L19 STIs

Common types of sexually transmitted infections in NZ:
• ❌ - Chlamydia trachomatis, Neisseria gonorrhoeae, Treponema pallidium
• ❌ - Trichomonas vaginalis
• ❌ – HSV, HPV, HIV

At risk populations:
• very young - infected in ❌ or at birth
• sexually active young adults, especially those who ❌

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

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

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

T. pallidum - Syphilis.
• spiral shaped ❌, obligate human pathogen
• increases risk of ❌ infection
• in pregnancy, infection can cause ❌ and infection of the newborn
• diagnosis - direct ❌ or specific ❌ (ELISA)
• treatment - ❌ penicillin: ❌-acting Bicillin (benzathine penicillin) ❌g, as short-acting formulations are ❌ for syphilis treatment.
82% of cases are ❌ who have sexual contact with ❌.
Is routine to screen for it in ❌ screening.

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

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

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

HIV
• Human immunodeficiency virus
• Cellular target of HIV are ❌ T cells
• gp120 binds to CD4 causing ❌ changes to take place; allows binding of gp120 to ❌
(CCR5 or CXCR4)
• gp41 can ❌ 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 ❌ in men who have sexual contact with men. ❌ cases of perinatally HIV
since 2007.

Stages of HIV lifecycle targeted by drugs:
1. Attachment & fusion - ❌ attachment or fusion
2. Reverse transcription - nucleoside & non nucleoside ❌
3. Integration – viral ❌ inhibitors
4. Processing of viral proteins - ❌ inhibitors

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

Managing HIV patients
• ❌ monitoring
• ❌ for diseases more common or more aggressive in patients with HIV
• ❌

If necessary/when required:
• ❌ Therapy (ART) – NZ 2018 - 2463 people on ART
• ❌ against opportunistic infections
• Treat infections/malignancies

Drugs:
- Current US guidelines - An antiretroviral regimen generally consists of ❌ nucleoside reverse transcriptase inhibitors (❌), in combination with a third ❌ 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 ❌
• Adherence is ❌
• Low ❌ profile – interactions ❌ - Many ARVs are metabolised by cytochrome ❌, & the CYP3A4 inhibitors (eg ritonavir) are give in ‘boosted’ regimens.
• High threshold for ❌
• Cure – get rid of latent virus?, transplant with CCR5-ve immune system

HIV/AIDS Prevention
• Education and behavior modification
• PrEP
• ❌ treatment (e.g. methadone)
• Condoms, clean ❌
• Treatment of other ❌ diseases
• Interruption of ❌ from mother to child
• Vaccine