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.