L19 STIs

Common types of sexually transmitted infections in NZ: • [blank_start]Bacterial[blank_end] - Chlamydia trachomatis, Neisseria gonorrhoeae, Treponema pallidium • [blank_start]Protozoal[blank_end] - Trichomonas vaginalis • [blank_start]Viral[blank_end] – HSV, HPV, HIV

At risk populations: • very young - infected in [blank_start]utero[blank_end] or at birth • sexually active young adults, especially those who [blank_start]drink[blank_end]

Chlamydia trachomatis: • non-motile [blank_start]gram –ve cocci[blank_end] • 2 specialised forms - intracellular & extracellular. Obligate [blank_start]intracellular[blank_end] pathogen. - Disease in Women: commonly asymptomatic [blank_start](75[blank_end]%), urethritis &/or cervicitis, purulent [blank_start]discharge[blank_end], burning [blank_start]sensation[blank_end]. If untreated an ascending infection can develop into [blank_start]pelvic inflammatory disease[blank_end] (PID) (40%). Involvement of uterus, fallopian tubes & ovaries - chronic pain (18%), infertility ([blank_start]20[blank_end]%), life threatening ectopic pregnancy (9%) - Disease in utero/neonates: [blank_start]premature[blank_end] birth, conjunctivitis, pneumonia - Disease in Men - asymptomatic infection ([blank_start]50[blank_end]%), urethritis - discharge, pain on urination, epididymitis - swollen, painful testicles, [blank_start]proctitis[blank_end] - (rectal infection; pain, bleeding, discharge), untreated – infertility • Diagnosis - direct culture not possible, [blank_start]PCR test[blank_end] is available • Treatment - [blank_start]contacts[blank_end] must also be treated, 1 or 7 day therapy • Prevention: Education, [blank_start]Screening[blank_end] programmes for high risk groups

Gonorrhoea - "The Clap" • Neisseria gonorrhoeae - [blank_start]gram negative diplococci[blank_end], closely related to N. meningitidis • person to person transmission • Infection limited to [blank_start]mucus[blank_end] membranes lined with [blank_start]columnar[blank_end] epithelium (urethra, cervix, rectum, pharynx, conjunctiva) - Disease in Adults: may be asymptomatic (~ [blank_start]50[blank_end]% females, [blank_start]30[blank_end]% males). Inflammation, dysuria, [blank_start]discharge[blank_end] (scant/copious, mucoid/purulent)/ in on urination may be extreme. Complications - ascending infection (male - [blank_start]prostate, testicles[blank_end]: female - [blank_start]PID[blank_end]) causing infertility - systemic spread (endocarditis, [blank_start]meningitis[blank_end]), - Neonates: 2016 – 4 cases < 1 year of age. Ocular infection can lead to [blank_start]blindness[blank_end]. • Testing/Diagnosis: routine testing should occur for high risk individuals ([blank_start]2[blank_end] weeks post contact), self collected sampling possible. First line test: [blank_start]nucleic acid amplification[blank_end] tests. [blank_start]Culture[blank_end] for detection of new/unknown resistance mutations. Follow up test at [blank_start]3 months[blank_end]. • Treatment: many strains now [blank_start]AMR[blank_end], should also treat for [blank_start]chlamydia[blank_end].

Trichomonas vaginalis (TV) • Protozoa, obligate human pathogen of [blank_start]genitourinary[blank_end] tract, twitching motility, sexually transmitted • Common - affects [blank_start]5-10[blank_end]% men & women • Often found with other [blank_start]STI[blank_end] pathogens - Disease in Women: asymptomatic (>[blank_start]50[blank_end]%). Thin [blank_start]frothy yellowish green[blank_end] discharge, foul [blank_start]odour[blank_end], vulva red and [blank_start]swollen[blank_end], itching, post-coital bleeding, cervical [blank_start]haemorrhage[blank_end], abdominal pain (+/-). Complications - risk factor for other STI, [blank_start]pre-term[blank_end] delivery, very [blank_start]rarely[blank_end] infertility if have severe disease with spread to fallopian tubes. - Disease in Men: asymptomatic, [blank_start]self-limiting[blank_end] infection, risk factor for other STI. [blank_start]Urethritis[blank_end], thin yellow-green discharge, pain on urination. - Disease in Neonates: 2-17% of female infants born to infected mothers will develop vaginal infections, usually [blank_start]asymptomatic, self-limiting[blank_end]. - Diagnosis & Treatment: microscopy, culture - also of [blank_start]contacts[blank_end]. Treat with [blank_start]metronidazole[blank_end] – oral better cure than topical. Resistance in 4-10% of cases & no vaccine.

T. pallidum - Syphilis. • spiral shaped [blank_start]bacteria[blank_end], obligate human pathogen • increases risk of [blank_start]HIV[blank_end] infection • in pregnancy, infection can cause [blank_start]miscarriage[blank_end] and infection of the newborn • diagnosis - direct [blank_start]microcopy[blank_end] or specific [blank_start]antibodies[blank_end] (ELISA) • treatment - [blank_start]intramuscular[blank_end] penicillin: [blank_start]long[blank_end]-acting Bicillin (benzathine penicillin) [blank_start]1.8[blank_end]g, as short-acting formulations are [blank_start]insufficient[blank_end] for syphilis treatment. 82% of cases are [blank_start]men[blank_end] who have sexual contact with [blank_start]other men[blank_end]. Is routine to screen for it in [blank_start]antenatal[blank_end] screening.

Syphilis - stages of infection • 65% men and [blank_start]50[blank_end]% of women symptomatic • primary - painless [blank_start]ulcerative[blank_end] sore on genitals, maybe internal or external, heal [blank_start]spontaneously[blank_end] within 3-6 weeks • secondary - skin [blank_start]rash[blank_end] with brown sores , always on [blank_start]palms[blank_end] of hands, [blank_start]soles[blank_end] of feet; mild [blank_start]fever[blank_end], aches etc. rash spontaneously resolves - sores highly [blank_start]infectious[blank_end]. • latent - no further symptoms, non-infectious • tertiary - systemic spread and damage to [blank_start]brain, heart, eyes[blank_end]; results in mental illness, blindness or even death

Genital warts are caused by [blank_start]human papillomavirus[blank_end] (HPV). • Extremely common ~ [blank_start]75[blank_end]% of sexually active adults will have been infected • Sexually transmissible; highly [blank_start]infectious[blank_end] when warts are present but still may be infectious when virus is [blank_start]latent[blank_end]. • HPVs that cause external warts do not generally cause [blank_start]cancer[blank_end] BUT co-infection with different HPV types is common. • Warts can [blank_start]vary[blank_end] in size and appearance, often appear in [blank_start]clusters[blank_end] • Women's are often [blank_start]internal[blank_end] (cervix and vagina) • Few other symptoms; recurrent disease

Genital Herpes • Herpes simplex virus type 1 & 2 (HSV-1, HSV-2) • Both [blank_start]oral[blank_end] (HSV-1) and [blank_start]genital[blank_end] lesions (HSV-2) • Infection is through [blank_start]broken[blank_end] skin via contact with person having an [blank_start]outbreak[blank_end] • Non-curable STI, virus remains latent in [blank_start]nerve endings[blank_end] • Oral [blank_start]antivirals[blank_end] can hasten resolution of disease (~1 [blank_start]day[blank_end]), no impact on risk or severity of recurrences - Adults - often asymptomatic, primary infection - systemic symptoms ([blank_start]fever, headache, malaise[blank_end]) + local symptoms (pain, itching, discharge, pustular or ulcerative [blank_start]lesions[blank_end]). \Outbreaks - no symptoms or local symptoms only, outbreak frequency [blank_start]decreases[blank_end] with time. Complications - disseminated/[blank_start]systemic[blank_end] infection, CNS complications ([blank_start]meningitis[blank_end]) - Neonates - infected at delivery, greater risk if [blank_start]primary[blank_end] infection (50%, < 5% for outbreak). Mortality rate of [blank_start]65[blank_end]% from disseminated disease.

HIV • Human immunodeficiency virus • Cellular target of HIV are [blank_start]CD4+ cells[blank_end] T cells • gp120 binds to CD4 causing [blank_start]conformational[blank_end] changes to take place; allows binding of gp120 to [blank_start]coreceptors[blank_end] (CCR5 or CXCR4) • gp41 can [blank_start]penetrate[blank_end] cell surface Epidemiology: • World: 2016 – 36.7 million people living with HIV & 18.2 on accessing therapy, 2 million new infections & 1.2 million deaths • NZ rate in low. Biggest [blank_start]decline[blank_end] in men who have sexual contact with men. [blank_start]No[blank_end] cases of perinatally HIV since 2007.

Stages of HIV lifecycle targeted by drugs: 1. Attachment & fusion - [blank_start]block[blank_end] attachment or fusion 2. Reverse transcription - nucleoside & non nucleoside [blank_start]RT inhibitors[blank_end] 3. Integration – viral [blank_start]integrase[blank_end] inhibitors 4. Processing of viral proteins - [blank_start]HIV protease[blank_end] inhibitors

NZ guidelines are: HIV testing of all pregnant women.

HIV Pathophysiology 1.Primary Infection • Infection initially establishes in [blank_start]lymphoid[blank_end] tissue - fever, malaise, headache, lymphadenopathy • active viral [blank_start]replication[blank_end] - 109 new virions produced each day, t1/2 of 1.6 days for cells • immune response kicks in - cytotoxic [blank_start]CD8[blank_end] T cell response + antibody (seroconversion) • infected cells are eliminated, virus titres [blank_start]decrease[blank_end] 2. Latent Disease • longest lasting stage of disease ([blank_start]2-3[blank_end] years for rapid progressors, up to [blank_start]10[blank_end] years for long term non progressors) • low level chronic [blank_start]immune[blank_end] activation & persistent viral replication, immune response ongoing • patients are [blank_start]asymptomatic[blank_end] • CD4 cells gradually [blank_start]decline[blank_end] due to direct viral killing and CD8 killing • new CD4 cells can not be [blank_start]generated[blank_end], CD8 response drops off due to viral [blank_start]mutation[blank_end] 3. Advanced Disease • characterised by either: - [blank_start]AIDS[blank_end]-defining illness (atypical infection or cancer eg Kaposi’s sarcoma) - decline in CD4 T cell counts below [blank_start]200 cells/mL[blank_end] • viral titres [blank_start]increase[blank_end], disintegration of lymphoid [blank_start]organs[blank_end], T & B cell responses decline, death from [blank_start]infection[blank_end] or cancer

Managing HIV patients • [blank_start]CD4 +/- viral load[blank_end] monitoring • [blank_start]Screening[blank_end] for diseases more common or more aggressive in patients with HIV • [blank_start]Immunisation[blank_end] If necessary/when required: • [blank_start]Anti-retroviral[blank_end] Therapy (ART) – NZ 2018 - 2463 people on ART • [blank_start]Prophylaxis[blank_end] against opportunistic infections • Treat infections/malignancies Drugs: - Current US guidelines - An antiretroviral regimen generally consists of [blank_start]two[blank_end] nucleoside reverse transcriptase inhibitors ([blank_start]NRTIs[blank_end]), in combination with a third [blank_start]active antiretroviral[blank_end] drug from one of three drug classes: 1. an integrase strand transfer inhibitor, 1. a non-nucleoside reverse transcriptase inhibitor (NNRTI), or 3. a protease inhibitor (PI) with a pharmacokinetic enhancer (cobicistat or ritonavir).

ART • Simple regimen, low [blank_start]pill burden[blank_end] • Adherence is [blank_start]critical[blank_end] • Low [blank_start]side effect[blank_end] profile – interactions [blank_start]common[blank_end] - Many ARVs are metabolised by cytochrome [blank_start]P450[blank_end], & the CYP3A4 inhibitors (eg ritonavir) are give in ‘boosted’ regimens. • High threshold for [blank_start]resistance[blank_end] • Cure – get rid of latent virus?, transplant with CCR5-ve immune system

HIV/AIDS Prevention • Education and behavior modification • PrEP • [blank_start]Drug abuse[blank_end] treatment (e.g. methadone) • Condoms, clean [blank_start]syringes[blank_end] • Treatment of other [blank_start]sexually transmitted[blank_end] diseases • Interruption of [blank_start]transmission[blank_end] from mother to child • Vaccine