SAGE IVD recommended including the P. jirovecii test category in the third EDL:
• as a disease-specific IVD for use in clinical laboratories (EDL 3, Section II.b);
• using a nucleic acid test format;
• to aid in the diagnosis of Pneumocystis pneumonia. The group requested the addition of a note to the test category entry in the EDL stating that it is particularly relevant in immunocompromised patients.

Pneumocystis pneumonia (PCP) is a significant public health problem, whose incidence in LMICs is closely linked with the burden of HIV disease and, more specifically, the proportion of patients who still present with advanced disease. P. jirovecii cannot be cultured and has historically been diagnosed by stains or antibody-based microscopy, with limited sensitivity. Molecular assays are valuable in confirming P. jirovecii as the causative agent of pneumonia, when combined with clinical signs and symptoms. In these cases, the assays are also reliable for excluding PCP and thus preventing inappropriate use of cotrimoxazole. But current tests are not inexpensive; and they are only appropriate for centralized testing. SAGE IVD also noted that while the submission broadly covers NAT formats, the evidence base provided is predominantly for PCR tests. Group members noted that LAMP tests tend not to be as sensitive as PCR, although LAMP tests do have advantages, particularly in LMICs. In considering the use of PCR tests, SAGE IVD raised some concerns about the potential for variability in results. Some procedures use conventional PCR, while others use real-time PCR. And the specimen type includes a broad range of respiratory tract specimens, from sputum to BAL to tracheal secretion. Diagnostic accuracies vary with both specimen and technology type. The group confirmed, however, that this potential for variability in results applies to many other conditions where different PCR types and specimens are used. SAGE-IVD also acknowledged that addressing quality assurance and standardization issues is beyond the scope of the EDL (although the group emphasized that this should be done as and when countries establish and implement their own national EDLs).

The guidelines related to the test used rigorous methods, and the recommendations were based on evidence varying from low to moderate quality. The meta-analysis suffered from high heterogeneity, but the confidence intervals were rather small. The primary studies selected children hospitalized with suspected PCP in a prospective manner and using valid reference standards. All patients were included in the analysis. The challenge is that PCR seems to detect more PCP cases than the current reference standard. In summary, the test was evaluated in various subgroups of patients on various specimens. No recommendations in guidelines were made specifically for children, and only two primary studies in children were added to the evidence portfolio. With the sensitivity of the test at more than 97%, it is safe to rule out patients to avoid inappropriate use of cotrimoxazole. But the test cannot distinguish infection from carriage, which might hamper clinical usefulness.

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