HIV + OI Flashcards
Through what TWO mechanism does HIV cause disease of the central nervous system (CNS)?
1) DIRECT impact from HIV
2) indirect due to CD4 DEPLETION
Space occupying lesion + HIV - differential diagnosis - INFECTIVE causes?
Toxoplasmosis TB Cryptococcus Syphilitic gummae PML
Space occupying lesion + HIV - differential diagnosis - NEOPLASTIC causes?
Primary CNS lymphoma
Metastatic non-Hodgkin lymphoma
Encephalitis + HIV - differential diagnosis?
HIV (directly)
VZV
HSV
syphilis
Meningitis + HIV - differential diagnosis?
HIV seroconversion Cryptococcus TB Syphilis Streptococcus pneumonia
Spastic paraparesis + HIV - differential diagnosis?
HIV-vacuolar myelopathy Transverse myelitis HSV HTLV-1 Toxoplasmosis Syphilis
Polyradiculitis + HIV - differential diagnosis?
CMV
Non-Hodgkin lymphoma
What is the most common systemic FUNGAL infection associated with immunosuppression from HIV?
CRYPTOCOCCUS
What type of organism is CRYPTOCOCCUS?
encapsulated YEAST
in environment
What is the most common STRAIN of cryptococcus?
CRYPTOCOCCUS neoformans GRUBII
In addition to grubii, which other strains of cryptococcus are common in HIV?
neoformans NEOFORMANS
or
neoformans GATTII
What has CRYPTOCOCCUS neoformans GATTII been found in?
EUCALYPTUS trees
What has CRYPTOCOCCUS neoformans NEOFORMANS been found in?
BIRD (Pigeon) droppings
In what region is CRYPTOCOCCUS neoformans GATTII most common?
TROPICAL or SUBTROPICAL region
How does CRYPTOCOCCUS enter the body?
INHALATION
rapidly spreads from LUNG to CNS
What common dermatological manifestation in HIV does cryptococcal skin disease resemble?
MOLLUSCUM
What is the most common symptoms of cryptococcus meningitis?
HEADACHE
FEVER
In addition to cryptococcus meningitis what other systems may be affected by cryptococcus?
RESPIRATORY
SKIN papule/molluscum-like
BLOOD
In cryptococcus disease what is the clinical presentation of haematological disease?
FEVER
NIGHT SWEATS
RIGORS
Which system does CRYPTOCOCCUS most commonly affect?
CNS
What is the most sensitive test for cryptococcus disease?
CSF for cryptococcal antigen
What is a useful initial investigation for cryptococcus disease to guide further management?
serumccryptococcal antigen (CRAG) (if positive, do LP)
If serum cryptococcal antigen (CRAG) is positive what investigation is indicated?
LP for CSF and manometry
Prior to lumbar puncture for neurology associated with HIV and low CD4 what investigation should be performed?
CT or MRI of brain
What are poor prognostic indicators for cryptococcal disease?
Blood CULTURE positive low white cell count on CSF high CSF cryptococcal ANTIGEN CONFUSED raised intracranial PRESSURE
What is INDUCTION therapy for cryptococcal meningitis?
LIPOSOMAL AMPHOTERICIN B 4mg/kg/day \+ 5-FLUCYTOSINE 100mg/kg/day TWO (2) weeks
What is MAINTENANCE therapy for cryptococcal meningitis?
FLUCONAZOLE 400mg daily
EIGHT (8) weeks
Is prophylaxis recommended for cryptococcal disease?
SECONDARY only
What is SECONDARY prophylaxis for cryptococcal meningitis?
FLUCONAZOLE 200mg daily
What is the BENEFIT of adding FLUCYTOSINE to induction treatment for cryptococcal disease?
quicker STERILISATION of CSF
What is the DISADVANTAGE of adding FLUCYTOSINE to induction treatment for cryptococcal disease?
haematological TOXICITY
What toxicity is amphotericin B associated with?
RENAL
Which preparation of amphotericin B is associated with less RENAL toxicity?
LIPOSOMAL
How is raised intracranial pressure managed in cryptococcal meningitis?
repeated lumbar puncture
reduce pressure to <200mmH20 or 50% opening
If repeat lumbar puncture does not improve ICP in cryptococcal meningitis what is recommended?
NEUROSURGICAL input
VP shunt
Cryptococcal meningitis + corticosteroid - is it useful?
NO
If cryptococcal disease is not involving CNS what is the treatment?
FLUCONAZOLE 400mg daily
then
secondary prophylaxis
When should ART be started following treatment for cryptococcal disease?
TWO weeks
What are common manifestations of cryptococcal IRIS?
aseptic meningitis raised ICP space occupying lesion pulmonary infiltrates/cavities lymphadenopathy hypercalcaemia
When can SECONDARY prophylaxis for CRYPTOCOCCAL disease be STOPPED?
CD4 >100
&
undetectable VL 3 months
What is the most common cause of CNS mass lesions in immunocompromised people with HIV?
Toxoplasma abscess
What type of organism is TOXOPLASMA GONDII?
obligate intracellular protozoan
Which site of which animal is toxoplasma gondii reliant on to complete its life cycle?
Feline (CAT) INTESTINAL tract
How do humans acquire toxoplasma gondii?
Eating dead animal
or
ingesting oocytes from contaminated soil, water, food
What is the mechanism of TOXOPLASMOSIS disease in immunocompromised people?
REACTIVATION of infection acquired in early life
What is the risk of developing toxoplasma encephalitis if IgG T gondii positive and HIV positive, not on ART?
25%
What is the typical presentation of toxoplasma abscess?
FOCAL neurology
headache
vomiting
seizures
What is the preferred imaging modality for toxoplasma abscess?
MRI
In addition to brain imaging, what other investigation is useful to help diagnose toxoplasma abscess?
LP for CSF PCR for T gondii
What is the main differential diagnosis for toxoplasma abscess?
Primary CNS Lymphoma
Tuberculoma
PML
What is the typical and appearance of toxoplasma abscess on brain imaging?
MULTIPLE
RING enhancing
Grey-White interface
DEEP GREY matter of basal ganglia or thalamus
What patient factor may result in a lack of ring enhancement of toxoplasma abscess?
Low CD4 cell count
What features of a CNS mass suggest LYMPHOMA more likely than toxoplasma abscess?
SINGLE
Periventricular
What features of a CNS mass suggest PML more likely than toxoplasma abscess?
WHITE matter
rarely enhancing
no mass effect
What imaging modality is useful to help distinguish between lymphoma and toxoplasma abscess?
SPECT - high uptake in lymphoma
What is first line treatment for toxoplasma encephalitis/abscess?
PYRIMETHAMINE loading 200mg then 50-75mg/day \+ FOLINIC acid 15mg/day \+ SULPHADIAZINE 1-2gram 4x/day
If a person cannot tolerate SULPHADIAZINE for toxoplasma abscess, what is the alternative?
CLINDAMYCIN
600mg 4x/day
Why is folinic acid given as part of treatment for toxoplasma abscess?
to counteract MYELOSUPPRESSIVE effect of PYRIMETHAMINE
How long is induction therapy for toxoplasma abscess?
SIX (6) weeks
What is the MAINTENANCE regimen for toxoplasma abscess?
same drugs as induction, LOWER dose PYRIMETHAMINE 25mg/day \+ FOLINIC acid 15mg/day \+ SULPHADIAZINE 500mg 4x/day or 1-2gram 2x/day
When are steroids indicated for toxoplasma encephalitis?
symptoms or signs of raised intracranial pressure
What is the dosing regimen for steroids in the event of raised intracranial pressure due to toxoplasma abscess?
DEXAMETHASONE 4mg 4x/day
wean gradually
Within what time frame is a response to antimicrobials expected when treating toxoplasma abscess?
TWO weeks
When should brain biopsy be considered in the context of treatment for toxoplasma abscess?
No response to treatment at 2 weeks
or
clinical deterioration on treatment
When do PLW HIV need PRIMARY prophylaxis for toxoplasmosis?
CD4 cell count <200
What is the first line primary PROPHYLAXIS for toxoplasma abscess?
Co-trimoxazole
480-960mg daily
How long should PROPHYLAXIS for toxoplasma abscess be continued?
until CD4 >200
&
on ART THREE (3) months
How long should MAINTENANCE for toxoplasma abscess/encephalitis be continued?
until CD4 >200
&
on ART SIX (6) months
When should ART be started in the context of toxoplasma abscess?
2 weeks after toxoplasma treatment started
What organism causes progressive multifocal leukoencephalopathy (PML)?
Virus JC
What proportion of the population are seropositive for JC virus?
70%
Where does JC virus remain latent in immunocompetent people?
spleen
bone marrow
kidneys
Blymphocytes
What happens to JC virus in IMMUNOSUPPRESSED people?
REPLICATES transported to BRAIN by B-LYMPHOCYTES infects OLIGODENDROCYTES via SEROTONIN receptor
What proportion of people with AIDS develop PML from JC virus?
5%
What is the pathological process of PML?
IRREVERSIBLE
DEMYELINATION
What is the typical presentation of PML?
SUBACUTE
PROGRESSIVE
FOCAL neurology
What investigations are required to make a diagnosis of PML?
MRI brain
CSF for JC PCR
What are the poor prognostic factors in PML?
OLDER age BRAINSTEM involvement LOW GCS HIGH JC viral load in CSF CD4 <100
What is the treatment for PML?
ART
What is the one year survival for PML on ART?
50%
What is the one year survival for PML not on ART?
10%
What type of virus is cytomegalovirus (CMV)?
Human B-Herpes virus (type 5)
Which population group at risk of HIV is most likely to be seropositive for CMV?
MSM (nearly all)
Through what mechanism is does CMV develop in PLW HIV?
REACTIVATION leads to
VIRAEMIA
+
END-ORGAN disease
At what CD4 count does risk of end organ disease from CMV increase?
<50
Which is the main site of CMV disease?
RETINA (3/4 of CMV disease)
Other than the retina, what other sites can have CMV disease?
GI tract LUNG LIVER HEART ADRENAL CNS
What proportion of CMV disease affects the RETINA?
3/4
What proportion of CMV disease affects the CNS?
<1%
What is the typical presentation of CMV ENCEPHALITIS?
progressive DISORIENTATION WITHDRAWAL APATHY Cranial nerve PALSY NYSTAGMUS
What is the typical presentation of CMV lumbosacral POLYRADICULITIS?
PAINFUL rapidly PROGRESSIVE BILATERAL ASCENDING flaccid paralysis saddle anaesthesia, areflexia, spincter dysfunction, urinary retention
What are the investigations for CMV CNS disease?
MRI brain
+
LP for CMV PCR on CSF
What are the CT findings in CMV encephalitis?
diffuse WHITE matter hypodensities
ventricular ENLARGEMENT
MENINGEAL enhancement
Ring-enhancing
What is the finding in CSF in CMV CNS disease?
polymorphonuclear cell PLEOCYTOSIS (wcc)
Which antivirals have efficacy against CMV retinitis?
GANCICLOVIR
FOSCARNET
valganciclovir
cidofovir
What is the preferred FIRST line treatment for CMV CNS disease?
Ganciclovir 5mg/kg TWICE daily THREE (3) weeks then maintenance
Is prophylaxis required for CMV CNS disease?
No
What is the maintenance therapy for CMV CNS disease?
IV Ganciclovir 5mg/kg DAILY
or
oral VALGANCICLOVIR 900mg daily
What are causes of NON-INFECTIOUS HIV-related lung disease?
KS Lymphoma Lung CANCER EMPHYSEMA Lymphoid interstitial pneumonitis (LIP) Non-specific interstitial pneumonitis (NSIP) IRIS SARCOID Pulmonary hypertension Pulmonary thromboembolic disease
What type of organism is pneumocystis jirovecii?
FUNGUS
What proportion of PCP occurs in PLW HIV with CD4 count <200?
90%
What is the typical presentation of PCP?
EXERTIONAL dyspnoea
PROGRESSES over weeks
MALAISE
dry COUGH
What should presentation of pneumothorax in a PLW HIV prompt investigation for?
PCP
What proportion of PCP have a normal CXR?
40%
What observation is useful to perform in suspected PCP with a normal CXR?
oxygen saturation on exercise
Through what TWO processes should respiratory sample be got for investigation of PCP?
INDUCED sputum
or
Broncho-alveolar lavage (BAL)
What is more specific, direct visualisation or NAAT for pneumocystis jirovecii?
direct visualisation
For how long can adequate respiratory samples be obtained for investigating PCP after starting treatment?
7-10 days (ie don’t delay Rx)
PCP - moderate/severe disease (for treatment purposes) - define?
PaO2 <9.3kPa (70mmHg)
or
SpO2 <92%
What is the FIRST line treatment of moderate/severe PCP?
IV co-trimoxazole
+
CORTICOSTEROIDS
TWENTY ONE (21 ) days
What is the dose of CO-TRIMOXAZOLE for moderate/severe PCP?
IV co-trimoxazole 120mg/kg/day (split 3x or 4x daily) THREE (3) days then 90mg/kg/day EIGHTEEN (18) days
Why is there a dose reduction of co-trimoxazole for PCP treatment?
Similar efficacy
less toxicity
than continuous high dose
What is the CORTICOSTEROID regimen for moderate/severe PCP?
PREDNISOLONE 40mg TWICE daily days 1-5 40mg ONCE daily days 6-10 20mg ONCE daily days 11-21 then stop
What is the appropriate conversion to methylprednisolone for PCP treatment if oral route is not available?
75% of oral regimen
30 BD/30 OD/15 OD
How long may treatment for PCP take to show improvement?
7 days or more
What are suitable alternative agents for treatment of PCP?
Clindamycin
Primaquine
Pentamidine
What is the definition of MILD PCP disease - presentation, O2, CXR?
- SOB on exertion +/- cough/sweats
- PaO2 >11kPa (83mmHg), SaO2 >96
- normal CXR
What is the definition of MODERATE PCP disease - presentation, O2, CXR?
- SOB on minimal exertion, cough + fever
- PaO2 8.1-11kPa (61-83), SaO2 91-96
- Diffuse interstitial changes
What is the definition of SEVERE PCP disease - presentation, O2, CXR?
- SOB at rest
- PaO2 <8.0kPa (<60), SaO2 <91
- Extensive interstitial changes
G6PD deficiency should be checked prior to which drugs used for PCP treatment?
Co-trimoxazole
Dapsone
Primaquine
Which groups of people are most likely to have G6PD deficiency?
African
Mediterranean
Sephardic Jews
Chinese
What is the risk in a person with G6PD?
Haemolysis with certain drugs
What non-invasive ventilation is useful for hypoxia related to PCP?
CPAP