Fagan L22-23 Flashcards
Why is the incidence of STIs increasing?
- Use of the pill since the 1950s has replaced barrier methods of contraception that help prevent spread of STIs.
- Change in public attitudes to sex – increased numbers of sexual partners in many western countries has occurred in the last several decades. Now driven by widespread internet use and dating apps
- Other factors: Problems of drug resistant strains of bacteria, poor attendance at STI clinics by some infected individuals, lack of appropriate sex education advice etc.
What are the characteristics of gonorrhea?
Neisseria gonorrhoeae. Gram negative coccus seen as diplococci in discharge. Non-motile. Humans are only host so no animal reservoir. Transmission caused by person to person contact through intimate mucosal contact.
What are the symptoms of gonorrhoea?
Usually appear 2-7 post infection. Male = thick urethral discharge. Pain on urination. Female = Vaginal discharge. Up to 50% of infected females may be asymptomatic or only have mild initial symptoms.
What complications can occur with gonorrhoea?
- Pelvic Inflammatory Disease (PID)
- Damage to fallopian tubes, leading to infertility
- Other disseminated symptoms
- In pregnancy, can be passed to the baby during birth, where the bacterium colonises the eyes, leading to blindness if not treated.
What are the virulence factors in gonorrhoea?
Many surface proteins and structures, involved in adhesion and invasion of epithelial cells lining urethra or vagina. Good adhesion essential for mucosal pathogen in this environment to prevent being dislodged by urine flow.
What is the gonococcal strategy for evading immune system?
The LPS can be modified by attaching sialic acid residues to it so it looks like the host tissue to the immune system and so does not provoke an immune response. This is molecular mimicry.
Many of the surface proteins are highly immunogenic, but gonococci can continuously produce sequence variants that make it difficult for the immune system to mount an effective response. Such proteins represent hypervariable surface antigens that allow immune evasion. This is antigenic variation.
What are the treatments for gonorrhoea?
- 1940s -1970s: Penicillin, but resistance became a major problem
- 1980s: Fluoroquinolones, e.g. ciprofloxacin (DNA gyrase inhibitor). Resistance now a major issue so they cannot be used.
- 2000s – present: Cephalosporins, e.g. ceftriaxone and cefixime - resistance is becoming quite common.
What are the characteristics of syphilis?
Treponema pallidum. Complex disease first described in 1400s. One theory (the “Columbian hypothesis”) suggests that returning crewmen from Christopher Columbus’ voyages to the Americas spread the disease to Europe. The “pre-Columbian” hypothesis suggests it was indigenous, but went unrecognized. The disease became increasingly common in the following centuries, becoming known as “The Great Pox” or “The French Disease”. Its symptoms can be varied and easily confused with other diseases, making traditional diagnosis difficult. A very fragile, slow-growing bacterium, with poor survival outside of the host. Infection requires intimate sexual contact, and is aided by minute tissue abrasions that occur during sex. Infection is CHRONIC and in untreated cases may last decades, with maybe 30-50% mortality.
How does syphilis survive?
- Lack of endo and exotoxins = T. pallidum lacks LPS, the endotoxin found in the outer membranes of many Gram-negative bacteria. The attachment of T. pallidum to cells does not harm the cells. This indicates that cytolytic enzymes or other cytotoxins most probably do not play a role in syphilis pathogenesis.
- Invasion of immune privileged tissues = T. pallidum penetrates a broad variety of tissues, including so-called “immune privileged”: the central nervous system, eye, and placenta, where there is less surveillance by the host’s innate immune system.
- Ability to maintain infection with few organisms = T. pallidum may also exploit its slow growth to survive in tissues, even those that are not immune privileged. By maintaining infection with very few organisms in anatomical sites distant from one another, T. pallidum may prevent its clearance by failing to trigger the host’s immune response, which was may require a “critical antigenic mass”.
- Lack of surface antigens = One of most prominent features of T. pallidum is that it has only rare integral proteins in its outer membrane, approximately 1% of the number found in the outer membrane of E. coli. However, these rare proteins are likely to be very important in interactions with the host; for this reason, their identity has been the subject of intense research.
- Low iron requirements, ability to obtain sequestered iron = T. pallidum may be able to acquire iron from host proteins. It may also overcome the iron sequestration problem by using enzymes that need metals other than iron as their cofactors. In addition it lacks an electron transport chain, which is made up of enzymes that use iron as a cofactor, which decreases its overall demand for iron.
What are the treatments for syphilis?
In 1910 Paul Ehrlich developed salvarsan – an organic arsenic containing drug- which was partially effective but quite toxic. T. pallidum is very sensitive to penicillin, which is still the best treatment, as little resistance has developed. Its introduction in the 1940s led to a massive reduction in the numbers of cases and the disease became rare. However, because the bacterium is so slow growing it is essential that a high level of penicillin is maintained in the body for several weeks; it must be injected either daily IV or 2 x injections of a slow release formulation in the buttocks over a 1 month period (painful!). In the 1970s numbers of cases started to rise again; it is now a significant STI. A particular problem is co-infection of syphilis and HIV – infection with syphilis makes it several times more likely that HIV infection occurs.
What are the characteristics of chlamydia?
Small wall-less bacteria which are obligate intracellular parasites. Have a complex life cycle based on two functionally distinct cell forms. Elementary body survives outside host cells and initiates infection. Reticulate body differentiates from EB and is responsible for intracellular growth.
What infections does the different strains of chlamydia cause?
A,B,C cause trachoma - a serious eye infection. D,K cause urethritis in men and cervicitis in women. L1-L3 cause lymphogranuloma venereum.
What are the symptoms of chlamydia?
Men = thin, watery urethral discharge. Pain on urination but can be asymptomatic. Females = Infection of cervix. Urethritis. Infertility and ectopic pregnancy. Very often asymptomatic.
What are the treatments available for chlamydia?
Insensitive to beta-lactam antibiotics as they have no peptidoglycan. Have to use alternatives like tetracycline/doxycycline or azithromycin which have some side effects.
What are the factors responsible for the emergence of new and re-emergence of old pathogens?
- Globalization and environmental change = Increased urbanization in tropical countries has led to massive increases in insect borne viral diseases like Dengue fever. Clearing forests in Africa has led to the emergence of Ebola virus by new zoonotic transfer to humans. Climate change (global warming) allows vector borne diseases to spread into new areas. Increased international travel and commerce - Long-haul flights with air re-circulation may lead to transfer of respiratory diseases.
- New ways of growing and handling food = “New” food-borne pathogens like Campylobacter, E. coli 0157 and other strains take advantage of modern high-volume meat production methods and inadequate cooking. More examples of increased zoonotic transfer of pathogens from animals to humans is occurring (eg COVID-19).
- Natural disasters and breakdowns in public health = Earthquakes, floods, tsunamis, political upheaval etc will lead to outbreaks of many otherwise well controlled diseases. Without clean water, cholera will become a problem. Inadequate take up or effective vaccination programmes will lead to outbreaks – Diptheria and whooping cough rates increase after natural disasters or civil wars etc. In the UK, the MMR (measles-mumps-rubella) vaccine scare led to lower uptake of the vaccine and outbreaks of measles.
- Changes in pathogens = Development and spread of antibiotic resistance has been increasing and is now a major problem for treatment. High mutation rates in some viruses (HIV). Acquisition of novel toxin genes by specific bacterial strains, from other bacteria.
- Recognition of new pathogens = Some “old” diseases have been discovered to be caused by “new” pathogens (e.g. Helicobacter pylori), and epidemic outbreaks of new diseases are attributed to previously unknown pathogens (e.g. Legionella pneumophila)
