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Cryptococcal disease Cheat Sheet by

This is an Infection with Cryptococcus species that impairs normal body function, detected by abnormal clinical symptoms or signs. Cryptococcal disease is an opportunistic infection that occurs primarily among people with advanced HIV disease and is an important cause of morbidity and mortality. we will discuss diagnosis and management of cryptococcal disease.

Definition

Infection of the brain and spinal column caused by Crypt­ococcus neofor­mans

Diagnosis

For adults, adoles­cents and children living with HIV suspected of having a first episode of crypto­coccal mening­itis, prompt lumbar puncture with measur­ement of cerebr­ospinal fluid (CSF) opening pressure and rapid crypto­coccal antigen assay is recomm­ended
In settings with ready access to and no contra­ind­ication for lumbar puncture: Do a lumbar puncture to obtain CSF for CrAg ,India Ink and Gene Xpert and VDRL
CSF CRAG positive, India Ink Positive or culture growth confirmed (any one positive):
Contra­ind­ica­tions include:
Signif­icant coagul­opathy or suspected space-­occ­upying lesion based on focal nervous system signs (excluding cranial nerve VI palsy) or recurrent seizures and, where possible, confirmed by computed tomography
Other contra­ind­ica­tions include major spinal deformity and patient refusal after fully informed consent was sought.

Treatment and Management

Routine use of adjunctive cortic­ost­eroid therapy during the induction phase is not recomm­ended in treating HIV-as­soc­iated crypto­coccal meningitis among adults, adoles­cents and children
 

Treatment for pregnant women

Amphot­ericin B therapy can be given to pregnant women with meningeal and non-me­ningeal
disease. Exposure to flucyt­osine and flucon­azole during pregnancy has been associated with an
increased risk of birth defects in animal studies and some uncont­rolled human studies.
The use of flucyt­osine and flucon­azole for treating crypto­coccal disease in pregnant women should be
evaluated on an individual basis, consid­ering the benefits and potential harm.

Preven­tion, monitoring and management of toxicity

Pre-em­ptive hydration and electr­olyte supple­men­tation
Adults and adoles­cents
1L of normal saline solution with 20 mEq of potassium chloride (KCl) over two hours before each controlled infusion of amphot­ericin B
 
If available, magnesium supple­men­tation should also be provided (two 250-mg tablets of magnesium trisil­icate or glycer­oph­osphate twice daily, or magnesium chloride 4 mEq twice daily).
Monitoring
Serum potassium
Baseline and 2–3 times weekly (espec­ially in the second week of amphot­ericin B admini­str­ation)
Serum creatinine
Baseline and 2–3 times weekly (espec­ially in the second week of amphot­ericin B admini­str­ation)
Haemog­lobin
Baseline and weekly
Management
Hypoka­laemia
If hypoka­laemia is signif­icant (K <3.3 mol/l), increase potassium supple­men­tation to 40 mEq KCl by intrav­enous infusion and/or one to two 8-mEq KCl tablets orally three times daily. Monitor potassium daily.
Elevated creatinine
≥2 fold from the baseline value, increase pre-hy­dration to 1 L every eight hours and consider tempor­arily omitting a dose of amphot­ericin B. Once creatinine improves, restart amphot­ericin B at 0.7 mg/ kg/day and consider altern­ate-day amphot­ericin B. If creatinine continues to rise, consider discon­tinuing amphot­ericin B and continuing with flucon­azole at 1200 mg/ day.
Severe anaemia
Transf­usion should be undertaken if possible for severe amphot­ericin B–related anaemia
Flucon­azole dose adjustment if signif­icant renal impair­ment.
Anaemia may be a reason to discon­tinue amphot­ericin B premat­urely in the second week of a planned two-week induction course of amphot­ericin B with flucon­azole.
Monitor intake and output of fluid and daily weight, especially among children.
Flucyt­osine requires regular monitoring of full blood count
 

symptoms and signs of raised intrac­ranial pressure

Symptoms
• Headache
• Nausea with or without vomiting
• Changes in vision or hearing (such as double vision, blindness or deafness)
Signs
• Change in mental status (ranging from confusion to lethargy to coma)
• Papill­oedema
• Seizures
• Cranial nerve palsies (such as eye movement problems, partic­ularly cranial nerve VI)
• Other focal neurol­ogical nervous system deficits

causes of persistent and recurrent symptoms

Persistent symptoms
• Raised intrac­ranial pressure
• Treatment failure caused by suboptimal induction treatment
• Inadequate drug regimen, dose or duration
• Flucon­azole drug resistance (rare)
• Other concom­itant illness (such as viral, bacterial, or tuberc­ulous mening­itis)
Recurrent symptoms
• Raised intrac­ranial pressure
• Treatment failure due to suboptimal induction, consol­idation or mainte­nance treatment
• Inadequate drug regimen, dose or duration
• Failure to prescribe or to adhere to flucon­azole consol­idation or mainte­nance
treatment
• Flucon­azole drug resistance (rare)
• Crypto­coccal immune recons­tit­ution inflam­matory syndrome (IRIS) following
ART initiation
• Other concom­itant illness (such as viral, bacterial or tuberc­ulous mening­itis)

managing crypto­coccal IRIS

1. Continue ART.
2. Promptly manage raised intrac­ranial pressure.
3. Optimize anti fungal therapy and consider restarting induction therapy
4. Short-­course oral steroid therapy may be considered if there is continued deteri­oration
and/or the develo­pment of life-t­hre­atening compli­cations (such as intrac­ranial space-­occ­upying
lesions with mass effect or extra-­cranial disease impinging on vital struct­ures) despite the
above measures.
Immediate ART initiation is not recomm­ended for adults, adoles­cents and children living
with HIV who have crypto­coccal meningitis because of the risk of increased mortality
and should be deferred by 4–6 weeks from the initiation of anti-f­ungal treatment.

Discon­tinuing flucon­azole mainte­nance treatment

Is HIV viral load monitoring is available
If stable on and adherent to ART and antifungal mainte­nance treatment for at least one year and has a CD4 cell count ≥100 cells/mm3 and a fully suppressed viral load
Is HIV viral load monitoring is not available
If stable on and adherent to ART and antifungal mainte­nance treatment for at least one year and has a CD4 cell count ≥200 cells/mm3
For children living with HIV who are 2–5 years old and have succes­sfully treated crypto­coccal
disease, discon­tinuing anti-f­ungal treatment mainte­nance is recomm­ended if the child is stable on and adherent to ART and anti-f­ungal mainte­nance treatment for at least one year and has a CD4 cell count percentage greater than 25% or an absolute count
>750 cells/mm3.
Mainte­nance treatment for crypto­coccal disease should not be discon­tinued for children younger
than two years.

References

Guidelines for managing advanced HIV disease and rapid initiation of antire­tro­viral therapy. Geneva: World Health Organi­zation; 2017 (http:­//w­ww.w­ho.in­t/h­iv/­pub­/gu­ide­lin­es/­adv­anced- HIV-di­sea­se/en, accessed 17 January 2018).
Speed BR, Kaldor J. Rarity of crypto­coccal infection in children. Pediatr Infect Dis J. 1997;1­6:5­36–7.
Lightowler JV, Cooke GS, Mutevedzi P, Lessells RJ, Newell ML, Dedicoat M. Treatment of crypto­coccal meningitis in KwaZul­u-N­atal, South Africa. PLoS One. 2010;5­:e8630.
Rapid advice: diagnosis, prevention and management of crypto­coccal disease in HIVinf­ected adults, adoles­cents and children. Geneva: World Health Organi­zation; 2011 (http:// www.wh­o.i­nt/­hiv­/pu­b/c­ryp­toc­occ­al_­dis­eas­e20­11/en/, accessed 17 January 2018).
Antifungal drug maps [website]. Geneva: Global Action Fund for Fungal Infect­ions; 2018 (http:­//w­ww.g­af­fi.o­rg­/an­tif­ung­al-­dru­g-maps, accessed 17 January 2018).

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