Urethritis and Cervicitis Flashcards
1
Q
Neisseria gonorrhoeae Physiology and Structure
A
- Gram-neg. cocci
- Obligate human pathogen
*no natural animal reservoirs
*doesn’t survive long outside of host
*Fastidious: requires complex media for growth
- Outer membrane contains LOS (lipooligosaccharide)
*no repeating O antigen
- Don’t survive outside the human body long (cant get from a toilet seat)
2
Q
Neisseria gonorrhoeae Virulence Factors
A
All the surface structures on NG undergo extensive antigenic and phase variation
- Type IV pili
- Opacity Assoc. Proteins (Opa proteins)
- Lipooligosaccharide
- IgA protease
- Porin Protein (Por A and Por B)
- Iron binding proteins
3
Q
Type IV Pili
A
- Virulence factor of NG
- Required for infection, mediates binding to mucosal epithelial cells and tissues
- Mediates natural comopetence and biofilm formation
- Undergoes extensive intra-strain antigenic and phase variation
4
Q
Opacity Assoc. Proteins (Opa proteins)
A
- Virulence factor of NG
- Promotes attachment and invasion of human cells
- A single cell can have up to 12 opa genes
- Undergoes antigenic and phase variation; a single cell can express zero to several diff. Opa proteins
5
Q
Lipooligosaccharide (LOS)
A
- Virulence factor of NG
- Similar to LPS but lacks the long sugar O antigen
- Toxic to fallopian tube mucosa
- Sialylation of LOS prevents serum killing
- Subject to antigenic variaton
6
Q
IgA protease
A
- Virulence factor of NG
- Targets and cleaves IgA1
- Cleaves LAMP1 —> lysosome modification —> survival
7
Q
Porin Protein (Por A and Por B)
A
- Virulence factor of NG
- Abundant outer membrane protein
- Allows transport into cell, and contributes to survival
- PorBIA most commonly assoc. w/ DGI (serum resitance)
- Protein varies b/w strains
8
Q
Iron Binding Proteins
A
- Virulence factor of NG
- NG can scavenge iron from transferrin, lactoferrin, and haemoglobin
- Transferrin binding proteins (TbpA, TbpB): large surface proteins; transferrin receptor required for infection
9
Q
Neisseria gonorrhoeae Pathogenesis and Immune Response
A
- Attachment to mucosal cells followed by penetration and multiplication in cells and passage into sub-epithelial space
- Can survive in leukocytes, get into subepithelial space and produce a PMN rich exudate; its the immune response that is really damaging
- LOS and peptidoglycan induces TNF-alpha expression and sloughing of ciliated cells (i.e. inflammation)
- LOS inflammatory response or dissemination
- A protective immune response is not elicited, and there is no immune memory
10
Q
Clinical Syndromes of NG
A
- Urethritis (males)
- Cervicitis (females)
- Disseminated gonococcal infection
- Pharyngitis
- Purulent conjunctivitis (mild to aggressive)
- Proctitis (anorectal gonorrhea)
11
Q
Ng Urethritis
A
- Male NG clinical syndrome
- Uncomplicated mucosal infection
- 2-5 days incubation —> mucopurulent discharge and dysuria (discharge may be indistinguishable from NGU)
- Some infections may be asymptomatic
- Complications (rare): include epididymitis, disseminated gonococcal infection and reactive arthritis
12
Q
Ng Cervicitis
A
- Female NG clinical syndrome
- Commonly asymptomatic (up to 70%)
- Inflammation of the columnar epithelium and subepithelium of the endocervix
- When symptomatic: vaginal pruritis and/or mucopurulent discharge. Dysuria is atypical
- Abdominal pain and dyspareunia: suspect upper genital tract disease (eg. PID)
- Serious sequelae more common in women: includes salpingitis, PID, and DGI —> sterility, ectopic pregnancy, septic arthritis
13
Q
Disseminated Gonococcal Infection
A
- NG clinical syndrome
- Occurs in 0.5-3% of infected pts. (more common in women)
- Most that disseminate do not cause urethritis
- Most common cuase of septic arthritis in sexually active adults
- Pts deficient in complement components that form the MAC more susceptible
- Manifestations include:
*dermatitis-arthritis-tenosynovitis syndrome
*septic (purulent) arthritis (one joint)
*rarely, endocarditis, or meningitis
14
Q
Ng Pharyngitis
A
- NG clinical syndrome
- Usually acquired by oral sex exposure
- Majority asymptomatic
- Symptoms: sore throat, pharyngeal exudates, cervical lymphadenitis
- Thought to be site of acquisition of antibiotic resistance genes for Ng; we contain commensal neisseria in our throat and so the 2 can exchange genes
15
Q
Purulent conjunctivitis (mild to aggressive)
A
- In newborns: opthalmia neonatorum
- In adults and adolescents: autoinoculation from an anogenital source
- Non-sexual transmission reported in outbreak settings
16
Q
Ng Proctitis
A
- Ng clinical syndrome
- Anorectal gonorrhea
- Usually asymptomatic
- Males: typically in MSM, uncommon in heterosexual males; assoc. w/ a 3-fold increase in the risk of HIV infection
- Females: transmission to anal canal from vagina or anal intercourse
- Symptoms include: tenesmus, anorectal pain, bleeding and mucopurulent discharge
- Must be distinguished from other infectious causes of proctitis
17
Q
Gonorrhea Diagnostic Techniques
A
- Should always include testing for Chlamydia (CT)
- Nucleic acid amplification tests
- Specimens
- Microscopy
- Culture
18
Q
Gonorrhea nucleic acid amplification tests
A
- NAAT
- Superior accuracy; can use various specimens
- Can detect nucleic acid of Ng and CT
- This method cannot detect antibiotic resistance of Ng
19
Q
Gonorrhea specimen diagnostic techniques
A
- Vaginal swabs preferred by CDC for asymptomatic females
- Swabs preferred for extragenital infections (eg. pharyngitis)
*can’t use cotton (toxic to gonorrhea), use plastic
- First-catch urine: appropriate for asymptomatic females and males regardless of symptomology
20
Q
Gonorrhea microscopic diagnostic techniques
A
- Gram stain: sensitive (>90%) and specific (98%) in detecting purulent urethritis in men
- Methylene blue/gentian violet stain
- Relatively insensitive in women w/ symptomatic or asymptomatic cervicitis
21
Q
Gonorrhea culture diagnostic technique
A
- Important for testing antibiotic resistance
- Specimen collection requires use of swabs w/ special hangling b/c of the fastidious nature of Ng (eg. Ng killed by fatty acids and trace metals)
22
Q
Gonorrhea Treatment
A
- Antibiotic resistance is a major problem
- Directly Observed Therapy (DOT) whenever possible; watch pt take antibiotic in office
- Should always include treatment for chlamydia
- Ceftriaxone 250mg IM + azithromycin 1g PO
- Cefixime 400mg PO + azithromycin 1g PO
*ONLY if unable to use ceftriaxone
*NOT for pharyngeal infection (low efficacy): TOC recommended for pharyngitis
23
Q
Gonorrhea Prophylactic Treatment
A
- Routine screening should be offered to sexually active pts at high risk of infection
*eg. young individuals entering correctional facilities
*MSM should be routinely screened for oropharyngeal and rectal Ng
- Treat pts w/ potential or known exposures empirically
- Treatment failures: suspect antibiotic resistance, test for w/ culture and antibiotic susceptibility testing
24
Q
Chlamydia Incidence and Harm
A
- Most common cause of sexually transmitted genital infections
- Rate of reported cases of chlamydia are highest among adolescents and young adults aged 15-24
- Rates are underestimated b/c of asymptomatic clinical course
- Repeat and chronic infections can have a deleterious impact on female reproductive health
- Highest rates in women
25
Chlamydia trachomatis (CT)
- Obligate intracellular bacteria
\*depends on host cell for nutrition and replication
\*once thought to be viruses b/c they could pass thru 0.45mm filters
- Possess inner and outer cell membranes like gram neg. bacteria
- Unlike other bacteria, do not have a peptidoglycan layer
26
CT Genotypes and Serovars
- Diff. strains; diff. genotypes and 20 distinct serovars
- 3 main patho-biotypes
\*A to C
\*D to K
\*L1 to L3
27
CT A to C patho-biotype
- Infect ocular epithelium causing acute conjunctivitis to trachoma; endemic in Africa and Asia; characterized by chronic conjunctivitis; leading cause of preventable blindness
28
CT **D to K** patho-biotype
- Causes STD's; infect squamocolumnar epithelial cells of female RT and male GU tract (cervicitis, urethritis, proctitis, conjunctivitis, pneumonia (in neonates))
29
CT **L1 to L3** patho-biotype
- Lymphogranuloma venereum, a systemic illness; assoc. w/ genital ulcer disease in tropical countries
30
CT Structure and Physiology
Exists in 2 morphologically distinct forms:
- Elementary body (EB): infectious
\*spore-like, resistant to harsh environment
\*bind to cell receptors for uptake
- Reticulate body (RB): non-infectious
\*metabolically active and replicative
31
CT Pathogenesis
- Infectious EBs enter genital mucosal epithelium of urethra, endocervix, endometrium, fallopian tubes, anorectum, respiratory tract, and conjunctivae
- Ability of CT to avoid the host immune system is impoprtant for pathogenicity
- Clinical manifestations due to direct destruction of host cells and a severe host inflammatory response
- Host immune response (ie. genetic predisposition) is a major determinate of pathology and development of infertility
32
CT Clinical Syndromes
- Urogenital infections
- Lymphogranuloma venereum (LGV)
- Conjunctivitis
- Pharyngitis
- Genital LGV
33
CT Urogenital Infections in Females
- D-K serovars
- Clincally the infection includes: **cervicitis**, urethritis, endometritis, salpingitis, bartholinitis, perihepatitis
- Most infections asymptomatic (~85%)
- Symptoms when present are non-specific: change in vaginal discharge, intermenstrual vaginal bleeding, post-coital bleeding
- **Complications**: PID, tubal obstruction, and female infertility
- Most common cuase of tubal infertility and adverse pregnancy outcome, so **screening important**
34
CT Urogenital Infections in Males
- D-K serovars
- Most common cause of non-gonococcal urethritis in men
\*usually symptomatic: mucoid or watery discharge (sometimes scant, may have to milk the urethra), and dysuria
\*one of most frequent pathogens of epididymitis (along w/ Ng)
\*Proctitis: inflammation of the distal rectal mucosa; occurs mainly in MSM that engage in receptive anal intercourse. Can be caused by D-K and L serovars (will determine clinical presentation)
- Reactive arthritis (formerly Reiter's syndrome)
35
Reactive Arthritis
- Formerly Reiter's Syndrome
- Urogenital CT infection
- Developed by ~1% of men w/ urethritis
- Known as reactive arthritis triad (RAT: arthritis, uveitis and urethritis)
36
Lymphogranuloma venereum (LGV)
- Caused by serovars L1, L2, L3, usually asymptomatic
- Historically, genital ulcer disease w/ lymphadenopathy (w/o proctitis) in heterosexuals in tropical and subtropical areas
- Appears to be more prominent in males
- Increasingly reported among MSM in temperate climates (outbreaks)
\*most HIV (+)
\*majority of cases presented as proctitis
37
Lymphogranuloma venereum Stages
- 1st Stage (1-4wks post-infection): a painless ulcer develops at the site of infection that spontaneously heals. Pt may have fever headache, myalgia
- 2nd Stage (2-6wks later): local extension to inguinal or femoral lymph nodes (inflammation and swelling, Groove sign) ---\> inguinal buboes which gradually enlarge and may rupture
- Can spread further thru lymphatics to the rectum (proctitis) and/or progress to invasive infection, often w/ systemic symptoms
\*abscesses can form in lymph nodes that suppurate and discharge thru the skin
- Late lymphogranuloma venereum: if left untreated can lead to other complications
38
CT Conjunctivitis
- Serovars D-K
- Conjunctival epithelial cells infected by autoinoculation from infected genitalia or by ocular-genital contact
- Neonatal ocular infections occur during passage thru an infected birth canal and can lead to neonatal pneumonia
39
CT Diagnostic Techniques
- NAAT (diagnostic choice for CT and Ng)
\*PCR amplification of RNA or DNA
\*Transcription mediated amplification (TMA)
\*Strand displacement amplification (SDA)
\*XPERT CT/Ng assay-provides results in 90min
\*women: first-catch urine, or endocervical or vaginal swabs
- Culture: Limited to research and reference laboratories
40
CT Treatment
- Uncomplicated cervicitis or urethritis:
\*Azithromycin 1gm po, single doese
\*-or Doxycycline 100mg po BID x 7 days
