3.1 Sexually transmitted bacterial diseases

STI

presence of a pathogen (bacteria, virus or parasite) in the body that has been transmitted through sexual contact - the person may be asymptomatic and unaware of the infection

STD

occurs when an STI progresses to cause symptoms, tissue damage or clinical manifestations - not all STIs become STDs, some are cleared by the IS or remain dormant

Divergent disease

when the same pathogen can lead to vastly different clinical consequences across different individuals

asymptomatic carrier

Some individuals harbour infections like Chlamydia trachomatis or Neisseria gonorrhoeae without symptoms, unknowingly transmitting to partners whilst remaining disease free

Localised vs systemic progression

untreated infections may remain localised (urethritis, cervicitis) or ascend to cause severe complications such as pelvic inflammatory disease (PID), leading to infertility, ectopic pregnancy or chronic pelvic pain

Immune response variation

Individual immune responses determine whether an infection is cleared, controlled or progresses to disease - immunocompromised individuals face higher risks of disseminated infection (into the bloodstream)

Co-infections and synergy

Presence of one STI increases susceptibility to others, including HIV, compounding disease severity and transmission risk

Chlamydia info

Bacterial, can be cured, fluid transmission

Gonorrhoea info

Bacterial, can be cured, fluid transmission

Syphilis info

Bacterial, can be cured, fluid and skin to skin transmission

Trichomoniasis info

Protozoa, can be cured, fluid transmission

HSV (Herpes) info

Viral, not curable, can be managed, fluid and skin to skin transmission

HPV (human papillomavirus) info

Viral, not curable, can be managed, fluid and skin to skin transmission

Factors contributing to rising STD cases

Increase substance use, decrease condom use, elevated rates in Native American reservation

chlamydia symptoms

Pain during sex and urination, green/yellow fluid discharge

Chlamydia trachomatis organism

Gram-negative-like (lacks peptidoglycan), obligate intracellular bacteria (lack several metabolic and biosynthetic pathways, depend on host cell for intermediates inc ATP), coccoid or rod shaped, non-motile, 2 forms: small infectious elementary bodies and larger replicating reticulate bodies

Chlamydia habitat/survival

Humans only, genital tract, cervix, urethra. Cannot survive outside host. Oral, vaginal or anal sex, mother → newborn in vaginal birth. No environmental reservoir

Chlamydia epidemiology

Trachoma - worldwide esp in Africa/Asia, inoculated into the eye by contaminated fingers or fomites or through vaginal birth. Genital infections - sexual contact. Respiratory infections - inhalation of infected droplets

Chlamydia genital infection in men

Commonly urethritis, incubation = 7-21 days (more than the 2-5 days for gonorrhoea)

Chlamydia genital infection in women

Typically infects columnar epithelial cells of endocervix, discharge from cervix, urethral syndrome, can develop PID, infertility, ectopic pregnancy

What is PID?

serious infection on women’s reproductive organs, caused by STDs like chlamydia/gonorrhoea, 1/8 women with PID have difficulty getting pregnant

PID symptoms

Pain in lower abdomen, fever, unusual discharge, bad odour from vagina, pain/bleeding during sex, burning urination

PID treatment

if diagnosed early can be treated, cannot undo damage

Lymphogranuloma Venereum (LGV)

3-12 days after chlamydia infection, three stages: small genital blister or ulcer; painful swollen lymph node in the groin; sores heal but left scars.

Neonatal pneumonia

Subacute afebrile (non-fever) pneumonia occurring in infants 4-12 weeks, acquired from mother in vaginal delivery, staccato cough, non-toxic

neonatal pink eye

6-21 days foe chlamydial infection, swelling of infant’s eyelid, conjunctival scarring

Two forms of chlamydia needed for infection/disease

1- infectious, extracellular form - elementary body (EB), 2- non-infectious, metabolically active intracellular - reticulate body (RB)

Chlamydia EB virulence factors

Small and infectious, rigid outer membrane, bind sialic acid receptors on epithelial cells and phagocytes

Chlamydia RB virulence factors

Large replicating form, metabolic, binary fission within the inclusion, reorganises EBs for release/further infection

Chlamydia LPS virulence factors

Endotoxin in outer membrane, triggers inflammatory response, contributes to tissue damage in chronic infections

Chlamydia T3SS virulence factors

Delivers effector proteins into host cells, manipulates host cell signalling pathways, facilitates intracellular survival and replicaiton

Chlamydia SemC protein virulence factors

Secreted by the bacteria during entry, recruits host protein SNX9 to infection site, exploits host cell machinery for bacterial uptake

Chlamydia inclusion membrane virulence factors

Creates protected intracellular niche, prevents fusion with lysosomes, allows nutrient acquisition from HC

Chlamydia evasion of immune response virulence factors

Intracellular location protects from antibodies, inhibits apoptosis to prolong infection, modulates antigen presentation

Chlamydia infection cycle

Image

Neisseria gonorrhoeae overview

sexually transmitted disease most common in young adults, infects genital tract/mouth/anus via vaginal/oral/anal sex, can be passed during vaginal birth

Gonorrhoea organism

Gram negative, diplococci, non-motile, aerobic, nutritionally fastidious (req. blood/hemoglobin), pink/brown colonies, survives few seconds in environment

Gonorrhoea habitat

human only host (repro tract), not normal microflora, sites of exposure, cannot survive well outside eukaryotic host

Gonorrhoea source

contact: unprotected sex, eyes/mouth contact, vaginal birth

Gonorrhoea epidemiology

2nd most common STI amongst 20-30yrs, can occur at any age, 20% risk for men (hetero), 60-80% risk for women (hetero), vaginal birth causing eye infection, cannot be spread on surfaces, most infections are aymptomatic

Gonorrhoea clinical disease women

50% of cases asymptomatic, abdominal pain during sex, vaginal discharge/bleeding

Gonorrhoea clinical disease men

Mainly acute urethritis → infected kidneys, UTI, burning urination, inflammation, swollen testicles, discharge

Gonorrhoea Lipo-oligosaccharide virulence factors

Endotoxin in outer membrane, triggers inflammatory response, undergoes antigenic variation to evade IS

Gonorrhoea Type IV pili (T4P)

mediate attachment to epithelial cells, enable twitching motility, undergo antigenic and phase variation, protect against phagocytosis

Gonorrhoea por protein virulence factors

Channel protein, major outer membrane porin protein, facilitates nutrient stability, provides structural stability, may contribute to immune evasion

Gonorrhoea opacity-associated protein (Opa) virulence factors

Mediates adherence to/invasion of epithelial cells, binds to CD66 receptors on human cells, undergoes phase and antigenic variation, promotes uptake by neutrophils

Neisseria gonorrhoeae infection

Gonorrhoea T4P + Opa infection

1. gonococci interact with the mucosal epithelium and neutrophils

2. pili retract allowing Opa-mediated attachment

3. after opa attachment, bacteria are engulfed and internalised into mucosal cells

4. Some cells can transcytose to the basolateral side of the mucosal epithelium

5. Opa offers immune evasion by multigene phase variation that results in antigenic variation

6. Following transcytosis, gonococci can enter the bloodstream where LOS renders the bacteria serum resistant

Gonorrhoea Major outer membrane porin (PorB)

As well as being an outer membrane pore, PorB also performs multiple functions contributing to pathogenesis: inducing/inhibiting apoptotic signalling in cells, serum resistance, epithelial cell invasion under low phosphate conditions, can affect generation of reactive oxygen species by innate immune cells

Virulence factors of gonorrhoea

LOS, T4P, Por/PorB, Opa

Treponema palladium (Syphilis) overview

difficult to detect at early stage, penicillin effective antibiotic, first symptom is a small, round sore (chancre), can develop anywhere on body but mainly affects anus/mouth/genitals. Painless sore but highly infectious

T. palladium organism

spirochaete, neither gram pos/neg, endoflagella for motility, obligate human pathogen, aetiological agent of venereal and congenital syphilis

T. palladium habitat/source

Oral cavity, intestines, rumen, genitals (animals/humans). Occurs primarily 15-40yrs, 1 million infants/year born congenital syphilis

syphilis epidemiology

via placenta, kissing, close contact with active lesion, blood transfusion, direct inoculation (clinical setting), sexual contact (vast majority)

Stage 1 syphilis

3-90 days after exposure, painless sore (chancre), anywhere on body, highly infectious, heals 3-6 weeks w/out treatment, bacteria remain in body and progress to stage 2 if not treated

Stage 2 syphilis

4-10 weeks after initial infection, body rash anywhere, common on palms and soles, may be fever, swollen lymph nodes, sore throat, fatigue, symptoms can come/go over several months, highly infectious

Stage 3 syphilis

Occurs if syphilis remains untreated, affects internal organs inc. heart, brain, blood vessels, liver, bones, joints, can cause serious complications like CV problems, neurosyphilis, gummatous lesions, blindness, dementia, death. Not contagious but damage irreversible

T. palladium endoflagella v factors

rotation produces cork-screw movement, hides antigens from host immune system, contained within periplasmic space

T. palladium outer membrane protein v factors

limited immunogenic surface proteins, helps evade immune detection

T. palladium hyaluronidase v factors

facilitates tissue penetration, aids in dissemination throughout the body

T. palladium adhesins v factors

enable attachment to host cells, facilitates colonisation of mucosal surfaces

start of infection - T. palladium

when it penetrates host usually through intact/abraded mucous membrane