Lecture Notes on Sexually Transmitted Infections (STIs)

Global and UK Importance of STIs

  • STIs are a significant area in microbiology.
  • The rise in antimicrobial resistance (AMR) related to STIs is concerning.

Overview of Specific Infections

  • Briefly covers gonorrhoea, chlamydia, and syphilis.
  • Touches on the bacteria that cause these infections and diagnostic tests.
  • Highlights the need for better diagnostic tests in microbiology research and development.

Global Significance of STIs

  • WHO estimates that over 1 million people acquire an STI daily.
  • More than 500 million people live with incurable herpes simplex virus infections.
  • The highest burden falls on low and middle-income countries, requiring global efforts.

Incidence of Curable STIs

  • Illustrates the large numbers and impact of these infections.
  • Public health initiatives are in place to prevent and control STIs like HPV.
  • Burden of infections largely affects lower and middle-income countries.
  • Research focuses on improving treatments, diagnostics, and public health interventions.

Normal Flora: Vaginal Microbiome

  • Urine is no longer considered sterile, based on sequencing studies.
  • Vaginal microbiome has a natural community dominated by Lactobacilli.
  • Lactobacilli are beneficial bacteria that colonise and form biofilms on epithelial cells.
  • They inhibit the growth of pathogenic organisms.
  • When a pathogen attempts to invade, if a dominant commensal species has already created a biofilm, it is harder for the pathogenic organism to take over.
  • Lactobacilli produce lactic acid, lowering pH.
  • The acidic environment inhibits the survival of many bacteria.
  • Lactobacilli prevent long-term colonisation by other species.
  • They produce hydrogen peroxide, which inhibits the growth of other species and inactivates viruses like HIV and herpes simplex virus.
  • They produce antimicrobial peptides called bacteriocins to kill other bacteria.

Semen Microbiome

  • Recent studies show semen has a microbiome related to fertility issues.
  • Microbiome studies aim to distinguish between healthy and unhealthy states, but it's complex.
  • Diversity in the microbiome often indicates a healthier environment.
  • Semen has antibacterial and antimicrobial activity with peptides, enzymes (like lysozyme), phospholipids, and lactoferrin.

Gonorrhoea

  • Caused by the bacterium Neisseria gonorrhoeae.
  • Infections can be uncomplicated (localized) or disseminated.
  • In uncomplicated infections, it generally infects mucous membranes of the urethra or cervix; it can also infect the eye causing conjunctivitis.
  • Disseminated gonorrhoea can cause arthritis or dermatitis throughout the body.
  • Most common in young adults.
  • There are various public health surveillance programs in place.

Complications and Prognosis

  • In males, it tends to manifest in an acute phase.
  • In women, it can be asymptomatic and undiagnosed, leading to implications during pregnancy like spontaneous abortion.
  • Disseminated gonorrhoea presents differently.

The Bacterium: Neisseria gonorrhoeae

  • Fastidious, gram-negative cocci.
  • Nucleic acid amplification tests are used for initial diagnosis because Neisseria is difficult to culture.
  • Cultures are still used to monitor antimicrobial resistance.
  • Has pili for attachment to epithelium, containing constant and hyper-variable regions.
  • Hyper-variable regions contribute to antigenic diversity and evade body defenses.

Virulence Factors

  • Pili are important for attachment to the epithelium.
  • Pore proteins create holes in host cell membranes.
  • Rmp proteins inhibit antimicrobial properties found in semen.
  • Enzymes destroy IgA1.
  • Has a capsule to resist phagocytosis by white blood cells.

Antimicrobial Resistance

  • High risk of multidrug resistance development.
  • Continuing concern about the rapid development of resistance in Neisseria.

Chlamydia

  • Most common curable bacterial STI in the UK, caused by Chlamydia trachomatis.
  • Obligate intracellular bacterium.
  • Infection patterns differ between males and females.
  • Large proportion of infections are asymptomatic.
  • Classified as uncomplicated or complicated based on whether it has ascended into the upper genital tract.
  • Highest rates in the young adult population.

Implications of Infection

  • Untreated infections can self-resolve or persist, leading to various presentations, including arthritis.
  • Impacts anxiety and distress, which can affect immune status.
  • Can cause severe implications in pregnancy.

Diagnostic Tests

  • Nucleic acid amplification tests are used for diagnosis.
  • Clinical tests balance fast results with sensitivity and specificity.
  • Cell culture has high specificity but takes weeks.
  • PCR-based methods offer a rapid result with adequate specificity and sensitivity.

Virulence Factors

  • Outer lipopolysaccharide membrane has cysteine-rich proteins that inhibit phagosome fusion.
  • Adhesion to receptors on mucous membranes.
  • Antigenic variation evades the host immune response.
  • A needle-like projection type three secretion apparatus injects bacterial proteins into the cell cytoplasm, which helps divert lipids.

Lifecycle of Chlamydia trachomatis

  • Obligate intracellular organism.
  • Exists as inert elementary bodies outside the host cell.
  • Inside the cell, elementary bodies become metabolically active reticulate bodies (RBs).
  • RBs replicate within the cell.
  • The conversion from an elementary body into a reticulate body takes 1 to 2 days after infection.
  • Host cell lysis releases elementary bodies to infect other cells.

Syphilis

  • Caused by the spirochete Treponema pallidum.
  • Presents as primary (painless ulcer) or secondary.
  • Secondary syphilis is a multisystem disease affecting mucous membranes and causing headaches.
  • Disease development varies; can have latent periods before late syphilis develops.
  • Syphilis rates are increasing globally and in the UK.

The Bacterium: Treponema pallidum

  • Obligate intracellular parasite.
  • Gram-negative, fastidious with a corkscrew shape.
  • Very thin (150-200 nm wide) and long (up to 10 μm).
  • Relies on host cells for nutrients.
    1 \,\mu m = 1000 \,nm

Structure and Replication

  • Outer layer composed of glycogen, glucose, and amino glycan.
  • Has an axial filament for stability.
  • Replicates by transverse fission instead of binary fission.

Virulence Factors

  • Outer membrane proteins aid adherence.
  • Produces highly variable antigens to invade cells and the bloodstream.
  • Coats itself with fibronectin from the host cell to evade the immune system.

Diagnosis

  • Difficult to culture, so diagnosis is based on microscopy and blood tests.

History and Ethical Issues

  • Notable historical and ethical issues, including the Tuskegee Syphilis Study where treatment was withheld from participants.
  • Reflects the importance of ethical practices in research.
  • Syphilis can significantly impact mental capacity and decision-making.