Opportunistic Infections Flashcards
Differentials - SOL
Toxo, primary CNS lymphoma, PML, TB, cryptococcus, NHL, syphilitic gummae
Differentials - encephalitis
HIV, varicella, herpes, syphilis
Differentials - meningitis
seroconversion, cryptococcus, TB, STS, bacterial
Differentials - spastic paraparesis
Hiv-vacuolar myelopathy, transverse myelitis from VZV, HSV, htlv, toxo, sts
Cryptococcus
Encapsulated yeast - inhaled - localised in lungs may spread through blood to brain
Most often acquired in childhood
Serotype A (c neoformans var grubii) most common, serotype D (car neoformans) second
May disseminate to skin and lungs
Cryptococcus - presentation
Meningitis most common - headache, fever, meningism (variable)
Raised ICP may cause nausea, vomitting, confusion, coma
Pulmonary disease may occur without CNS but less common - fever, cough
Cryptococcus diagnosis
Serum CRAG - latex agglutination LP for CRAG most sensitive diagnostic test (after MRI) (or India ink stain or culture if can’t do crag) Manometry - common raised ICP CSF fungal culture Blood cultures Susceptibilities
False pos cryptococcal antigen can be caused by
Presence of rheumatoid factor, heterophile antibodies, anti-idiotypic antibodies, biegelii infection
Cryptococcal meningitis - poor prognostic indicators
Blood culture positive Low WCC in CSF (<20) High CSF CRAG (>1:1024) Confused state Raised ICP
Cryptococcal meningitis treatment - induction
liposomal amphotericin B 4mg/kg/day IV (kinder on kidneys than standard type deoxycholate 0.7-1mg/kg/day)
Flucytosine 100mg/kg day - daily blood counts and drug levels needed
F speeds rate of sterilisation, reduces incidence of relapse however no impact on mortality, possibly enhanced toxicity
Alternative - fluconazole 400mg/day
Other Azoles if nothing else tolerated
Raised ICP management (cryptococcal meningitis)
Manometry at baseline or if deterioration
Serial LP or neurosurg required if opening pressure >250mmh2o
Reduce to <200 or 50%
Repeat daily until stable
Resistant cases may require shunt
Cryptococcal meningitis - maintenance therapy
After 2 weeks induction or once CSF cultures neg
400mg fluconazole OD
Reduce to 200mg OD after 10 weeks
If initial poor prognostic factors repeat LP and consider longer induction
Non CNS cryptococcal infection management
Should have LP anyway
If neg tx with fluconazole followed by secondary prophylaxis
If positive tx for cryptococcal meningitis
Commencement of ARVs in cryptococcal meningitis
Commence at 2 weeks once induction completed
Increased mortality if started within 72hrs
Risk of IRIS - if happens tx is to continue ARVs and if no active infection consider steroids
Stop secondary prophylaxis once VL undetectable, CD4 >100 for 3 months
Toxoplasma Gondii
Commonest cause of mass lesions in PLWH CD4 <200
Obligate intracellular protozoan who’s hosts are cat family
Humans acquire this from eating animals with disseminated infection or ingestion of oocytes shed in cat faeces that have contaminated stool/water
Toxo serology at diagnosis - risk of igG seropos developing toxoplasma encephalitis is around 25%
Toxoplasma presentation
Cerebral abscess symptoms develop days to weeks - focal neurology, sometimes seizures
Movement issues as predilection for basal ganglia
Encephalitis symptoms
If raised ICP can have headaches and vomitting
May have myelitis
Outside CNS - pneumonia, chorioretinitis
Toxoplasma diagnosis
MRI > CT
MRI views posterior fossa lesions better
Multiple ring enhancing lesions at grey/white interface and basal ganglia or thalamus
Cerebral oedema and mass effect
PCNSL a differential - SPECT May help here - may be single peri ventricular lesion mainly white matter do not enhance or exhibit mass effect
IgG proves previous infection only
LP if not contraindicated (mass lesions contraindicated due to raised ICP) - CSF toxo PCR sensitivity 50% specificity >94%
Toxoplasma treatment
Screen for G6PD
6 weeks initial therapy -
200mg pyrimethamine stat then 50mg/day < 60kg or 75mg m/day > 60kg (oral or NG)
Plus folinic acid 15mg/day - counteracts myelosuppressive effect of pyrimethamine
Plus sulphadiazine 1-2g QDS (or weight based dosing 15mg/kg qds) OR Clindamycin (both oral)
If a rash - most likely to be sulphadiazine or clindamycin so stop and swap
Alternatives - septrin if needs iv
If no improvement in 2 weeks - brain biopsy
Toxoplasma - maintenance therapy
Pyrimethamine 25mg/day plus sulphadiazine 500mg qds or 1-2g bd or clindamycin 300mg qds or 600mg TDS
Folinic acid 15mg/day
Data suggests bd just as effective as QDS but no studies
Stop once cd4 >200 for 6/12
Steroids for toxoplasma??
Not routinely as cannot tell if tx working
Used for raised ICP - gradually reducing from 4mg QDS
Indication for brain biopsy in ?toxoplasmosis
Failure to respond to 2 weeks of treatment
Clinical deterioration on therapy
Single (particularly periventricular) lesion on MRI
Mass lesions with CD4 > 200
Toxoplasmosis prophylaxis
For those with CD4 <200
Septrin as for PCP will cover
Dapsone 50mg/day and weekly pyrimethamine 50mg if allergic
Avoid undercooked meat, wash hands after contact with soil, avoid cat litter trays (or empty daily and wash hands)
Stop once CD4 >200 3/12 and VL suppressed
When to start ARVs - toxo
2 weeks after commencing tx to reduce risk of IRIS
PML
JC virus
Spread through resp secretions
Lies latent in spleen bone marrow kidneys B cells
With subsequent immune suppression is transported to brain by b lymphocytes
How does PML present?
Subacute illness without constitutional symptoms
Focal neurology mainly motor
Altered mental or mood status
Ataxia
Cortical visual symptoms
Weeks to months
How to diagnose PML
MRI and LP - JC virus in CSF
Usually sufficient to avoid brain biopsy which was prev gold standard
MRI bilateral symmetrical non enhancing white matter lesions no oedema
T2 hyperintense t1 hypointense
Pml - poor prognostic factors
Older age
Brain stem involvement
Lower GCS
High JC VL
CD4 <100
Treatment for PML
HAART including drugs which penetrate CMS
Increased 1yr survival from 10% to 50%
CMV
Beta herpesvirus
Latent infection
Nearly all MSM exposed, 50-75% in Hetero and IDU
Latent CMV reactivates with worsening immune function
End organ disease incidence higher with CD4 <50
Retina (75% of cases) gi tract, lungs, liver, biliary tract, heart, adrenals, nervous system (<1%)
Nervous system CMV - how does it present??
Similar to aids dementia
Subacute
Progressive disorientation, withdrawl, apathy, cranial nerve palsies, nystagmus
Depression and mental slowing LESS common
Lumbrosacral polyradiculitis - rapidly progressing, painful, bilateral flaccid paralysis, saddle anaesthesia, urinary retention
Diagnoses nervous system CMV
MRI and CSF PCR are preferred
CT first pre LP
Imaging lacks sensitivity can be nonspecific or normal
MRI with gad - periventricular enhancement commonly seen
Tx nervous system CMV
Ganciclovir with or without foscarnetz seed
Churchy
