Sexually Transmitted Diseases PDF

03/03/2021 Sexually Transmitted Infections Learning Objectives A BDS 3 Human Disease Discuss the epidemiology of STIs in the UK Narrated lecture Describe the microbial strategies utilised to overcome host defense PMI02-3005 Describe the common STIs in the UK, including bacterial / viral / fungal / i...

03/03/2021 Sexually Transmitted Infections Learning Objectives A BDS 3 Human Disease Discuss the epidemiology of STIs in the UK Narrated lecture Describe the microbial strategies utilised to overcome host defense PMI02-3005 Describe the common STIs in the UK, including bacterial / viral / fungal / infestation Outline principles of a sexual history Dr Martyn Ormond & Prof. Richard Cook 1 2 Introduction Overview STI = infection spread by sexual contact 1. Chlamydia No longer use term STD as STIs are not always symptomatic 2. Genital warts Sole / predominant mode of transmission Chlamydia Gonorrhoea 3. Gonorrhoea 4. Herpes One of several modes Hep A, B, C HIV 5. HIV 6. Syphilis 3 4 1 03/03/2021 Background – STIs in UK (2015) Background – HIV in UK (2015) Total new STI diagnoses was 434,456 (3.4%) Disproportionate increase in MSM Young people are more likely to be diagnosed than older age groups Heterosexual 15 to 24-year-olds accounted for 62% of those with chlamydia, 52% of those with gonorrhoea, 51% of those with genital warts 41% of those with genital herpes Older age groups vulnerable 28,113 STIs were diagnosed among 45 to 64-year-olds Significant geographic variation with highest rates in urban areas, especially in London 5 6 Background Overview Risk factors for STIs 7 Young age (especially 2 partners in preceding 6/12 Use of non-barrier contraception Residence in inner city Symptoms in partner Current STI & history of previous STIs Sexual orientation Chemsex Category STD STI Bacterial Chlamydia Chlamydia trachomatis Gonorrhoea Neisseria gonorrhoea Syphilis Treponema pallidum Genital herpes Herpes simplex virus (HSV) types 1 & 2 Genital warts Human papillomavirus (HPV) HIV Human immunodeficiency virus (HIV) Fungal Candidiasis Candida albicans Parasitic Pediculosis pubis Phthirus pubis Genital scabies Sarcoptes scabiei Viral 8 2 03/03/2021 Host Defences Host Defences Host defences Microbial strategies Examples Host defences Microbial strategies Examples Integrity of mucosal surfaces Specific attachment mechanism Neisseria gonorrhoea Chlamydia trachomatis Antibodies (esp. IgA) Produce IgA protease Neisseria gonorrhoea Urine flow (urethral infections) Specific attachment; induce uptake and transfer across urethral epithelial surface in phagocytic vacuole Neisseria gonorrhoea Cell-mediated immune response (T cells, NK cells, lympokines) Antigenic variation; allows reinfection of a given individual with antigenic variant Neisseria gonorrhoea Chlamydia trachomatis Human papillomavirus (HPV) Infection of urethral epithelial or subepithelial cells Herpes simplex virus (HSV) Chlamydia trachomatis Poorly understood factors cause ineffective cell-mediated immune response Treponema pallidum Human immunodeficiency virus (HIV) Induce negligible inflammation Treponema pallidum Resist phagocytosis Neisseria gonorrhoea Treponema pallidum Complement C3d receptor on microbe binds C3b/d reducing phagocytosis Candida albicans Inflammation Induce strong inflammation, yet evade consequences Neisseria gonorrhoea Candida albicans Chlamydia trachomatis Herpes simplex virus (HSV) Phagocytes (esp. PMNs) 9 10 Bacterial Chlamydia Causative organism Chlamydia trachomatis Obligate intracellular bacterium Extra-cellular (elementary body) and intra-cellular (reticulate body) forms Multiple serotypes A-K and L1, L2 & L3 (D-K genital and L types LGV) Binds to specific receptors and enters via parasite-specified endocytosis 11 12 3 03/03/2021 Chlamydia Chlamydia – Symptoms & Signs Transmission Female Most common Symptoms bacterial STI in UK Congenital transmission (peri-natal) 80% asymptomatic PV bleeding / purulent discharge / lower abdominal pain / dyspareunia / Neonatal proctitis conjunctivitis in 30-50% Signs Rarely Normal pneumonitis Cervicitis (discharge / contact bleeding) / adenexal tenderness 13 14 Chlamydia – Symptoms & Signs Male Symptoms Chlamydia – Complications Female 50% asymptomatic Urethral discharge / dysuria / testicular pain / proctitis Ascending infection can lead to pelvic inflammatory disease (PID) PID = endometritis / salpingitis / tubule damage / chronic pelvic pain Increased risk of ectopic pregnancy and infertility Male Signs Normal Epididymitis In either auto-inoculation may cause chlamydial conjunctivitis Urethral discharge 15 16 4 03/03/2021 Chlamydia – Diagnosis & Treatment Gonorrhoea Diagnosis Causative organism Nucleic acid amplification Neisseria gonorrhoea testing (NAAT) Gram negative diplococci which are facultatively High sensitivity and intracellular specificity for genital sites Site of entry = mucosal surfaces (vaginal / urethral / rectal) Also used for extra-genital Adhesive mechanism ensures it evades mechanical removal sites (rectal / pharyngeal / by secretions ophthalmic) Produces IgA protease to disable host secretory antibodies Replicate in intracellular vacuoles which fuse with Treatment Azithromycin 1g STAT Doxycycline 100mg BD 7/7 basement membrane releasing bacterium into connective tissue Elicit host inflammatory response will resultant tissue damage 17 18 Gonorrhoea Gonorrhoea Transmission Always sexually transmitted Congenital transmission (peri-natal) Neonatal conjunctivitis 19 20 5 03/03/2021 Gonorrhoea – Symptoms & Signs Gonorrhoea – Symptoms & Signs Female Male Symptoms Symptoms 70% asymptomatic 85% with urethral infection Vaginal discharge develop symptoms in 10/7 Low abdominal or pelvic pain Commonly discharge or dysuria Rarely asymptomatic Signs Urethral discharge Signs Cervicitis Meatitis Cervical discharge Urethral discharge Cervical excitation 21 22 Gonorrhoea – Symptoms & Signs Gonorrhoea – Complications Extra-genital sites Female Conjunctivitis Bartholinitis Pharyngitis Endometritis Pharyngeal exudate Salpingitis Proctitis Peritonitis Rectal discharge Tubo-ovarian abscess Male Epididymitis Local abscess formation Rarely disseminated infection (septicaemia / arthritis /skin lesions) 23 24 6 03/03/2021 Gonorrhoea – Diagnosis & Treatment Syphilis Diagnosis Causative organism NAAT as per Chlamydia Due to resistance always perform culture and sensitivity Treponema pallidum Motile spirochaete Transmission Treatment Depends on local guidelines and resistance pattern Sexual contact Transmitted transplacentally Ceftriaxone 500mg IM STAT + Azithromycin 1g PO STAT 25 26 Syphilis – Stages Syphilis – Stages Primary Secondary 10-90 days post-exposure 4-10 weeks Develop papule at site of inoculation Constitutional symptoms (fever / sore throat Ulcerates and becomes painless, firm chancre / malaise / arthralgia) May go unnoticed (cervical / rectal ulcer) Generalised lymphadenopathy Spontaneous resolution within 2-3 weeks Generalised skin rashes (classically palms and soles) Condylomata lata (warty, plaque-like lesions typically peri-anal region) Superficial confluent ulceration of mucosal surfaces (‘snail track ulcers’) Acute neurological signs (aseptic meningitis) Without treatment, resolves after 3-12 weeks 27 28 7 03/03/2021 Syphilis – Stages Syphilis – Diagnosis Tertiary Dark field microscopy detects T. pallidum directly from lesion exudate or tissue is the definitive method for diagnosing early syphilis Years after inoculation Gumma (granulomatous, A presumptive diagnosis of syphilis requires use of two tests : ulcerating lesions) affecting Treponemal specific skin typically at sites of trauma Can affect bone and visceral organs Fluorescent treponemal antibody absorbed test (FTA-ABS) T. pallidum passive particle agglutination assay([TP-PA) Enzyme immunoassays (EIAs) Non-treponemal specific Cardiovascular manifestations (aorititis / Venereal Disease Research Laboratory (VDRL) Rapid Plasma Reagin (RPR) aortic regurgitation) One serologic test only is insufficient for diagnosis (false-negative in primary syphilis and false-positive) Neurosyphilis 29 30 Syphilis – Treatment Viral Penicillin G, administered parenterally, is the preferred drug for treating persons in all stages of syphilis Dosage, and length of treatment depend on the stage and clinical manifestations of the disease 31 32 8 03/03/2021 Genital herpes Genital herpes – Symptoms & Signs Causative organism Variable Herpes simplex virus (HSV) types 1 & 2 (both can infect mouth or genitals) Severe primary episode within 2-12/7 of acquisition Ubiquitous 70-80% asymptomatic First severe clinical episode (does not necessarily imply recent infection) Febrile illness (prodrome) 5-7/7 Dysuria, urinary frequency Painful inguinal lymphadenopathy Tingling / neuropathic pain (genitals / buttocks / legs) Genital blisters, ulcers, fissures Transmission Untreated episode may last 3/52 Close physical contact (sexual or oro-genital) Viral shedding by infected partner Complications Sporadic, not necessarily associated with symptoms 33 Rarely acute urinary retention / constipation / aseptic meningitis 34 Genital herpes – Symptoms & Signs Genital herpes – Symptoms & Signs Reactivation Recurrent episodes usually mild Neuropathic prodrome (tingling / burning) Erythema / blisters / fissures / ulcers Resolution within 3-4/7 Risk factors Age (6 episodes / yr or episodes last > 4/7 Consider prophylactic therapy Immunosuppressed Specific regimens 37 38 Genital warts Genital warts – Symptoms & Signs Causative organism Genital lumps (hard / soft, solitary / multiple) Human papillomavirus (HPV) Over 80 types of which 30 associated with genital infection Bleeding (typically urethral) Most common 6, 11, 16, 18, 31 and 33 Itchiness Hyperpigmentation Transmission Close physical contact (skin to skin) Almost always genital for genital warts Commonly vulva / perianal region / cervix Auto-inoculation from other sites rare Less commonly vagina / urethra Incubation Period 39 Female 3-18mths (can be longer) Frequently transmitted without presence of visible wart Male Commonly penis / urethra / perianal region (regardless of sexual behaviour) / scrotum 40 10 03/03/2021 Genital warts – Diagnosis & Treatment HPV – Complications Diagnosis ~12 HPV types (including 16, 18, 31, and 45) are called "high-risk” Clinical appearance Linked to number of cancers: Occasionally biopsy required Treatment Eradicate visible warts – NOT virus Vulval Penile Vaginal Anal Cervical Podophyllotoxin cream for external warts Strongest association with cervical cancer Weekly cryotherapy Serotypes 16 & 18 are part of HPV Vaxine – both are also known drivers of oro-pharyngeal Cancer…. Will the HPV Vax have an impact in oro-pharyngeal cancer incidence? Progressive pre-cancerous changes detected via national cervical screening programme (do not cause visible warts) All females >25yrs invited to participate 41 42 HPV – Vaccination HIV All girls 11-14yrs offered vaccination since 2008 Causative organism 2 vaccines (serotypes 16 & 18 or 6, 11, 16 & 18) Human immunodeficiency virus Member of lentovirus group of retrovirus family Moves to include MSM Australia and USA also offered to boys HIV-1 (most virulent) HIV-2 (almost entirely West Africa) Structure UK recently changed to include boys 43 Two types 3 major structural genes: Gag - encodes nuclear proteins Pol - encodes viral enzymes (reverse transcriptase, integrase, protease) Env - encodes envelope glycoproteins 44 11 03/03/2021 HIV – Structure HIV – Replication Reverse transcriptase Viral replication DNA polymerase enzyme transcribes single-stranded RNA into double-stranded DNA Complementary DNA (cDNA) strand produced from viral DNA by reverse No proof reading mechanism, replication is highly error-prone (mutations) transcriptase Second cDNA strand synthesised Viral envelope Lipid bilayer cDNA transported to cytoplasm Expresses gp120 and gp41 which Integrase cleaves cDNA and inserts into host genome Viral products transcribed by host cell produce a complex to bind to CD4 Cleaved into proteins by HIV protease enzyme Assemble into new virus HIV entry into CD4 cells Virus buds from cell surface gp120 mediates target recognition gp41 mediates fusion Co-receptors Present on host cells and are required for viral entry (CCR5 and CXCR4) 45 46 HIV – Immune Response HIV – Natural History Humoral response Primary infection (seroconversion) B cells produce a ‘neutralising antibody’ against gp120 in all patients but this fails to 60% develop symptoms of seroconversion (often mild) clear the virus Usually 2-6 weeks after infection Diagnosis of primary important Cytotoxic response May not be unwell again until late in infection Cytotoxic lymphocytes can control HIV replication in early infection but this is Prevent onward transmission eventually overcome by progressive damage to the immune system Treatment Symptoms & Signs 47 Fever Or0-gential ulceration Sore throat Rash Malaise Headache Arthralgia / myalgia Diarrhoea Lymphadenopathy Oral candida 48 12 03/03/2021 HIV – Natural History 49 HIV – Classification 50 HIV – Categories 51 HIV – Categories 52 13 03/03/2021 HIV – Diagnosis & Tests HIV – Treatment HIV antibody test Nucleoside Reverse Transcriptase Inhibitors Standard test Mimic naturally occurring molecules Can take up to 3mths to become positive Prevent attachment of next chain resulting in DNA breakage HIV p24 antigen (superseded by antibody test) Non-Nucleoside Reverse Transcriptase Inhibitors Detects viral antigen rather than antibody Disparate group of drugs which fit into a molecular cleft, with reverse transcriptase which reduces catalytic activity CD4 count (CD4 or helper T lymphocytes) Most useful indicator of current immune status Protease Inhibitors Inhibit the enzyme required for post-translational modification of viral gene products HIV load (viral load / HIV RNA) Current lower limit of detection