IC18 Sexually Transmitted Infections Flashcards
What are the modes of transmission for STIs?
- Sexual intercourse
- Close body contact e.g. coming into contact with broken skins, open sores, wounds, blood, genital fluids
- Contaminated blood
- Illicit Drug use (sharing of needles)
- Mother to child during pregnancy (syphilis, HIV), childbirth (Gonorrhea, chlamydia, HSV), breastmilk (HIV)
What are the risk factors for STIs?
- Sexual intercourse without protection (barrier methods –> condoms)
- Having multiple partners
- Having sex with a partner that had sex with multiple partners
- MSM
- CSW (prostitutes)
- Use of illicit drugs (engage in risky behaviour, sharing of needles)
What are the Pharmacological and Non-pharmacological prevention of STIs?
- Use barrier methods e,g, condoms
- Stick to one sexual partner or abstinence
- Avoid drug abuse and sharing needles
- Pre-exposure Vaccinations e.g. HPV, hepatitis B
- Pre- and post-exposure prophylaxis for HIV
Which one out of the 4 STIs is chronic and uncurable?
Genital Herpes (caused by HSV1 or HSV2)
What are the clinical presentations and complications of Uncomplicated Urogenital Gonorrhea (curable)?
Can be asymptomatic
Purulent Discharge, dysuria, increase urine frequency
Can infect various sites
Complications: infertility, ectopic pregnancy (implant outside of the womb e.g. fallopian tube), disseminated disease (rash, skin lesions, tenosynovitis, monoarticular arthritis)
What is used in diagnosis of Uncomplicated Urogenital Gonorrhea (curable)?
Diagnosis:
1) Gram stain and culture
2) NAAT (rapid)
What is the bacteria that caused Uncomplicated Urogenital Gonorrhea (curable)?
Neisseria Gonorrhea (intracellular gram negative diplococcus)
What antibiotics can be given for urogenital gonorrhea?
Need to treat for chlamydia infection as well, as having gonorrhea puts you at higher risk of getting chlamydial infection
- IM Ceftriaxone 500mg single dose (<150kg)
- IM Ceftriaxone 1g single dose (>150kg)
AND - PO doxycycline 100mg BD (7 days)
If allergic to cephalosporins/ceftriaxone is not available
1. IM Gentamicin 240mg single dose
AND
2. PO Azithromycin 2g single dose (have some gonorrhea and chlamydial coverage)
OR
3. PO doxycycline 100mg BD (7 days)
**FQ not recommended due to resistance
What to monitor for urogenital gonorrhea and how to manage sexual partners?
ADR
Sg want patients to come back 14 days after to test of cure
Evaluate and treat all sexual partners in the last 60 days. If sexual intercourse was more than 60 days ago, then evaluate the most recent sexual partner
Patient should abstain from sexual intercourse 7 days after completion of treatment.
Patient should abstain from sexual intercourse until all sexual partners are treated.
What are the clinical presentations and complications of chlamydial infections?
Purulent Discharge, dysuria, increase urine frequency
(but milder than gonorrhea)
Can infect various sites
Complications same as gonorrhea
What is used to diagnose chlamydial infection?
Diagnosis:
1) NAAT
What is the pathogen that causes chlamydial infection?
Chlamydia trachomatis
What antibiotics can be given for chlamydial infection?
- PO doxycycline 100mg BD (7 days)
OR - PO Azithromycin 1g single dose (for adherence issue)
OR - PO Levofloxacin 500mg OD (7 days)
What to monitor for chlamydial infection and how to manage sexual partners?
ADR
NO need test of cure
Evaluate and treat all sexual partners in the last 60 days. If sexual intercourse was more than 60 days ago, then evaluate the most recent sexual partner
Patient should abstain from sexual intercourse 7 days after completion of single dose treatment OR after completion of 7 days treatment and resolution of symptoms.
Patient should abstain from sexual intercourse until all sexual partners are treated.
What are the clinical presentations of syphilis?
ulcers
Primary –> localized external genitalia, mouth and throat
Secondary –> multisystem
Early latent (<1 year) –> multisystem, asymptomatic but picked by serology test
Late latent (>1 year) –> multisystem, asymptomatic but picked by serology test
Tertiary –> multisystem
Neurosyphilis –> CNS
What is used to diagnose syphilis?
Diagnosis:
1) *Darkfield microscopy of exudate from lesions
2) Serological Tests
*Treponemal test (confirmatory test)
- Treponemal antigens to detect antibodies
- more specific and sensitive than non-treponemal test
- remain reactive for life (can indicate current or past syphilis infection)
Non-treponemal (for monitoring, but also done together with treponemal test in the first time diagnosing)
- use non-treponemal antigen (Cardiolipin)
- quantitative VDRL or RPR (not interchangeable)
- Most diluted serum concentration with a positive result e.g. 1:16
- Antibody titre will correlate with disease activity, the more dilutions needed, the more antibodies present means the more active the disease is
- Will become non-reactive (when successfully treated, it will show negative results)
What pathogen causes syphilis?
Treponema Pallidum
What to monitor for syphilis? How to manage sexual partners?
Jarisch-Herxheimer reaction
- Acute febrile episode
- Accompanied by headache and myalgia
- Occur within 1st 24 hours of administration
Primary/secondary/latent syphilis monitoring:
- Non-treponemal test every 3,6,12,18,24 months
- Decrease from e.g. 1:64 to 1:16 shows improvement
Neurosyphilis monitoring:
- Lumbar puncture every 6 months
If treatment failure at 6 months:
- Signs and symptoms appear
- Antibody titre doesn’t decrease
- Re-evaluate and treat unrecognized neurosyphilis
Evaluate and treat all sexual partners if tested positive.
Patient should abstain from sexual intercourse until completely cured. Need go doctor and check whether their symptoms have fully resolved.
What antibiotics can be used to treat primary, secondary, or early latent (<1 year) syphilis?
Primary/ Secondary/
Early latent
(<1 year)
1st line:
- IM Benzathine Penicillin G 2.4 MU single dose
If penicillin allergy
- PO doxycycline 100mg BD (14 days)
o Take with food (reduce GI upset)
o Drink lots of water
o Take 2hrs apart from Ca or Fe/milk/antacids
o Sit up right for at least 30 mins to prevent heartburn
o Photosensitivity
What antibiotics can be used to treat late latent or tertiary syphilis?
Late latent (>1 year)/ tertiary
1st line:
1. IM Benzathine Penicillin G 2.4 MU once a week x 3 doses
If penicillin allergy
2. PO doxycycline 100mg BD (28 days)
What antibiotics can be used to treat neurosyphilis?
- IV Crystalline Penicillin G 3-4MU q4hrly (10-14 days)
OR 18-24MU continuous infusion (10-14 days)
OR - IM Procaine Penicillin G 2.4MU OD
AND PO Probenecid 500mg QDS (10-14 days)
If penicillin allergy
- IV/IM ceftriaxone 2g daily (10-14 days)
What are the clinical symptoms of genital herpes?
Vesicles, ulcers (on both genital areas, face and extremities), itching, pain, tender inguinal lymphadenopathy
Flu-like symptoms e.g. fever, headache, malaise
Prodromal symptoms (e.g. itching, tingling) prior to appearance of recurrent lesions
Less severe in recurrent episodes
What is used to diagnose genital herpes?
Diagnosis:
1) History taking
2) Clinical presentation
3) NAAT/PCR (virologic test for HSV DNA)
4) Type-specific (HSV1 or 2) serologic test
- detect antibodies to HSV
(but usually takes 6 weeks, so would just rely on the clinical presentation and NAAT)
What pathogen causes genital herpes? Which one is the more common one?
Herpes Simplex Virus (HPV) 1 and 2
HSV 2 is the most common virus that causes genital herpes
What are the supportive care methods for genital herpes?
- Warm saline bath
- Analgesia, anti-itch
- Good genital hygiene
- Counselling on natural history (cause of infection)
What antibiotics can be given for 1st episode of genital herpes?
Start within 72 hours (for max benefit)
Benefits:
- Reduce shedding
- Reduce duration of episodes
- Reduce time to heal
Acyclovir & valacyclovir:
Inhibits viral DNA polymerase (inhibit DNA synthesis and replication)
- PO Acyclovir 400mg TDS (7-10 days)
o Low F
o T1/2 = 3hrs
o Take with a lot of water to prevent crystallization of acyclovir at renal tubules
o SE: headache, malaise, nausea, vomiting, diarrhea
OR - PO Valacyclovir 1g BD (7-10 days)
o High F (55%)
o T1/2 = 3hrs
o Take with a lot of water to prevent crystallization of acyclovir at renal tubules
o SE: headache
Severe disease or complications requiring hospitalization:
- IV Acyclovir 5-10mg/kg q8hr (2-7 days) and complete with PO for a total of 10 days
What are the pros and cons of chronic suppression therapy for genital herpes recurrence? What are the chronic suppression therapies?
Pros:
- No symptomatic outbreaks when on the suppression therapy
- Reduce frequency of recurrences
- Reduce risk of transmission
Cons:
- Costly
- Adherence issue
- PO Acyclovir 400mg BD
- PO Valacyclovir 500mg OD
- PO Valacyclovir 1g OD (if have >10 episodes / year)
Duration depends on patients, but immunocompromised patients need to take it lifelong
Need to drink a lot of water to prevent cystallization of acyclovir at the renal tubules
What are the pros and cons of episodic suppression therapy for genital herpes? What are the episodic suppression therapies?
Pros:
- Cheaper
- More compliant
- Reduce duration and severity
Cons:
- Cannot reduce risk of transmission
- Must start within 1 day lesion onset or when have the prodromal symptoms
- PO Acyclovir 800mg BD (5 days)
- PO Acyclovir 800mg TDS (2 days)
- PO Valacyclovir 500mg BD (3 days)
- PO Valacyclovir 1g OD (5 days)
What are the counselling tips for genital herpes?
- Educate on natural history
- Inform all sexual partner that patient himself/herself have genital herpes
- Shedding can still occur during asymptomatic periods
- Patient should abstain when have lesions or prodromal symptoms (means soon have lesions)
- Daily use of acyclovir/valacyclovir (chronic suppression therapy) can reduce transmission
- Use latex condoms
- Risk for Neonatal HSV infection
- Increase risk for HIV acquisition
How to manage sexual partners for patients with genital herpes?
Evaluate and treat symptomatic sexual partners.
Asymptomatic sexual partners: History taking of genital lesions, encourage examining themselves and seek medical attention early if lesions occur. Offer type-specific serologic testing for HSV 2.
What are the Modes of Transmission For HIV?
Contact with body fluids: blood, semen, genital fluids, breast milk
1. Unprotected sexual intercourse
2. Illicit drug use and sharing of needles
3. Mother to child through pregnancy, childbirth, breastmilk
4. Transfusion of contaminated blood or blood products
What are the Goals of Antiretroviral therapy (ART) in HIV Infection?
- Reduce morbidity and mortality of HIV infection
- Prolong duration and quality of life
- Restore and preserve immunologic function (T cells)
- Suppress / Keep plasma HIV viral load at a minimum
- Reduce risk of transmission
- Reduce complications both opportunistic infection and non-opportunistic conditions (CVD, renal disease)
Describe use of CD4 cell count and HIV viral load as surrogate markers in managing patients on ART.
CD4 cell count:
- Most important marker to tell us about the immunologic function
- Important to tell us about the subsequent disease progression
- Normal: 500-1200 cells/mm3
- AIDS: <200 cells/mm3
- Adequate CD4 response: increase in 50-150 cells/mm3 in the first year of initiation
- May start prophylaxis for other opportunistic infections e.g. for pneumocystis pneumonia when CD4 cell count <200 cells/mm3
- Monitor frequency:
o Every 3-6months after initiating ART
o Every 12 months after adequate response
HIV viral load:
- Most important marker to tell us about HIV response to ART
- > 500,000 is a lot, want it to be as low as possible
- Adequate suppression is usually achieved by 8-24 weeks
- Monitor frequency:
o Monitored before starting treatment
o 2-4 weeks after initiating ART
o Every 4-8 weeks until viral load is suppressed
o Every 3-6/12 months once stable
What are the Benefits and limitations of earlier ART initiation?
Benefits:
1. Maintain high CD4 count and preserve immunologic function (T cells)
2. Prevent irreversible damage to immune system
3. Reduce complications (which can occur when CD4 count > 350 cells/mm3) and non-opportunistic conditions
4. Reduce risk of transmission
Limitations
1. ADR
2. Drug resistance
3. Transmission of virus for patients who do not maintain full virologic suppression
4. Less time to learn about HIV
5. Costly
6. Compliance issue (daily and forever)
7. Medication fatigue
What are the available targets for antiretroviral therapy + list common drugs in each class?
- NRTIs e.g. Tenofovir, emtricitabine, lamivudine, abacavir, zidovudine
- reverse transcriptase –> prevent conversion of viral RNA to DNA
- INSTIs e.g. Dolutegravir, bictegravir, raltegravir
- prevent integration of viral DNA into host DNA
- NNRTIs e.g. Efavirenz, Rilpivirine
- reverse transcriptase –> prevent conversion of viral RNA to DNA
- Protease Inhibtors e.g. Ritonavir, Lopinavir, atazanavir, cobicistat
- prevent cleavage of proteins and assembly
- Fusion inhibitor e.g. enfuvirtide
- prevent fusion of HIV and host cells
- CCR5 receptor inhibitor e.g. Maraviroc
- prevent entry of HIV that uses CCR5 receptor to enter host cell
What are the major toxicities and DDIs of NRTIs?
Class toxicities (rare, more in zidovudine): mitochondrial toxicity –> cause lipoatrophy, lactic acidosis and hepatic steatosis
Tenofovir: renal adjustment, decrease bone mineral density
Abacavir: hypersensitivity in patients with HLA-B*5701
Zidovudine: bone marrow suppression (anemia, neutropenia)
DDI: need renal dose adjustment (except for abacavir)
What are the major toxicities and DDIs of INSTIs?
Generally well tolerated, weight gain, diarrhea, N&V, headache, depression, suicidality
Bictegravir/ Dolutegravir: Increase serum concentration (no impact on glomerular function)
Raltegravir: creatine kinase elevation (rhabdomyolysis)
DDI:
- with Polyvalent cations
- CYP3A4 substrate
What are the major toxicities and DDI of NNRTIs?
QTc prolongation
Efavirenz: rash, SJS, hyperlipidemia, neuropsychiatric SE
Rilpivirine: headache, depression
DDI:
Efavirenz: CYP3A4 substrate and CYP2B6 and 2C19 inducer
Rilpivirine: CYP3A4 substrate, reduce with PPIs
What are the major toxicities and DDIs of Protease inhibitors?
Metabolic complications (hyperlipidemia, insulin resistance), GI SE, liver toxicity, lipohypertrophy, osteopenia/ osteoporosis
DDI:
Ritonavir: CYP3A4 substrate and 2D6 inhibitor
Atazanavir: with PPIs
What are the major toxicities and DDIs of fusion inhibitor?
Enfuvirtide
ADR: injection site reaction
DDI: none
What are the major toxicities and DDIs of CCR5 recpetor inhibitor?
Maraviroc
ADR: abdominal pain, cough, dizziness, musculoskeletal symptoms, pyrexia (increase temp), rash, URTI
DDI:
- CYP3A4 substrate
- Use coreceptor tropism assay
What needs to be done before giving CCR5 antagonist for HIV infection?
Co-receptor tropism assay before initiation
What are the combination therapies that can be given for patient who is ART naiive?
Triple Therapy combinations:
(Patient naiive to ART)
2NRTIs + 1INSTI:
1. Tenofovir + Emtricitabine + Bictegravir
2. Tenofovir + Emtricitabine + Dolutegravir
3. Abacavir + Lamivudine + Dolutegravir
Dual Therapy:
(Patient naiive to ART)
1NRTIs + 1INSTI:
1. Emtricitabine + Dolutegravir
DO NOT use this for:
- HIV viral load RNA > 500,000 copies/mL
- HBV coinfection
- Those who need to start before genotypic drug resistance testing OR HBV testing
