Bibliographic Info
GuidelineRapid advice : diagnosis, prevention and management of cryptococcal disease in HIV-infected adults, adolescents and children
Year of Publication2011
Issuing InstitutionWorld Health Organization
Recommendation
Status
Maintained
Recommended in favor
Strong
Certainty of evidence
Moderate
Prompt lumbar puncture with measurement of cerebrospinal fluid (CSF) opening pressure and rapid CSF cryptococcal antigen (CrAg) assay or rapid serum CrAg (either LA or LFA) is the preferred diagnostic approach.
Notes and Remarks
- 1)In developing these recommendations, the Guideline Development Group placed very high value on early diagnosis of cryptococcal disease and, therefore, prompt antifungal therapy, to reduce the high pre and post ART early mortality and morbidity. There was high value placed on the use of simple low cost assays for RLS that are less labour intensive or laboratory dependent.
- 2)The Guideline Development Group recognised the importance of a high index of suspicion for CM among health care professionals, and the importance of LP to confirm CM, exclude other diagnoses, and both measure and manage intracranial pressure.
- 3)The conventional approach to diagnosis of CM requires LP with an India ink test, positive cryptococcal antigen test or culture. The Guideline Development Group reviewed GRADE evidence profiles based on pooled data from more than 30 observational studies on the performance (sensitivity, specificity and predictive value) of three types of CrAg assays in CSF and serum (LA, enzyme immunoassay (EIA) and LFA), as well as CSF India ink test, compared to CSF culture (in most cases) as the gold standard, in participants with either suspected or confirmed cryptococcal disease.
- 4)The Guideline Development Group’s recommendations for the preferred use of a rapid CrAg assay (either LA or LFA) in CSF or serum (depending on access to lumbar puncture), was 18 Rapid Advice Diagnosis, Prevention and Management of Cryptococcal Disease in HIV-infected Adults, Adolescents and Children based on the CrAg assays much higher sensitivity and specificity than the India ink test (especially in patients with low CSF fungal burden), and that it is easier to perform and less dependent on technician skill than the India ink test. The EIA assay was not included as a recommended CrAg assay because of its higher cost. The LFA has several advantages over the LA CrAg assay: it is less expensive, has a rapid 5-15 minute turnaround time, requires little training for its use and interpretation, can be performed with minimal laboratory infrastructure and without refrigeration since it is stable at room temperature, and satisfies most of the WHO ASSURED criteria for point-of-care tests (POCT)11. However, the Guideline Development Group recognized the more limited evaluation to date of the LFA, particularly regarding specificity, and so both the LA and LFA were included as recommended CrAg assays.
- 5)There is currently a lack of data on CrAg assay performance in other relevant populations, such as children, patients with pulmonary disease, and in lower-prevalence settings.
- 6)A serum or plasma CrAg was recommended as an initial diagnostic option in settings where access to LP was limited or contraindicated, despite its slightly lower sensitivity, to expedite diagnosis and initiation of anti-fungal therapy. The Guideline Development Group emphasised that serum CrAg diagnosis should not replace the need for referral and CSF examination, which should be undertaken whenever it is feasible and clinically appropriate.
- 7)The Guideline Development Group recognised the need for cost reduction of CrAg assays to make them more widely available in RLS. Countries should develop plans to improve access to rapid CrAg assays, although the speed and completeness of access will be determined by each country’s health system capacity, cryptococcal burden, ART coverage and available funding.
Also Featured In
This recommendation also appears in the following guidelines:
Guideline
Consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection: recommendations for a public health approach
Year2016
InstitutionWHO