Guideline

Guidelines for diagnosing, preventing and managing cryptococcal disease among adults, adolescents and children living with HIV.

Year of Publication

2022

Issuing Institution

World Health Organization

Links

WHO IRIS

Recommendations

20 included recommendations

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 as the preferred diagnostic approach

Status

Maintained

Recommended in favor

Strong

Certainty of evidence

Low

In settings with ready access to and no contraindication for lumbar puncture: i) If both access to a cryptococcal antigen assay (either lateral flow assay or latex agglutination assay) and rapid results (less than 24 hours) are available: Lumbar puncture with rapid cerebrospinal fluidcryptococcal antigen assay is the preferred diagnostic approach.

Status

Maintained

Recommended in favor

Strong

Certainty of evidence

Low

In settings with ready access to and no contraindication for lumbar puncture: If access to a cryptococcal antigen assay is not available and/or rapid results are not available: Lumbar puncture with cerebrospinal fluid (CSF) India ink test examination is the preferred diagnostic approach.

Status

Maintained

Recommended in favor

Strong

Certainty of evidence

Moderate

In settings without immediate access to lumbar puncture or when lumbar puncture is clinically contraindicated: a i) If both access to a cryptococcal antigen assay and rapid results (less than 24 hours) are available: Rapid serum, plasma or whole-blood cryptococcal antigen assays are the preferred diagnostic approaches.

Status

Maintained

Recommended in favor

Strong

Certainty of evidence

Low

In settings without immediate access to lumbar puncture or when lumbar puncture is clinically contraindicated: If a cryptococcal antigen assay is not available and/or rapid access to results is not ensured: Prompt referral for further investigation and treatment as appropriate.

Status

Maintained

Recommended in favor

Strong

Certainty of evidence

Low

Screening for cryptococcal antigen followed by pre-emptive antifungal therapy among cryptococcal antigen–positive people to prevent the development of invasive cryptococcal disease is recommended before initiating or reinitiating ART for adults and adolescents living with HIV who have a CD4 cell count <100 cells/mm3

Status

Maintained

Recommended in favor

Strong

Certainty of evidence

Moderate

When cryptococcal antigen screening is not available, fluconazole primary prophylaxis should be given to adults and adolescents living with HIV who have a CD4 cell count <100 cells/mm3

Status

Maintained

Recommended in favor

Strong

Certainty of evidence

Moderate

All people living with HIV with a positive cryptococcal antigen result on screening should be carefully evaluated for signs and symptoms of meningitis and undergo a lumbar puncture if feasible with cerebrospinal fluid (CSF) examination aand cryptococcal antigen assay (or India ink if cryptococcal antigen assay is not available) to exclude active cryptococcal disease

Status

Maintained

Certainty of evidence

Moderate

For adults, adolescents and children, a short-course (one-week) induction regimen with amphotericin B deoxycholate (1.0 mg/kg/day) and flucytosine (100 mg/kg/ day, divided into four doses per day), followed by 1 week of fluconazole (1200 mg/day for adults, 12 mg/kg/day for children and adolescents, up to a maximum dose of 800mg daily), is the preferred option for treating cryptococcal meningitis among people living with HIV

Status

Maintained

Recommended in favor

Strong

Certainty of evidence

Moderate

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

Status

Maintained

Recommended against

Strong

Certainty of evidence

High

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 antifungal treatment.

Status

Maintained

Recommended against

Strong

Certainty of evidence

Low

Fluconazole (800 mg daily for adults, 6–12 mg/kg/day for children and adolescents up to a maximum of 800 mg daily) is recommended for the consolidation phase (for eight weeks following the induction phase)

Status

Maintained

Recommended in favor

Strong

Certainty of evidence

Low

Fluconazole (200 mg daily for adults, 6 mg/kg/day for adolescents and children) is recommended for the maintenance phase (or secondary prophilaxys)

Status

Maintained

Recommended in favor

Strong

Certainty of evidence

High

A single high dose (10 mg/kg) of liposomal amphotericin B with 14 days of flucytosine (100 mg/kg per day divided into four doses per day) and fluconazole (1200 mg/daily for adults; 12 mg/kg per day for children and adolescents up to a maximum of 800 mg daily) should be used as the preferred induction regimen for treating people with cryptococcal meningitis.

Status

Maintained

Recommended in favor

Strong

Certainty of evidence

Moderate

(Treating people with cryptococcal meningitis) If liposomal amphotericin is not available: A seven-day course of amphotericin B deoxycholate (1 mg/kg per day) and flucytosine (100 mg/kg per day, divided into four doses per day) followed by seven days of fluconazole (1200 mg daily for adults and 12 mg/kg per day for children and adolescents up to a maximum of 800 mg daily).

Status

Maintained

Recommended in favor

Strong

Certainty of evidence

Moderate

(Treating people with cryptococcal meningitis) If no amphotericin formulation is available: 14 days of fluconazole (1200 mg daily, 12 mg/kg per day for children and adolescents) and flucytosine (100 mg/kg per day, divided into four doses per day)

Status

Maintained

Recommended in favor

Strong

Certainty of evidence

Moderate

(Treating people with cryptococcal meningitis) If flucytosine is not available: 14 days of liposomal amphotericin B (3–4 mg/kg per day) and fluconazole (1200 mg daily, 12 mg/kg per day for children and adolescents up to a maximum of 800 mg daily).

Status

Maintained

Recommended in favor

Strong

Certainty of evidence

Moderate

(Treating people with cryptococcal meningitis) If liposomal amphotericin B and flucytosine are not available: 14 days of amphotericin B deoxycholate (1 mg/kg per day) and fluconazole (1200 mg daily, 12 mg/kg per day for children and adolescents up to a maximum of 800 mg daily).

Status

Maintained

Recommended in favor

Strong

Certainty of evidence

Moderate

Screening for cryptococcal antigen followed by pre-emptive antifungal therapy (3 among cryptococcal antigen– positive people to prevent the development of invasive cryptococcal disease may be considered before initiating or reinitiating ART for adults and adolescents living with HIV at a higher CD4 cell count threshold of <200 cells/mm3

Status

Maintained

Recommended in favor

Conditional

Certainty of evidence

Moderate

When cryptococcal antigen screening is not available, fluconazole primary prophylaxis may be considered at a higher CD4 cell count threshold of < 200 cells/mm3

Status

Maintained

Recommended in favor

Conditional

Certainty of evidence

Moderate