The Diagnostic Accuracy of Metagenomic Next-Generation Sequencing in Diagnosing Pneumocystis Pneumonia: A Systemic Review and Meta-analysis

Aysun Tekin; Hong Hieu Truong; Lucrezia Rovati; Amos Lal; Danielle J Gerberi; Ognjen Gajic; John C O'Horo

doi:10.1093/ofid/ofad442

The Diagnostic Accuracy of Metagenomic Next-Generation Sequencing in Diagnosing Pneumocystis Pneumonia: A Systemic Review and Meta-analysis

Open Forum Infect Dis. 2023 Aug 18;10(9):ofad442. doi: 10.1093/ofid/ofad442. eCollection 2023 Sep.

Authors

Aysun Tekin¹, Hong Hieu Truong¹, Lucrezia Rovati^{2

3}, Amos Lal², Danielle J Gerberi⁴, Ognjen Gajic², John C O'Horo^{2

5}

Affiliations

¹ Division of Nephrology and Hypertension, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota, USA.
² Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota, USA.
³ School of Medicine and Surgery, University of Milano-Bicocca, Milan, Italy.
⁴ Mayo Clinic Library Services, Mayo Clinic College of Medicine and Science, Mayo Clinic, Rochester, Minnesota, USA.
⁵ Division of Infectious Diseases, Mayo Clinic, Rochester, Minnesota, USA.

Abstract

Background: Pneumocystis pneumonia (PCP) is a growing concern as the immunocompromised population expands. Current laboratory approaches are limited. This systematic review aimed to evaluate metagenomic next-generation sequencing (MNGS) tests' performance in detecting PCP.

Methods: Five databases were searched through December 19, 2022, to identify original studies comparing MNGS with clinically diagnosed PCP. To assess the accuracy, symmetric hierarchical summary receiver operating characteristic models were used.

Results: Eleven observational studies reporting 1442 patients (424 with PCP) were included. Six studies focused exclusively on recipients of biologic immunosuppression (none with HIV-associated immunosuppression). Six were exclusively on bronchoalveolar lavage, while 1 was on blood samples. The sensitivity of MGNS was 0.96 (95% CI, 0.90-0.99), and specificity was 0.96 (95% CI, 0.92-0.98), with negative and positive likelihood ratios of 0.02 (95% CI, 0.01-0.05) and 19.31 (95% CI, 10.26-36.36), respectively. A subgroup analysis of studies exclusively including bronchoalveolar lavage (BAL) and blood samples demonstrated a sensitivity of 0.94 (95% CI, 0.78-0.99) and 0.93 (95% CI, 0.80-0.98) and a specificity of 0.96 (95% CI, 0.88-0.99) and 0.98 (95% CI, 0.76-1.00), respectively. The sensitivity analysis on recipients of biologic immunosuppression showed a sensitivity and specificity of 0.96 (95% CI, 0.90-0.98) and 0.94 (95% CI, 0.84-0.98), respectively. The overall confidence in the estimates was low.

Conclusions: Despite the low certainty of evidence, MNGS detects PCP with high sensitivity and specificity. This also applies to recipients of biologic immunosuppression and tests performed exclusively on blood samples without the need for BAL. Further studies are required in individuals with HIV-associated immunosuppression.

Keywords: PCP; Pneumocystis; diagnostic accuracy; meta-analysis; metagenomic next-generation sequencing; systematic review.