Sexually Transmissible infections

agents of STIs - bacteria (3)

• Chlamydia trachomatis -> Chlamydia

• Neisseria gonorrhoeae -> Gonorrhoea

• Treponema pallidum -> Gonorrhoea

agents of STIs - viral (4)

• Herpes simplex virus (HSV) -> genital ulcers

• Human immunodeficiency virus (HIV) -> HIV and AIDS

• Human papillomavirus (HPV) -> genital warts

• Hepatitis B virus -> Hep B

agents of STIs - protozoa (1)

Trichomonas vaginalis -> vaginitis

agents of STIs - arthropods (2)

• Phthirus pubis -> public lice

• Sacroptes scabiei -> scabies

features of bacteria commonly causing STIs - list (7)

• Highly infectious

• No animal reservoir

• Don't survive well outside host

• Damage predominantly caused by immune response

• Effectively treated by antibiotics -> patients and contacts

• Prevented by condoms

• Can be asymptomatic

strain - def

population of organisms that descend from single organism or pure culture

serovar (serotype) - def

variant strain of microbe that has distinct antigenic properties

genotype - def

specific set of alleles or genes carried in genome of an organism

infections caused by chlamydia - list (3)

genital infections

ocular infections

respiratory infections

infections and conditions caused by chlamydia trachomatis serovars D-K (4)

• Conjunctivitis

• Uro-genital tract infections

• Reactive arthritis

• Pneumonitis

chlamydia as an STI - features (4)

Most common bacterial STI globally

Typical symptom = discharge -> urethritis and cervicitis

Most infections = asymptomatic -> still infectious

Persistent infections common

chlamydia trachomatis - common sites of infection (5)

• Cervix

• Urethra

• Pharynx

• Rectum

• Eye -> where columnar epithelial cells present

chlamydia trachomatis - infection summary (3)

Can ascend upper genital tract to cause infection, damage and infertility

Eg. endometritis, salpingitis, pelvic inflammatory disease, epididymitis, proctitis

Infection in newborn contraction during birth process -> conjunctivitis

chlamydia trachomatis - morphology (4)

Gram negative -> outer membrane LPS is truncated and not very endotoxic

Abnormal peptidoglycan

Small and non-motile

Obligate intracellular bacteria -> need host cell mitochondria for energy

chlamydia trachomatis - lifecycle stages (2)

Unique replication cycle (2-3 days) with distinct developmental stages

EB = infectious extracellular particles

RB = intracellular and in replicative phase -> do not survive outside cells

chlamydia trachomatis - lifecycle steps (5)

1. Elementary body (EB) binds columnar epithelial cells by adhesins to enter via receptor mediated endocytosis

2. No fusion of EB-containing endosome with lysosome -> multiple endosomes fuse to form an inclusion

3. EB transforms into metabolically active reticulate body (RB) -> replicates inside inclusions

   • Prolonged RB phase -> persistence

4. RB converted back to EB

5. Release of EB from epithelial cell

chlamydia trachomatis - tissue damage summary

Damage caused predominantly by host immune response -> chronic inflammation

chlamydia trachomatis - recurrence of infection

Infections can recur -> more damage = no lasting immunity

Long term sequelae = ascending inflammatory damage -> non-invasive infection

Eg. pelvic inflammatory disease, infertility, ectopic pregnancy

chlamydia trachomatis - tissue damage steps (4)

1. Infected epithelial cells produce chemokines and other immune mediators → influx of immune cells inc. neutrophils

2. Innate and adaptive immune activation and cell death

3. Continued immune activation → chronic inflammation -> cell damage and scar tissue formation

4. Activated CD4+ and CD8+ T cells and macrophages produce IFN-gamma → prolonged RB phase

chlamydia diagnosis - methods list and summary (2)

1. specimens → (self-administered) cervical or urethral swabs or first-pass urine

2. tests → PCR on first pass urine or discharge samples or antigen detect via EIA RAT on self-collected vaginal swabs

chlamydia diagnosis - reasoning for first pass urine

First-pass urine = more concentrated epithelial cells as opposed to mid-stream sample for UTIs

chlamydia - treatment (4)

Antimicrobials target RBs -> require good penetration of tissues and cells

Preferred treatment = single dose of long-acting macrolide or 1 week dose of tetracycline

• Macrolide antibiotics and tetracyclines = good tissue/ cell penetration a

• Long acting or multiple doses required because life cycle is asynchronous and 2-3 days

Neisseria gonorrhoea - morphology (5)

• Gram negative diplococcus -> often intracellular

• Extremely fastidious

• Grows best in CO2 enriched atmosphere

• Similar clinical presentations to chlamydia

• Motile

Neisseria gonorrhoea - implications of being motile

Females: bacteria may ascend genital tract -> PID

May also cause disseminated disease but rare

Neisseria gonorrhoea - symptoms (4)

When symptomatic, presents as urethritis a few days after contact -> other sites may be asymptomatic

Females have more asymptomatic infection than males

Newborns may contract conjunctivitis

Symptoms of pus and pain generally more severe than in chlamydial infection

neisseria gonorrhoea - life cycle steps (4)

1. Targets mucosal columnar epithelial cells -> attaches via adhesins

Eg. pili, outer membrane proteins, lipo-oligosaccharide (form of LPS)

2. Typically replicates at cell surface and spreads in mucosal secretions → pili have twitching motility

3. May invade some cells -> translocation to sub-epithelial tissues to cause inflammation and dissemination

• Invasion to cause systemic disease rare but possible

4. Antigenic variation in pili and gonococcal surface proteins allows avoidance of antibody responses and prolongs infections

neisseria gonorrhoea - method to cause tissue damage and evade immune response (4)

Inflammatory response stimulated by LPS and peptidoglycan -> interaction with PRR and TLR

Can avoid killing by neutrophils and complement → invasive strains have altered LPS which lack certain outer membrane proteins

Production of IgA protease -> cleaves IgA so it can't opsonize bacteria and mark for phagocytosis

TNR production -> loss of ciliated epithelial cells

neisseria gonorrhoea - immunity

Re-infections common so no immunity from prior infection

neisseria gonorrhoea - importance of diagnosis and treatment

Early diagnosis and treatment needed to reduce possible sequalae of PID and infertility

neisseria gonorrhoea diagnosis - methods list summarised (3)

1. Specimens:

• collect discharge/ swab from urethra, cervix or other and gram stain and culture

• PCR -> collect urine, self-administered vaginal swab

• antigen detection via EIA RAT on self-collected vaginal swabs now available

2. microscopy → gram stain shows intracellular and extracellular Gram-negative diplococci and polymorphonuclear neutrophils

3. culture on GC biplate → has lysed blood and other components to control growth of normal microbiota, non-antibiotic side used as control and to identify antib

neisseria gonorrhoea - implications if not treated properly

Rapid antibiotic resistance and persistence if treatment incorrect -> efficient acquisition of genetic material from other sources

Horizontal gene transfer and naturally competent

neisseria gonorrhoea - treatment process (3)

Use antibiotic guidelines for current recommendations for empirical treatment

Culture = essential to determine antibiotic susceptibility

Currently: injectable beta-lactamase resistant cephalosporin and azithromycin → high rate of co-infection with chlamydia so beneficial to treat all patients with gonorrhoea with azithromycin as well

treponema pallidum - morphology (5)

• Slender, spiral rod

• Need special techniques to visualise -> eg. dark field microscopy

• Motile -> periplasmic contractile flagella for corkscrew like movement

• Very labile -> easily inactivated

• Difficult to culture -> requires mammalian cell culture

treponema pallidum - infection summary (3)

Infection may be asymptomatic or symptomatic

Infection = invasive and spreads to region beyond initial infection

Can spread via placenta to foetus -> congenital infection

treponema pallidum - stages of infection and transmission list (4)

1. Infection  -> ~3 week incubation period

2. Primary syphilis

3. Secondary syphilis

4. Tertiary syphilis

   • Less common since testing/ treatment available

   • Targets eyes, ears, heart, brain -> eg. neurosyphilis

   • Patients may present with gummas -> non malignant tumours that degrade bone

treponema pallidum - primary syphilis symptoms (2)

Chancre (ulcer on point of infection site) or asymptomatic -> lesions very infections

Asymptomatic/ latent for 2-24 weeks

treponema pallidum - secondary syphilis symptoms (4)

• Rash typically on hands and feet → lesions are infectious

• Warty genital lesions

• Lymphadenopathy

• Asymptomatic/ latent for 3-30 years

treponema pallidum - tertiary syphilis symptoms (3)

• Less common since testing/ treatment available

• Targets eyes, ears, heart, brain -> eg. neurosyphilis

• Patients may present with gummas -> non malignant tumours that degrade bone

treponema pallidum diagnosis - methods list (2)

1. Swab from primary or mucosal secondary lesion → dark-ground microscopy or PCR from exudate

2. Blood specimen → serological test for specific antibodies to treponemal antigens or for cross reactive antibodies to cardiolipin

treponema pallidum diagnosis - downside of serological testing for specific antibodies to treponemal antigens

Usually remain positive for life -> can only tell you if you have active syphilis or previously infected

treponema pallidum diagnosis - benefit of serological testing for cross reactive antibodies to cardiolipin

Correlates with disease activity -> identify if syphilis is active

Used to confirm active infection and to monitor response to treatment

treponema pallidum - treatment

Sensitive to penicillin -> use long acting penicillin

No reported resistance to penicillin -> some to azithromycin

treponema pallidum - importance of treatment (2)

prevents:

• progression to tertiary syphilis that can develop from latent infection

• congenital syphilis and its complications -> screen for antibodies during all pregnancies