Opportunistic Infections

Question 1

Differentials - SOL

Answer 1

Toxo, primary CNS lymphoma, PML, TB, cryptococcus, NHL, syphilitic gummae

Question 2

Differentials - encephalitis

Answer 2

HIV, varicella, herpes, syphilis

Question 3

Differentials - meningitis

Answer 3

seroconversion, cryptococcus, TB, STS, bacterial

Question 4

Differentials - spastic paraparesis

Answer 4

Hiv-vacuolar myelopathy, transverse myelitis from VZV, HSV, htlv, toxo, sts

Question 5

Cryptococcus

Answer 5

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

Question 6

Cryptococcus - presentation

Answer 6

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

Question 7

Cryptococcus diagnosis

Answer 7

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

Question 8

False pos cryptococcal antigen can be caused by

Answer 8

Presence of rheumatoid factor, heterophile antibodies, anti-idiotypic antibodies, biegelii infection

Question 9

Cryptococcal meningitis - poor prognostic indicators

Answer 9

Blood culture positive
Low WCC in CSF (<20)
High CSF CRAG (>1:1024)
Confused state
Raised ICP

Question 10

Cryptococcal meningitis treatment - induction

Answer 10

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

Question 11

Raised ICP management (cryptococcal meningitis)

Answer 11

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

Question 12

Cryptococcal meningitis - maintenance therapy

Answer 12

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

Question 13

Non CNS cryptococcal infection management

Answer 13

Should have LP anyway
If neg tx with fluconazole followed by secondary prophylaxis
If positive tx for cryptococcal meningitis

Question 14

Commencement of ARVs in cryptococcal meningitis

Answer 14

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

Question 15

Toxoplasma Gondii

Answer 15

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%

Question 16

Toxoplasma presentation

Answer 16

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

Question 17

Toxoplasma diagnosis

Answer 17

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%

Question 18

Toxoplasma treatment

Answer 18

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

Question 19

Toxoplasma - maintenance therapy

Answer 19

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

Question 20

Steroids for toxoplasma??

Answer 20

Not routinely as cannot tell if tx working

Used for raised ICP - gradually reducing from 4mg QDS

Question 21

Indication for brain biopsy in ?toxoplasmosis

Answer 21

Failure to respond to 2 weeks of treatment
Clinical deterioration on therapy
Single (particularly periventricular) lesion on MRI
Mass lesions with CD4 > 200

Question 22

Toxoplasmosis prophylaxis

Answer 22

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

Question 23

When to start ARVs - toxo

Answer 23

2 weeks after commencing tx to reduce risk of IRIS

Question 24

PML

Answer 24

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

Question 25

How does PML present?

Answer 25

Subacute illness without constitutional symptoms

Focal neurology mainly motor
Altered mental or mood status
Ataxia
Cortical visual symptoms

Weeks to months

Question 26

How to diagnose PML

Answer 26

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

Question 27

Pml - poor prognostic factors

Answer 27

Older age
Brain stem involvement
Lower GCS

High JC VL

CD4 <100

Question 28

Treatment for PML

Answer 28

HAART including drugs which penetrate CMS

Increased 1yr survival from 10% to 50%

Question 29

CMV

Answer 29

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%)

Question 30

Nervous system CMV - how does it present??

Answer 30

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

Question 31

Diagnoses nervous system CMV

Answer 31

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

Question 32

Tx nervous system CMV

Answer 32

Ganciclovir with or without foscarnetz seed

Churchy