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Tropical Medicine > HIV & STI's > Flashcards

HIV & STI's Flashcards

1
Q

Oral Candidiasis in HIV suggests what about CD4 count?

WHO Stage?

Treatment options

A
  • CD4<100
  • WHO Stage III
  • Treatment Options
    • nystatin
    • miconazole gel
    • fluconazole 50-200 mg od
    • ketoconazole 200 mg od or bd
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2
Q

What cells express CD4 receptors?

A
  • T helper cells (primary target)
  • monocytes
  • macrophages
  • dendritic cells
  • NK cells
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3
Q
  • What are the steps of viral integration?
  • At which steps to HIV drugs work?
A
  • Steps of viral replication:
      1. Binding- when the virus binds to the CD4 receptor and co-receptor on the target cell
      1. Fusion- The virus merges with the cell membrane and spills its contents into the cell
      1. Reverse transcription- The viral RT (reverse transcriptase) enzyme is used to make a DNA copy of the viral RNA
      1. Integration of viral DNA into the host cell genome to produce proviral DNA using the enzyme integrase
      1. Transcription of proviral DNA into mRNA, production of viral proteins and budding of viral components from cell.
      1. Protease cleaves the long chain polyprotein into active components eg. viral enzymes. The virus is now infectious and will bind to other CD4 cells.
  • Mechanism of action of antiretrovirals:
    • Fusion inhibitors
    • Nucloside reverse transcriptase inhibitors (NRTIs)
    • Non-nucloside reverse transcriptase inhibitors (NNRTIs)
    • Integrase strand transfer inhibitors (INSTIs)
    • Protease inhibitors (PIs)
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4
Q

What are the AIDS Defining Conditions?

A
  • PCP
  • Histoplasmosis\Coccidiodomycosis
  • Cryptococcoccosis
  • Toxoplasmosis
  • Atypical herpes simplex virus disease
  • Cryptosporidiosis
  • CMV
  • MAC

CDC also requires CD4<200; WHO definition does not.

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5
Q

WHO Staging System for HIV

A
  1. Asymptomatic or persistent generalised lymphadenopathy
  2. Mild opportunistic infections (OIs) or weight loss (adults)
  3. More serious or persistent OIs
    • More severe weight loss or malnutrition
    • Pulmonary tuberculosis (+ lymph node tuberculosis in children) Cytopaenias
  4. AIDS defining conditions (infections/malignancies/organ dysfunction)
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6
Q

What is WHO definition of treatment failure in HIV

A
  • Viral load persistently >1000 copies/ml i.e. on 2 occasions
  • Confirmed on second test within 3-6 months
  • Adherence support between measurements
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7
Q

How do you define Treatment Failure if you can’t measure viral load in HIV?

A
  • Clinical Failure
    • New AIDS defining event after 6 months of treatment.
  • Immunological Failure
    • CD4 count falls to baseline or is persistently <100 cells/mm3
    • Without active infection
    • nb CD4 non-inferior to viral load on study using death as clinical endpoint, but took longer to switch (12 vs 25 months) and duration of viremia (7.2 vs 15.8 months) so potentially higher risk of resistance and transmission of resistance (but clinical significance?)
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8
Q

Compare and contrast monitoring of HIV ART in high and low resourced settings.

A
  • Well Resourced
    • Start ARVs when diagnosed
    • Drug Regime chosen by resistance profile
    • CD4 count q 3-4 months
    • routine monitoring of VL
    • several 2nd and 3rd line and ‘salvage’ regimes; novel classes available
  • Low Resources - Ideal
    • Start ARVs when dx
    • Drug regime according to first-line national policy
    • CD4 q 6 mo until stable
    • VL @ 6 & 12 months, then annual
    • Ltd 2nd line options only, 3rd line may require central committee approval
    • Public Health Approach
  • Low Resources - Reality
    • Start ARV’s based on immunological criteria (eg cd4< 500, 350 etc)
    • Drug regime according to first-line national policy, often limited by cost and supply chain issues
    • CD4 at baseline if available
    • VL if failure suspected if available
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9
Q

What are the commonest neurological OIs in low resourced settings?

A
  • The commonest opportunistic infections (neurological Ols) encountered in resource poor settings are:
  • Cryptococal meningitis
  • Cerebral toxoplasmosis
  • Tuberculous meningitis
  • Cytomegalovirus
  • HIV+ patients also suffer from other endemic neuropathic diseases e.g malaria, Japanese B encephalitis and Chagas
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10
Q

How does the epidemiology of CNS OI’s in HIV vary by geographic setting?

A

See attached chart.

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11
Q

Which species of cryptococcus are considered human pathogens?

A
  • cryptococcus neoformans
  • cryptococcus gattii
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12
Q
  • Cryptococcus neoformans
    • Where found?
    • which patients
A
  • ubiquitous in aged bird droppings
  • sig defects in cell mediated immunity
    • esp AIDS
    • also reticuloendothelial malignancy
    • organ transplant recipients
    • sarcoid
    • long term steroids
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13
Q
  • Cryptococcus gatti
    • Where found?
A
  • in litter around certain species of eucalyptus
  • ​​highest incidence Papua New Guinea and Northern Australia
    • also North America and Europe
  • usually immunocompetent patients, not associated with HIV
  • intracerebral masses more common
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14
Q

Cryptococcus: Clinical Features

A
  • headache, mild fever, few days N & V
  • may mimic other meningitides esp tb, but less aggressive meningeal inflammatory response
    • only 1/3 have meningism (photophobia, neck stiffness, +ve Kernigs)
  • severely immunocompromised may be very non-specific: confusion and low grade fever only
  • prevents arachnoid from absorbing CSF; therefore elevated ICP with papilledema and communicating hydrocephalus
  • cryptococcomas: abscesses & granulomas in up to 11% with focal signs, seizures
  • more common basal ganglia & cerebellum
  • blood vessel invasion my cause stroke
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15
Q

Space occupying lesions in HIV: differential diagnosis?

A
  • toxoplasmosis
  • primary cns lymphoma
  • tuberculoma
  • cryptococcoma
  • ?PML
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16
Q

What is cryptococcal IRIS?

How may it present?

How is it managed?

A
  • cryptococcal Immune Reconstitution Inflammatory Syndrome
    • HIV +ve pts starting ART develop atypical manifestations of opportunistic pathogens as CD4 improves
    • cryptococcal IRIS may present with lymphadenitis, meningitis or pulmonary lesions, intracerebral mass lesions
    • tends to occur a few months after starting ARV tx, but may be delayed years
    • tx aimed at controlling immune response, systemic steroids beneficial
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17
Q

How common is cryptococcus in other sites?

Where?

A
  • 10-15% of cases
  • anywhere
    • lympadenitis
    • prostatitis
    • skin
      • umbilicated lesions like molluscom later coalesce and form large ulcerated lesions
    • bone
    • lung
    • rare:
      • chorioretinitis, hepatitis, renal abscess
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18
Q

Diagnosis for cryptococcus?

Approach?

Investigations?

A
  • low threshold for headache, confusion etc
  • brain imaging:
    • communicating hydrocephalus
    • mass lesions (cryptococcoma)
    • basal meningeal enhancement
    • LP
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19
Q

What are typical findings in LP for cryptococcus?

What studies are useful?

A
  • Findings
    • opening pressure is always high
    • moderate mononuclear cell pleocytosis 20-200 cells/mm3
    • elevated protein and csf/plasma glucose mildly decreased
  • Identification of fungal hyphae by India Ink staining makes dx in 60-80% of cases
    • repeating LP 3 or more times increases yield as does centrifuging CSF
    • CrAg (crypotococcal Ag +ve in 95%, highly sensitive
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20
Q

Is papilledema a contraindication to LP in suspected cryptococcus?

A
  • not if imaging excludes space occupying lesion because
    • usually due to communicating hydrocephalus from decreased resorption
    • as pressure raised evenly throughout CSF compartment, no increased risk herniation
    • repeated LP may lower CSF pressure and is essential for treatment
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21
Q

What is consequence of elevated CSF pressure in cryptococcus and how is it managed?

A
  • may lead to blindness through pressure on optic nerve
  • tx is repeated LP to bring opening pressure to below 20 mm Hg.
  • refractory cases may need lumbo-peritoneal or ventriculoperitoneal shunt
  • acetazolamide may help in milder cases
  • steroids ineffective with communicating hydrocephalus like this
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22
Q

At what CD4 does cryptococcus tend to occur?

A
  • usually < 100, very rarely seen at CD4 above 200.
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23
Q

Cryptococcus: what blood tests may be done and what is their significance?

A
  • CBC and routine bloods often normal even in advanced disease
  • Fungal blood cultures may be positive indicating disseminated cryptococcemia
  • Cryptococcal Ag (CrAG) titre >1:8 almost as sensitive as CSF
  • not a reliable measure of response to treatment
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24
Q

Cryptococcal meningitis.

Mortality rate?

How is it managed?

A
  • Mortality
    • with effective tx, mortality remains high, up to 25%
  • Acute Treatment
    • (IV amphotericin B + oral flucytosine) x 2 weeks followed by
      • fluconazole x 8-10 weeks
      • current research indicates may be possible to shorten induction phase with high dose Ambisome
      • fluconazole may be used as less toxic alternative
      • itraconazole less effective
      • if opening pressure >25, then ​repeated LP’s to remove 20-30 ml/day to reduce opening pressure by half
  • Maintenance treatment
    • continue fluconazole until CD4>200 for 6 months and serum CrAg is negative
  • start ART 5 weeks later (2015 NEJM Boulware etal comparing early vs late start)
  • No steroids (2016 NEJM comparison +/- dexamethasone stopped early because excess mortality).
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25
Q

Cryptococcomas:

How treated?

What is response to treatment?

What is usual organism?

A
  • treatment same as cryptococcal mengitis
    • i.e. (iv ampho (preferably Abmisome) + oral flucytosine) x 2 wks followed by oral fluconazole x 8-10 weeks
    • flucytosine hard to get because one company makes it an upped the price
  • early in therapy new lesions may arise and existing lesions may enlarge as result of inflammatory response to treatment
  • does not mean failure and lesions tend to shrink over time as treatment continued
  • Cryptococcomas usuall C. gatti, not in immunocompromised pts
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26
Q

Cryptococcal meningitis:

Prognosis.

A
  • invariably fatal without treatment
  • with treatment mortality remains at 25%
    • 40% have neurological deficits including
      • Loss of vision
      • cognitive impairment
      • cranial nerve palsies
    • hydrocephalus may be late complication
    • relapse in up to 25%
    • some pts may need life-long antifungals
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27
Q

CNS Toxoplasmosis:

Pathogenesis

Presentation

Neuroimaging

A
  • reactivation of latent Toxoplasm gondii
  • indolent over several days
  • hypodense, ring-enhancing lesions, esp basal ganglia and thalamus
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28
Q

Describe the stages in the replication of HIV

A
  1. Binding: virus binds to CD4 recepter and co-receptor on target cell
  2. Fusion: the viral envelop merges with cell membrane and spills its contents into cell
  3. Reverse transcription: the viral RT enzyme is used to make a DNA copy of the viral RNA
  4. Viral DNA is integrated into the host cell genomic DNA located in the cell nucleus - using the enzyme integrase.​
    • once integrated viral DNA is known as proviral DNA and cannot be removed without destroying host cell
    • proviral DNA is transcribed by host cell into mRNA and used to make viral proteins that will form the components of a new virus
  5. Budding: components of new virus leave the host cell by budding, using the host cell wall as the envelope of new HIV virion
  6. Protease cleaves the long chain polyprotein into active components eg. viral enzymes. Virus now capable of infecting other cells
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29
Q
  • What do the 2013 WHO guidelines say about when to start ART?
  • What about the 2015 guidelines?
A
  • 2013 guidelines say start ART when CD4 <500 cells/m3 or for WHO stage 3 or 4 disease although each country will have own guidelines
  • 2015 say start when dx of HIV +ve is made regardless of CD4
    • goal is to maintain viral suppression for life
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30
Q

Which classes of drugs are widely available in low and middle income countries and which are not?

A
  • Available:
    • Reverse Transcriptase inhibitors
      • Nukes
      • non-nukes
    • Protease inhibitors
  • Not
    • CCR5 receptor antagonists
    • Fusion inhibitors
    • Integrase Strand Transfer Inhibitors
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31
Q

Whic drugs does WHO recommend for first line ART?

A
  1. Tenovovir (TDF) 1st NRTI-nucleoside reverse transcriptase inhibitor
  2. Lamivudine (3TC) 2nd NRTI
  3. Efavirenz (EFV) NNRTI - non-nucleoside rti
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32
Q

What are main side effects of Tenofovir?

Dose?

Mechanism?

A
  1. renal impairment (prox tubular nephropathy with proteinuria, hypophosphatemia)
  2. osteoporosis
  • (Good against Hep B)
  • 245 mg daily
  • nrti
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33
Q

Main side effects of lamivudine?

Dose?

Mech?

A
  • 3TC
  • generally well tolerated
  • rarely peripheral neuropathy
  • good against Hep B
  • 300 mg daily or 150 mg bid
  • nrti
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34
Q

Main side effects of Efavirenz?

Dose?

Mech?

A
  1. Rash
  2. psychiatric symptoms (dizziness, vivid dreams, insomnia, psychosis)
  3. hepatotoxicity
  • 600 mg daily
  • NNRTI
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35
Q

Other than TLE, what other combinations are recommended as 1st line ART

A
  • 1st NRTI:
    • Tenovofir (TDF) 245 mg od or
    • AZT 250 mg bid or
    • Abacavir
  • 2nd NRTI:
    • lamivudine (3TC) or emtricitabine
  • NNRTI
    • Evavirenz (EFV) or nevirapine (NVP)
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36
Q

Zidovudine

Dose

Adverse effects.

A
  • AZT
  • 250 mg po bid
  • adverse effects:
    • anemia (macrocytic)
    • nausea
    • lipodystrophy
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37
Q

Abacavir

Dose

Mechanism & role

Adverse Effects

A
  • ABC
  • 600 mg daily
  • 1st NRTI
  1. hypersensitivity in those with HLA-B5701; rash & flu like illness; less common in African population
  2. Nausea, anorexia
  3. Controversial evidence of increasing CV risk
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38
Q

Emtricitabine

Dose

Role

Adverse Effects

A
  • FTC
  • NRTI, prescribed in most regimens as 2nd NRTI
  • 200 mg od
  • Generally well tolerated
    • Rarely pruritis, hyperpigmentation
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39
Q

Neviraping

Mech, Role

Adverse Effects

A
  • NVP
  • NNRTI, 3rd drug
  • 200 mg od for 2 wks then 200 mg bid
  • a/e similar to efavirenz
    • mild rash during first 6 wks - continue
    • SJS/TEN discontinue
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40
Q

Possible options for 1st line ART

A
  • 1st NRTI
    • Tenofovir or zidovudine or abacavir
    • (TDF or AZT or ABC)
  • 2nd NRTI
    • Lamivudine or emtricitabine
    • (3TC or FTC)
  • NNRTI
    • Efavirenz or nevirapine
    • (EFV or NVP)
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41
Q

2nd line drugs for HIV

Why?

What?

A
  • in event of treatment failure
  1. change the 1st nrti eg TDF to AZT or ABC
  2. stay on 3TC or FTC
  3. change from NNRTI to protease inhibitor, i.e
    1. ​Lopinavir/ritonavir (LPV/r) or
    2. Atazanivir/r (ATZ/r)
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42
Q

Ritonavir

role/mech

adverse effects

A
  • used to boost concentration of other PI’s by inhibiting cytochrome CYP3A4 in intestine and liver; no activity at doses used to boost
  • a/e
    1. hyperlipidemia & triglyceridemia
    2. hepatitis
    3. pancreatitis
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43
Q

Lopinavir

dose

Role/mech

adverse effects

A
  • LPV/r
  • 400 mg/100 mg bid
  • boosted PI, 3rd drug in 2nd line regimen
  1. diarrhea common, tx loperamide
  2. hepatic dysfx
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44
Q

Atazanivir

dose

mech/role

adverse effects

A
  • ATZ/r
  • 300 mg od/100 mg
  • boosted PI/ 3rd drug in 2nd line regimen
  • a/e
    • hyperbilirubinemia/assymptomatic icterus
    • diarrhea - tx loperamide
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45
Q

Available 1st line combination pills.

What are they?

Dosing?

A
  • 2 nrti + 1 nnrti: 1st line combinations
    • Trioday
      • tenofovir/lamivudine/efavirenz
      • (TDF/3TC/EFV)
      • 300 mg/300 mg/600 mg 1 tab daily
    • Viraday or atripla
      • tenofovir/emtricitabine/efavirenz
      • (TDF/FTC/EFV)
      • 300 mg/200 mg/600 mg 1 tab daily
    • Triomune 40
      • stavudine/lamivudine/nevirapine
      • (D4T/3TC/NVP)
      • 40 mg/150 mg/200 mg, 1 tab bid
      • no longer recommended by WHO because of neuropathy
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46
Q

2 NRTI combination pills

What are they?

What role?

Dose?

A
  • Combivir
    • AZT/3TC 300 mg/150 mg bid
  • Truvada
    • Tenofovir/emtricitabine 245 mg/200 mg od
    • (TDF/FTC)
  • Kivexa
    • abacavir/lamivudine 600 mg/300 mg od
    • (ABC/3TC)
  • In 2nd line treatments; must be combined with boosted PI
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47
Q
  • CRYPTOCOCCUS:
    • Pathogenesis?
    • Presentation?
    • Neuroimaging?
    • Complications?
A
  • Pathogenesis: reactivation of latent Cryptococcus neoformans infection.
  • Presentation: most commonly meningitis, can include blurred vision due to raised ICP, seizure (due to parenchymal cryptococcoma) or confusion
  • Neuroimaging: meningitis, cryptococcomas, gelatinous pseudocysts
  • Complications: communicating hydrocephalus, IRIS with ARV
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48
Q

What level of adherence is required for successful use of ART to prevent accumulation of RAMs (Resistance Associated Mutations)?

A
  • around 90% or greater
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49
Q

What is the genetic barrier to resistance?

  • Which antiretroviral drugs have the lowest genetic barrier to resistance?*
  • Moderate?*
  • Highest*
A
  • It is a function of how many mutations are required for resistance & how easily such mutations occur.
  • Lowest:
    • NRTI’s: 3TC, Emtricitabine (FTC)
    • NNRTI’s: Efavirenz (EFV) & NVP
  • Moderate:
    • Tenofovir (TDF), AZT, ABC, d4T
  • High:
    • PI’s: Lopinavir (LPV), Atazanavir (ATZ), Darunavir (DRV)
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50
Q

How long before expect VL to be fully suppressed on ARV?

How soon should quantitative RNA (viral load) be used after starting treatement and what can we expect to see.

A
  • VL should be fully suppressed by 9 months after starting successfull ARV.
  • Check at 6 months. Should see significant downward trend at least below 1000 copies/ml.
  • WHO recommends q 12 month monitoring while on ART (but q 6 months preferred if resources allow.)
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51
Q

CNS Toxoplasmosis:

Pathogenesis?

Presentation?

NeuroImaging?

A
  • Pathogenesis: reactivation of latent Toxoplasma gondii infection.
  • Presentation: non-specific, indolent over several days.
  • Neuroimaging: hypodense, ring-enhancing lesions, especially basal ganglia, thalamus.
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52
Q

What is Sanger sequencing?

What HIV gene encodes reverse transcriptase and protease?

What percent of the HIV quasispecies must carry a mutation for it to be detectable by Sanger sequencing?

A

HIV viral genotyping for resistance.

The pol gene.

20%

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53
Q

Toxoplasmosis: Epidemiology

Distribution?

Seroprevalence rates?

A
  • worldwide distribution
  • seroprevalence varies from 15% US & Canada to 50-88% in Europe and Africa
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54
Q

CNS Toxo & HIV:

At what CD4 count?

How common?

In adults vs kids?

A
  • CD4 generally < 100, very rare above 200
  • commonest cause of CNS mass lesion in an HIV person, even in TB endemic areas.
  • rare in children
  • in HIV persons with CD4 <100 and where not on toxo prophlaxis there is a 30% chance of developing cns toxo
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55
Q

CNS Toxo: Presentaion

A
  • usually present with focal signs realating to one or more brain mass lesions
  • defuse encephalitis can occur
  • headache, confusion, fever, behavioural changes and altered mental status common
  • focal neuro deficits an seizures common
  • expyramidal sx due to affinity for basal ganglia
  • onset may be insidious ro rapid
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56
Q

CNS Toxoplasmosis:

Differential in HIV pos individual with focal signs, encephalopathy or seizures.

A

Primary CNS lymphoma

tuberculous granulomata or abscess

?PML

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57
Q

Toxoplasma Microbiology and Serology

Serology in Acute Infection?

How useful is it in excluding reinfection?

A
  • In Acute Infection:
    • IgG and IgM negative at onset.
    • IgM rises first, +ve within 1 wk
    • IgG +ve by 2 weeks
  • However, CNS toxo almost always reactivation, serology +ve in 85% of cases
    • Absence of Ab’s makes dx less likely but negative serology does not exclude CNS toxo as loss of AB may occur with immunosuppression
    • IgM rarely +ve, usually not helpful
    • PCR testing variable sensitivities and specificities
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58
Q

CNS Toxo:

NeuroImaging

A
  • MRI more sensitive than CT
  • usually multiple solid or cystic spherical lesion with ring enhancement, surrounding edema and mass effect
  • may be anywhere but predilictino for grey/white interface or basal ganglia
  • the more lesions there are, the more likely the cause is toxo
59
Q

CNS Toxo:

Neuroimaging:

Differential Dx.

A
  • neither MRI nor CT can differentiate among many possible etiologies of brain lesions in AIDS pts
  • DDX
    • Cryptococcus
    • Histoplasmosis
    • Aspergillosis
    • Tuberculosis: tuberculoma may look very much like toxo. Look for meningeal enhancement.
    • Trypanosomiasis
    • cysticercosis
    • angiostrongylus cantonensis
    • CNS lymphoma
    • PML
  • single lesion favours lymphoma
  • CNS tuberculomas look similar to toxo: 60% will have abnormal CXR
  • Progressive Multifocal Leukoencephalopathy does not produce mass effect
60
Q

CNS Toxo:

CSF exam

What role?

What findings?

Findings in CNS lymphoma? TB?

A
  • LP frequently contraindicated due to mass lesion, usually not needed as suggestive radiology with +ve serology sufficient to start presumptive treatment
  • CSF:
    • usually mononuclear pleocytosis with normal glucose ratio.
    • toxo pcr specific but low sensitivity
    • CSF Ab’s not helpful
  • CNS lymphoma: EB virus may be present
  • TB: CSF PCR +ve in 60% of cases
61
Q

CNS Toxo:

What are the criteria for Presumptive diagnosis sufficient for treatment?

If these criteria are met what is the probability of toxoplasma?

A
  1. IgG positive
  2. No effective prophylaxis was being taken AND
  3. There are multiple ring enhancing lesion on the neuroimaging
  • If all 3 not present then biopsy or other dx tests should be performed
    • eg PCR for EBV, Tb, Cryptococcus neoformans
  • If no response within 2 wks then consider brain biopsy
  • With single cerebral lesion, particularly if serology neg then consider biopsy to r/o CNS lymphoma
62
Q

CNS Toxo:

Treatment

A
  • 1st line:
    • (pyrimethamine + sulphadiazine or clindamycin) x 6 wks
    • (nb also covers against PJP)
    • Adverse effects:
      • Pyrimethamine mylotoxic, must be given with folinic acid. Rash, nausea, vomiting
      • sulphadiazine: rash, fever, leukopenia, hepatitis, n, v, crystalluria
      • clindamycin: rash, fever, n, v, c. diff.
  • Alternatives:
    • pyrimethamine + folinic acid + azithromycin
    • pyrimethamine + folinic acid + atovaquone
    • sulphadiazine + atovaquone
    • co-trimoxazole as for PJP
63
Q

CNS Toxo: monitoring treatment

A
  • careful clinical neuro f/u needed
  • if no clinical or radiological improvement within 2 wks of tx, then dx prob not toxo
  • consider alternative dx, brain biopsy
  • after 6 weeks reduce doses to prophylactic doses
64
Q

CNS Toxoplasmosis: adjunctive tx

A
  • steroids may be necessary for raised icp but minimize duration to minimize risk of oi’s
    • CNS lymphoma may improve with steroids so complicates trial of treatment
  • anti-convulsants for seizures only, NOT seizure prevention
  • 86% improve by day 7, 90+% by 2 weeks
  • surgical decompression rarely necessary
65
Q

Toxo & HIV: Prophylaxis

Primary

Secondary

A
  • Primary prophylaxis:
    • All IgG +ve patients with CD4<100 should start prophylaxis with co-trimoxazole
    • if allergic consider desensitization
    • alternatives include dapsone + pyrimethamine or high dose dapsone
    • discontinue if CD4>200 for 3 months
  • Secondary prophylaxis
    • following treated cns infection, continue maintenance until CD4>200 for 6 months and restart if falls below 200 again
    • secondary prophylaxis same drugs as treatment but half the dose
66
Q

CNS Toxo: prognosis

A
  • depends on immune restoration
  • residual neuro impairment in 40%
  • seizures common
  • relapses common, even remotely and at higher CD4 counts
67
Q

CNS CMV

Pathogenesis

Presentation

Neuroimaging

A
  • Pathogenesis: reactivation of latent CMV infection
  • Presentation: very advanced immunosuppression, cd4<50
    • non-specific cognitive decline, less often meningism and/or focal findings
    • retina “bushfire” appearance, “tomato ketchup”
  • Neuroimaging: meningoencephalitis
68
Q

LP

Urgent indications.

Non-urgent indications

A
  • Urgent:
    • suspected CNS infection
    • suspected subarachnoid hemorrhage
  • Non-urgent:
    • Idiopathic Intracranial hypertension
    • NPH
    • Carcinomatous meningitis
    • CNS vasculitis
    • Other CNS infections: e.g. syphilis, lyme disease
    • consider in MS, paraneoplastic syndromes, Guillain Barré syndrome
69
Q

CSF physiology

How much usual volume in adults?

Where produced?

How much produced?

Turnover?

A
  • usual adult volume 150 ml
  • secreted by choroid plexus
  • approx 500 ml/day = 0.35 ml/min
  • turnover 14% per hour (i.e. 100% in about 7 hrs)
70
Q

What are the clinical signs of herniation?

A
  • Respiration: irregular breathing/tachypneia
  • Oculocephalic reflex: absent - Dolls eyes movement
  • Posture: decorticate or worsening decerebrate
  • Eyes: poor or absent response to light/ fixed/dilated pupils
  • Yuk: bradycardia and hypertension
71
Q

What are relative non-neurological CI to LP?

A
  1. local superficial infection at LP site
  2. shock
  3. extensive or spreading purpura
  4. coagulation abnormalities
    • prolonged inr
    • platelets < 100 x 109/L
    • receiving anticoagulant therapy
  5. respiratory insufficiency
72
Q

How do you distinguish between Toxo and CNS Lymphoma?

A
  • may be difficult, based on
    • toxo more likely to be multiple
    • toxo more likely to be frontal/basal ganglia/parietal vs periventriculare, frontal, cerebellar, temporal for cns lymphoma
    • see diagram
73
Q

PML what are the CT findings?

A
  • no or rare mass effect
  • 50% are solitary lesions
  • typical location: subcortical white matter, cerebellum, brainstem
  • 25% show enhancement
  • corpus callosum can be involved, sparing grey matter and cortical ribbon
  • caused by JC (John Cunningham) virus
74
Q

How common relative to non-HIV persons are ischemic and hemorrhagic stroke in HIV+ve persons?

Name 3 possible mechanisms?

A
  • 5 times as common
  1. direct damage from HIV virion
  2. indirect damage from inflammatory cells
  3. atherogenic effects of antiretrovirals
75
Q

What is this?

When first described?

What causes it ?

Treatment?

WHO Stage?

A
  • Oral Hairy Leukoplakia
  • first described 1984, non-HIV 1999
  • EBV-related in setting of immunosuppression
  • Tx:
    • Gentian violet/retinoids/podophylin/acyclovir cream
    • Tx superadded infections
    • ART!
  • WHO STAGE III
76
Q

What is this?

How Treated?

WHO Stage?

A
  • Esophageal Candidiasis
  • 2 weeks fluconazole 50-200 mg/d
  • WHO Stage IV
77
Q

What is the differential diagnosis of dysphagia in HIV?

How are each of these treated?

A
  • CMV esophagitis
    • cd4<50
    • linear/longitudinal ulcers
    • “Owl’s eyes” inclusion bodies on biopsy
    • Concurrent retinitis?
    • IV gancyclovir 2-4 weeks
  • HSV esophagitis
    • oropharyngeal ulcers more common
    • well circumscribed “volcano-like ulcers”
    • eosinophilic inclusions
    • Aciclovir 14 days
  • Esophageal candidiasis
    • treat 2 wks fluconazole 50-200 mg daily
  • Non-Infectious
    • Peptic
    • Cancer (HPV 22%)
78
Q

Outline a practical dysphagia algorithm in a patient with HIV with low cd4 count low resource setting.

A
79
Q

What is the risk of the baby of an HIV +ve Mum becoming infected?

What is risk with ARV?

A
  • 15 to 25% of infants infected during pregnancy, labour & delivery
  • 5-40% infected during breastfeeding, the longer breast-fed the more the risk
  • overall 15-45% of infants will be HIV infected
  • With ARV risk reduced to <5%
80
Q

What maternal and infant factors increase the risk of vertical transmission of HIV?

A
  • Pregnancy
    • High viral load
    • placental infections
    • STI’s
    • maternal malnutrition
    • anemia
  • Labour and delivery
    • High viral load
    • rupture of membranes>4 hours
    • Invasive delivery procedures
    • premature birth
    • Low birth weight infant
  • Breast Feeding
    • High viral load
    • Mixed feeding
    • duration of breastfeeding
    • breast abscesses, mastitis etc
    • oral disease in baby
    • maternal malnutrition
81
Q

What are the 4 prongs of the 2002 Comprehensive approach to Prevention of Maternal-Child Transmission of HIV (PMTCT)?

A
  1. primary prevention of HIV infection among women of childbearing age.
  2. preventing unintended pregnancies among women living with HIV
  3. preventing HIV transmission from pregnant women living with HIV to their infants
  4. providing appropriate treatment, care and support to mothers living with HIV and their children and their families.
82
Q

Practical approach to PMTCT

WHO guidelines 2016

A
  • start pregnant HIV +ve mom on appropriate ART to continue for life.
  • Babe to start Nevirapine od or AZT bid until 4-6 weeks
  • start co-trimoxazole from 4-6 weeks to 18 months if proven HIV negative
  • encourage breast feeding, discourage mixed feeding for first 6 months
83
Q

Infant feeding and ARV.

  1. What for infants born to mothers on ART and breast fed?
  2. What for such infants at high risk of acquiring HIV?
  3. What for high risk infants who are breast-feeding?
A
  1. Nevirapine once daily x 6 weeks
  2. (Nevirapine od + AZT bid) x 6 weeks
  3. (Nevirapine od + AZT bid) x 12 weeks
84
Q

What are the recommendations for co-trimoxazole for HIV exposed neonates?

How about HIV infected children?

(CHAP study 2004

Arrow trial 2014)

A
  • All HIV exposed children from 4-6 weeks of age should be on cotrimoxazole prophylaxis until 18 months of age (when off breast mild and HIV ruled out)
  • all HIV infected children should remain on lifelong cotrimoxazole prophylaxis
85
Q

What is Pre-exposure prophylaxis in pregnancy?

A
  • daily oral tenofovir disoproxil fumarate (TDF) or coformulated TDF/emcitabine in areas of high HIV prevalence to prevent HIV acquisition in pregancy
  • potential to complement existing prevention strategies
  • high risk groups
    • serodiscordant couples
    • sex workers
    • ?adolescents
86
Q

What is this?

What complication might ensue?

How treated?

WHO Stage?

A
  • Kaposi’s sarcoma stomach
  • Throughout GIT
  • often aggressive, blood loss
  • Tx: chemo: vincristine, bleomycin
  • WHO Stage IV
87
Q

Approach to Diarrhea.

If chronic, WHO stage?

A
  • Chronic diarrhea implies WHO stage III
88
Q

What organisms are the commonest causes of acute diarrhea in HIV infection?

A
  • salmonella sp
  • shigella spp
  • campylobacter spp
  • E. coli (ETEC/EAEC)
  • C. dificile
  • also
    • C. Perfringens
    • Yersinia enterocolitica
89
Q
  • compare acute diarrhea in HIV vs non-HIV
A
  • greater risk of prolonged infection/invasive disease
  • 2-300 times increased risk of invasive nontyphoidal salmonella in advanced HIV
    • may be recurrent, in which case WHO Stage IV
  • 40 fold increased risk of Campylobacter jejunii in AIDS
    • worse outcomes, mortality up to 40%
90
Q

What does this imply in acute bloody diarrhea in HIV?

what is the cause?

how diagnosed?

treatment?

A
  • lymphogranuloma venereum
  • caused by chlamydia trachomatis infection, serovars L1-3
    • endemic in Africa and Caribean
    • causes inguinal buboes
    • DX by PCR when available
    • associated with ulcerative rectocolitis in MSM
      • appearance indistinguishable from IBD
    • Treatment: tetracyclines & macrolides
91
Q

Outline a practical approach to treatment of bloody diarrhea with abd pain and fever.

A
  • Prolonged / fever / abdominal pain / blood -> treat:
    • •Ciprofloxacin/azithromycin 3-5 days
    • •Nb Cipro resistance, esp in South Asia
    • •Know local resistance
      • If no response: Treat for amoebic dysentery
  • Metronidazole 800 mg tds x 5-10 days
  • If no response:
    • Stool for ova and parasites
    • Look for other causes of diarrhoea
92
Q

Chronic Diarrhea: What is CD4 Count?

Which causes of diarrhea pertain at what CD4 levels?

A
  • initial seroconversian related diarrhea
  • then causes as HIV disease progresses
  • CD4 ~400:
    • Bacterial infection
    • Tuberclosis
    • Isospora belli
  • CD4 ~ 200
    • ​Cyclospora cayatanensis
    • Strongyloides
  • CD$ ~ 100
    • ​Cryptosporidia
    • microsporidia
    • GI malignancies
    • MAC
    • CMV
93
Q

Infectious causes of diarrhea: What are the opportunistic pathogens?

A
  • Parasitic
    • Cryptosporidia spp.
    • Cyclospora spp.
    • Isospora belli (now cystioisospora)
    • Microsporidia (Enterocytozoon bienneusi and Encephalocytozoon intestinalis)
  • Viral
    • ​CMV
  • Fungal
    • ​Histoplasmosis
    • Cryptococcosis
  • Mycobacterial
    • ​TB
    • MAI
94
Q

What is this organism?

Natural cycle, ie. where found?

Disease spectrum

Usually at what CD4 does it become an issue in HIV?

How identified?

A
  • Cryptosporidium parvum
  • ubiquitous coccidial protozoa
  • causes 5-10% of diarrhea in the immunocompetent
  • nb Milwaukee outbreak
  • can cause significant chronic diarrhea if CD4<100
  • Microscopy: modified acid fast stain oocyst 3-6 µm diameter, PCR, ELISA
  • Treatment
    • nitazoxanide
    • paramomycin
    • START ART
95
Q

What is this organism?

Where found? Natural cycle?

Disease?

Diagnosis?

Treatment?

A
  • Isospora belli
  • protozoal parasite
  • human only host
  • endemic in Tropis and subtropics
  • unusual cause of diarrhea without immune suppression in temperate areas
  • may cause chronic diarrhea in HIV, usually with CD4 2-300
  • Diagnosis: Acid fast stain. PCR.
  • Treatment: Co-trimoxazole - response rates up to 100%
  • ART
96
Q

What organism is this? What stain?

Disease? What CD4 count?

What genus usually?

Treatment?

A
  • microsporidiosis
  • Trichrome stain for diagnosis
  • rare in humans with normal immune system
  • CD4 usually<100
  • most intestinal infections due to Enterocytozoon bienusi/intestinalis
  • Treatment:
    • ​Albendazole
    • START ART
97
Q

What viral infection is the commonest viral cause of diarrhea in HIV?

What kind of virus?

CD4?

How common in HIV?

What kind of presentation? Complications?

Diagnosis?

Treatment?

A
  • Cytomegalovirus
  • herpes DNA virus
  • CD4<50
  • 15% of chronic diarrhea
  • Clinical: diarrhea, cramps, tenesmus, fever, abd pain, wt loss, melena
  • Complications: enteritis, colitis, ulcers, appendicitis, ileocecal obstruction, toxic megacolon, perforations, GI hemorrhage
  • Diagnosis: Biopsy, direct EM visualization, ELISA, PCR
  • Treatment: IV ganciclovir, valaganciclovir (foscarnet, cidofivir)
  • “CMV is a nightmare.”
98
Q

What kind of Mycobacteria presents with diarrhea?

What CD4

Tb?

A
  • chance of extrapulmonary or disseminated mycobacterial infection increase with reducing CD4 count (Usually < 50)
  • colitis, terminal ileitis possible but relatively rare
  • MAI may present as diarrhea
  • MTB less likely to present as diarrhea
99
Q

What are the noninfectious causes of chronic diarrhea in HIV?

What percent of diarrhea remain undiagnosed?

A
  • in 50% no cause is identified
  • Neoplastic
    • Lymphoma
    • Kaposi’s sarcoma
  • Drugs (HAART) esp PIs
  • HIV Enteropathy
  • Pancreatic disease
    • ddi (didanosine)
100
Q

HIV Enteropathy

What effects does it have on the gut?

How is it managed?

A
  • Effects
    • villous blunting, inflammation and malabsorption
    • reduced micronutrient absorption
    • reduced fat absorption
    • ?increased motility
    • marked early reduction in gut CD4 in excess of total body CD4 loss
  • Management
    • ART
    • antimotility agents (crofelemer?)
    • probiotics?
    • Zinc?
    • thalidomide?
101
Q

Drugs causing diarrhea

A
  • all ARV’s but PI especially
    • ​Diarrhea accounts for 20% of all missed doses
      • 2-4%: Darunavir, Atazanavir
      • 12-50%: Saquinavir, Ritonavir. Kaletra (lopinavir/r), Nelfinavir
  • Antibiotics
  • NSAIDS
  • Propranolol, methyldopa
  • Digoxin
  • Metformin
  • Laxatives
  • Traditional and complementary medicines
102
Q

Diagnostic approach

Outline a logical and pragmatic approach to chronic diarrhea in HIV

A
  • good history: alcohol, drugs, endocrine
  • Examination
  • Investigations:
    • 30-40% parasite found
    • >50% no infectious etiology
    • Rule out malaria
    • Stool: what is available? x 3 samples
      • Wet prep
      • Culture
      • Staining for OCP (Zn, trichrome)
      • Molecular
      • 50% no pathogen found
      • Flex sigmoid or colonoscopy: Yield 27-39%
      • If no dx, after available investigations proceed to treatment algorithm
103
Q

Chronic diarrhea > 4 wks:

What is the treatment algorithm?

A
  • 1. Co-trimoxazole 960 mg qid x 7 days
    • (Isospora, cyclospora, Cryptosporidium, bacterial infections)
      • If no response:
        • 2. Metronidazole 400 mg tid x 10 days
          1. (Giardia, Clostidium, E. Hystolytica, Microsporidia)
            • If not response
              • 3. Albendazole 400 mg bid x 21 days
                • (Microsporidia, enteric helminths)
104
Q

List factors associated with increased risk of HIV infection.

A
  • increased probability of transmission
    • Increasing viral load
    • man infected
    • anal vs vaginal sex
    • man not circumcised
    • concurrent STI’s
    • Younger age
    • Host genetics
    • violent sex
    • African countries
    • Viral Type
    • Acute and advanced HIV stage
  • Increased number of contacts
    • multiple concurrent partnerships?
      • because of increasing rate of infecting new partners at time of seroconversion
  • increased duration of infectiousness
    • ?suboptimal ART
105
Q

At what time in natural history of HIV and by how much is risk of transmission increased?

A
  • 26 fold increase in relative transmissability
    • during acute seroconversion and
    • at advanced stage of HIV (low CD4)
    • see attached graph
106
Q

Summarize key evidence in favour of Treatment as Prevention (TASP)

A
  • Cohen 2011 RCT of ART immediate vs delayed to CD4 350-500 in HIV discordant couples
    • demonstrated 93% durable reduction in transmission to HIVE neg partner in immediate treatment group
  • START (2015) study shows major reduction in disability, disease and death in early ART groupl
  • WHAT SUPPORTING EVIDENCE DO WE HAVE FOR TASP?
    • Biological plausibility
    • Mathematical modelling evidence of high potential for effectiveness
    • Individual-level evidence of protective efficacy
    • Ecological evidence of prevention of transmission
    • Strong evidence for improved clinical outcomes
    • Prospective individual-level evidence of cost-effectiveness
    • Is this enough?
      • No randomised evidence yet on effect on HIV incidence at community level (But coming soon!)
      • Affordability
      • Operational and implementation science
      • Surveillance for outcomes under programmatic conditions
107
Q

What is PreP in HIV?

A
  • Pre-exposure prophylaxis: the use of antiretrovirals in HIV uninfected individuals to block the acquisition of HIV viral infection.
    • may be daily or intermittent prior to risk exposure
108
Q

What is PEP?

Discuss the risk of acquisition by exposure event related to an HIV +ve individual.

A
  • much less than commonly perceived per event
    • e.g. receptive anal intercourse 1.1%; insertive .06%
    • receptive vaginal intercourse 0.1%; insertive .08%
    • receptive oral sex .02%; insertive oral sex 0%
    • needlestick injury 0.3%
109
Q

Describe the steps in providing PEP.

Which drugs?

When and for how long

A
  • Assess⇒Counsel & support⇒Prescribe⇒Follow-up
  • (TDF & 3TC/FTC ) + LPV/r (or ATV/r)
  • ideally within 2 hours, but up to 72 hours
  • Prescribe for 28 days, test at 3 months post exposure
110
Q

What is the differential diagnosis for liver injury in an HIV patient?

A
  • Broad differential diagnosis!
    • Viral: viral hepatitis (HBV / HCV), HIV
    • Mycobacterial: MTB complex and non-tuberculous mycobacteria
    • Fungal: cryptococcus, histoplasmosis, candidiasis, PCP
    • Parasitic: liver flukes, cryptosporidium, microsporidium
    • Malignancy: lymphoma and Kaposi sarcoma
    • Drugs: allARVs–ATV/NVP/3TC/EFV/DDI… Plus anything that effects HIV negative individuals!
    • Plus anything that affects HIV-negative individuals!
111
Q

What TB drugs and antiretrovirals are particularly associated with liver injury?

A
112
Q

Outline a pragmantic approach to jaundice in the context of ART-initiation?

What is the particular concern?

A
  • the possibility of IRIS-associated hepatitis is a particular concern
  • Approach:
    • Full clinical assessment - US if possible
    • Consider drug induced hepatitis if:
      • AST/bili>5xULN, or 3.5 x baseline
      • coagulopathy, eosinophilia, rash, lactic acidosis
    • Consider TB IRIS if:
      • evidence of IRIS in another system
      • New tender hepatomegaly
      • predominantly cholestatic
      • ultrasound: diffusely abnormal liver texture, LN, normal biliary tree
    • Stop treatment:
      • ALT/AST
        • >5 times ULN without symptoms
        • >3 times ULN with sx (anorexia, nausea, abd pain)
      • sig rise in bili
    • Restart treatment once bili normalised or ALT/AST < 2xnormal
    • If infectious/unwell then for ‘holding regimen’
      • ethambutol and
      • moxifloxacin or streptomycin
113
Q

What is IRIS?

Risk factors?

Treatment?

Prevention?

A
  • IRIS is a consequence of excessive pathogen- specific immune recovery reaction
    • occurs in a subset of patients on antiretroviral therapy (ART).
  • Infective forms
    • present as ‘unmasking’ of a previously subclinical infection or
    • paradoxical clinical deterioration of treated infection
  • most important risk factors for IRIS:
    • low CD4+ T-cell count
    • short time between treatment of infection and commencement of ART
  • Treatment
    • continue ART
    • provide antimicrobial therapy for the provoking infection
    • most cases self- limiting
    • mortality and hospitalisation esp high for CNS TB or cryptococcus
    • Corticosteroid therapy should be considered in certain forms of IRIS after the exclusion of other conditions
  • Prevention
    • start ART with CD4>350 will prevent most
114
Q

What diseases may be associated with IRIS or unmasked by IRIS?

A
  • mycobacteria
    • TB - start ART within 2 weeks after starting TB treatment to reduce mortality
      • consider steroids with CNS disease
    • non-tuberculous
    • including BCG IRIS
  • cryptococcal infections
    • consider steroids with CNS disease
  • Viral infections - in general don’t use steroids with exception of CMV eye disease where IRIS likely response to residual antigen
    • Herpes, warts, molluscum contagiosum - don’t use steroids
    • CMV - retinitis and uveitis likely due to residual antigens - usually responds well to topical or systemic steroids
    • JC Virus/PML - controversy about steroids, likely don’t use
    • Hepatitis B & C
    • ?neuro IRIS caused by HIV
    • Kaposi’s sarcoma: may get paradoxical worsening after starting ART, usually delayed by few months. Treatment with chemo may be necessary. Prevent by treating severe forms of KS prior to starting ARV.
  • Parasitic Infections
    • toxoplasmosis
    • schistosomiasis
    • strongyloides stercoralis
    • leishmaniasis
    • cryptosporidium
115
Q
  • What are current (2017) WHO guidelines regarding timing of treatment of ART and TB at diagnosis?
A
  • TB treatment should be initiated first
    • followed by ART as soon as possible within the first 8 weeks of treatment (Strong recommendation, high certainty in the evidence).
    • HIV-positive patients with profound immunosuppression (e.g. CD4 counts less than 50 cells/mm3) should receive ART within the first 2 weeks of initiating TB treatment
116
Q

WHO Clinical Stage 2

A
117
Q

WHO Clinical Stage 1

A
118
Q

WHO Clinical Stage 3

A
119
Q

WHO Clinical Stage 4

A
120
Q

Compare the CDC with WHO HIV staging system.

A
  • CDC
    • defines AIDS as CD4<200 plus Aids defining Condition
  • WHO
    • staging clinical only to allow definition of treatment failure on clinical grounds if cd4 not available
    • Stage 1: assymptomatic or lymphadenopathy only
    • Stage 2: mild OIs or wt loss
    • Stage 3: More serious OIs, more severe wt loss
      • recurrent infections
      • pulmonary TB or (scrofula in kids)
      • cytopenias
    • Stage 4: AIDS defining conditions
      • OI’s, cancer, organ failure
121
Q

What is standard treatment of cryptococcal meningitis?

What is an acceptable cheaper alternative according to Molloy et al, NEJM 2018; 378:1004-1017?

A
  • 2 wks of amphoB + fluctyosine for induction followed by 10 weeks of fluconazole
  • According to this article, for induction:
    • 1 wk of amphoB + flucytosine or
    • 2 wks of fluconazole + flucytosine
  • followed by 10 wks of fluconazole
122
Q

What is PML?

A
  • Progressive multifocal leukoencephalopathy (PML) is a rare and usually fatal viral disease characterized by progressive damage (-pathy) or inflammation of the white matter (leuko-) of the brain (-encephalo-) at multiple locations (multifocal)
  • caused by JC virus
  • usually seen in advanced HIV, sometimes associated with biologic agents/monoclonal Ab’s
123
Q

What is the risk of perinatal transmission with breastfeeding in HIV?

A
  • In untreated HIV infection, with breastfeeding, around 30% of infants will become infected.
  • The risk is not eliminated by avoidance of breastfeeding, but is reduced to around 20%, since there is also a risk during gestation and delivery.
  • The risk is not eliminated by Caesarian section, but in untreated HIV infection it is reduced.
  • The most significant factor in transmission risk is maternal viral load. Women can be advised that they can choose vaginal delivery if the viral load is undetectable on treatment at that time.
  • In developed settings, vertical transmission of HIV is very rare, thanks largely to antiretroviral treatment of pregnant women and avoidance of breastfeeding.
124
Q

What is the preferred treatment for CNS toxo?

A
  • sulfadiazine + pyrimimethamine x 6 wks or
    • or sulfadoxime pyrimethamine (Fansidar) 2 tabs bid x 6 wks or
    • cotrimoxazole
    • (these may be more readily available in resource-limited settings)
  • ART should be started if new dx HIV and should be followed by secondary prophylaxis with either cotrimoxazole or same drug fr treatmet at half dose
125
Q

What is the WHO Syndromic approach to STI’s?

A
  • One of four distinct cardinal signs guides the therapeutic approach: urethral discharge, vaginal discharge, genital ulceration and bubo. The WHO proposes a flowchart based on urethral discharge (men), vaginal discharge, lower abdominal pain (women) and genital ulceration (either sex). The syndromic approach has dramatically reduced STIs in East Africa. Remember that HIV becomes more virulent and far more easily transmitted in the presence of an STI in either partner.
126
Q

What are the 5 “C”’s of the WHO syndromic approach to managing STI’s?

A
  • The five Cs are Counselling, Confidentiality, Contact tracing, Compliance and Condoms. The nine elements of the management of STIs are history, physical examination, diagnosis, early effective treatment, advice on sexual behaviour, promotion and provision of condoms, partner notification and treatment, and case reporting. Add a tenth, clinical follow-up. In all cases one must take account of the patient’s genuinely held ethical values, whether one disagrees with them or not, provided they are not clearly damaging to others.

The provision and teaching of how to use well-designed flow charts is vital in the provision of any STI service.

127
Q

What are the 5 common causes of genital ulcers in the tropics.

Describe and differentiate.

A
  • (a) Treponema pallidum
    (b) Herpes simplex virus (HSV-1, HSV-2)
    (c) Haemophilus ducreyi
  • (d) Lymphogranuloma venereum (Chlamydia trachomatis) - painless ulcers
    (e) Epstein-Barr virus (EBV)

Chancroid is caused by H. ducreyi, a gram-negative bacillus. This condition is extremely common in developing countries. It is characterized by a ‘soft chancre’ in contrast to the ‘hard chancre’ of syphilis. The chancre quickly becomes a painful ulcer. ‘Kissing ulcers’ are common in females and spread by direct contact from one labium to another. As expected, dyspareunia and dysuria are frequent symptoms. Chancroid is an important risk factor for HIV and should be vigorously treated with azithromycin, quinolones, erythromycin or ceftriaxone. Tetracyclines are ineffective.

  • Herpes Simplex causes painful genital ulcers.
  • T. pallidum causes syphilis while EBV causes infective mononucleosis and herpes simplex-like lesions called Lipschütz ulcers or “ulcus vulvae acutum”.
  • Symptomatic EBV shows clusters of inflamed papules and vesicles on the genitalia resembling cold sores.

HPV (human papilloma virus) is the most common sexually transmitted infection. More than 40 types of HPV are infectious and these may affect the mouth and throat as well as the genitalia. HPV is important in that some types can initiate carcinoma. The current vaccines only offer protection against a few specific types of HPV.

  • Do not confuse HSV (herpes simplex virus) with HPV (human papilloma virus).
128
Q

When to start ART in

  1. TB Meningitis
  2. Cryptococcal meningitis
  3. Toxo
  4. PML
A
  1. TBM: (within) 2 wks with CD4<50
    • otherwise upon completion of TB intensive phase (8wk)
    • start steroids with tx of TB meningitis
  2. CM: 2-4 wk seems obtimal
  3. Toxo: little data but early seems appropriate
  4. PML: early cART
129
Q

What are WHP HIV treatment targets for 2020?

What are obstacles to reaching targets?

Approaches?

A
  • Targets?
    • 90% hiv +ve diagnosed
    • 90% treated
    • 90% virally durally suppressed
  • Obstacles
    • delay dx, lack of care facilities
  • Home dx HIV
    • decentralization of care
    • home visits and home start of ARV
    • task shifting
130
Q

What are commonest orgs in HIV+ve pt presenting with breathlessness

A
  • Bacteria
    • Strep. pneumoniae, staph, Klebsiella
    • NTS, pseudomonas, H flu, Mycoplasma
    • Rhodococcus equi, Nocardia (tend to mimic Tb)
  • Mycobacteria (Tb and non Tb)
    • consider Tb even in acute cough
  • Fungi
    • Pneumocystis jirovecii (PCP)
    • crypto, histo, penicillium, coccicoides, candida
    • aspergillus
  • Viruses
    • flu, adeno, rhino, cmv …
131
Q

When to start ART in pts newly presenting with TB

A
  • ASAP
132
Q

What forms of pulmonary prophylaxis are proven and reliant in HIV +ve pts

A
  • Against TB - INH
  • against pneumonia - cotrimoxazole, PCV
    • cotrimoxazole reduces mortality, pneumonia, malaria, hospitalization, diarrhea
    • therefore where malaria and/or severe bacterial infections prevalent WHO recommends starting Cotrimoxazole prophylaxis regardless of CD4 or stage
  • stop smoking
  • hiv test and ART
133
Q

Causes of pericardial effusion

Which of these do you use steroids for?

A
  • Tb - use steroids with TB tx
  • malignancy eg lung, other solid organ tumors, hematological
  • Kaposi’s
  • pyogenic bacterial infection
  • uremic
  • other transudative
  • connective tissue
  • trauma/post-op
  • idiopathic
134
Q

Toxoplasma

brief life cycle

Modes of aquisition:

A
  • cats definitive host, excrete oocysts in feces, rodents are usual intermediate host
  • humans accidental host, ingest oocysts, disseminate to tissues and encyst as bradyzoites
  • tachyzoites develop from oocysts or bradyzoites, travel to liver, taken up by macrophages, disseminate esp to brain and muscle and then give rise to cysts
  • Aquisition:
    1. ingesting oocysts from contaminated water, food, soil or cat feces
    2. ingesten of tissue cysts (bradyzoites) in raw meat (important in France)
    3. vertical transmission pregnancy
    4. less commonly blood transfusion or
    5. unpasteurized goats milk
135
Q

Toxoplasma in pregnancy

When is risk of transplacental toxo highest?

A
  • when acquired late in pregnancy
    • 15% in 1st trimester
    • 71% after 36 wks
136
Q

What are the problems with diagnosing Toxo in HIV?

What about MRI findings? Are they specific?

what is the MRI differential?

A
  • serology may be negative
  • +ve serology indicates past infection but negative does not exclude it
  • MRI findings do not differentiate amongs multiple possible etiologies including
    • crypto
    • histo
    • lymphoma
    • tb
    • trypanosomiasis
    • cns lymphoma
  • However, toxo findings do not include meningeal enhancement, which would point more towards tb or crypto
137
Q

CSF findings in suspected toxo

A
  • mononuclear pleocytosis with normal glucose ratio
  • pcr specific but low sensitivity
  • csf ab testing unhelpful, don’t do it
  • EBV by PSR indicates primary CNS lymphoma
  • PCR may be pos for TB (60% of abscesses)
138
Q

Toxo treatment

?steroids

A

6 wks

  • pyrimethamine + sulfadiazine + folinic acid
  • alternatives include
  • pyrmimethamin + folinic acid + azithrom
  • pyrimethamine + folin acid + atovaquone
  • sulfadiazine + atovoquone
  • cotrimoxazole in pcp doses
  • short term steroids may be indicated but complicate interpreting response to tx becuase cns lymphoma tx or tb sx may improve with this
139
Q

What is the most common cause of space occupying lesions in HIV

A
  • toxo
  • this is true even in regions where TB is endemic
140
Q

Cryptococcal meningitis

Are extra-neurological features common.

A
  • yes, in 20% of cases
    • chest xray may show diffuse pul infiltrated, lobar consolidation or cavitatin lesions that may resemple tb
141
Q
  • TB-HIV Coinfection
  1. What percent of the world’s population has latent TB?
  2. How much does HIV increase the lifetime risk of developing TB?
  3. How does CD4 relate to risk of acquiring TB?
  4. What percent of TB patients worldwide are coinfected with HIV.
  5. What percent of coinfected HIV-TB patiens are in SSA? In Asia
A
  1. 30% of world population has latent TB
  2. HIV increases liftime risk of dev TB by >20%
  3. Risk is high from acute seroconversion to HIV on and then it rises as CD4 falls.
  4. 15% of TB pts worldwide are coinfected with HIV
  5. 79% in SSA. 11% in Asia
142
Q

What are WHO guidelines wrt the 3 “I”s of preventive therapy for TB in HIV infected people?

A
  1. Establish Intensified Case Finding.
  2. Introduce Izoniazid Preventive Therapy
    • minimum 6 months ?up to 36
    • if available and feasible TST prior and start IPT on those +ve
  3. Ensure TB Infection control measures in health care.
143
Q
  1. Is TST or IGRA always necessary before offering INH prophylaxis?
  2. How much does INH prophylaxis reduce risk of developing TB?
  3. Should INH be offered to TST negative pts.
  4. How long should HIV positive patients be offered INH for?
  5. To which TB patients should HIV testing be offered?
A
  1. Although studies have shown benefit with those TST or IGRA positive, WHO suggests offering it where feasible, but testing is not necessary before starting INH.
  2. IPT reduces risk of developing TB by about 30%(actually prob a bit more).
  3. INH should not be offered to TST neg pts.
  4. 6 months, but some evidence to suggest benefit prolonged with 36 months.
  5. To all of them.

Tropical Medicine (17 decks)

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