfate proteoglycans [HSPG] • Immune Evasion Antigenic Variation & Phase Variation
  • 12. Pathogenesis factors • Surface structures • Adhesion, Invasion & Immune Evasion  Major outer membrane protein porin • Binds C4b-binding protein & Factor H • Suppresses neutrophil oxidative burst & neutrophil apoptosis
  • 13. Pathogenesis factors • Surface structures • Adhesion, Invasion & Immune Evasion  LOS • Similar LPS • Activation of inflammatory transcription factors Release of cytokines & chemokines
  • 14. Pathogenesis factors  Efflux Pump • Protect from Antimicrobials & Fatty acid stress  Membrane Transporters • Allow to co-opt nutrients from the surrounding environment  Transcriptional Regulators • Respond to changing growth requirements, oxidative stress, DNA & protein damage & antimicrobials  Protective enzymes • Detoxify various ROS
  • 17. Establishment of infection OMVs: Outer Membrane Vesicles , NOD: Nucleotide-binding Oligomerization Domain-containing Protein, TLR: Toll Like Receptor, HSP: Heptose-1,7-bisphosphate, TIFA: TRAF-interacting Protein With FHA Domain-containing Protein A
  • 18. Immune Evasion  Prevents Complement Activation, Opsonization & Bacterial Killing  Modulates the Activities of Macrophages, DCs & Neutrophils  Modulates T Cell Function & Varies its Surface Components
  • 21. Immune Evasion  Prevents Complement Activation, Opsonization & Bacterial Killing Sialylates its lipooligosaccharide Binds host Factor H, Factor I & C4b-binding protein
  • 22. Immune Evasion  Modulates the Activities of Macrophages, DCs & Neutrophils Prevents PMN granules from releasing their contents at the plasma membrane or into phagosomes TGFβ is inhibitory for Th1 and Th2 cells IL-10 inhibits the activity of Th1 cells, NK cells, & macrophages PD-L1 counteract T cell-activating signals
  • 23. Immune Evasion  Modulates T Cell Function & Varies its Surface Components
  • 24. Clinical Aspects Neonates • Exposed to infected exudate during vaginal delivery  Ophthalmia neonatorum [Purulent Conjunctivitis]  Scalp abscesses  Disseminated disease
  • 25. Clinical Aspects Prepubertal Children • Occurs typically via sexual abuse  Can occur in Pharynx, Rectum, & most commonly Vagina  Purulent Vaginal Discharge  Vaginitis  Erythematous, Swollen Vulva
  • 26. Clinical Aspects Adolescents & Adults • Either symptomatic or asymptomatic • In Males • Urethritis • In Females • Cervicitis, Urethritis, PID, Menometrorrhagia, Dyspareunia • In Either Sex • Dysuria , Proctitis, Pharyngitis, & DGI
  • 27. Complications • In Males • Epididymitis, Prostatitis, Seminal Vesiculitis, Infection of Cowper & Tyson Glands • In Females • Acute Endometritis, Salpingitis, Tuboovarian Abscess, Peritonitis, Perihepatitis • Ectopic pregnancy [6 – 10 fold risk] • Infertility [3% to 21% risk] • In Either Sex • Disseminated Gonococcal Infection
  • 28. Disseminated Gonococcal Infection • Two Common Classifications • Tenosynovitis – Dermatitis Syndrome [Most Common] • Suppurative Arthritis Syndrome • Fever, Chills • Arthralgia • Skin Lesions • Hemorrhagic or vesiculopapular lesions • Painful • On palmar & plantar surfaces
  • 29. Disseminated Gonococcal Infection • Less Common • Endocarditis • Pericarditis, • Meningitis
  • 30. Diagnosis • Appropriate Sexual History  The five “P”s : 1. Partners 2. Practices 3. Protection from STDs 4. Past history of STDs 5. Prevention of pregnancy Areas that you should openly discuss with your patients
  • 31. Diagnosis  Dialogue With Patient ℚ Are you currently sexually active? (Are you having sex?) ℚ If no, have you ever been sexually active? ℚ In recent months, how many sex partners have you had? ℚ In the past 12 months, how many sex partners have you had? ℚ Are your sex partners men, women, or both? ℚ If a patient answers “both” repeat first two questions for each specific gender. Partners
  • 32. Diagnosis  Dialogue With Patient ℚ What kind of sexual contact do you have or have you had? ℚ Genital (penis in the vagina)? ℚ Anal (penis in the anus)? ℚ Oral (mouth on penis, vagina, or anus)? Practices
  • 33. Diagnosis  Dialogue With Patient ℚ Do you and your partner(s) use any protection against STDs? ℚ If not, could you tell me the reason? ℚ If so, what kind of protection do you use? ℚ How often do you use this protection? ℚ If “sometimes,” in what situations or with whom do you use protection? ProtectionfromSTDs
  • 34. Diagnosis  Dialogue With Patient ℚ Have you ever been diagnosed with an STD? When? How were you treated? ℚ Have you had any recurring symptoms or diagnoses? ℚ Have you ever been tested for HIV, or other STDs? Would you like to be tested? ℚ Has your current partner or any former partners ever been diagnosed or treated for an STD? Were you tested for the same STD(s)? ℚ If yes, when were you tested? What was the diagnosis? How was it treated? PastHistoryofSTDs
  • 35. Diagnosis  Dialogue With Patient ℚ Are you currently trying to conceive or father a child? ℚ Are you concerned about getting pregnant or getting your partner pregnant? ℚ Are you using contraception or practicing any form of birth control? Do you need any information on birth control? Questions should be gender appropriate PreventionofPregnancy
  • 36. Diagnosis  Dialogue With Patient ℚ What other things about your sexual health and sexual practices should we discuss to help ensure your good health? ℚ What other concerns or questions regarding your sexual health or sexual practices would you like to discuss?  Thank the patient for being open and honest and praise any protective practices  Ensure that this information is kept in strict confidence CompletingtheHistory
  • 37. Laboratory Diagnosis • Specimens • Genital Specimens • In females • Endocervical swab/discharge • Vaginal Swab/discharge • In males • Urethral swab/discharge in males • Urine (First Voided) • Non Genital Specimens • Rectal, Pharynx, & Conjunctival swab • Body Fluids from Arthritic Joints
  • 39. Laboratory Diagnosis • Transport of Specimens • Stuart’s Medium Specimens should be collected with Dacron or Rayon swabs because Calcium alginate may be toxic to gonococci
  • 40. Laboratory Diagnosis • Methods • Gram Stain • Gram Negative Intracellular Diplococci • Sensitivity: • Urethral Smear: 90% • Endocervical Smear: 50-70% • Specificity: • Urethral Smear: 95% • Endocervical Smear: 90%
  • 41. Laboratory Diagnosis • Methods • Culture • Culture Media: • Chocolate Agar • Thayer-Martin • Martin Lewis • New York City • GC agar • Culture Conditions: • 35°C to 37°C • CO2 (3% to 7%) Convex, 1-2mm, Moist, Transparent ( Dew Drop)
  • 42. Laboratory Diagnosis • Methods • Identification • Gram Negative Cocci • Catalase: Positive • Oxidase: Positive • Ferment: Only Glucose [Glucose+Maltose by N. meningitidis] • Chromogenic enzyme substrate • DIF • Coagglutination tests • Neuclic Acid Test
  • 44. Laboratory Diagnosis • Methods • Non Culture Methods  NAAT  DNA probe system (AccuProbe, Gen-Probe, USA)  PCR  Ligase chain reaction  Strand displacement amplification system  Nucleic acid sequence-based amplification
  • 46. Treatment • Uncomplicated Gonococcal Infections Recommended Regimen Ceftriaxone 250 mg in a single intramuscular dose PLUS Azithromycin 1 g orally in a single dose or Doxycycline 100 mg orally twice daily for 7 days Alternative Regimens Cefixime 400 mg in a single oral dose PLUS Azithromycin 1 g orally in a single dose or Doxycycline 100 mg orally twice daily for 7 days
  • 48. 48 • Counseling and Education  Nature of the disease  Transmission  Treatment and follow-up  Risk reduction • Management of Sex Partners Prevention
  • 49. Remember… Its your health. Protect yourself.