Page 27 - SAHCS HIVMed Journal Vol 20 No 1 2019

Page 14 of 16 Guideline

14 days of incubation in the laboratory) on at least 1200 mg daily with regular review and follow-up of the CSF
3 mL – 5 mL of CSF. There is no role for India ink staining fungal culture result. If the CSF fungal culture is subsequently
or CSF/blood CrAg assays in establishing the cause of confirmed as negative, the dose of fluconazole can be reduced
recurrence as these tests may remain positive for months to what it was (800 mg or 200 mg daily depending on the
to years even in patients after successful treatment – refer timing of the CM-IRIS event).
to Recommendation 2.
• If the CSF is culture-positive and non-adherence does not Suspected cryptococcal meningitis-immune
appear to be the cause, then fluconazole susceptibility reconstitution inflammatory syndrome
testing should be considered. Susceptibility testing with severe symptoms or clinical
should be performed in an academic/reference laboratory. deterioration
The panel recommends this when there has been at least If patients have severe symptoms or deteriorate with the
one documented relapse despite reported good adherence approach above, the panel recommends treating with
(Recommendation 2). amphotericin B deoxycholate 1 mg/kg/day plus either
flucytosine (100 mg/kg/day divided into four doses per day)
If the cause of the recurrence is attributed to non-adherence, or fluconazole 1200 mg daily until the CSF culture is
then the patient should be treated as for the first episode confirmed as negative. If the CSF culture is still negative after
(Recommendation 3). The reasons for non-adherence 7 days’ incubation, amphotericin B can be stopped. If the
should be explored and the patient should receive additional fungal culture is positive by 7 days, then amphotericin B
adherence counselling, preferably together with a treatment should be continued for 14 days if it is given with fluconazole
supporter. If the patient also interrupted ART, this should (if it is given with flucytosine, then 7 days is sufficient). Daily
be re-initiated 4–6 weeks after induction antifungal therapeutic LPs may be required if opening pressure is raised.
treatment is re-started. Antiretroviral treatment may need A CT brain scan should be considered as mass lesions and
to be adjusted if there is a concern that there has been cerebral oedema can occur with IRIS. Analgesia should be
virological failure. provided. Among patients with severe IRIS who do not
respond to the above treatment, corticosteroids should be
Paradoxical cryptococcal IRIS occurs among patients treated considered: prednisone 1 mg/kg/day or an equivalent dose
for cryptococcal disease who start ART and develop a of dexamethasone for up to 2 weeks or until clinical
recurrence or worsening of clinical manifestations of improvement occurs, tapered over 2–6 weeks. Longer
cryptococcal disease. Immune reconstitution inflammatory treatment may be required depending on the symptom
syndrome is thought to be the result of an immunopathological response. The panel recommends that corticosteroids
reaction directed at residual fungal antigens at sites of preferably should be used among patients with IRIS who are
disease. IRIS occurs on average 6 weeks after ART is documented to be CSF fungal culture-negative and when
40
commenced but delayed cases (> 1 year after ART initiation) other aetiologies (including tuberculous meningitis [TBM]
41
have been described. Cryptococcal meningitis IRIS- and neurotropic viral infections) are excluded. However,
associated mortality may be substantial. The most frequent if there is life-threatening neurological deterioration,
42
manifestation is recurrence of symptoms of meningitis often corticosteroids should be started immediately.
with raised intracranial pressure. Typically, the CSF fungal
culture is negative at the time of IRIS presentation – IRIS Among patients with meningitis caused by fluconazole-
represents an immunological reaction rather than a resistant Cryptococcus, subsequent management should be
microbiological recurrence. However, in cases where discussed with a medical practitioner experienced in the
induction therapy was recent (< 2 months), the CSF fungal treatment of CM. Such patients should receive induction
culture may still be positive. Other cryptococcal IRIS therapy with amphotericin B again. Consolidation and
manifestations include lymphadenitis and cryptococcomas. 40 maintenance options will depend on the fluconazole MIC
and may include high doses of fluconazole, voriconazole or
In all patients with suspected paradoxical CM-IRIS, an LP posaconazole with or without weekly amphotericin B
should be performed to measure pressure and obtain a fungal infusions. 25
culture incubated for up to 14 days. It is not possible to
make a diagnosis of IRIS with certainty prior to excluding Among patients with multiple relapses, it is important to
microbiological relapse on CSF fungal culture. document conversion of CSF from culture-positive to culture-
negative before stopping amphotericin B and such cases
Suspected cryptococcal meningitis-immune should be discussed with a medical practitioner experienced
reconstitution inflammatory with mild in CM management and fluconazole susceptibility testing
symptoms should be performed.

If the symptoms are mild, the panel recommends performing
therapeutic LPs if there is raised intracranial pressure, Distinguishing CM relapse or IRIS from TBM: Immune-
providing analgesia and increasing the fluconazole dose to suppressed HIV-seropositive adults are at high risk of

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