Lecture 7 STI Flashcards
In the UK STIs are the second most communicable disease problem , T or F
False, it is the greatest communicable disease problem!
How many attendances at GUM clinics in uk are accounted to STIs
> 1.5 million
Wwhat is the STI cost burden to NHS per year
£750 million/annum
What is the cost of HIV and other STI respectively to nhs each year
Hiv £580 million
Others £65 million
Which social groups are most likely to be affected by STI
MSM (homosexual men)
Young people high risk lifestyles - multiple partners and lack of condoms use
Disadvantaged socio-economic communities (africa, secondary schools (lower understanding))
What bacteria are associated with STIs and what conditions do they cause
Chlamydia trachomatis - non specific urethritis (approx 200,000 new cases in uk per year
Neisseria gonorrhoae - Gonorrhoea (approx 40,000 new cases in uk per year
Treponema pallidum - syphilis (approx 5,000 new cases in uk per year
what viruses are associated with STIs and what diseases do they cause
Human papilloma virus (DNA virus) - genital warts - (approx 68,000 new cases in uk per year
Herpes simplex - genital herpes (approx 33,000 new cases in uk per year
Hepatitis B/C - hepatitis - 5 million in uk
HIV - AIDS - (approx 6000 new cases in uk per year - 54% MSM)
What fungi is associated with STIs and what disease does it cause
C albicans and thrush (approx 80,000 new cases in uk per year
What parasites are associated with STIs and what disease do they cause
Trichomonas vaginalis - vaginitis - (approx 8,000 new cases in uk per year
What arthropods are associated with STIs and what disease do the cause
Sarcoptes scabei - genital scabies Phthirus pubis (crab louse) - pediculosis pubis
Name some capnophilic organisms and explain what it means
Microorganisms that thrive in presence of high conc of co2. E.g. Gram negative cocci Neisseria spp.
What symptom does parasitic vaginitis cause
Inflammation with frothy green vaginal discharge
How has the morning after pill and contraceptive pill contributed to STI
Prevent pregnancy but doesnt protect against sti
What is the correlation between grindr use and gonorrhoea& syphilis increase
More likely for casual one night stands - very quick contact with people
Name some factors linked with an increase in STI cases
Drugs/alcohol - lowered inhibitions
MSM- more likely for partner exchange
Contraceptive pill
Lack of education / awareness
In what year was the outbreak of super-gonorrhoea in leeds
2015
Resistant to every antibiotic !!
Which microbe causes chlamydia
Chlamydia trachomatis
How is chlamydia spread
Vaginal, anal and oral sex and can be transmitted during pregnancy from mother to baby
Incubation time 1-3 weeks
What are the clinical manifestations of chlamydia
Often asymptomatic - 75% o women and 50% of men therefore become reservoirs.
If symptoms:
Male - urethritis (watery, white discharge)
Female - urethritis/cervicitis/vaginitis and dysuria
What complications can occur from chlamydia
Pelvic inflammatory disease )PID) in 40% of cases
Infertility in males (descend into tests and high affinity for sperm attachment) and F ( ascend into fallopian tube)
Occular infection e.g conjunctivitis in neonates (chlamydia conjuvictis of newborn baby) and adults.
What programme was established in 2003 for chlamydia
The national chlamydia screening programme (NCSP) - control and prevention
What was the aim of the NCSP in 2003
Detect and treat asymptomatic carriers of chlamydia, targeting people <25 sexually active in contraceptive services, GP surgeries, community pharmacies, outreach clinics etc
Between 2003 and 2012 how many tests were performed and chlamydia infections detected by NCSP
5.5 million tests
370,000 ‘silent infection’ diagnoses from urine samples.
What statistic regarding under 25s and chlamydia was stated by NCSP
1:10 who are sexually active carried chlamydia and didnt know they had it.
What is the treatment for chlamydia q
Clamelle (azithromycin) single day dose of 2 tablets at 500mg
Or doxycycline (vibramycin) for 7-14 days at 200mg
Which 4 antigenic types HPV virus cause more than 70% of infections
6,11,16,18. 16/18 risk for cervical cancer
Which antigenic types of HPV are mainly responsible for genital warts
6 and 11
Where do genital warts occur?
Upon point of contact e.g. Mouth, vagina, penis etc
How is HPV transmitted
Vaginal,anal and oral sex
Incubation period 1-6 months or even years
What age range are mostly affected by HPV infections
17-33 year olds.
How does HPV infection manifest clinically
Warts (90% by HPV types 6/11.) . Multiple, dry, keratinised, ‘cauliflower in appearance’ but painless.
What is neoplastic conversion in regards to HPV
Cervical cancer caused by high risk HPV 16/18
What percentage of cervix cancers in 2002 was caused by HPV
100%
What are the treatment options for HPV genital warts
Podophyllin (cytotoxic)- 50% success
Imiquimod (immunostimulatory agent which boost immune response)
What are the treatment options for HPV cervical/intraurethral
Co2 laser removal deep within anatomy
What are the prevention options for HPV
Vaccination using Gardasil against HPV 6,11,16 and 18
Girls currently vaccinated
What microbe causes herpes
Herpes simplex virus (HSV1 = 40% HSV2 = 60%)
How is herpes transmitted
Vaginal, anal and oral sex with an incubation of 3-7 days
What are the primary clinical manifestations of Herpes
Primary - asymptomatic 70%, symptoms constitutional and localised such as feeling unwell in general, untreated can last approximately 28 days however it becomes latent.
What are the reactivation clinical manifestations of Herpes
Tenderness, pain and burning at site of eruption lasting 2hr to 2 days.
Women - lesions on labia and perineum
Men - lesions on the shaft, prepuce (foreskin), glans
Lesions heal in 7-10 days, dissemination and encephalitis
When may reactivation occur and why
Herpes lives in nerve cells and can reactivate due to stress and get oral or genital herpes.
If immunocompromised then virus can spread and cause mild inflammation of the brain (encephalitis - fevers, headaches and seizures)
What is the treatment and prevention for herpes
Acyclovir (zovirax) : 200mg 5x daily for one week
Famciclovir : 200-250mg 3x daily for 1 week
Safe sex
What microorganism causes gonorrhoea
Neisseria gonorrhoeae
N gonorrhoeae is a obligate human pathogen , t or f
true
How is gonorrhoea transmitted
Vaginal, anal, and oral sex
Incubation period 2-7 days
Only through DIRECT CONTACT
What other infection may occur with gonorrhoea
Rectal infection may follow anal intercourse and in women by local spread of gonococcus from vaginal introitus .
Often asymptomatic but pain, itching, tenesmus (feeling of need to empty bowel constantly), discharge and bloody diarrhoea may occur
What are the transmission rates after one exposure with an infected individual for M and F and explain why
Males - 20%
Females 80%
Ejaculate contain more bacteria so women more likely to get infected
When may conjunctivitis occur with gonorrhoea
Mother to baby transmission
What is the epidemiology of gonorrhoea
Rates higher in urban regions esp london
Men form 70% of these - of which MSM and black ethnic groups account for 1/3 of these
Female 16-19 years, male 20-24years
What are the clinical manifestations of gonorrhoea in males and females
Asymptomatic in many cases (70% female, 10% male)
Male - urethritis , dysuria, thick purulent penile discharge (due to LPS on gram neg surface- high inflammatory response)
Female - dysuria, cervicitis , thick purulent (sometimes bloody) vaginal discharge
Rectal infection with anal discharge and pain on anal sex
Throat infection : tonsilitis and purulent exudate
What other sexually transmitted infections may you see with gonorrhoea
chlamydia and genital warts
What complications can arise from untreated gonorrhoea in males, females and newborns
Males; epididymitis and prostatitis
Females (20%); spread to Fallopian tubes (salpingitis) , pelvic inflammatory disease (PID) , infertility
Ophthalmia neonatorum (like conjunctivitis but thicker and more purulent)
If immunosuppressed disseminated gonococcal infection (DGI) - organism in blood stream and get sepsis
Laboratory diagnosis of gonococcal infection - sample collection process
Sample collection
Males - urethral swab (3cm insertion and rotation)
Females - multiple swabs, urethral/endocervical/vaginal
Other samples depend on patient history e.g. Throat, rectal or blood cultures
Transported in stuarts medium - preferably to GUM clinic lab
What is important to consider with gonorrhoea transportation
Very fastidious organism - need good transport media e.g. Stuarts
What non culture techniques can be used to diagnose gonorrhoea
Direct microscopy of discharge - presumptive diagnosis if positive and initiate treatment - if see lots of WBC and diplococci as urethra is sterile except for the tip
Nucleic acid amplification tests - PCR based 0 rapid detect/amplifies specific DNA; bacteria doesnt need to be viable.
What culture techniques can be used to diagnose gonorrhoea
Enriched agar such as blood or chocolate agar - will not grow on nutrient!
Selective agar : modified thayer-martin/New york city agar; vancomycin , colistin, nystatin, trimethoprim (can get contamination from urethral tip)
What colonies would you expect for gonorrhoea after 48hr incubation at 37dg with 5% co2.
Opaque, convex, grey, glistening colonies approx 2mm
Why are there antimicrobials in selective agar
Prevent bacteria and fungi growth
What ID tests can be performed after isolated colonies from culture
Gram neg diplocci on gram stain
Oxidase positive - test for cytochrome c oxidase in ETC (aerobes have it)
Catalase +
CHO fermentation (glucose + but maltose and sucrose negative) FROM API. Other neisseria may also have maltose and sucrose but gonorrhoea is ONLY GLUCOSE +
Prolyl aminopeptidase (gonochek II) - other neisseria dont have enzyme
What percentage of gonoiccoal infections are resistant to
I) penicillin
II) ciprofloxacin
III) tetracycline
I) 18%
II) 22%
III) 48%
What are the guidelines of single antibiotic (not combination) dosages etc - non drug resistant
Ceftriaxone (250mg, Intramuscularly, injection X1) and cefixime (400mg, oral, single dose) both high spectrum cephalosporin (beta lactam antibiotics)
Also can treat with azithromycin (2g single dose)
When should combination therapy be used for gonorrhoea and what is the treatment
Uncomplicated drug resistant gonorrhoea 500mg ceftriaxone (single dose IM) AND 1g azithromycin (single dose, orally)
Why has there been an increase in resistant to azithromycin
Hypothesised to be due to treat chlamydia therefore n gonorrhoeae exposed to it and become resistant - super strains
What can prevent gonorrhoea infections
Safe sex
- minimise number of sexual partners
- use condoms during mouth to penis sex, vaginal and anal intercourse
What is the trial drug in phase 3 against Neisseria gonorrhoeae and what is its MOA
2017 trial for ETX-0914, worked against all strains so far, patients successfully treated
MOA: act on topiosomeriase type II - like old quinolone
What are n gon adherence and endocytosis mechanisms
Pili (attach to nonciliated columnar epithelial cells found in urethra, mucus membranes, throat and eye. Hence diseases conjunctivitis, urethritis, tonsilitis
Opa (opacity) proteins aid attachment alongside pili. Also can attach to LOS of microorganisms next to them to form microcolonies of neisseria gonorrhoeae forming inside urethra . LOS another mechanism of adherence
Por proteins - form pores in cells and become intracelullar - survive inside WBC
What evasion virulence factors do n gon have
Sialic acid capsule - molecular mimicry of human cells
IgA protease - break down IgA common in genitourinary system
What attack mechanisms does n gon use
Formation of transferrin and lactoferrin binding receptors
Tbp1, Tbp2
Lbp1
Genitourinary system is low in iron content therefore produce surface proteins that bind to transferrin and lactoferrin (blood proteins carrying iron which n gon can extract.
What is unusual in structure for neisseria spp in their cell wall structure
Normal gram neg envelope but outer leaflet of outer membrane contains lipooligosaccharide (LOS) instead of lipopolysaccharide (LPS).
How does the LOS core polysaccharide of gonoccous and meningococcus express a variety of epitopes on cell surface
Via undergoing antigenic variation
What type of pili is present on gonococcal and meningococcal spp and describe the structures (with their binding partners)
Type IV pili, composed of polymers of structural protein PilE. PilC is located at the tip of the pilus as is the adhesin which mediates initial attachment of bacterium of surface of mucosal epithelium.
PilC binds CD46 - a complement regulatory protein that has a co-factor activity that inactivates the complement components c3b and c4b by serum factor I
How many groups can the Opa proteins be divided into and why of gonoccus and meningococcus
2 major groups based on cellular receptors they bind.
Opa HS - bind heparan sulfate and ECM molecules fibronectin and vitronectin
Opa CEA - bind carcinoembryonic antigen-related- cell-adhesion molecule (CEACAM).
What do Opa HS and Opa CEA mediate
Internalisation of gonoccoci by human cells. Directly through engagment with heparan sulfate proteoglycans on cell surface or indirectly using fibronectin or vitronectin to bridge Opa HS type proteins and cell surface integrins - the actin cytoskeleton of epithelial cell signalled to rearrange for engulfment of bacterial celll.
Opa CEA with members of CEACAM receptor family trigger actin cytoskeleton rearrangement -permitting internalisation by Neutrophils, macs and other cells.
After rearrangement of the actin cytoskeleton, what stages occur for internalisation and spread of gonococci
Bacteria pass through the cells via transcytosis and released at basolateral surface into the subepithelial space where infection is established. From here gonococci may spread to bloodstream and finally joints and skin
Upregulation of CEACAM1 on endothelium from LOS and inflammatory cytokines contributes to bacteria transgression into the blood
What does innate immunity in female and male urinary tract primarily compose of
Antimicrobial proteins b -defensins (HBD), cathelicidin, lactoferrin and lipocalin.
What is Tamm-Horsfall protein and what does it do
Tamm- Horsfall protein (THP) is an abnbdant urinary glycoprotein that binds specific mannosylated residues and blocks adhesion of certain bacterial urinary tract pathogens such as escherichia coli.
Fill in the gaps.
The endocervix provides a protective mucus layer rich in _, _, _ and _ for the vagina
HBD-1
HD-5
Lysozyme
Lactoferrin
Fill in the gaps
LOs and other components of the outer cell membrane of gonococci ( as well as IgA protease) are _ -inflammatory and induce release of _, _, _ and _ from phagocytes which induces a florid inflammatory reaction
Pro TNFa IL-1b IL6 IL8
Despite local and systemic antibodies, why do they tend not to protect against re-infection
Extensive and rapid variation of pili, LOS and Opas
