GUM Flashcards
Herpes in Pregnancy: when to c-section
Primary maternal infections, if
(a) >equal 28 weeks
(b) if <28 weeks but CS expected within the next 6 weeks.
Neonatal Herpes:
Incidence
Risk of infection infection
Incidence (2019-2022) - 6.9/100,000 live births
Transmission via contact with infected maternal secretions
Aetiology HSV-1 (52%) or HSV-2 (48%)
Greatest risk of transmission is primary infection within 6 weeks of delivery due to the absence of maternal transplacental antibodies (41% chance)
Risk of neonatal transmission:
Primary: 41%
Recurrent: 0-3%
Significant associated morbidity and mortality:
Overall mortality (all presentations of neonatal HSV) 24% - more common in premature and HSV-2
What’s new in the 2024 management of genital herpes in pregnancy guideline
· Use of ulcer panel PCR testing for herpetic lesions in pregnancy.
· Antiviral suppressive therapy to start earlier at 32 weeks of pregnancy for all mothers and pregnant people requiring this, and at 22 weeks if there is a high risk of preterm delivery.
· Use of valaciclovir as an alternative to aciclovir for treatment and/or suppression of genital herpes in the pregnant woman or person.
· A new section on the use of serology in the third trimester, and virology involvement in writing this guideline.
· Expansion of the neonatal management section, including risk stratification to guide investigations and treatment.
· Expansion of the prevention of postnatal transmission section, including a new section on breastfeeding.
· A new section on the management of clinically or serodiscordant couples
Neonatal herpes sub groups
- disease localised to only skin, eye and/or mouth (SEM)
- local central nervous system (CNS) disease (encephalitis alone or with SEM lesions)
- disseminated -disease with multiple organ involvement.
when does Neonatal infection occur?
infection at
1. the time of birth (85%),
2. in the immediate postnatal period
(10% - HSV1 only) or,
3. very rarely, in utero (5)% - termed congenital
herpes.4
Disease localised to skin, eye and/or mouth (SEM)
Mortality
Morbidity
Approx 32% of neonatal herpes cases
Median presentation at 8 days of life.
Typically present with vesicular lesions or ulcers on the skin, eye or mouth and
have no CNS or visceral organ involvement.
With appropriate antiviral treatment to prevent progression, mortality is 0% and neurological and/or ocular morbidity is around 6% and more likely in those with at least 3 lesions or HSV-2
at risk of recurrent SEM disease during childhood
Central nervous system disease/meningoencephalitis
Mortality
Morbidity
35% have CNS disease with a
Median presentation of 14 days
They may present with a variety of signs including lethargy, poor feeding, or seizures and may not have skin, eye and/or mouth lesions
With antiviral treatment, mortality from CNS disease is around 15% and more likely in those who are semi-comatose or comatose, in premature infants, and in those with delayed time to treatment.
Neurological morbidity (including developmental delay, epilepsy, blindness and cognitive disabilities) is common at 64%, and more frequent in those with seizures, HSV-2 infection, and those with delayed time to antiviral treatment
Disseminated infection
Define
%
% fever, % sepsis
Mortality
Morbidity
33% of infants with neonatal herpes have disseminated disease with a median presentation of 6 days
Multiple organs are involved and may include the liver, lungs and brain, and skin, eye and/or mouth symptoms may be absent.
Features of dissemination are typically nonspecific with only 18% presenting with fever and 79% presenting with ‘sepsis’.
Disseminated disease carries the worst prognosis – with appropriate antiviral
treatment, mortality is still around 66% and more likely in those who are semi-comatose or comatose, have HSV pneumonitis, disseminated intravascular coagulopathy, are premature, or with delayed antiviral treatment
41% of infants have long term morbidity and this is more likely in those with seizures, HSV-2 infection, or delayed antiviral
treatment
Liver, lungs, brain
33, 66, 44,
20% fever, 80% sepsis
HSV transmission
- INITIAL EPISODE (1/3rd present)
(A) PRIMARY INFECTION (first infection with either HSV-1 orHSV-2 in an individual with no pre-existing antibodies to
either type)
(B) NON-PRIMARY INFECTION first infection with either HSV-1 or HSV-2 in an individual with pre-existing antibodies to the other type.
- RECURRENT EPISODE
recurrence of clinical symptoms due to reactivation of pre-existent HSV-1 or HSV-2 infection after a period of latency.
Factors associated with transmission of neonatal herpes
Type (primary/non-primary or recurrent) and
timing of maternal infection,
The absence of transplacentally-acquired maternal neutralising antibodies
The duration of rupture of membranes before delivery,
The mode of delivery,
The use of assistance (vacuum, forceps or fetal scalp electrodes)
Syphilis on dg microscopy
Appearances of spirochaetes such as Treponema pallidum (grem neg) on dark-field microscopy:
Tightly spiralled / helically coiled / corkscrew shaped
Contain endoflagella (axial filaments)
Motile (if recent sample)
May appear straight or flexed
Congenital syphilis
Transplacental passage only occurs when placenta fully developed at 14/40 - wont cause 1st trimester miscx
2/3 asymptomyatic at birth but most will develop symptoms within 5 days
MOSH PITS
Early disease (first 2 years)
mosh
Maculopapular rash (hands and feet)
Optic neuritis
Snuffles (secretions in the nose sometimes contain spirochetes, hemorrhagic)
Hepatosplenomegally
(also rhagades - linear cracks at angles of mouth)
Late disease (>2 years)
PITSS
Pitch Inability (Hearing loss)
Teeth - Hutchinson teeth (notched teeth)
Saber shins (bent tibia)
Saddle nose
(also mulberry molars)
Hutchinsons triad
congen syphilis
hutcHINsons
Hutchinsons teeth (peg-shaped and notched incisors, mulberry molars)
Intersistial keratitis
Sensorineural deafness (CN8)
Antigens on Treponema pallidum
- Group specific antigen (present on all treponemas)
- Species specific antigen (specific to T. pallidum)
- Cardiolipin (lipid antigen in spirochetes and cells in our body)
Diagnosis of syphilis: acquired
Dark field microscopy (from chancre)
Serological tests: Non-treponema tests
Detect ANTI-CARDIOLIPIN ANTIBODY (“Reagin”), not specific to syphilis
* Rapid plasmin reagin test (RPR)
* Venereal disease research laboratory test (VDRL)
Serological tests: Treponemal tests
Detect antibodies that specifically target T. pallidum
*Treponema pallidum particle agglutination test (TPPA)
*Fluorescent treponemal antibody absorbed (FTA-ABS)
Diagnosis of syphilis: congenital
- Serology:
Look at mom compared to baby
Non treponemal serological titer
4 x higher in baby - CSF fluid
VDRL, cell count, protein - Long bone XR
- Eye exam
- Hearing screen
Treponema pallidum particle agglutination (TPPA) test
What is the most infective stage of syphilis?
Secondary
Latent syphilis: Early vs Late phase
Early latent: within a year of infection - spirochetes can still be found in the blood, can cause symptoms.
Late latent: after a year, tend to stay in tiny capillaries in organs/ tissues.
Tertiary syphilis: organs effected
CVS
Neurological
Liver
Joints
Testes
Tertiary syphilis: cardiovascular sequelae
Endarteritis - inflammation of the vasa vasorum (supply the aorta) - aortitis -> aortic aneurysms
Tertiary syphilis: neurosyphilis
POST SC
Inflammation in capillaries (due to presence of spirochetes) that supply posterior spinal cord - TABES DORSALIS (wasting/ loss of back of spinal cord) - loss of vibration sense, loss of proprioception.
ANT SC
Sometimes, inflammation of caps that supply anterior sc - general paresis (loss of sensation, weakness, lower limb paralysis)
BRAIN
Slurred speech, altered behaviour, memory loss, difficulty coordinating movement, paralysis
ARGYLL ROBERTSON PUPIL (pupil loses light reflex BUT does still have accommodation, so still adjust when near object)
Tertiary syphilis
Tertiary syphilis hypersensitivity reaction
Type 4 hypersensitivity reaction (lead by T cells, macrophages secrete : TNF, IL1, IL6)
Plasma cells
Type 4 hypersensitivity reaction
Types of hypersensitivity reactions
ACID
Type 1: IgE - medicated; quick onset after exposure (meds, latex)
ALLERGIC
Type 2: Ig-G mediated cytotoxic: Cells destroyed by bound ab, either by activation of compliment or by cytotoxic T cell (phagocytosis). (Rh Incompatibility in Pregnancy - hemolytic, Antiphospholipid Syndrome)
CYTOTOXIC
Type 3: Immune complex - mediated: Ag-Ab complexes are deposited in tissues, causing activation of complement which attracts neutrophils to the site (Postpartum Endometritis, SLE, PID, non-septic Post-Gonococcal Arthritis, HIV assoc GN, drug induced serum sickness like reactions, vasculitis, SJS partially)
IMMUNE COMPLEX DEPOSITION
Type 4: Delayed or cell-mediated T cell mediated. Th1 cells secrete cytokines which activate macrophafes and cytotocic t calls (Latex, nickel, contact detmatitis, tertiary syphilis, TB, endometriosis?, SDI rejection, Reactive arthritis, abacavir hypersensitivity syndrome, SJS partially)
DELAYED
MHC class II
Function: Presents exogenous antigens (e.g., from extracellular bacteria or other pathogens) to CD4+ helper T cells.
This activates the immune system to produce antibodies or recruit other immune cells.
Structure: Composed of an α-chain and a β-chain, both anchored in the membrane.
Expression: Restricted to antigen-presenting cells (APCs) like dendritic cells, macrophages, and B cells.
Antigen Source: Extracellular proteins are taken up via phagocytosis or endocytosis, processed in endosomes, and loaded onto MHC class II.
Examples: Immune response to bacterial or parasitic infections.
HLA Genes: HLA-DP, HLA-DQ, HLA-DR.
Function: Critical for:
Activation of Th cells.
Cytokine release and coordination of the immune response.
MHC class I
Function: Presents endogenous antigens (e.g., viral or tumor-derived proteins) to CD8+ cytotoxic T cells. This helps identify and eliminate infected or abnormal cells.
Structure: Composed of a heavy chain (α-chain) and β2-microglobulin.
Expression: Found on almost all nucleated cells.
Antigen Source: Intracellular proteins processed by the proteasome and transported to the endoplasmic reticulum by TAP (Transporter Associated with Antigen Processing).
Examples: Viral infection detection, tumor surveillance.
HLA Genes: HLA-A, HLA-B, HLA-C (human equivalents of MHC class I).
In HIV, initially MCH1 but then it is downregulated as HIV adapts.
MHC i vs ii
MHC molecules are central to immune surveillance and activation. Variants in MHC genes (e.g., HLA subtypes) influence susceptibility to infections, autoimmune diseases, and hypersensitivity reactions.
Key Differences Between MHC I and MHC II
MHC Class I MHC Class II
Ag Intracell (endog) Ag Ext(exog)
Present toCD8+ CD4+ Helper
All nucleated cells APCs
Genes:HLA-A,B,C HLA-DP,DQ,DR
Detect infected cell Coord respons
What are HLA genes
HLA genes (Human Leukocyte Antigen genes) are a group of genes located in the major histocompatibility complex (MHC) region on chromosome 6 in humans.
These genes encode proteins that play a critical role in the immune system by helping the body distinguish between self and non-self (e.g., pathogens, foreign tissues).
HLA genes define an individual’s immune profile. Their extreme variability ensures population-level diversity, improving defense against a wide range of pathogens. However, this variability also contributes to challenges in organ transplantation, autoimmunity, and drug hypersensitivity.
What is a GUMMA
A gumma is a soft, tumor-like growth of inflamed tissue that occurs in the late (tertiary) stage of syphilis/
Characteristics:
Gummas are granulomatous lesions, meaning they consist of clusters of immune cells attempting to wall off the infection.
They can appear in various tissues and organs, including the skin, bones, liver, and other internal organs.
Presentation:
They may present as painless, rubbery masses or ulcers.
Over time, they can cause tissue destruction and scarring.
Pathophysiology:
Gummas result from a chronic inflammatory response to the bacteria and are a sign of prolonged, untreated syphilis. No spirochetes in gumma, but can get coagulative necrosis in the middle of the gumma.
Jarisch-herxheimer reaction
Spirochetes die and break open releasing a lot of antigens - immune system goes into overdrive - fevers, sweating, joint pains (last for hours days, conservative management)
p24 antigen
The p24 antigen is a protein found in the HIV virus that is used to diagnose early HIV infection.
It is present in high levels in the blood of people who are newly infected with HIV.
How it’s used
The p24 antigen is detected in blood tests to diagnose HIV infection. These tests are often used in combination with tests that detect HIV antibodies, which are produced by the body in response to the virus.
When it’s used
The p24 antigen is used to diagnose HIV infection early, when antibody levels are still low. This is important because early detection allows for prompt treatment and can significantly improve quality of life.
Limitations
The p24 antigen is not reliable for diagnosing HIV infection after the earliest stages. This is because antibodies to p24 are produced during seroconversion, making the p24 antigen undetectable.
HIV screening and dx
Combination assay: HIV ab, p24 antigen
If NEG: HIV NAAT
HIV NAAT pos - dx HIV; neg - neg HIV
If POS: HIV1/HIV2 antibody differentiation assay - dx HIV
Then if dx:
Viral load
T cell subtype
Viral resistant testing
FBC, UE, LFT, Glucose
Fasting lipid studies
Latent TB
Hep b/c serology
STIs
Toxoplasmosis serology
Cervical smear
Fourth generation HIV tests:
Combination test: detects HIV IgM and IgG antibodies as for third generation tests + p24 antigen using monoclonal antibodies
Window period = 45 days
BHIVA recommend as first line using a venous sample
Studies have shown the median time to detection was 17.8 days, with 99% detected by 44.3 days
Ct Serovar
Serovar A, B, C: Trachoma (keratoconjunctivitis)
* Low income countries, highest in Africa
* Infection of the eye could cause blindness
* Spread through hand to eye contact or by insect vector
Serovar D, E, F: Common cause of genital disease (DEF DEFINITELY, BUT DICK D-K ALL GENITAL )
Serovar G, H, I, J, K: Less common cause of genital disease
* in infected newborns cause keratoconjunctivitis or pneumonia
Serovar L2: Common cause of Lymphogranuloma venereum
Serovar L1, L3: Less common cause of Lymphogranuloma venereum
* Tropical and subtropical regions
* STD: painless papule or shallow ulcer at the site of inoculation, untreated could
progress into perirectal abscesses or lymphedema of the genitals
A-H of BV
Amsel criteria
BV
Clue cells
Discharge - white/grey/yellow
Essence - amines
Four.5 pH below
Gardnerella and prevotella
H is like M: metronidazole (/ clindamycin)
Supressive antiviral therapy for recurrent anogenital herpes (as per BASHH):
Aciclovir 400mg twice daily (TDS in preg) or
Aciclovir 200mg four times daily or
Famciclovir 250mg twice daily or
Valaciclovir 500mg once daily
Causes of non-gonococcal urethritis:
Chlamydia trachomatis (most common)
Mycoplasma genitalium
Ureaplasmas
Trichomonas vaginalis
Adenoviruses
Herpes simplex virus
Cell wall synthesis inhibitors antibiotics
how do they work and examples
Properties:
Beta-lactams
Contain a beta-lactam ring
Bind to the active sites of penicillin binding proteins (transpeptidases) during synthesis of peptidoglycan
Example:
Penicillins
Cephalosporins
Carbapenems
Syphilis: Lesions not suitable for dark-field microscopy:
Oral lesions: PCR should be used instead (commensal treponemes are found in the oral cavity so increasing the false positive rate)
Dry lesions seen in secondary syphilis (condyloma lata or mucous patches)
PEP summary
Start within 24 hours, no later than 72 hours
First line: Tenofovir disoproxil 245mg/emtricitabine 200mg + Raltegravir 1200mg OD for 28 days.
PEP is available from GUM clinics and A&E
Factors that increase risk of HIV transmission when index case is not on ART:
*High viral load in index case
*Mucosal barrier breaches: ulceration, tissue trauma
*Menstruation or other bleeding
*Pregnancy/post-partum
*STI in the index case
*Genital ulceration in the recipient
An undetectable viral load is <200 copies/ml
> 200 copies/ml is considered detectable and transmissible
Ct abx regimens in pregnancy:
Azithromycin 1g orally as a single dose, followed by 500mg once daily for two days
Erythromycin 500mg four times daily for seven days
Erythromycin 500mg twice daily for 14 days
Amoxicillin 500mg three time a day for seven days
Eukaryote vs Prokaryote
Nucleus
Organelles:
Size:
DNA:
Cell Division:
Ribosomes:
Cell Wall:
Energy Production:
Reproduction:
Examples:
Nucleus:
E: Have a nucleus
P: No nucleus (DNA in nucleoid)
Organelles:
E: Membrane-bound organelles (e.g., mitochondria, ER)
P: No membrane-bound organelles
Size:
E: Larger (10-100 µm)
P: Smaller (0.2-2 µm)
DNA:
E: Linear chromosomes in nucleus
P: Circular DNA in nucleoid
Cell Division:
E: Mitosis & meiosis
P: Binary fission
Ribosomes:
E: 80S ribosomes
P: 70S ribosomes
Cell Wall:
E: Present in plants/fungi, absent in animals
P: Present (made of peptidoglycan)
Energy Production:
E: Mitochondria (aerobic respiration)
P: Plasma membrane (varied respiration)
Reproduction:
E: Sexual & asexual reproduction
P: Asexual reproduction (binary fission)
Examples:
E: Plants, animals, fungi
P: Bacteria, archaea
Gram pos vs gram neg bacteria
Cell wall
Gram pos
+/- capsule (more virulent)
Thick layer peptidoglycan (polymer of sugar and aa) - RETAINS DYE -
Plasma membrane (phospholipid bilayer)
Gram neg
+/- capsule (more virulent)
Surface/ outer membrane membrane (LPS and protein)
Thin layer peptidoglycan (superfical)
Plasma membrane
Sequence of gram stain
- Application of crystal violet (enters and stains all bacteria)
- Application of iodine (forms a complex with cv that partially traps it in the peptidoglycan layer)
- Alcohol wash (thin layer peptidoglycan in gram NEG, all washed out) (Gram POS stay purple)
- Application safranin (stains NEG cells pink)
Types of bacteria
Gram positive cocci (Stap, Strep, Enterococcus)
Gram neg cocci (Neisseria)
Gram pos rods/ bacilli (Clostridium, Actinomyces)
Gram negative rods / bacilli (Enterobacteriaceae, Bacteroides)
Gram positive cocci
Clusters - Staphylococcus
S. Aureus and Coagulase neg staph (e.g., Staphylococcus epidermidis)
**Clinical relevance **
Toxic Shock Syndrome (TSS): S. aureus produces toxins associated with TSS, especially linked to prolonged tampon use or menstrual cups.
Skin and ST infections
Short chains and pairs (diplococci) - Streptococcus, Enterococcus, and Peptostreptococcus (can sometimes appear as short chains or pairs depending on the strain and preparation method).
**Clinical relevance **
*Streptococcus agalactiae (Group B strep, GBS can cause neonatal sepsis, meningitis, or pneumonia if transmitted during delivery).
*Streptococcus pyogenes (Group A - endometritis or wound infections).
*Enterococcus spp. (Enterococcus faecalis, Enterococcus faecium) - complicated UTIs
Gram neg cocci
Neisseria
Moraxella
**Clinical relevance **
Gonorrhea
Gram pos rods (bacilli)
Clostridium (aerobic)
Clostridium perfringens (gas gangrene), Clostridium difficile, Clostridium tetani
**Clinical relevance **
Postpartum or post-abortion infections, particularly in unsafe conditions. Necrotizing infections in the pelvic area.
Actinomyces (facultative anaerobe, branching morphology)
Actinomyces israelii.
**Clinical relevance **
Pelvic actinomycosis,
Gram negative rods (Bacilli)
Enterobacteriaceae family
Escherichia coli, Klebsiella, Proteus, etc
**Clinical relevance **
UTIs: E. coli
Pelvic Infections: Secondary infections during PID, postpartum infections, or after gynecological surgery.
Bacteroides spp. (Anaerobic gram-negative rods)
**Clinical relevance **
Commonly involved in polymicrobial infections in the pelvic region, such as pelvic inflammatory disease (PID), abscesses, and postpartum endometritis.
Key Anaerobic Bacteria
Bacteroides spp. (Gram-negative rods)
Part of normal gut and vaginal flora but become pathogenic when they invade sterile sites.
**Clinical relevance **
Polymicrobial infections like PID, post-surgical infections, postpartum endometritis, and tubo-ovarian abscesses.
Peptostreptococcus spp. (Gram-positive cocci)
Normal flora of the mouth, gut, and vagina.
**Clinical relevance **
Often found in mixed anaerobic infections, including pelvic abscesses, PID, and post-abortion infections.
Clostridium spp. (Gram-positive rods)
(A) Clostridium perfringens: Gas gangrene, often post-abortion or after gynecological surgery.
(B) Clostridium difficile: Antibiotic-associated diarrhea, which can complicate care in SRH settings.
Fusobacterium spp. (Gram-negative rods)
Involved in polymicrobial pelvic infections, such as tubo-ovarian abscesses or necrotizing infections.
Key Fastidious Bacteria
Microorganisms that are difficult to grow in the laboratory because they have complex or restricted nutritional and/or environmental requirements. DIFFICULT TO CULTURE.
- Non growing or intracellular (chlamydia, mycoplasma)
- Slow growing
- Dormant = non growing, resistant
- Dead bacteria (take sample before giving abx!)
Lactobacillus
Gardnerella vaginalis
Chlamydia trachomatis
Neisseria gonorrhoeae
Treponema pallidum
Ureaplasma spp. and Mycoplasma spp.
Campylobacter sp.
Enterobacteriaceae Family
Gram-negative rods: All members of this family are rod-shaped and stain pink with the Gram stain.
Facultative anaerobes: They can survive in both aerobic and anaerobic conditions.
Ferment glucose: They can metabolize glucose to produce acid.
Oxidase-negative: They lack the enzyme cytochrome oxidase.
Catalase-positive: Most members produce the enzyme catalase.
Nitrate reducers: Many reduce nitrate to nitrite.
Ribosome
Protein synthesis
In cytoplasm or plasma memb
Plasmids
Small, contain dsDNA
Independent
Round or circular
Few genes often confer selective advantage to the bacteria e.g. resistance
Structures found on the surface of bacteria
PILI - hair like, allow to attache to other cells
FIMBRIAE - small pili
FLAGELLA - tail like, movement
ENDOFLAGELLA
Mycoplasma sp
Small facultative anaerobes pleomorphic without cell wall (peptidoglycan) with small genome. Parasites of human and animals
- Sensitive to environmental factors – limited survival
STD: Mycoplasma hominis, M. genitalium, Ureaplasma, urealyticum - usually commensal/ opportunistic.
(Respiratory patogen: Mycoplasma pneumoniae)
Could cause infection:
* Non-Gonococcal Urethritis (NGU) - M. genitalium or Ureaplasma urealyticum
* Pelvic inflammatory disease (PID) - M. hominis or M. genitalium
Diagnosis
PCR (quantitative – could differentiate
colonisation and infection)
Culture detection based on urease and other enzyms activity
Therapy tetracyclines, macrolides, fluoroquinolones
M Gen rx
Doxycycline 100mg bd for seven days followed by azithromycin 1g orally as a single dose then 500mg orally once daily for 2 days where organism is known to be macrolide-sensitive or where resistance status is unknown (1D)
Moxifloxacin 400mg orally once daily for 7 days if organism known to be macrolide-resistant or where treatment with azithromycin has failed (1B)
complicated (pid, e-o)
Moxifloxacin 400mg orally once daily for 14 days (1D)
Clostridium difficile
- Spore forming gram-positive anaerobic bacterium
- Difficult to culture - difficille
- Disease cause only toxin producing strains
- Colonizer of gatrointestinal tract human (5%) andanimals, common in water and soil
- Post antibiotic diarhoea (clindamycin,
fluoroquinolones, 2nd and higher gen. of
cephalosporines), toxic megacolon,
pseudomembranous colitis - Nosocomial infection
Treatment
* Metronidazol, vancomycin, fidaxomicin
* Fecal transplantation
Prevention
* Hand washing
* !Alcohol desinfection does not work – alcohol promotes spore germination!
M Gen testing indications BASHH
Recommend in
Dx of NGU
S+S of PID
Current sexual partners of persons infected with M. gen
Consider in
S+S muco-purulent cervicitis, particularly PCB
Dx of epididymitis
Dx of sexually-acquired proctitis
M Gen treatment BASHH
Uncomplicated (urethritis, cervicitis)
(A) where organism is known to be macrolide-sensitive or where resistance status is unknown:
Doxy 100mg bd for 7 days followed by azithromycin 1g orally as a single dose then 500mg orally once daily for 2 days
(B) where organism known to be macrolide-resistant or treatment with azithromycin has failed:
Moxifloxacin 400mg orally once daily for 7 days
Complicated (PID, epididymo-orchitis)
Moxifloxacin 400mg orally once daily for 14 days (1D)
Preg/BF
Uncomplicated
3 day course of azithromycin
In women with likely macrolide resistance, or with upper genital tract infection in pregnancy, options are limited. (Moxi not safe in preg, doxy considered safe in 1st trimester but BNF advises against)
Chlamydia
Obligate intracellular pathogens
* Unable to syntetize ATP
* Peptidoglycan is missing
* EB – infection
* RB – reproduction
Could grow on cell culture
* But low sensitivity
Serotype determines type of infection
Treatment: macrolides, tetracyclines, fluoroquinolones
?TB
Lentivirus characteristics:
RNA viruses
Single-stranded
Positive sense
Enveloped
Contain ‘gag’, ‘pol’ and ‘env’ genes
Cause long-duration illnesses with long incubation times
Candida and contraception
Oestrogen containing contraceptives increases recurrence risk.
Candida and diabetes
In patients with diabetes, Candida galbrata is more common
Mycoplasma genitalium
Single stranded circular DNA
Self-replicating
Genome of only 580 kilobases
Does not contain a cell wall or membrane bound organelles
What is the recommended empirical treatment for epididymo-orchitis likely caused by sexually transmitted pathogens?
Empirical treatment includes ceftriaxone 500 mg intramuscularly as a single dose plus doxycycline 100 mg orally twice daily for 10-14 days.
For likely ct/gc and enteric, consider 1g ceftriaxone intramuscularly + ofloxacin 200 mg twice daily
For enteric organisms, recommended treatment is ofloxacin 200 mg orally twice daily or levofloxacin 500 mg orally once daily for 10 days.
Where Mycoplasma genitalium has been tested and
identified, treatment should be guided to include an
appropriate antibiotic (e.g. moxifloxacin).
Check them in 14 days
When to think epididymo-orchitis most probably due to an enteric pathogen
older patient, not sexually active,
recent
instrumentation (such as prostatic biopsy, vasectomy or
catheterisation),
men who practice insertive anal intercourse,
men with known abnormalities of the urinary tract or positive urine dipstick for leucocytes and nitrites
TOC timeline GC
DNA NAAT tests usually take 14 days to reliably exclude ongoing infection.
RNA NAAT tests take 7 days.
What is molluscum contagiosum?
Molluscum contagiosum is a viral skin infection caused by a poxvirus, leading to small, painless, dome-shaped papules with a central dimple.
How long does molluscum contagiosum typically take to resolve spontaneously?
Lesions generally resolve within 6–12 months but may persist longer in some cases.
When should treatment for molluscum contagiosum be considered? What is treatment?
Treatment is considered for cosmetic reasons, persistent cases, or if lesions are causing significant discomfort or psychosocial distress.
Options include cryotherapy, curettage, topical treatments like podophyllotoxin or imiquimod, and laser therapy.
Protease inhibitors
Ritonavir
Atazanavir
Fosamprenavir
Tipranavir
Lentivirus characteristics
RNA
Single stranded
Positive sense
Enveloped
Contain gag, pol and env genes
Cause long duration illnesses with long incubation times
Heamolysis for strep
alpha heamolysis - partial / greening hemolysis assoc with reduced red cell hb
beta hemolysis complete lysis with yellow/ pale blood agar appearance
gamma - absent haemolysis with no change in appearance
LGV: presentation
Painless papule/pustule/shallow erosion/ulcer in coronal sulcus, fourchette, posterior vulva, posterior vaginal wall, cervix.
Can be extra-genital – peri-anal, lip, oral cavity, extra-genital LNs
3 – 30 days after acquisition
Common manifestations:
MSM most likely to present with LGV proctitis – PR bleeding, D/C +/- mucous, tenesmus, constipation. Fever and malaise.
Heterosexual individuals most likely to present with unilateral (2/3rds) tender inguinal +/- femoral lymphadenopathy. Bubo formation 🡪 ulcerate 🡪 discharge pus 🡪 chronic fistulae.
Groove sign: inguinal LNs and femoral LNs enlarge above and below the inguinal ligament, ligament creates groove between the enlarged LN chains.
Pathopneumonic for LGV but only arises in 15 – 20% cases
Examples:
MSM with haemorrhagic proctitis
Heterosexual cis-male with unilateral tender inguinal and femoral lymphadenopathy
Heterosexual cis-female with large fluctuant “bubo” lymph nodes discharging pus in right inguinal region
MSM with rectal pain and discharge, fever and tenesmus
LGV dx
PMNLs >10 on microscopy
Swab from ulcer base exudate
Urethral swab/first-pass urine in urethritis
NAATs/swabs from rectal/pharyngeal sites
LT complications LGV
Proctocolitis
Rectal cancer
Fistulae and stricture formation
Chronic granulomatous disfiguring fibrosis/scarring
Tertiary infective changes occur more commonly in women reflecting involvement of retroperitoneal lymphatics. Note male anatomy = most drainage is to superficial inguinal lymph nodes.
LGV treatment
Doxy 100bd for 21 days
Allergy: tetracycline allergy use macrolides and TOC
Pregnancy/breastfeeding: avoid tetracyclines, use macrolides and TOC
Fluctuant buboes: aspirated through healthy adjacent skin, surgical incision contraindicated
Chancroid
Gram –ve (rods) bacterium H. ducreyi
3 – 7 day incubation period after sexual intercourse
Tender erythematous papules (prepuce, frenulum, vulva, cervix, perianal) 🡪 pustules 🡪 rupture to superficial painful ulcers (ragged edges, granulomatous base, purulent exudate)
50% inguinal lymphadenitis – unilateral and painful – may progress to buboes
Dx = painful genital ulcers, regional lymphadenopathy, STS & HSV –ve
Microscopy (gram –ve rods), NAATs, culture
Rx – ceftriaxone 250mg IM stat, azithromycin 1g PO stat
2nd line = cipro and erythromycin
PN = those who had sex with patient since 10 days prior to symptom onset
All should be followed-up
LGV TOC and PN
If symptomatic – look back 4 weeks for PN. If asymptomatic – look back 12 weeks for PN.
TOC should be performed 2 weeks after completing treatment. Routine TOC not necessary.
Ulverative STIs - 5
- Chancroid (painful)
Haemophilus ducreyi
Multiple and deep ulcers
Base have gray/yellow exudate
Organisms clamp in long parallel school of fish - Genital herpes (painful)
HSV1/2
Multiple small grouped ulcer
Shallow with erythematous base
Multinucleated giant cells and intranuclear inclusions - Granuloma inguinale/ Donovanosis (painless)
Klebsiella granulomatis
Extensive and progressive ulcers without lymphadenopathy
Base will have granulation tissue
Deep staining showing gram negative intracytoplasmic cysts (Donovan bodies) - Syphilis (painless)
Treponema pallidum
Single indurated well circumscribed ulcer (chancre)
Clean base
Thin, delicate, corkscrew-shaped organism on df microscopy - LGV (painless)
Chlamydia Trachomatus L1-3
Small and shallow ulcers
Large painful injuinal LN (groove sign)
Tabes dorsalis
Wasting of posterior spinal cord
Loss of vibration sense and proprioception
VPLS
Vibration sense
Prioprioception
Lightnening pains
Sensory ataxia
If wasting of anterior spinal cord then get general paresis - loss of sensation, weakness, paralysis
AR pupil
lose light reflex
keeps accom reflex
Neurosyphilis symptoms
slurred speech
altered behaviour
memory loss
difficulty coordinating mm movements
paralysis
Sts CVS
15-30 years after infection
ASCENDING AORTA is predominant site of damage causing aortitis and anyreusm
Endarteritis (inflammation of vasa vasorum)
How does HPV induce cancer?
HPV is thought to induce cancer via onco-proteins. The primary onco-proteins are E6 and E7 which inactivate two tumor suppressor proteins, p53 (inactivated by E6) and pRb (inactivated by E7)
The HPV vaccine Gardasilµ is what type of vaccine?
Gardasilµ is a recombinant vaccine of virus-like particles (VLPs).
These resemble HPV virions but lack viral DNA. They therefore provoke an antibody response but cannot induce infection or cancer.
Toxic Shock causative organisms
(B hem strep)
Most Staphylococcus aureus or Group A Strep (Streptococcus pyogenes)
Can also be:
Group G streptococcus
Streptococcis dysgalactiae
toxic shock = sunburn like rash
HIV genus
Genus is lentivirus
which is a member of the retroviridae family
Rubella genus is Rubivirsu a member of the Togaviridae family
Rubella genus is Rubivirsu
which is a member of the Togaviridae family
Hepatitis C genus
Hepatitis C genus is Hepacivirus
which is a member of the Flaviviridae family
Bacteria: gram pos
Cocci
Staphylococcus (Facultative anaerobes)
Streptococcus (Facultative anaerobes)
Bacilli OR ‘Rods’
Bacillus (spore forming Facultative anaerobe)
Clostridium (spore forming Obligate anaerobe)
Actinomyces (spore forming Facultative anaerobe)
Bacteria: Gram neg
Cocci
Nisseria gonorrhoeae (Obligate aerobes)
Neisseria meningitidis (Obligate aerobes)
Moraxella catarrhalis (Obligate aerobes)
Bacilli OR ‘Rods’
Bacteroides (Obligate anaerobes)
Escherichia coli (Facultative anaerobe)
Proteus mirabilis (Facultative anaerobe)
Enterobacter cloacae (Facultative anaerobe)
Helicobacter/Compylobacter (spiral rod) (Facultative anaerobes)
Salmonella (Facultative anaerobe)
Bacteria: intracellular
Chlamydia Obligate aerobes
Spirochaetes OR Spiral Shaped
Treponema pallidum
Toxoplasma gondii is an intracellular protozoan parasite
Primary host and source of infection is domestic cats
T. gondii oocysts excreted in cat faeces, mature in environment and then ingested by secondary hosts which include humans
Fetal consequences more severe if infection takes place within 10 weeks of conception
Maternal-fetal transmission risk increases as the pregnancy proceeds but the consequences become less severe
May cause miscarriage or fetal abnormalities such as microcephaly, hydrocephalus, cerebral calcifications, cerebral palsy, epilepsy choroidoretinitis and thrombocytopenia.
Diagnosis can be via PCR or Immunoglobulins (IgM,IgG and IgA). MRI/CT may show ring enhancing lesions in CNS tissues.
Treatment not usually required in the immunocompetent.
In pregnancy treatment is indicated if recent infection suspected
Treatment varies depending on local protocols (Spiromycin or combination of pyrimethamine, sulfadiazine, and folinic acid)
ART: TEGRA
InTEGRAse inhibitors - RalTEGRAvir
Inhibits HIV genome integration into host cell chromosome by inhibiting HIV integrase.
ART: Have you dined with my nuclear family?
Drugs that end in “-vudine” are Nucleoside Reverse Transcriptase Inhibitors!
ART: Never tease a pro-tease.
Drugs that end in “-navir” are Protease Inhibitors!
ALL protease inhibitors are enzyme inducers and reduce contraception efficacy (do not effect: Depo injection, intrauterine contraception, barrier contraception)
Notifiable SRH/GUM diseases
Campylobacter – MSM diarrhoea
Chlamydia psittaci (NB avian chlamydia spread through exposure to birds; NOT sexually transmitted)
Cryptosporidium - MSM diarrhoea and chronic diarrhoeal illness in HIV + people (especially if low CD4)
Giardia - MSM diarrhoea
Hepatitis (A, B, C, D + E)
Monkeypox
Salmonella - MSM diarrhoea
Shigella - MSM diarrhoea
Ct what is it
Obligate intracellular
gram negative - no uptake of purple
WITHOUT cell wall murein - no uptake of pink
(so not typically seen on micro but do see puss cells)
Ct life cycle
48-72 hours
Elementary bodies (infectious form)
Reticular bodies (metabolically active/ dividing form – divides via binary fission as no nucleus)
Ct serovars
Serovars A-C: chlamydial conjunctivitis
Serovars D-K of trachoma biovar: genital chlamydial infection
Serovars L1-3: infect lymph nodes causing LGV (L2 most commonly)
Ct transmission
10% transmission rate, with 75% concordance within partners
Correct use of condoms reduces risk by ~40%
Ct spont clearing
Spontaneous bacterial clearance estimated in 20-28% in 3 months, 50% at 12 months
Ct symptoms: women
Majority of women (up to 80%) have asymptomatic vaginal infection
If symptoms: increased discharge, PCB/IMB, lower abdominal pain, deep dyspareunia, dysuria
Complications: PID (up to 30% of cases if left untreated), endometritis/ salpingitis, SARA (rare) –> Increased future risk of tubal infertility and ectopic pregnancy following PID, also risk of PID associated perihepatitis (Fitz-Hugh Curtis Syndrome FHCS)
Ct symptoms:men
~50% of men have symptoms, the rest are typically asymptomatic
Male urethral symptoms can be very mild -> lack of reporting
Dysuria, urethral discharge
CT makes up ~35-50% of all non-gonococcal urethritis (NGU)
Complications: SARA, epididymitis/ epididymo-orchitis
Ct symptoms: rectal
asymptomatic in >60% of cases
If symptoms: discomfort, discharge
Rectal CT has up to 10% prevalence in MSM attending sexual health clinics à need LGV subtyping
Can occur in women with no history of anal sex, and can be harder to clear rectally
Ct rx and pn
1 7/7 100mg doxycycline BD (teratogenic)
Pregnancy or tetracycline allergy #2 first choice azithromycin 1g STAT followed by 500mg OD for 2/7
OR erythromycin 500mg BD 10-14 days
OR ofloxacin 200mg BD 10-14 days (also not recommended for use in pregnancy)
Partner notification for 6 months prior to diagnosis, except for symptomatic men (only 4 weeks needed)
No routine TOC needed if #1 treatment completed
TOC for all treated in pregnancy/ with #2 treatment options
TOC should be performed at least 5 weeks following completion of treatment
Pharmacology of doxycycline for rx of Ct
Tetracycline class antimicrobial
98-100% effective at treating genital chlamydia with low resistance rates
92% for rectal chlamydia/LGV
No significant metabolism occurs - excreted largely unchanged in urine and feces
Should not be taken with calcium, magnesium, iron (metal ions) -> unabsorbable deposits
Side effects primarily GI and skin/photosensitivity
Contraindicated in pregnancy and breastfeeding – effects on skeletal and dental development
Ct: Pregnancy and the neonate
AN screening for 16-25yo
The most common symptomatic presentation in babies if conjunctivitis
— 30-50% of exposed infants -> “chlamydia ophthalmia neonatorum”
— Incubation period 5-14 days average (can be up to 2 months) following exposure (delivery/ PROM)
— Can be mild -> severe with any corneal scarring being very rare
Nasopharyngeal infection occurs in majority of exposed infants (70-80%) and is often asymptomatic
~1/3 can develop an apyrexial pneumonia from 1-3 months of age
– Can have adverse long term outcomes including obstructive pulmonary disease
– Can also cause a chronic otitis media if left untreated
Vaginal and rectal infection of babies exposed at delivery can occur in ~10-15% of babies
– Typically asymptomatic
– Pre-pubertal infection ++ indicator of sexual abuse, however perinatal infection can persist for up to 3 years
LGV
L1,2,3 serovars, L2 most common
Traditionally endemic to Africa/India/Caribbean etc - outbreaks in UK since 2003
High risk in HIV + MSM and those involved in dense social networks (sex parties/ clubs)
PRIMARY
Early/ primary infective lesion is often, mild/ transient and unnoticed
Painless papule/ pustule
Shallow erosion / ulcer – coronal sulcus /peri-anal
SECONDARY
Secondary infective stage is significant lymphadenopathy – inguinal +/- femoral, often tender and unilateral
TERTIARY
Most commonly presentation is at tertiary stage of infection, with rectal symptoms of haemorrhagic proctitis
Can get significant associated systemic symptoms ie fever / malaise
If left untreated LGV can cause significant morbidity and can mimic Crohn’s disease
Fistulae, strictures etc
TREATMENT
BASHH state asymptomatic rectal CT is unlikely to be LGV and standard 7/7 treatment should be given with no need for LGV sub-testing (unless HIV + MSM)
**If CT + result from symptomatic rectal sample or from any site in HIV + MSM –> LGV sub-testing ***
Rectal pus cells (PMNLs >10/20 per field on microscopy) are predictive of LGV proctitis
Treated with a 3 week prolonged course of
#1 doxycycline 100mg BD
OR Tetracycline 2g OD
OR Minocycline (300mg loading -> 200mg BD)
If tetracycline allergy or unsuitability (ie pregnant or breastfeeding) second line treatment is necessitated
#2 erythromycin 500mg QDS, again for 3 weeks (preferred)
OR azithromycin 1g weekly for 3 weeks (less preferable)
High rates of co-infection with HIV and HCV so ensure risk reduction discussion and full BBV screening
LGV TOC not routinely recommended if full first line treatment is completed
TOC should be done for pregnant/ breastfeeding patients or any other groups not treated with #1 abx
If required TOC should be done 2 weeks following completion of treatment (BASHH)
All patients should be clinically followed up until symptoms have resolved
Partner notification is recommended for 4 weeks if symptomatic/ 3 months if asymptomatic
Should be treated epidemiologically /presumptively (BASHH)
Co-infection of CT in pts with GC
40% in females with GC
25% in males with GC
GC infectivity
Single episode of UPSI M–>F spread in 60-80%, reduced by 40% with condom use
Single episode of UPSI F–>M spread in 20%, reduced by 75% with condom use
GC culture requirements, sensitivity
GC is cultured at 35-37 degrees, 5-7% CO2 on selective and enriched culture media
Culture sensitivity predicts successful treatment to >95%
Intermediate sensitivity suggests 5-15% failure rate and higher doses of abx may be more effective
Resistance mechanism is typically due to plasmids (independent circular DNA fragments separate to chromosomes) or chromosomal mutations
GC Treatment
IM 1g STAT ceftriaxone #1 recommendation (also suitable for breastfeeding/ pregnancy)
Ciprofloxacin 500mg PO STAT does can be used if sensitivity is known
Ciprofloxacin = quinolone abx, not suitable in pregnancy or breastfeeding
GC ciprofloxacin resistance rate and what to give insteat
High prevalence of GC ciprofloxacin resistance in the UK ~36%
Other alternatives if regional resistance <5%:
Cefixime 400mg PO STAT + azithromycin 2g PO STAT (recommended if IM injection refused by patient or contraindicated)
Gentamycin 240mg IM STAT + azithromycin 2g PO STAT (appt treatment for true penicillin allergy with unknown resistances, as likely not suitable for cipro alone)
Spectinomycin 2g IM STAT + azithromycin 2g PO STAT (not recommended for pharyngeal infection)
Due to increasing antimicrobial resistance a routine TOC is recommended 2 weeks following treatment*
GC PN
Symptomatic men with urethritis – 2 weeks prior to onset of symptoms
Asymptomatic or infection at any other site – 3 months prior to diagnosis
Pharmacology of ceftriaxone
Beta lactam antimicrobial, third generation cephalosporin
Metabolism by gut flora»_space; inactive metabolites
When given parenterally it is not metabolised»_space; excreted unchanged in urine and bile
Can form precipitates with calcium (do not use concurrently)»_space; risk of cardiorespiratory arrest
~10% cross-reactivity of cephalosporins for those with true penicillin allergies
From limited data, appears to be safe in pregnancy and breastfeeding
Ciprofloxacin
Ciprofloxacin is a bactericidal antibiotic of the fluoroquinolone drug class. It inhibits DNA replication by inhibiting bacterial DNA topoisomerase and DNA-gyrase
GC effect on preg
Infection is associated with adverse pregnancy outcomes:
3-6x increased in pre-term delivery and low birth weight babies
Increased PROM
Infection of chorio-amnion can occur and lead to septic abortion
Increased rate of intrapartum pyrexia and post-partum/ post-abortion endometritis
GC effect on neonate
Mild infections can cause rhinitis and pharyngitis –> vaginitis and urethritis –> severe infections are usually relating to ophthalmia neonatorum and sepsis
Gonococcal ophthalmia neonatorum is a notifiable disease in the UK
Conjunctivitis with purulent discharge in an infant within 21 days of birth (though more typically develops within 2-5 days of birth)
Occurs in ~1/3 of exposed infants
Associated with significant oedema of eyelids
If untreated»_space; extends to subconjunctival connective tissue»_space; corneal ulceration and blindness
Trichomoniasis vaginalis
What is it
How does it grow
Incubation period
Detection rates in male contacts
Symptoms
Flagellated protozoan parasite in human genitourinary tract
Multiplication by mitosis every 8-12 hours; grows in moist environments at 35-27 degrees
Average incubation period of 4-28 days
Detection rates in male contacts are very dependent on timing of sexual activity
<48 hours since last sex – 70% detection
<5 days since last sex – 40% detection
14 days since last sex – 33% detection
21 days since last sex – 12% detection only
Woman 50% symptomatic - frothy yellow dc
Men 25% symptomatic
TV testing and diagnosing
Women should be tested when presenting with vulvitis/ vaginitis
Swab from posterior fornix for wet mount microscopy (40-80% sensitivity, highly specific)
Self taken VVS for NAAT (88-97% sensitivity)
Men should be tested if contact of TV or presenting with persistent urethritis
Urine NAAT
Consider urethral specimen (only 30% sensitivity of microscopy for males, remains highly specific)
Direct wet microscopy slides must be read within 10 minutes of preparation as motility of the protozoa quickly declines
NAAT PCR superior to culture testing – culture sensitivity only 34-59%
TV treatment
uncomplicated vs refractory
1 400-500mg metronidazole BD for 5-7 days OR 2g single dose STAT (lower cure rate)
UNCOMPLICATED:
The only effective agents for TV treatment are the 5-nitroimidazoles with a good overall cure rate (>95%)
Given limited treatment options, if true allergy, consider metronidazole desensitisation
2g STAT tinidazole is an alternative, but cross-reactivity unknown and not considered safe in metronidazole allergy. Also not suitable for use in pregnancy.
No alcohol during and for 48 hours post-completion due to disulfiram-like (Antabuse) reaction.
Metronidazole should be avoided during breastfeeding – caution is advised against high dose use during pregnancy (400mg BD 7/7 acceptable»_space; 2g STAT).
In cases of refractory infection consider:
#1 Repeat 7/7 treatment course of metronidazole (~40% response rate)
Metronidazole or tinidazole 2g OD 5-7 days OR metronidazole 800mg TDS 7/7
Following this if ongoing infection consider resistance testing
TV and PN
Partner notification and TV treatment (irrespective of result) for the last 4 weeks is recommended
No TOC
Pharmacology of metronidazole
Anaerobic cover; protozoa, anaerobic bacteria (and some streptococci)
Works by gaining entry into anaerobic organisms»_space; cytotoxic reaction
Very good oral bioavailability
Side effects – nausea/ vomiting, dry mouth, metallic taste
Limited evidence for safety in pregnancy but is widely used where benefits felt to outweigh risks
Does pass in to breast milk but no evidence of harm, high dose regimes should be avoided
Thrush causative organisms
Candida albicans main organism responsible (85-90%),
Candida glabrata (3-15%)
replicate via production of ‘buds’ from a blastospore (yeast cell)
Candida albicans
Hyphae (long tubes of multiple cell units)
Pseudo-hyphae (single elongated cells)
(Chlamydo)spores (refractory bodies with double layered cell-walls)
“mycelium” = entire yeast aggregate (spores, hyphae and branches of)
C. glabrata does not produce hyphae or pseudo-hyphae
Recurrent vulvovaginal candidiasis (RVVC)
Recurrent vulvovaginal candidiasis (RVVC) = 4 or more episodes annually
At least partial resolution of symptoms between episodes
+ microscopy or culture on at least 2 occasions of symptoms
Chronic, persistent candidiasis that is not treated»_space; vulval lichenification and oedema
Most commonly in older and obese diabetic patients
Thrush diagnosis
Diagnosis gold standard is with laboratory culturing (95-100% accuracy)
Allows for speciation and resistance testing
Can be fluconazole resistant so this is especially important in recurrent cases
Microscopy of gram stained sample has limited sensitivity (~65%)
Spores and hyphae stain gram + (purple)
Thrush treatment uncomplicated
Standard treatment recommends
#1 150mg fluconazole STAT
Not suitable in pregnancy or breastfeeding
Clotrimazole pessary instead
500mg ON one dose OR
200mg ON 3/7 OR
100mg ON 6/7
If presence of dermatitis should be given Canesten HC (antimycotic -hydrocortisone combination cream)
Balanitis should be managed with fluconazole 50mg PO OD 7/7 (+/- Canesten HC if very irritated)
Trush treatment recurrent
Recurrent cases can be trialled with longer term suppressive treatment
Induce with 150mg/ 72 hours PO for 3 doses
Maintain with 150mg fluconazole weekly for up to 6 months
Trial withdrawal (recurrence on withdrawal in up to 40%)
BV Protective factors (2)
Presence of H2O2 (hydrogen peroxide) producing lactobacillus protective factor
Most commonly lactobacillus crispatus and jensenii species
Prevalence of BV only 4% in presence of these organisms, compared to 32% for those without
CHC use also appears to be protective
BV causative organism
Gardnerella species (particularly Gardnerella vaginalis)»_space;»> Gram variable coccobacillus
Found in high concentrations in >95% of cases of BV
Presence of high levels of Gardnerella»_space; proliferation of other anaerobic species»_space; mixed infection:
Mobiluncus
Bacteroides
Prevotella
Gardnerella has asymptomatic commensal carriage in ~58% of women without BV
Gardnerella forms a biofilm, strongly adherent to vaginal epithelium
Formation of a biofilm»_space; increased resistance to protective mechanisms of normal vaginal flora (release of H2O2 and lactic acid from lactobacillus) and reduced penetration from antibiotics
Biofilm structure implicated»_space; high rates of BV relapse and recurrence
Prevalence BV
5-10%
Symptoms BV
Asymptomatic in 50%
Abnormal discharge most common symptom
Increased volume
Thinner
Grey»_space; white > yellow
Offensive “fishy” odour ((Smell can be enhanced when vaginal pH raised i.e. during menstruation/ after sex))
Generally non-inflammatory and not associated with vaginitis/ irritational symptoms
BV partner
Gardnerella isolated from urethral samples in up to 80% of male partners of women with BV
However their concurrent treatment does not appear to reduce recurrence/ relapse rates
Male condom use appears to reduce BV recurrence rates by ~5 fold
Amsel’s criteria
3 of 4 criteria to be met
(1) Characteristic discharge
(2) pH >4.5 (alkaline); indicative of lack of lactobacilli producing H2O2/ lactic acid
NB: TV also causes alkaline discharge pH >4.5 vs candida is associated with pH <4.5
(3) Vaginal clue cells on microscopy
((Not done anymore in practice, but 4th criteria previously was + whiff test)) – > Addition 10% potassium hydroxide to vaginal fluid àreleases fishy smelling amines
Hay-Ison Gram-stain method
BV on gram stain
(1) Reduced or absent lactobacilli (Gram + rods) –> Replaced by small gram variable bacilli adhering to shed epithelial cells (“Clue cells”)
(2) Absence of polymorphs (pus cells)
Use of Hay-Ison Gram-stain method for scoring:
Grade 0 – epithelial cells with no bacteria
Grade 1/ normal – epithelial cells with lactobacilli dominant
Grade 2/ intermediate – epithelial cells w some lactobacilli and mixed bacteria
Grade 3/BV consistent – epithelial cells w mixed bacteria and few/ absent lacto
Grade 4 – epithelial cells with gram + cocci only (typically streptococci)
BV treatment
Treatment is typically with metronidazole 400mg PO BD 7/7
Option of 2g STAT dose metronidazole but associated higher rates of recurrence
Metronidazole 0.75% intravaginal gel OD (nightly) 5/7
Similar efficacy demonstrated with 7/7 PO and 5/7 intravaginal gel treatment regimes*
Non-metronidazole treatments not often used in practice but do show similar efficacy for treatment:
Clindamycin 300mg PO BD 7/7
Clindamycin 2% vaginal cream OD (nightly) 7/7
Both oral and topical clindamycin associated with pseudomembranous colitis
BV and pregnancy
Treatment of any BV present is advised in pregnancy, but screening for BV is not recommended
Treatment prior to 20 weeks gestation reduces risks of BV associated pre-term birth
No evidence of metronidazole causing birth defects but cautious use is advised
High dose regimes of metronidazole not recommended in pregnancy/ breastfeeding
Systemic metronidazole changes taste of breastmilk
Clindamycin is known to pass into the breastmilk
Systemic treatment NOT contraindicated, but intravaginal treatment should be considered
Persistent and recurrent BV
Persistent
Trial alternative treatment (metronidazole -> clindamycin)
Consider removing Cu-IUD if present
Recurrent
Consider stopping menstrual flow via contraception to maintain lower vaginal pH
10 days induction therapy with intravaginal metronidazole gel -> twice weekly use for 16 weeks: Cures 75%
Alternative options/ adjuncts
Lactic or acetic acid gel for maintenance therapy in those with recurrent cases -> Either continuous use or cyclically i.e. for 3 days post-menstruation
Vaginal or oral probiotics containing lactobacillus can be considered; evidence of benefit lacking
BV and HIV
HIV transmission rates are 2-5 x increased in the presence of concurrent BV
Some evidence of reduced efficacy of traditional TDF tenofovir vaginal PrEP in the presence of BV
H2O2 producing lactobacilli species (BV protective species) are associated with lower HIV RNA within female genital secretions
Absence of H2O2 producing lactobacilli species is associated with higher HIV RNA within female genital secretions, even in absence of BV
Syphilis (treponema pallidum)
Gram negative parasitic bacterium; SPIROCHETE
Mobile using flagella
Syphilis diagnosis
Dark ground microscopy of sample from chancre (79-86% sensitivity)
Syphilis PCR swab to be sent from chancre
Syphilis serology
Usually turns positive from 4 weeks post-infection; full window period of 3 months
Treponemal-specific antibody tests; done first when screening
(1) TPHA/TPPA (Treponema pallidum HaemAgglutination test)
(2) Treponemal EIA (IgG/ IgM)
Remains positive for life including after treatment
Cardiolipin tests (not treponeme specific)
(1) VDRL (Venereal Disease Research Laboratory)
(2) RPR (Rapid Plasma Reagin)
Insensitive in late syphilis (levels drop off as infection persists) but useful in acute infections (acutely rise)
Becomes negative / decrease logarithmically after treatment
RPR is the test of cure (AIMING FOR A 4X DECREASE IN RPR = SUCCESSFUL TREATMENT)
Negative -> 1/2 = best result
1/8 -> 1/16 = worse and so on
Note – 4x increase in RPR from test of cure level –> reinfection with syphilis
Early/primary syphilis infection
Syphilitic chancre; classically painless single ulcer with indurated edge
Associated regional lymphadenopathy
Typically develops ~ 21 days post-infection (9-90 days incubation)
Self resolves within <8 weeks, may go unnoticed, especially if vaginal, oral or rectal
Early/secondary syphilis infection
Dissemination of infection
Occurs at 6 weeks à 6 months post-infection
Typically causes generalised lymphadenopathy and non-specific, non-itchy, macular rash
Rash classically starts on trunk à spreads outwards, effecting palms and soles
Eventually self-resolves if infection not identified and treated at this stage
Latent syphilis
Asymptomatic ongoing infection
Early latent if <2 years since infection
Can cause recurrence of secondary syphilis symptoms in ~25% in first 2 years
Late latent if >2 years since infection
Late/tertiary syphilis infection
Occurs in ~ 1/3 of people with untreated infection
Multisystemic complications of chronic infection, via type VI hypersensitivity reaction
Can take decades to manifest
Types
(1) Gummatous – 2-15 years
Musculoskeletal/mucosal ‘gumma’ (growths/lumps as immune cells -> granulomas with central regions of coagulative necrosis)
(2) Cardiovascular – 10-30 years
Aortitis -> aortic regurgitation (30%) and aortic aneurysm formation
(3) Neurosyphilis
(A) Meningovascular 2-7 years: Focal arteritis -> infarction. Most common neurosyphilis manifestation. Consider in young adults presenting with CVAs.
(B) General paresis 10-20 years
(C) Tabes dorsalis 15-25 years: Spinal dorsal column inflammation -> degeneration. Loss of proprioception and vibration sense. Argyll Robertson pupil in 80%: Pupillary constriction with accommodation but not to light.
approximate risk of HIV transmission following a sexual exposure by type
(%)
Receptive anal intercourse 1.11
Insertive anal intercourse 0.06
Receptive vaginal intercourse 0.1
Insertive vaginal intercourse 0.082
Receptive oral sex 0.02
Insertive oral sex 0.0
Blood transfusion (one unit) 90-100
Needlestick injury 0.3
Sharing injecting equipment 0.67
Mucous membrane exposure 0.63
Syphilis: treatment
Benzathine penicillin (majority) or procaine penicillin (neurosyphilis)
Early syphilis – benzathine penicillin 2.4M units IM single dose
Later infection – 2.4M units IM weekly, for 3 weeks
Neurosyphilis: Procaine penicillin 1.8 – 2.4M units IM daily for 14 days
Plus PO probenecid (500mg QDS) for 14 days
For cardiovascular and neurosyphilis, prednisolone should be given for 3 days starting 24 hours prior to treatment initiation
Minimum serological review is needed at + 3, 6 and 12 months from treatment AND until serofast result
Rubella Key Points
Caused by Rubella virus:
A togavirus
Single-stranded RNA genome
Transmission primarily via the respiratory route
Incubation period 14 days
Congenital rubella infection teratogenic with poor prognosis and significant complications (sensorineural deafness, cataracts and cardiac abnormalities most common)
No specific treatment. Key is prevention through vaccination programme
Vaccination is via live attenuated virus so cannot be given to pregnant women who are found to be non-immune.
If IgG and IgM are negative the patient is susceptible to Rubella infection.
If IgG +ve and IgM -ve the patient should be considered immune.
If IgM +ve this suggests acute infection or false positive IgM (not uncommon)
‘Blueberry muffin’ rash
Pharmacology of benzathine penicillin
Beta-lactam, naturally occurring penicillin
Narrow spectrum and poor oral absorption -> IM administration; acts as depot, absorbed slowly
Reduced dose required in renal impairment
Crosses the placenta but is safe to use in pregnancy and breastfeeding
Toxoplasmosis treatment
There are 2 treatment options:
Spiramycin ASAP if fetus not infected or status of the fetus not known. This reduces risk of transplacental infection. This is continued until term, or until fetal infection is documented.
Pyrimethamine, sulfadiazine and folinic acid where fetal infection is known e.g. positive amniotic fluid PCR. Monitoring for haemotoxicity required. Pyrimethamine should be avoided in the 1st trimester as teratogenic
Procaine reaction
Feeling of impending doom, hallucinations or seizures can occur immediately following inadvertent administration of procaine benzylpenicillin IV (neurosyphilis treatment)(rather than IM as intended)
Self-resolving and lasts <20 minutes
Jarisch-Herxheimer reaction
can occur within 24 hours of treatment for spirochete infections
Release of lots of spirochete material at once as they die -> fever, chills, myalgia, hypotension
Febrile illness with onset within 4 hours of treatment administration
Resolves within 24 hours
Syphilis in pregnancy
If tested and treated in the 1st trimester -> repeat test (+/- treatment) later in pregnancy: RPR at +1 months and +3 months to ensure adequately dropping
Congenital syphilis is transplacental spread ONLY (most common cause of preventable stillbirth)
**Can occur at any gestation
**More likely to occur in early syphilis / with RPR >1:8 (rare after >=4 years infection)
**No increased risk depending on mode of delivery
**No increased risk depending on breastfeeding
Infants tested at delivery and at +3 months (wp), even if maternal antenatal treatment successful
HSV
dsDNA
within an icosahedral “nucleocapsid” which is then enveloped in a lipid protein membrane (derived from host cell)
Incubation period generally 3-14 days
HSV-1 is the most common cause of genital herpes in the UK
HSV-2 is the strain most likely to cause recurrent anogenital herpes
Where does hsv lie dormant?
Typically sacral ganglia (S2-S5) for anogenital herpes
HSV recurrence
90% of patients with HSV-2 symptoms have at least one recurrence in the following year
60% of patients with HSV-1 symptoms have at least one recurrent in the following year - recurrence beyond 1 yr rare
HSV treatment
Total average resolution time (without treatment) 17-20 days
How long do you have asymptomatic shedding with HSV following infection - worsening / protective factors
More common in first 6 months from infection
In women, use of hormonal contraception and concurrent BV appear to increase HSV-2 shedding
In men, circumcision may confer a weak protective effect against HSV-2 infection
HSV prevalence / symptoms
HSV is common, with a lifetime seroprevalence of up to 80%
Only 5-20% of HSV-2 seropositive individuals recall history of symptoms
HSV transmission between discordant couples
HSV-2 rate of transmission between discordant couples is 15-20% per year
HSV diagnosis
PCR swab from active lesions: Highly specific, and most sensitive method of diagnosis
Antibodies typically appear within 2-3 weeks of infection - > Type specific serology for HSV-1 and 2 possible
IgM detection = unreliable
It is not possible to state if the infection is pre-existing or recent, only that infection has occurred
Limited value given high rates of asymptomatic seropositive cases in general population
When should treatment for hsv be started
If started within 5 days of onset, evidence demonstrates 50% reduction in duration of symptoms as well as 60% reduction in viral shedding.
Pharmacology of acyclovir
Synthetic purine nucleoside analogue
Enzyme thymidine kinase (within HSV) converts aciclovir -> aciclovir triphosphate which interferes with viral DNA and inhibits it’s replication
Does not eradicate persistent/ latent infection (supresses but doesn’t cure)
Aciclovir is not licensed for use in pregnancy, however it is widely used and is not known to be harmful in pregnancy or breastfeeding
When used as suppressive treatment, the usual dose is 400mg BD -> 400mg TDS is recommend for suppression in pregnancy due to the greater volume across which the drug is distributed (BASHH/RCOG)
Hepatitis A
ssRNA
Faeco-oral spread
Incubation period 4 weeks
Diagnosed using serology
Usually self-limiting condition (higher risk if liver disease or immunosuppressed / elderly)
Hep A vaccination
Vaccination offered for high risk groups and those at risk of more serious infection:
Chronic liver disease
HIV
Occupational risks – sewage workers, homeless shelters, working with apes/monkeys
Men who have sex with men
Transgender
Injecting drug users
Close contacts of someone with Hepatitis A
If travelling to a high risk country
2 doses ideally given 6-12 months apart
If 2nd dose delayed by >3 years then ‘course’ should be restarted
Booster after 25 years
Hepatitis B
ds DNA virus!
Spread through exposure to infected body fluids, including blood, semen and vaginal fluids: Sexual exposure, Injecting drug users, Vertical transmission mother-child.
The UK is a very low prevalence country
In areas of high endemicity, majority of infections are acquired during childhood (high rates of chronic infection)
In low endemicity countries, majority of infections are acquired in adulthood via sexual activity of needle sharing in IVDU (lower rates of chronic infection)
Average incubation period 3 months
95% of adult Hepatitis B –> spontaneous clearance
Only small number of chronic infections (opposite of Hepatitis C)
Significant number of childhood cases –> chronic infection (opposite of Hepatitis C)
>90% of those exposed neonatally, and ~ 1/3 of those infected in early childhood
Diagnosed with serology
HbsAg + = infected
HbeAg + = most infectious
Chronic Hepatitis B is defined as presence of HbsAg in the blood for 6 months or more
Hep B vaccination - 3 situations
(1) INFANT VACCINES
From 2017 onwards the UK childhood vaccination schedule introduced Hepatitis B coverage
Given at 8, 12 and 16 weeks of age (2, 3 and 4 months)
Given as hexavalent vaccine which also covers for diphtheria, tetanus, pertussis, polio and Hib
Additional doses of monovalent Hepatitis B vaccine given at birth, 1 month and 1 year for neonates born to Hepatitis B + mothers
(2) HIGH RISK GROUPS
Vaccination additionally recommended in the UK for those adults at higher risk:
» Injecting drug users
»HIV + (4 dose regime > usual 3 dose regime and immunity check 4-8 weeks following completion)
»MSM
»CSW
»Close/ familial contacts of infected individual »_space;Prison inmates
»Those with chronic liver or renal disease
»Occupational risk – healthcare workers, laboratory staff, residential home staff etc
»Travelling to higher prevalence country
Monovalent vaccine, given at 0, 1 and 6 months
Additional 5 year booster if still high risk
If HIV + additional dose is given at 2 months; 4 doses given at 0, 1, 2 and 6 months
Additional 5 year booster if still high risk
(3) AS PEP
Hepatitis B vaccine is also highly effective at preventing infection if given shortly after possible exposure
Ideally within 24 hours of exposure; considered up to 1 week post-exposure as PEP (skin exposures ie needlesticks, sharing injecting equipment)
Note: post-sexual assault guidelines recommend offer of Hepatitis B vaccine up to 6 weeks
(A) VERY Rapid scheme
Very-rapid/ super-accelerated course the given at 0, 7 and 21 days
(B) Rapid scheme
Accelerated course is given at 0, 1 and 2 months
Additional 5 year booster if still high risk given at usual interval
Note: The vaccine is safe to use in pregnancy and breastfeeding
When to check for immunity following hep B vaccine
For most people an immunity check is not required. Check if
(1) RAPID SCHEME
Consider checking immunity at 1-4 months post completion of primary vaccine course for those having accelerated vaccine post-exposure
(2) HIV POS
Immunity should be checked at 4-8 weeks post completion of primary vaccine course for HIV + patients
WHAT ARE YOU LOOKING FOR ON RESULTS
Ideal immunity >100.
Immunity >10 = response
Immunity <10 = no response.
–> If 10-100 should receive further 1 dose of the vaccine. No further monitoring required here if immunocompetent. If HIV + recheck at + 4-8 weeks.
–> If <10 should repeat vaccine course and further immunity check following completion. If <10 again = non-responder. Would require HBIG if exposed to Hepatitis B.
Treatment of chronic hep B
treatment is with tenofovir
There is no curative treatment for chronic Hepatitis B infection and treatment is usually lifelong
Hence very important to check Hep B status prior to using HIV PrEP or PEP (both contain tenofovir)
Hep B serology
Antibodies to HBc are only acquired through NATURAL infection, not immunisation (c = caught)
IgM anti-HBc implies acute infection – usually present for around 6 months following infection
Hepatitis C
2 Hep C RNA
ssRNA
Spread via blood
Long incubation period of up to 6 months
Acute infection is often asymptomatic -> silent chronic infection and long term sequalae -> presentation
Inversely to Hep B, acute infection acquired in neonatal period/ childhood -> good spontaneous clearance rates
Acute infection acquired in adulthood has a tendency to not fully clear and -> chronic infection in >75%
Unlike Hepatitis B, Hepatitis A is a curable condition
Antibodies to Hep C remain + after successful treatment
However this does not confer immunity and reinfection is possible
Diagnosed with serology
#1Hep C Ab
Check Hep C Ab presence -> if –ve then no current or previous exposure/infection
If + Hep C Ab then check Hep C RNA -> if –ve then previous cleared/ treated infection
If Hep C RNA +ve then current infection is present
TREATMENT
Treated with Direct Acting Anti-viral (DAA) medications
Treatment depends on viral genotype, many regimes
Currently complex multi-drug regimes with sofosbuvir being commonly included
The aim of treatment is sustained virological response (SVR). Undetectable serum HCV RNA at + 6/12 after the end of therapy –> Patient “cured” if this is achieved.
Usually 8-12 week treatment course
Very well tolerated with few side effects
Clearance rate of >90%
Sofosbuvir
nucleotide polymerase inhibitor
USed in hep C treatment
Hepatitis E
important causes of peri-natal mortality
treated with ribavirin – nucleoside analogue
HIV
4th gen
antibody and antigen test
uses monoclonal antibodies to test for
HIV IgM
HIV IgG
p24 antigen
WP 45 days from exposure
If PEP given then 73 days from exposure (minimum of 45 days post completion of 28 days PEP)
Third generation tests / POCT
Antibody only
WP 90 days from exposure
HIV criteria for Exposure Prone Procedures (EPPs)
Have 3/12 viral load monitoring
Have a viral load <200 on 2 occasions >3/12 apart
Are under joint supervision by HIV specialist and occupational health (registered)
Define late dx hiv
HIV diagnosis is considered LATE if CD4 count is <350
Viral load at which U=U
<200
Viral load and contraception counselling
NOT recommended for women with HIV and a CD4 count <200
Advise viral load is supressed <200 for at least 6 months prior to conception
HIV vertical transmission,
In utero – 5-10% without ART with majority occurring in the third trimester
Intra-partum – 10-20% without ART (viral load as main risk factor)
Breastfeeding – 5-15% without ART
HIV VL in blood vs in breast milk
HIV RNA (VL) in breastmilk correlates with plasma VL
Generally sit ~ 100 fold LOWER than plasma levels
Higher transmission rates at onset of breastfeeding due to higher cellular content of colostrum
Also higher transmission rates with increasing duration of feeding (more opportunities)
HIV and BV in pregnancy
both increase risk of preterm delivery
Women with HIV are recommended to have screening and treatment for BV in pregnancy
ARTs and pregnancy
Dolutegravir – some limited evidence of link with neural tube defects (discuss with women at conception/ when planning conception) but more research is needed
HIV VL and MOD
VL <50 = normal vaginal delivery/ no restriction on options
VL 50 – 399 = consider planned LSCS
Consider CS trajectory, time on treatment, obstetric factors and woman’s view
Risk of transmission increases from ~0.26% with LSCS to 1.1% with SVD in these VL ranges
VL >=400 = planned LSCS at 38-39/40 (prevent/reduce chance of spontaneous labour)
Neonatal PEP
Neonatal PEP with zidovudine recommended for babies born to mothers without undetectable (<50) VL
NRTI
HIV and breast feeding
PROMISE trial – breastfeeding risk 0.3% at 6 months, 0.6% at 9 months, 0.7% at 12 months
Risk of transmission via breastfeeding increased with:
VL >50
Lower CD4 counts
Longer duration of feeding
Breast or nipple inflammation/ infections
Neonatal gut/mouth inflammation/ infections
Mixed feeding with food at <4 months
Breastfeeding CAN be supported for women who are undetectable (VL <50) on treatment who are amenable to attending for regular (monthly) bloods monitoring and support from HIV teams
HIV treatment
Triple ART
2 nucleoside reverse transcrip inhibs (NRTIs)
AND EITHER
(A) a non-nucleoside rev transcript inhib(NNRTI)
(B) OR a protease inhibitor (PI)
(C) OR an integrase inhibitor (II)
NRTI
examples
SEs
Zidovudine (AZT), Emtricitabine and Tenofovir (Truvada combo) and many more
General NRTI side-effects = peripheral neuropathy
NNRTI
examples
SEs
Nevirapine, Efavirenz
Side-effects = P450 enzyme INDUCERS, rash
PI
Examples
SE
How to remember
Indinavir, Nelfinavir, Ritonavir, Saquinavir
Side-effects = diabetes, hyperlipidaemia, buffalo hump, central obesity, P450 enzyme INHIBITORS (especially Ritonavir)
‘Navir tease a pro’: HIV drugs that end with -navir are protease inhibitors
Integrase inhibitor (II)
Examples
SE
Ways to remember
Raltegravir, Elvitegravir, Dolutegravir
NB dolutegravir associated with neural tube defects (5mg folic acid)
‘It’s grave/great you integrate’: HIV drugs that end with -gravir are integrase inhibitors
ARTs and resistance
ARTs must not be stopped suddenly – resistance is an issue
> 95% compliance is optimal to avoid resistance
Equates to not taking the drug LATE on >2 occasions/week OR not missing >1 dose/ 2 weeks
If taking with compliance between 50-95% this is maximal risk for resistance
ART absorption and metabolism
A majority of ART medications are metabolised by p450 enzymes
Beware concurrent long-term steroids, warfarin, phenytoin and rifampicin etc
Absorption of ART requires stomach acid so omeprazole/ other PPIs can decrease absorption
General side effects of #1 ART
Allergic rash may occur within first 4 weeks -> do NOT suddenly stop taking:
Risk of resistance and also of sensitisation -> future anaphylactic reaction
Mild GI upset
Jaundice
Long term toxicity can develop – regularly monitor U+Es, LFTs, FBC, urinalysis
If Q risk >10% agents which increase CV risk (mainly protease inhibitors) avoided –> Monitor lipids, HbA1c and Q risk score
Tenofovir disoproxil fumarate (traditional tenofovir; cheaper) can contribute to osteoporosis
Monitor FRAX score +/- DEXA as per scoring
Also important consideration for PrEP users as contains TDF Tenofovir typically
Traditional TDF Tenofovir -> TAF Tenofovir (tenofovir alfenamide) = safer for bones and ?Kidneys
Branded name Descovy; often called “TAF PrEP” (++ more expensive)
HIV PEP
Within 72 hours of potential exposure to HIV
2 x NRTIs PLUS 1 x II
Fixed-dose combination tablet combining emtricitabine and tenofovir (2 x NRTIs)
(Previously branded Truvada, now often generic)
AND raltegravir (integrase inhibitor)
Most effective and best evidence base if started within 24 hours from exposure
Evidence suggests PEP may reduce the chances of HIV infection by approximately 80%
Weak evidence based compared to PrEP
28 day course
PEP is recommended when risk is > 1/1000
PEP is considered if risk if >1/10,000
PEP is NOT recommended if risk if < 1/10,000
Your HIV positive partner has undetectable virus levels on treatment
Human bites
Another person’s semen gets in your eye
You had oral sex only
When starting HIV PEP check LFTs and U+Es and Hepatitis B screening
This is because Tenofovir is also active against Hep B
HIV PrEP
Tenofovir and emtricitabine (2 x NRTIs)
Must have U+Es monitored at least annually
Traditional “Truvada” PrEP = tenofovir disoproxil fumarate (TD or TDF PrEP) with emtricitabine
!! Concurrent use of depot contraception should be avoided due to BMD concerns
Newer “Descovy” PrEP = tenofovir alfenamide (TAF PrEP) with emtricitabine
Descovy/TAF safer for those with osteoporosis risk or chronic kidney disease, + expensive
Can be taken daily (must be taken daily by anyone having frontal sex and generally recommended for those on gender affirming hormone therapy)
OR only taken event based (evidence for cisgender MSM groups only – only evidence of efficacy for anal sex)
2 tablets between 2 - 24 hours before sex, then 1 tablet a day for 48 hours following the last episode of sex
Daily dosing has the strongest evidence base (UK PROUD trial)
NHS funded in England since April 2020
NHS funded in Scotland since April 2017
BBVs and needlestick injuries
Hepatitis B 20-30%
Hepatitis C 0.5-2%
HIV 0.3%
Hepatitis B - HR
PEP available via vaccination +/- immune globulin (HBIG)
Known HBsAg + source
–> for known responders to HBV vaccine a BOOSTER dose should be given (majority)
–> If they are in the process of being vaccinated OR are a non-responder they need to have hepatitis B HBIG + vaccine
Unknown source
–> for known responders, green book advises a booster dose of HBV vaccine (majority)
–> For known non-responders HBIG + vaccine should be given
–> Those in the process of being vaccinated should have an accelerated course of HBV vaccine
Hepatitis C
No PEP
Followed up with serial serology for 24 weeks (6 months)
If seroconversion, then treat (interferon +/- ribavirin)
HIV
PEP
Single tablet tenofovir/emtricitabine – 2 x nucleoside reverse transcriptase inhibitors NRTIs (Now often generic but previously branded Truvada)
PLUS 2 tablets of raltegravir (integrase inhibitor – “it’s great, you integrate”)
ASAP following exposure, but may be started up to 72 hours following exposure
28 day course
Serological testing at + 45 days minimum following completion of PEP
Minimum of 73 days after exposure (if 28 day course of PEP completed)
If sexual exposure, recommendation is for final testing to be done at 12 weeks (with STS serology) –> Reduces risk of transmission by 80%
Scabies
what is name of infector
life span
eggs and hatching
transmission
In the human host, infection is with sarcoptes scabiei var hominis.
Parasite: 8 legged mite infestation with a lifespan of 4-6 weeks.
Viable on inanimate objects for 2-3 days
Female mites burrow into the skin and lay eggs which hatch in 3-4 days
Total time from hatching –> gravid mature females is 14 days.
Transmission via prolonged skin to skin contact >10-20 minutes
Holding hands is the most common route of transmission
Scabies symptoms
Symptoms of classical scabies:
Often asymptomatic for first 4-6 weeks in first episode of infestation
People are infectious BEFORE the rash and itching develop
–> Intense itching and skin irritation occurs via type IV delayed hypersensitivity reaction to mites
Itch typically worse at night
–> Symmetrical polymorphic lesions of skin, most commonly on hands in interdigital webs
–> Classical nodules and papules seen on penis and scrotum if this area is effected
In reinfections symptoms occur much sooner due to previous sensitisation, within 24-48 hours
Scabies and immunocompromised groups
Norwegian or “crusted” scabies occurs immunocompromised groups - failure of sensitisation to mites- itch less intense - rash more extensive - crusted lesions with thick hyperkeratotic scales– highly contagious as bigger mite burden
Classical scabies treatment
(1) Permethrin (a pyrethoid) 5% cream is first line, 2 applications one week apart
Apply to whole body from chin and ears -> down
Apply to cool skin (not following bath /shower)
Wash off after 8-12 hours
If hands washed with soap within this window, reapply permethrin to hand area
Reapply +1 week
Suitable in pregnancy and breastfeeding; wash cream from nipples before feeds
(2) Malathion (an organophosphate) 0.5% aqueous lotion
If permethrin not appropriate (allergy to chrysanthemums - flowers!)
Must be left on for 24 hours (less practical than permethrin)
(3) Ivermectin oral – only for treatment resistant cases in classical scabies
Note: Symptoms of irritation often persist for several weeks following successful treatment
Sedative antihistamines and calamine lotion for symptomatic relief in addition to permethrin
-> itch beyond 1 month post completion of treatment may suggest failure -> retreat.
Crusted scabies treatment
Permethrin application OD for 7 consecutive days -> twice weekly until cure
PLUS oral ivermectin
Scabies PN
Household contacts and sexual contacts should be concurrently treated to avoid reinfections
Partner tracing for 4 weeks prior to symptoms is recommended
Pediculosis pubis (lice)
Pthiriasis or pediculosis = pubic lice
Wingless insects, unable to fly/ jump, feed from human host via blood sucking (typically at hair follicle base)
3 species of lice effect humans:
(1) Pthirus pubis (pubic or “crab” lice)
(2) Pediculus humanus capitis and (3) corporis (head /body lice)
Pubic lice, unlike body/head lice, are NOT known to be vectors of BBV or human disease
95% of sexual contacts of an active carrier -> develop infestation
Symptoms:
Itching/ irritation (hypersensitivity reaction)
~40% develop skin erythema
If very hairy -> thighs, perineum, trunk, abdomen
Occasionally can infest eyelashes / eyebrows ->blepharoconjunctivitis
Treatment should be applied to all body hair (leave on as per scabies instructions and repeat +1 week):
Permethrin 5% cream
Malathion 0.5% aqueous solution
Clothes and bed linen should be washed at >50 degrees
Contact tracing of all partners in past 3 months recommended
HPV
non-enveloped double stranded DNA virus
LR genital warts – HPV type 6, 11, 42 and 44
Highest risk strains 16 and 18 responsible for >70% of cases
(Other high risk oncogenic strains include 31, 53 and 58)
HPV and anal cancer
Responsible for >90% of anal intra-epithelial neoplasia (AIN)
AIN is a pre-invasive lesion -> anal cancer if left undiagnosed/ untreated
Majority of subsequent invasive anal cancers that do occur are squamous cell carcinomas
HPV and penile cancer
Responsible for >40% of penile intra-epithelial neoplasia (PIN)
HPV and vulval/ vaginal cancers
Responsible for >40% of vulval and vaginal cancers
2 types of vulval intra-epithelial neoplasia
(1) Usual type VIN
More strongly associated with HPV, smoking and immunosuppression
Not associated with inflammatory skin conditions
More common in pre-menopausal population (~40s)
Some cases may self-resolve
Less likely to progress to squamous cell carcinoma than differentiated VIN
If left untreated/unmonitored, time to squamous cell carcinoma –> 6-7 years
(2) Differentiated VIN
Associated with inflammatory skin conditions, lichen sclerosis AND lichen planus
More common in post-menopausal population (>60s)
More likely to progress to squamous cell carcinoma»_space; usual type VIN
Average time to progression if left untreated –> 2-4 years
HPV mechanism: viral oncogenes E6 and E7
E6 -> P53 inhibition
P53 usually acts as tumour suppressor
E7 -> pRB (retinoblastoma protein) inhibition
HPV (Gardasil-9) vaccine
Recombinant protein vaccine
Should ideally be given before first sexual contact
In UK children (all genders) receive at 12-13 years of age (during school Year 8) since 2008 (since 2019 all gender kids)
Covers 9 important HPV strains; 6, 11, 16, 18, 31, 33, 45, 52 and 58
Other eligible groups:
Men <45 years who have sex with other men
Girls aged <25 years who missed school
Transgender people
Sex workers
People living with HIV
People <25 years only need 1 dose generally
If aged 25 – 45 years may need 2 doses (given at 6 months – 2 years apart)
If weakened immune system i.e. HIV + then 3 doses are recommended, ideally within 1 year
Management of warts
40% of warts resolve spont in 4 months (immunocompetent)
Smoking cessation increases rates of spontaneous clearance
Treatment comes with risk of scarring and pigmented skin changes
If patient wishing for treatment, there is no single first line option; choices include:
(A) Cryotherapy (usually weekly for 4 weeks) – more practical for smaller number/ volume warts
(B) Imiquimod (Aldara)
(C) Podophyllotoxin (Warticon)
Imiquimod (Aldara)
Wart treatment
Immune response stimulator (I with I)
Application 3 x weekly (alternate nights) –> wash off 10-16 hours later, for up to 16 weeks
Better for keratinized warts, but also suitable for soft/ non-keratinized lesions
Generally takes longer to work than podophyllotoxin
Generally accepted as safe in pregnancy (though not licensed)
Podophyllotoxin (Warticon)v
Ward treatment
Anti-mitotic agent which should cause local tissue necrosis
0.5% solution or 0.15% cream
Application for BD 3 consecutive days, repeated at weekly intervals for one month
Better for softer, non-keratinized warts
Podophyllotoxin is contraindicated in pregnancy (teratogenic)
Molluscum contagiosum
Benign skin eruption caused by molloscum contagiosum virus (MCV) - DNA virus
4 subtypes MCV 1-4 clinically indistinguishable (mcv 1 common, 2 in immunosup)
Incubation period (contact à lesions) for most is between 2-12 weeks (some cases up to 6 months)
Causes smooth, pearly umbilicated lesions 2-6mm in size
Usually lesions spontaneously resolve within 3 months
Options as per wart management in exceptional cases warranting treatment
Molloscum can be an indicator condition for HIV, and is found in up to 20% of HIV + individuals
Children <15 years (account for 90% of GP attendances for molloscum) .
Autoinoculation can occur from itching/ picking –> 10-15% of children have genital lesions
STI More common in 20-29 year demographic
Lesions prone to koebnerization
(new skin lesions of a pre-existing dermatosis on areas of cutaneous injury in otherwise healthy skin. I)
vaccination recommendations and regimes Hepatitis A
The hepatitis A monovalent vaccine is given in two doses, 6–12 months apart.
vaccination recommendations and regimes Hepatitis B
Injecting drug users
MSM
CSW
Close/ familial contacts of infected individual
Prison inmates
Those with chronic liver or renal disease
Occupational risk
Travelling
HIV+ve
Monovalent vaccine, given at 0, 1 and 6 months
–> Additional 5 year booster if still high risk
–> HIV - 4 dose regime (0, 1, 2, and 6) and immunity check 4-8 weeks following completion(10-100 should receive further dose)
Accel is 0, 1, 2 months
Super accel is 0, 7 and 21 days
(check immunity 1-4 months post primary vacc)
Also used as PEP one week after (although offer post SA 6weeks after)
combi hep a and b
Twinrix Adult
Twinrix® is given in three doses, at 0, 1, and 6 months.
If Twinrix® is given as a rapid schedule (on days 0, 7, and 21), a booster dose is needed at 1 year.
vaccination recommendations and regimes HPV
now anyone under age of 25 who hasnt had.
Or MSM < 45
2 doses 6-24 months apart
Monkeypox (smallpox) vaccine
Uses the smallpox vaccine outside of it’s licence
2 doses given 28 days (1 month) apart
–> protected from 7 days following second dose
–> Optional booster dose at + 2years
–> Could also be used as a form of PEP – recommended within 4 days of exposure (considered up to 14 days)
(ended but ?restarted?)
Thought to be up to 85% effective at preventing MPX (after full course – 2 doses)
Was recommended for:
MSM
Group sex /sex on premises attenders
Sex on premises staff
Sexual health and relevant hospital department staff
Full course wa
Tanner stages of breast development
1 = none/ prepubertal
2 = breast buds only, onset of puberty
3 = enlargement of breast and areola continue with no separation in breast-areola contour
4 = nipple and areola project to form secondary mounds above the level of the surrounding breast
5 = adult; nipple only projected, areola is confluent with the breast
Tanner stages of pubic hair growth
1 = none/ prepubertal
2 = very sparse hair growth, light/soft hair quality still
3 = hair becomes darker and thicker but remains sparse
4 = more like adult coverage but not full, spares the inner thighs
5 = full adult coverage including inner thighs
Prior to puberty, what is GnRH release is inhibited by?
neurotransmitters including GABA and neuropeptide-Y
