Lecture 14: Bacterial STIs Flashcards
Syphilis, Gonorrhoea, Chlamydia
There have been 2 major proposed theories of the origins of Syphilis in Europe: A Columbian Origin or a far earlier European Origin.
What evidence is there to support or challenge these theories?
Columbian Origin
- + First Large scale outbreak shortly after Colombus and crew crossed the Atlantic.
- + Modern Genomic medicine suggests that closest related organisms to current Syphilis strains are found in the Northern parts of South America.
Earlier European Origin
- + Bones from individuals who died far earlier containing deformities characteristic of late-stage symphilis.
- - These symptoms may be been associated with a different related Treponial disease that originated in Northern-Africa.
When considering the progression of Syphilis, there are 3 distinct phases. Describe how the disease progresses through these 3 stages.
There is a separate question on symptoms of tertiary syphilis.
Infection with Treponema pallidum
1. Primary Syphilis: Chancre (painless, may not be readily visible) at site of infection, also regional lymphadenopathy. Chancre spontaneously resolves after a few days, patient feels better.
If treatment is not administered…
2. Secondary Syphilis: Months after infection, development of disseminated rash and generalised lymphadenopathy.
3. Latent Syphilis: Around 75% of individuals have no further complications, but remain infected so can transmit the disease. The other 25% of individuals may develop Tertiary Syphilis.
Lymphadenopathy: Swelling of the lymph nodes.
There are 4 that I should learn.
Around 25% of individuals develop tertiary syphilis following secondary syphilis. What are the symptoms associated with this?
- Bone deformities.
- Cardiovascular damage leading to arrhythmias.
- Neurological complications.
- Necrotic black lesions (gumma) on skin surface.
How is syphilis acquired?
- Sexual Intercourse.
- Congenital: infected pregnant mother can pass disease on to offspring, resulting in developmental abnormalities (both physical and mental) before and after birth.
The Tuskegee Experiement is responsible for the source of some of our knowledge of the progression of Syphilis diseases. Briefly outline what it involved.
- Study in Alabama, USA that lasted 40 years (1932-1972).
- Afro-Caribbean males diagnosed with early stage syphilis were recruited for the study.
- They were told that they had ‘bad blood’.
- Aim to identify progression of untreated syphilis until all individuals had died, and then to carry out autopsies.
- Ethical Concerns: Available treatment and information were withheld.
Which species of bacteria causes syphilis? What are its key properties?
Treponema pallidum.
- Gram-negative.
- Spirochaete (another member of this group is the organism that causes Lyme’s Disease).
- Extremely slow-growing (difficulties to culture).
- Obigate Parasite (highly dependent on presence of host factors for growth).
- Small genome.
- Lots of membrane-boudn transports enabling it to parasitise upon its host for nutrients.
- Sensitive to oxygen: highly adapted to survive only in host environments.
What are the unusual properties of Treponema pallidum?
- Despite being a Gram-negative bacteria: it does not contain LPS (this is indicative of spirochaetes).
- Flagelli unusually sit in the periplasmic space between inner and outer membranes of the bacterial cell wall. These are termed Endoflagelli. They are located at the poles of the organism allowing movement in a corkscrew motion.
What are the virulence factors that enable Treponema pallidum to cause disease?
- Highly motility allows rapid dissemination throughout host body.
- Able to penetrate tight junctions between epithelial cells toaccess underlying vasculature and lymphatic system.
- Symptoms result from host eliciting inflammatory response to presence of Treponema lipoproteins found on outer surface of the bacteria.
- Periodic emergence of symptoms: bacteria persists in areas of host that are immune-privellaged (under less comprehensive surveillance by immune system).
What are the treatments used for Syphilis (caused by Treponema pallidum)?
- Breakthrough in early 1900s using a compound containing arsenic.
- Since WWII, it has been superseded by penicillin (limited issues with antibiotic resistance). A single high-dose treatment should be sufficient.
What are the common symptoms for males with Gonorrhoea? How does this differ in females?
Males
- Pain on urination.
- Perulent urethral discharge.
Women: 50% of cases are assymptomatic
- Abdominal pain.
- Localised Inflammation.
Even in cases where individuals are assymptomatic, untreated gonorrhoea can lead to:
- Scarring of fallopian tubes resulting in ectopic pregnancies and infertility.
What are the characteristics of Neisseria gonorrhoeae?
- Gram-negative coccus that travels in pairs (often referred to as a diplococcus).
- Very similar in terms of properties to Neisseria meningitidis.
- Fastidious organism - requires lots of nutrient supplement to culture. It is grown on specialised agar media such as chocolate agar (simply reference to colour).
How does Neisseria gonorrhoeae to cause disease?
- Neisseris gonorrhoeae enters host epithelial cells by endocytosis. It traverses the cell and leaves at the basement membrane where it encounters macrophages and leukocytes.
- Neisseris gonorrhoeae are taken up into macrophage by endocytosis: some will be killed by phagocytosis; endotoxin (LPS) triggers inflammatory response leading to cell damage.
What are the virulence factors of Neisseria gonorrhoeae that enable adhesion to host cells and evasion of host immune response?
- Adhesion: Mediated by Type IV Pili that are made up of many copies of a single pilin subunits: each subunit contains a site of adhesion.
- Evasion of Immune Response: Phase and antigenic variation in the expression of pili.
Explain how phase variation in the pili structure of Neisseria gonorrhoeae may enable evasion of host immune response.
- Bacteria either expresses a phenotype containing pili or not containing pili.
- This depends on the site of proteolytic cleavage in post-translational modification of pilin subunits.
- The resulting protein subunit will either be able to assemble into a long pili structure or it will be secreted as soluble components.
Explain how antigenic variation in the pilin gene in Neisseria gonorrhoeae may enable evasion of host immune response.
- There are 2 allele of the gene that encodes the pilin gene: pilS (silent) and pilE (expressed).
- Recombination of the gene using a mixture of components from pilS and pilE alleles, enables formation of a new hybrid pilin protein with a different amino acid sequence.
- Immune system will be unable to recognise all different pili.
How is Gonorrhoea treated?
- In the past: Single high dose of penicillin was very effective.
- Mutations in pencilin binding protein led to penicilin resistance (evolutionarily advantageous for Neisseria gonorrhoea).
- Penicilin is no longer the recommended treatment.
- Neisseria gonorrhoea has since become resistant to many different antibiotics.
- Now reliant on Ceftriaxone and Cefixime as primary antibiotic treatments, sometimes in combination with azithromycin.
What is the World Health Organisation’s (WHO) recommendations regarding use of antibiotics against bacteria that are becoming increasingly resistant?
If incidence of resistance to a single antibiotic treatment rises to above 5%, it is not longer recommended as a suitable treatment.
Chlamydia is the most common bacterial STI in the UK. What percentages of men and women infected with Chlamydia are asymptomatic?
50% of men and 70% of women.
There are 3 unique to female, 2 unique to males and 1 common symptom.
What are the symptoms of Chlamydia in men and women?
Women: Unusual vaginal discharge, bleeding between periods, painful urination, lower abdominal pain.
Men: Discharge from the penis, genital itching/burning, painful urination.
There are 4 unique to women and 2 unique to men.
What are the potential complications for men and women with untreated Chlamydia infections?
Women: Chronic pelvic pain, Pelvic Inflammatory Disease (PID), Ectopic Pregnancy, Infertility.
Men: Epididymtis (inflammation of the tube at the back of the testis containing sperm), Reiter’s Syndrome (reactive arthritis).
What is the causitive pathogen of Chlamydia?
Chlamydia Trachomatis
How is Chlamydia treated?
A high, single dose of azithromycin should be sufficient.
