Pathogenesis of HIV and the major sexually transmitted infections Flashcards
1
Q
What is the difference between an STD and a genital infectious disease?
A
STD - sexually transmitted by definition
GID - not all are acquired by sexual transmission, though act my precipitate e.g. bacterial vaginosis (normal vaginal commensal flora or GI flora)
2
Q
What are the common bacterial pathogens causing STIs in the UK?
A
- N. gonorrhoea
- C.trachomatis
- Ureaplasma
- Mycoplasma
- G. Vaginalis
- Anaerobes
3
Q
What are the uncommon bacterial pathogens causing STIs in the UK?
A
T. pallidum
H. ducreyi
K. granulomatis
C. trachomatis (LGS)
4
Q
What are the common viral pathogens causing STIs in the UK?
A
- HSV
- HPV
- Molluscum (pox virus)
5
Q
What are the uncommon viral pathogens causing STIs in the UK?
A
- HIV
- Hep B
6
Q
What are the common protozoan/fungal/ectoparasites pathogens causing STIs in the UK?
A
- Trichomonas vaginalis
- Candida albicans
- Phthirus pubis (crabs)
Saroptes scabiei
7
Q
What is the most common STI in the UK?
A
Chlamydia
8
Q
What is the route of transmission for STIs?
A
- Mucous membrane contact
- Exchange of bodily fluids
9
Q
Which STIs remain at local sites of infection?
A
- T. vaginalis
- Chlamydia
- HSV
- HPV
- N.gonorrhoeae
10
Q
Which STIs have mixed sites of infection?
A
- T. pallidum (tertiary syphilis - brain)
- N. gonorrhoeae
11
Q
Which STI’s have other (i.e. not genital) sites of infection?
A
- HIV
- HBV
12
Q
What are the various forms of vertical transmission?
A
- In utero - trans placental
- Perinatal - passage through infected birth canal
- Eye mucous membrane - conjunctivitis/keratitis
- Present in breast milk
13
Q
What is the risk of transmission/acquisition related to?
A
- Number of sexual partners
- Use of non-barrier or no contrception
14
Q
Are patients with one STI likely to have another STI?
A
Yes - hence universal screening for HIV
15
Q
Why is contact tracing very important?
A
Infection may be asymptomatic
16
Q
Describe the morphology of N. gonorrhoeae.
A
Gram negative diplococci
17
Q
Where do N.gonorrhoeae replicate?
A
Are phagocytosed and replicate intracellulary.
18
Q
What virulence factor do some N.gonorrhoeae cells possess which makes them more infective, and how?
A
- Pili on cell surface
- ↑ ability to attach to mucosal epithelial cells
- Primarily infect columnar / cuboidal epithelium
19
Q
What is the incubation period for gonorrhoea?
A
2-5 days
20
Q
What percentage of women are asymptomatic?
A
60%
21
Q
What are the symptoms of gonorrhoea in women?
A
- Urethral discharge
- Dysuria
22
Q
What are the local complications of gonorrhoea?
A
- epididymitis, prostatitis;
- barthonilitis, salpingitis, PID, peritonitis
- Fitz-Hugh-Curtis Syndrome (perihepatitis): Usually co-infected with C trachomatis
23
Q
What are the systemic complications of gonorrhoea?
A
Metastatic: Disseminated Gonococcal Infection (DGI)
- 0.5-3% of untreated – ↑ with specific strains
- bacteraemia, arthritis, dermatitis (meningitis).
- (up to 13% DGI: Complement deficiency)
24
Q
What are the complications of gonorrhoea in pregnancy?
A
- Spontaneous abortion
- Premature labour
25
How can conjunctivitis be caused by gonorrhoea?
Self-inoculation
26
What are the neonatal complications of gonorrhoea?
- Ophthalmia neonatorum
| - Acute purulent conjunctivitis,
27
How is microscopy used in the diagnosis of gonorrhoea?
- urethral swab : GNID: high sensitivity / specificity
| - (Other sites: commensal Neisseria spp)
28
How are cultures used in the diagnosis of gonorrhoea?
- Selective plates, 48 hours, fastidious
- Endocervical (not High Vaginal) [Sens: 80-90%]
- (1o locus = columnar epithelial cells endocervix)
- urethral swab [Sens >/ 95% in men]
- High specificity (confirm not N meningitidis / other spp)
- Antibiotic sensitivity testing, (typing).
29
What is the nucleic acid amplification test?
- Multiplexed with C trachomatis
| - Urine / vaginal swab: specificity > 99%;
30
What is the treatment for gonorrhoea?
β-lactams:
- (BenzylPenicillin, amoxicillin)
- 1970s – resistance: β-lactamase; PBP change
Cephalosporins:
- cefixime (oral)
- ceftriaxone (iv or im route)
Fluoroquinolones:
- Ciprofloxacin (↑ resistance)
Others:
- Spectinomycin, azithromycin.
- (Tetracycline – widespread resistance)
31
Which antibiotic has the least resistance to N.gonorrhoeae?
Ceftriaxone
32
What are the likely causes of non-gonococcal urethritis (NGU)?
- Chlamydia trachomatis types D-K
| - Ureaplasma urealyticum (Mycoplasma genitalium)
33
How is NGU diagnosed?
Currently: NAAT for chlamydia
34
How is NGU treated?
Doxycycline; macrolide: erythro- / azithro-mycin
35
What kind of pathogen is C.trachomatis?
Obligate intracellular pathogens.
Unique lifecycle:
- extracellular infectious form: Elementary body
- Intracellular replicative form: Reticulate body
36
What are the target cells for C.trachomatis?
- squamocolumnar epithelial cells of
- endocervix / upper genital tract in ♀;
- Conjunctiva, urethra, rectum in ♀ & ♂
- Also respiratory tract cells in infants
37
What is the national chlamydia screening programme?
Screen (i.e asymptomatic)
| - All sexually active
38
What is the prevalence of of chlamydia in the UK?
- 16-44 yr olds: 1.5% sexually experienced ♀, 1.1% ♂
| - 16-24 yr olds: 3.1% ♀, 2.3% ♂
39
What are the features of chlamydia cervicitis?
- cervical friability,
- oedema
- ectopy
- mucopurulant discharge
40
Why is chlamydia often the cause of 'acute urethral syndrome'?
May have dysuria / frequency but sterile pyuria on standard urinalysis.
41
What are the adult complications of chlamydia infection?
PID (> 9.5% within one yr w/out Rx), perihepatitis
- Tubal infertility (10.6% PID),ectopic pregnancy, chronic pain
Epididymitis (2%)
Conjunctivitis
Reiter’s syndrome:
- arthritis, conjunctivitis, urethritis, skin lesions
42
What are the neonatal complications of chlamydia infection?
- conjunctivitis (later onset than with N gonorrhoeae, 5-12 days)
- Infant Pneumonia: usually present at 4-11 weeks
43
How is the diagnosis of chlamydia performed?
(Histology: Inclusion bodies)
(Cell culture)
NAAT (superseded EIA)
- Sensitivity: cervix 81-100%, urine ♀: 80-96%, urine ♂: 90-96%
- Specificity:99.7%
(Serology – limited value in most oculogenital infections)
44
What is the treatment for chlamydia?
- Azithromycin 1g PO single dose
| - Doxycycline 100mg BD for 7 days
45
What is the treatment for paediatric chlamydia?
- conjunctivitis / pneumonia: erythromycin, 14 days.
| - (Treat parents as well)
46
What is the association between PID and infertility?
1st, 2nd, 3rd episode associated with 10%, 30%, 50% risk of infertility
47
Which subtypes of HPV cause 90% of genital warts?
6 and 11
48
Which subtypes of HPV cause 70% of cervical carcinomas?
16 and 18
49
What are the treatments for genital warts?
Burn - podophyllin, salicylic acid, trichloracetic acid
Freeze - Liquid nitrogen
Cut
Imiquimod
50
Which HSV is more common in women than men?
HSV - 2`
51
What kind of virus is HSV?
dsDNA
52
What are the symptoms of primary genital herpes?
- pain, itching, dysuria, vaginal / urethral discharge –
- bilateral vesicles / ulcers - viral shedding,
- Accompanied by constitutional symptoms
53
Where does HSV become latent?
Sensory neuron cells – sacral nerve ganglia
54
Why does HSV reactive?
- local trauma, menstruation, stress
- may have asymptomatic shedding
(more common in men)
55
How is HSV diagnosed?
- Clinica
- PCR (HSV 1 or 2)
- histology
56
What is the treatment for HSV?
- Aciclovir
57
What are the
- dissemination
- meningitis
- encephalitis
- sacral nerve parasthesiae
- urinary retention
58
Describe the morphology of T.pallidum.
- Slender, helical, tightly coiled cells
| - 0.18 μ wide, 6 – 20 long (too thin for Light Microscopy)
59
What is the mode of infection for T.pallidum?
Penetrates intact mucous membranes or via abraded skin
Disseminated within days via lymphatics / bloodstream
Subsequent clinical symptoms & signs
60
What is the histology of T.pallidm infection?
- obliterative endarteritis
- Concentric endothelial / fibroblastic proliferation
- microscopic vascular compromise
61
What is the incubation period for T.pallidum?
Median - 21 days
62
What are the clinical features of primary syphilis?
1°: chancre
- site of inoculation, painless indurated lesion
- Heals spontaneously, within 3 – 6 weeks.
63
What are the clinical features of secondary syphilis?
Most florid phase 2-8 weeks post onset of chancre
Skin:
- Rash: macular / maculopapular, trunk, limbs -palms / soles
- Condylomata lata – as coalesce in warm body areas – grey
- erythematous plaques, highly infectious
- “mucous patches” – silvery-grey erosions, muc membranes
Constitutional symptoms – fever, malaise, weight loss
Generalised lymphadenopathy (may include epitrochlear)
CNS involvement (40%), headache, meningismus
Spontaneous resolution after 3-12 weeks.
Latent: No clinical manifestation, positive serology
Without treatment: ~ 30% will develop late / 3o syphilis
64
What are the tertiary manifestations of syphilis?
- Neurosyphilis
- Aortitis
- Late benign syphilis
65
What is neurosyphilis?
Meningovascular: Hemiplegia, seizures
Parenchymatous:
- general paresis (cortex): personality changes, Argyll Robertson pupils: accommodate to near vision, don’t react to light
- tabes dorsalis (spinal cord): demyelinisation of posterior column / dorsal roots / dorsal root ganglia: ataxic wide–based gait, lightening pains in legs, loss of position / vibratory sense
66
What are the clinical features of aortitis?
- aortic regurgitation
| - saccular aneurysm
67
What is late benign syphilis?
- non-specific granulomatous reaction,
| - Any organ, most commonly bone / skin / soft tissue
68
What are the signs and symptoms of congenital (in utero transmission) syphilis?
- Greatest risk: Spirochaetaemia of early syphilis
- Early signs: snuffles, rash, hepatosplenomegaly
Late: include frontal bosses, saddle nose, sabre shins
Hutchinson’s incisors.
69
What tests are used in the diagnosis of syphilis?
(Lack of culture)
Direct detection:
- Darkfield microscopy – 1o or 2o lesions
- PCR – more sensitive than microscopy, Sensitivity 89-95% when compared to serology (..NOT necess “false” +ve)
Indirect tests – serology: mainstay – two groups of tests:
- Specific: anti-treponemal antibodies: EIA, TPHA, FTA. Sensitive / specific, but won’t sero-convert post Rx
- Non-specific: reaginic antibodies versus lipoidal antigens: VDRL, RPR (Rapid Plasma Reagin) tests. False positives, but usually sero-convert post
- successful Rx – can monitor with titres
70
How is syphilis treated?
- Standard: Penicillin – based
- Length / route (IM / IV) depends on stage / site
Alternatives (depend on stage / site):
amoxicillin, ceftriaxone, doxycycline,
71
What is the Jarish-Herxheimer reaction?
```
Commonest in 2o syphilis
Fever, chills, myalgia
Hypersensitivity reaction – organism lysis:
release of heat stable protein.
Self-limiting.
```
72
What is the cause of trichomoniasis?
- Trichomonas vaginalis
- Trophozoite transmitted, no known cyst.
- Humans only natural host
73
What are the symptoms of trichomoniasis?
- profuse greenish frothy vaginal discharge
- mucosal inflammation
- males are usually asymptomatic but may have urethritis + be a source of re-infection
74
How is the diagnosis of trichomoniasis performed?
Microscopy/culture (high vaginal swab):
75
What is the treatment of trichomoniasis?
Metronidazole
76
What is the cause of bacterial vaginosis (BV)?
- reduced vaginal lactobacilli
| - increased Gardnerella vaginalis & anaerobes
77
What are the symptoms of BV?
- watery discharge
- +ve KOH test (10% KOH - fishy odour)
- vaginal pH >4.5
- clue cells on microscopy
78
What is the treatment for BV?
- metronidazole
- amoxycillin
- topical clindamycin
79
What factors might contribute to thrush/balanitis?
- oral contraceptives, poorly controlled diabetes,
| - antibiotics – inhibition of normal flora
80
What is the source of the Candida albicans?
- bowel source
| - (sexual transmission)
81
What are the symptoms of candidiasis?
- vulval, vaginal and penile erythema; itching / irritation
- Classically: thick / adherent discharge; white plaques
- maculopapular & fissuring lesions
82
What is the treatment for uncomplicated C.albicans?
- (C albicans, not recurrent, not severe)
- Topical agent: e.g. clo-trimazole (Canesten™)
- Fluconazole: single 150mg oral dose
83
What is the treatment for complicated C.albicans?
- Treatment for 10-14 days (topical or oral)
(? Obtain in vitro sensitivities)
- Consider treatment of partner(s)
- (Longterm suppressive treatment if frequent recurrence)
84
What is AIDS?
The end-stage manifestation of HIV infection?
85
What are the features of HIV?
A retrovirus: possesses reverse transcriptase
- RNA dependent DNA polymerase
- - converts viral RNA into linear ds DNA
- - subsequently incorporated into host genome
- Error prone – high rate of mutability.
RNA – based:
- survival advantage - great genetic diversity
DNA intermediary –
- latency, & can incorporate into host genome
CD4 / macrophage tropic
- reduction of host immune response.
86
What are the transmission routes for HIV?
- Sexual – transmission at genital or colonic mucosa
- Exposure to other infected fluids: blood / blood products
(including accidental occupational exposure)
- Mother to infant
87
What is the role of viral glycoprotein gp120?
Interacts with cellular receptor CD4 and chemokine receptor CCR5 for virion to gain host cell entry.
88
Where does reverse transcription occur?
In cytoplasm
89
What happens to the dsDNA once reverse transcription has occured?
- dsDNA imported into nucleus
- Integration into cell genome
- Latency / immune evasion
90
What is produced by the complex interaction between virion production & T-cell turnover?
Rapid emergence of viral mutants
- may promote immune escape, drug resistance
Progressive / fluctuating T-cell depletion.
91
What is the result of loss of CD4+ve T-cells?
Allows “opportunistic” infections
- Organisms not normally pathogenic in immune competent patient.
Risk of different infections related to degree of immune suppression (“CD4 count”)
92
What are the stages of HIV infection?
Stage I: CD4 count > 500 cells / μL
Stage 2: 349 – 499;
Stage 3 (Advanced HIV): 200 – 349
Stage 4 (AIDS):
93
What are characteristics of primary infection?
Acute retroviral Syndrome
- fever, pharyngitis, lymphadenopathy, rash et al
- Then asymptomatic phase
94
What are the signs of the early symptomatic phase of HIV?
- Pulmonary TB
consider HIV test in all new TB cases
- Persistent oral candidiasis
- Unexplained chronic diarrhoea (> one month)
- Unexplained persistent fever (> 37.6, for > one month)
- Severe bacterial infections (e.g. S pneumoniae bacteraemia)
95
What are the opportunistic infections seen in AIDS?
- HIV wasting syndrome, HIV encephalopathy.
- Oesophageal candidiasis
- Pneumocystis jirovecii (formerly carinii) pneumonia
- CMV disease (including retinitis),
- CNS toxoplasmosis;
- Progressive multifocal leukoencephalopathy (PML)
- extra-pulmonary cryptococcosis
- Disseminated non-tuberculous mycobacterial disease
- Extra-pulmonary tuberculosis
- Chronic cryptosporidiosis; chronic isosporiasis
- Kaposi’s sarcoma, lymphoma (cerebral or non-Hodgkin’s)
96
What percentage of HIV in the UK is undiagnosed?
- ~ 25% cases in UK undiagnosed
- Account for approximately 70% of transmission
- New case rates doubled in past 10 years
97
Which patients are screened for HIV?
- GUM
- patients with TB or lymphoma
- Ante-natal.
98
What are the various test used in the diagnosis of HIV?
```
Antibody testing (sero-conversion)
- Confirm with second sample.
```
Polymerase Chain Reaction (PCR)
- Detects viral nucleic acid:
- Quantitative: viral copy numbers - “viral load”- in blood / (other fluids)
- Genotypic mutations conferring drug resistance
(Opportunistic infections)
CD4 cell count
