Page 18 - SAHCS HIVMed Journal Vol 20 No 1 2019

Page 5 of 16 Guideline

daily until the second trimester. All women exposed to TABLE 2: Summary of recommendation 2.
fluconazole in the first trimester should be referred for a Scenario Sub-recommendations
high-resolution ultrasound scan before 20 weeks of gestation Diagnosis of first • All HIV-seropositive adults and adolescents with
episode of
clinically suspected meningitis or a positive blood
to detect congenital abnormalities. For mothers who are suspected CM CrAg test should be investigated for CM. HIV-
seropositive children aged < 5 years are considered
breastfeeding, consultation with an experienced medical to have advanced HIV and, if symptomatic, should
also be investigated for CM.
practitioner is also recommended as fluconazole is present at • An LP should be performed to obtain CSF which
concentrations similar to maternal plasma concentrations in should be submitted to a laboratory for a CrAg test
and fungal culture.
breast milk and can be transmitted in large amounts through • If laboratory facilities are unavailable, a CrAg
lateral flow assay may be performed at the bedside
breast milk to the infant. 26 on CSF.
• If opening pressure was not measured at the time of
diagnostic LP, an LP should be repeated to measure
the pressure once a diagnosis of CM is confirmed –
Clinical liver disease refer to Recommendation 6.
• We do not recommend baseline CSF CrAg titre or
Patients with a history of liver disease or with evidence antifungal susceptibility testing.
of clinical liver disease deserve careful monitoring of Diagnosis of CM if LP • Serum/plasma/finger prick whole blood may be
serum liver enzyme and bilirubin levels (with specialist is not immediately tested for CrAg to determine if the patient has
available or if focal
disseminated cryptococcal disease.
referral if there is a rising trend, or if jaundice develops) neurological signs are • Patients with a positive blood CrAg test and
present
symptoms/signs of meningitis should be empirically
because fluconazole may cause liver injury. Consultation started on antifungal treatment (Figure 1,
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Recommendation 3) and referred to a centre where
with a medical practitioner experienced in the care of LP can be performed. A CT brain scan should be
HIV-seropositive patients is recommended. obtained if there are neurological contraindications
to immediate LP.
Diagnosis of • The patient should be assessed clinically for signs
Recommendation 2: Laboratory subsequent episode • An LP should be performed to obtain CSF which
and symptoms of meningitis.
of suspected CM
diagnosis and monitoring should be submitted to a laboratory for prolonged
fungal culture (minimum 14 days) (Note – India ink
and CrAg tests are not useful for the diagnosis of
Background subsequent episodes of cryptococcal meningitis as
they can stay positive for a prolonged period despite
successful treatment).
Cryptococcus neoformans is the most commonly detected • Opening pressure should be measured.
pathogen causing meningitis in South Africa. All • Antifungal susceptibility testing should be considered
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if the CSF fungal culture is positive and other causes
HIV-seropositive adults and adolescents with clinically for symptomatic relapse are excluded.
suspected meningitis or a positive blood CrAg test should Monitoring response • Resolution of symptoms and signs can be used to
monitor response to treatment.
to antifungal
be investigated for CM. HIV-seropositive children aged treatment • Unless there is a specific indication (e.g. persistent
symptoms or signs suggesting ongoing or late-onset
< 5 years are considered to have advanced HIV and, raised intracranial pressure), LP should not be
routinely performed after 7–14 days of antifungal
if symptomatic, should also be investigated for CM. treatment to document conversion of CSF from
3
culture-positive to culture-negative.†
Patients with CM usually seek care with symptoms and • CSF and serum/plasma CrAg titres should not be
signs related to inflamed meninges (including neck monitored.
Suspected antifungal- • Consider antifungal susceptibility testing if a patient
stiffness), raised intracranial pressure (including headache, resistant isolate has a relapse episode and the causes listed in
Table 10 have been excluded (Recommendation 7).
confusion, altered level of consciousness, sixth cranial • Fluconazole MICs should be determined at an
nerve palsies with diplopia and visual impairment and academic/reference laboratory and interpreted by an
experienced clinical microbiologist in conjunction
papilloedema) and encephalitis (including memory loss with clinical findings.
and new-onset psychiatric symptoms). Cutaneous lesions Screening for • Refer to Recommendation 1.
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cryptococcal
and pulmonary involvement (including cavitation, nodular antigenaemia
infiltrates and consolidation) may also occur. Symptomatic CM, cryptococcal meningitis; LP, lumbar puncture; CSF, cerebrospinal fluid; CrAg,
cryptococcal antigen; LFA, lateral flow assay; MIC, minimum inhibitory concentration; CT,
relapses are common and are most often because of computed tomography.
inadequate or premature cessation of maintenance †, If symptoms re-appear or persist during induction treatment, LP should be repeated to
re-measure the opening pressure, which may increase despite successful CSF sterilisation –
fluconazole treatment. The incidence of CM is much refer to Recommendation 6.
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15
lower among children ; children with CM may present
with an acute onset of illness and focal neurological signs performed and found negative, the laboratory should either
may be less common (Table 2). perform a CSF CrAg test or refer the specimen for this test.
A CrAg LFA is the preferred format of testing; there are now
several kits on the market although the innovator product
Detailed recommendations (IMMY, Norman, OK) has been most widely studied in pre-
Diagnosis of a first episode of cryptococcal meningitis clinical and clinical evaluations, 5,17,32 and the accuracy of
An LP is required to confirm the diagnosis and establish the other assays is still unclear. Cryptococcus neoformans can be
aetiology of suspected meningitis. Lumbar puncture may cultured from CSF within 72 h among patients with a first
also alleviate symptoms that are a direct result of raised episode of CM. Cryptococcus gattii is occasionally confirmed
intracranial pressure. For a suspected first episode of CM, on culture (2% of all cases in South Africa) and these
CSF should be submitted to the laboratory for a CrAg test infections should be managed as for C. neoformans among
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and fungal culture. India ink test is not recommended as the HIV-seropositive patients. There is no need to routinely
only rapid test because of its lower sensitivity (78% order a baseline CSF CrAg titre because most patients are
compared to CSF CrAg test). If a CSF India ink test is diagnosed when the CSF fungal burden is already high and
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