SAGE IVD recommended the inclusion of the Aspergillus antigen test category in the third EDL:
• as a disease-specific IVD for clinical laboratories (EDL 3; Section II.b; Aspergillosis);
• using an RDT or immunoassay format;
• to aid in the diagnosis of invasive aspergillosis in immunocompromised patients. In considering the test formats available, SAGE IVD noted that while both lateral flow assay (LFA) and ELISA devices should be listed in the EDL, the use of LFA devices should be limited to bronchoalveolar lavage (BAL) specimens until more data can be obtained on the accuracy of these devices using serum. SAGE IVD further recommended comparing LFA devices with PCR for EDL 4 as an alternative, because many tertiary institutions already have PCR technologies available. The group also noted that in the case of this IVD, it is particularly important that the EDL is clearly linked to relevant guidelines so that users of the test are aware of the potential cross-reactivity issues associated with GM assays.

Invasive aspergillosis (IA) is a WHO priority and a very severe disease. Its incidence may not be high, but it is an almost uniformly fatal disease in LMICs, where the mortality rate is mainly affected by the timing and initiation of antifungal therapy. It is a difficult disease to diagnose, and Aspergillus antigen testing is imperfect. For example, it has a highly variable sensitivity in serum testing in lateral flow assay (LFA) test formats and the antigen detected, galactomannan (GM), can sometimes cross-react with other species. In all cases, Aspergillus antigen tests should only be used when accompanied by a strong clinical suspicion of IA. The cost per test seems prohibitive, but it likely comes at the benefit of better or more selective use of voriconazole, which is on the WHO Essential Medicines List (EML) specifically to treat IA. The submission contains convincing evidence on the public health relevance of the conditions and the usefulness, performance and accessibility of the test. And clinical practice guidelines around the world already include Aspergillus antigen testing in the diagnostic workup for IA. The test is easy to perform compared with other methods, although availability in LMICs is doubtful.

There is substantial evidence of the accuracy of both serum and bronchoalveolar lavage (BAL) galactomannan (GM) ELISA tests for diagnosing invasive aspergillosis (IA) in patients receiving intensive chemotherapy or stem cell transplants with high likelihood of neutropenia. Choice of threshold is critical to balance risks of missing cases against false positives. Evidence is from both using the test for diagnosis in those suspected of having infection (for BAL and serum) and using it for surveillance for infection in those at high risk (serum). There has been little evaluation of the benefits of using GM ELISA tests to improve patient care and outcomes, or of using the test in formal screening or monitoring programmes. Guideline panels have judged the accuracy and evidence as adequate to recommend using the test across several different patient groups. There are few published studies of the accuracy of the newer lateral flow assay (LFA) versions of the antigen tests. Available evidence suggests similar performance to the ELISA tests in BAL samples, but estimates of accuracy remain uncertain. The full evidence review for this test category is available at: https://iris.who.int/handle/10665/339064

World Health Organization. (‎2021)‎. The selection and use of essential in vitro diagnostics: report of the third meeting of the WHO Strategic Advisory Group of Experts on In Vitro Diagnostics, 2020 (‎including the third WHO model list of essential in vitro diagnostics)‎. World Health Organization. https://iris.who.int/handle/10665/339064