Cryptococcal Meningitis

Last updated: November 18, 2025

Table Of Contents

Cryptococcal Meningitis

Cryptococcal menigitis is an invasive fungal infection of the central nervous system caused by Cryptococcus neoformans or Cryptococcus gatti. It is common in immunocompromised patients and presents as a “meningoencephalitis” rather than a pure meningitis since brain parenchyma is almost always involved. It occurs in patients with CD4 < 100/mL. It is clinically similar to CNS tuberculosis, although presentation as a mass lesion (cryptococcomas) is rare. It can presents as a fulminant infection (coma → death), especially since patients present late.

Cryptococci and their characteristics

Fungus	Characteristics
Cryptococcus neoformans	Isolated from soil in areas frequented by pigeons and chicken. Associated with rotting vegetation
Cryptococcus gatti	From river red gum trees. Affects immune-competent individuals

Signs and symptoms
- Insidious onset
- Fever
- Malaise
- Intermittent painful headaches
- Meningismus (Neck stiffness, Positive Kerning’s and Brudzinski’s sign)
Investigations
- Head CT: before performing a lumbar puncture if patient has signs of raised intracranial pressure. To rule out other causes of mass lesions.
- Lumbar puncture for CSF analysis, India ink test and culture: best initial test. Repeat CSF culture at 14 days after induction to monitor remission
  - Very high opening pressure (> 200 mm on initial tap in 70% of patients)
  - Slightly elevated WBCs (<50/uL) predominantly lymphocytes
  - Slightly elevated proteins
  - Low glucose
  - Encapsulated yeast forms on india ink
- Serum CRAG (serology): may remain positive for years after treating cryptococcal meningitis 25 – 30% of patients with AIDS presenting with cryptococcal meningitis have normal CSF cell counts, glucose and proteins
Treatment of cryptococcal meningitis
- Pre-treatment with acetaminophen, diphenhydramine or corticosteroids 30 minutes before infusion of amphotericin B to prevent infusion-related reactions e.g. fever and chills
- U/E/Cs to monitor renal function and electrolytes
- Induction therapy (duration based on culture and clinical response)
  - Liposomal amphotericin B +/- flucytosine for 2 weeks
  - Liposomal amphotericin B for 2 – 6 weeks
  - Liposomal amphotericin B or fluconazole for 2 – 6 weeks
- Consolidation therapy
  - Fluconazole for 8 weeks
- Maintenance therapy
  - Discharge on maintenance PO fluconazole or itraconazole indefinitely or until CD4 > 100
- Beign HAART 2 – 10 weeks after starting antifungals to reduce the risk of immune reconstitution inflammatory response (IRIS)
- Serial lumbar puncture or lumbar drains to untile openng pressure reduces to < 20 cmH20 or 50% of the initial value.
There is no role for acetazolamide, mannitol or corticosteroids for reducing raised ICP

Reference Intervals ›

Biochemistry

ACTH	P: <80 ng/L
ALT	P: 5–35 U/L
Albumin	P: 35–50 g/L
Aldosterone	P: 100–500 pmol/L
Alk. phosphatase	P: 30–130 U/L
α-Amylase	P: 0–180 IU/dL
α-Fetoprotein	S: <10 kU/L
Angiotensin II	P: 5–35 pmol/L
ADH	P: 0.9–4.6 pmol/L
AST	P: 5–35 U/L
Bicarbonate	P: 24–30 mmol/L
Bilirubin	P: 3–17 μmol/L
BNP	P: <50 ng/L
CRP	P: <10 mg/L
Calcitonin	P: <0.1 mcg/L
Calcium (ionized)	P: 1.0–1.25 mmol/L
Calcium (total)	P: 2.12–2.60 mmol/L
Chloride	P: 95–105 mmol/L
Cholesterol	P: <5.0 mmol/L
VLDL	P: 0.128–0.645 mmol/L
LDL	P: <2.0 mmol/L
HDL	P: 0.9–1.93 mmol/L
Cortisol AM	P: 450–700 nmol/L
Cortisol Midnight	P: 80–280 nmol/L
CK ♂	P: 25–195 U/L
CK ♀	P: 25–170 U/L
Creatinine	P: 70–100 μmol/L
Ferritin	P: 12–200 mcg/L
Folate	S: 2.1 mcg/L
FSH	P: 2–8 U/L ♂; >25 menopause
GGT ♂	P: 11–51 U/L
GGT ♀	P: 7–33 U/L
Glucose (fasting)	P: 3.5–5.5 mmol/L
Growth hormone	P: <20 mu/L
HbA1C (DCCT)	B: 4–6%
HbA1C (IFCC)	B: 20–42 mmol/mol
Iron ♂	S: 14–31 μmol/L
Iron ♀	S: 11–30 μmol/L
Lactate (venous)	P: 0.6–2.4 mmol/L
Lactate (arterial)	P: 0.6–1.8 mmol/L
LDH	P: 70–250 U/L
LH	P: 3–16 U/L
Magnesium	P: 0.75–1.05 mmol/L
Osmolality	P: 278–305 mosmol/kg
PTH	P: 0.8–8.5 pmol/L
Potassium	P: 3.5–5.3 mmol/L
Prolactin ♂	P: <450 U/L
Prolactin ♀	P: <600 U/L
PSA	P: 0–4 mcg/mL
Protein (total)	P: 60–80 g/L
Red cell folate	B: 0.36–1.44 μmol/L
Renin (erect)	P: 2.8–4.5 pmol/mL/h
Renin (recumbent)	P: 1.1–2.7 pmol/mL/h
Sodium	P: 135–145 mmol/L
TBG	P: 7–17 mg/L
TSH	P: 0.5–4.2 mU/L
T4	P: 70–140 nmol/L
Free T4	P: 9–22 pmol/L
TIBC	S: 54–75 μmol/L
Triglycerides	P: 0.50–2.3 mmol/L
T3	P: 1.2–3.0 nmol/L
Troponin T	P: <0.1 mcg/L
Urate ♂	P: 210–480 μmol/L
Urate ♀	P: 150–390 μmol/L
Urea	P: 2.5–6.7 mmol/L
Vitamin B12	S: 0.13–0.68 nmol/L
Vitamin D	S: 50 nmol/L

Arterial Blood Gases

pH	7.35–7.45
PaCO₂	4.7–6.0 kPa
PaO₂	>10.6 kPa
Base excess	±2 mmol/L

Urine

Cortisol (free)	<280 nmol/24h
Hydroxyindole acetic acid	16–73 μmol/24h
Hydroxymethylmandelic acid	16–48 μmol/24h
Metanephrines	0.03–0.69 μmol/mmol cr.
Osmolality	350–1000 mosmol/kg
17-Oxogenic steroids ♂	28–30 μmol/24h
17-Oxogenic steroids ♀	21–66 μmol/24h
17-Oxosteroids ♂	17–76 μmol/24h
17-Oxosteroids ♀	14–59 μmol/24h
Phosphate (inorganic)	15–50 mmol/24h
Potassium	14–120 mmol/24h
Protein	<150 mg/24h
Protein/creatinine ratio	<3 mg/mmol
Sodium	100–250 mmol/24h

Haematology

WCC	4.0–11.0 ×10⁹/L
RBC ♂	4.5–6.5 ×10¹²/L
RBC ♀	3.9–5.6 ×10¹²/L
Hb ♂	130–180 g/L
Hb ♀	115–160 g/L
PCV ♂	0.4–0.54 L/L
PCV ♀	0.37–0.47 L/L
MCV	76–96 fL
MCH	27–32 pg
MCHC	300–360 g/L
RDW	11.6–14.6%
Neutrophils	2.0–7.5 ×10⁹/L (40–75%)
Lymphocytes	1.0–4.5 ×10⁹/L (20–45%)
Eosinophils	0.04–0.44 ×10⁹/L (1–6%)
Basophils	0–0.10 ×10⁹/L (0–1%)
Monocytes	0.2–0.8 ×10⁹/L (2–10%)
Platelets	150–400 ×10⁹/L
Reticulocytes	0.8–2.0% / 25–100 ×10⁹/L
Prothrombin time	10–14 s
APTT	35–45 s

Paediatric

Pulse Rate (bpm)
Neonate	140–160
Infant <1yr	120–140
1–5 years	110–130
5–12 years	80–120
>12 years	70–100
Respiratory Rate (tachypnoea)
0–2 months	≥60/min
2–12 months	≥50/min
1–5 years	≥40/min
>5 years	≥30/min
Blood Pressure (mmHg)
Term	65/45
1 year	75/50
4 years	85/60
8 years	95/65
10 years	100/70
Weight Formulas
3–12 months	(a + 9)/2 kg
1–6 years	2a + 8 kg
>6 years	(7a − 5)/2 kg
Haemoglobin (g/dL)
Term newborn	13–20
1 month	11–18
2 months	10–15
1–2 years	10–13
>2 years	11–14
MUAC (6 months–5 years)
Obese	>17.5 cm
Normal	13.5–17.4 cm
At risk	12.5–13.4 cm
Moderate malnutrition	11.5–12.4 cm
Severe malnutrition	<11.5 cm
Developmental Milestones
Social smile	1.5 months
Head control	4 months
Sits unsupported	7 months
Crawls	10 months
Stands unsupported	10–12 months
Walks	12–13 months
Talks	18 months
CSF WBC (/mm³)
Term newborn	0–25
>2 weeks	0–5

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Cryptococcal Meningitis

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